SAMJ Vol 104, No 12 (2014)

DECEMBER 2014

VOL. 104 NO. 12

Amniocentesis and risk of HIV transmission

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Call for neonatal premedication prior to intubation

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Early detection of retinoblastoma

856, 859

Why aren’t women getting safe abortions?

857, 864

Increased MTCT of HIV in adolescent pregnancy

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VTE – profiling of patient risk

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CME: Tuberculosis and HIV

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DECEMBER 2014

FROM THE EDITOR

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Making us fat (and sick) B Farham

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EDITOR’S CHOICE

VOL. 104 NO. 12

EDITOR Janet Seggie, BSc (Hons), MD (Birm), FRCP (Lond), FCP (SA) EDITOR EMERITUS Daniel J Ncayiyana, MD (Groningen), FACOG, MD (Hon), FCM (Hon)

CORRESPONDENCE

CONSULTING EDITOR JP de V van Niekerk, MD, FRCR

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DEPUTY EDITOR Bridget Farham, BSc (Hons), PhD, MB ChB

Insulin receptor substrate-1 Gly972Arg variant and type 2 diabetes mellitus S S Tin, V Wiwanitkit

EDITORIAL SYSTEMS MANAGER Melissa Raemaekers, BSc (Hons), PhD

IZINDABA 838 839 841 842

HIV research for prevention – huge potential but no ‘magic bullet’ Using basic technology – and corporate social responsibility – to save lives Health minister’s ex-legal advisor slams Certificate of Need law New HASA board: The right mix at the right time

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OBITUARY/HULDEBLYK Lorna Macdougall

SAMJ FORUM

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CLINICAL PRACTICE Recommendations for amniocentesis in HIV-positive women S N Constantatos, A H Boutall, C J Stewart

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Newborns should be receiving premedication before elective intubation M S Raban, Y Joolay, A R Horn, M C Harrison

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The structured communication tool SBAR (Situation, Background, Assessment and Recommendation) improves communication in neonatology M Raymond, M C Harrison

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CLINICAL ALERT Tricuspid valve endocarditis associated with intravenous nyoape use: A report of 3 cases R Meel, F Peters, M R Essop

SCIENTIFIC EDITOR Ingrid Nye, BSc TECHNICAL EDITORS Paula van der Bijl, BA, HDipLib Emma Buchanan, BA NEWS EDITOR Chris Bateman | Email: chrisb@hmpg.co.za

EDITORIALS

HEAD OF PUBLISHING Robert Arendse PRODUCTION COORDINATOR Bronlyne Granger ART DIRECTOR Brent Meder DTP & DESIGN Carl Sampson ONLINE MANAGER Gertrude Fani DISTRIBUTION MANAGER Edward Macdonald | Tel. 021-681-7085 HEAD OF SALES AND MARKETING Diane Smith | Tel. 012-481-2069 Email: dianes@samedical.org

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Towards early detection of retinoblastoma N Freeman, D Meyer

PROFESSIONAL ADVERTISING Bronlyne Granger | Tel. 021-681-7000 E-mail: bronlyne.granger@hmpg.co.za

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Why aren’t women getting safe abortions?

R Jacobs, N Hornsby

HMPG BOARD OF DIRECTORS Prof. M G Veller (Chair), Prof. M Lukhele, Dr M Mbokota, Prof. A A Stulting, Dr M R Abbas, Dr G Wolvaardt

RESEARCH 859

Retinoblastoma outcome at a single institution in South Africa M Kruger, D Reynders, F Omar, J Schoeman, O Wedi, J Harvey

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Unwanted pregnancies in Gauteng and Mpumalanga provinces, South Africa: Examining mortality data on dumped aborted fetuses and babies R Jacobs, N Hornsby, S Marais

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Blood pressure measurements in the ankle are not equivalent to blood pressure measurements in the arm* L N Goldstein, M Wells, K Sliwa

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Adolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa G Fatti, N Shaikh, B Eley, D Jackson, A Grimwood

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The Use of VTE prophylaxis in relatioN to patiEnt risk profiling (TUNE-IN) Wave 2 study* B F Jacobson, S Louw, W J Riback

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December 2014, Vol. 104, No. 12

ASSOCIATE EDITORS Q Abdool Karim, A Dhai, N Khumalo, R C Pattinson, A Rothberg, A A Stulting, J Surka, B Taylor, M Blockman ISSN 0256-9574 Publisher website: www.hmpg.co.za SAMA website: www.samedical.org Journal website: www.samj.org.za

CONTENTS LISTED IN Index Medicus (Medline).

Excerpta Medica (EMBASE).

Biological Abstracts (BIOSIS).

Science Citation Index (SciSearch). Current Contents/Clinical Medicine

CONTINUING MEDICAL EDUCATION

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GUEST EDITORIAL Management challenges in tuberculosis and HIV G Meintjes

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REVIEW The diagnosis, management and prevention of HIV-associated tuberculosis S Wasserman, G Meintjes

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ARTICLES Diagnosis and management of drug-resistant tuberculosis in South African adults J Hughes, M Osman

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The diagnosis and medical management of tuberculous meningitis in adults S Marais, R J Wilkinson

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Management of HIV-associated cryptococcal disease in South Africa N P Govender, S Dlamini

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Focus on adolescents with HIV and AIDS L Fairlie, N Sipambo, C Fick, H Moultrie

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Antiretroviral therapy for the management of HIV in children L Frigati, M F Cotton, H Rabie

*Full article available online only.

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A lone tree photographed against the night sky near Leliefontein in Namaqualand, Northern Cape Province.

Photo and text: Eric Nathan Email: eric@ericnathan.com

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December 2014, Vol. 104, No. 12

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FIRST PUBLISHED IN 1884

Making us fat (and sick) In May this year, the Lancet published an analysis of global, regional and national prevalence of overweight and obesity in children and adults during 1980 - 2013, for the Global Burden of Disease Study 2013.[1] The findings are salutary. Worldwide, the proportion of adults with a body mass index of ≥25 kg/m2 increased between 1980 and 2013 from 28.8% to 36.9% in men, and from 29.8% to 38.0% in women.

The prevalence of obesity has also substantially increased among children and adolescents in both developed and developing countries.

South Africans are the fattest population in sub-Saharan Africa – 7 in 10 women (69.3%) and 4 in 10 men (38.8%) are overweight or obese.

These rates are reflected in our children as well, with 7% of boys and 9.6% of girls classified as obese.

These global and local changes have taken place over a mere 33 years, an incredibly short time in terms of population biology. And with the rising prevalence of obesity comes an increase in the associated noncommunicable diseases, type 2 diabetes probably epitomising the worst effects of too much fat on our bones.

The prevailing view of many of those in the public health arena is that this epidemic is caused by people eating too much and exercising too little. But there is little evidence to support this. The sheer numbers involved – and the spread of the epidemic to regions of the world where people traditionally have less to eat than those in the West, and often walk long distances as part of their daily lives – make this simple approach to the problem less and less plausible. We can no longer simply blame the individual. As in any other biological system, where we see major changes across a whole population, we have to start looking at the environment.

Walk down a supermarket aisle and take a good look at the foods arranged on the shelves – colourful packaging, prominent marketing messages, highly processed foods, and very few items that your grandmother would recognise as food. Does some of the problem start here? Earlier this year, the BBC broadcast two of a series of three documentaries by Jacques Peretti looking at the role of the food industry in changing our size and relationship with food – ‘The Men Who Made us Fat’.[2] Peretti starts with the 1977 US dietary guidelines, at least partly informed by Ancel Keys’ landmark study[3] on the relationship between saturated fat in the diet and the incidence of cardiovascular disease. What many people do not realise is that, at the same time, John Yudkin was blaming sugar.[4] Keys became conventional wisdom, while Yudkin was literally ridiculed. I am not going to go into the politics behind the formulation of the 1977 guidelines. Suffice it to say that guidelines that made carbohydrates the basis of a prudent diet and demonised fats gave the food industry the trigger it needed to change the way that we eat.

During the early part of the last century, agriculture and the food industry were starting to grow massively and had a lot of political clout.

But people tended to eat simply – processed foods were not common, and you bought your food from local high-street grocers, butchers and bakers. And people ate three meals a day. This led the food industry to identify what they called ‘down time’ – time when people weren’t eating. So aggressive marketing started to push the idea of ‘snacking’.

Some of our older readers will remember advertising campaigns such as ‘Milky Way – the sweet you can eat between meals’ – a relatively small bar made up almost entirely of sugar.

As you follow Peretti through three programmes examining the food industry in minute detail – and in the final episode such embarrassing detail that the BBC did not show it (you can see it on You Tube) – you realise that the 1977 dietary guidelines gave the industry almost carte

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blanche to completely change the composition of the food on our tables.

Low-fat foods, such as yoghurt without the fat, taste dreadful, so sugar was added for taste. And as the prevailing view was that sugar was simply empty calories, no one thought anything of it. Low-fat foods multiplied on the shelves, all packed with refined carbohydrates of one type or another. At the same time, snacking (and eating in public) became the norm. By the mid- to late 1980s you could not walk down a street in a city in just about any Western country without seeing somewhere to buy and consume food. And those Milky Way bars got larger and larger, as did servings of carbonated soft drinks containing staggering amounts of sugar. The fast-food outlets realised that all they had to do to make more money (a lot more money) was to increase their serving sizes just a little, for very little more money from the consumer, and the average calorie content of a fast-food meal inexorably increased – and the calories were made up of sugars, other refined carbohydrates, and some pretty dreadful fats, few of them saturated. For the less well off, a fast-food meal is a cheap and tasty way to eat – hence the high prevalence of obesity among lower socieconomic groups.

So yes, people have started to eat more, no doubt about it – it is almost impossible not to, if you eat what is presented to you in such tempting and convenient ways. Relatively small amounts of modern foods are so calorie dense that you are consuming more without realising it. There is also the controversial idea that these sugars and refined carbohydrates are addictive as well, but I won’t get into that.

The third of Peretti’s programmes – the one that the BBC pulled (no doubt on the advice of their legal department) – is the most damning.

Not content with touting ‘low-fat’ products, industry marketing campaigns turned to wealthier people’s increasing realisation that there is something wrong, and their wanting to eat ‘healthier’ foods. Now we started to see words such as ‘organic’ and ‘vitamin’ (as in vitamin water – check the sugar content!), all aimed at a section of the market who want to be careful what they eat. But the content of the food is no ‘healthier’ than it was previously – it’s still packed with sugars and refined carbohydrates of various kinds.

I am not going to get involved in the argument about diets low in carbohydrates and high in fats v. diets high in carbohydrates to replace saturated fats. But the epidemiological evidence for our increasing girth is not in dispute. And a simple trip to a supermarket bears out Peretti’s arguments (and research) pretty well. The message to individuals who are fortunate enough to be able to control their own environment is ‘eat real food’. The public health approach is rather more complex, but a more rational approach to the highcarbohydrate food pyramid still pushed by the various disease groupings would be a start. We have to undo 33 years of bad advice, and soon.

Bridget Farham

Deputy Editor ugqirha@iafrica.com 1. Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014;384(9945):766-781. [http://dx.doi.org/10.1016/S0140-6736(14)60460-8] 2. https://www.youtube.com/watch?v=iE-H__aIEFE (accessed 27 October 2014).

3. Keys A, ed. Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease.

Cambridge, Mass: Harvard University Press, 1980.

4. Judkin J. Pure, White and Deadly: The Problem of Sugar. London: Davis-Poynter, 1972.

S Afr Med J 2014;104(12):835. DOI:10.7196/SAMJ.9063

December 2014, Vol. 104, No. 12

EDITOR’S CHOICE

CME: Tuberculosis and HIV

On a global scale, South Africa (SA) is disproportionately affected by the epidemics of both tuberculosis (TB) and human immunodeficiency virus 1 (HIV-1), and the intersection of these two diseases has resulted in an unprecedented disease burden in our country. It is estimated that 12.2% of South Africans are HIVinfected – a total of 6.4 million people, the largest number of any country in the world. SA has the second highest annual incidence of TB after Swaziland. Approximately 1% of the population develop active TB disease each year (an estimated 530 000 people in 2012).

While SA comprises 0.7% of the world’s population, it is estimated that of all cases of HIV-associated TB that occur worldwide annually, 30% occur here.

Important gains have been made in the public health response to HIV in the past decade, but despite these TB and HIV, often as co-infection, are still the most important causes of morbidity and mortality among adult South Africans. HIV-related complications remain the commonest cause for admission to hospital medical wards. At Khayelitsha Hospital in Cape Town, over 50% of patients admitted to the medical wards are HIV-infected, and many of these patients also have active TB. While we have the largest antiretroviral therapy (ART) programme in the world, we have not seen the same dramatic impact on the prevention of HIV opportunistic infections as occurred in industrialised countries when ART was first introduced.

This important issue of CME, guest edited by Graeme Meintjes, addresses the management challenges in tuberculosis and HIV.

Recommendations for amniocentesis in HIV-positive women

All women should be able to opt for prenatal screening and diag­ nosis, and for an amniocentesis if required, regardless of their HIV status. Constantatos et al.[1] provide recommendations for amnio­ centesis in HIV-positive women and advise that it is safe to perform this procedure in women on highly active antiretroviral therapy (HAART) with suppressed viral loads (preferably undetectable) and when transplacental passage of the needle is avoided.

If an HIV-positive patient accepts amniocentesis, HAART should be initiated and amniocentesis delayed until the viral load is undetectable. If there is not enough time to attain an undetectable viral load, however, it is reasonable for the patient to be on HAART for as long as possible before amniocentesis. The nature of the fetal abnormality may influence the decision to proceed even when the viral load is not suppressed – if the abnormality is severe and will be associated with significant morbidity, exposing the fetus to a very small risk of HIV transmission at amniocentesis is outweighed by the benefit of a prenatal diagnosis.

It is worth noting that there is a non-invasive prenatal screening test (the Harmony test) that analyses cell-free DNA in the maternal blood and will identify 99% of fetuses with trisomy 21, 97% of fetuses with trisomy 18, and 92% of fetuses with trisomy 13. Although not available in the state sector or to many private patients because of the cost, this highly effective screening test does not carry the risk of miscarriage and HIV transmission.

Premedication for newborns before elective intubation

Newborns should be receiving premedication before elective intubation,[2] as has become the standard of care in over 90% of neonatal units in the UK. Premedication for elective and semiurgent intubation of infants significantly improves intubation conditions, decreases the time and number of attempts needed to complete the intubation procedure, and minimises the potential for

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intubation-related airway trauma that arises from the noxious stimuli of intubation, potentially results in raised intracranial pressure, hypoxaemia and cardiovascular instability, and may have long-term deleterious effects.

Retinoblastoma – early detection improves outcome

Kruger et al.[3] report the generally poor outcome in children with retinoblastoma at a single institution in SA, reflecting its late diagnosis. Overall survival was only 33 - 43%, compared with the 95% achievable in developed countries. The simple reason is lack of effective screening, and this unacceptably high mortality rate can be significantly reduced by the early detection of retinoblastoma that may be achieved by ensuring that the ‘red reflex’ is tested for on all newborns and toddlers. The ‘red reflex’ or ‘retinal reflex’ refers to the reddish-orange reflection of light from normal retina, and it is observed with a direct ophthalmoscope held close to the examiner’s eye while observing the patient’s eyes from a distance of approximately 30 cm. Normally the reflections of the two eyes are equivalent in colour, intensity and clarity. Retinoblastoma is suggested by a whitening of the reflex, white spots in the reflex, an absent red reflex, or asymmetry of the two red reflexes when viewed from various angles.

As the editorial by Meyer[4] points out, while retinoblastoma is a rare and life-threatening condition, when it is managed optimally by a competent health team there is excellent prognosis for survival and good visual outcomes. The ‘red reflex’ test should be mandatory at discharge from all neonatal services and at all subsequent routine health supervision visits. Parents are similarly able to detect a problem by noticing an abnormality in the red reflex in photographs taken when the ‘red eye reduction’ function happens to be switched off on their camera. It would not be too idealistic to suggest that all physicians attending to neonates and toddlers use this humble camera technique and digitally save the red reflex images to the patient’s file at each visit. In the meantime, diabetic screening programmes using portable digital imaging systems are already established in many areas in the world, including the Cape Town metropole. The development of portable digital retinal imaging systems is ongoing, and it will be feasible to screen the retinas of all neonates in the future using this technology.

Unwanted pregnancies in Gauteng and Mpumalanga

Examining mortality data on dumped aborted fetuses and babies, Jacobs et al.[5] report that despite progressive abortion laws, many SA women of all ages still appear to be resorting to unsafe terminations outside legal, designated facilities. There is an increase in the illegal dumping of fetuses and abandoned babies, suggesting an increase in unsafe termination practices as well as concealed births. For the southern African region (including Botswana, Lesotho, Namibia, SA and Swaziland, of which SA forms the major component), 120 000 unsafe abortions were estimated to have occurred in 2008.

Poor or restricted access to contraceptive services and the fact that women experience considerable difficulties in negotiating safe sex practices account for unintended pregnancies. Young girls who partner with older men are especially vulnerable to sexual exploitation because of their financial dependency.

SA decriminalised abortion in 1996 by introducing the Choice on Termination of Pregnancy Act. SA law also protects the individual choice of minors, who are encouraged to consult with their parents, guardians, family and friends but may terminate a pregnancy without parental consent. An undisclosed number of women affected by

December 2014, Vol. 104, No. 12

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EDITOR’S CHOICE

unwanted pregnancies are nevertheless unable to rely on the existing services available. This reflects a lack of information and perceived poor quality of services, as well as women being misinformed by hospital staff regarding services and legislation. Furthermore, women who are able to access these services are stigmatised and report experiencing judgemental attitudes from service providers. Accessibility to services is further limited because half of the designated facilities that are registered providers of termination services are in reality not providing this service, reflecting an unwillingness of healthcare workers to be trained to undertake termination of pregnancy.

Risks associated with pregnancy in young HIV-infected women

Fatti et al.[6] report that adolescent and young pregnant women are at increased risk of mother-to-child transmission of HIV and poor maternal and infant health outcomes. An increasing proportion of pregnant HIV-positive women in the Nelson Mandela Bay Metropolitan district, Eastern Cape Province, SA, are young, and they have poorer maternal and infant outcomes than older women. These young women are less aware of their HIV status when booking, and had slower antenatal ART uptake, reduced uptake of early infant diagnosis, and increased mother-to-child transmission (MTCT) of HIV (despite having less advanced immunosuppression). Adolescents had increased risks of maternal mortality, first presentation in labour and stillbirth, all findings that have important public health relevance to SA. There is a critical need for sexual and reproductive health rights to be rolled out at clinics and schools, to include increased access to HIV counselling and testing, barrier methods to prevent transmission, and family planning. Interventions targeting young women are increasingly needed to reduce pregnancy, HIV infection and MTCT and improve maternal and infant outcomes if SA is to attain its Millennium Development Goals.

Venous thromboembolism (VTE) risk assessment

The Use of VTE prophylaxis in relatioN to patiEnt risk profiling (TUNE-IN) Wave 2 study[7] was conducted to evaluate common practice in the assessment of VTE risk in the inpatient healthcare setting in Gauteng, SA. Public sector patients were more commonly clinically assessed as being at risk for VTE than those in the private sector (87.0% v. 47.3%), but a greater percentage of patients across all risk levels received prophylaxis in the private than in the public sector (96.8% v. 79.7%), possibly as a result of availability of chemoprophylaxis drug preparations, costs and VTE prophylaxis protocols.

There is a need for improvement in VTE risk assessment and prophylaxis in both the public and private sectors. The implementation of a formalised VTE risk assessment tool – as outlined in the article – will ensure standardisation of VTE risk assessment and administration of adequate prophylaxis.

JS 1. Constantatos SN, Boutall AH, Stewart CJ. Recommendations for amniocentesis in HIV-positive women. S Afr Med J 2014;104(12):844-845. [http://dx.doi.org/10.7196/SAMJ.8660] 2. Raban MS, Joolay Y, Horn AR, Harrison MC. Newborns should be receiving premedication before elective intubation. S Afr Med J 2014;104(12):846-849. [http://dx.doi.org/10.7196/SAMJ.8305] 3. Kruger M, Reynders D, Omar F, Schoeman J, Wedi O, Harvey J. Retinoblastoma outcome at a single institution in South Africa. S Afr Med J 2014;104(12):859-863. [http://dx.doi.org/10.7196/ SAMJ.8255] 4. Freeman N, Meyer D. Towards early detection of retinoblastoma. S Afr Med J 2014;104(12):856. [http://dx.doi.org/10.7196/SAMJ.8741 5. Jacobs R, Hornsby N, Marais S. Unwanted pregnancies in Gauteng and Mpumalanga provinces, South Africa: Examining mortality data on dumped aborted fetuses and babies. S Afr Med J 2014;104(12):864-869. [http://dx.doi.org/10.7196/SAMJ.8504] 6. Fatti G, Shaikh N, Eley B, Jackson, D, Grimwood A. Adolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa. S Afr Med J 2014;104(12):874-880. [http://dx.doi.org/10.7196/SAMJ.8207] 7. Jacobson BF, Louw S, Riback WJ. The Use of VTE prophylaxis in relatioN to patiEnt risk profiling (TUNE-IN) Wave 2 study. S Afr Med J 2014;104(12):880-884. [http://dx.doi.org/10.7196/ SAMJ.8456]

CORRESPONDENCE Insulin receptor substrate-1 Gly972Arg variant and type 2 diabetes mellitus

Sim Sai Tin

Medical Center, Shantou, China simsaitin@gmail.com

To the Editor: In their article, Vergotine et al. [1] concluded that ‘the Gly972Arg variant may not aid diabetes risk evaluation in this setting’. In fact, the insulin receptor substrate-1 Gly972Arg variant is widely studied in terms of its relationship to diabetes mellitus. Different observations have been made in different settings. In a report from Mexico, Burguete-Garcia et al. [2] found ‘participation of Gly972Arg polymorphism of IRS1 in the genetic susceptibility to TD2 in Mexican population’. An interesting point is that there are many possible genetic polymorphisms that can relate to diabetes mellitus. However, a polymorphism study alone cannot tell the exact relationship. In a previous study from Mexico,[3] a polygenic polymorphism effect on diabetes could be confirmed.

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Viroj Wiwanitkit

Visiting professor, Hainan Medical University, Haikou City, Hainan Province, China 1. Vergotine Z, Kengne AP, Erasmus RT, Matsha TE. No evidence for association of insulin receptor substrate-1 Gly972Arg variant with type 2 diabetes mellitus in a mixed-ancestry population of South Africa. S Afr Med J 2014;104(6):420-423. [http://dx.doi.org/10.7196/SAMJ.7419] 2. Burguete-Garcia AI, Cruz-Lopez M, Madrid-Marina V, et al. Association of Gly972Arg polymorphism of IRS1 gene with type 2 diabetes mellitus in lean participants of a national health survey in Mexico: A candidate gene study. Metabolism 2010;59(1):38-45. [http://dx.doi.org/10.1016/j.metabol.2009.07.007] 3. García-Escalante MG, Suárez-Solís VM, López-Avila MT, Pinto-Escalante D del C, Laviada-Molina H. Effect of the Gly972Arg, SNP43 and Prol2Ala polymorphisms of the genes IRS1, CAPN10 and PPARG2 on secondary failure to sulphonylurea and metformin in patients with type 2 diabetes in Yucatán, México. Invest Clin 2009;50(1):65-76.

S Afr Med J 2014;104(12):837. DOI:10.7196/SAMJ.8922

December 2014, Vol. 104, No. 12

IZINDABA

HIV research for prevention – huge potential but no ‘magic bullet’ HIV research for preven­ tion has so far produced a mixed bag with no magic bullet, but results for an anti­retroviral (ARV)-in­ fused vaginal ring that stays in place for 30 days, potentially offering women up to 50% (or more) protection against HIV and theoretically saving millions of lives over time, will be reported in 2016.

Women lack practical and discreet tools they can use to protect themselves from HIV infection.

There are two parallel, almost identical major microbicide ring trials currently underway, the ASPIRE trial and the Ring trial. The results of the former are due in early 2016 – and if positive with high efficacy, the device will almost certainly be licensed for use. This potentially major leap forward in adherence to interventions for women, in addition to the HIV prevention armament of circumcision, male and female condoms, prevention of motherto-child transmission and oral ARVs (among others), is generating the most excitement among the South African (SA)led global community of HIV researchers, because of how far advanced its twinned international studies are. The research focus on female-initiated methods of HIV prevention makes solid sense on taking a quick glance at the statistics: of more than 35.3 million people living with HIV, over half are women. In sub-Saharan Africa, where unprotected heterosexual sex is the primary HIV driver, women account for nearly 60% of adults with HIV. Young women are especially vulnerable, those aged 15 - 24 being twice as likely as young men to be infected with HIV. Efforts to promote abstinence, monogamy and the use of male condoms have either not done enough to stop the HIV epidemic or are not realistic in many settings. Women lack practical and discreet tools they can use to protect themselves from HIV infection.

Many women are unable to negotiate successfully with their male partners to use condoms or to be faithful. Abstinence

is simply not realistic for women who are married, who want children or who are at risk of violence.

ARV gel well ahead in the efficacy stakes

Findings of a confirmatory trial of the far earlier Durban-based CAPRISA 004 trial led by Prof. Salim Karim that showed an ARV-based microbicide gel to be 39% effec­ tive, which are being confirmed through the FACTS 001 trial by Prof. Helen Rees of the Wits Reproductive Health and HIV Institute and Prof. Glenda Gray, now Medical Research Council (MRC) CEO, will be released at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, USA, in late February next year. One of the major challenges with pre-exposure prophylaxis, including vaginal gel, is its low adherence threshold (the gel needs to be applied 12 hours before and 12 hours after coitus). However, the CAPRISA 004 trial is the only ‘proof of concept’ trial of a vaginal microbicide so far, and an improved efficacy result through the FACTS 001 trial would increase options for those women who have a preference for gel as an HIV prevention method. The CAPRISA 004 trial also showed efficacy of 50% protection against herpes simplex virus 2.

Other scientific advances are novel formulation of pre-exposure prophylaxis in the form of long-acting injectables. It is hoped that a decade from now we will have injectable ARVs offering prevention and treatment for HIV-negative and HIVpositive people, respectively. The concept has gone through preclinical and animal studies and is currently being tested in earlyphase human trials. Based on safety and pharmacokinetic and pharmacodynamic data, the products are slated to move to phase 2/2b trials.

HIV vaccine candidate.

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December 2014, Vol. 104, No. 12

Vaccines to prevent HIV are much-needed options to add to the current toolbox of HIV prevention options. Prof. Gita Ramjee, Director of the HIV Prevention Research Unit at the MRC, speaking at the HIV Research for Prevention Conference in Cape Town (the first global conference to feature all forms of biomedical HIV intervention), said that the most exciting news on the vaccine front would be adapting the partially successful Thai HIV vaccine trial to a local HIV sub-type C virus. New local trials are planned, building on the moderate success of the Thai RV144 trial.

Nobody expects the vaccine to offer complete protection from the virus, but even 30 - 40% protection will significantly reduce the rate of new infections. Gray said that should this kind of efficacy be shown, in 2019 researchers will apply for approval by the Medicines Control Council for use and sale. Should the local vaccine enhancement boost efficacy to 50%, the vaccine would be ‘a global game changer’.

Adapted, longer-acting HIV vaccine would be a ‘global game changer’

Gray told the conference that after 30 years of trying to find a vaccine for HIV, scientists in Thailand announced this success in 2009. The vaccine offered people who received it almost 60% protection from the virus, for the first year. After 3 years, recipients were 31% less likely to contract the virus.

Researchers in SA have managed to show two things so far: that it is safe to use on South Africans, and that it (i.e. the Thai clade) provokes an immune response. A new trial will start in January with the Thai vaccine modified to fight against the African strain of the virus, and strengthened to offer protection from HIV for a longer period than the Thai

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vaccine does. Participants will receive a booster vaccination after a year. No one expects the vaccine to offer complete protection from the virus, but even 30 40% protection will significantly reduce the rate of new infections. Gray said that should this kind of efficacy be shown, in 2019 researchers will apply for approval by the Medicines Control Council (MCC) for use and sale. Should the local vaccine enhancement boost efficacy to 50%, the vaccine would be ‘a global game changer’.

For now, all eyes on microbicide ring study results

Ramjee, an MRC veteran of two decades, said that her institution was the biggest contributor to the twinned microbicide ring studies, with six sites in Durban.

Other sites include CAPRISA, Cape Town, Johannesburg, Malawi, Uganda and Zimbabwe. Underpinned by the Inter­ national Microbicides Partnership and the US National Institutes of Healthfunded Microbicide Trials Network, the ‘sister studies’ involve 4 500 women and are being run concurrently to keep the timeline to potential approval and product access as short as possible. (Two efficacy trials are usually needed for a product to be considered for regulatory approval.)

When the datasets are merged and the

Prof. Gita Ramjee, Director of the HIV Prevention Research Unit at the MRC.

MCC takes a decision on the efficacy threshold (Ramjee speculates that the MCC will go for safety and efficacy, with an upper bound of 60% and lower bound of 50%), the product can be licensed.

‘We’ve completed enrolment with followup by June next year. Then we begin the process of data cleaning, and we’re hoping for results by December 2015 or early in 2016.’ Asked how she felt, given that

she’s been involved in all the large-scale microbicide trials so far, Ramjee said she was ‘a bit confident that this may show something, given that we are alleviating some of the daily adherence issues’.

Emphasising that the other products may have been ‘perfectly good’, she said that adherence was historically the single biggest issue. Products for HIV prevention and treatment would only work if they were taken or used as required.

Ramjee said that another exciting product was a similar flexible ring that delivered both an ARV drug and a contraceptive drug for 3 months (currently in the early testing phase). This multipurpose technology is being developed to protect women from HIV and unintended pregnancies. The rings are being developed by various groups using ARV agents such as dapivirine and tenofovir. She said that given the high incidence of HIV among women in Africa, it was ‘imperative’ that women’s needs for HIV prevention were met. This included providing choices of various formulations and dosages for prevention of both HIV and unintended pregnancies.

Chris Bateman chrisb@hmpg.co.za S Afr Med J 2014;104(12):838-839.

DOI:10.7196/SAMJ.9129

Using basic technology – and corporate social responsi­bility – to save lives While South Africa (SA) will almost certainly fail to meet next year’s Millenn­ium Development Goals (MDGs) of reducing deaths of children under 5 by two-thirds and the maternal mortality rate by three-quarters, one brilliantly simple technological innovation is accelerating progress.

It’s called ‘MomConnect’ – a free SMS (text message) pregnancy information and advice service targeting the 1.2 million women who fall pregnant every year (one million using the public sector and 200 000 the private).

After registering at their clinic or private health facility, the expectant (and existing) mothers get SMSed fortnightly advice and information tailored to their stage of

pregnancy, or appropriate to their newborn infant or child of up to 18 months. For hundreds of thousands of pregnant women, many in far-flung, poverty-stricken rural areas or in their vulnerable teenage years, the service is a veritable lifeline. Teenage girls, for example, many of them first-time mothers, account for a disproportionate 36% of maternal deaths, while representing only 8% of all annual pregnancies.

The National Department of Health (NDoH), realising that more South Africans use a mobile phone than watch television or listen to the radio (there are more SIM cards than people), decided it was time to knock on the doors of the locally operating cell phone companies to see whether they would help make the initiative fly. Vodacom, MTN, Cell C and Telkom all promptly agreed

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to provide a 50% discount on all SMSs sent to MomConnect-registered mothers.

The NDoH also secured R49 million in funding from the US government and R5 million each from Johnson & Johnson and ELMA Philanthropies, thus retaining its own precious budget for other vital lifesaving interventions that have finally and belatedly begun to make an impact on the shocking death statistics for mothers and children. National health minister

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Dr Aaron Motsoaledi conducted a national MomConnect tour this August, addressing many of the 10 000 public healthcare workers newly trained in the programme and checking that every health facility had a dedicated registration facilitator, backed by a provincial counterpart and co-ordinated nationally.

Presenting in labour is too often fatally late

‘Many women end up with a complicated pregnancy simply because they didn’t know what to do,’ explained Motsoaledi. ‘You [the healthcare workers] are helpless to change the outcome if their first point of contact is the labour ward,’ he emphasised.

‘This way we can give advice and share what could be lifesaving knowledge during pregnancy – and afterwards – on exclusive breastfeeding, nutrition, immunisation, oral rehydration during diarrhoea – not to mention family planning.’ Complications can be identified early, and information on safe abortions and future contraception come with the package. The service also crucially reminds its users when they are due for a clinic check-up. Between its launch in October (Women’s Month) this year and 23 October, some 103 000 women had enrolled, with the number increasing at a rate of more than 10 000 per week and 69% of clinics participating, according to the NDoH. Currently available in English, Afrikaans, Zulu, Xhosa, Sotho and Tswana, the service will be available in all 11 official languages by early next year, an NDoH spokesman added.

Complications can be identified early, and information on safe abortions and future contraception come with the package. The service also crucially reminds its users when they are due for a clinic check-up.

Maternal deaths in SA climbed steadily from 1998, when 150 mothers died per 100 000 live births, to 2009, when the fig­ ure reached 312, before dropping back to

269 in late 2010 – after the 2009 findings of the health ministry’s Confidential Enquiry into Maternal Deaths began to be speedily acted upon. It now stands at 140, making SA’s MDG target of 38 for the end of next year ‘a possible or impossible dream’, as Motsoaledi put it, in a seemingly clumsy attempt to sound both upbeat and realistic.

The Saving Babies 2010 - 2011 report showed the early neonatal death rate to be 21/1 000 live births, with the majority of these deaths occurring in the 1 000 1 499 g weight category. SA has reduced the overall under-5 child mortality rate from 61/1 000 births in 1990 (the MDG inception date) to 45 currently. Reaching the MDG goal of 20 would need more to be done in the next 16 months than was done in the past 24 years.

Bright light at the end of the tunnel

Yet SA has much cause for hope. The largest HIV testing and antiretroviral (ARV) rollout campaign the world has yet seen, plus a massive push on the programme for prevention of mother-to-child transmission (PMTCT) of HIV over the past 10 years, now has over 98% of public health facilities providing these vital services. An estimated 99% of women receive an HIV test during pregnancy, and 93% of HIV-positive mothers are receiving ARV treatment or prophylaxis. A national evaluation involving 10 178 infants in 572 health facilities showed that the 6-week vertical HIV transmission rate now stands at 2.7%, compared with rates of 20 - 30% less than 10 years ago.

So just how will an intervention like MomConnect impact? Only proper research will eventually tell, but for now it will encourage pregnant women to start antenatal care early and enable testing for the killers of hypertension, HIV/ AIDS and diabetes very early on in their pregnancy, thus significantly boosting an already successful PMTCT campaign.

The MomConnect programme has an additional benefit; mothers will be able to send the NDoH free SMS messages (a ‘please call me’) to share their concerns about and experiences of public healthcare facilities, providing an invaluable ‘feedback loop’ for potential improvement as the national campaign to improve public sector

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caregiving standards gathers momentum.

It’s also the answer to tracking SA’s highly mobile population, enabling healthcare workers to plug into their patients’ history by linking the existing medical registry to an electronic database that can be accessed from all MomConnect clinics. This will mean that a woman can be more effectively treated at any participating facility.

After registering at their clinic or private health facility, the expectant (and existing) mothers get SMSed fortnightly advice and information tailored to their stage of pregnancy, or appropriate to their newborn infant or child of up to 18 months.

One independent mobile strategy firm, Tomi Ahonen Consulting, gave an insight into how smartphones (comprising 21% of SA’s mobile phones, but not required for MomConnect) can additionally broaden the educational reach of users. By exploiting the Android youth platform and free instant messaging service Mxit Reach, educational packages such as Babyinfo provide free basic day-to-day updates about pregnancy and tips on how to make a pregnancy more comfortable. Paying only for the internet connection, users can also download counselling applications such as Angel and LoveLife (substance abuse and HIV counselling, respectively). Mxit Reach is only one of several applications. Others include Hi4Life (‘information on HIV, pregnancy and baby health’, an initiative co-ordinated by the organisation HIVSA with financial support from the Elton John Foundation).

There are over 100 mobile health services of varying sizes, focuses and quality currently on offer in SA. It’s a classic example of how user-friendly First-World technology can help uplift and support Third-World communities – and save countless thousands of lives.

Chris Bateman chrisb@hmpg.co.za S Afr Med J 2014;104(12):839-840.

DOI:10.7196/SAMJ.9118

Proactive preventative strategies

essential for improving efficacy of HIV management More medical schemes and employers are exploring proactive preventative strategies to reduce the risk of HIV infection and improve management of the disease. This is according to Siraaj Adams, Executive Manager for the Metropolitan Health HIV YourLife Programme.

Healthcare providers are essential partners in leveraging optimal value from these preventative interventions and improving the efficacy of HIV management across the nation.

Scale up screening

Compared to the public sector, HIV screening as part of antenatal screening in the private sector is very low. Research conducted by the HIV YourLife Programme shows that the percentage of pregnant women in the private sector who had an HIV test as part of antenatal screening increased from 58.4% in 2011 to 63% in 2013. However, Adams believes these figures are still far too low. To help prevent mother-to-child HIV transmission, the HIV YourLife Programme actively encourages HIV testing and screening of pregnant women.

The HIV YourLife Programme also promotes STI and cervical cancer screening for women. Human Papillomavirus (HPV) is a very common sexually transmitted infection (STI). Women with HIV are at greater risk for persistent HPV and cervical cancer. The programme actively encourages regular screening for cervical cancer for all women with HIV, and endorses the use of the HPV vaccination for all HIV positive females and males aged nine to 26 years.

Voluntary Medical Male Circumcision

Randomized controlled trials have shown that voluntary medical male circumcision (VMMC) reduces HIV acquisition in heterosexual men by up to 60%. The World Health Organization and UNAIDS recommends that VMMC is offered to heterosexual men in combination with other effective HIV risk reduction interventions. The South African National Department of Health also actively supports VMMC as an important HIV prevention method.

Improving awareness levels is essential In order to inform effective implementation of VMMC programmes, the HIV YourLife programme initiated research to obtain insights into the current understanding and attitudes towards VMMC. This involved a survey across the male main members on three large medical schemes administered by Metropolitan Health, along with data analysis related to VMMCs performed by Metropolitan Health contracted providers. Highlevel results included: • Between January 2007 and December 2013, a total of 179 000 circumcisions were performed. According to UNAIDS studies, one HIV infection is averted for every five to 15 VMMCs. This suggests that

• Of those who were not already circumcised, only 38% indicated that they would consider MMC. The balance either didn’t know (9%), with more than half (53%) indicating that they would not consider a MMC. Members appear to be largely unaware of the value MMC offers in terms of preventing HIV and STI infection and see little value in having a MMC. These low levels of awareness highlight the significant work required in improving awareness levels around the role of MMC in HIV prevention.

Adams actively encourages healthcare providers to assess the benefits of medical male circumcision among male patients in order to enhance the uptake, decrease STIs and promote health awareness and positive living.

Is HIV self-testing a viable option?

HIV self-tests have been approved in certain countries, such as the United States and Kenya. They offer an alternative screening option and the potential to increase screening access, especially for people in resourceconstrained settings. However, many countries are skeptical about selftesting due to limited feasibility data on patient testing behaviours and concerns about access to counseling and care following at-home testing.

Metropolitan Health’s Siraaj Adams believes any mechanism that overcomes obstacles to knowing one’s status and supports regular HIV screening is to be welcomed. In this respect, self-testing certainly has the potential to add value. However, Adams is quick to point out that the supporting framework linking the HIV test result to a healthcare provider is critical.

A comparable model already exists in the form of the recently launched UdoTest - a HPV testing service that allows women to test themselves for the HPV virus in the privacy of their own homes. This HPV model has a direct link to the patient’s healthcare provider if the HPV test is positive.

Adams believes that there is opportunity for technology companies to link up with rapid test diagnostic companies and develop a smart HIV test kit device that can link the test kit to the patient’s details and digitally link the result to the patient’s healthcare provider. This is an opportunity to leverage private sector healthcare infrastructure and expertise, so as to engage more South Africans in regular HIV screening.

approximately 20 000 new HIV infections have been prevented through the 179 000 circumcisions conducted over this period.

• 34% of circumcisions took place in the GP practice, while 62% took place as day cases in hospitals. Only 0.17% had adverse effects reported (such as post operative infection).

Funding the cost of VMMC through scheme insured benefits and implementing the Metropolitan Health HIV YourLife programme, inherently structured around encouraging preventative behaviour, are some of the proactive strategies progressive employers and schemes are adopting for improving the efficacy of HIV management. Healthcare providers are essential partners for the success of these strategies.

However, when it came to understanding the role of VMMC in HIV prevention, awareness levels amongst medical scheme members remain very low.

Newsbyte: Guidelines for claims against scheme benefits for these preventative services are:

• Only 49% of participating members believed that medical male circumcision prevents HIV infection. The balance either did not know (30%), or believed MMC does not prevent HIV (21%).

• For HIV screening, capture via the Metropolitan Health provider portal and access an enhanced fee.

• For MMC, use ICD-10 Z41.2 with tariff 2137 for the procedure.

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Health minister’s ex-legal advisor slams Certificate of Need law A former legal advisor to the national Minister of Health and legal expert in the medical scheme and private hospital industries, Dr Debbie Pearmain, has criticised government for ‘overmanaging’ healthcare service distribution and ignoring demand-side drivers.

Dr Debbie Pearmain, former legal advisor to the national Minister of Health and legal expert in the medical scheme and private hospital industries.

One of several speakers who attacked the government’s temporarily delayed Certi­ ficate of Need (CoN) legislation at the annual Hospital Association of South Africa (HASA) conference in Johannesburg this October, Pearmain said that health services were generally located where there was a strong likelihood of patients finding them.

Yet there seemed to be no cohesive plan at national level to manage healthcare demand.

Instead, a disproportionate emphasis was placed on the proposed CoN, a supply-side management tool.

The CoN legislation was temporarily put on ice earlier this year when the National Department of Health (NDoH) suddenly realised that its ambitious implementation deadline of 1 April 2016 was impractical, not to mention virtually impossible to meet.

More than 70 000 healthcare establishments

would have had to apply for a certificate by then, not to mention tens of thousands of healthcare providers consulted via their groupings to inform regulations before they were actually drafted and published for comment. 1 April 2016 was also the date by which every single healthcare provider in the country would have had to apply to NDoH Director-General Precious Matsoso for a CoN, whether they were setting up, modifying or buying a health establishment, increasing bed numbers, acquiring expensive technology, or just simply continuing to practise in the same place. The legal animal (hatched as provisions 36 - 40 of the National Health Amendment Act) has a noble purpose – to meet the govern­ment’s constitutional obligations of progressive and universal access to healthcare. However, its penalties are anything but benign – 5 years’ imprison­ment and/or a fine for noncompliance.

Pearmain said it was possible to filter patients through primary care, using telephone advice and interactive information services, sharing knowledge and community agencies. The location of doctors’ practices, particularly those of specialists, would always depend on the proximity of technology, whether this was the basics of electricity and running water or a private laboratory. ‘No private provider can logically be expected to set up a practice or a hospital in a place where there is a scarcity of patients and in the absence of other incentives,’ she said.

would help connect rural and urban areas.

Technology was the one area where the current mismatch between supply and demand would help make resources more accessible. Instead of taking clinicians to outlying areas, technology would bring the work to the specialists. Pearmain said that the key issue was to work out how the country could bring together the pro-poor strength of the public health system with the technical capacity and higher quality of the private healthcare system. She said that European Union laws were aimed at actually freeing up health professionals to move between member states, adding, ‘the best aspects of capitalism encourage innovation, reward inefficiency and efficacy and promote quality, enhancing the experience of the consumer’. South Africa’s health system was in ‘desperate need’ of all of these. Government should focus on these aspects of the private sector instead of trying to over-regulate it.

Specialists predict dire consequences

Dentists grind their teeth

Dr Chris Archer, CEO of the South African Private Practitioners Forum, predicted negative consequences for the country’s healthcare system if the CoN legislation was revived with no amendments except for the application date – as is expected. Citing increased costs, decreased competition and higher barriers to entry in the USA after a similar system was introduced, he said that local judges in the relatively recent dispensing doctors Constitutional Court challenge had wanted to know how restricting the number of providers in an area (through licensing) actually promoted access to healthcare services.

Echoing Pearmain, Archer said that new technology and restructuring the private health system with outreach satellites

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There seemed to be no cohesive plan at national level to manage healthcare demand.

Instead, a disproportionate emphasis was placed on the proposed CoN, a supply-side management tool.

Also speaking at the conference, the theme of which was ‘Converge, Connect, Co-create – Embracing Change’, Maretha Smit, CEO of the South African Dental Association, said there were less restrictive ways to bring healthcare to rural and other underserved geographical areas.

These included improved working conditions, incentivised employment, subsidies, rural allowances and tax rebates, plus ensuring that healthcare providers in rural areas could more easily earn continuing professional development (CPD) points. Lowering barriers to entry would encourage more people to consider healthcare careers. Examples included making it easier for foreign-qualified doctors to register (verification criteria

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sector to do medical and dental training, training students of rural origin, and allowing the private sector to employ doctors (at present no private hospital may employ a doctor). ‘We need to revisit the Health Professions Council of South Africa’s ethical rules and engage the private sector to help with facilities management,’ she asserted.

Maretha Smit, CEO of the SA Dental Associ­ ation.

were recently severely stiffened following intermittent incidents of corrupt and false documentation being submitted to the relevant Medical and Dental Professions Board committee), allowing the private

Pearmain said that the key issue was to work out how the country could bring together the pro-poor strength of the public health system with the technical capacity and higher quality of the private healthcare system.

Smit expressed concern that the medical profession would become disenfranchised if the CoN went ahead as proposed. ‘You

have to weigh up the constitutional rights of the patients, establishments and healthcare providers as well as the consumer rights of the patients,’ she said. If the certificate was issued ‘per facility’ it would artificially increase a medical practice’s value, leading to more ‘seller power’. However, if practitioners themselves were issued with the CoN, the regulations would artificially limit the market, resulting in increased ‘buyer power’. With the current critical shortage of healthcare practitioners, overregulation would discourage people from entering the medical profession, increase existing migration overseas and encourage career changes. Backing Pearmain, she said that market forces ‘respond most effectively to demand’.

Chris Bateman chrisb@hmpg.co.za S Afr Med J 2014;104(12):841-842.

DOI:10.7196/SAMJ.9119

New HASA board: The right mix at the right time The new board of the Hospital Association of South Africa (HASA), elec­ ted at its annual general meeting shortly after the association’s annual conference in Sandton this October, brings added depth and a wide variety of skills to the seismic shifts changing the face of healthcare delivery in South Africa.

Pledging her association to work with government in fulfilling its vision of increased access to healthcare, chairperson Melanie Da Costa (elected for a second term) said that HASA would continue to seek innovative ways to deliver private healthcare to more South Africans. She described HASA, which represents 80% of private hospital beds in the country, as ‘a national asset which we believe offers patients value for money and quality healthcare’. She said the election of its members came at an important time for the organisation, which was embracing change and helping government and other healthcare players ‘converge, connect and co-create’ new scenarios – a theme that defined its recent conference. HASA CEO

Dumisani Bomela said he expected the ‘highly functional and fruitful’ co-operation between his management and the board to continue, allowing his team to implement their strategic plans successfully.

The new HASA board of directors con­sists of Melanie Da Costa, Director: Strategy and Health at Netcare (Chairperson), Kamy Chetty, Strategic Relations and Health Policy at Life Healthcare and former Deputy Director, Service Delivery in the National Department of Health (one of the chief architects of the controversial Certificate of Need legislation) (Deputy Chairperson), Biren Valodia, Chief Marketing Officer at Mediclinic, Jacques du Plessis, MD, Hospitals at Netcare, Nkaki Matlala, Director: Government and Industry Affairs at Mediclinic, Steve Taylor, General Manager: Coastal Region at Life Healthcare, Otto Wypkema, CEO, National Hospital Network, Amil Devchand, Chief Operating Officer at Lenmed (all members), Tinnie van den Berg, Manager; Zuid Afrikaans Hospital (Treasurer), and Dumisani Bomela (HASA CEO and ex-officio member).

Chris Bateman chrisb@hmpg.co.za

Hospital Association of South Africa Chairperson and Netcare executive, Melanie da Costa. Picture: Chris Bateman.

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S Afr Med J 2014;104(12):842.

DOI:10.7196/SAMJ.9120

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OBITUARY

Lorna Macdougall, 1924 - 2014

Prof. Lorna Macdougall was one of the pioneers in paediatric oncology/haema­tology in Johannesburg and South Africa and a founder of CHOC (Children’s Haematology and Oncology Clinics), an NGO to support the families and children with cancer that has blossomed from being a local Johannes­ burg organisation to a national one over the years.

Born into a medical family in Glasgow, Scotland, her mother being one of the first female psychiatrists in that country, Lorna trained in medicine in Glasgow before spen­ ding some time as a medical officer in Kenya.

I have no doubt that her experiences there were responsible for her yearning to return to Africa after training as a paediatric haematologist in the USA and mana­ging a haematological laboratory in Buffalo, NY. Prof. John Hansen, then head of paed­ia­ trics at the University of the Wit­watersrand, enticed Lorna to join the Department of Paediatrics at Baragwanath Hospital (now Chris Hani Baragwanath Hospital) in 1975, where she participated in the research activities of the newly formed Metabolic and Nutrition Research Unit and slowly developed what was to become the largest paediatric oncology unit in South Africa. It was during this period that I came to know Lorna well, as we had offices opposite each other and would often spend the late afternoons talking about our patients and the issues of the day. Lorna was committed to ensuring that children with cancer or haematological disease from Soweto, and the many referred from neighbouring provinces and countries, received optimal care and support, particularly during the years of apartheid health­ care. Although her first love was paediatric haematology and she had published quite extensively on the immune changes in iron deficiency, she realised on arriving in Johannesburg that a major problem facing children with cancer was the lack of a dedicated team of appropriately trained paediatric oncologists and the facilities to care for these children. As a result of her enthusiasm and persistence, Goldfields SA

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funded the first of a number of renovations to develop the paediatric oncology wards at Baragwanath Hospital, much to the envy of the other paediatric subspecialties.

During Lorna’s years as head of paed­ia­ tric oncology/haematology at Baragwanath she was responsible for training a number of paediatric oncologists, who have become well known in various parts of the world or stayed in South Africa to continue the legacy she left on her retirement in 1989. I am sure that the thriving and well-staffed paediatric oncology unit created through her drive and personality is the envy of many in Africa.

It is perhaps one of the ironies of life that Lorna spent much of her spare time doing calligraphy, glass engraving and miniature painting, yet was to be frustrated by failing eyesight and hearing in the last few years of her life.

I believe that I can speak on behalf of all healthcare professionals who came into contact with Lorna, and say that oncology in Johannesburg and the children of Soweto are the poorer for her passing. We offer our condolences to her family overseas.

John Pettifor Emeritus Professor, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa john.pettifor@wits.ac.za

FORUM

CLINICAL PRACTICE

Recommendations for amniocentesis in HIV-positive women S N Constantatos, A H Boutall, C J Stewart Sonia Constantatos, MB ChB, Dip Obst (SA), Alison Boutall, MB ChB, DA (SA), and Chantal Stewart, MB ChB, FCOG, are based in the Department of Obstetrics and Gynaecology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa.

Corresponding author: S N Constantatos (drsoj@yahoo.co.uk)

There is limited literature on the known risk of HIV transmission during amniocentesis. Before the introduction of highly active antiretroviral therapy (HAART), amniocentesis was avoided owing to the increased risk of HIV transmission. Recent literature suggests that it is safe to perform amniocentesis in women on HAART with undetectable viral loads. In South Africa (SA), many women access antenatal care late in pregnancy and there is often insufficient time to attain undetectable viral loads within a pre-viability period. Guidelines and recommendations for invasive testing in HIV-positive women in the SA setting are lacking. This article provides recommendations to healthcare practitioners who are faced with an HIV-positive patient requiring amniocentesis.

S Afr Med J 2014;104(12):844-845. DOI:10.7196/SAMJ.8660

Aneuploidy is a major cause of perinatal death and childhood handicap.[1] Improved methods of screening for aneuploidy such as the nuchal translucency (NT) scan, first- and second-trimester serum biochemistry and assessment of fetal anatomy and markers by ultrasound at 18 - 22 weeks’ gestation have replaced maternal age, which is known to be a poor method of screening. With improved screening methods, there is a need for diagnostic tests such as a chorionic villous sample and amniocentesis to confirm or exclude aneuploidy. These invasive tests are associated with a risk of miscarriage, and should therefore only be carried out in high-risk pregnancies.

HIV and birth defects

The situation is complicated further if a woman at high risk for aneuploidy is also HIV-positive. Knowledge of the risks of HIV transmission to the fetus from invasive procedures is important to ensure adequate counselling and management.

More than half of the estimated 33 million people in South Africa (SA) living with HIV/AIDS are women, and most are of childbearing age.[2] The SA Department of Health study estimates that in 2011, 29.5% of pregnant women were HIV-positive. KwaZuluNatal recorded the highest HIV prevalence of 37.4%, while the Northern Cape recorded the lowest at 17%.[3] The use of highly active antiretroviral therapy (HAART) has led to a significant reduction in morbidity and mortality from HIV infection and a decline in motherto-child transmission (MTCT).

Globally, birth defects occur in approximately 2 - 3% of live births, although minor anomalies are more frequent.[4] The birth prevalence of serious defects is lower in industrialised countries than in developing countries. An HIV-positive woman is not at increased risk of having a child with a birth defect compared with the average population, even if she is on antiretroviral therapy (ART).[5,6]

HIV and amniocentesis

There is limited literature on the known risk of HIV transmission during amniocentesis. Before HAART, invasive procedures such as amniocentesis were avoided owing to the increased risk of MTCT.[7-12] Recent literature suggests that it is safe to perform amnio­

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centesis in women on HAART with suppressed viral loads (preferably undetectable) and when transplacental passage of the needle is avoided.[7,10-15] HIV counselling and testing at the booking antenatal visit is routine, and many patients will only discover their HIV status during the pregnancy. Unfortunately, in SA many women initiate antenatal care late in pregnancy – in a recent study of over 27 000 pregnancies in the Peninsula Maternity and Neonatal Service in the Western Cape, 62% of women booked after 20 weeks[16] – thus missing the opportunity for firsttrimester screening. All women, regardless of whether they have had first-trimester screening, will ideally be offered a fetal abnormality scan between 18 and 22 weeks if resources are available. If a fetal abnormality is detected and amniocentesis is offered, there is often insufficient time to attain an undetectable viral load within the pre-viability period (i.e. before the generally accepted cut-off period of 24 weeks).

Groote Schuur Hospital (GSH) experience

At GSH, Cape Town, we undertook a survey of a case series of 27 HIV-positive women who attended our genetics clinic over a 3-year period and accepted amniocentesis on the basis of screening tests that showed them to be at high risk. A total of 642 amniocenteses were undertaken over the period. Four per cent of these were in HIV-positive women, a small proportion because many HIV-positive patients declined amniocentesis after counselling and learning of the possible HIV transmission risk. The duration of HAART prior to amniocentesis, outcomes and postnatal care were recorded. In this group of 27 women, there were 6 pregnancy losses, 1 early neonatal death, 3 chromosomal abnormalities and 10 structural abnormalities.

Although there were no cases of vertical HIV transmission in the 21 liveborns, the number of patients was small and the duration of ART prior to amniocentesis varied widely from no treatment in 3 patients to more than 3 years of HAART in 4. Eighteen out of 21 patients had at least 10 days of HAART.

Discussion

All women should be able to opt for prenatal screening and diag­nosis, and for amniocentesis if required, regardless of their

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HIV status. It is a challenge to counsel patients about the risk of abnormality in their unborn child. In addition to this challenge, the risk of miscarriage and possible risk of HIV transmission associated with amniocentesis needs to be discussed in women who test positive for HIV. We know that the overall risk of HIV transmission when amniocentesis is performed in early pregnancy is very low, and the addition of HAART reduces this risk significantly. It is reasonable to deduce that the longer the patient has been on HAART prior to amniocentesis, the lower the chance of HIV transmission. However, it is unclear what the minimum duration of treatment should be, and very large numbers of patients would be required to deduce the potential transmission rate with any reliability. While it is recognised that one of the biggest limitations in all studies is the absence of a control group, it would be unethical to do randomised controlled trials in this setting.

As clinicians, we have a responsibility to the mother to offer care that is standardised and does not discriminate in the presence of HIV infection. However, we also have a responsibility to the fetus and should not be exposing that fetus to an unnecessary risk of HIV transmission.

As with any diagnostic test, there should be a strong indication to do invasive testing, and this should only be offered when the risk of an abnormality is high. The risk of miscarriage and possible HIV transmission in HIV-positive women undergoing amniocentesis needs to be weighed against the benefits of a prenatal diagnosis, all of which needs to be communicated clearly to the patient so that she can make an informed decision. For some patients, having a child with a disability is not an option, and the benefit of a prenatal diagnosis outweighs the risks associated with amniocentesis. Conversely, amniocentesis should probably be avoided in patients who would not accept termination of pregnancy if the karyotype is abnormal.

Recommendations for management

If an HIV-positive patient accepts amniocentesis after counselling and consideration of the risks, HAART should be initiated and the procedure delayed until the viral load is undetectable. If there is not enough time to attain an undetectable viral load, it is reasonable for the patient to be on HAART for as long as possible prior to amniocentesis, as long as she understands the possible risks.

The nature of the fetal abnormality may influence the decision to proceed with amniocentesis even when the viral load is not suppressed. If the abnormality is severe and will be associated with significant morbidity, exposing the fetus to a very low risk of HIV transmission will be outweighed by the benefit of a prenatal diagnosis.

Although not available in the state sector, and to many private patients because of the cost, it is worth noting that there is the option of having a non-invasive prenatal screening test (e.g. the Harmony test, which analyses cell-free DNA in the maternal blood and will identify 99% of fetuses with trisomy 21, 97% of fetuses with trisomy 18 and 92% of fetuses with trisomy 13).[17] This highly effective screening test does not carry the risk of miscarriage and HIV transmission. However, it does not identify other chromosomal abnormalities, and the high cost makes it inaccessible to many patients.

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Summary

• There must be a strong indication to offer invasive testing. More effective screening methods such as an NT scan and a detailed fetal ultrasound scan looking for markers and defects must replace maternal age, which we know to be a poor method of screening.

• All women who have been offered and accept invasive testing must have an HIV test as part of their routine work-up.

• It is probably safe to perform amniocentesis in HIV-positive women on HAART, as long as their viral load is low (preferably undetectable) and transplacental passage of the needle is avoided.

• It may not be possible to wait for the viral load to become undetectable, and in carefully selected cases amniocentesis may be performed when the viral load is not suppressed.

• The risks of the amniocentesis must always be weighed against the benefit of a prenatal diagnosis.

• Amniocentesis should not be performed on HIV-positive women who are not on HAART. • Careful consideration should be given to the patient who would not terminate the pregnancy if the karyotype is abnormal. In this case, invasive testing should preferably be avoided.

• Third-trimester amniocentesis, chorionic villous sampling and cordocentesis are not recommended in HIV-positive women.

• Consider a non-invasive – though costly – prenatal screening test.

1. Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn 2011;31(1):7-15. [http://dx.doi.org/10.1002/pd.2637] 2. World Health Organization. UNAIDS: AIDS Epidemic Update. Geneva: World Health Organization, 2009. http://data.unaids.org/pub/report/2009 (accessed 1 March 2011).

3. Department of Health. National Antenatal Sentinel HIV and Syphilis Prevalence Survey in South Africa. 2011. Pretoria: Department of Health, 2012. http://www.doh.gov.za/docs/reports/2011/hiv_ aids_survey.pdf (accessed 25 February 2014).

4. Woods DL, ed. Birth defects: Counselling and caring for children with birth defects. Perinantal Education Programme, 2010. http://www.scribd.com/doc/31657154/Birth-Defects-Free-OnlineEdition (accessed 13 February 2014).

5. Nam Publications. National Aids Manual, 2014. http://www.aidsmap.com/Side-effects-and-birthdefects/page/1730605/ (accessed 1 March 2014).

6. European Collaborative Study. Does highly active antiretroviral therapy increase the risk of congenital abnormalities in HIV-infected women? J Acquir Immune Defic Syndr 2005;40(1):116-118. [http:// dx.doi.org/10.1097/01.qai.0000156854.99769.a5] 7. Shapiro DE, Sperling RS, Mandelbrot L, Britto P, Cunningham BE. Risk factors for perinatal human immunodeficiency virus transmission in patients receiving zidovudine prophylaxis. Pediatric AIDS Clinical Trials Group protocol 076 Study Group. Obstet Gynecol 1999;94(6):897-908. [http://dx.doi. org/10.1016/S0029-7844(99)00451-2] 8. Mandelbrot L, Mayaux MJ, Bongain A, et al. Obstetric factors and mother-to-child transmission of human immunodeficiency virus type 1: The French perinatal cohorts. Obstet Gynecol 1996;175(3):661667. [http://dx.doi.org/10.1053/ob.1996.v175.a75478] 9. Tess BH, Rodrigues LC, Newell ML, Dunn DT, Lago TDG. Breastfeeding, genetic, obstetric and other risk factors associated with mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil. AIDS 1998;12(5):513-520. [http://dx.doi.org/10.1097/00002030-199805000-00013] 10. Maiques V, García-Tejedor A, Perales A, Córdoba J, Esteban RJ. HIV detection in amniotic fluid samples: Amniocentesis can be performed in HIV pregnant women? Eur J Obstet Gynaecol Reprod Biol 2003;108(2):137-141. [http://dx.doi.org/10.1016/S0301-2115(02)00405-0] 11. Mandelbrot L. Amniocentesis and mother-to-child human immunodeficiency virus transmission in the Agence Nationale de Recherches sur le SIDA et les Hepatites Virales French Perinatal Cohort. Am J Obstet Gynecol 2009;200(2):160.e1-160.e9. [http://dx.doi.org/10.1016/j.ajog.2008.08.049] 12. Bucceri AM, Somigliana E, Vignali M. Early invasive diagnostic techniques during pregnancy in HIVinfected women. Acta Obstet Gynecol Scand 2001;80(1):82-82. [http://dx.doi.org/10.1080/791201840] 13. Somigliana E, Bucceri AM, Tibaldi C, et al. Early invasive diagnostic techniques in pregnant women who are infected with the HIV: A multicenter case series. Am J Obstet Gynecol 2005;193(2):437-442. [http://dx.doi.org/10.1016/j.ajog.2004.12.087] 14. Coll O, Suy A, Hernandez S, et al. Prenatal diagnosis in human immunodeficiency virus-infected women: A new screening program for chromosomal anomalies. Am J Obstet Gynecol 2006;194(1):192198. [http://dx.doi.org/10.1016/j.ajog.2005.06.045] 15. Ekoukou D, Khuong-Josses M, Ghibaudo N, Mechali D, Rotten D. Amniocentesis in pregnant HIVinfected patients: Absence of mother-to-child viral transmission in a series of selected patients. Eur J Obstet Gynaecol Reprod Biol 2008;140(2):212-217. [http://dx.doi.org/10.1016/j.ejogrb.2008.04.004/] 16. Beauclair R. Adverse outcomes associated with timing of antenatal care initiation: A retrospective cohort study of pregnancies in Cape Town, South Africa. 2012. Master’s thesis. Cape Town: School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, 2012:Part C: Manuscript-6-8.

17. Nicolaides KH, Syngelaki A, Ashoor G, et al. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol 2012;207(5):374.e1-374.e6. [http:// dx.doi.org/ 10.1016/j.ajog.2012.08.033]

Accepted 21 July 2014.

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CLINICAL PRACTICE

Newborns should be receiving premedication before elective intubation M S Raban, Y Joolay, A R Horn, M C Harrison Dr Shukri Raban completed his neonatal fellowship at Groote Schuur Hospital, Cape Town, South Africa, and qualified as a neonatologist in 2012. His main interest is improving infant nutrition, and he is currently involved in research to improve breastmilk provision in the neonatal unit. Additional interests include clinical governance, infection surveillance and less invasive measures to provide surfactant to infants. Dr Yaseen Joolay is a neonatologist at Groote Schuur Hospital. An avid fan of innovative technologies, his current interests are quality improvement, standardisation of practices and the appropriate application of technologies in neonatal care. Assoc. Prof. Alan Horn is a neonatologist at Groote Schuur Hospital. He was recently awarded a PhD for his research on hypoxic ischaemic encephalopathy – he has a special interest in the use of amplified electroencephalography and therapeutic cooling and has published work in this field. Assoc. Prof. Michael Harrison is a neonatolo­gist and head of the Division of Neonatal Medicine, Groote Schuur Hospital and Department of Paediatrics, Faculty of Health Sciences, University of Cape Town, to which all the authors are affiliated. He completed his paediatric and subspecialty training in the UK. He is an advocate for clinical governance and places strong emphasis on translational research.

Corresponding author: M S Raban (shukriraban@yahoo.co.uk)

Background. Intubation is a common neonatal procedure. Premedication is accepted as a standard of care, but its use is not universal and wide variations exist in practice.

Objective. To evaluate current practices for premedication use prior to elective neonatal intubation in South Africa (SA).

Method. We invited 481 clinicians to participate in a cross-sectional web-based survey.

Results. We received responses from 28.3% of the clinicians surveyed; 54.1% were from the private sector and 45.9% from the state sector.

Most respondents worked in medium-sized neonatal units with six to ten beds. Most paediatricians (76.0%) worked in the private sector, and 78.6% of neonatologists in the state sector. Premedication was practised by 71.9% of the respondents, but only 38.5% of neonatal units had a written policy. Sedatives were used for premedication by 63.2% of the respondents. Midazolam (41.5%), morphine (34.0%) and ketamine (20.8%) were most commonly used. Muscle relaxants and atropine were not routinely administered. Suxamethonium was the muscle relaxant of choice. Varied combinations of agents or single agents were used. Midazolam used alone was the preferred option.

Conclusion. This first survey of premedication for neonatal intubation in SA revealed variations in practice, with a minority of clinicians following a written policy. The findings can be used to benchmark practice and inform the design of local collaborative trials aimed at determining optimal premedication prior to neonatal intubation. The survey demonstrates clinicians’ reluctance to participate in surveys, suggesting a need for a national collaborative network to obtain representative data.

S Afr Med J 2014;104(12):846-849. DOI:10.7196/SAMJ.8305

Endotracheal intubation is a common neonatal procedure and essential for the provision of neonatal intensive care. The procedure induces noxious stimuli often associated with adverse physiological events such as raised intracranial pressure,[1] hypoxaemia and cardiovascular instability.[2] Premedication regimens may include a vagolytic to reduce vagal-induced bradycardia, a narcotic/sedative agent that attenuates increases in systemic blood pressure, and a muscle relaxant that attenuates increases in intracranial pressure.[3] Recent studies have shown that premedication for elective and semi-urgent intubation of infants significantly improves intubation conditions, decreases the time and number of attempts needed to complete the intubation procedure, and minimises the potential for intubation-related airway trauma.[4-6] However, despite the growing body of evidence and acceptance of premedication as a standard of care, its use is still not universal, and wide variations occur in practice.[7,8] Premedication practices have been surveyed in Europe,[7,9,10] North America[8,11] and Australia.[12] The European surveys had a profound effect on current practice. Whyte et al.[7] demonstrated in a study conducted in 1998 that 63% of UK neonatal units did not use

846

premedication prior to intubation, their study prompting much discussion. A decade later, when the survey was repeated, ≥90% of neonatal units had adopted premedication as standard of care.[9,10] Because current neonatal premedication practices have not previously been surveyed in South Africa (SA), we designed a survey with the objective of determining the current practice and standard of care. This survey may provide data that could inform the design of collaborative trials and/or stimulate debate that ultimately leads to change and standardisation of practice.

Methods

The study was designed as a cross-sectional survey of clinicians working in SA state and private neonatal intensive care units. This research was approved by the Human Research Ethics Committee, Faculty of Health Sciences, University of Cape Town.

Potential participants were identified from an online listing of 147 neonatal intensive care units in hospitals across SA on the Medpages directory website.[13] The names and contact details of the clinicians working in those units were obtained by searching the websites of the respective hospitals. Additional names and contact details of clinicians involved in neonatal care

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were obtained from a local departmental database. Clinicians who did not treat neonates in their practice were excluded.

Clinicians did not receive incentives to participate in the survey.

The survey questionnaire was created and hosted using Survey Monkey, an online survey website. The questionnaire enabled compilation of data regarding use of premedication and whether a written policy existed for sedating preterm infants before elective or semi-elective intubation.

The questionnaire was designed to determine which agent/s were most used for premedication, as well as the doses used. The questionnaire was brief, taking no more than 3 minutes to complete.

Each question addressed a single point and in most cases required a ‘yes’ or ‘no’ response. An e-mail containing an individualised link to the survey was sent to 481 clinicians on 1 October 2013. The Survey Monkey collector tool collected all responses anonymously and automatically sent reminder e-mails to those who had not responded. Survey collection closed on 14 November 2013.

Results

We received responses to 136 of the 481 emails sent (28.3%). The characteristics of the respondents surveyed are shown in Table 1. Sixty-six responses (54.1%) were from clinicians in the private sector and 56 (45.9%) from those in the state sector. The majority of respondents were paediatricians or neonatologists. The majority of paediatricians (76.0%) worked in the private sector, whereas 78.6% of neonatologists worked in the state sector, typically in medium-sized neonatal units with six to ten beds.

A subgroup analysis comparing pre­ medication practices between the public and private sectors is reported in Table 2. A written policy was used by a minority of clinicians, more often in the public sector (p<0.0001).

Premedication prior to intubation was practised by 71.9% of respondents; however, only 38.5% of neonatal units had a written policy. The respondents routinely used sedatives for premedication, but not Table 2. Subgroup analysis Premedication practice

Data analysis

Responses were exported to a Microsoft Excel file. Data were analysed with Stata version 12 (Stata Corporation, USA). Chisquare and Fisher’s exact tests were used for comparison of categorical variables.

Descriptive results were expressed as numbers and proportions (%). A p-value of <0.05 was considered significant.

muscle relaxants or atropine. These data are reported in Table 3 and Fig. 1. Midazolam, morphine and ketamine were the most commonly used sedative agents (Fig. 2).

When muscle relaxants were administered, suxamethonium (95.2%) was the muscle relaxant of choice.

Table 4 illustrates varied combinations of agents or single agents used for premedication. Seven premedication drugs were used in 16 different combinations/ regimens, utilising one to three drugs.

Midazolam was the drug most commonly used as a single agent.

Table 5 illustrates the drug dose ranges. Most respondents stated specific doses for the choice of drug used: 33.3% speci­ f ied a morphine dose of 0.1 mg/ kg, whereas 39.0% said that they would administer a dose of 0.2 mg/kg. Midazolam dosing varied, respondents using doses of 0.1 mg/kg (36.4%), 0.15 mg/kg (13.6%), 0.2 mg/kg (22.7%) and 0.4 mg/kg (4.5%).

For suxa­methonium, 55.0% of respondents used a dose of 2 mg/kg.

Private sector, n (%)

Public sector, n (%)

p-value

Written policy present

15 (31.9)

32 (68.0)

<0.0001

Routine use of any premedication agent

46 (52.9)

41 (47.1)

0.8

Routine use of sedatives

25 (45.5)

30 (54.6)

0.13

Routine use of muscle relaxants

10 (47.6)

11 (52.4)

0.62

Routine use of atropine

15 (45.5)

18 (54.6)

0.315

Table 1. Characteristics of neonatal units surveyed (N=136) n (%) Nature of practice Private health sector

66 (54.1)

Public health sector

56 (45.9)

Only when bradycardic

11.8%

Rank Medical officer

9 (6.6)

Registrar

6 (4.4)

Paediatrician

78 (57.4)

Neonatologist

28 (20.6)

Other specialist

5 (3.7)

Not a medical doctor

10 (7.4)

Never

49.4%

Routine

38.8%

ICU beds 0

3 (2.5)

1-5

35 (28.7)

6 - 10

50 (41.0)

>10

34 (27.9)

0

10

20

30 Percentage

Fig. 1. Atropine use for premedication.

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40

50

60

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Table 3. Premedication practices Premedication practice

Yes, n (%)

No, n (%)

Written policy

47 (38.5)

75 (61.5)

Use of premedication

87 (71.9)

34 (28.1)

Routine use of sedatives

55 (63.2)

32 (36.8)

Routine use of muscle relaxants

21 (24.4)

65 (75.6)

Table 4. Combinations of premedication used Agents

Respondents (N=87) n (%)

Midazolam + suxamethonium + atropine

1 (1.15)

Midazolam + atropine (when bradycardic)

5 (5.7)

Midazolam alone

16 (18.4)

Morphine + suxamethonium + atropine

7 (8.0)

Morphine + atropine

2 (2.3)

Morphine alone

7 (8.0)

Morphine + atropine (when bradycardic)

2 (2.3)

Ketamine + suxamethonium + atropine

6 (6.9)

Ketamine + cisatricurium + atropine

1 (1.15)

Ketamine + atropine

4 (4.6)

Fentanyl + suxamethonium + atropine

1 (1.15)

Propofol alone

1 (1.15)

Suxamethonium alone

1 (1.15)

Suxamethonium + atropine

4 (4.6)

Atropine alone

7 (8.0)

Atropine when bradycardic

3 (3.4)

Answered ‘yes’ for premed, no agents ticked

19 (21.8)

Table 5. Doses for premedication drugs Drug

Dose

Fentanyl

10 µg/kg

Ketamine

1 - 2 mg/kg

Midazolam

0.05 - 0.4 mg/kg

Morphine

0.05 - 0.2 mg/kg

Propofol

1 - 2 mg/kg

Suxamethonium

1 - 2 mg/kg

Discussion

A greater understanding of neonatal pain and the knowledge that noxious stimuli such as intubation may have long-term deleterious effects[13] have prompted consensus statements[14-16] advocating the use of premedication as standard of care.

This study illustrates that almost 30% of the SA clinicians surveyed were not administering premedication to infants before elective or semi-elective intubation,

in stark contrast to practice in the UK or Australasia, where recent surveys[9,10,12] indicate that >90% of units are providing premedication. No consensus exists regarding the choice of agent/s, their dose/s or the ideal route of administration,[6] mirroring the findings of the present study and other surveys.[7-12] Suxamethonium, as in other national surveys,[7-12] was the most commonly used muscle relaxant and is currently considered to be the best choice[17] because of its rapid onset, short duration of action and good side-effect profile.

In contrast to findings in the other national surveys,[7-12] midazolam was the preferred sedative in this SA study. Many participants used midazolam as the only premedication drug. Midazolam, a short-acting benzo­ diazepine with sedative properties, is inappropriate[17] because it has no analgesic properties. There are additional pitfalls to the use of midazolam as a single agent for intubation: Harte et al.,[18] examining the

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haemodynamic effect and pharmokinetic properties of midazolam, demonstrated no mitigation of the physiological changes attributed to intubation and found that the drug was associated with serious adverse effects during intubation. The use of midazolam has also been associated with hypotension and adverse neurological outcomes.[19,20] A Cochrane review found no evidence to support the use of midazolam as a sedative for infants, particularly preterm ones.[21] Infants receiving midazolam had longer hospital stays, and there were more adverse effects in the midazolam group when compared with placebo.[21] A survey of premedication practices in the UK by Singh et al.[22] found the combin­ ation of fentanyl, atropine and suxameth­ onium to be the most common, followed by morphine, atropine and suxamethonium. A recent randomised controlled trial (RCT) in which either morphine alone or placebo was given 5 minutes before intubation demon­ strated inability of morphine to reduce either the adverse physiological changes attributed to intubation or the time required to complete the intubation process.[23] Moreover, safety concerns regarding the use of morphine for premedication in preterm infants have been raised, as it has been associated with prolonged amplified electroence­ phalo­ graphy (aEEG) depression, inde­ pendent of blood pressure changes.[24] Fen­ tanyl is preferred to morphine, as its more rapid onset of action may improve pain control during intubation.[25] Hamon et al.[26] have shown that short-term fentanyl infusion in preterm infants is not associated with changes in systemic and cerebral perfusion pressures.

Propofol was listed by one respondent as their premedication drug of choice. Propofol is a hypnotic agent without anaesthetic properties. Spontaneous breathing effort is maintained during the intubation process.

Ghanta et al.[5] compared propofol with a combination of morphine, atropine and suxamethonium, which took 5 times longer to prepare. They reported faster intubation times, better oxygen saturation maintenance and shorter recovery times in the propofol group, and there was no difference in bradycardia or hypotension between the two groups.[5] A paucity of data remains regarding the use of propofol in infants; the Cochrane review by Shah et al.[27] only included the 63 infants in Ghanta et al.’s RCT. There are also significant concerns regarding the safety of propofol, Welzing et al.[28] demonstrating a significant drop in arterial blood pressure when propofol was injected as a fast push. Current pharmacokinetic

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Propofol

1.9%

Ketamine

20.8%

Midazolam

41.5%

Fentanyl

1.9%

Morphine

34% 0

10

20

30

40

50

Percentage Fig. 2. Sedative agents used.

studies on the use of propofol in infants indicate marked inter-individual variability and reduced clearance of propofol.[29] The Exploratory Propofol Dose Finding Study in Neonates (NEOPROP) is currently under way and aims to evaluate pharmacokinetics and pharmacodynamics of propofol and to determine the optimal dose in infants.[30] Following identification of a safe dose, RCTs are needed to assess safety and efficacy of propofol, both as a single agent and in combination with an analgesic agent.

The UK and Australasian surveys enjoyed high response rates from clinicians surveyed.

The low rate of response to the current survey may not reflect true premedication practices, as SA doctors respond poorly to mail surveys despite high internet penetration, which influenced our decision to conduct a web-based survey.[31] This is the first study to survey premedication practice prior to elective neonatal intubation in SA. The findings highlight a wide variation in practices and the need for written policies, particularly in the private sector. Further research is needed to determine the outcomes associated with premedication, the most appropriate agent/s and their optimal dose/s. A national network of neonatal units needs to be established to ensure representative data collection.

The findings of this study could be used to inform local collaborative trials aimed

at studying premedication for intubation in the neonatal period. Importantly, this survey may stimulate debate and discussion, culminating in a national premedication practice guideline.

Acknowledgements. The authors thank all the participants for providing data for this survey.

1. Friesen RH, Honda AT, Thieme RE. Changes in anterior fontanel pressure in preterm neonates during tracheal intubation. Anesth Analg 1987;66(9):874-878. [http://dx.doi. org/10.1213/00000539-198709000-00012] 2. Kelly MA, Finer NN. Nasotracheal intubation in the neonate: Physiologic responses and effects of atropine and pancuronium.

J Pediatr 1984;105(2):303-309. [http://dx.doi.org/10.1016/ S0022-3476(84)80137-7] 3. Mayock DE, Gleason CA. Pain and sedation in the NICU. Neoreviews 2013;14(1):e22-e31. [http://dx.doi.org/10.1542/neo.14-1-e22] 4. Pereira e Silva Y, Gomez RS, Marcatto J, Maximo TA, Barbosa RF, Simões e Silva AC. Morphine versus remifentanil for intubating preterm neonates. Arch Dis Child Fetal Neonatal Ed 2007;92(4):F293–F294. [http://dx.doi.org/10.1136/adc.2006.105262] 5. Ghanta S, Abdel-Latif ME, Lui K, Ravindranathan H, Awad J, Oei J. Propofol compared with the morphine, atropine, and suxamethonium regimen as induction agents for neonatal endotracheal intubation: A randomized controlled trial.

Pediatrics 2007;119(6):e1248-e1255. [http://dx.doi.org/10.1542/ peds.2006-2708] 6. Carbajal R, Eble B, Anand KJS. Premedication for tracheal intubation in neonates: Confusion or controversy? Semin Perinatol 2007;31(5):309-317. [http://dx.doi.org/10.1053/j. semperi.2007.07.006] 7. Whyte S, Birrell G, Wyllie J, Woolf A. Premedication before intubation in UK neonatal units. Arch Dis Child Fetal Neonatal Ed 2000;82(1):F38-F41. [http://dx.doi.org/10.1136/fn.82.1.F38] 8. Sarkar S, Schumaker RE, Baumgart S, Donn SM. Are newborns receiving premedication before elective intubation? J Perinatol 2006;26(5):286-289. [http://dx.doi.org/10.1038/sj.jp.7211499] 9. Kelleher J, Mallya P, Wyllie J. Premedication before intubation in UK neonatal units: A decade of change? Arch Dis Child Fetal Neonatal Ed 2009;9(4):F332-F335. [http://dx.doi.org/10.1136/ adc.2008.154518] 10. Chaudhary R, Chonat S, Gowda H, Clarke P, Curley A. Use of premedication for intubation in tertiary neonatal units in the

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United Kingdom. Paediatr Anaesth 2009;19(7):653-658. [http:// dx.doi.org/10.1111/j.1460-9592.2008.02829.x] 11. Ziegler JW, Todres ID. Intubation of newborns (Letter). Am J Dis Child 1992;146(2):147-149.

12. Wheeler B, Broadbent R, Reith D. Premedication for neonatal intubation in Australia and New Zealand: A survey of current practice. J Paediatr Child Health 2012;48(11):997-1000. [http:// dx.doi.org/10.1111/j.1440-1754.2012.02589.x] 13. Medpages. South Africa – Hospital Depts – Neonatal ICU – Total records per region. http://medpages.co.za (accessed 15 August 2011).

14. American Academy of Pediatrics, Committee on Fetus and Newborn; American Academy of Pediatrics, Section on Surgery; Canadian Paediatric Society, Fetus and Newborn Committee.

Prevention and management of pain in the neonate: An update [published correction appears in Pediatrics 2007;119(2):425].

Pediatrics 2006;118(5):2231-2241. [http://dx.doi.org/10.1542/ peds.2006-2277] 15. Kumar P, Denson SE, Mancuso TJ, and Committee on Fetus and Newborn, Section on Anesthesiology and Pain Medicine.

Premedication for nonemergency endotracheal intubation in the neonate. Pediatrics 2010;125(3):608-615. [http://dx.doi. org/10.1542/peds.2009-2863] 16. Anand KJS; International Evidence-Based Group for Neonatal Pain. Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med 2001;155(2):173-180. [http://dx.doi.org/10.1001/ archpedi.155.2.173] 17. Barrington KJ; Canadian Paediatric Society Fetus and Newborn Commitee. Premedication for endotracheal intubation in the newborn infant. Paediatr Child Health 2011;16(3):159-164.

18. Harte GJ, Gray PH, Lee TC, Steer PA, Charles BG. Haemodynamic responses and population pharmacokinetics of midazolam following administration to ventilated, preterm neonates. J Paediatr Child Health 1997;33(4):335-338. [http:// dx.doi.org/10.1111/j.1440-1754.1997.tb01611.x] 19. Jacqz-Aigrain E, Daoud P, Burtin P, et al. Placebo-controlled trial of midazolam sedation in mechanically ventilated newborn babies. Lancet 1994;344(8923):646-650. [http://dx.doi. org/10.1016/S0140-6736(94)92085-0] 20. Anand KJS, McIntosh N, Lagercrantz H, et al. Analgesia and sedation in preterm neonates who require ventilatory support: Results from the NOPAIN trial. Arch Pediatr Adolesc Med 1999;153(4):331-338. [http://dx.doi.org/10.1001/ archpedi.153.4.331] 21. Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database of Systematic Reviews 2012, Issue 6. Art. No.: CD002052. [http://dx.doi.org/10.1002/14651858.CD002052. pub2] 22. Singh Y, Lester M, Ng V, Miall L. Premedication for neonatal intubation: Current practice in the tertiary neonatal units in the United Kingdom. Arch Dis Child 2012;97(Suppl 2):A1-A539. [http://dx.doi.org/10.1136/archdischild-2012-302724.1636] 23. Lemyre B, Doucette J, Kalyn A, Gray S, Marrin M. Morphine for elective endotracheal intubation in neonates: A randomized trial. BMC Pediatr 2004;4:20. [http://dx.doi.org/10.1186/14712431-4-20] 24. Norman E, Wikström S, Rosén I, Fellman V, HellströmWestas L. Premedication for intubation with morphine causes prolonged depression of electrocortical background activity in preterm infants. Pediatr Res 2013;73(1):87-94. [http://dx.doi. org/10.1038/pr.2012.153] 25. Brunson LL, Lazo JS, Parker KL, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw Hill, 2006.

26. Hamon I, Hascoet JM, Debbiche A, Vert P. Effects of fentanyl administration on general and cerebral haemodynamics in sick newborn infants. Acta Paediatr 1996;85(3):361-365. [http:// dx.doi.org/10.1111/j.1651-2227.1996.tb14033.x] 27. Shah PS, Shah VS. Propofol for procedural sedation/ anaesthesia in neonates. Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No.: CD007248. [http://dx.doi. org/10.1002/14651858.CD007248.pub2] 28. Welzing L, Kribs A, Eifinger F, Huenseler C, Oberthuer A, Roth B. Propofol as an induction agent for endotracheal intubation can cause significant arterial hypotension in preterm neonates. Pediatric Anesthesia 2010;20(7):605-611. [http:// dx.doi.org/10.1111/j.1460-9592.2010.03330.x] 29. Allegaert K. Is propofol the perfect hypnotic agent for procedural sedation in neonates? Curr Clin Pharmacol 2009;4(2):84-86. [http://dx.doi.org/10.2174/157488409788184927] 30. Thewissen L. Exploratory Propofol Dose Finding Study in Neonates (NEOPROP). ClinicalTrials.gov identifier: NCT01621373 http://clinicaltrials.gov/show/NCT01621373.

31. Joolay Y, Horn AR, Harrison MC. Therapeutic hypothermia and hypoxic ischaemic encephalopathy: Opinion and practice of paediatricians in South Africa. J Perinatal Med 2012;40(4):447453. [http://dx.doi.org/10.1515/jpm-2011-0292]

Accepted 14 August 2014.

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CLINICAL PRACTICE

The structured communication tool SBAR (Situation, Background, Assessment and Recommendation) improves communication in neonatology M Raymond, M C Harrison Meriel Raymond is a UK-trained general practitioner. The project described in this article was undertaken as part of the NHS Improving Global Health Scheme, in the Division of Neonatal Medicine at Groote Schuur Hospital, Cape Town, South Africa. She is returning to work in South Africa in a rural hospital setting in 2015, to expand her interest in tropical and developing world medicine. Michael Harrison is Head of the Division of Neonatal Medicine. He is a Fellow of the Royal College of Paediatrics and Child Health, has dual accreditation in paediatrics and neonatal medicine, is currently Vice-President of the United South African Neonatal Association, and is fully committed to making a significant contribution to one of the key Millennium Development Goals of reducing neonatal mortality. He has directed his research efforts into making real, translational effects on the outcomes of babies born prematurely in South Africa.

Corresponding author: M Raymond (mellieraymond@gmail.com)

Background. Effective communication, co-operation and teamwork have been identified as key determinants of patient safety. SBAR (Situation, Background, Assessment and Recommendation) is a communication tool recommended by the World Health Organization and the UK National Health Service. SBAR is a structured method for communicating critical information that requires immediate attention and action, contributing to effective escalation of management and increased patient safety. To our knowledge, this is the first study showing use of SBAR in South Africa (SA).

Objective. To determine the effectiveness of adopting the SBAR communication tool in an acute clinical setting in SA. Methods. In the first phase of this study, neonatal nurses and doctors at Groote Schuur Hospital, Cape Town, were gathered in a focus group and given a questionnaire asking about communication in the neonatal department. Neonatal nurses and doctors were then trained to use SBAR. Results. A telephone audit demonstrated an increase in SBAR use by registrars from 29% to 70% when calling consultants for help. After training, the majority of staff agreed that SBAR had helped with communication, confidence, and quality of patient care. There was qualitative evidence that SBAR led to greater promptness in care of acutely ill patients.

Conclusions. Adopting SBAR was associated with perceived improvement in communication between professionals and in the quality and safety of patient care. It is suggested that this simple tool be introduced to many other hospitals in SA. S Afr Med J 2014;104(12):850-852. DOI:10.7196/SAMJ.8684

Effective communication, co-operation and team­ work have been identified as key determinants of patient safety. SBAR (Situation, Background, Assessment and Recommendation) is a structured method for communicating critical information that requires immediate attention and action. It contributes to effective escalation of management and increased patient safety and is recommended by the World Health Organization (WHO)[1] and the UK National Health Service.[2] WHO Millennium Development Goal 4 is aimed at reducing the number of deaths of children under the age of 5 years by two-thirds from 95/1 000 to 31/1 000 by 2015.[3] In South Africa (SA), early neonatal mortality accounts for 33% of deaths of children under the age of 5.[4] In root-cause analysis of nationally reported cases of infant death and permanent disability in the USA, communication issues among team members were the single most important factor identified.[5] Faulty or delayed communication was considered the primary cause of adverse events in 72% of cases.

The WHO Collaborating Centre on Patient Safety Solutions[1] has suggested a ‘standardized approach to hand-over communication between staff ’, proposing the use of the SBAR technique. This can be simplified as follows:[6]

850

• • • •

Situation: What is going on with the patient?

Background: What is the clinical background or context?

Assessment: What do I think the problem is?

Recommendation: What would I do to correct it?

The use of SBAR has been shown to increase the impact of telephone referrals between doctors,[7] and decreases the time taken for junior doctors to relay key facts in an emergency situation.[8] Doctors are assisted in making clinical decisions from a nursing report when SBAR is used.[9] Most notably, SBAR decreases unexpected patient deaths when taught to nursing staff, along with training in airway-breathing-circulation resuscitation.[10] SBAR is currently in use in the UK,[2] Europe,[10] the USA[7] and Australia.[8]

Objective

To determine the effectiveness of adopting the SBAR communication tool in an acute clinical setting in SA.

Methods

The nursery at Groote Schuur Hospital, Cape Town, is a 75-bed tertiary unit that admits over 2 000 infants a year, of whom about 530 have a birth weight of <1 500 g.

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Fig. 1. Neonatal escalation SBAR table, adapted.[11] (SBAR = Situation, Background, Assessment and Recommendation.)

SBAR training, over a number of sessions, was given to 95% of neonatal doctors and 87% of neonatal nursing staff in November 2013. Each session lasted 1 hour and included case scenario practice. Nurses and doctors were trained separately.

Posters and stickers were placed by telephones to remind staff to use the structure when communicating. A neonatal SBAR escalation table was developed to encourage standardisation of information over the telephone (Fig. 1).

Laminated sheets were developed to act as a prompt for nursing handover, as were escalation and handover stickers for the patient notes. Tools for obstetric training, together with handover and escalation stickers, were also developed and trialled. Links to all these resources can be found on the internet (http://www. tvwleadershipacademy.nhs.uk/improvingglobal-health-through-leadershipdevelopment).

A qualitative questionnaire was admini­ stered 1 month after training to evaluate perceptions of SBAR in the nursery. Nurses and doctors were asked how often they were using SBAR and whether it had helped with certain domains, with the option of replying agree strongly/agree slightly/neutral/disagree slightly/disagree strongly. They were also

Table 1. Results from second neonatal staff questionnaire Nurses (%)

Doctors (%)

Using SBAR daily or every other day

76

76

Agree has affected clinical practice

44

76

Ease of communication

86

94

Asking for help

86

71

Confidence with structure

86

94

Confidence with making a recommendation

86

94

Doctors giving clearer instruction

76

53

Doctors attending more promptly

79

41

Quality of patient care

86

88

Training and learning

77

82

Agree has helped with

Senior perception Juniors’ confidence with structure

65

Juniors’ confidence with diagnosis

59

Being able to give clearer instructions

100

Being able to attend more promptly

71

Agree should be taught to incoming staff

90

100

SBAR = Situation, Background, Assessment and Recommendation.

asked for examples of how SBAR had helped in a clinical situation.

A telephone audit was performed before and 2 weeks after SBAR training. On-call consultants

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covering the nursery recorded the outcome of their telephone consultations and whether SBAR was used. Fifty calls were compared over two 3-week periods before and after training.

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Ethics approval for this study was obtained from the Human Research Ethics Committee, Faculty of Health Sciences, University of Cape Town.

Results

The telephone audit demonstrated an increase in SBAR use from 29% before training to 70% after training.

The questionnaires, filled in 1 month after SBAR training, were returned by 21 nurses and 17 doctors, of whom 70% and 100%, respectively, had attended SBAR training. The results are set out in Table 1.

There was qualitative evidence that SBAR had facilitated prompter patient care and senior review. The following were responses to the question ‘Describe a clinical situation in which SBAR was helpful’: ‘There was an infant on nasal ventilation who was experiencing apnoeas with no breath movement. The doctor was informed immediately ... and intervention was dealt with appropriately and effectively.’ (Neonatal nurse) ‘Was on-call: the registrar was busy in a different department. I was called to theatre for C-section – baby came out and needed resuscitation. I could give clear explanation of the scenario to the registrar and he could respond with clear instructions using SBAR.’ (Neonatal intern) ‘New admission to nursery – very unstable – understood issues and realised I needed to attend promptly.’ (Neonatal consultant) There was additional qualitative evidence that SBAR had facilitated patient transfer, structured ward rounds and training.

Discussion

SBAR is a structured method for communicating critical information that requires immediate attention and action, contributing to effective escalation of management and increased patient safety. It reduces the barrier to effective communication across different hierarchies and levels of staff by acting as a memory prompt that encourages prior preparation for communication.

To our knowledge, this is the first study showing implementation of the use of SBAR in SA. The concept was successfully implemented despite certain challenges, e.g. reluctance on the part of nursing staff to write in the notes and use the handover stickers owing to

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perceived hierarchy, lack of space in the patient record(s), and time constraints. As a result, laminated handover prompts were developed to enable standardised verbal handover. As seen in Table 1, the nurses embraced regular use of SBAR. Among doctors, the juniors were the most enthusiastic about using SBAR. SBAR was shown to be helpful in a wide range of domains (Table 1). In SA, SBAR is due to be introduced to maternity services in the Western Cape Province following a recommendation from the National Committee on Confidential Enquiries into Maternal Deaths (Dr Stefan Gebhardt, personal communication 21 December 2013).

Conclusions

Adopting SBAR was associated with improvement in communi­ cation between professionals and in the perception of quality and safety of patient care. With the proven link between mortality and poor communication and the need to meet Millennium Development Goal 4, it is hoped that SBAR will be introduced to neonatal and maternity services across the country.

1. WHO Collaborating Centre for Patient Safety Solutions. Patient Safety Solutions Preamble – May 2007. Geneva: World Health Organization, 2007. http://www.jointcommissioninternational.org/ assets/3/7/PreambleandSolutionsENGLISH.pdf (accessed 4 November 2014).

2. NHS Institute for Innovation and Improvement. Quality and Service Improvement Tools. SBAR - Situation Background - Assessment - Recommendation. NHS Institute for Innovation and Improvement, 2008. http:// www.institute.nhs.uk/quality_and_service_improvement_tools/quality_and_service_improvement_tools/ sbar_-_situation_-_background_-_assessment_-_recommendation.html (accessed 19 September 2013).

3. United Nations. Millennium Development Goals and Beyond 2015. Goal 4: Reduce Child Mortality – Fact Sheet. United Nations, 2013. http://www.un.org/millenniumgoals/childhealth.shtml (accessed 25 September 2013).

4. Pattinson R, Woods D, Greenfield D, et al. Improving survival rates of newborn infants in South Africa.

Reprod Health 2005;2(4):1-13. [http://dx.doi.org/10.1186/1742-4755-2-4] 5. Joint Commission on Accreditation of Healthcare Organizations. Sentinel Event Alert Issue 30, 2004.

Joint Commission on Accreditation of Healthcare Organizations, 2004. http://www.jointcommission. org/assets/1/18/sea_30.pdf (accessed 4 November 2014).

6. Leonard M, Graham S, Bonacum D. The human factor: The critical importance of effective teamwork and communication in providing safe care. Qual Saf Health Care 2004;13:85-90. [http://dx.doi. org/10.1136/qshc.2004.010033] 7. Cunningham NJ, Weiland TJ, van Dijk J, et al. Telephone referrals by junior doctors: A randomised controlled trial assessing the impact of SBAR in a simulated setting. Postgrad Med J 2012;88(1045):619626. [http://dx.doi.org/ 10.1136/postgradmedj-2011-130719] 8. McCrory MC, Aboumatar H, Custer JW, et al. ABC-SBAR training improves simulated critical patient hand-off by pediatric interns. Pediatr Emerg Care 2012;28(6):538-543. [http://dx.doi.org/10.1097/ PEC.0b013e3182587f6e] 9. Compton J, Copeland K, Flanders S, et al. Implementing SBAR across a large multihospital health system. Jt Comm J Qual Patient Saf 2012;38(6):261-268.

10. De Meester K, Verspuy M, Monsieurs KG, et al. SBAR improves nurse-physician communication and reduces unexpected death: A pre and post intervention study. Resuscitation 2013;84(9):1192-1196. [http://dx.doi.org/10.1016/j.resuscitation.2013.03.016] 11. Premier Inc. Perinatal SBAR 2005. https://www.pdffiller.com/en/project/23815498.htm?form_ id=100036182 (accessed 4 November 2014).

Accepted 3 September 2014.

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CLINICAL ALERT

Tricuspid valve endocarditis associated with intravenous nyoape use: A report of 3 cases R Meel, F Peters, M R Essop Dr Ruchika Meel is a cardiologist in the Division of Cardiology, Department of Internal Medicine, Chris Hani Baragwanath Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. She is currently completing a PhD in valvular heart disease. Dr Ferande Peters is a senior cardiologist in the Division of Cardiology and heads the echocardiography laboratory. Prof. Mohammed R Essop is head of the Division of Cardiology.

Corresponding author: R Meel (ruchikameel@gmail.com)

We report three cases of tricuspid valve infective endocarditis associated with intravenous nyoape use. Nyoape is a variable drug combination of an antiretroviral (efavirenz or ritonavir), heroin, metamphetamines and cannabis. Its use is becoming increasingly common among poor communities in South Africa. All our patients were young HIV-positive men from disadvantaged backgrounds. They all presented with tricuspid regurgitation and septic pulmonary emboli. They were treated with prolonged intravenous antibiotic courses, and one required referral for surgery.

S Afr Med J 2014;104(12):853-855. DOI:10.7196/SAMJ.8291

In developed countries, right-sided infective endocarditis (RSIE) frequently complicates intravenous drug use (IDU) and retroviral disease (HIV).[1] RSIE has been rare in sub-Saharan Africa in both the pre- and post-HIV eras, probably owing to the low frequency of IDU.[2,3] We report three cases of RSIE seen at a single hospital. All the patients were HIV-positive and were abusers of intravenous nyoape. The purpose of this report is to to alert the medical community to a new pattern of disease in at-risk populations.

Failure to detect RSIE early may result in poor long-term outcomes.

Case summaries

Three young HIV-positive men were referred from peripheral hospitals to Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, South Africa (SA). None of the patients was on highly active antiretroviral therapy. All admitted to intravenous nyoape abuse.

Case 1

The first patient was 29 years old and presented with a 1-week history of fever, dyspnoea and features suggestive of right heart failure and severe tricuspid regurgitation (TR). He had tachycardia (136 bpm), was tachypnoeic (respiratory rate 30/min) and had normal blood pressure.

He had a raised jugular venous pressure, a soft first heart sound and a 4/6 pansystolic murmur, typically loudest over the epigastrium and accentuated by manoeuvres that increase venous return. The liver was enlarged and pulsatile. No peripheral stigmata of infective endocarditis were noted. A chest radiograph showed an increased cardiothoracic index with an opacified right costophrenic angle. An initial electrocardiogram (ECG) revealed only sinus tachycardia.

Inflammatory markers were elevated (white cell count (WCC) 18.7 × 109/L and C-reactive protein (CRP) 331 mg/L). The patient had a normochromic, normocytic anaemia (haemoglobin concentration 9.7 g/dL). The CD4+ count was 576 cells/µL. Blood cultures revealed Escherichia coli and salmonella (both only on a single set of cultures).

Transthoracic echocardiography (TTE) demonstrated severe TR (Fig. 1) secondary to a flail anterior tricuspid leaflet. The left-sided

853

valves were normal. Large oscillating masses were noted on the leaflets (the largest measuring 25 mm), extending to the subvalvular apparatus and periannular area (Fig. 2). The pulmonary valve was normal. The right ventricle (RV) was mildly enlarged with normal systolic function but abnormal diastolic function with initially normal systolic pulmonary artery pressure and later pulmonary hypertension. The latter finding could be attributed to pulmonary emboli (Fig. 3). The later ECG showed new T-wave inversion in the anterior leads indicative of RV pressure overload with ischaemia.

Definite tricuspid valve infective endocarditis (IE) was diagnosed based on the modified Duke criteria of one major criterion (oscillating masses on the valve leaflets) and three minor criteria (single positive blood cultures, IDU, fever (39°C) and suspected septic pulmonary emboli). A computed tomography pulmonary angiogram confirmed the presence of multiple bilateral pulmonary emboli complicated by infarction and cavitation.

The patient was commenced on treatment for IE, initially with gentamicin and cloxacillin. Five days later meropenem was substituted according to bacterial culture results. He also received

Fig. 1. Colour Doppler ultrasound scan showing severe tricuspid regurg­itation.

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The inflammatory markers improved, and he remained stable and was treated medically.

Discussion

Fig. 2. Modified apical four-chamber view showing multiple vegetations on the tricuspid valve (arrow) with a dilated right atrium and right ventricle.

Fig. 3. Multiple areas of consolidation suggestive of infarction and dilated right heart chambers on a computed tomography scan of the chest.

diuretics. The inflammatory markers declined (CRP to 28 mg/L and the WCC to 10 × 109/L). The patient was referred for debridement and bioprosthetic tricuspid valve replacement because of severe TR, large vegetation size (>20 mm) and persistent pulmonary embolisation despite adequate antibiotic therapy.

Case 2

The second patient was 30 years old and presented with subacute, progressive dyspnoea as the primary complaint. Findings on clinical and special investigations were similar to the first case. A diagnosis of definite tricuspid valve IE was made based on the modified Duke criteria with one major (oscillating valve mass) and four minor criteria (IDU, suspected septic pulmonary infarcts, fever and a typical micro-organism (Staphylococcus aureus) on one blood culture). The patient continued to embolise to the lungs despite antibiotic therapy, and there was no improvement in the right heart failure. The patient had a history of defaulting from treatment, absconded from the hospital while on antibiotic therapy, and showed poor insight. He was treated conservatively.

Case 3

The third patient, 20 years old, had a 3-week history of fever and vague chest and right upper quadrant pain. A diagnosis of possible tricuspid valve IE was made based on the modified Duke criteria with one major (oscillating valve mass) and three minor criteria (IDU, fever, suspected septic pulmonary infarcts). No organisms were cultured owing to prior antibiotic administration. The patient was empirically treated with intravenous vancomycin and gentamicin.

854

To the best of our knowledge, these three cases are the first reported cases of RSIE secondary to intravenous nyoape use. Nyoape use is common in SA, especially among people from poor backgrounds.[4] Nyoape, also called whoonga or wunga, is a drug sold on the streets and has come to widespread use in SA since about 2010, initially among poor communities in Durban.[5] The ingredients are not exact or constant, but it usually contains an antiretroviral (ARV) such as efavirenz or ritonavir.[5] Other components include heroin, crystal methamphetamine, cannabis, cocaine and even rat poison.[5] Although nyoape was initially smoked, it is now being injected, as these cases suggest. This indicates a new pattern of drug use, which is likely to lead to an increase in cases of RSIE. Heroin is the primary substance of abuse for 8% of individuals in treatment centres in Gauteng Province, SA. Nyoape is the most common form in which heroin is used by black South Africans, in particular, owing to its low cost. Users become addicted to the heroin component, but the neurological effects of efavirenz may play a role, as it is known to cause psychoactive symptoms.[5] ARVs may also potentiate the hypnotic effects of the other ingredients.[5] ARVs are sourced illegally from healthcare workers or are stolen from patients on ARVs.[5] This in turn may cause emergence of resistant HIV strains.[5] IE affects right-sided valves in 5 - 10% of cases.[6] IE is most commonly seen in IDUs, especially in patients with concomitant HIV infection, as observed in our cases. The valve damage in RSIE is postulated to be secondary to poor hygiene in IDU, injection of contaminated matter or abnormalities of immune function.[6] The most common organism cultured is S. aureus, which accounts for 60 - 90% of cases.[6] S. aureus was cultured in only one of our patients, possibly because treatment with antibiotics had been instituted at the referring hospitals prior to a diagnosis being established.

All our patients were HIV-positive, and the following aspects specific to HIV and IE should be taken into consideration when managing these patients. Cardiac surgery is not contraindicated in patients with concurrent HIV and IE.[7] There is no increase in complications and mortality postoperatively.[7] In general, patients with HIV and IDU tend to have involvement of the left-sided valves more commonly than the right-sided valves.[8] In HIV-infected IDUs, the most common causative organism is still S. aureus.[9,10] In HIVreactive (CD4+ count >350 cells/µL) IDUs, the odds ratio (OR) of developing IE is 2.31 compared with non-HIV-infected individuals.

The OR increases to 8.31 at a CD4+ count of <350 cells/uL.[11] The mortality in patients with HIV and concomitant IE with a CD4+ count <200 cells/uL tends to be higher than in other groups.[12] More recent work, however, does not support the higher mortality in patients with low CD4+ counts.[10] There is no significant difference in terms of mortality and response to treatment with antimicrobials between HIV-infected and non-HIV-infected IDUs.[8,9,13,14] A high level of suspicion needs to be maintained, as RSIE may present with nonspecific symptoms and lacks the usual peripheral stigmata associated with left-sided IE.[15] This results in delayed diagnosis and therapy of IE, as evident in all three of our cases.

These cases highlight the importance of considering IE in a patient presenting with features suggestive of pneumonia coupled with right heart failure. Blood for culture (ideally three sets of cultures) should be drawn immediately in this context.

The more common complications of RSIE include fever and respiratory symptoms secondary to septic pulmonary emboli, as in

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our patients. Right-sided heart failure is uncommon. When it occurs, it is usually secondary to volume overload due to severe, organic TR or to pressure overload due to pulmonary hypertension caused by septic pulmonary emboli (or both).[6] The diagnosis of IE on the tricuspid valve is made with TTE, which allows good visualisation of the valve because of its anterior location.[6] The overall sensitivity of TTE is 60 - 70%, but sensitivity increases to 80% in detection of right-sided endocarditis.[16] In most cases of RSIE, TTE is therefore sufficient. Transoesophageal echocardiography (TEE) is useful when the image quality is poor with TTE, TTE is negative in the presence of high clinical suspicion, or S. aureus septicaemia or a complication of IE is suspected.[6] The modified Dukes criteria are useful for the diagnosis of IE[6] but do not replace clinical judgement in cases where its sensitivity is reduced, such as in RSIE, especially in IDUs.[6] The management of RSIE is largely conservative, with most cases treated medically. Empirical antibiotic treatment must cover S. aureus, for which vancomycin would be the drug of choice. The choice of empirical treatment will also be dictated by the suspected organism, IDU, and the valve involved.[6] Duration of antibiotic therapy ranges from 2 weeks in certain uncomplicated cases to up to 6 weeks in complicated cases.[6] Surgery is only considered in patients with intractable right-sided heart failure, unresponsive to heart failure treatment in the form of diuretics; difficult-to-eliminate organisms; persistent bacteraemia (minimum of 1 week’s duration), despite appropriate antibiotics; and large tricuspid valve vegetations of ≥2 cm that persist and are complicated by recurrent embolisation to the lung, in the presence or absence of right heart failure.[6] Our first patient was referred for surgery because of recurrent pulmonary emboli with worsening pulmonary hypertension, despite being on appropriate antibiotic therapy.

The goal of surgery in RSIE is to achieve complete debridement of the infected tissue, and preferably valve repair. If repair is not feasible owing to extensive valve destruction, valve replacement with a bioprosthetic valve should be undertaken. A simple valvectomy, as advocated traditionally, may result in worsening of right-sided haemodynamics postoperatively, if pulmonary hypertension has been present preoperatively.[6] Lastly, the second patient with poor insight constitutes an ethical dilemma regarding conservative v. surgical treatment, especially in a

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resource-limited setting. From the limited available literature, surgery should be offered for the first episode of IE in IDUs who are willing to undergo rehabilitation. If the patient presents with a second episode of IE secondary to lack of compliance, he or she should probably not qualify for further surgical intervention.[17] Since the time of writing, an additional three cases with a similar presentation have been seen.

Conclusion

We are likely to encounter more cases of RSIE secondary to intravenous nyoape use with concurrent HIV infection. A high level of vigilance should be maintained and diagnosis made early before complications arise.

1. Akinosoglou K, Apostolakis E, Marangos M, et al. Native valve right sided infective endocarditis. Eur J Intern Med 2013;24(6):510-519.

2. Naidoo DP. Right-sided endocarditis in the non-drug addict. Postgrad Med J 1993;69(814):615-620.

3. Ndiaye MB, Diao M, Pessinaba S, et al. Epidemiological, clinical and ultrasonographic aspects of rightsided infective endocarditis in Senegal: 6 cases. Med Trop (Mars) 2011;71(5):484-486.

4. South African Community Epidemiology Network on Drug Use report. www.sahealthinfo.org/ admodule/sacendu/Sacenduphase34.pdf (accessed 9 January 2014).

5. Whoonga. Wikipedia encyclopedia. http://en.wikipedia.org/wiki/Whoonga (accessed 9 January 2014).

6. Habib G, Hoen B, Tornos P, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis. Eur Heart J 2009;30(19):2369-2413. [http://dx.doi.org/10.1093/eurheartj/ehp285] 7. Mestres C-A, Chuqoiure JE, Claramonte X, et al. Long term results after cardiac surgery in patients infected with the human immunodeficiency virus type-1 (HIV). Eur J Cardiothorac Surg 2003;23(6):1007-1016.

8. Nahass R, Weinstein MP, Bartels J, et al. Infective endocarditis in intravenous drug user: A comparison of human immunodeficiency virus type1-negative and -positive patients. J Infect Dis 1990;162(4):967970. [http://dx.doi.org/10.1093/infdis/162.4.967] 9. Miro JM, del Rio A, Mestres CA. Infective endocarditis in intravenous drug abusers and HIV-1 infected patients. Infect Dis Clin North Am 2002;16(2):273-295.

10. Fernández Guerrero M, González López JJ, Goyenechea A, et al. Endocarditis caused by Staphylococcus aureus: A reappraisal of the epidemiologic, clinical, and pathologic manifestations with analysis of factors determining outcome. Medicine (Baltimore) 2009;88(1):1-22. [http://dx.doi.org/10.1097/ MD.0b013e318194da65] 11. Manoff S, Vlahov D, Herskowitz A, et al. Human immunodeficiency virus and infective endocarditis among injecting drug users. Epidemiology 1996;7(6):566-570.

12. Ribera E, Miro JM. Influence of HIV 1 infection and degree of immunosuppression in the clinical characteristics and outcome of infective endocarditis in intravenous drug users. Arch Intern Med 1998;158(18):2043-2050. [http://dx.doi.org/10.1001/archinte.158.18.2043] 13. Valencia E, Miro J. Endocarditis in the setting of HIV infection. AIDS Rev 2004;6(2):97-106.

14. Miro JM, del Rio A, Mestres CA. Infective endocarditis and cardiac surgery in intravenous drug abusers and HIV-1 infected patients. Cardiol Clin 2003;21(2):167-184.

15. Fernandez Guerrero ML, Alvarez B, Manzarbeitia F, Renedo G. Infective endocarditis at autopsy: A review of pathologic manifestations and clinical correlates. Medicine (Baltimore) 2012;91(3):152-164. [http://dx.doi.org/10.1097/MD.0b013e31825631ea] 16. San Roman JA, Vilacosta I, Zamorano JL, Almeria C, et al. Transesophageal echocardiography in right-sided endocarditis. J Am Coll Cardiol 1993;21(5):1226-1230. [http://dx.doi.org/10.1016/07351097(93)90250-5] 17. Yeo KK, Chang WS, Lau JM, et al. Valve replacement in endocarditis: Setting limits in noncompliant intravenous drug abusers. Hawaii Med J 2006;65(6):168-171.

Accepted 4 June 2014.

December 2014, Vol. 104, No. 12

EDITORIAL

Towards early detection of retinoblastoma Retinoblastoma (RB) is a rare but life-threatening condition. If it is managed optimally by a competent health team there is an excellent prognosis for life, with survival rates of 95% in developed countries.

Moreover, good visual outcomes are possible.

Kruger et al.[1] in this issue of SAMJ have shown survival rates in a region of South Africa (SA) of only 50%, reflecting the high frequency of late presentation, the simple reason for which is lack of effective screening. Early detection of suspected RB would significantly reduce this unacceptably high mortality rate.

Early detection may be achieved by performing a simple clinical test on all newborns and toddlers: the red reflex. The red reflex or retinal reflex refers to the reddish-orange reflection of light from normal retina, and it is observed with a direct ophthalmoscope held close to the examiner’s eye, while observing the patient’s eyes from a distance of approximately 30 cm. Normally, the reflections of the two eyes are equivalent in colour, intensity and clarity. The examiner is looking for the presence of a whitening of the reflex, white spots in the reflex, an absent red reflex or asymmetry of the two red reflexes when viewed from various angles.[2,3] It is considered standard of care that all newborn babies are tested for a red reflex at discharge from the neonatal nursery. Parents are similarly able to detect a problem by noticing an abnormality in the red reflex in photographs taken when the ‘red eye reduction’ function happens to be switched off on their camera. It would not be too idealistic to suggest that all doctors attending to neonates and toddlers use this humble camera technique and digitally save the red reflex images to the patient’s file at each visit.

In the not-too-distant future, neonatal screening will include universal digital retinal imaging. The roll-out of diabetic screening programmes using portable digital imaging systems is already established in many parts of the world, including the Cape Town metropole. These systems could be expanded to also serve as screening units for neonates.

‘Should eye imaging be part of a standard newborn examin­ation?’ was the theme of a session presented at the 2014 World Ophthalmol­ ogy Congress of the International Council of Ophthalmology on 3 April 2014 in Tokyo, Japan. Speakers from the USA, Russia, India, China and Taiwan shared their experience with modern retinal imaging systems used in universal eye imaging programmes in their countries, convincing the audience about the value of such systems in neonates. The RetCam (Clarity Medical Systems, USA) is an example of a medical device utilising innovative 21st-century optical, electronic and information technologies to image the retina of neonates. Its ability to perform wide-field imaging on neonatal retinas has revolutionised neonatal retinal disease management in the developed world. It has been shown to be a safe screening tool when operated by trained technicians.[4] Owing to the current cost of this technology, it is not yet realistic to propose universal digital retinal imaging of all neonatal retinas in SA. However, the development of portable digital retinal imaging systems is ongoing, and it will be feasible to screen the retinas of all neonates in the future using this technology.

While we were mulling over this editorial, a 3-month-old boy presented with bilateral RB. The father had had one eye enucleated by us for RB 25 years ago. Patients who were treated decades ago may have forgotten that their children are at risk, and they may not be aware that genetic testing and/or counselling can now be offered. Once a heritable mutation is identified, molecular testing can

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determine which members of a family are at risk of developing RB. Children who carry the mutation need to be screened clinically by an ophthalmologist 1 week after birth, monthly for 3 months, every 2 months for 6 months, every 3 months for 2 years and then every 6 months. This is initially best achieved under general anaesthesia until the child is co-operative enough for retinal examination while awake.

This approach allows for early detection of small tumours. Children who do not carry the family’s RB1 mutation are not at increased risk and do not require repeated retinal examinations. The benefits and cost-effectiveness of genetic screening in affected RB families have been well demonstrated.[5] All the modern ophthalmological treatment modalities for RB are available in several centres in SA. For its size and population, SA has an adequate number of these tertiary centres and even boasts a quaternary centre offering radiation plaque therapy.[6] Appropriate and timely treatment can be simultaneously curative and vision preserving. Since management of a child diagnosed with RB requires a multidisciplinary approach, affected children are best referred to tertiary/quaternary facilities that provide specialist paediatric ophthalmology and oncology services. The various provincial departments of health need to co-operate and ensure referral of these patients to the existing treatment centres.

As a country we can be proud that our health system has the expertise to manage a child with RB well. The issue at stake is timely referral of the affected child to one of the specialist treatment centres.

Our national mortality and morbidity figures for this malignancy will only improve if universal eye screening proves successful at primary care level.[7,8] Until universal screening with digital imaging becomes a reality, the tried-and-trusted, old-fashioned red reflex test should be mandatory at discharge from all neonatal services and at all subsequent routine health supervision visits. Most RBs would then be detected early. An added benefit of compliance with such a screening regimen would be the detection of other serious vision-threatening disorders such as cataracts, glaucoma and eye muscle imbalances.

Nicola Freeman David Meyer Division of Ophthalmology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa Corresponding author: D Meyer (dm2@sun.ac.za) 1. Kruger M, Reynders D, Omar F, Schoeman J, Wedi O, Harvey J. Retinoblastoma outcome at a single institution in South Africa. S Afr Med J 2014;104(12):859-863. [http://dx.doi.org/10.7196/SAMJ.8255] 2. Minnesota Department of Health, Vision Screening Online Training Program, Module 5: Retinal Reflex (Red Reflex). http://www.health.state.mn.us/divs/fh/mch/webcourse/vision/mod5a.cfm (accessed 27 October 2014).

3. American Academy of Pediatrics, Section on Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American Academy of Ophthalmology, American Association of Certified Orthoptists. Red reflex examination in neonates, infants, and children. Pediatrics 2008;122(6):1401-1404. [http://dx.doi.org/10.1542/peds.2008-2624] 4. Vinekar A, Gilbert C, Dogra M, et al. The KIDROP model of combining strategies for providing retinopathy of prematurity screening in underserved areas in India using wide-field imaging, telemedicine, non-physician graders and smart phone reporting. Indian J Ophthalmol 2014;62(1):41-49. [http://dx.doi.org/10.4103/0301-4738.126178] 5. Joseph B, Shanmugam MP, Srinivasan MK, Kumaramanickavel G. Retinoblastoma: Genetic testing versus conventional clinical screening in India. Mol Diagn 2004;8(4):237-243. [http://dx.doi. org/10.2165/00066982-200408040-00005] 6. Stannard C, Sauerwein W, Maree G, Lecuona K. Radiotherapy for ocular tumours. Eye 2013;27(2):119127. [http://dx.doi.org/10.1038/eye.2012.241] 7. Leander C, Fu LC, Peña A, et al. Impact of an education program on late diagnosis of retinoblastoma in Honduras. Pediatr Blood Cancer 2007;49(6):817-819. [http://dx.doi.org/10.1002/pbc.21052] 8. Epelman S. Preserving vision in retinoblastoma through early detection and intervention. Curr Oncol Rep 2012;14(2):213-219. [http://dx.doi.org/10.1007/s11912-012-0226-z]

S Afr Med J 2014;104(12):856. DOI:10.7196/SAMJ.8741

December 2014, Vol. 104, No. 12

EDITORIAL

Why aren’t women getting safe abortions?

Many women in South Africa (SA) risk their lives to end an unwanted pregnancy. Despite the liberalisation of laws and formalisation of services dedicated to abortions, women continue to resort to illegal and unsafe solutions that render them vulnerable to health and social risks, serious morbidity and even death.

For many women in SA, access to safe reproductive health services remains a challenge. Even where formal services are available, women prefer and seek quick, private responses to their problem and often avoid seeking help at designated healthcare facilities. Various reasons are offered in explanation, ranging from a fear of ill treatment by facility staff and lack of confidentiality to long waiting lists and ambiguity surrounding rights to, access to and availability of services (particularly restricted in rural areas).

At a social as well as a structural level, the role of stigma requires underscoring. Women express a need for secrecy out of fear of a social aftermath, while healthcare practitioners can be influenced by their right to conscientious objection to being designated as an abortion service provider and the covert peer social sanctions experienced by those who do choose to provide these services. Conscientious objection has been identified as an important issue in understanding the obstacles associated with implementation of and access to legal abortion services. It is a particularly complex matter in both the local and the global contexts, and needs comprehensive engagement and appropriate response at the broader policy and institutional levels as well as at community and individual levels. Conscientious objection gives healthcare professionals the constitutional right[1,2] to freedom of moral belief, religion, and conscience with regard to rendering services to women seeking to access legal abortions.

Stated more simply, a trained healthcare provider may object to offering legal abortions on moral or religious grounds even where designated facilities for these services exist. SA legislation[2,3] further states that when a practitioner refuses to provide services, based on their constitutional right of freedom of thought, belief, and religion, they are obligated to inform the woman and refer her to an alternative service facility. This in itself could prove problematic if the practitioner believes that the offering of this information and referral may be interpreted as an endorsement of abortion: effectively, the practice of referral also becomes subject to conscientious objection.

As result, the pool of designated services that are actually operational is extremely small in relation to the need for these services, and despair drives women of all ages to conceal and terminate their pregnancies under dangerous and often life-threatening conditions.

It is evident that challenges to accessible and acceptable reproductive healthcare services are driven by an array of sociopolitical and historical factors that create barriers to effective service delivery.

Structural and social pathologies deter women from accessing formal, safer abortion services and expose them to harm by preventing them from exercising a basic human right to safe reproductive healthcare.

These ‘pathologies’ represent structural violence[4] whereby the social structures or institutions surrounding reproductive healthcare needs harm women by preventing them from meeting their basic need for effective and efficient care. The status of women seeking abortion services (both socially and structurally) denies them access to the utility of these services, rendering them susceptible to premature death, distress, and feelings of guilt and shame. This form of structural violence against women is often legitimised and maintained through cultural processes in SA. Cultural ideologies and religious beliefs in society, as well as in professional healthcare

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circles, play a key role in denying women access to abortion services via processes of stigmatisation, judgement, isolation and alienation.

These prejudices and discriminatory practices at a cultural level not only support structural violence against women, but also make the denial of abortion-related services culturally and socially acceptable.

Aside from these social and structural pathologies, we need to ask ourselves why women are finding themselves in a position where they deem their pregnancies unwanted. Although many women legitimately choose not to have children, or not to have additional children, many others’ choices are influenced by external factors such as poverty, ineffective support structures, fear of rejection by a partner, and abandonment by partner and/or family, to name just a few. In other words, a pregnancy being ‘unwanted’ has much to do with the circumstances surrounding a woman and her unborn child. We should therefore really be asking ourselves who or what is failing this woman that she feels she has no choice but to deem her pregnancy unwanted and abort – or worse, give birth and then dump her baby.[5] What does this woman need in order for her to believe that she has a choice and may have her child instead of feeling obligated to terminate? Are we satisfied that the acceptable response rests in a discourse that advocates a ‘solution’ to ‘fix’ her by terminating her pregnancy, instead of addressing the needs that drive her to believe she has no other choice?

We believe that the answer lies somewhere between including men as partners who share responsibility in reproductive choices and practices, and structural support that includes effective, accessible prevention and intervention initiatives for women. In the reproductive healthcare environment, the right of practitioners to refuse to perform abortion-related services, based on their democratic right to conscientiously object, inadvertently places women at risk of harm, injury and death. Simply put, one individual’s democratic right to choose impairs another’s human right to determine the status of her future. The state’s responsibility to resolve this conflict between this almost immutable juxtaposition of the constitutional right of the practitioner to refuse abortion services v. that of the woman wishing to access legal abortion is complicated by the heterogeneity of these populations. In some instances, research has shown that practitioners who have previously objected on moral or religious grounds agree to perform these services when offered monetary rewards such as overtime or special rates. Without disputing earnest objections, conscientious objection in this situation becomes highly questionable and demands closer examination of this constitutional right. It would be easy to propose rigorous regulation of these rights at policy level, but much empirical research has shown that policy does not necessarily translate to action and that implementation of policy at grassroots level is one of the greatest challenges our country faces.

Too often men are excluded from reproductive health initiatives, with devastating effects, especially considering the patriarchal nature of SA society.[6] Empowering women about their rights and choices is simply not enough when women in our society are subjugated by power imbalances between men and women. Progress in shifting these gender imbalances in accepting responsibility for reproductive health has been slow and unequal, while the clandestine nature of abortions and unplanned pregnancies confounds scientific progress in understanding the true nature of these phenomena.

Although accessibility to and acceptability of abortion services in SA requires serious attention as a public health priority, we should also be critical in our approach when we propose to prevent and intervene. The need for abortion among women in SA is such a

December 2014, Vol. 104, No. 12

EDITORIAL

convoluted issue that its outcome is as much a choice for women as it is against women. We need to be cognisant of the complexities outlined above when proposing and implementing prevention and/ or intervention strategies if we hope to confront this formidable public health concern. State initiatives should therefore not only be redressing the effects of stigma, both socially and structurally; the state should also invest in supporting the non-profit sector that provides specialised reproductive healthcare services outside of conventional state structures and clinics. While maintaining existing structures, supporting the specialisation of reproductive health and abortion services outside state community clinics would improve privacy and confidentiality for women approaching and utilising service providers. It would also maximise commitment of staff specially recruited to provide these services, while minimising structural pathologies such as the effects of stigma in the immediate work environment. The National Health Insurance (NHI) Fund, with the Green Paper launched in 2011[7,8] and the White Paper launched in 2014 and due to be tabled in Cabinet in the near future,[9] would offer a further avenue for broadening of specialised services outside existing governmental facilities, such as specialised reproductive health services including family planning and abortion services.

With NHI, which is being phased in over a 14-year period, all private healthcare providers will be bound to provide services to a quota of state-subsidised patients from low-income settings. Its formalisation should increase access to improved healthcare services as a whole; however, it does not guarantee effective and efficient abortion and preventive reproductive health services. Specialising service provision in the reproductive healthcare spectrum may be critical in promoting services tailored to the needs of women and

their partners. Multisector, multidisciplinary support in this regard is crucial if the needs of women, and their partners, are to be met holistically, comprehensively and equally – it is worth exploring.

Roxanne Jacobs Nancy Hornsby SAMRC-UNISA (South African Medical Research Council-University of South Africa) Violence, Injury and Peace Research Unit, Tygerberg, Cape Town, South Africa Corresponding author: R Jacobs (roxanne.jacobs@mrc.ac.za, roxy. september01@gmail.com) 1. Cooper D, Morroni C, Orner P, et al. Ten years of democracy in South Africa: Documenting transformation in reproductive health policy and status. Reprod Health Matters 2004;12(24):70-85. [http://dx.doi.org/10.1016/S0968-8080(04)24143-X] 2. Harries J. Abortion services in South Africa: Challenges and barriers to safe abortions: Healthcare providers’ perspectives. PhD thesis. Cape Town: Department of Public Health and Family Medicine, University of Cape Town, 2010.

3. Choice on Termination of Pregnancy Act, No. 92 of 1996. http://www.parliament.gov.za/live/ commonrepository/Processed/20110729/67169_1.pdf (accessed 7 November 2014).

4. Ho K. Structural violence as a human rights violation. Essex Human Rights Review 2007;4(2):1-17. http://projects.essex.ac.uk/ehrr/V4N2/ho.pdf (accessed 7 November 2014).

5. Jacobs R, Hornsby N, Marais S. Unwanted pregnancies in Gauteng and Mpumalanga provinces, South Africa: Examining mortality data on dumped aborted fetuses and babies. S Afr Med J 2014;104(12):864-869. [http://dx.doi.org/10.7196/SAMJ.8504] 6. Thege B. Rural black women’s agency within intimate partnerships amid the South African HIV epidemic. African Journal of AIDS Research 2009;8(4):455-464. [http://dx.doi.org/10.2989/ AJAR.2009.8.4.9.1046] 7. Matsoso MP, Fryatt R. National Health Insurance: The first 18 months. S Afr Med J 2013;103(3):156158. [http://dx.doi.org/10.7196/SAMJ.6601] 8. Health Systems Trust. Green paper: National Health Insurance in South Africa. http://www.hst.org. za/publications/green-paper-national-health-insurance-south-africa (accessed 3 November 2014).

9. Barry H. NHI White Paper Complete. http://www.moneyweb.co.za/moneyweb-2014-budget/nhiwhite-paper-complete (accessed 12 November 2014).

S Afr Med J 2014;104(12):857-858. DOI:10.7196/SAMJ.9133

This month in the SAMJ ...

Mariana Kruger* is a paediatric oncologist and ethicist. She is currently a full professor and executive head of the Department of Paediatrics and Child Health at Tygerberg Hospital and Stellenbosch University. She is a founder member (2003) and co-principal investigator of the South African Research Ethics Training Initiative (SARETI), funded by the Fogarty International Center, National Institutes of Health, USA, which aims to build African research ethics review capacity. She has served on several ethics review committees (including as either chair or deputy chair for the past 10 years) and is currently a member of the Stellenbosch University Senate Ethics Review Committee. She is also the current African Continental President for the International Society for Paediatric Oncology (SIOP). She has been principal investigator for several paediatric clinical trials with a number of scientific and ethics publications. * Kruger M, Reynders D, Omar F, Schoeman J, Wedi O, Harvey J. Retinoblastoma outcome at a single institution in South Africa. S Afr Med J 2014;104(12):859-863. [http:// dx.doi.org/10.7196/SAMJ.8255]

Geoff Fatti* is an epidemiologist at Kheth’Impilo, a non-profit organisation that supports the National Department of Health with health systems strengthening and technical assistance. He holds an MB ChB and MPH, and is involved with evaluating the effectiveness of programmes providing antiretroviral treatment in South Africa. * Fatti G, Shaikh N, Eley B, Jackson D. Adolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa. S Afr Med J 2014;104(12):874-880. [http:// dx.doi.org/10.7196/SAMJ.8207]

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December 2014, Vol. 104, No. 12

RESEARCH

Retinoblastoma outcome at a single institution in South Africa M Kruger,1 MD, PhD; D Reynders,2 MD; F Omar,2 MD; J Schoeman,3 MSc; O Wedi,4 MD; J Harvey,5 PhD epartment of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, D Cape Town, South Africa 2 Department of Paediatrics, Faculty of Health Sciences, University of Pretoria, South Africa 3 Department of Dietetics, Steve Biko Academic Hospital, Pretoria, South Africa 4 Department of Paediatrics, Faculty of Health Sciences, University of Limpopo, South Africa 5 Centre for Statistical Consultation, Faculty of Economic and Management Sciences, Stellenbosch University, Western Cape, South Africa 1

Corresponding author: M Kruger (marianakruger@sun.ac.za)

Introduction. Retinoblastoma (RB) is the most common eye cancer in children. Early detection is necessary for cure.

Objective. To compare stage and outcome of children with RB treated at Kalafong Hospital, Pretoria, South Africa (SA), during two time periods (1993 - 2000 and 2001 - 2008, after outreach interventions in 2000 and introduction of compulsory community service for doctors in 1998).

Methods. Data collected included demography (age, gender, date of birth), stage and treatment received. The main outcome measure was disease-free survival and the study end-point was 60 months after diagnosis.

Results. There were 51 patients during the time period 1993 - 2000 (group 1) and 73 during 2001 - 2008 (group 2), with median ages of 32 and 26 months, respectively (marginally significantly younger in group 2; p=0.046). In group 1, the majority (57%) presented with advanced disease (stages III and IV), with a decline in this proportion in group 2 (40%) indicating a downward but not significant trend (p=0.075). Bilateral disease was diagnosed in 22% of patients in group 1 and 33% in group 2. Overall survival was 33% and 43% for groups 1 and 2, respectively. Excluding absconding patients, event-free survival was 50% in group 1, improving to 68% in group 2 (not statistically significant; p=0.18). Fewer patients needed radiotherapy during the second period (statistically significant; p=0.04), probably because of less advanced disease.

Conclusion. Poor outcome is probably a result of late diagnosis. It is important to implement a strategy that will ensure early diagnosis and optimal management of RB in SA. S Afr Med J 2014;104(12):859-863. DOI:10.7196/SAMJ.8255

Retinoblastoma (RB) is the most common eye cancer in children aged <15 years, accounting for 3% of all cancers in children.[1] Diagnosis is usually made at a young age (<2 years). The tumour presents unilaterally in the majority of patients (70 - 75%).[1] The majority of bilateral tumours (75%) and about 15% of unilateral tumours are hereditary, and these patients usually present with more than one tumour in one or both eyes.[2] RB appears to be more common in Africa and Latin America.[3,4] Survival is excellent in developed countries, where the survival rate is >95%, but it is only ~50% in developing countries, mostly because of late diagnosis and extraocular disease at diagnosis.[1,4-6] Late diagnosis of childhood cancer is common in developing countries, and it is important to document the outcome of children with advanced RB who were treated according to standard treatment protocols.[4,5] In South Africa (SA), several public health interventions have been introduced in the past 20 years, particularly to improve the healthcare of children. Of note is the free healthcare for children under 6 years of age introduced in 1994 and community service for doctors since 1998 in all regions of the country, including rural hospitals with human resource shortages.[7-9] The National Department of Health (NDoH) and the Childhood Cancer Foundation (CHOC), acting in collaboration, introduced an awareness programme with posters depicting the danger signs of childhood cancer in primary healthcare clinics in 2000.[10] Doctors from the universities of the Witwatersrand and Pretoria also undertook outreach visits to referral hospitals in 2001 - 2004 to train staff in early detection of childhood cancer, and especially to

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check for the absence of a red reflex in the eye in order to detect RB early. Parents were encouraged to note absent red reflex of an eye in photos taken with a flashlight. A satellite paediatric oncology unit (POU) of the POU at Kalafong Hospital, Pretoria, was established in Polokwane, Limpopo Province, in 2007 to assist with early diagnosis, treatment, and referral (only if necessary) as part of improving cancer care for children.

The aim of this research was to compare stage and outcome of children with RB during two time periods, namely 1993â&#x20AC;&#x201E;-â&#x20AC;&#x201E;2000, before the outreach interventions, and 2001 - 2008, after the outreach interventions.

Patients and methods Setting

Kalafong Hospital, a large regional hospital, housed the POU before it was moved to Steve Biko Academic Hospital, Pretoria, in December 2009. The POU was established at Kalafong in 1993 and served all children with cancer in the Northern Gauteng region and the provinces of Mpumalanga and Limpopo who were enrolled on prospective treatment protocols between 1993 and 2008.

Design

We prospectively documented the following data for all patients treated for RB between 1993 and 2008: demographics (date of birth, age, gender and place of birth), medical history, clinical findings, diagnostic procedures, treatment protocol and referral pathway.

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RESEARCH

Staging

The diagnostic procedures for all patients included eye examination under general anaesthesia, a computed tomography scan of the eyes and skull, bone scintigraphy (except in cases of intraocular disease), lumbar puncture for cerebrospinal fluid cell examination and count, and bone marrow aspiration. The patients were staged according to the Grabowski-Abramson classification and the Ellsworth Clinic pathological classification, as follows:[11] • Stage I. Intraocular disease – amenable to local therapy or eye enucleated • Stage II. Orbital disease (IIa orbital involvement only; IIb post-laminar optic nerve involvement as well) – eye enucleated, microscopic residual tumour, tumour in excision line of the optic nerve • Stage III. Central nervous system involve­ ment – regional extension and central nervous system metastasis • Stage IV. Haematogenous metastatic disease • Stage V. Bilateral disease with or without metastasis.

Table 1. Demography and management of patients Group 1, 1993 - 2000

Group 2, 2001 - 2008

Patients, N

51

73

Age (months), median (range)

32 (3 - 83)

26 (0 - 119)

0.046 (NS)

Male/female ratio

2.4:1

1.7:1

0.32 (NS)

Eyes amenable to local therapy, n (%)

8 (15.7)

15 (20.5)

0.35 (NS)

Eyes enucleated, n (%)

41 (80.4)*

56 (76.7)†

0.62 (NS)

Radiotherapy, n (%)

18 (35.3)

18 (24.7)

0.004 (SS)

Unilateral/bilateral ratio

3.6:1

2.2:1

0.22 (NS)

NS = not statistically significant; SS = statistically significant. *2% surgery refusal, 2% unknown. † 3% surgery refusal, 1% unknown.

100 90 80 70 60

Patient groups

The patients were assigned to two groups for two time periods, defined as group 1

1993 - 2000

% 50

Treatment outline

2001 - 2008

40 30 20 10 0 Stage I

Stage II

Stage III

Stage IV

Stage V

Fig. 1. Stage at diagnosis of RB for the two study groups. (RB = retinoblastoma; group 1: 1993 - 2000; group 2: 2001 - 2008.)

100 90 Cumulative proportion surviving, %

Patients with stage I disease received either local therapy (cryotherapy or brachytherapy) or enucleation, depending on the size of the intraocular tumours and whether it was possible to salvage vision. All patients except those with intraocular disease (stage I) received neoadjuvant chemotherapy. Enu­ cleation or exenteration was performed after two cycles of chemotherapy. Patients with advanced disease (stages III and IV) received either cranial-spinal radiotherapy (external beam radiotherapy) after six cycles of chemotherapy had been completed or iodine-125 brachytherapy in Cape Town.[12,13] The first 12 patients received treatment according to treatment protocol 1 (1993 1994) with the following drugs: ifosfamide 2 000 mg/m2, carboplatin 550 mg/m2 and etoposide 150 mg/m2 every 4 weeks for six cycles. Patients with stages II - IV disease also received intrathecal therapy, consisting of methotrexate, cytarabine and Solu-Cortef weekly for 6 weeks. Owing to associated severe haematological toxicity (World Health Organization grade 4), the treatment was changed to treatment protocol 2 (1995 - 2008) with the following drugs: vincristine 1.5 mg/ m2, etoposide 300 mg/m2 and carboplatin 550 mg/m2 every 4 weeks for six cycles with intrathecal therapy weekly for 6 weeks.

p-value

80 70 60 50 40 30 20

Group 2 Group 1

10 0 0

10

20 30 40 50 Time after diagnosis, months

60

Fig. 2. Overall survival for the two study groups, including absconding patients. (Group 1: 1993 - 2000; group 2: 2001 - 2008.)

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RESEARCH

Pearsonâ&#x20AC;&#x2122;s Ď&#x2021;2 test was used to determine whether differences were significant or not.

Kaplan-Meier plots were used to calculate overall survival, and log-rank tests to compare survival rates for different subgroups of patients. A significance level of p<0.05 was applied throughout.

100

Cumulative proportion surviving, %

90 80 70 60

Ethics

The Research Ethics Committee, Faculty of Health Sciences, University of Pretoria, approved this retrospective review of patient records with a waiver of informed consent.

50 40 30 20

Group 2 Group 1

10 0 0

10

20 30 40 50 Time after diagnosis, months

60

Fig. 3. Overall survival for the two study groups, excluding absconding patients. (Group 1: 1993 - 2000; group 2: 2001 - 2008.)

100

Cumulative proportion survivng, %

90 80 70 60 50 40 30

Stage I Stage II Stage III Stage IV Stage V

20 10 0 0

10

20 30 40 50 Time after diagnosis, months

60

Fig. 4. Survival according to stage at diagnosis for group 1, excluding absconding patients (1993 - 2000).

for the time period 1993 - 2000, before the outreach interventions, and group 2 for the time period 2001 - 2008, during and after the outreach interventions.

The second period followed several educational outreach activities to referral centres by staff from the universities of the Witwatersrand and Pretoria, as well as interventions undertaken to improve early diagnosis of childhood cancer by the joint CHOC and NDoH awareness campaign. [10] The joint South African Children Cancer Study Group and NDoH awareness campaign distributed posters depicting the danger signs of childhood cancer to all primary care clinics, district

and regional hospitals, as well as central hospitals in the country.

Study end-point

The study end-point was defined as 60 months (5 years) after diagnosis.

Statistical analysis

Continuous variables were described using medians and ranges, and categorical variables using frequency distributions and ratios.

Comparisons of continuous variables between binary variables were performed using the Mann-Whitney U-test. Contingency tables were used to analyse the association between group and a binary classification of staging.

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Results

One hundred and twenty-four patients (51 in group 1 and 73 in group 2) were included in the final data analysis (Table 1). Ten patients were excluded owing to incomplete data (4 patients), transferral to another treatment facility (4 patients) and absconding within an hour from the POU (2 patients).

The median age was 35 months for the combined patient population with unilateral disease and 21 months for patients with bilateral disease (Table 1). The median age was 32 months for group 1 and 26 months for group 2, the second group being slightly younger, with a difference that was marginally statistically significant (p=0.046).

Eleven patients (22%) in group 1 and 23 (33%) in group 2 had bilateral disease. The majority (57%) in group 1 had advanced disease (29/51 patients: 19 had stage IV disease, 7 had stage III disease and 3 had metastatic bilateral disease (stage V)). There was a downward but not yet statistically significant trend (40%) in group 2 (29/73 patients: 14 had stage IV disease, 5 had stage III disease and 10 had metastatic bilateral disease) (p=0.075) (Fig. 1). More boys than girls were affected, although the difference was not statistically significant (male/female ratio 2.4:1 for group 1 and 1.7:1 for group 2) (Table 1).

Only 8 eyes were amenable to local therapy in group 1 v. 15 eyes in group 2 (Table 1). Thirty-eight eyes were enucleated and 3 eyes were exenterated in group 1 v. 52 eyes enucleated and 3 eyes exenterated (1 patient with bilateral disease) in group 2. The parents of three patients refused surgery (1 in group 1, 2 in group 2), and type of surgery was not documented for one child in each group. Fewer patients received radiotherapy in the second group (18/73 patients in group 2 v. 18/51 in group 1), which was statistically significant (p=0.004). Fourteen patients received external beam radiation in group 1 v. only 6 in group 2, while only 4 patients received iodine-125 brachytherapy in group

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100

Cumulative proportion surviving, %

90 80 70 60 50 40 30

Stage I Stage II Stage III Stage IV Stage V

20 10 0 0

10

20 30 40 50 Time after diagnosis, months

60

Fig. 5. Survival according to stage at diagnosis for group 2, excluding absconding patients (2001 - 2008).

100

Cumulative proportion surviving, %

90 80 70 60 50 40 30 20 10

Unilateral Bilateral

0 0

10

20 30 40 50 Time after diagnosis, months

60

Fig. 6. Overall survival of patients with unilateral v. bilateral disease.

1, increasing to 12 patients in group 2.

Of the patients who received iodine-125 brachytherapy, 2 had stage I disease and 14 bilateral disease. Unilateral disease was more common, as expected, with a ratio of 3.6:1 in the first period and 2.2:1 in the second.

Overall survival was 33% and 43% for groups 1 and 2, respectively, with a trend towards better survival in the second period (not statistically significant) (Fig. 2). If absconding patients were excluded, event-free survival was 50% for group 1 and improved to 68% for group 2, not yet statistically significant but with a trend towards significance (p=0.18) (Fig. 3).

Absconding patients were patients lost to follow-up during active treatment or on completion of treatment. Eight patients (16%) absconded from active treatment and 5 (10%) were lost to follow-up after treatment in group 1, while 5 patients (7%) absconded during treatment and 13 (18%) were lost to follow-up in group 2. Limited disease had an excellent outcome, with 100% disease-free survival for patients with stage I disease in both groups and 79% and 84% for stage II disease in groups 1 and 2, respectively (Figs 4 and 5). The mean time to absconding for groups 1 and 2 combined was 31 months (median 14 months, range

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6 - 129). Overall survival for children with unilateral disease was 59% v. 62% for bilateral disease (combined data for groups 1 and 2, excluding absconders). As mentioned above, 13/34 patients with bilateral disease had metastasis at diagnosis (38%) (Fig. 6).

The major reason for poor outcome was progression of disease (9 patients in group 1, 11 in group 2), followed by relapse in 5 patients in each group (28% and 22% for groups 1 and 2, respectively). Other reasons included sepsis in 4 patients (2 with limited and bilateral disease, 2 with metastatic disease), an underlying congenital heart lesion in 1 patient, underlying renal disease in 1 patient, and unexpected death of 1 patient at home. One of the patients with limited bilateral disease, who died of sepsis (Pseudomonas aeruginosa), also had concomitant HIV infection.

Discussion

Limited disease at diagnosis of RB offers the best chance of cure, with >90% of children surviving in developed countries, and also ensures that these children qualify for conservative eye-sparing treatment with decreased morbidity, especially as it is possible to avoid external beam radiation therapy.[1] Late diagnosis and advanced disease are common in developing countries, however, and associated with an increased risk of extraocular disease and poor outcome.[4,5] Canturk et al.[14] reported estimated survival for low-income countries as 40%, for lower middle-income countries (LMICs) as 77% and for upper middle-income countries (UMICs) as 79%. In our study, survival rates were 50% and 68%, respectively, in the two time periods, excluding absconding patients, which is lower than the survival achieved in either LMICs or UMICs. Of concern is that about 25% of patients in each study period absconded during or after treatment, which lowered overall survival to 33% and 43%, respectively, for the two time periods and contrasts with an Indian report for 2008 - 2011, where a statistically significant downward trend in the rate of absconders was seen.[15] Kumar et al.[15] further reported that the major reasons for abandonment of treatment were either financial constraints (30%) or refusal of enucleation (20%), which was probably also true for our study population.

The gender distribution of our patients was similar to that in developed countries, but the unilateral v. bilateral ratio was 73% v. 27%. This ratio correlated with a previous SA study in the 1970s in which Freedman and Goldberg[16] found that 82% of patients

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had unilateral disease, which was different from developed countries, which had a 60% v. 40% ratio. Age was higher for unilateral disease (35 months) than for bilateral disease (21 months), which has been reported previously in developing countries, but overall our patients were older than those in developed countries.[1,4] Canturk et al.[14] further reported that the presence of metastatic disease was significantly associated with physician density. There is a general shortage of health professionals in SA state hospitals, and Hlangani[17] reported in 2002 that more than 29 000 doctors’ posts were vacant throughout hospitals in SA. This may explain the large proportion of patients in this study with advanced disease at diagnosis (57% for the earlier and 40% for the later time period). Long distances from tertiary healthcare facilities that provide comprehensive therapy to children with RB are another factor that may result in late diagnosis. Access to POUs is available in eight centres in SA, but these centres are concentrated mainly in the large cities, whereas the majority of the patients in our study were from rural communities, far from these cities. The distances between cities and rural areas might have caused delays in the referral of these patients as a result of transport issues, added to late recognition of the cancer due to low physician density.[14,17] There was improvement between the two study periods, with a trend towards more limited disease and better survival in the second period. Public healthcare interventions such as free healthcare for children under 6 years of age in SA and compulsory community service for doctors since 1998 did not seem to have influenced early diagnosis of childhood cancer significantly, which was contrary to our expectations.[7-9] Early diagnosis campaigns are probably the solution.[18,19] Parents should be taught to look for the presence of a red reflex of the eye by taking a flash photograph of their children younger than 1 year of age and to report the absence of this reflex, or the presence of any white spot in the eye, at the nearest primary care facility, which may improve early diagnosis. Healthcare workers also need training to increase their awareness that leucocoria in a young child is probably due to RB, and refer these patients urgently to a tertiary healthcare facility for further management. In Honduras information about leucocoria was distributed at vaccination clinics, targeting mothers to recognise the symptoms to improve early diagnosis.[20] Kenya launched a 5-year capacity-building national strategy to improve the survival of children with RB in 2008.[21] Key components of the Kenyan National Retinoblastoma Strategy are efforts to create RB awareness among healthcare workers and the public at large, to improve diagnostic pathology services, and to implement a support programme for families with a child suffering from RB. A similar programme is needed in SA to assist in early recognition of RB by creating awareness, and ensure optimal care to cure the disease and save vision.

Conclusion

Advanced disease in this study was associated with an overall survival rate of <70%. A strategy is necessary in SA to ensure that

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children with RB are diagnosed early and that >90% of them are cured. This will require mass education programmes directed at the public at large to sensitise them to the significance of leucocoria, as well as at healthcare workers to teach them to diagnose the disease early and refer patients timeously to the multidisciplinary teams at the existing POUs in SA, of which the majority initiated a standardised RB management protocol in January 2013.

Acknowledgements. We acknowledge the assistance of the Department of Radiation Oncology, Faculty of Health Sciences, University of Pretoria, for external beam radiotherapy, and Drs Clare Stannard and Karin Lecouna of the Departments of Radiation Oncology and Opthalmology, respectively, Groote Schuur Hospital and University of Cape Town, for iodine-125 brachytherapy.

References 1. Hurwitz RL, Shields CL, Shields JA, et al. Retinoblastoma. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 6th ed. Philadelphia: Lippincott-Raven, 2011:809-837.

2. Theriault BL, Dimaras H, Gallie BL, et al. The genomic landscape of retinoblastoma: A review. Clin Exp Ophthalmol 2014;42(1):33-52. [http://dx.doi.org/10.1111/ceo.12132] 3. Stiller CA, Parkin DM. Geographic and ethnic variations in the incidence of childhood cancer. Br Med Bull 1996;52(4):682-703. [http://dx.doi.org/10.1093/oxfordjournals.bmb.a011577] 4. Chantada GL, Fandiňo A, Manzitti J, et al. Late diagnosis of retinoblastoma in a developing country.

Arch Dis Child 1999;80(2):171-174. [http://dx.doi.org/10.1136/adc.80.2.171] 5. Boubacar T, Fatou S, Fousseyni T, et al. A 30-month prospective study on the treatment of retinoblastoma in the Gebriel Toure Teaching Hospital, Bamako, Mali. Br J Ophthalmol 2010;94(4):467-469. [http:// dx.doi.org/10.1136/bjo.2009.159699] 6. Navo E, Teplisky D, Albero R, et al. Clinical presentation of retinoblastoma in a middle income country.

J Pediatr Hematol Oncol 2012;34(3):97-101. [http://dx.doi.org/10.1097/MPH.0b013e31821d18f9] 7. McCoy D. Free Health Care for Pregnant Women and Children Under Six in South Africa. http:// www.hst.org.za/publications/free-health-care-pregnant-women-and-children-under-six-south-africa (accessed 13 January 2014).

8. Reid SJ. Compulsory community service for doctors in South Africa – an evaluation of the first year.

S Afr Med J 2001;91(4):329-336.

9. Nemutandani MS, Maluleke FRS, Rudolph MJ. Community service doctors in Limpopo Province. S Afr Med J 2006;96(3):180-182.

10. Poyiadjis, S, Wainwright L, Naidu G, et al. The Saint Siluan warning signs of cancer in children: Impact of education in rural South Africa. Pediatr Blood Cancer 2011;56(2):314-316. [http://dx.doi. org/10.1002/pbc.22853] 11. Grabowski EF, Abramson DH. Intraocular and extraocular retinoblastoma. Hematol Oncol Clin North Am 1987;1(4):721-735.

12. Stannard C, Sealy R, Hering E, et al. Localized whole eye radiotherapy for retinoblastoma using a 125I applicator, ‘claws’. Int J Radiat Oncol Biol Phys 2001;51(2):399-409. [http://dx.doi.org/10.1016/S03603016(01)01638-8] 13. Stannard C, Sealy R, Hering E, et al. Postenucleation orbits in retinoblastoma: Treatment with 125I brachytherapy. Int J Radiat Oncol Biol Phys 2002;54(5):1446-1454. [http://dx.doi.org/10.1016/S03603016(02)03756-2] 14. Canturk S, Qaddoumi I, Khetan V, et al. Survival of retinoblastoma in less-developed countries impact of socioeconomic and health-related indicators. Br J Ophthalmol 2010;94(11):1432-1436. [http:// dx.doi.org/10.1136/bjo.2009.168062] 15. Kumar A, Moulik NR, Mishra RK, et al. Causes, outcome and prevention of abandonment in retinoblastoma in India. Pediatr Blood Cancer 2013;60(5):771-775. [http://dx.doi.org/10.1002/ pbc.24454] 16. Freedman J, Goldberg L. Incidence of retinoblastoma in the Bantu of South Africa. Br J Ophthalmol 1976;60(9):655-656.

17. Hlangani M. Brain drain: Systems on life support. The Star 2002; 22 October. http://www.healthlink. org.za/news/20021030 (accessed 13 January 2014).

18. MacCarthy A, Birch JM, Draper GJ, et al. Retinoblastoma: Treatment and survival in Great Britain 1963 to 2002. Br J Ophthalmol 2009;93(1):38-39. [http://dx.doi.org/10.1136/bjo.2008.139626] 19. Bowman RJ, Mafwiri M, Luthert P, et al. Outcome of retinoblastoma in East Africa. Pediatr Blood Cancer 2008;50(1):160-162. [http://dx.doi.org/10.1002/pbc.21080] 20. Leander C, Fu LC, Pena A, Howard SC, Rodriguez-Galindo C, et al. Impact of an education program on late diagnosis of retinoblastoma in Honduras. Pediatr Blood Cancer 2007;49(6):817-819. [http:// dx.doi.org/10.1002/pbc.21052] 21. Dimaras H, White A, Gallie B. The Kenyan national retinoblastoma strategy: Building local capacity in the diagnosis and management of pediatric eye cancer in Kenya. Ophthalmology Rounds 2008;6(4). www.ophthalmologyrounds.ca/crus/ophthcdneng0708_08.pdf (accessed 13 November 2013).

Accepted 5 September 2014.

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Unwanted pregnancies in Gauteng and Mpumalanga provinces, South Africa: Examining mortality data on dumped aborted fetuses and babies R Jacobs, MA (Research Psychology); N Hornsby, MA (Research Psychology); S Marais, D Litt et Phil (Sociology of Health) SAMRC-UNISA (South African Medical Research Council-University of South Africa) Violence, Injury and Peace Research Unit, Tygerberg, Cape Town, South Africa Corresponding author: R Jacobs (roxanne.jacobs@mrc.ac.za and roxy.september01@gmail.com)

Background. Across the world, millions of women unintentionally become pregnant and decide to terminate the pregnancy. Despite progressive abortion laws in South Africa (SA), evidence suggests that many women of all ages still resort to unsafe terminations outside legal, designated facilities. Media reports alert the public to an increase in the illegal dumping of fetuses and abandoned babies, suggesting an increase in unsafe termination practices as well as concealed births.

Objective. To examine mortality data to identify trends in the dumping of aborted fetuses and abandoned babies in SA. Method. This study utilised data from the National Injury Mortality Surveillance System in two provinces, namely Gauteng and Mpumalanga. A total sample of mortality data was used to analyse trends associated with this phenomenon from 2009 to 2011. Descriptive, exploratory statistics were used and included the calculation of crude population incidence rates for abortions and abandoned babies as well as figures (n) and percentages (%) for each category under investigation.

Results. An increase in the rate of discovery of non-viable fetuses was noted for both provinces over the 3-year period, while there was a significant decrease in the discovery of deceased abandoned babies in Gauteng only.

Conclusion. The illegal dumping of fetuses and babies is a very real public health concern in both Gauteng and Mpumalanga. Information is insufficient for adequate surveillance, and improved data collection systems should be prioritised.

S Afr Med J 2014;104(12):864-869. DOI:10.7196/SAMJ.8504

In 1999, a total of 210 million women became pregnant globally; 80 million of these pregnancies were reported to be unintentional.[1] Poor or restricted access to contraceptive services[1] and lack of social and financial support[2] are some of the main reasons why women are faced with unintended pregnancies. Research has shown that women in South Africa (SA) experience considerable difficulties in negotiating safe sex practices.[2,3] Women often face the realities of abuse, forced sex, and/or desertion when insisting on the use of condoms, a request that is stigmatised and interpreted as a sign of infidelity or admission to having a sexually transmitted disease.[3] Poverty also plays a significant role in unwanted pregnancies where unfavourable economic and social circumstances can lead women to opt for an abortion, especially in the context of ‘deepened economic hardships’ associated with health concerns relating to HIV/AIDS.[2] Young girls who partner with older men are identified as especially vulnerable to sexual exploitation owing to their financial dependency.

They find that their access to and control over resources (or lack thereof) greatly influence the degree to which they are able to exercise their rights, especially with regard to having protected sex and the choice to terminate an unwanted pregnancy.[3]

Unsafe abortion

Abortion legislation varies from very conservative to liberal posi­ tions across the globe. Research shows that where legislation tends to be restrictive, abortion mortality and morbidity tend to be high­ est.[4,5] For example, where women seen as victims of circumstances are permitted to terminate a pregnancy (e.g. in cases of a medical emergency, fetal abnormality, rape or incest), others who do not

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meet these criteria are forced to seek alternatives that render them vulnerable to the dangers associated with illicit and unsafe abortion.

According to the World Health Organization (WHO), abortions are deemed ‘unsafe’ when a procedure is ‘characterised by the lack or inadequacy of skills of the provider, hazardous techniques and unsanitary facilities’.[1] In 1995, a total of 46 million women across the world voluntarily terminated their unwanted pregnancies. Of these terminations, 27 million were legal, with an estimated 19 million believed to have occurred outside the legal system.[6] In 2003, almost half (48%) of about 42 million abortions were reportedly unsafe, of which an alarming 97% were in developing countries.[6-8] In the southern African region (including Botswana, Lesotho, Namibia, SA and Swaziland, of which SA forms the major component), 120 000 unsafe abortions were estimated to have occurred in 2008.[9]

Abortion in SA

SA decriminalised abortion in 1996 by introducing the Choice on Termination of Pregnancy Act,[10] which states that a pregnancy may be terminated up to 12 weeks’ gestation at a woman’s request.

Termination from weeks 13 - 20 will only be allowed if a medical risk exists, the pregnancy is the result of rape or incest, or the pregnancy would adversely affect the woman’s social or economic circumstances. The Act goes on to describe the circumstances under which a pregnancy may be terminated after 20 weeks’ gestation, who is legally permitted to perform these procedures, and under what physical conditions surgical termination may take place. Unlike 27 other countries, SA law also protects the individual choice of minors.[4] Minors are encouraged to consult with their parents, guardians, family and friends; however, should they choose

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not to, they may not be denied these services and may terminate a pregnancy without parental consent.[10] Despite these major developments in policy and legislation, since 1994 research has shown that women are still having abortions outside the designated facilities, even in areas where many formal services exist.[11] Women have been found to prefer a quick, private response to their problem and to seek help ranging from the broader medical sector, which includes doctors, nurses, pharmacists and traditional healers, or resort to self-induced methods such as use of laxatives, medicines, household products and oral contraceptives.[11] Hazardous methods such as these have been shown to lead to immediate, medium- and long-term complications including severe bleeding, infertility and even death.[12,13] There are other explanations for why women opt for unsafe methods instead of utilising legitimate services. A WHO study in 2010 showed that about 30% of women in SA continue to believe that abortion is illegal.[12] Many were found to lack knowledge about circumstances in which abortion can be performed or facilities that perform it.[11] Those who knew about these services found them to be inaccessible and/or unacceptable, and reported that they feared staff rudeness, gossip and judgement. Furthermore, they had general concerns about their privacy, and were forced to seek alternatives (even illegal ones) because of long waiting lists for second-trimester terminations.[11] Services are also disproportionately concentrated in major urban centres, particularly in Gauteng Province.[11] Inaccessible or unacceptable services encourage women to seek alternatives that place them at risk.

Illegal dumping of fetuses after abortions and abandoned babies

Evidence of fetuses being illegally dumped has been found all over the world, ranging from those dumped illegally after legal abortions to those aborted and dumped outside the legal system.

In 2010, a news report revealed that Thai police had found just over 2 000 fetuses in a Buddhist temple morgue in Bangkok.[14] Investigations later revealed that these abortions were illegally performed to circumvent Thailand’s restrictive abortion laws, and that the fetuses were collected from various clinics all over the country and secretly cremated at regular intervals in the temple’s furnace.[15] In 2011, it was reported that legitimate abortion clinics in Texas, USA, were fined for illegally dumping aborted fetuses,[16] and a year later boxes containing illegally aborted fetuses were found in a Russian forest.[17] Media reports in SA are alerting the public to what is believed to be an increase in babies as well as fetuses being left in dustbins, gutters and dumps.[18-20] These discoveries are often made by random strangers such as garbage collectors and pedestrians, who then alert the authorities. Although there is no research on which to base their claims, media reports offer poverty, teen pregnancies, rape, incest and unemployment as being at the root cause of dumping of newborns and fetuses.

With the exception of a study that investigated why women are still having abortions outside designated abortion facilities,[11] research related to unsafe reproductive practices in SA tends to focus on the legislative environment and unsafe abortions,[3,21-23] as well as barriers to service delivery in the reproductive health sector.[24-26] No research was found that specifically investigates the phenomenon of dumping babies and fetuses, which represent concealed births and abortions.

Objective

The purpose of this study was to examine mortality data to determine whether the illicit dumping of non-viable fetuses (defined as the

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remains of aborted fetuses that are found and recorded in the National Injury Mortality and Surveillance System (NIMSS)) and abandoned babies (defined as the remains of full-term newborns that died as result of abandonment and are recorded in the NIMSS) are indeed increasing, as is reported in SA media.

Methods

The study utilised data from the NIMSS and reports trends in fatalities of all deaths in two of the country’s provinces, namely Gauteng (predominantly urban) and Mpumalanga (predominantly rural). This system has coverage of nine out of ten mortuaries (it excludes Pretoria mortuary) in Gauteng as well as all 19 mortuaries in Mpumalanga. The NIMSS was first established in 1999 and collects information from Forensic Pathology Services and State Forensic Chemistry laboratories using a single data form that is filled in for every deceased person entering each facility. It incorporates information from postmortem reports, SA Police 180 forms, chemical pathology laboratory results, and criminal justice system reports on a total of 21 items.

For the purposes of our investigation, descriptive, exploratory statistics were utilised to investigate the trends associated with the illegal dumping of fetuses in a densely populated urban area characterised by improved infrastructure (Gauteng), as well as a less populated rural area with limited infrastructure (Mpumalanga). Data analysis included the calculation of crude population incidence rates for cases of abortion and abandoned babies, as well as figures (n) and percentages (%) for each category under investigation. No distinction was made between males and females, as gender and any associated implications were not investigated. Likewise, gestation/age of the fetuses/babies was not included in these analyses, as this information currently simply does not exist. For the above reasons, population rates were not adjusted for age and gender, and only crude population rates were reported.

The NIMSS currently captures abortions and stillbirths as one category and has a separate category for abandoned babies. In order to ensure a sample representative of our interest, all reported cases of natural death were therefore excluded from our analysis on the assumption that this would also exclude any stillbirth cases from the dataset. Analysis comprised preliminary descriptive statistics investigating differences in reporting rates, total numbers of cases and percentages in each province, as well as between the two provinces.

In terms of inferential statistics, χ2 analyses were performed to investigate statistical significance of within-group differences (i.e. differences within each province). Between-group analyses were not performed, as the two provinces were too disparate in sample size to allow for meaningful comparison. Areas analysed included external cause of injury (i.e. the circumstance under which the injury occurred), scene of injury (the place or scene where the actual injury occurred) and other scenes of injury (includes additional places where injury occurred that are not categorised under scene of injury) for further assessment of other, additional places of injury. All terms and descriptions for categories in the current study are in accordance with the definitions used by the NIMSS reporting system.

Results

This section reports on the external cause and scenes of injury for Gauteng and Mpumalanga provinces for the period 2009 - 2011.

External cause of injury

Overall comparisons When data from 2009 to 2011 were aggregated, figures for deaths due to abortion were noticeably higher than for deaths attributed

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17 (6.5)

262 (100.0) 2.4

to abandonment of babies in both Gau­ teng and Mpumalanga (Table 1). For Gauteng, abortions (n=1 321, 94.6%) resulted in significantly more deaths than abandonment (n=75, 5.4%). Similarly, for Mpumalanga there were more abortionrelated deaths (n=245, 93.5%) than deaths following abandonment (n=17, 6.5%).

4.4 533 (100.0) 4.2 501 (100.0) 3.1 362 (100.0) Total

*

Crude rates were calculated, as numbers could not be adjusted for age or gender owing to the nature of this study.

1 396 (100.0)

68 (100)

1.8

96 (100.0)

2.5

98 (100.0)

245 (93.5)

0.1 4 (4.1)

2.3 2.3

0.2 6 (6.3)

90 (93.8) 1.6

0.2 7 (10.3)

61 (89.7)

0.1

1 321 (94.6) 4.3

12 (2.3) 0.3 39

521 (97.7) 3.9 462 (92.2)

0.2

2.9

24 bandoned A babies

(6.6)

338 (93.4) Abortions

External cause

n (%) Deaths

(7.8)

n (%)

n (%)

75 (5.4)

94 (95.9)

Total deaths N (%) Rate/ 100 000* n (%) n (%) n (%)

2011, 4 022 088 2010, 3 969 606

Rate/ 100 000* Rate/ 100 000* Rate/ 100 000*

2011, 12 202 306 2010, 11 946 060

Rate/ 100 000* Rate/ 100 000*

2009, 11 693 933 Year, population

Gauteng (N=1 396 deaths)

Table 1. External causes of death for Gauteng and Mpumalanga provinces, 2009 - 2011

Total deaths (%)

2009, 3 917 408

Mpumalanga (N=262 deaths)

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Comparisons by year With disaggregation of figures across the years (Table 1), the death rates for abortions show a steady increase for Gauteng (2009: rate 2.9/100 000; 95% confidence interval (CI) 2.58 - 3.20; 2010: 3.9/100 000; 95% CI 3.51 - 4.22; 2011: 4.3/100 000; 95% CI 3.90 - 4.64), while the rate for Mpumalanga increased between 2009 and 2010 (1.6/100 000; 95% CI 1.17 - 1.95 and 2.3/100 000; 95% CI 1.80 - 2.74, respectively), but remained constant between 2010 and 2011 (2011: 2.3/100 000; 95% CI 1.86 - 2.81). The death rate for abandoned babies in Gauteng, on the other hand, declined between 2010 (0.3/100 000; 95% CI 0.22 - 0.43) and 2011 (0.1/100 000; 95% CI 0.04 - 0.15), as it did in Mpumalanga (2010: 0.2/100 000; 95% CI 0.03 - 0.27; 2011: 0.1/100 000; 95% CI 0.00 - 0.20).

Analyses of differences between the years were performed at both the conven­ tional significance level (p=0.05) and the adjusted significance level (p=0.01) to minimise family-wise type I error. Only Gauteng showed significant differences in abandonment-related deaths across the 3 years at both significance levels. At p=0.05, for Gauteng the increase in deaths due to abandonment in 2010 (n=39, 52.0%) and the decrease in deaths due to abandonment in 2011 (n=12, 16.0%) were found to be statistically significant (χ2 (2 degrees of freedom, N=1 396) = 17.07; p<0001). At the adjusted p=0.01, only the decrease in deaths due to abandonment in 2011 was found to be significant.

Scenes of injury

For scenes of injury (including other scenes of injury), analyses were performed on an aggregate of both abortions and abandoned babies. The phenomenon of illegal dumping of babies and fetuses and its association with certain scenes of injury were of specific interest. From 2009 to 2011 the top three scenes of injury in Gauteng were roads (n=325, 23.3%), open land (n=287, 20.6%) and ‘place unknown’ (n=206, 14.8%). Comparisons by year show that roads were the leading scene of injury for 2010 (n=120, 24.0%) and

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2011 (n=134, 25.1%), while open land was the leading scene of injury in 2009 (n=74, 20.4%) (Table 2).

A different profile emerged for Mpuma­ langa, where the leading scene of injury was ‘place unknown’ (n=66, 25.2 %), followed by ‘other’ (n=45, 17.2%) and private house (n=27, 10.3%). On year-specific analysis, the leading scene of injury for 2009 was ‘place unknown’ (n=34, 50.0%), for 2010 ‘other’ (n=25, 26.0%), and for 2011 informal settlements (n=23, 23.5%) (Table 2).

Other scenes of injury

Analysis of other scenes of injury provided seven additional scenes of injury for Gauteng, including cemetery, dump site, military base, public toilet, rubbish bin and sewer/drain (both included in this category), with only dump site and sewer/drain for Mpumalanga.

For Gauteng, dump sites remained the most common other scene of injury for 2009 (n=10, 50.0%), 2010 (n=10, 41.7%) and 2011 (n=49, 59.0%) followed by sewer/drain sites in 2009 (n=6, 28.6%), 2010 (n=9, 37.5%), and 2011 (n=25, 30.1%).

In contrast to Gauteng, in Mpumalanga sewers/drains were the most common site for illegal dumping of babies and fetuses for 2009 (n=5, 83.0%), 2010 (n=14, 56.0%) and 2011(n=13, 71.0%). The number of babies dumped in cemeteries showed a marked increase between 2009 (n=1, 17.0%) and 2010 (n=11, 44.0%), with a decline in 2011 (n=1, 29.0%) (Table 3). For 2010, the difference between numbers of babies dumped in cemeteries v. sewers/drains (n=11, 44.0% and n=14, 56.0% respectively) was not as pronounced as in other years.

Discussion

The evidence presented here reveals that the illegal dumping of fetuses and babies is a real public health concern in both Gauteng and Mpumalanga provinces. Our study revealed that there was an increase in the rate of discovery of non-viable fetuses in both provinces over the 3-year period, while at the same time there was a slight decrease in discoveries of deceased, abandoned babies.

The first of these findings suggests that more people are discovering the remains of illicit abortions, indicating a possible increase in this phenomenon. When inferential testing was used, only Gauteng produced significant changes in the number of cases of death due to abandonment reported between 2009 and 2011, with a statistically significant increase in 2010 and a significant decrease in 2011. The decrease may be attributed to various factors, such as an increase in media attention to the baby/fetus dumping

RESEARCH

Table 2. Top ten scenes of injury* for Gauteng and Mpumalanga provinces, 2009 - 2011 n

Table 2. (continued) Top ten scenes of injury* for Gauteng and Mpumalanga provinces, 2009 - 2011

%

Gauteng (N=1 396) 2009

n

%

Medical service area

1

1.5

Farm/primary production area

1

1.5

Open land/beaches

74

20.4

Roads

71

19.6

Other

25

26.0

Place unknown

68

18.8

Place unknown

19

19.8

Private house/yard

39

10.8

Open land/beach

11

11.5

Informal settlement

22

6.1

Industrial/construction area/mine

9

9.4

Other

20

5.5

Private house/yard

8

8.3

Residential institute

17

4.7

Roads

8

8.3

Lake/river/dam

14

3.9

Residential institute

6

6.3

Countryside

11

3.0

Farm/primary production area

3

3.1

Amusement park/sports area

7

1.9

Amusement park/sports area

2

2.1

Informal settlement

2

2.1

2010

2010

Roads

120

24.0

Open land/beach

117

23.4

Informal settlement

23

23.5

Place unknown

100

20.0

Private house/yard

15

15.3

Private house/yard

32

6.4

Other

14

14.3

Informal settlement

30

6.0

Place unknown

13

13.3

Other

24

4.8

Open land/beach

10

10.2

Residential institute

20

4.0

Roads

4

4.1

Countryside

13

2.6

Industrial/construction area/mine

4

4.1

Lake/river/dam

10

2.0

Lake/river/dam

3

3.1

Railway

9

1.8

Residential institute

2

2.0

Railway

2

2.0

2011 Roads

134

25.1

Open land/beach

96

18.0

Other

83

15.6

Private house/yard

46

8.6

Informal settlement

40

7.5

Place unknown

38

7.1

Residential institute

27

5.1

Lake/river/dam

16

3.0

Industrial/construction area/mine

15

2.8

Railway

11

3.1

Place unknown

34

50.0

Other

6

8.8

Roads

5

7.4

Industrial/construction area/mine

5

7.4

Open land/beach

5

7.4

Private house/yard

4

5.9

Residential institute

4

5.9

School/educational area

1

1.5

Mpumalanga (N=262) 2009

Continued ...

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2011

*Scenes of injury listed in accordance with NIMSS reporting system.

phenomenon[18-20] and the introduction of ‘baby safes’ across the country (that provide a safe place where unwanted babies can be dropped off anonymously).[19,27] Our finding that differences were only significant in Gauteng may be attributable solely to that province’s larger population compared with Mpumalanga, and does not in any way indicate that this problem is not significant in Mpumalanga. The decline noted may not conclusively prove a decrease in this phenomenon per se, but rather indicate that fewer babies were found dead after being abandoned during the period of investigation, as opposed to being found alive and rescued. For these reasons, there is a need for more rigorous, scientific investigation into the illicit dumping of fetuses and babies.

Where scenes of injury were known, the commonest scenes for Gauteng were roads and open land, whereas for Mpumalanga they were ‘place unknown’ and ‘other’, among which sewers/drains and dump sites were most often used. These places are accessible by the public and provide a degree of anonymity.

The increase in the phenomenon of dumping in both provinces is indicative of the following. Firstly, the need for secrecy is outweighing the risks involved in seeking an unsafe abortion. Some women who use unsafe methods seek options that offer a quick and private response to their situation, while others wish to avoid the perceived poor-quality healthcare in hospitals.[11] Lack of access to acceptable healthcare services places women of all ages at risk of negative health consequences, including serious morbidity, risk of

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Table 3. Other scenes of injury for Gauteng and Mpumalanga provinces, 2009 - 2011 Gauteng 2009

Mpumalanga

2010

2011

2009

2010

2011

Other scenes of injury

n

%

n

%

n

%

n

%

n

%

n

%

Cemetery

0

0

1

4.2

1

1.2

1

17.0

11

44.0

13

7.0

Dump site

10

50.0

10

41.7

49

59.0

0

0

0

0

0

0

Military base

1

5.0

1

4.2

0

0

0

0

0

0

0

0

Public toilet

2

10

1

4.2

5

6.0

0

0

0

0

0

0

Rubbish bin

1

5.0

2

8.3

3

3.6

0

0

0

0

0

0

Sewer/drain

6

28.6

9

37.5

25

30.1

5

83.0

14

56.0

32

93.0

Total

20

100.0

24

100.0

83

100.0

6

100.0

25

100.0

45

100.0

future infertility and death,[12,13,28] as well as endangering the lives of full-term babies who are abandoned after a concealed birth.

Secondly, despite an increase in designated facilities providing reproductive health services as well as attempts to create a public service environment that is accessible to women of all ages,[25] an undisclosed population of women affected by unwanted pregnancies are not able to rely on the available services. This is believed to be a result of lack of information, perceived poor quality of services,[11] and women being misinformed by hospital staff regarding services and legislation.[2] Furthermore, women who are able to access these services, despite existing limitations, are often stigmatised and report facing judgemental attitudes from service providers.[3] Accessibility to services is further limited by our finding that more than half the designated facilities that are registered providers of termination services are in reality not providing this service.[23] This reflects an unwillingness of healthcare workers to be trained to undertake termination of pregnancy.[23] Since no research has investigated the persons involved in the dumping of fetuses and babies, the best we can do at this stage is to rely on proxies identified by previous research to indicate who these vulnerable groups could be, namely young women and women vulnerable to circumstances of poverty, unemployment and financial dependence, as well as a lack of social and financial support.[3] Our findings indicate that there is a need for comprehensive, detailed surveillance of this phenomenon, including information on the remains discovered and circumstances surrounding the deaths, as well as information about the mothers and fathers of dumped babies and fetuses. The latter represents a considerable challenge.

Conclusion

This study supports existing evidence that unsafe abortions remain a major concern in SA despite significant developments in the country’s legislation and reproductive health environment.[5,22,23] It furthermore suggests that women in all age groups: (i) are in need of reproductive health education and support to prevent unwanted pregnancies; (ii) may be unaware of progressive legislation and services in SA; (iii) may be unfamiliar with alternatives (e.g. adoption services); and (iv) may not know how and where to access services. Despite legal reform and improved access to and knowledge of services, the termination of unwanted pregnancies in Gauteng and Mpumalanga provinces may be highly stigmatised – hence the overwhelming need for secrecy. There is a need to prioritise the development of initiatives and health promotion activities that not only identify particularly vulnerable groups but also specifically tailor policy responses and programme

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interventions to meet the needs of those vulnerable to these clandestine practices. Since women’s negotiating power in safe sex practices remains a concern, state attempts to increase the availability and accessibility of reproductive health services should include a focus on men as partners who share responsibility for decisions regarding reproductive health choices. Surveillance of this public health concern is currently inadequate, and improved data collection systems should be prioritised. Future investigations should be geared towards developing appropriate strategies aimed at the prevention of illegal dumping of fetuses and abandoned babies.

Study limitations

Because the NIMSS provides coverage only for Gauteng and Mpumalanga, analysis was limited to these two provinces. Owing to the limitations of the NIMSS, cases from the Pretoria mortuary were not included and the nature of the data limited analyses to withinprovince comparison. The lack of data available on the gestation/ age of fetuses/babies dumped limited the scope of the analysis.

Even though natural deaths were excluded, the possibility exists that some stillbirth cases were unavoidably included in the analysis.

This is because some stillbirths may be recorded as ‘undetermined’ instead of ‘natural’ when the case is still under police investigation (Prof. Jeanine Vellema, personal communication, January 2014; Ms Janneate van Dyk, personal communication, December 2013).

Another limitation is the possibility that the remains of legally aborted fetuses/stillbirths are handed back to the mother/family for burial, who incorrectly dispose of the remains (Ms Mariette Smith, personal communication, February 2014). The data needed to identify or distinguish these cases do not exist, so they would be included in our analysis. Finally, discrepancies were noted in how scenes of injury were recorded. In some instances, data capturers applied the correct definition for this category and identified it as ‘place unknown’, whereas others indicated it as the scene where the remains were found. There is a need for greater clarity in the current NIMSS and for distinction between scene of injury and where the remains were in fact discovered. We therefore recommend that a ‘scene of discovery’ category be created for a more accurate reflection of the true nature of the data.

Acknowledgements. We thank Prof. Jeanine Vellema and Ms Janneate van Dyk of the Gauteng and Mpumalanga forensic pathology services for providing clarification surrounding NIMSS data, and Ms Mariette Smith and Prof. Kopano Ratele for their insights.

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References 1. Fawcus SR. Maternal mortality and unsafe abortion. Best Pract Res Clin Obstet Gynaecol 2008;22(3):533-548. [http://dx.doi.org/10.1016/j.bpobgyn.2007.10.006] 2. Orner P, de Bruyn M, Cooper D. ‘It hurts, but I don’t have a choice, I’m not working and I’m sick’: Decisions and experiences regarding abortion of women living with HIV in Cape Town, South Africa.

Culture Health Sex 2011;13(7):781-795. [http://dx.doi.org/10.1080/13691058.2011.577907] 3. Varkey SJ, Fonn S, Ketlhapile M. The role of advocacy in implementing the South African abortion law. Reprod Health Matters 2000;8(16):103-111. [http://dx.doi.org/10.1016/S0968-8080(00)90192-7] 4. Berer M. Making abortions safe: A matter of good public health policy and practice. Reprod Health Matters 2002;10(19):31-44. [http://dx.doi.org/10.1016/S0968-8080(02)00021-6] 5. Jewkes R, Rees H, Dickson K, Brown H, Levin J. The impact of age on the epidemiology of incomplete abortions in South Africa after legislative change. BJOG 2005;112(3):355-359. [http://dx.doi. org/10.1111/j.1471-0528.2004.00422.x] 6. Shah I, Ahman E. Age patterns of unsafe abortion in developing country regions. Reprod Health Matters 2004;12(24):9-17. [http://dx.doi.org/10.1016/S0968-8080(04)24002-2] 7. Sedgh G, Henshaw S, Singh S, Ahman E, Shah I. Induced abortion: Estimated rates and trends worldwide. Lancet 2007;370(9595):1338-1345. [http://dx.doi.org/10.1016/S0140-6736(07)61575-X] 8. Ahman E, Shah I. Unsafe abortion: Worldwide estimates for 2000. Reprod Health Matters 2002;10(19):13-17. [http://dx.doi.org/10.1016/S0968-8080(02)00012-5] 9. World Health Organization. Global and Regional Estimates of the Incidence of Unsafe Abortion and Associated Mortality in 2008. 6th ed. Geneva: World Health Organization, 2011. http://www. whqlibdoc.who.int/publications/2011/9789241501118­eng.pdf?ua=1 (accessed 13 February 2014).

10. Choice on Termination of Pregnancy Act, No. 92 of 1996. http://www.parliament.gov.za/live/ commonrepository/Processed/20110729/67169_1.pdf (accessed 29 October 2014).

11. Jewkes RK, Gumede T, Westaway MS, Dickson K, Brown H, Rees H. Why are women still aborting outside designated facilities in metropolitan South Africa? BJOG 2005;112(112):1236-1242. [http:// dx.doi.org/10.1111/j.1471-0528.2005.00697.x] 12. Osman S, Thompson A. A preventative pandemic: Unsafe abortion in South Africa. South Africa: Marie Stopes, 2012. http://www.ngopulse.org/category/tags/marie-stopes (accessed 24 December 2013).

13. Grimes DA, Benson J, Singh S, et al. Unsafe abortion: The preventable pandemic. Lancet 2006;368(9550):1908-1919. [http://dx.doi.org/10.1016/S0140-6736(06)69481-6].

14. BBC News. Thailand police find 2,000 foetuses in temple. Thailand: BBC-news Asia-Pacific, 2010. http://www.bbc.co.uk/news/world-asia-pacific-11785333 (accessed 26 July 2013).

15. Cohen E. Fetuses in a Thai Buddhist temple as chaotic irruption and public embarrassment. Asian Anthropol 2012;11(1):1-20. [http://dx.doi.org/10.1080/1683478X.2012.10600851] 16. Jones J. Texas abortion clinics fined for illegal dumping of aborted fetuses. USA: Examiner.com, 2011. http://www.examiner.com/article/texas-abortion-clinics-fined-for-illegal-dumping-of-abortedfetuses (accessed 26 July 2013).

17. UPI.com. Fetuses dumped illegally in Russian forest. Russia: UPI Top News, 2012. http://www. upi.com/Top_News/World-News/2012/08/03/Fetuses-dumped-illegally-in-Russian-forest/UPI78691344017060/ (accessed 26 July 2013).

18. News24. Dumping of babies increasing. Johannesburg: News24, 2010. http://www.news24.com/ SouthAfrica/News/Dumping-of-babies-increasing-20101104 (accessed 26 July 2013).

19. Farber T. Baby dumping on the rise in W Cape. Cape Town: IOL-news, 2012. http://www.iol.co.za/ news/south-africa/western-cape/baby-dumping-on-the-rise-in-w-cape-1.1267814#.Uo4Q-NIW2Qs (accessed 22 November 2013).

20. Child K, Hosken G. Born to be dumped. Gauteng: Times Live, 2012. http://www.timeslive.co.za/ local/2012/05/29/born-to-be-dumped (accessed 22 November 2013).

21. Buchmann E, Kunene B, Pattinson R. Legalized pregnancy termination and septic abortion mortality in South Africa. Int J Gynaecol Obstet 2008;101(2):191-192. [http://dx.doi.org/10.1016/j. ijgo.2007.10.017] 22. Meel BL, Kaswa RP. The impact of the Choice on Termination of Pregnancy Act of 1996 (Act 92 of 1996) on criminal abortions in the Mthatha area of South Africa. African Journal of Primary Health Care & Family Medicine 2009;1(1):79-81. [http://dx.doi.org/10.4102/phcfm.v1i1.36] 23. Cooper D, Morroni C, Orner P, et al. Ten years of democracy in South Africa: Documenting transformation in reproductive health policy and status. Reprod Health Matters 2004;12(24):70-85. [http://dx.doi.org/10.1016/S0968-8080(04)24143-X] 24. Jewkes RK, Abrahams N, Muo Z. Why do nurses abuse patients? Reflections from South African obstetric services. Soc Sci Med 1998;47(11):1781-1795. [http://dx.doi.org/10.1016/S02779536(98)00240-8] 25. Department of Health. An Evaluation of the Implementation of the Choice on Termination of Pregnancy Act. South Africa: National Department of Health, 2000. http://www.doh.gov.za/docs/ reports/2000/abortion01.pdf (accessed 22 November 2013).

26. Trueman KA, Magwentshu M. Abortion in progressive legal environment: The need for vigilance in protecting and promoting access to safe abortion services in South Africa. Am J Public Health 2013;103(3):397-399. [http://dx.doi.org/10.2105/AJPH.2012.301194] 27. Maclean S. New scheme in South Africa allows mothers to dump unwanted newborns in ‘baby safe’ mounted on a wall. South Africa: Mail Online, 2011. http://www.dailymail.co.uk/news/ article-1385510/Unwanted-South-African-babies-dumped-baby-safe-mounted-wall-streetcontroversial-new-scheme.html (accessed 22 November 2013).

28. Singh S. Hospital admissions resulting from unsafe abortion: Estimates from 13 developing countries.

Lancet 2006;368(9550):1887-1892. [http://dx.doi.org/10.1016/S0140-6736(06)69778-X]

Accepted 18 July 2014.

Blood pressure measurements in the ankle are not equivalent to blood pressure measurements in the arm L N Goldstein,1 MB BCh, MMed (Emergency Medicine), FCEM (SA), Cert Critical Care (SA); M Wells,1 MB BCh, MSc (Emergency Medicine), Dip PEC (SA), FCEM (SA); K Sliwa,2,3 MD, PhD, FESC, FACC, DTM&H ivision of Emergency Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa D Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 3 Soweto Cardiovascular Research Unit (SOCRU), Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 1 2

Corresponding author: L N Goldstein (drg666@gmail.com)

Background. Blood pressure (BP) is often measured on the ankle in the emergency department (ED), but this has never been shown to be an acceptable alternative to measurements performed on the arm.

Objective. To establish whether the differences between arm and ankle non-invasive BP measurements were clinically relevant (i.e. a difference of ≥10 mmHg).

Methods. This was a prospective cross-sectional study in an urban ED making use of a convenience sample of 201 patients (18 - 50 years of age) who were not in need of emergency medical treatment. BP was measured in the supine position on both arms and ankles with the correct size cuff according to the manufacturer’s guidelines. The arm and ankle BP measurements were compared.

Results. There was a clinically and statistically significant difference between arm and ankle systolic BP (SBP) and mean arterial pressure (MAP) (–13 mmHg, 95% confidence interval (CI) –28 - 1 mmHg and –5 mmHg, 95% CI –13 - 4 mmHg, respectively), with less difference in diastolic BP (DBP) (2 mmHg, 95% CI –7 - 10 mmHg). Only 37% of SBP measurements and 83% of MAP measurements were within an error range of 10 mmHg, while 95% of DBP measurements agreed within 10 mmHg. While the average differences (or the bias) were generally not large, large variations in individual patients (indicating poor precision) made the prediction of arm BP from ankle measurements unreliable.

Conclusion. Ankle BP cannot be used as a substitute for arm BP in the ED. S Afr Med J 2014;104(12):869-873. DOI:10.7196/SAMJ.8102

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Blood pressure (BP) is an important vital sign in patients admitted to the emergency department (ED) and is used to guide resuscitation of the critically ill or injured patient. Ideally, BP should be measured directly or invasively when precise or continuous monitoring is required, but this can be time consuming and impractical in the resuscitation setting. The utility of non-invasive BP (NIBP) measurements, along with other clinical signs, includes detection of an abnormally high or low BP in symptomatic or asymptomatic patients.

In patients who are not severely ill or injured, it is reasonable to expect that BP measurements will be performed on one of the patient’s arms according to standard practice guidelines.[1] This is not necessarily the case with the critically ill or injured patient, who may not be able to be positioned correctly or where access to an arm may not be feasible because of injuries or the presence of intravenous catheters. Healthcare providers sometimes then place the BP cuff on the patient’s ankle. There is limited evidence regarding the interchangeable use of arm and ankle BPs in the ED, or in other clinical settings. Similarly, the NIBP machines that are generally used in clinical settings are unlikely to be validated for use on the ankle.

As early as 1925, it was found that the systolic BP was 20 - 40 mmHg higher in the leg than in the arm in normal subjects at rest.[2] This is the premise on which the ankle-brachial index (ABI) is employed to non-invasively determine whether patients have peripheral arterial disease. Normal values for this ratio are considered to be between 0.9 and 1.3. It is abnormal if the ABI is ≤0.9. The prevalence of peripheral arterial disease increases with age. The prevalence in patients older than 55 years is ~16%, whereas that in patients older than 85 years is ~22%.[3] By applying the normal ABI ratio to an arm systolic BP (SBP) of 120 mmHg, the measured ankle SBP would be considered normal if it is anywhere between 108 and 156 mmHg, i.e. up to a 36 mmHg difference, which is certainly clinically significant.

In a study looking at the differences in BP between the arm and the calf (i.e. proximal leg, not ankle) by Zahn et al.,[4] pregnant patients had significant differences in their SBP and diastolic BP (DBP), but no differences in their mean arterial pressure (MAP).

There was, however, a large degree of variability among the patients and a tendency for the SBP to be higher in the arm than in the calf and the DBP to be lower in the calf than in the arm.

Sanghera et al.[5] found no association between arm and ankle BPs in pregnant patients during caesarean section. Although the average differences for SBP, MAP and DBP that they observed were below clinical significance, the limits of agreement were wide. This would have resulted in hypotension being missed in 20% of the patient population, with potentially dire consequences.

This finding confirmed that the ankle position is not an alternative option in pregnant patients.[5] Anaesthetised children have also been found to have inconsistent results with arm and ankle BP measurements. In children 8 years and younger, BPs were found to be lower in the leg than in the arm,[6] whereas another study showed no link between arm and ankle BP.[7] Wilkes and DiPalma[8] advised that although ankle SBPs and MAPs were higher than those in the arm in their cohort of anaesthetised patients, the ankle was an acceptable alternative should the arm not be available. Conversely, Block and Schulte[9] found that although the SBP was higher in the ankle than in the arm, the MAPs were statistically equivalent, suggesting that ankle cuff placement is a reliable alternative. The inconsistency in the results of these studies

870

does not support the routine use of ankle BP measurements in management decisions for critically and injured patients.

BP measurements are fundamental to management of patients in the resuscitation setting in the ED. Whether there is a clinically significant difference between arm and ankle BPs in this setting has not yet been determined. Before assessing this in the hypo- or hypertensive seriously ill or injured patient, the equivalence should be evaluated in haemodynamically normal patients.

Methods

This was a prospective cross-sectional study of a convenience sample of adult patients presenting to an urban ED from 21 October 2010 to 19 January 2011. Patients with significant cardiovascular pathology or musculoskeletal abnormalities, pregnant women, and patients known to have peripheral arterial disease or diabetes were excluded. The data collection process is shown in Fig. 1.

The research was approved by the Human Research Ethics Committee of the Faculty of Health Sciences, University of the Witwatersrand. Written informed consent was obtained from the patients before enrolment.

Obtain consent from patient

Place patient supine on examination bed, undress

Capture demographic data

Measure circumference of left arm and left ankle − determine cuff size from manufacturer’s recommendation

Starting limb based on randomisation table Measure blood pressure on left arm/left ankle/right arm/right ankle (after at least 5 minutes of rest) Measure blood pressure on left arm/left ankle/right arm/right ankle (after 1 minute) Measure blood pressure on left arm/left ankle/right arm/right ankle (after 1 minute) Measure blood pressure on left arm/left ankle/right arm/right ankle (after 1 minute)

Measure patient’s height and weight Fig. 1. Procedure used for data collection.

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Table 1. Basic demographic data Total (N=201)

Males (n=138)

Females (n=63)

Age (years), mean (95% CI)

34 (21 - 49)

34 (21 - 49)

35 (22 - 49)

Height (cm), mean (95% CI)

171 (154 - 186)

175 (164 - 188)

161 (150 - 174)

Weight (kg), mean (95% CI)

74 (52 - 109)

75 (53 - 100)

72 (46 - 111)

BMI (kg/m2), mean (95% CI)

25.6 (18.1 - 36.2)

24.6 (18.2 - 33.1)

27.8 (17.9 - 41.5)

Arm circumference (cm), mean (95% CI)

29 (23 - 36)

29 (23 - 36)

29 (23 - 40)

Ankle circumference (cm), mean (95% CI)

27 (22 - 34)

27 (22 - 32)

28 (23 - 35)

Trauma, n (%)

136 (67.7)

109 (79.0)

27 (42.9)

Non-trauma, n (%)

65 (32.3)

29 (21.0)

36 (57.1)

CI = confidence interval; BMI = body mass index.

Measuring instrument

The NIBP was measured with a GE Healthcare Carescape V100 Vital Signs Monitor. SBP, DBP, MAP and the heart rate were recorded.

This is a typical NIBP device used in the ED that might be used on the ankle in the clinical setting, despite not being validated for this purpose. The machine was reset after each reading.

Data analysis

In line with previous studies, this study made use of Bland-Altman,[10] actual and absolute (root mean square) differences and categorical analysis. The paired t-test was used for comparisons of paired parametric data and the McNemar test for paired categorical data.

The t-test was used for unpaired parametric data and Fisher’s exact test for unpaired categorical data.

Results

Table 2. Differences between mean arm and mean ankle BPs* BP (mmHg) Arm

Ankle

p-value†

Male

126

141

<0.0001

Female

117

127

<0.0001

All

123

137

<0.0001

Male

74

73

0.0115

Female

70

67

<0.0001

All

73

71

<0.0001

Male

94

100

<0.0001

Female

88

90

<0.0001

All

92

97

<0.0001

SBP

DBP

MAP

Two hundred and one adult patients were enrolled into the study.

There were 138 males (68.7%) and 63 females (31.3%). The basic demographic data are summarised in Table 1.

There were statistically significant differences in BP measurements between the male and female patients, although further subgroup analysis showed no change in the relationship between arm and ankle BPs. There were no statistically significant differences between the left and right sides for either the arm or the ankle position. The order in which the BPs were measured did not affect the comparison between the arm and the ankle readings.

In almost 91% of the study population, the same cuff could be used for both the patient’s arm and ankle. One-third of fatter patients and one-third of thinner patients had an arm cuff size that differed from their ankle cuff size. This meant that different cuffs were required for the BP measurements on their arms.

There was a statistically and clinically significant difference between arm and ankle SBP in both males and females. There was a statistically but not clinically significant difference between arm and ankle DBP and MAP in males and females (Table 2).

The mean actual, absolute (root mean square) and percentage differences between the arm and ankle SBPs were clinically significantly different, while those between the arm and ankle DBPs were within the clinically acceptable range. The mean actual, absolute and percentage differences between the arm and ankle MAPs were within the clinically acceptable range, but the range of the confidence interval (CI) was not (Table 3, and Fig. 2 for the Bland-Altman graphic representation).

Non-parametric analysis of differences between the arm and the ankle BPs by category showed that 40% of SBP, 5% of DBP and 16% of MAP measurements differed by >10 mmHg (Fig. 3).

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BP = blood pressure; SBP = systolic blood pressure; DBP = diastolic blood pressure; MAP = mean arterial pressure. * The differences between blood pressure readings in males and females were also significantly different for each measurement. † Paired t-test.

Discussion

The fact that the ankle BP is generally higher than arm BP has been known for a long time,[2] but whether there is a clinically useful and predictable link between the two readings in the haemodynamically normal patient, let alone in the resuscitation setting, has not been evaluated.

In this study, there was a larger difference between arm and ankle SBP in males than in females, with the BPs for both genders being outside the clinically acceptable range. There was no clinically significant difference between the patient age groups or between race groups. The smaller difference in females may be related to their shorter heights and hence a shorter distance between the upper and lower limb arteries.

The mean SBP measured in the ankle was 13 mmHg higher than that measured in the arm. This in itself is not clinically acceptable, but what is more worrying is that this difference is not constant between patients. The ankle SBP was up to 28 mmHg higher, or conversely 1 mmHg lower, than the measured SBP in the arm (95% CI). This difference in SBP translates to a mean percentage difference of 11%.

These large differences are similar to those predicted by a normal

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Residual arm MAP − ankle MAP, mmHg

Residual arm DBP − ankle DBP, mmHg

Residual arm SBP − ankle SBP, mmHg

RESEARCH

20 10 0 –10 –20 –30 –40 –50

80

100 120 140 160 180 200 Average of arm SBP and ankle SBP, mmHg

20 15 10 5 0 –5 –10 –15 –20 40

60 80 100 120 Average of arm DBP and ankle DBP, mmHg

15 10 5 0 –5 –10 –15 –20 –25 60

80 100 120 140 Average of arm MAP and ankle MAP, mmHg

Fig. 2. Bland-Altman plots of arm v. ankle systolic, diastolic and mean BPs. (BP = blood pressure; SBP = systolic blood pressure; DBP = diastolic blood pressure; MAP = mean arterial pressure.)

ABI.[3] Ankle SBP therefore cannot be used to reliably estimate the SBP in the individual.

Surprisingly, DBP fared best, with the absolute and actual differences between the arm and the ankle being 4 mmHg and 2 mmHg, respectively. The ankle reading was on average only 2% higher than the measured arm DBP. This is surprising, because the oscillatory BP machine measures the MAP and calculates the SBP and DBP. The CI for the absolute average DBP extended beyond the clinically significant range of 10 mmHg, however, with the actual CI range being –7 - 10 mmHg. This means that a measured DBP at the ankle could be 7 mmHg lower, or up to 10 mmHg higher, than that in the arm. While within the ‘clinically acceptable’ range, the fact that the measured DBP can be higher or lower than the true arm DBP is potentially problematic should decisions be based on that measured DBP. However, DBP is rarely the value on which clinical decisions are based in the emergency setting.

The MAP was also statistically significantly different between the arm and the ankle, with higher MAPs noted in the ankle. The MAP actual mean difference between the arm and the ankle fell within the clinically acceptable error range of 10 mmHg, but was 5 mmHg higher than the mean arm MAP. Unfortunately, the 95% CIs show that the range extends beyond the acceptable range, with values up to 13 mmHg higher in the ankle than in the arm. The percentage difference in the ankle was on average 5%, but up to 20% higher or 6% lower than true arm values.

Sixty per cent of SBP measurements in the ankle were >10 mmHg different from the arm SBP. Conversely, DBP ankle readings were within 10 mmHg of the arm DBP in the majority of cases (95%).

MAP ankle readings were also within 10 mmHg of the arm MAP in the majority of cases (84%). Arm-ankle differences in SBP tended to be higher if the measured SBP was ≤150 mmHg, but were greater than the clinically acceptable error of 10 mmHg. Where the SBP exceeded 150 mmHg, the measured ankle SBP was always higher than the arm, but was an alarming 24 mmHg (on average) to 38 mmHg different.

The higher the BP, the more inaccurate the SBP became. This was reaffirmed in the MAP differences. DBP was more reliable across the SBP range, but performed best at SBP ≤120 mmHg. These findings may be beneficial with regard to DBP measurement in hypotensive patients, but since the lowest recorded SBP was 92 mmHg in this study, accuracy of the DBP requires validation in a more severely hypotensive population.

There are various explanations for the generally higher ankle SBP than arm SBP: (i) following the law of LaPlace, BP is increased as a result of the higher resistance from the decreased radius of more distal vessels; (ii) arterial pulsations may be dampened distally; (iii) ankle readings may be inaccurate owing to inability of the cuff to compress the dorsalis pedis/posterior tibial artery; and (iv) differences in subcutaneous fat and/or muscle may interfere with compression of the artery and detection of the oscillations.

In the emergency setting, the SBP or the MAP is the preferred target.

For example, in a hypotensive polytrauma patient, current practice is

Table 3. Mean actual, absolute and percentage differences between arm and ankle BPs Difference, mean (CI) Arm and ankle SBP (mmHg)

Arm and ankle DBP (mmHg)

Arm and ankle MAP (mmHg)

Actual

–13 (–28 - 1)

2 (–7 - 10)

–5 (–13 - 4)

Absolute

14 (2 - 28)

4 (1 - 11)

6 (1 - 13)

%

–11 (–22 - 1)

2 (–6 - 8)

–5 (–19 - 6)

BP = blood pressure; CI = confidence interval; SBP = systolic blood pressure; DBP = diastolic blood pressure; MAP = mean arterial pressure.

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Recommendations

160 140 SBP

Patients, n

120

DBP

MAP

100 80 60 40

• Ensure that the correct cuff size is used for BP measurements.

• If the BP cuff was initially placed on the ankle in the resuscitation, ensure that it is transferred to an arm when feasible.

• If the BP cuff is to remain on the ankle, note that the only reliable reading is the DBP. • Ankle BP readings are more inaccurate with higher BPs. Funding. No external funding was obtained from any source.

20 0 0-5

5 - 10

10 - 20

>20

Difference between arm and ankle BP, mmHg

Fig. 3. Error categories of absolute differences in SBP, DBP and MAP between arm and ankle measurements. (SBP = systolic blood pressure; DBP = diastolic blood pressure; MAP = mean arterial pressure; BP = blood pressure.)

not to raise the SBP >100 mmHg – so-called ‘permissive hypotension’. This subsequently evolved to a target MAP of ~65 mmHg,[11,12] or even a MAP as low as 50 mmHg, as part of ‘damage control resuscitation’.[13,14] This is different from a patient with acute coronary syndrome and a hypertensive emergency requiring that the SBP brought down to <180 mmHg to decrease the risk of intracerebral haemorrhage during thrombolysis. The septic patient requires early goal-directed therapy – maintenance of the MAP at 65 mmHg with fluids and vasoactive agents as part of shock treat­ment.[15] In each of these examples, differences between a measured arm and ankle BP of >10 mmHg higher or lower would significantly change management goals for each patient and potentially have deleterious effects.

Wilkes and DiPalma[8] suggested that the ankle can be used as an alternative to the arm should the arm not be available, ‘recognising that the readings are generally higher than the corresponding brachial pressures’. The problem with their suggestion, as can be seen from our data, is that the ‘general rule’ does not always apply.

A practice suggested by one of the authors of the study by Moore et al.[16] is to initially take the BP in the arm before proceeding to the ankle in order to get an idea of the degree of difference between the two sites – a so-called ‘calibration of the ankle BP’.

While this may seem a logical option, there are two inherent problems: in the ED it is not always feasible to take the initial arm BP measurement for comparison, and there

is no guarantee that the initial difference in readings noted will remain consistent throughout a range of BPs. The suggestion is that BP will come to mirror central venous pressure as an indicator of fluid status, and be used as a trend over several readings rather than taken as an absolute, based on only one reading.

Study limitations

Only patients with non-life-threatening conditions in the ED were evaluated, which may preclude extrapolation of our findings to hypotensive or hypertensive patients in other settings. The BP in the ankle was compared with the NIBP of the arm and not the intra-arterial actual BP, this being the typical scenario in practice.

Conclusions

A comparison of NIBP in the arm and ankle in patients in the ED has shown that, in general, the ankle NIBP cannot be used interchangeably with the arm NIBP. The most reliable reading that can be obtained at the ankle as opposed to the arm is the DBP, which unfortunately does not have many clinical applications as a target in the resuscitation setting. Although the ankle can be seen as a convenient alternative site to the arm in the resuscitation environment, there is too much interpatient variability to give a meaningful value.

The search for an accurate, instantaneous, easily repeatable, non-invasive measure of BP must continue, or an alternative to BP monitoring be found.

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References 1. Pickering TG, Hall JE, Appel LJ, et al. Recommendations for blood pressure measurement in humans and experimental animals.

Part 1: Blood pressure measurement in humans: A statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension 2005;45(1):142-161. [http://dx.doi.org/10.1161/01.HYP.0000150859.47929.8e] 2. Burdick W, Clarke N, Garlichs R, et al. Differences in blood pressure in the arm and leg in normal subjects. Am J Physiol 1925;72(1):169-176.

3. Newman AB, Siscovick DS, Manolio TA, et al. Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group. Circulation 1993;88(3):837-845. [http://dx.doi. org/10.1161/01.CIR.88.3.837] 4. Zahn J, Bernstein H, Hossain S, et al. Comparison of noninvasive blood pressure measurements on the arm and calf during cesarean delivery. J Clin Monit Comput 2000;16(8):557562. [http://dx.doi.org/10.1023/A:1012267312308] 5. Sanghera S, North A, Abernethy S, et al. Arm and ankle blood pressure during caesarean section. Int J Obstet Anesth 2006;15(1):24-27. [http://dx.doi.org/10.1016/j.ijoa.2005.04.016] 6. Short JA. Noninvasive blood pressure measurement in the upper and lower limbs of anaesthetized children. Paediatr Anaesth 2000;10(6):591-593. [http://dx.doi.org/10.1111/j.14609592.2000.00558.x] 7. Crapanzano MS, Strong WB, Newman IR, et al. Calf blood pressure: Clinical implications and correlations with arm blood pressure in infants and young children. Pediatrics 1996;97(2):220-224.

8. Wilkes JM, DiPalma JA. Brachial blood pressure monitoring versus ankle monitoring during colono­scopy. South Med J 2004;97(10):939941. [http://dx.doi.org/10.1097/01.SMJ.0000129929.28792.77] 9. Block FE, Schulte GT. Ankle blood pressure measurement, an acceptable alternative to arm measure­ ments. Int J Clin Monit Comput 1996;13(3):167-171. [http://dx.doi. org/10.1023/A:1016997232542] 10. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1(8476):307310. [http://dx.doi.org/10.1016/S0140-6736(86)90837-8] 11. Dutton RP, Mackenzie CF, Scalea TM. Hypotensive resuscitation during active hemorrhage: Impact on in-hospital mortality. J Trauma 2002;52(6):1141-1146. [http://dx.doi. org/10.1097/00005373-200206000-00020] 12. Bilkovski RN, Rivers EP, Horst HM. Targeted resuscitation strategies after injury. Curr Opin Crit Care 2004;10(6):529-538. [http://dx.doi.org/10.1097/01.ccx.0000144771.96342.2c] 13. Cotton BA, Reddy N, Hatch QM, et al. Damage control resuscitation is associated with a reduction in resuscitation volumes and improvement in survival in 390 damage control laparotomy patients. Ann Surg 2011;254(4):598-605. [http:// dx.doi.org/10.1097/SLA.0b013e318230089e] 14. Morrison CA, Carrick MM, Norman MA, et al. Hypotensive resuscitation strategy reduces transfusion requirements and severe postoperative coagulopathy in trauma patients with hemorrhagic shock: Preliminary results of a randomized controlled trial. J Trauma 2011;70(3):652-663. [http://dx.doi. org/10.1097/TA.0b013e31820e77ea] 15. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345(19):1368-1377. [http://dx.doi.org/10.1056/NEJMoa010307] 16. Moore C, Dobson A, Kinagi M, et al. Comparison of blood pressure measured at the arm, ankle and calf. Anaesthesia 2008;63(12):13271331. [http://dx.doi.org/10.1111/j.1365-2044.2008.05633.x]

Accepted 25 July 2014.

RESEARCH

Adolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa G Fatti,1 MB ChB, MPH; N Shaikh,1 MCHD, MPH; B Eley,2 MB ChB, BSc (Hons), FCPaed (SA); D Jackson,3,4 RNC, MPH, DSc; A Grimwood,1 MB ChB, MPH Kheth’Impilo, 16th Floor, Triangle House, 22 Riebeek Street, Cape Town, South Africa Red Cross War Memorial Children’s Hospital and Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, South Africa 3 UNICEF, 3 United Nations Plaza, New York, USA 4 School of Public Health, Faculty of Community and Health Sciences, University of the Western Cape, Bellville, Cape Town, South Africa 1 2

Corresponding author: G Fatti (geoffrey.fatti@khethimpilo.org)

Background. South Africa (SA) has the highest burden of childhood HIV infection globally, and has high rates of adolescent and youth pregnancy.

Objective. To explore risks associated with pregnancy in young HIV-infected women, we compared mother-to-child transmission (MTCT) of HIV and maternal and infant health outcomes according to maternal age categories.

Methods. A cohort of HIV-positive pregnant women and their infants were followed up at three sentinel surveillance facilities in the Nelson Mandela Bay Metropolitan (NMBM) district, Eastern Cape Province, SA. Young women were defined as ≤24 years old and adolescents as ≤19 years. The effect of younger maternal age categories on MTCT and maternal and child health outcomes was assessed using log-binomial and Cox regression controlling for confounding, using women aged >24 years as the comparison group.

Results. Of 956 mothers, 312 (32.6%) were young women; of these, 65 (20.8%) were adolescents. The proportion of young pregnant women increased by 24% between 2009/10 and 2011/12 (from 28.3% to 35.1%). Young women had an increased risk of being unaware of their HIV status when booking (adjusted risk ratio (aRR) 1.37; 95% confidence interval (CI) 1.21 - 1.54), a reduced rate of antenatal antiretroviral therapy (ART) uptake (adjusted hazard ratio 0.46; 95% CI 0.31 - 0.67), reduced early infant HIV diagnosis (aRR 0.94; 95% CI 0.94 - 0.94), and increased MTCT (aRR 3.07; 95% CI 1.18 - 7.96; adjusted for ART use). Of all vertical transmissions, 56% occurred among young women. Additionally, adolescents had increased risks of first presentation during labour (aRR 3.78; 95% CI 1.06 - 13.4); maternal mortality (aRR 35.1; 95% CI 2.89 - 426) and stillbirth (aRR 3.33; 95% CI 1.53 - 7.25).

Conclusion. An increasing proportion of pregnant HIV-positive women in NMBM were young, and they had increased MTCT and poorer maternal and infant outcomes than older women. Interventions targeting young women are increasingly needed to reduce pregnancy, HIV infection and MTCT and improve maternal and infant outcomes if SA is to attain its Millennium Development Goals.

S Afr Med J 2014;104(12):874-880. DOI:10.7196/SAMJ.8207

Globally, South Africa (SA) has the highest burden of childhood HIV infection and the greatest number of pregnant women living with HIV, with approxi­ mately 280 000 annually[1] needing antiretrovirals to prevent mother-to-child transmission (MTCT) of HIV. Although similar to those in other sub-Saharan African (SSA) countries, SA adolescent pregnancy rates are high compared with other world regions, with approximately 30% of all 15 - 19-yearold women reporting having ever been pregnant.[2,3] Women are at a much greater risk of acquiring HIV than men, particularly at younger ages, as young women have a range of contextual and behavioural factors increasing their risk of HIV acquisition.[4] A high proportion of the lifetime risk of acquiring HIV in women occurs while they are young.[4] Women aged 15 - 19 years have the highest incidence of HIV in SA, estimated to remain at over 2% per annum until at least 2025,[5] up to four times that of boys in the same age range. (Beyond age 50 years, HIV prevalence in women is similar to or lower than that of men.[5,6])

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Maternal and perinatal outcomes in SA are poor,[7] and HIV-infected women have poorer pregnancy outcomes than HIV-uninfected women.[8] The United Nations has declared the health of adolescent girls and pregnant women to be a global public health priority.[9] There are, however, few cohort data investigating MTCT and pregnancy outcomes among young HIV-infected women and adolescents in SSA, and minimal SA cohort data from prevention of MTCT (PMTCT) programmes outside of KwaZulu-Natal Province, Cape Town and Johannesburg.

The aim of this study was to investigate the association between younger maternal age and MTCT and maternal and infant health outcomes in routine healthcare settings in the Nelson Mandela Bay Metropolitan (NMBM) district of the Eastern Cape Province.

Methods

Study design, setting and inclusion criteria

A cohort of pregnant women and their infants were followed up at three facilities offering maternal and child health services in subdistrict B of the NMBM (Laetitia Bam Community Health Centre,

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Table 1. Maternal and infant characteristics among HIV-positive pregnant women* according to age category Young women Age ≤19 years (adolescents)

Age 20 - 24 years

Older women (age >24 years)

65 (6.8)

247 (25.8)

644 (67.4)

2009 & 2010

22 (6.4)

75 (21.9)

246 (71.7)

2011 & 2012

43 (7.0)

172 (28.1)

398 (64.9)

n (%) Year of first antenatal visit, n (%)

p-trend 0.073

Unaware of positive HIV status at first antenatal visit, n (%)

49 (75.4)

142 (57.5)

288 (44.7)

<0.0001

Gestational age at booking (weeks), median (IQR) (N=736)

22 (18 - 26)

21 (16 - 26)

22 (17 - 27)

0.76

CD4+ cell count at booking, median (IQR) (N=922)

383 (296 - 465)

377.5 (246 - 519)

339 (217 - 477)

0.005

CD4+ cell count <200 cells/µL, n (%)

6 (9.5)

37 (15.5)

134 (21.5)

0.010

CD4+ cell count >350 cells/µL, n (%)

36 (57.1)

128 (54.2)

297 (47.7)

0.115

Received support from community-based adherence support worker, n (%) (N=956)

14 (21.5)

53 (21.5)

129 (20.0)

0.87

Antiretroviral regimen, n (%)

<0.0001

On lifelong ART at first booking visit

0 (0)

17 (6.9)

136 (21.1)

Commenced lifelong ART during pregnancy

18 (27.7)

62 (25.1)

155 (24.1)

Antenatal ZDV and sdNVP

34 (52.3)

114 (46.2)

222 (34.5)

Antenatal ZDV only

6 (9.2)

16 (6.5)

47(7.3

sdNVP only

4 (6.2)

8 (3.2)

15 (2.3)

Nil

1 (1.5)

3 (1.2)

7 (1.1)

Unknown

2 (3.1)

27 (10.9)

62 (9.6)

Time till starting ZDV after first antenatal visit as prophylaxis for MTCT (days), median (IQR) (N=430)†

0 (0 - 46.5)

1.5 (0 - 44)

7 (0 - 50)

0.26

Time till starting lifelong ART after first antenatal visit (days), median (IQR) (N=148)†‡

64 (28 - 92)

48 (26 - 77)

34 (17 - 60)

0.001

Time receiving lifelong ART prior to delivery (weeks), median (IQR) (N=260)§

15.1 (10.7 - 21.1)

14.4 (5.7 - 19.7)

21.1 (10.8 125)

<0.0001

Time receiving lifelong ART prior to delivery (among women who started lifelong ART during pregnancy) (weeks), median (IQR) (N=155)

15.1 (10.7 - 21.1)

9.3 (5.1 - 16.1)

12.0 (5.3 - 17.3)

0.89

Received ART for <14 weeks prior to delivery, n (%)§

5 (50.0)

28 (48.3)

57 (29.7)

0.0038

Presented for the first time during labour, n (%) (N=956)

3 (4.6)

6 (2.4)

11 (1.7)

0.129

Elected to breastfeed, n (%) (N=909)¶

44 (74.6)

146 (62.4)

313 (50.8)

<0.0001

Recorded maternal deaths, n (%) (N=581)

1 (2.5)

1 (0.6)

0 (0)

0.0132

Stillborn infant, n (%) (N=946)

6 (9.4)

8 (3.3)

32 (5.0)

0.63

Liveborn infants with recorded first HIV DNA PCR test result, n (%) (N=910)||

24 (40.7)

108 (45.2)

336 (54.9)

0.0025

Positive HIV DNA PCR test, n/N (%) (95% CI) (N=468)

2/24 (8.3) (1.0 - 7.0)

7/108 (6.5) (2.6 - 12.9)

7/336 (2.1) (0.8 - 4.2)

0.011

IQR = interquartile range; ART = antiretroviral therapy; ZDV = zidovudine; sdNVP = single-dose nevirapine; MTCT = mother-to-child transmission of HIV; PCR = polymerase chain reaction. *N=956 unless otherwise stated. † Excluding women who tested HIV-positive in late gestation after testing HIV-negative at booking. ‡ Among women who started lifelong ART during pregnancy. § Among women booking after 1 April 2010 who started ART before or during pregnancy. ¶ Following antenatal counselling, the remainder of the women elected to formula feed. || Total infants born less number of stillborn infants.

Rosedale Community Health Centre and Uitenhage Provincial Hospital). These were sentinel surveillance facilities for evaluating the effectiveness of the PMTCT programme.[10] The facilities were supported by Kheth’Impilo, a non-profit organisation that supports the SA Department of Health. Kheth’Impilo has supported direct

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HIV service delivery by providing clinical staff and communitybased adherence support,[10] and now includes supporting general health system strengthening and technical assistance emphasising quality improvement, human resource development, supply chain management and monitoring and evaluation.

December 2014, Vol. 104, No. 12

876 aRR 3.33 (1.53 - 7.25) aRR 0.94 (0.94 - 0.94) aRR 4.48 (1.32 - 15.2)

aRR 1.87 (0.81 - 4.30)

RR 4.0 (0.88 - 18.2)

2/24

Vertical HIV transmission at 6 weeks††

6/64

0.016

<0.0001

0.002

0.005

0.040

<0.0001

0.021

<0.0001

Adjusted p-value

7/108

108/239

8/243

1/541†

6/247

138/217

44/44

142/247

Events/N at risk

ART = antiretroviral therapy; CI = confidence interval; RR = risk ratio; aRR = adjusted risk ratio; HR = hazard ratio; aHR = adjusted hazard ratio. *Time-to-event analysis among women who initiated ART during pregnancy. Adjusted effect measures adjusted for baseline CD4+ cell count and year of first antenatal visit. † Adjusted effect measures adjusted for baseline CD4+ cell count and gestational age at booking. ‡ Adjusted effect measures adjusted for awareness of HIV status at booking. § Adjusted effect measures adjusted for baseline CD4+ cell count, ART regimen at delivery, year of booking and unbooked status. ¶ Owing to zero maternal deaths among women aged >24 years, ages ≥20 years was used as the comparison group. || Adjusted effect measures adjusted for baseline CD4+ cell count, year of booking and gestational age at booking. **Adjusted effect measures adjusted for year of booking. †† Adjusted effect measures adjusted for ART regimen at delivery and unbooked status.

Multivariable models followed a complete-case approach (i.e. included women with non-missing values for all covariates included in the models).

||

RR 0.74 (0.54 - 1.02)

aRR 35.1 (2.89 - 426)

RR 13.5 (0.86 - 212)

1/40

Maternal mortality§

24/59

aRR 3.78 (1.06 - 13.4)

RR 2.70 (0.77 - 9.43)

3/65

Presented for the first time during labour‡

Uptake of early infant diagnosis of HIV**

aRR 1.37 (1.29 - 1.45)

RR 1.44 (1.20 - 1.72)

44/62

Probability of not receiving lifelong ART by delivery†

Stillborn infant

aHR 0.44 (0.22 - 0.88)

HR 0.59 (0.30 - 1.16)

11/11

Rate of antenatal ART uptake*

aRR 1.69 (1.43 - 1.98)

RR 1.69 (1.43 - 1.98)

49/65

Adjusted effect measure (95% CI)

Crude effect measure (95% CI)

Unaware of positive HIV status at first visit

Events/N at risk

Adolescents aged ≤19 years

3.11 (1.12 - 8.67)

RR 0.82 (0.70 - 0.96)

RR 0.65 (0.30 - 1.40)

-¶

RR 1.42 (0.53 - 3.80)

RR 1.29 (1.13 - 1.47)

HR 0.63 (0.44 - 0.91)

RR 1.29 (1.12 - 1.48)

Crude effect measure (95% CI)

aRR 2.84 (1.02 - 7.90)

aRR 0.93 (0.93 - 0.93)

aRR 0.91 (0.40 - 2.07)

-¶

aRR 1.60 (0.60 - 4.31)

aRR 1.13 (1.05 - 1.21)

aHR 0.46 (0.30 - 0.69)

aRR 1.29 (1.12 - 1.48)

Adjusted effect measure (95% CI)

Women aged 20 - 24 years

0.045

<0.0001

0.83

0.35

<0.0001

<0.0001

<0.0001

Adjusted p-value

Table 2. Crude and adjusted associations of younger maternal age categories with maternal and infant health outcomes (in comparison with pregnant women aged >24 years)

RESEARCH

December 2014, Vol. 104, No. 12

All HIV-positive pregnant women (and their infants) who first attended the maternal facilities between 1 January 2009 and 31 March 2012 and had available maternal dates of birth and dates of first antenatal visit (booking visit) were included in the analysis.

Infants and their mothers were followed up (where possible) until the infants’ first HIV DNA polymerase chain reaction (PCR) test approximately 6 weeks after delivery.

Before April 2010, HIV-positive pregnant women with CD4+ cell counts ≤200 cells/µL or in World Health Organization (WHO) clinical stage IV were eligible to start lifelong triple antiretroviral therapy (ART). If ineligible for ART, pregnant women were to receive antenatal zidovudine (ZDV) from 28 weeks’ gestation until delivery and intrapartum single-dose nevirapine (sdNVP). Infants were to receive sdNVP immediately after delivery and a 7-day course of ZDV. From April 2010, ART eligibility criteria for pregnant women were expanded to include women with CD4+ cell counts ≤350 cells/µL or in WHO clinical stages III or IV. Women ineligible for ART were to receive antenatal ZDV from 14 weeks’ gestation and intrapartum sdNVP, as well as single-dose tenofovir/emtricitabine after delivery to cover the ‘NVP tail’.

Infants received an extended NVP course, the duration being dependent on the duration of breastfeeding.

Antenatal and intrapartum care was provided by nurses at the community health centres. Clinical mentoring for nurses was provided by quality nurse mentors (experienced roving nurses who support nurse clinical management skills) using a data-driven approach.

Adolescents were defined as aged ≤19 years (at the first antenatal visit) and young women as aged ≤24 years, according to WHO definitions.[11] Older women were defined as >24 years of age.

The MTCT-related (primary) out­ comes analysed were: (i) proportions of HIV-positive pregnant women who were unaware of their positive HIV status at the booking visit;[12] (ii) duration of time from booking visit until initiation of lifelong ART antenatally, i.e. rate of antenatal ART take-up;[13] (iii) proportions of women who were receiving lifelong ART by delivery (initiated either before or

Definitions and outcomes

RESEARCH

1.00

0.75 Probability of ART initiation

during pregnancy);[14] (iv) proportions of women presenting for the first time when in labour (unbooked);[15] (v) proportions of liveborn infants with available first HIV DNA PCR test results at ~6 weeks of age (uptake of early infant diagnosis of HIV (EID));[16] and (vi) proportions of positive PCR tests (vertical HIV transmission at 6 weeks).[14] Other maternal and child health (secondary) outcomes were: (i) proportions of women known to have died during the antenatal or early postnatal period (maternal mortality);[8] and (ii) proportions of stillborn infants.[8]

Ages >24 years Ages 20 - 24 years Ages ≤19 years

0.50

0.25

Data collection and statistical analysis

Enhanced routine clinical data (individuallevel patient data) were collected pro­ spectively by clinic-based data capturers in an electronic database after patient visits.

Maternal HIV status and antenatal clinical details were captured from clinical files and clinic-based registers. Maternal mortality was recorded as reported to clinic staff.

Infant follow-up data were sourced from child health services in the surrounding area by a PMTCT co-ordinator, as mothers would not necessarily return to the same maternal facility for child health visits. Clinical data were reviewed by quality nurse mentors as well as the district data co-ordinator before being sent to the Kheth’Impilo national office, where data from different facilities were merged.

Linear trends in maternal characteristics between women’s age categories were assessed using the Cochrane-Armitage and Cuzick’s non-parametric tests for categorical and continuous variables, respectively.

Multivariable log-binomial regression was used to assess the effect of maternal age on binary outcomes. Kaplan-Meier curves, the log-rank trend test and multivariable Cox proportional hazards regression were used to estimate the association between maternal age and time to ART initiation during pregnancy among women who initiated ART antenatally. Women aged >24 years were used as the comparison group in all regression models. Available a prioriidentified covariates considered as potential confounders that were eligible for inclusion in multivariable models were:[13,14] (i) year of first antenatal visit; (ii) newly diagnosed HIV-positive; (iii) gestational age at booking; (iv) maternal CD4+ cell count at booking; (v) antiretroviral regimen at delivery; (vi) duration of receiving antiretrovirals prior to delivery; (vii) presenting for the first time during labour (unbooked); (viii) infant feeding choice; and (ix) receipt of support

p-trend =0.0027 0.00 0

30

60

90

120

150

180

Days after first antenatal visit

Fig. 1. Kaplan-Meier failure estimates of time to ART initiation (among women who initiated ART during pregnancy) according to age categories. (ART = antiretroviral therapy.)

from a community-based adherence worker.

Plausible confounding covariates that produced a ≥10% shift in the crude effect measure of the main exposure of interest were included in multivariable models.[17] Data were analysed using Stata version 11.1.

Ethical permission for the study was granted by the University of Cape Town Human Research Ethics Committee.

Results

Database records of 1 136 HIV-positive pregnant women and their infants were reviewed for inclusion in the study; 166 who booked after 31 March 2012, 6 with missing maternal dates of birth and 8 with missing dates of first antenatal visit were excluded, leaving 956 mother-infant pairs to be included in analyses. Of the women, 312 (32.6%) were ≤24 years old, and among these 65 (20.8%) were adolescents (age range 13 - 19 years).

Maternal and infant characteristics are shown in Table 1, and associations between age categories and health outcomes in Table 2. There was a relative increase of 24% (from 28.3% to 35.1%) in the proportion of HIV-positive women aged ≤24 years between 2009/2010 and 2011/2012 (crude risk ratio (RR) 1.24; 95% confidence interval (CI) 1.02 - 1.51). The median gestational age at booking was 22 weeks (interquartile range (IQR) 17 - 26), with no difference between age categories (p=0.76). Young women were progressively more unaware of their positive HIV status at booking, with 75.3% unawareness among adolescents

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compared with 44.7% among older women (crude RR 1.69; 95% CI 1.43 - 1.98). Young women had higher median CD4+ cell counts at booking (378 cells/µL (IQR 256 500) v. 339 (217 - 477) in older women; p=0.005) and lower proportions with CD4+ cell counts <200 cells/µL (14.4% v. 21.5% in older women; p=0.010). None of the adolescents were receiving lifelong ART at booking (despite 10% having CD4+ cell counts <200 cells/µL), compared with 6.9% of women aged 20 - 24 years and 21.1% of older women who were receiving ART (p<0.0001).

The median time between the booking visit and commencement of antenatal ZDV for PMTCT was 5 days (IQR 0 - 48), with no difference between age groups (p=0.26).

The median time between booking and ART initiation during pregnancy was substantially longer in adolescents (64 days) and women aged 20 - 24 years (48 days) compared with older women (34 days). Fig. 1 shows the Kaplan-Meier estimates of time to initiating lifelong ART between booking and delivery, indicating that younger women had lower probabilities of ART uptake at each time point after booking (p-trend = 0.0027). Following adjustment, adolescents and women aged 20 - 24 years had rates of antenatal ART uptake that were more than 50% slower than that of older women (adjusted hazard ratio (aHR) 0.44; 95% CI 0.22 - 0.88 and aHR 0.46; 95% CI 0.30 - 0.69, respectively). Other findings of interest were that ART uptake was more rapid in 2012 compared with previous years (p=0.0019), ART uptake was slower in

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A)

1.00

Probability of ART initiation

2012

2011 and prior

0.75

0.50

0.25 p=0.0019 0.00 0

B)

30

1.00

60

90

120

150

180

GA >16 weeks GA ≤16 weeks

Probability of ART initiation

0.75

0.50

0.25 p=0.0001 0.00

C)

1.00

Probability of ART initiation

0

0.75

30

60

90

120

150

180

With community adherence support worker 0.50

Without community adherence support worker

0.25 p=0.0053 0.00 0

30

60

90

120

150

180

Fig. 2. Kaplan-Meier failure estimatesDays of time antenatal ART initiation according to: A) year of aftertofirst antenatal visit booking, B) gestational age at booking categories, and C) receipt of community adherence support worker. (ART = antiretroviral therapy; GA = gestational age at first antenatal clinic visit.)

women with booking gestational ages of ≤16 weeks (p=0.0001), and ART uptake was more rapid among women who received support from a community-based adherence support worker (p=0.0053) (Fig. 2).

The proportion of women who were first identified as HIV-positive in late gestation

(32 - 34 weeks) after testing HIV-negative at the booking visit was higher among young women (3.0% v. 1.5% in older women: crude RR 2.06; 95% CI 0.90 - 4.70).

By the time of delivery, the proportions of women who were receiving lifelong ART were 27.7%, 32.0% and 45.2% among

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adolescents, women aged 20 - 24 years and older women, respectively (p=0.001).

Despite adjusting for CD4+ cell counts and gestational age at booking, young women had increased probabilities of not receiving lifelong ART by delivery (adjusted risk ratio (aRR) 1.37; 95% CI 1.29 - 1.45 for adolescents and aRR 1.13; 95% CI 1.05 - 1.21 for women aged 20 - 24 years).

The median duration of receiving lifelong ART prior to delivery was significantly shorter in adolescents (15.1 weeks) and women aged 20 - 24 years (14.4 weeks) compared with older women (21.1 weeks) (p<0.0001). The proportions of women who received lifelong ART for <14 weeks prior to delivery were 50.0% in adolescents, 48.3% in women aged 20 - 24 years and 29.5% in older women (crude RR 1.64; 95% CI 1.18 - 2.28 for young women v. older women). In contrast, there was no difference in the median duration of receiving ZDV for prophylaxis of MTCT before delivery according to maternal age (16.9 weeks (IQR 10 - 21.4); p=0.34).

Adolescents had a substantially increased risk of first presentation during labour (4.6% v. 1.7% in older women: aRR 3.78; 95% CI 1.06 - 13.4). In addition, women with known HIV-positive status (included in the adjusted model as a confounder) also had a higher risk of presenting for the first time during labour (aRR 2.80; 95% CI 1.06 - 7.40).

Maternal mortality was increased in adolescents (2.5% v. 0% in older women: aRR 35.1; 95% CI 2.89 - 426; p=0.005) (adjusted for baseline CD4+ cell count, ART regimen, year of booking and unbooked status). The risk of stillbirth was also substantially greater in adolescents (9.4% v. 5.0% in older women: aRR 3.33; 95% CI 1.53 - 7.25; p=0.002) (adjusted for maternal CD4+ cell count, year of booking, gestational age at booking, and receipt of communitybased adherence worker). Women who were supported by community-based adherence support workers had a substantially lower risk of stillbirth (0.5% v. 5.9% among women without a community support worker: aRR=0.09; 95% CI 0.12 - 0.65; p=0.017).

HIV transmission

Four hundred and sixty-eight results of first infant HIV PCR tests were available, with overall uptake of EID of 51.4% (468/910) and overall HIV transmission of 3.4% (16/468). Young women had a slightly reduced uptake of EID (aRR 0.94; 95% CI 0.94 - 0.94). Crude vertical HIV transmission rates were 8.3%, 6.5% and 2.1% among adolescent mothers, women aged 20 - 24 years and older women, respectively (p-trend = 0.011). The majority

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of vertical transmissions (56.3%) occurred among young women (p=0.011), even though young women constituted only a third of the total cohort. In multivariable analyses, younger women had progressively increased risks of vertical HIV transmission (aRR 4.48; 95% CI 1.32 - 15.2; p=0.016 among adolescents and aRR 2.84; 95% CI 1.02 - 7.90; p=0.045 among women aged 20 - 24 years) (adjusted for ART regimen and unbooked status). Women who presented for the first time during labour had a greatly increased risk of vertical transmission (aRR 10.5; 95% CI 3.62 - 30.2; p<0.0001).

Discussion

We found that young women in the NMBM district in the Eastern Cape were less aware of their HIV status when booking than older women, and had slower antenatal ART uptake, reduced uptake of EID and increased MTCT of HIV (despite having less advanced immunosuppression). In addition, adolescents had increased risks of maternal mortality, first presentation in labour, and stillbirth. These findings have important public health relevance in SA, particularly as young women formed a third of all pregnant women, and increasing proportions of young women presented over time.

Younger women are probably less aware of their HIV status because they are more likely to be having their first pregnancy; as antenatal attendance is an important entry point for HIV testing, women with previous pregnancies are more likely to know their HIV status. High rates of undiagnosed HIV infection among adolescents have also been found in Zimbabwe.[18] The increased HIV transmission in younger women is probably related to a combination of factors. Few young women became pregnant while already receiving ART (probably primarily because they were less aware of their HIV status, and secondarily, for those accessing services, because they were earlier in the course of HIV disease and so less likely to be eligible for ART). Initiation of ART during pregnancy was also slower in young women. Eligible women were referred to start ART at dedicated ART clinics at these facilities, and delays among younger women may have been related to challenges that particularly affect that age group, including concerns over confidentiality, social stigma[19] and interpersonal relational barriers with healthcare workers.[20] By the time of delivery, smaller proportions of young women were receiving ART, and for shorter durations of time. In contrast, older women were more likely to start ART before becoming pregnant, and started ART more rapidly during pregnancy. Each additional week of antenatal ART is known to significantly reduce vertical transmission.[14] Increased seroconversion during late pregnancy among young women may also play a role, as 34% of MTCT in South Africa has been estimated to be due to women seroconverting after their first antenatal visit.[21] An additional contributory factor may have been decreased adherence to antiretrovirals, as has been found among adolescents receiving lifelong ART.[22] A recently published cross-sectional survey from KwaZuluNatal also found increased MTCT among adolescent mothers,[23] but did not analyse young women as a separate group. Further research should be conducted to establish the relative contribution of factors resulting in vertical transmission among young women.

Since April 2013, HIV-positive pregnant SA women have been eligible to start triple ART at the time of diagnosis irrespective of CD4+ cell count, and a pilot study had shown this approach to be safe and feasible and to be associated with low MTCT.[24] The results of our study suggest that programmes to reduce adolescent pregnancies, expanded adolescent HIV counselling and testing programmes (including implementation of the Integrated School Health Programme), early detection of young women who seroconvert

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during pregnancy, and transforming reproductive health services to be more youth and adolescent friendly[9,10] may also lead to reduced MTCT. Early identification of young pregnant women who are HIVpositive, swift initiation of triple ART and providing youth-centred ART adherence support to these women need to be important priorities for prevention of MTCT programmes. Measures to improve EID among young mothers in particular, to identify infants eligible to start ART, also need to be prioritised. There is a critical need for sexual and reproductive health rights to be rolled out at clinics as well as at schools, with increased access to HIV counselling and testing, barrier methods and family planning.

Study strengths and limitations

A strength of the study is that it is from an under-resourced area from which there are few published data on MTCT programme outcomes.

The limitations of the study include the use of routine data, and missing early infant HIV DNA PCR results that may have led to bias and reduced the precision of transmission effect measures. However, all the outcomes pointed in the same direction. Estimates of EID uptake in SA have previously been as low as 35% in 2010.[16] This highlights the difficulty of tracking mother-infant pairs in routine settings, and is due to a combination of reasons: mothers taking infants for testing at a number of different child health facilities so that infants are not able to be traced; mothers not bringing infants for testing; late testing of infants; and results not being able to be tracked from the laboratory. An additional study limitation was that accurate ART eligibility among pregnant women was not able to be ascertained, as WHO clinical stages were not captured electronically.

Conclusion

Adolescent and young pregnant women were found to have a high risk of MTCT and to have poorer maternal and infant health outcomes than older women. Programmes targeting a reduction in adolescent pregnancies, expanded adolescent HIV testing, transforming reproductive services to be more adolescent and youth friendly, and improving early infant HIV diagnosis, particularly among babies born to young mothers, may be important interventions to improve maternal and children’s health outcomes in SA. Acknowledgements. The authors thank the mothers and infants included in the study, staff at the participating clinics, the Kheth’Impilo monitoring and evaluation team, the Eastern Cape Department of Health, the President’s Emergency Plan for AIDS Relief and USAID. References 1. UNAIDS. Global Report: UNAIDS Report on the Global AIDS Epidemic 2013. Geneva: WHO, 2013. http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/ UNAIDS_Global_Report_2013_en.pdf (accessed 26 February 2014).

2. Willan S. A review of teenage pregnancy in South Africa – experiences of schooling, and knowledge and access to sexual & reproductive health services. 2013. http://www.hst.org.za/sites/default/files/Teenage%20 Pregnancy%20in%20South%20Africa%20Final%2010%20May%202013.pdf (accessed 26 February 2014).

3. Khan S, Mishra V. Youth Reproductive and Sexual Health. DHS Comparative Reports No. 19.

Calverton, Md, USA, 2008. http://pdf.usaid.gov/pdf_docs/PNADM644.pdf (accessed 2 March 2014).

4. Pettifor AE, Rees HV, Kleinschmidt I, et al. Young people’s sexual health in South Africa: HIV prevalence and sexual behaviors from a nationally representative household survey. AIDS 2005;19(14):1525-1534.

5. Actuarial Society of South Africa. ASSA2008 AIDS and Demographic Model. 2011. http://aids. actuarialsociety.org.za/ASSA2008-Model-3480.htm (accessed 18 March 2011).

6. Simbayi LC, Shisana O, Rehle T, et al. South African National HIV Prevalence, Incidence and Behaviour Survey. Cape Town, 2012. http://www.hsrc.ac.za/en/research-outputs/view/6871 (accessed 15 June 2014).

7. Schoon M, Motlolometsi M. Poor maternal outcomes: A factor of poor professional systems design. S Afr Med J 2012;102(10):784-786. [http://dx.doi.org/10.7196/SAMJ.6130] 8. Rollins N, Coovadia H, Bland R, et al. Pregnancy outcomes in HIV-infected and uninfected women in rural and urban South Africa. J Acquir Immune Defic Syndr 2007;44(3):321-328. [http://dx.doi. org/10.1097/QAI.0b013e31802ea4b0] 9. United Nations. Global Strategy for Women’s and Children’s Health. New York, 2010. http://www.who. int/pmnch/topics/maternal/20100914_gswch_en.pdf (accessed 27 February 2014).

10. Fatti G, Meintjes G, Shea J, et al. Improved survival and antiretroviral treatment outcomes in adults receiving community-based adherence support: 5-year results from a multicentre cohort study in South Africa. J Acquir Immune Def Syndr 2012;61(4):e50-e58. [http://dx.doi.org/10.1097/ QAI.0b013e31826a6aee]

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11. World Health Organization. The Health of Youth. Document A42/Technical Discussions/2. Geneva: WHO, 1989.

12. Grimwood A, Fatti G, Mothibi E, et al. Progress of preventing mother-to-child transmission of HIV at primary healthcare facilities and district hospitals in three South African provinces. S Afr Med J 2012;102(2):81-83.

13. Stinson K, Jennings K, Myer L. Integration of antiretroviral therapy services into antenatal care increases treatment initiation during pregnancy: A cohort study. PLoS ONE 2013;8(5):e63328. [http:// dx.doi.org/10.1371/journal.pone.0063328] 14. Hoffman RM, Black V, Technau K, et al. Effects of highly active antiretroviral therapy duration and regimen on risk for mother-to-child transmission of HIV in Johannesburg, South Africa. J Acquir Immune Defic Syndr 2010;54(1):35-41. [http://dx.doi.org/10.1097/QAI.0b013e3181cf9979] 15. Okeudo C, Ezem B, Ojiyi E. Unbooked status: A predictor of adverse perinatal outcome in HIV positive women at a tertiary hospital in the South Eastern Nigeria. Afrimedic J 2011;2(2):17-20.

16. Goga AE, Dinh TH, Jackson DJ, et al. Evaluation of the Effectiveness of the National Prevention of Mother-to-Child Transmission (PMTCT) Programme on Infant HIV Measured at Six Weeks Postpartum in South Africa, 2010. South African Medical Research Council, National Department of Health of South Africa and PEPFAR/US Centers for Disease Control and Prevention, 2012. http:// www.mrc.ac.za/healthsystems/SAPMTCTE2010.pdf (accessed 17 August 2012).

17. Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol 1993;138(11):923-936.

18. Ferrand RA, Munaiwa L, Matsekete J, et al. Undiagnosed HIV infection among adolescents seeking primary health care in Zimbabwe. Clin Infect Dis 2010;51(7):844-851. [http://dx.doi. org/10.1086/656361]

19. Forrest J, Kaida A, Dietrich J, et al. Perceptions of HIV and fertility among adolescents in Soweto, South Africa: Stigma and social barriers continue to hinder progress. AIDS Behav 2009;13(1):55-61. [http://dx.doi.org/10.1007/s10461-009-9552-z] 20. Alli F, Maharaj P, Vawda M. Interpersonal relations between health care workers and young clients: Barriers to accessing sexual and reproductive health care. J Commun Health 2013;38(1):150-155. [http://dx.doi.org/10.1007/s10900-012-9595-3] 21. Johnson LF, Stinson K, Newell M-L, et al. The contribution of maternal HIV seroconversion during late pregnancy and breastfeeding to mother-to-child transmission of HIV. J Acquir Immune Defic Syndr 2012;59(4):417-425. [http://dx.doi.org/10.1097/QAI.0b013e3182432f27] 22. Nachega JB, Hislop M, Nguyen H, et al. Antiretroviral therapy adherence, virologic and immunologic outcomes in adolescents compared with adults in southern Africa. J Acquir Immune Defic Syndr 2009;51(1):65-71. [http://dx.doi.org/10.1097/QAI.0b013e318199072e] 23. Horwood C, Butler LM, Haskins L, et al. HIV-infected adolescent mothers and their infants: Low coverage of HIV services and high risk of HIV transmission in KwaZulu-Natal, South Africa. PLoS ONE 2013;8(9):e74568. [http://dx.doi.org/10.1371/journal.pone.0074568] 24. Black S, Zulliger R, Myer L, et al. Safety, feasibility and efficacy of a rapid ART initiation in pregnancy pilot programme in Cape Town, South Africa. S Afr Med J 2013;103(8):557-562. [http://dx.doi. org/10.7196/SAMJ.6565]

Accepted 14 August 2014.

The Use of VTE prophylaxis in relatioN to patiEnt risk profiling (TUNE-IN) Wave 2 study B F Jacobson,1 MB ChB, FRCS (Glasg), MMed (Haem), FCPath (SA), PhD (Med); S Louw,1 MB BCh, FCPath (Haem), MMed (Haem); W J Riback,2 MB BCh, DA (CMSA) epartment of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand and D National Health Laboratory Service, Johannesburg, South Africa 2 Sanofi, South Africa 1

Corresponding author: S Louw (susan.louw@nhls.ac.za)

Background. The TUNE-IN (The Use of VTE prophylaxis in relatioN to patiEnt risk profiling) study evaluated venous thromboembolism (VTE) risk assessment and prophylaxis in private medical and surgical inpatients in Gauteng Province, South Africa. The study concluded that of the 608 patients enrolled, 54.1% were clinically evaluated to be at risk for VTE. A VTE risk assessment model (RAM), the Caprini score, increased the rate to 74.6%.

Objectives. TUNE-IN Wave 2, an extension of TUNE-IN, was conducted on a national level including the public sector, focusing on surgical inpatients.

Methods. The study was a national, prospective, non-interventional, multisite, epidemiological disease registry enrolling 453 surgical inpatients. The perceived clinical VTE risk, VTE risk score on Caprini RAM, VTE prophylaxis and clinical details were documented during a baseline visit. A bleeding risk score was provided.

Results. Of the cohort, 269 patients (59.4%) were assessed to be at risk for VTE before applying the RAM. All patients (100%), however, were at risk on the RAM score. Early mobilisation and assessment of the VTE risk as low were the most frequent reasons for non-prescription of prophylaxis. Only 15 patients in the private and 2 in the public sector were assessed as having a bleeding risk. Chemoprophylaxis differed between the healthcare sectors, with low-molecular-weight heparin predominating in the private sector and unfractionated heparin being prescribed only in the public sector.

Conclusion. VTE risk assessment and prophylaxis need to improve in both the public and the private sectors. A formal RAM will improve identification of patients at risk of VTE. S Afr Med J 2014;104(12):880-884. DOI:10.7196/SAMJ.8456

The ENDORSE (Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting) study[1] demonstrated that, globally, more than 50% of hospitalised patients are at risk of venous thromboembolism (VTE). However, adequate prophylaxis, as defined by the 7th American College of Chest Physicians (ACCP) guidelines,[2] was given to only approximately 58% of surgical patients and 40% of medical patients. The proportion of patients

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likely to benefit from receiving adequate VTE prophylaxis now needs to be determined.

The TUNE-IN (The Use of VTE prophylaxis in relatioN to patiEnt risk profiling) study[3] was conducted to evaluate common practice in the assessment of VTE risk and concurrent prescription of prophylaxis in the private inpatient healthcare setting in Gauteng Province, South Africa (SA). The study documented the perceived clinical VTE risk, actual VTE risk score according to the modified Caprini risk assessment model (RAM) (Table 1), VTE prophylaxis

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Table 1. Modified Caprini risk model

Table 1. (continued) Modified Caprini risk model

Each of the following risk factors represents 1 point:

For women only (each risk factor represents 1 point):

Age 41 - 59 years

Oral contraceptives or HRT

Minor surgery planned

Pregnancy or postpartum (<1 month)

History of previous major surgery (<1 month)

History of unexplained stillborn infant, recurrent spontaneous

Varicose veins

abortion (≥3), premature birth with toxaemia or growth-restricted infant

History of inflammatory bowel disease

BMI = body mass index; COPD = chronic obstructive pulmonary disease; SVT = superficial venous thrombosis; DVT/PE = deep-vein thrombosis/pulmonary embolism; HIT = heparininduced thrombocytopenia; HRT = hormone replacement therapy.

Swollen legs (current) Obesity (BMI >30 kg/m2) Acute myocardial infarction (<1 month)

prescribed and mobilisation at varying post-discharge dates. The TUNE-IN study was published in the SAMJ in February 2012,[4] with the following findings: • Of the patients, 54.1% were considered to be at risk for VTE on clinical assessment.

• Concurrent use of a VTE RAM increased this figure to 74.6%.

• Adequate prophylaxis, as per VTE prophylaxis guidelines, was only administered to 67.9% of surgical and 70.9% of medical patients who were at risk of VTE.

Congestive heart failure (<1 month) Sepsis (<1 month) Serious lung disease incl. pneumonia (<1 month) Abnormal pulmonary function (COPD) Medical patient currently on bed rest Leg plaster cast or brace Central venous access Each of the following risk factors represents 2 points:

The TUNE-IN Wave 2 study was an extension of the original TUNEIN to a national level and included public sector hospitals to assess whether the results of the original study were reflective of both healthcare sectors across SA. In addition, TUNE-IN Wave 2 focused exclusively on surgical patients and data were only collected once at baseline, with no subsequent mobilisation assessment.

Age 60 - 74 years Major surgery (>60 minutes) Arthroscopic surgery (>60 minutes) Laparoscopic surgery (>60 minutes) Previous malignancy

Methods

Morbid obesity (BMI >40 kg/m2)

Settings and patients

Each of the following risk factors represents 3 points:

The TUNE-IN Wave 2 study enrolled 453 patients in a national, prospective, non-interventional, multisite, epidemiological disease registry over the period September 2009 - October 2010. The patients were surgical inpatients at 18 sites in private and public sector hospitals across the country. The sites were randomly selected.

Age ≥75 years Major surgery lasting 2 - 3 hours BMI >50 kg/m2 (venous stasis syndrome) History of SVT, DVT/PE

Data collection

Family history of DVT/PE

The perceived clinical VTE risk, VTE risk score according to the modified Caprini RAM (Table 1), VTE prophylaxis prescribed and surgical subspecialty were documented during a baseline visit.

Present cancer or chemotherapy Congenital thrombophilia Positive factor V Leiden

VTE risk scoring

Positive prothrombin 20210A

Treating doctors (surgeons, gynaecologists and anaesthetists) at participating sites were asked to evaluate VTE risk clinically, i.e. without using any official scoring system. The patients were then re-evaluated via an approved RAM (Table 1). This scoring system assigns various risk factors a specific value. The total VTE risk is then calculated by adding the values and assigns the patient to a risk category, i.e. low, moderate, high and highest (Table 2). The decision regarding administration of VTE prophylaxis was left to the treating doctor. A bleeding risk reminder was also provided (Table 3). Consecutive patients meeting the entry criteria were enrolled. A baseline VTE risk assessment was undertaken and VTE prophylaxis documented. No risk factor score for HIV disease was given; however, as it poses a significant risk for VTE, it was noted as an additional comment wherever relevant.

Elevated serum homocysteine Acquired thrombophilia Positive lupus anticoagulant Elevated anticardiolipin antibodies HIT Other thrombophilia Each of the following risk factors represents 5 points: Elective major lower extremity arthroplasty Hip, pelvis or leg fracture (<1 month) Stroke (<1 month) Multiple trauma (<1 month) Acute spinal cord injury (paralysis) (<1 month)

Patient characteristics

Major surgery >3 hours Continued ...

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TUNE-IN Wave 2 enrolled 453 surgical inpatients within the allo­ cated time period; this was deemed adequate for statistical analysis.

The majority of the patients (69.5%) were from the private sector, with

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30.5% from the public sector. The inclusion criteria for the study were as follows: surgical inpatient, ≥18 years old, with signed patient informed consent and data release consent form available. Patients not meeting the inclusion criteria, those currently on anticoagulation therapy, e.g. warfarin, and pregnant women were excluded.

The mean age of patients in the private sector was 50.1 years v. 45.4 in the public sector. Interestingly, the patients in the private sector had higher weights (77.9 kg v. 70.0

kg) and body mass indices than the public sector patients. The majority of the patients were female, with a female/male ratio of 69:31. Just over half (50.2%) were classified as being general surgery patients and 21.8% as gynaecological patients. The remainder of the patients were distributed across various surgical subspecialties including orthopaedics (8.0%), vascular surgery (2.5%) and urology (2.2%). A significant proportion (13.3%) of primarily surgical patients had concomitant medical comorbidities.

Table 2. Risk levels and recommendation according to risk level Total risk factor score

Incidence of DVT

Risk level

Prophylaxis regimen

0-1

<10%

Low

No specific measures, early ambulation

2

10 - 20%

Moderate

ES/GCS, IPC, LDUH or LMWH

3-4

20 - 40%

High

IPC, LDUH or LMWH

≥5

40 - 60% (1 - 5% mortality)

Highest

Pharmacological LDUH, LMWH, warfarin or F-Xa inhibitor alone or in combination with ES/GCS or IPC

ES/GCS = elastic stockings/graduated compression stockings; IPC = intermittent pneumatic compression; LDUH = low-dose unfractionated heparin; LMWH = low-molecular-weight heparin; F-Xa = factor Xa.

Statistical analysis

The following were key measurements at the once-off baseline assessment: (i) clinical VTE risk assessment; (ii) VTE risk assessment with the Caprini RAM; (iii) surgical subspecialty; and (iv) type, duration and dosage of VTE prophylaxis prescribed.

Results and discussion

Before applying the Caprini VTE risk factor assessment scale, the treating doctors deemed 269 patients (59.4%) to be at risk for VTE (private n=149 (47.3%), public n=120 (87.0%)) and 182 (40.2%) not to be at risk (private n=164 (52.1%), public n=18 (13.0%)) (Table 4 and Fig. 1). VTE risk assessments were not recorded for two private patients.

The 269 patients clinically assessed as being at risk for VTE were assigned the following risk levels: ‘low’ risk n=3, ‘moderate’ risk n=18, ‘high’ risk n=88, and ‘highest’ risk n=160. However, all the patients included in the study were at risk to a greater or lesser extent as assessed on the Caprini RAM (Table 4 and Fig. 1). Applying the RAM resulted in an additional 184 patients being classified as at risk for VTE.

Reasons for not prescribing prophylaxis

Table 3. Bleeding risk assessment Has the patient, or a blood relative, ever received medical care for a bleeding tendency, e.g.:

Why prophylaxis was not prescribed was reported for 91 patients (private n=63, public n=28), early mobilisation and low VTE risk being the most frequent reasons cited.

Mobilisation (sometimes early) was reported 65 times as the reason why prophylaxis was not prescribed. ‘Early and aggressive mobilisation’ was actually listed as a prophylactic measure in the study case report form. Fifteen patients in the private and 2 in the public sector were assessed as being at risk of bleeding according to the bleeding risk assessment (Table 3).

There was an increased perception of bleeding risk in the private sector, probably reflecting the fact that a higher proportion of patients were on antiplatelet drugs such as aspirin and thienopyridines, e.g. clopidogrel. Notably, the surgeon scheduled to perform the procedure

Nose bleeds (epistaxis) Excessive bleeding after a dental procedure or extraction Excessive bleeding after trauma or surgery Excessive bleeding after tonsillectomy Excessive bleeding during childbirth or during menstruation Excessive bleeding from minor cuts?

Does the patient bruise easily?

Does the patient have a history of heparin-induced thrombocytopenia?

Is the patient’s platelet count <100 × 109/L or >1 000 × 109/L? Is the patient taking aspirin or clopidogrel?

Does the patient have kidney or liver disease?

Is the patient on any medication (such as NSAIDs, and including natural/homeopathic medication, e.g. garlic tablets, arnica, Procydin) that increases the risk of bleeding?

NSAIDs = non-steroidal anti-inflammatory drugs.

Table 4. VTE risk assessment of patients before (clinically at risk) and after applying the Caprini RAM Private (N=315)

Public (N=138)

All (N=453)

Caprini VTE risk level determined on TRFS

Clinically at risk, n (%)

RAM at risk, n (%)

Clinically at risk, n (%)

RAM at risk, n (%)

Clinically at risk, n (%)

RAM at risk, n (%)

Low (TRFS 0 - 1)

- (0)

15 (4.7)

3 (33.3)

9 (6.5)

3 (12.5)

24 (5.3)

Moderate (TRFS 2)

6 (12.2)

49 15.6)

12 (63.2)

19 (13.8)

18 (26.5)

68 (15.0)

High (TRFS 3 - 4)

46 (39.0)

118 (37.5)

42 (93.3)

45 (32.6)

88 (54.0)

163 (36.0)

Highest (TRFS ≥5)

97 (72.9)

133 (42.2)

63 (96.9)

65 (47.1)

160 (80.1)

198 (43.7)

Total

149 (47.3)

315 (100)

120 (87.0)

138 (100)

269 (59.4)

453 (100)

VTE = venous thromboembolism; RAM = risk assessment model; TRFS = total risk factor score.

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RESEARCH

Table 5. VTE prophylaxis according to the Caprini RAM Private (N=315)

Public (N=138)

All (N=453)

Caprini VTE risk level determined on TRFS

Patients, n (%)

Prophylaxis prescribed, n (%)*

Patients, n (%)

Prophylaxis prescribed, n (%)*

Patients, n(%)

Prophylaxis prescribed, n (%)*

Low (TRFS 0 - 1)

11 (3.5)

9 (81.8)

9 (6.5%)

2 (22.2)

20 (2.4)

11 (55.0)

Moderate (TRFS 2)

42 (13.3)

40 (95.2)

19 (13.8)

15 (78.9)

61 (13.5)

55 (90.2)

High (TRFS 3 - 4)

125 (39.7)

121 (96.8)

43 (31.2)

35 (81.4)

168 (37.1)

156 (92.9)

Highest (TRFS â&#x2030;Ľ5)

137 (43.5)

135 (98.5)

67 (48.5)

58 (86.6)

204 (45.0)

193 (94.6)

Total

315 (100)

305 (96.8)

138 (100)

110 (79.7)

453 (100)

415 (91.6)

VTE = venous thromboembolism; RAM = risk assessment model; TRFS = total risk factor score. *Percentages of patients according to Caprini RAM levels in whom prophylaxis was prescribed.

100% 100 90 80 70 60 % 50 40 30 20 10 0

100% 87%

59.4% 47.3%

Private sector

sector probably relates to the longer duration of admission in the public sector.

100% At risk as clinically assessed At risk according to RAM

Public sector

All

Fig. 1. VTE risk assessment: clinical v. RAM TRFS (VTE = venous thromboembolism; RAM = risk assessment model; TRFS = total risk factor score.)

was also the assessor of bleeding risk in the private sector. A bias therefore existed to prevent postoperative bleeding, and possible litigation, in the private sector. Other reasons for omitting prophylaxis included need for ventilation, surgery in a vulnerable site, e.g. the spine, and presence of a haematoma. More than one reason for the omission of VTE prophylaxis was reported for some patients.

Prophylaxis prescribed

The distribution of patients according to healthcare sector, Caprini risk score and VTE prophylaxis prescribed is set out in Table 5. Percentages were calculated out of the sample sizes for private (n=315), public (n=138) and all (N=453) patients.

VTE prophylaxis was prescribed to 110 (79.7%) of the 138 public sector patients, of whom 81.4% in the high-risk level and 86.6% in the highest-risk level received prophylaxis.

VTE prophylaxis was prescribed to 305 of the 315 private patients (96.8%), of whom 96.8% in the high-risk level and 98.5% in the highest-risk level received prophylaxis.

The chemoprophylaxis regimens differed between the private and public sectors, possibly owing to availability of preparations (reflecting state tenders in the public sector),

drug cost (unfractionated heparin (UFH) costs less than low-molecular-weight heparin (LMWH)), and VTE prophylaxis protocols in specific medical institutions.

The use of LMWH predominated in the private sector, with 92% of patients receiving LMWH and the balance (8%) oral factor Xa inhibitors. Low-dose UFH was not prescribed in the private sector. Conversely, only 67.5% of public sector patients received LMWH, the rest receiving UFH. There was no use of oral factor Xa inhibitors in the public sector. The LMWH dose was most commonly 40 mg once daily in both sectors and that of UFH 5 000 IU twice daily. The use of non-chemotherapeutic prophylactic VTE prophylaxis was extremely limited in both the private and the public sectors, with pneumatic stockings being used in <3% of patients.

Duration of prophylaxis

The overall duration of prophylaxis across all risk levels was 6.5 days and was similar in both healthcare sectors. The average duration of prophylaxis for high- and highest-risk patients, however, was 4.89 and 7.33 days in the private and public sectors, respectively. The longer duration of prophylaxis in patients in the high/ highest-risk groups in the public v. the private

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Conclusion

The TUNE-IN Wave 2 registry provided valuable insight regarding the use of routine patient risk assessment in surgical inpatients in both the private and the public sectors.

The registry determined that all the surgical inpatients in the study population were at risk of VTE to some extent. Doctors do not routinely formally risk-assess patients, and use of a formal RAM increases their awareness of patient risk. The results of this study mirror those of the TUNE-IN study, confirming the Caprini RAM to be applicable across all healthcare sectors in SA. Before applying the Caprini RAM, the admitting doctors clinically diagnosed only 269 (59.4%) of the patients to be at risk for VTE. Public sector patients were clinically assessed as being at risk for VTE more commonly than those in the private sector (87.0% v. 47.3%). However, all the patients in the study were at risk to a greater or lesser extent as assessed on the RAM. After applying the Caprini RAM, VTE prophylaxis was prescribed to 415 (91.6%) of the 453 patients in the study. Prophylaxis was prescribed for 92.9% of the patients in the high-risk category and to 94.6% of those in the highest-risk category. A greater percentage of patients across all risk levels in the private v. the public sector received prophylaxis (96.8% v. 79.7%), possibly owing to availability of chemoprophylaxis drug preparations, costs and VTE prophylaxis protocols. Despite all the patients in the study being at risk to some extent, 8.4% did not receive any form of prophylaxis.

Assessment of VTE risk as being low was the most frequent reason for not prescribing prophylaxis in both healthcare sectors.

Early and aggressive mobilisation con­ tinues to be seen as an active form of VTE prophylaxis in both sectors. It was the sole

RESEARCH

form of prophylaxis in 47.6% of the private and 20.3% of the public sector patients. Chemoprophylaxis prescribed included LMWH, lowdose UFH and oral factor Xa inhibitors, and was prescribed to 41.6% of the private and 58.7% of the public sector patients with or without concomitant use of graduated compression stockings or intermittent pneumatic compression.

The recommended doses of chemo­prophylaxis in VTE prophylaxis guidelines appear to be being adhered to in both sectors. Forty milli­ grams of LMWH daily and 5 000 IU UFH twice daily were the doses most commonly prescribed. The average duration of prophylaxis across all risk levels was similar in the two sectors (6.2 days in the private and 7.0 days in the public sector), with an overall average of 6.5 days.

There is room for improvement in both the public and the private sectors with respect to identifying and assessing patients at risk of VTE, as well as provision of correct prophylaxis. The implementation of a formalised VTE risk assessment tool will benefit patients and ensure standardisation of VTE risk assessment and administration of adequate prophylaxis.

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Declarations and ethics approval. This study was funded by Sanofi South Africa (Pty) Ltd. Dr Wayne Riback is employed by Sanofi as Senior Medical Advisor. Data analysis was prepared and compiled by the Data Management Department of Sanofi, supported by an independent data report via a contracted third party. Ethical approval for the study was obtained from Pharma Ethics and the relevant ethics committees of the participating hospitals.

References 1. Cohen AT, Tapson VF, Bermann J-F, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): A multinational cross-sectional study. Lancet 2008;371(9610):387-394. [http://dx.doi.org/10.1016/S0140-6736(08)60202-0] 2. Guyatt GH, Akl EA, Crowther M, et al. American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Antithrombotic therapy and prevention of thrombosis. 9th ed.

Chest 2012;141(2 Suppl):7S-47S. [http://dx.doi.org/10.1378/chest.1412S3] 3. Jacobson BF, Louw S, Büller H, et al. Venous thromboembolism – prophylaxis and therapeutic practice guidelines. S Afr Med J 2013;103(4):261-267. [http://dx.doi.org/10.7196/samj.6706] 4. Wessels P, Riback WJ. DVT prophylaxis in relation to patient risk profiling – the TUNE-IN study. S Afr Med J 2012;102(2):85-89.

Accepted 9 September 2014.

December 2014, Vol. 104, No. 12

GUEST EDITORIAL

Management challenges in tuberculosis and HIV Globally, South Africa (SA) is disproportionately affected by the epidemics of tuberculosis (TB) and the human immunodeficiency virus-1 (HIV-1). The intersection of these two diseases has resulted in an unprecedented disease burden. It is estimated that 12.2% of South Africans are HIV-infected – a total of 6.4 million people, the largest number in any country in the world.[1] SA has the second highest annual incidence of TB after Swaziland – approximately 1% of the population develop active TB disease each year (an estimated 530 000 people in 2012).[2] While SA comprises 0.7% of the world’s population, it is estimated that of all cases of HIVassociated TB that occur worldwide annually, 30% are in SA.[2] Important gains have been made in the public health response to HIV in the past decade. Starting in 2004, the public sector antiretroviral therapy (ART) programme has enabled over 2 million South Africans to start ART – the largest ART treatment programme in the world.[1] Modelling studies have suggested that ART, when initiated before advanced immunosuppression, allows for a nearnormal life expectancy.[3] An expanded treatment programme has reversed the alarming decreases in life expectancy of South Africans in the 1990s. In rural KwaZulu-Natal, life expectancy rose by 11.3 years between 2003 and 2011.[4] The prevention of mother-tochild transmission (PMTCT) scale-up of antiretroviral strategies, starting with single-dose nevirapine, then adding zidovudine and most recently offering all pregnant mothers triple-drug ART, has dramatically reduced the transmission rates and consequently the prevalence of HIV in the paediatric population. However, HIV incidence rates remain high in the adolescent and adult population owing to sexual transmission.[1] Despite the abovementioned gains, TB and HIV, often as co-infection, remain the most important causes of morbidity and mortality among adult South Africans.[5] HIV-related complications are the most common cause for admission to hospital medical wards in SA. At Khayelitsha Hospital in Cape Town, >50% of patients admitted to the medical wards are HIV-infected; many of them also have active TB (G Meintjes – unpublished data).

Therefore, while SA has the largest ART programme in the world, there has not been the same dramatic impact in the prevention of HIV opportunistic infections as in industrialised countries when ART was first introduced.[6] There are many reasons for this, including the following: the number of people living with HIV infection in SA; many patients are diagnosed with HIV when they have advanced immunosuppression; some patients experience virological failure while on ART owing to adherence problems; some patients disengage from care and default ART; even with successful immune reconstitution on ART, HIV-infected patients remain at higher risk of TB disease than HIV-uninfected people in the same community; and the high rates of transmission of TB infection in many communities.

In light of this TB and HIV disease burden, this edition of CME focuses on a number of key topics in the management of HIV, TB and co-infection. Six topics were chosen because these are common clinical scenarios in which diagnosis and management can be challenging and for which there are recent research findings to inform changes in clinical practice.

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Wasserman and Meintjes[7] review HIV-associated TB, focusing on diagnostic advances, complications that arise when providing simultaneous treatment for TB and HIV, when to start ART in HIVinfected TB patients, and use of isoniazid preventive therapy (IPT) for TB. The additive benefit of IPT in patients on ART in preventing incident TB has recently been shown.[8] About 15 000 cases of multidrug-resistant TB were diagnosed in SA in 2012.[2] This condition is difficult to manage, particularly as current treatments are less effective than first-line TB treatment, of prolonged duration (18 - 24 months), and difficult to tolerate – with significant toxicities. Outcomes are currently particularly poor for patients with extensively drug-resistant TB (DR-TB).[9] Hughes and Osman,[10] both of whom have expertise in managing DR-TB at primary care level, provide practical insights on its diagnosis and management and also cover new drug options that are becoming available.

TB meningitis has the highest mortality rate of all forms of TB – up to 60% in patients with HIV co-infection.[11] Patients who survive, frequently remain with a neurological disability. Diagnosis is made challenging by the limited sensitivity of TB diagnostic tests in the cerebrospinal fluid.

The clinical course may be complicated by the immune reconstitution inflammatory syndrome in HIV-infected patients who start ART. An approach to these issues, informed by recent research findings, is covered in the article by Marais and Wilkinson.[12] After TB, cryptococcal meningitis is probably the most important co-infection contributing to mortality in HIV-infected adults in SA. More than 6 000 cases were diagnosed in laboratories in SA in 2013.[13] Management of this condition involves initial amphotericin B-based combination antifungal therapy and subsequent consolidation and maintenance with fluconazole, control of raised intracranial pressure with therapeutic lumbar punctures and initiation of ART 4 - 6 weeks after diagnosis.[14] Govender and Dlamini[15] discuss issues related to cryptococcal meninigitis prevention and management.

Finally, there are two articles that focus on paediatric HIV management.

Adherence to ART is a critical determinant of its long-term success.

Adherence is particularly challenging in adolescents. Fairlie et al.[16] address the medical aspects of ART management in adolescents, as well as approaches to optimise adherence and ensure successful transition to adult care when appropriate. While new infections in children have decreased owing to SA’s PMTCT programme, vertical transmission of HIV still occurs. Frigati et al.[17] deal with ART management of paediatric patients prior to adoles­ cence, emphasising the importance of early diagnosis and early ART initiation to limit morbidity and mortality. This may also potentially limit the size of the HIV viral reservoir.

Graeme Meintjes Guest editor graemein@mweb.co.za S Afr Med J 2014;104(12):885. DOI:10.7196/SAMJ.9121

December 2014, Vol. 104, No. 12

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REVIEW

The diagnosis, management and prevention of HIV-associated tuberculosis S Wasserman,1 MB ChB, MMed, FCP (SA), Cert ID (SA) Phys; G Meintjes,1,2 MB ChB, FRCP (Glasg), FCP (SA), Dip HIV Man, MPH, PhD Division of Infectious Diseases and HIV Medicine, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa; and Department of Medicine, Imperial College London, UK

1 2

Corresponding author: S Wasserman (sean.wasserman@gmail.com)

Tuberculosis (TB) and its strong association with HIV infection are the most important causes of the high rates of infectious morbidity and mortality in South African adults. The interaction between HIV and TB leads to more frequent smear-negative and extrapulmonary disease, resulting in atypical clinical presentations and altered performance characteristics of diagnostic tests. New and emerging diagnostics are being used to support earlier initiation of therapy and detection of drug resistance, although these have inherent limitations and empirical therapy is often still required. The management of HIV-associated TB is complicated by rapid clinical progression of disease, immune reconstitution inflammatory syndrome, drug-drug interactions and shared toxicities. A strong evidence base now provides guidance on the timing of initiation of antiretroviral therapy, the use of corticosteroids in TB and the use of isoniazid preventive therapy. This article provides a clinically oriented overview of the diagnosis, management and prevention of HIV-associated TB, with a focus on recent evidence in the field.

S Afr Med J 2014;104(12):886-893. DOI:10.7196/SAMJ.9090

The aim of this article is to update readers on recent evidence-based advances in the field and it is not intended to provide a comprehensive review of HIV-associated TB. Information was mainly sourced from personal archives and from citations in recently published reviews. Our references were selected based on relevance to the topic and impact on current practice. We have expressed the quality of evidence for each recommendation by describing the study methodology.

The colliding risk factors of HIV, poverty and a large mining workforce have resulted in an unparalleled burden of tuberculosis (TB) in South Africa (SA) and neighbouring countries in terms of incidence rates.[1] According to the most recent World Health Organization (WHO) global report, over half a million incident cases of TB occurred in SA in 2012 with an estimated 65% of these in HIV-co-infected patients.[2] However, despite the availability of effective first-line antituberculous drugs and large-scale rollout of antiretroviral therapy (ART), TB is still the most common opportunistic disease and main driver of mortality in HIV, causing up to 100 000 deaths in SA in 2012.[2] Latent infection with TB has a much higher chance of reactivating in HIV as a result of loss of competent immune

control, translating into an annual risk of up to 10%, at least 12- to 20-fold higher than in immunocompetent individuals.[3] Because TB causes higher rates of disease and mortality in HIV,[4] it is a priority to make an early diagnosis, initiate antituberculous therapy timeously, provide appropriate HIV care (including ART and co-trimoxazole preventive therapy) and implement evidencebased interventions for prevention.

In this article we review the diagnosis, management and prevention of drug-susceptible TB in HIV-infected patients, with a focus on recent evidence. Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) has been reviewed in a recent CME article[5] and a review of drug-resistant TB is included in this edition, so these topics will not be covered here.

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Table 1. Key performance characteristics of diagnostic tests for tuberculosis performed in HIV-infected patients

Test

Limit of detection (bacilli/mL of sputum)

Sensitivity

Comments

Sputum culture (liquid system)

10 - 100

80%[11] (relative to clinical reference standard)

Reference test Can be used for speciation and drug susceptibility testing Used to monitor response to therapy 1 - 6 weeks for result

Sputum smear microscopy

>10 000

30 - 40%[12-14]

Cannot distinguish non-tuberculous mycobacteria from TB Used to monitor response to therapy

Sputum Xpert MTB/RIF

10 - 100

Single specimen • Overall 79 - 84%[15,16] • Smear-negative disease 68%[15] (incremental yield from 2 and 3 specimens)[17]

Rapid turnaround time Detects rifampicin resistance Cannot be used to monitor response to therapy Positive results are not reliable after a recent episode of TB treatment

Determine TB-LAM Ag (urine)

NA

Screening 67% (at CD4+ counts <50)[18] Inpatients 40%[19]

High specificity Best performance in CD4+ counts <50 Very poor sensitivity with CD4+ counts >100

NA = not applicable; TB = tuberculosis.

Diagnosis

The clinical presentation of HIV-associated TB is often nonspecific: cough is less frequent,[6] and patients commonly present with extrapulmonary disease in the absence of respiratory symptoms and radiological abnormalities.[7] The prevalence of smearnegative pulmonary TB is high, ranging from 25% to 61%,[8] and is associated with a poorer prognosis.[9-11] It is therefore critical to understand how to select and interpret available diagnostics. These are discussed below and key performance characteristics are summarised in Table 1.[11-19]

Supportive investigations

Basic radiological and laboratory investiga­ tions are widely available and provide valuable information when assessing TB suspects with HIV. The drawbacks of these ancillary tests are limited sensitivity and specificity, but they have potential to support early empirical therapy when there is a high clinical pre-test probability of TB.

The chest X-ray (CXR) findings of TB in patients with CD4+ <200 cells/µL are often atypical compared with the classic upperlobe cavitation seen in immunocompetent individuals, and may include nodular infiltrates, pleural effusions and intrathoracic lymphadenopathy.[20,21] While these CXR patterns can be strongly supportive of TB in the correct clinical setting, up to 30% of patients with culture-confirmed HIV-associated pulmonary TB may have completely normal CXRs,[22] limiting the sensitivity of this investigation.

Abdominal ultrasonography is useful as a rule-in test for HIV-infected TB suspects, especially in patients presenting with abdominal tenderness or otherwise unexplained systemic symptoms.[23] Sugges­ tive features include intra-abdominal lymph­ adenopathy, ascites, bowel-wall thick­ ening and splenic hypodensities.

The finding of a lymphocyte-predominant exudate in pleural or pericardial fluid is strongly suggestive of TB in high-prevalence

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settings, and can often be used as a basis for empirical antituberculous therapy. But similarly to CXR and abdominal ultrasound, these findings are not specific for TB and may occur with other HIV-associated diseases such as cryptococcosis and lymphoma.

Growth-based detection

The reference standard for diagnosing TB is a positive culture of Mycobacterium tuberculosis on a clinical specimen. Culture remains the most sensitive method for diagnosis and allows for subsequent speciation, drug susceptibility testing and monitoring of microbiological response to therapy. Automated liquid culture systems have largely replaced solid media techniques because of simpler laboratory workflows, higher sensitivity and earlier detection times.

However, the median time to detection still ranges between 11 and 15 days,[24,25] and therefore cultures cannot be used to guide initial treatment decisions in a patient who is deteriorating rapidly.

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Growth of M. tuberculosis from a clinical site represents viable replicating bacilli, and should be interpreted as indicating active disease and the need for therapy. However, there is a substantial proportion of patients with culture-negative disease who respond to antituberculous therapy[11] who should be evaluated according to the WHO 2007 clinical algorithm.[26] This phenomenon may be related to an inadequate sample or a sample from an inappropriate clinical site being sent to the laboratory.

Smear microscopy Sputum smear microscopy, traditionally performed with ZiehlNeelsen (ZN) staining, is a rapid, specific method of detecting infectious patients with TB and for monitoring microbiological response to therapy. Microscopy requires at least 10 000 organisms per mL of sputum, and therefore will detect fewer cases in HIV-infected patients who frequently have paucibacillary or extrapulmonary disease.[6] Yield can be increased by collecting two early morning specimens, but the gain in sensitivity with a third sputum specimen is very small, resulting in 2 - 5% more positives.[27] Sputum induction with nebulised hypertonic saline potentially identifies approximately 25% additional cases in symptomatic patients who are smear-negative or unable to spontaneously produce sputum.[28] In some settings, over two-thirds of HIV-infected patients with active TB requiring therapy may be missed by smear microscopy.[12,29] Although staining with auramine O and fluorescence microscopy improves sensitivity by about 10%,[13] overall performance remains suboptimal, meaning that a negative smear does not exclude the diagnosis of TB in HIV co-infected patients.

Molecular methods Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is a closed real-time polymerase chain reaction (PCR) assay that amplifies an 81 base-pair region of the M. tuberculosis RNA polymerase β subunit (rpoB) gene.

This target is specific for M. tuberculosis-complex and is the site of the majority of mutations associated with rifampicin resistance, therefore allowing rapid detection of rifampicin-resistant TB directly from clinical specimens.

Compared with culture as the reference test, the overall sensitivity of a single Xpert is 89%, and about 10% lower in patients with HIV. As an add-on test after negative smear microscopy, the sensitivity drops to 67%,[15] thus still missing a third of sputum smear-negative culture-confirmed TB. Because PCR is able to detect DNA within both live and dead organisms, molecular-based diagnostics may test positive despite being culture-negative. There are reports that the Xpert assay may remain positive after successful treatment of TB, [30] and evidence that around a quarter of patients successfully treated for TB will be Xpert positive at 6 months. [31] Therefore, Xpert should not be used to monitor response to therapy, and cannot

Table 2. Performance of Xpert for the diagnosis of extrapulmonary tuberculosis on selected specimens (compared against culture) Lymph node[32]

CSF[32]

Pleural fluid[32]

Sensitivity, %

84.9

79.5

43.7

Specificity, %

92.5

98.6

98.1

CSF = cerebrospinal fluid.

be used alone to confirm a recurrent episode of TB after a recent treatment episode (the precise duration has not been defined but we suggest confirming with culture if treated for TB within the last year).

Xpert performs well on lymph-node aspirates, pus and cerebrospinal fluid (CSF), and the WHO recommends its use on these specimens as a replacement for smear microscopy for patients with suspected extrapulmonary tuberculosis (EPTB) or tuberculous meningitis (TBM).[32] Clinicians should, however, be aware that Xpert still lacks sensitivity to exclude TBM in patients in whom the diagnosis is clinically suspected, and empirical therapy should not be withheld because of a negative CSF result. Xpert performs poorly with blood and pleural fluid, and is not recommended for use on these specimens (Table 2).

There is emerging evidence that the assay has good performance characteristics on urine when used in patients with low CD4+ counts and disseminated TB. Other molecular diagnostic tests are available, including line probe assays (LPA) that use reverse hybridisation technology to speciate and detect drug resistance mutations in mycobacteria. Unlike Xpert, the LPA is prone to contamination and is less reliable when performed directly on clinical specimens. The value of LPA is its ability to detect resistance to other antituberculous drugs in addition to rifampicin, as well as detecting dual-strain infection. Its use on microscopypositive specimens or culture isolates has reduced time to initiation of multidrug-resistant TB therapy.[33]

Urinary lipoarabinomannan (LAM)

LAM is a lipopolysaccharide molecule in the mycobacterial cell wall and serves as a virulence factor by promoting intracellular survival of M. tuberculosis. Detection of LAM in the urine of HIV-infected patients probably represents renal tract involvement with TB.[34] The test is available as an immunochromatographic lateral flow assay or dipstick test (Determine TB-LAM Ag [urine LAM], Alere, Waltham, MA, USA) that can be used at point of care by adding unprocessed urine onto the test strip.

When LAM was used for screening outpatients entering an ART programme, the overall sensitivity of the urine LAM for diagnosing culture-confirmed TB was only 28.2%, but was much

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higher (66.7%) in the subgroup with CD4+ counts <50 cells/µL. When combined with smear microscopy the sensitivity rose further to 72.2%, similar to a single-sputum Xpert. The specificity is excellent, exceeding 98%, and the positive predictive value is over 90% in patients with advanced HIV.[18] In another study, urine LAM provided a rapid diagnosis with a sensitivity of almost 40% among unselected HIV-infected medical admissions with a high prevalence of newly diagnosed EPTB. When urine LAM was combined with urine Xpert, TB was rapidly diagnosed in 85% of patients with CD4+ counts <100 cells/µL.[19] Despite a growing evidence base, urine LAM has not yet been endorsed as a diagnostic test by the WHO and is currently considered to be investigational, but it may become available for clinical use in the future.

In summary, culture-based diagnostics remain the gold standard for microbiological diagnosis of TB. Smear microscopy is insensitive but important for identifying the most infectious patients and for monitoring response to therapy. Xpert represents a major advance in TB diagnostics with rapid identification of rifampicin resistance and a 30% higher yield than microscopy for pulmonary disease.[16] However, it performs poorly for HIV-infected inpatients who are unable to produce sputum[19] and cannot be used alone to diagnose recurrent episodes after recent treatment for TB. The use of Xpert on selected extrapulmonary specimens is now recommended by the WHO and will soon be introduced into local guidelines. Urine LAM is valuable for rapid point-of-care diagnosis, but should be reserved for admitted HIV-infected patients or those with CD4+ counts <100 cells/µL as it performs poorly in other groups of patients.

Management Approach

TB results in more rapid clinical deterioration in HIV infection.

Clinicians should have a high index of suspicion for TB in any HIV-infected patient with rapid loss of weight in the absence of diarrhoea, or with impairment in daily functions due to systemic symptoms, whether or not they have a cough. TB suspects with any of the following danger signs require hospitalisation for urgent investigation and consideration for empirical broad-spectrum antibiotics: unable to walk unaided, respiratory rate ³30/minute, fever ³39°C or pulse rate ³120/minute.[26] These patients should also be assessed for other life-threatening opportunistic infections such as Pneumocystis pneumonia, bacterial sepsis and cryptococcal disease with CXRs, blood cultures and serum cryptococcal antigen testing (if CD4+ counts <100 cells/µL). The decision to start empirical antituberculous therapy depends on the severity of the clinical presentation, response to initial antibiotics and access to diagnostic tests, with a low threshold to start early in ill patients or those with a rapidly deteriorating condition, even if the CXR is normal.

Potential pitfalls of empirical treatment include missing another serious opportunistic disease or drug-resistant TB and exposing a patient unnecessarily to a course of antituberculous therapy.

Therefore, it is important to confirm the diagnosis with an appropriate culture-based or molecular assay. However, empirical therapy should not be delayed while awaiting results in patients with a high clinical pre-test probability of TB. Patients started on empirical therapy must be followed up closely and the diagnosis should be reconsidered if there is no clinical response after, or deterioration within, 2 - 4 weeks, especially if cultures are negative. An important cause of failure to respond to empirical antituberculous therapy is unrecognised drug-resistant TB, further emphasising the need to collect adequate specimens for culture and drug susceptibility testing prior to initiating therapy.

Antituberculous therapy

The treatment of HIV-associated TB is the same as in HIV-negative patients. The WHO recommends a standard regimen of 2 months of rifampicin, isoniazid, ethambutol and pyrazinamide followed by 4 months of rifampicin and isoniazid, preferably in fixed-dose combination tablets and dosed according to weight. Therapy should be administered 7 days a week throughout the course.[35,36]

Adjunctive therapy

Unless contraindicated because of previous intolerance, all HIVinfected patients with TB should receive co-trimoxazole preventive therapy (2 single-strength tablets or 1 double-strength tablet daily) and pyridoxine (25 mg daily). Co-trimoxazole prophylaxis may prevent opportunistic infections such as Pneumocystis, isosporiasis and invasive Salmonella disease, and has been shown to reduce mortality by up to 46% in patients with HIV-associated TB.[37] Although the optimal duration of therapy is unclear, it can be discontinued in nonmalaria endemic settings when the CD4+ count is >200 cells/µL. The recommendation for pyridoxine supplementation is based on the observation that sensory polyneuropathy is more common in patients with HIV and TB, possibly because of vitamin B6 deficiency caused by isoniazid therapy.[38] Unless there is another compelling indication, the use of corticosteroids in HIV-associated TB is reserved for patients with significant symptoms related to TB-IRIS[39] and for all cases of TBM. A randomised controlled trial (RCT) conducted in Vietnam demonstrated a 31% reduction in mortality in patients with TBM treated with high doses of steroids, regardless of severity of symptoms.

There was also a trend towards improved survival in the subgroup of HIV-infected patients although this did not reach statistical significance.[40] Prednisone is not recommended for tuberculous pericarditis in HIV, as it conferred no survival benefit and was associated with an increased risk of HIV-related malignancies in an RCT.[41]

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Antiretroviral therapy

Observational studies have demonstrated a reduction in mortality risk of 64 - 95% in patients with HIV-associated TB who are receiving concurrent ART,[42] and an RCT performed in Durban showed improved survival for patients with CD4+ counts ≤500 cells/µL who started ART during antituberculous therapy.[43] Both WHO and the SA National Department of Health (NDoH) guidelines recommend that all HIV-infected patients with active TB be initiated on ART regardless of CD4+ count.

The benefits of starting ART early in patients with TB need to be balanced against the risks of TB-IRIS and overlapping drug toxicities, which are more likely to occur if ART is started early after the start of TB therapy. Three RCTs have recently provided clarity on the issue of timing of ART in TB, all showing a survival benefit (or benefit in terms of a cumulative endpoint of mortality and AIDS progression) for patients with CD4 counts <50 cells/µL starting ART after ~2 weeks of antituberculous therapy compared with deferring to around 8 weeks.[43-45] Patients with CD4+ counts >50 cells/µL

Table 3. Common drug interactions between antituberculous therapy and ART Antituberculous therapy Rifampicin-based

Rifabutin-based

Antiretroviral

Interaction

Comments

Efavirenz

Efavirenz concentrations not reduced

• No dose adjustment required

Nevirapine

Reduced concentrations of nevirapine

• Preferably use efavirenz • Omit 200 mg daily lead-in dose and start with 200 mg bd

Rilpivirine

Reduced concentrations of rilpivirine

• Do not co-administer

Etravirine

Reduced concentrations of etravirine

• Do not co-administer

Lopinavir/ ritonavir

Reduced concentrations of lopinavir

• Requires double dose with 4 tablets (800/200 mg) bd in adults (guidelines in children are different) • Increase the dose gradually: 3 tabs bd for a week then 4 tabs bd for duration of rifampicin use • Reduce dose back to 2 tabs bd 1 - 2 weeks after rifampicin stopped

Atazanavir/ ritonavir

Reduced concentrations of atazanavir

• Do not co-administer

Darunavir/ ritonavir

Reduced concentrations of darunavir

• Do not co-administer

Raltegravir

Reduced concentrations of raltegravir

• A recent clinical trial suggests that dose increase is not required[48]

Efavirenz

Reduced concentration of rifabutin

• Requires increased dose of rifabutin 450 mg daily

Nevirapine

Non-significant increase in rifabutin

• No dose adjustment required

Rilpivirine

Reduced concentrations of rilpivirine

• Avoid if possible, otherwise requires increased dose of rilpivirine 50 mg daily

Etravirine

Reduced concentrations of etravirine

• Do not co-administer if used together with a boosted protease inhibitor

Ritonavir-boosted protease inhibitors

Increased concentrations of rifabutin

• Requires reduced dose of rifabutin 150 mg alternate days • Can be used with standard doses of ritonavirboosted lopinavir, atazanavir and darunavir

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do not have an increased risk of death or AIDS-defining events if ART is delayed for up to 8 weeks, thus providing an important opportunity to establish patients on antituberculous therapy and provide counselling for lifelong treatment before starting ART. Patients with all forms of TB and CD4+ counts >50 cells/µL should therefore start ART within 8 weeks of TB treatment, and clinicians should ensure that they remain engaged in ART counselling until they start ART. However, it is advised that if these patients have other stage 4 defining conditions then ART should also be started at 2 weeks (except for cryptococcal meningitis, where ART should be deferred to 4 - 6 weeks after diagnosis). ART should be delayed for 4 - 8 weeks in patients with TBM regardless of CD4+ count.[46] The WHO-recommended ART regimen for patients with TB is tenofovir, lamivudine/emtricitabine and efavirenz (EFV). These drugs are available in fixed-dose combination tablets and do not require dose adjustment when given with antituberculous therapy. Despite a US Food and Drug Administration (FDA) recommendation to use higher doses of EFV during treatment with rifampicin, there is no evidence that EFV concentrations are significantly lower or virological outcomes worse in patients being treated for TB and with standard EFV dose, and the practice of increasing EFV dose to 800 mg daily is not advised.

Nevirapine (NVP)-based ART is inferior to EFV-based regimens in patients with TB. This was recently demonstrated in the CARINEMO trial, where fewer patients on NVP-based ART achieved HIV viral suppression compared with those taking EFV.[47] NVP also results in higher rates of cutaneous drug reactions and liver injury than EFV, and its use should therefore be limited to patients who are unable to tolerate EFV. If NVP is prescribed for patients with TB, the starting dose should be 200 mg twice daily (the lead-in dose of 200 mg daily is omitted) because of enzyme induction by rifampicin.

Drug toxicity and interactions

There are multiple potential drug interactions and shared toxicities between ART and antituberculous therapy, especially when treating drug-resistant TB or using second-line ART. Tables 3 and 4 list the most clinically significant drug interactions and toxicities of commonly used agents, with advice on co-administration. There are also important potential interactions between antituberculous drugs and other commonly used drugs in HIV such as antifungals, macrolides and steroids, and it is important to check these before prescribing.

Cutaneous drug reactions (CDRs) are common in HIV-infected patients with TB and have a wide spectrum of clinical presentations.

These range from mild morbiliform rashes to Stevens-Johnson syndrome or systemic involvement with eosinophilia and hepatitis.

Mild rash can be treated symptomatically with continuation of all drugs and close clinical observation. Patients with severe CDRs need to immediately stop all potentially offending agents and be admitted to hospital. Co-trimoxazole is an important cause of adverse drug reactions in HIV and should be stopped in all cases of suspected drug rash. In general, non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be avoided once implicated in a severe CDR, but it is often possible to successfully rechallenge antituberculous drugs. Expert advice should be sought in all cases.

The Southern African HIV Clinicians Society has recently published a comprehensive guideline on drug-induced liver injury (DILI) in HIV-associated TB.[49] Table 5 lists important indications for stopping drugs implicated in CDRs and DILI.

Isoniazid preventive therapy (IPT)

IPT is established as a safe and effective measure to reduce TB in HIV-infected individuals,[50] and has an additive effect when given

Table 4. Important shared toxicities Adverse effect

Antituberculous drug

Antiretroviral

Other

Gastrointestinal disturbance

All TB drugs especially ethionamide and PAS

AZT, PIs, ddI

Macrolides

Liver injury

RIF, INH, PZA, quinolones, ethionamide, PAS

NNRTIs, PIs

Co-trimoxazole, azole antifungals, anticonvulsants

Nephrotoxicity

Injectables, RIF

TDF*

Amphotericin B

Drug rash

All TB drugs

NNRTIs (NVP > EFV), DRV, RAL

Co-trimoxazole

Peripheral neuropathy

INH, terizidone,† ethionamide, linezolid

d4T, ddI

Neuropsychiatric

INH (especially high dose), terizidone, ethionamide

EFV

TB = tuberculosis; PAS = para-aminosalicylic acid; AZT = zidovudine; PIs = protease inhibitors; ddI = didanosine; RIF = rifampicin; INH = isoniazid; PZA = pyrazinamide; NNRTIs = non-nucleoside reverse transcriptase inhibitors; TDF = tenofovir; NVP = nevirapine; EFV = efavirenz; DRV = darunavir; RAL = raltegravir; d4T = stavudine. * Avoid TDF if using an injectable agent for a prolonged period. † Terizidone side-effects also apply to cycloserine.

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together with ART.[51] A meta-analysis of RCTs conducted in the pre-ART era demonstrated that IPT reduces the incidence of TB by 33% overall, with greater benefit (62%) and a reduction in mortality in those who are tuberculin skin test (TST) positive.[50] In a trial subsequently conducted in Botswana the risk of TB was reduced by 74% in TST-positive individuals with HIV who took IPT for 3 years compared with 6 months.[52] Observational data from Soweto also suggest that continuous IPT is safe and effective.[53] Yet despite this compelling evidence and inclusion in NDoH guidelines, uptake has been poor.

An ideal setting to upscale IPT is in ART clinics, where patients are already established in care and are more likely to adhere to IPT.[54] With the implementation of a higher CD4+ count threshold for ART initiation in SA, more individuals will be attending ART clinics, further increasing the numbers that will potentially derive

Patient on ART

clinical benefit from this intervention. Findings from a recent RCT involving clinic patients on ART in Cape Town support this approach, where the reduction in incident TB was 37% in the group assigned IPT (versus placebo) for 12 months. Importantly, benefit was also seen in the subgroup of TST-negative patients, thus removing the requirement for TST testing prior to a 12-month course of IPT in patients on ART.[51] This study has informed national guidelines,[55] which now recommend 1 year of isoniazid 300 mg daily (plus pyridoxine) for all HIV-infected patients on ART, regardless of TST status. In patients who are TST-positive this should be extended to 36 months or longer, based on the Botswana study findings.[52] An evidence-based approach to IPT is presented in Fig. 1.

Although the rates of isoniazid monoresistance in people who develop TB while on IPT are similar to those of controls,[56,57] the

Patient not on ART

CD4+ ≤500

Yes

Start ART

No

Perform TST

Not done

+ve

-ve

Exclude medical contraindications to INH* and screen for active TB†

IPT for ≥3 years

IPT for ≥1 year‡

IPT for 6 months

No IPT

Fig. 1. Approach to prescribing isoniazid preventive therapy (IPT) (based on South African National Department of Health Guidelines[55] and evidence from clinical trials[50-52]). *Hypersensitivity or intolerance to isoniazid, peripheral neuropathy, pre-existing liver disease or alcohol abuse. †WHO symptom screen: any cough, fever, night sweats or weight loss. If any symptom is present, defer IPT until confirmed culture-negative and symptoms have resolved. ‡If TST is negative or not done, continue for 1 year; if TST is positive, continue for ≥3 years. (INH = isoniazid; TST = tuberculin skin test.)

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Table 5. Indications for stopping suspected culprit drugs in CDRs and DILI CDR

DILI

Systemic symptoms Mucosal involvement Severe skin involvement Deranged liver enzymes

Symptomatic* with ALT >120 IU/L Asymptomatic with ALT >200 IU/L Any transaminitis with bilirubin >40 Îźmol/L Prolonged INR or encephalopathy

CDR = cutaneous drug reaction; DILI = drug-induced liver injury; ALT = alanine transaminase; INR = international normalised ratio (prothrombin time). *Nausea, vomiting, abdominal pain, jaundice.

potential for this complication is greater if patients with active TB are inadvertently placed on isoniazid monotherapy. The WHO recommends using a four-symptom screen to exclude active TB prior to

initiating IPT,[58] and any patient with current cough, fever, night sweats or weight loss should not receive IPT until active TB is ruled out by a negative sputum culture and the symptoms have resolved.

Conclusions

TB is the most important cause of morbidity and mortality among HIV-infected people in SA. TB in HIV-infected patients poses complex clinical challenges because of atypical presentations, delayed diagnosis, more rapid clinical deterioration, drug interactions, TB-IRIS and overlapping toxicities. However, with the development of more rapid and accurate diagnostic tests, guidelines on empirical TB treatment, clear guidelines on initiation and timing of ART, an improved understanding of IRIS and adverse drug effects, and widespread implementation of IPT, we as clinicians can make an impact on the epidemic and its consequences.

References available online at http://dx.doi.org/10.7196/SAMJ.9090

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ARTICLE SUMMARY

Diagnosis and management of drug-resistant tuberculosis in South African adults J Hughes,1 MB BCh (Cardiff); M Osman,2 MB ChB, PG Dip Health Management MÊdecins sans Frontières (MSF, Doctors without Borders), Khayelitsha, Cape Town, South Africa City Health, Cape Town, South Africa

1 2

Corresponding author: J Hughes (msfocb-khayelitsha-tbdoc@brussels.msf.org)

The detection of drug-resistant tuberculosis (DR-TB) in South Africa (SA) increases yearly. Most cases result from airborne transmission of already resistant TB strains. Epidemic control relies on rapid diagnosis and initiation of effective treatment to reduce the period of infectiousness and ongoing transmission.

Approximately 1.8% of new TB cases and 6.7% of previously treated TB cases in SA are multidrug resistant (MDR). Mycobacterium tuberculosis (MTB) may acquire resistance to certain drugs through selective drug pressure from suboptimal treatment, such as when adherence is poor. However, the majority of new DR-TB cases diagnosed in SA are due to transmission of already resistant strains.

The rapid diagnostic test, Xpert MTB/RIF, has replaced smear microscopy for routine screening of all cases of presumptive TB in SA. Xpert also detects rifampicin (RIF) resistance, which indicates more extensive drug resistance, allowing rapid initiation of effective secondline treatment. Definitive diagnosis of DR-TB relies on laboratory confirmation of MTB along with drug-susceptibility testing (DST) using culture-based (phenotypic) and/or molecular (genotypic) techniques.

A standardised treatment regimen consisting of five (or six) drugs (pyrazinamide (PZA), (ethambutol (EMB)), kanamycin, moxifloxacin, ethionamide, terizidone) is offered to individuals following initial diagnosis of RIF resistance. Treatment regimens are individualised if and when molecular mutation details and secondline DST results indicate more extensive second-line drug resistance.

Unfortunately, clinical outcomes remain poor in SA, with <45% of MDR-TB cases treated successfully (cure or completion). The current standard MDR regimen is toxic and lengthy, with fewer than four potentially effective drugs, and should therefore be optimised where possible. DST for PZA and EMB is not carried out routinely owing to poor reliability of the testing methods available, but genotyping studies have estimated that roughly 50% of MDR strains in SA are susceptible to PZA and/or EMB. Therefore, their routine addition to the standard regimen may benefit half of all MDR cases.

Case detection of DR-TB in SA has increased following the nationwide roll-out of Xpert MTB/RIF. However, this may have limited impact on ongoing transmission of the disease unless the majority of patients rapidly initiate effective treatment. While an initial standardised treatment regimen may be more easily implemented at decentralised treatment initiation sites, the current MDR regimen should be optimised as soon as second-line susceptibility results are obtained to prevent acquisition of further resistance. Pre-extensively drug-resistant (pre-XDR), XDR and MDR failure cases require early individualised treatment with all available potentially effective drugs. However, treatment options remain severely limited. New and repurposed drugs may be made available for these patients through the national treatment programme within the framework of expert guidance, while awaiting results of clinical trials for shorter, more effective and more tolerable regimens for all patients with DR-TB. S Afr Med J 2014;104(12):894. DOI:10.7196/SAMJ.9097

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ARTICLE SUMMARY

The diagnosis and medical management of tuberculous meningitis in adults S Marais,1 MBÂ ChB, FCNeurol (SA), PhD; R J Wilkinson,1,2 MA, PhD, BM BCh, DTM&H, FRCP Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Neurology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 2 Division of Mycobacterial Research, MRC National Institute for Medical Research, London, and Department of Medicine, Imperial College London, UK 1

Corresponding author: S Marais (marais.suzaan@gmail.com)

Tuberculous meningitis (TBM) is a frequent cause of meningitis in South Africa and carries a dismal prognosis.

The diagnosis of TBM is often complicated and optimal management strategies are uncertain; such challenges are likely to contribute to poor outcome in affected patients.

Diagnosis

Early diagnosis and treatment initiation are crucial to improve the outcome in TBM as advanced disease, prolonged symptom duration and delayed treatment initiation are associated with increased mortality during hospitalisation, when the majority of deaths occur.

Confirmatory microbiological tests are insensitive and therefore diagnosis and tuberculosis (TB) treatment initiation are usually based on a combination of suggestive clinical and cerebrospinal fluid (CSF) findings, evidence of TB outside of the central nervous system (CNS), supportive features on brain imaging (if available) and exclusion of other common causes for meningitis, such as cryptococcal meningitis. The Xpert MTB/RIF test (Xpert, Cepheid, Sunnyvale, CA, USA), a real-time polymerase chain reaction assay for Mycobacterium tuberculosis, which simultaneously detects rifampicin (RIF) resistance, is of potential value in the rapid diagnosis of TBM.

Treatment of TBM

The principles of treating TBM are based on those used in pulmonary TB and not informed by randomised controlled trials (RCTs) in TBM. The evidence for the current recommended dose of RIF (10 mg/kg/d) in TBM treatment is scant and the dose may be too low. Isoniazid and pyrazinamide have good CSF penetration and are therefore considered critical drugs in TBM treatment. However, the choice of the fourth drug during the treatment initiation phase is contentious. Ethambutol crosses the meninges poorly at the recommended dose. Alternatives such as streptomycin and ethionamide are of limited use in TBM owing to poor CNS penetration and dose-limiting toxicity, and intolerable gastrointestinal side-effects in adults, respectively. Fluoroquinolones such as levofloxacin and moxifloxacin have

high bactericidal activity, are safe and well tolerated, and have good CSF penetration; they are therefore attractive treatment options for TBM. There is increasing interest in exploring alternative evidence-based treatment regimens for TBM, such as those that include higher doses of RIF and the addition of a fluoroquinolone. An RCT that includes such strategies is ongoing in Vietnam and will inform treatment guidelines once completed.

Adjunctive corticosteroid treatment is associated with improved survival in HIV-uninfected patients with TBM and recommended in all affected patients, regardless of HIV status.

Treatment of HIV

A large proportion of HIV-infected patients are antiretroviral therapy (ART)-naive, or have defaulted ART, at TBM presentation. Starting ART during TB treatment improves outcome in HIV/TB co-infected patients. In an RCT of patients with HIV-associated TBM, there was no difference in 9-month mortality between severely immunosuppressed HIV-infected TBM patients (median CD4+ count = 41 cells/ÂľL) who started ART immediately (within 7 days of TB treatment) and those who started later (2 months after initiating TB treatment). Grade 4 adverse events were significantly more frequent in the immediate ART group (80% v. 69%; p=0.04), suggesting that delayed treatment may be preferable. Furthermore, early ART initiation in TB patients increases the risk of developing TB-immune reconstitution inflammatory syndrome (IRIS), which is not infrequently fatal when the CNS is involved. Current South African Department of Health guidelines therefore recommend that TBM patients start ART no sooner than 4 - 6 weeks after TB treatment, regardless of CD4+ count. Paradoxical neurological TB-IRIS frequently occurs in TBM patients after starting ART and may present as meningitis, intracerebral tuberculoma(s), tuberculous brain abscess, radiculomyelitis or spinal epidural abscess. Corticosteroids are the only evidence-based treatment modality currently available for TB-IRIS and should be considered in all cases of neurological TB-IRIS. S Afr Med J 2014;104(12):895. DOI:10.7196/SAMJ.9060

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Management of HIV-associated cryptococcal disease in South Africa N P Govender,1 MB BCh, MMed (Micro), FCPath (SA) Micro, MSc, DTM&H, Dip HIV Man (SA); S Dlamini,2 MB ChB, FCP (SA), Cert ID (SA) National Institute for Communicable Diseases (Centre for Opportunistic, Tropical and Hospital Infections), Division of the National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 2 Division of Infectious Diseases and HIV Medicine, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 1

Corresponding author: N P Govender (neleshg@nicd.ac.za) In routine-care settings, the 10-week mortality associated with cryptococcal meningitis (CM) is high, even with prompt, appropriate antifungal treatment and correctly timed initiation of antiretroviral therapy (ART). While early diagnosis of HIV infection and initiation of ART prior to the development of AIDS is the most important way to reduce the incidence of CM, a cryptococcal antigenaemia screen-and-treat intervention has the potential to reduce mortality by identifying patients before onset of CM. Antifungal treatment for HIV-associated CM is divided into three phases over a minimum period of 1 year: (i) a 2-week induction phase including intravenous amphotericin B deoxycholate as a backbone; (ii) an 8-week consolidation phase with fluconazole 400 mg daily; and (iii) a maintenance phase with fluconazole 200 mg daily.

Amphotericin B should be paired with another antifungal agent to maximise cerebrospinal fluid fungal clearance. Access to flucytosine is limited, because this agent is not registered in South Africa (SA) and is only available on a compassionate basis. In conjunction with antifungal

therapy, an important aspect of management includes adequate control of raised intracranial pressure, achieved by performing lumbar punctures daily until pressure has normalised and symptoms/signs have resolved.

The administration of amphotericin B deoxycholate may lead to a number of complications, including renal toxicity, hypokalaemia and phlebitis; these need to be managed proactively. ART should be initiated 4 - 6 weeks after starting antifungal therapy. Tuberculosis and cryptococcal disease are often comorbid conditions and their simultaneous management poses a challenge in terms of drug burden and drug-drug interactions. Furthermore, relapse following an initial episode is common, which should be fully investigated to determine and manage the underlying cause. In many cases, relapse CM among SA patients occurs because of suboptimal adherence to secondary prophylaxis with fluconazole and/or the antifungal not being prescribed.

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ARTICLE SUMMARY

Focus on adolescents with HIV and AIDS L Fairlie,1 MB ChB, DCH (UK), FCPaed (SA), MMed; N Sipambo,1,2 MB BCh, FCPaed (SA); C Fick,1 MB BCh, Dip HIV Man; H Moultrie,1 MB BCh, MSc Wits Reproductive Health and HIV Institute (WRHI), University of the Witwatersrand, Johannesburg, South Africa Department of Paediatrics, Chris Hani Baragwanath Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

1 2

Corresponding author: L Fairlie (lfairlie@wrhi.ac.za)

Adolescents bear a disproportionate burden of the HIV epidemic in South Africa (SA). In 2012, the estimated HIV prevalence (range) in 15 - 24-yearold SA women and men was 13.9% (12.9 - 16.8) and 3.9% (2.5 - 5.7) respectively, equating to ~720 000 adolescents and young people living with HIV. The population of adolescents living with HIV (ALHIV) in SA is comprised of adolescents with perinatal HIV infection (PHIV) who have moved into adolescence (PHIA) and those who acquired HIV at an older age through sexual activity, intravenous drug use or other less common modes of transmission (non-PHIV).

Initiation of antiretroviral therapy (ART) in ALHIV in SA, including criteria for initiation and ART choice, uses a cut-off age of 15 years and weight of 40 kg to determine whether paediatric or adult guidelines are followed. Pregnant adolescents >12 years and >40 kg follow recommendations of adult treatment guidelines. Particular caution is necessary in using tenofovir in younger adolescents, given the possible renal tubular toxicities and bone mineral density reductions, particularly with protease inhibitor (PI) co-treatment.

Many adolescents have good anthropometric outcomes on ART, robust CD4+ responses and reduction in mortality rates. However, adolescence is a time of potentially poor adherence, with virological suppression rates of 24 - 78% in longitudinal cohorts, low compared with adults receiving ART. The physical, sexual, emotional and psychological changes associated with adolescence and potentially reduced parental oversight may affect adherence to ART. Additionally, factors such as day-to-day lifestyle barriers, medication-related factors, patientrelated factors and socioeconomic constraints limiting access to care may affect adherence (Table 3, online article).

Since both adherence and barriers may change over time, it is necessary to assess adherence and modifiable barriers at each visit and, together with the adolescent, to tailor interventions to support adherence (Table 4, online article). At each visit the following adherence reinforcements are necessary: identify and resolve any

confusion with their regimen; manage any emerging drug side-effects; enquire about changes in lifestyle and need for adjustments; and provide ongoing psychosocial counselling and management of new or unresolved issues. A multidisciplinary approach is often required.

Adolescents with virological failure (VF) are managed according to the guidelines of the hospital-level Essential Drug Programme South Africa. VF, defined as two elevated viral loads >1 000 copies/mL, is the most accurate by-proxy measure of adherence. Adolescents receiving an efavirenz-based first-line regimen require rapid change to second-line, if viral load (VL) remains elevated >1 000 copies/mL once adherence issues have been addressed, to avoid the development of further non-nucleoside reverse transcriptase inhibitor (NNRTI) and/or NRTI resistance mutations. There is less urgency in switching those on a PI-based regimen as accumulation of NRTI resistance mutations is less likely, even at high VLs (>30 000 copies/mL).

Drug resistance testing (DRT) should be conducted when an adolescent with reported good adherence is failing an NNRTI- or boosted PI-based regimen for >12 months. To optimise results, the VL should be >1 000 copies/mL and the adolescent should have received ART for the preceding 4 weeks. A composite of all previous DRT results together with a detailed treatment history is required for interpretation.

Additional issues requiring attention in adolescents are the following: sexual and reproductive health needs, with attention to drug-drug interactions between ART and hormonal contraceptive methods; disclosure to the adolescent prior to 12 years of age as recommended by the World Health Organization with sufficient support and education to the caregiver and the adolescent; support for the adolescent to disclose to sexual partners and others where they desire to do so.

Successful adolescent transition requires communication of previous medical, sexual and reproductive health issues to the adult-care practitioner. Careful planning and ongoing support with attention to specific adolescent needs are required to make the transition successful.

S Afr Med J 2014;104(12):897. DOI:10.7196/SAMJ.9110

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ARTICLE SUMMARY

Antiretroviral therapy for the management of HIV in children L Frigati, MB ChB, DCH, Dip HIV, MMed, FCPaed (SA), MSc TMIH (UK), Cert ID (SA) Paed; M F Cotton, MB ChB, DCH, FCPaed (SA), PhD; H Rabie, MB ChB, MMed, FCPaed (SA), MSc ID Division of Paediatric Infectious Diseases, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Tygerberg Academic Hospital and Stellenbosch University, Cape Town, South Africa Corresponding author: L Frigati (frigati@sun.ac.za)

Guidance on the indications for starting antiretroviral therapy (ART) and the preferred initial drugs has evolved over the past 15 years as a result of a better understanding of the rate of disease progression, the high early morbidity and mortality and our inability to predict which children will not have rapid disease progression or die.

The 2013 World Health Organization (WHO) and South African (SA) ART guidelines recommend starting ART for all children <5 years of age and fast-tracking those who are very young and have severe disease.

In the absence of ART, the majority of infants progress to AIDS and death within 18 months. There has been a significant reduction in mortality and HIV progression in children on early therapy. Some notable advantages are a reduction in tuberculosis (TB) incidence and an improvement of developmental outcomes. Griffiths Mental Development Scales scores were significantly higher for children who started early treatment.

The evidence for starting children on ART between 2 years and 5 years of age is less clear. The current recommendations are only partially based on evidence of clinical benefit, but are also an attempt to simplify complex operational and programmatic issues.

Children still receiving first-line stavudine (d4T) should be switched to abacavir (ABC) if the viral load is undetectable and so avoid lipoatrophy. Children on efavirenz (EFV) with a viral load of >1 000 copies/mL and those on lopinavir/ritonavir (LPV/r) with a viral load of >5 000 copies/mL, should be managed as for treatment failure. When the viral load is detectable, but below these thresholds for regimen switching, a single drug substitution with ABC should not be done. If considered essential, consult an experienced clinician.

Both ABC and lamivudine (3TC) can be given once daily from 20 kg and 3 years of age, although some experts recommend daily 3TC from 25 kg. The latest weight-based therapy chart allows for this (available on the SA HIV Clinicians Society website: http://www.sahivsoc.org).

The availability of the lower-dose ABC tablets (60 mg) and ABC/3TC (600/300 mg) fixed-dose combination allows for simplification and reduction of pill burden and an earlier switch from liquid to solid formulations.

TB remains a common problem in HIV-infected children. In SA, the incidence of TB disease is estimated at 23 per 100 child-years among HIV-infected children not on ART. Access to ART remains an essential intervention to prevent TB – in children on therapy rates have declined substantially. Co-treatment with rifampicin affects the metabolism of certain antiretroviral drugs, especially LPV/r, which may affect the virological outcomes. Limited data suggest that, unlike in adults, doubling the LPV/r dosage does not achieve adequate protease inhibitor bioavailability in young children on rifampicin. LPV/r ‘super-boosted’ with additional ritonavir (RTV), giving a 1:1 ratio for LPV and RTV, is the preferred strategy.

Despite access to ART, 7% of children given ART die in the first year in a programmatic setting. In older children (mean age at starting ART 4.3 years), virological suppression rates of 96% by 12 months are reported from Soweto.

Clinicians caring for HIV-infected children are currently focusing on improving prevention, very early diagnosis and therapy, and quality of care.

S Afr Med J 2014;104(12):898. DOI:10.7196/SAMJ.9091

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PULSE

Manufactured by BLES Biochemicals Inc., Canada, using the lavage method as opposed to mincing, Liposurf is indicated for rescue treatment of neonatal respiratory distress syndrome (NRDS/hyaline membrane disease). Liposurf restores surfactant activity in neonates with NRDS, thereby improving gaseous exchange by decreasing alveolar surface tension and promoting lung compliance.

Details are set out in the table below.

Enquires: Dr Jaco van Zyl, (021) 917-5620 (medical queries), Kevin Grant, (011) 315-9150 (other product queries). References available on request.

New HIV mobile app guides patient treatment

Cipla launches first-to-market generic ciclesonide

Cipla is proud to announce Ciclovent pressurised metered-dose inhalers, targeting large- and small-airway inflammation in asthma.

Ciclovent, an inhaled corticosteroid, is indicated for the prophylactic treatment of asthma in adults and adolescents. Each inhaler delivers either 80 µg or 160 µg of ciclesonide per puff. Ciclovent contains small ciclesonide particles that sufficiently penetrate into the smaller airways of the lungs. Ciclesonide has a total lung deposition of 52% and is highly lipophilic, enhancing its slow release in the lung.

Details are set out in the table below.

Enquiries: Dr Jaco van Zyl, (021) 917-5620. References available on request.

Cipla launches an original surfactant

Cipla is proud to announce the introduction of Liposurf (bovine lipid extract surfactant suspension), an addition to the growing Cipla Hospital basket of products.

Metropolitan Health, the largest admini­strator of medical schemes in South Africa, has launched a first-of-its-kind HIV treatment guideline app aimed at healthcare professionals.

The HIV Clinical Guide mobile appli­cation, which was awarded a Silver in the category of ‘Most Innovative App’ at the New Generation Social and Digital Media Awards in October, was developed to assist healthcare professionals at all levels to treat patients with HIV effectively. The app was also lauded as one of the top five mobile apps (out of 400) at the MTN App of the Year Awards held in August.

Siraaj Adams, Executive Manager of the HIV YourLife Programme at Metropolitan Health, explained: ‘The prevalence of HIV in developing countries has led to task shifting within the healthcare workforce to accommodate the increased demand for health services.

Consequently, the nurse-initiated management of antiretroviral therapy (NIMART) often requires further support. Clinical decision support tools are extremely valuable in maximising quality healthcare.’

The app, developed in conjunction with The Open Medical Project South Africa (TOMPSA), reflects the latest developments in HIV medicine and clinical care and serves as a comprehensive HIV treatment guideline for all levels of healthcare professionals.

Adams explained: ‘The app allows health­ care professionals to prescribe appropriate treatment for those suffering from HIV, in line with the patient’s unique condition and symptoms. Simply put, it allows you to look at the patient on an individual level. How are they responding to their current treatment programme? What are their unique symptoms and what could this possibly indicate? Then it supplies an appropriate guideline for treatment, taking these factors into account. Thus it acts as a provider support tool, improving the quality of care given to patients.’

The easy-to-use ‘how to’ guide contains recommendations based on available data and guidelines from authoritative sources such as the Southern African HIV Clinicians Society, Metropolitan Health HIV YourLife Programme and National Department of Health.

Ciclovent product details Product name

Active ingredients

Pack size

Schedule

NAPPI code

SEP excl. VAT

SEP incl. VAT

Saving v. originator

Ciclovent 80

Ciclesonide

120 doses

3

720711001

R196.00

R223.44

30%

Ciclovent 160

Ciclesonide

120 doses

3

720735001

R349.40

R398.31

50%

SEP = single exit price; VAT = value-added tax.

Liposurf product details Product name

Active ingredients

Pack size

Schedule

Nappi code

SEP excl. VAT

SEP incl. VAT

Liposurf

27 mg/ml

3 ml

4

720750001

R 2 061.40

R2 350.00

Liposurf

27 mg/ml

5 ml

4

720768001

R 4 627.19

R5 275.00

SEP = single exit price; VAT = value-added tax.

December 2014, Vol. 104, No. 12

PULSE

Ongoing research and testing means that it can be difficult for healthcare professionals to stay totally up to date with the latest developments in treatment. Instead of having to consult multiple journals and sources of information to ascertain the best course of treatment for a patient, the health worker can simply tap into it in one convenient place.

‘For healthcare professionals that work in outlying or rural areas, access to information resources can sometimes prove challenging, so the app enables them to swiftly peruse the latest information available and accurately prescribe treatment,’ said Adams.

The app covers all aspects of HIV care, from diagnosis to starting criteria for antiretrovirals to switching treatment regimens.

The toxicity and adverse reaction pathology calculator determines whether a patient should remain on a specific treatment or switch. The paediatric and renal dosage calculator is extremely useful in verifying that dosages are appropriately prescribed, and a comprehensive HIV drug formulary allows for easy reference of information such as contraindications and pharmacokinetics.

Adams went on to say that another other benefit is that the technology does not require Wi-Fi to function. ‘It’s localised to the device and therefore only requires Wi-Fi when the information receives an update. This is helpful, particularly in areas where internet access is limited. As a result, it is a very cost-effective way to provide decision support tools to public/private sector healthcare providers.’

In September 2014, the second version of the app was released in partnership with the Medicines Information Centre at the University of Cape Town, and it now includes a drug interaction checker that monitors drug-to-drug interactions.

‘We are looking forward to seeing how the app facilitates better treatment and individualised care for patients as part of a comprehensive disease management programme,’ concluded Adams.

The HIV Clinical Guide mobile app is developed locally and available for download via the Apple or Google Play app stores.

Let’s get the good news about red meat out there!

There are two very different perceptions of the role of red meat in the global diet. In developing countries, red meat from all species offers a means of reducing malnutrition and increasing food security, while in the developed world, it is often viewed as a culprit in the development of diet-related non-communicable diseases such as obesity, high blood

pressure and cancer. Yet a diet high in lean red meat has been shown to lower plasma cholesterol and contribute significantly to healthy omega-3 fatty acids, and red meat is a good source of iron, zinc and vitamin B12.

South African (SA) red meat is not always fully or positively presented to the modern consumer, however, and there is therefore a need to increase awareness of where our red meat comes from, how it is produced, and the benefits consumption of fresh red meat holds.

• More than 80% of SA sheep are pasture fed, which means that they graze naturally on open fields, while approximately 60% of cattle are produced on natural or cultivated pastures, with the majority finished off for two months in feedlots. Apart from livestock production on semi-arid land contributing to increased food production in SA, the image of SA red meat production systems as respectful and protective of biodiversity and ecosystems needs to be communicated to the increasingly concerned consumer.

• Red meat contains high biological value protein proven to assist in maintaining lean body mass. Reasons why red meat may help maintain lean mass and reduce excess weight include the satiating properties of protein, which may result in decreased food intake, as well as the effect of increased protein intake on thermogenesis, body composition and energy efficiency.

• Although red meat is a nutrient-dense food, i.e. it contains many nutrients in ample amounts, it also contains many of these nutrients, such as protein, iron and vitamin A, in their most bioavailable forms.

Haem iron is the most bioavailable form of iron and is found only in animal products, with red meat being an excellent source.

• According to the SA food-based dietary guidelines, up to 560 g lean red meat per week can be consumed (approximately 80 - 90 g per day). It is recommended that the portion of cooked red meat should be roughly the size of a deck of cards.

• Red meat contributes to the total fat in the diet. As a result of consumer demand, the fat content of SA red meat has decreased to less than 10 g/100 g through breeding, farming and butchering techniques. Contrary to popular belief, lean red meat such as SA lamb, mutton and beef compares favourably in terms of fat content to other animal source foods, including chicken with or without the skin. Red meat, including SA lamb and mutton, contains less than 10% fat when trimmed.

For more information on the role of red meat in a balanced diet, visit www.healthymeat.co.za or email info@healthymeat.co.za

December 2014, Vol. 104, No. 12

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CPD

DECEMBER 2014

Effective in 2014, the CPD programme for SAMJ will be administered by Medical Practice Consulting: CPD questionnaires must be completed online at www.mpconsulting.co.za

True (A) or false (B): Recommendations for amniocentesis in HIV-positive women 1. Amniocentesis is safe to perform in women on highly active antiretroviral therapy with suppressed viral loads (preferably undetectable), provided transplacental passage of the needle is avoided.

Newborns should be receiving premedication before elective intubation 2. Premedication for elective and semi-urgent intubation of infants minimises the potential for intubation-related cardiovascular instability.

Retinoblastoma outcome at a single institution in South Africa (SA) 3. Overall survival in SA is only 33 - 43%, compared with the 95% achievable in developed countries.

4. Retinoblastoma may be detected early by undertaking a simple clinical test for the â&#x20AC;&#x2DC;red reflexâ&#x20AC;&#x2122; on all newborns and toddlers.

Unwanted pregnancies in Gauteng and Mpumalanga: Examining mortality data on dumped abortions and babies 5. SA decriminalised abortion in 1996 by introducing the Choice on Termination of Pregnancy Act. 6. To obtain an abortion, minors require the permission of their parents or guardians.

Adolescent and young pregnant women at increased risk of motherto-child transmission (MTCT) of HIV and poorer maternal and infant health outcomes 7.

Adolescents had increased risks of maternal mortality, first presentation in labour and stillbirth, all findings that have important public health relevance in SA. 8. Early identification of HIV positivity in young pregnant women is required for success of prevention of MTCT, since it potentially facilitates swift initiation of triple antiretroviral therapy (ART) and youth-centred ART adherence support.

The Use of VTE prophylaxis in relatioN to patiEnt risk profiling (TUNE-IN) Wave 2 study 9. More than 50% of hospitalised patients are at risk of venous thromboembolism (VTE).

10. Private sector patients were more commonly clinically assessed as being at risk for VTE than those in the public sector (87.0% v.

47.3%).

The diagnosis, management and prevention of HIV-associated tuberculosis 11. The use of steroids results in a mortality benefit in tuberculous meningitis, regardless of the severity of disease.

12. Eligible HIV-infected patients on ART derive benefit from isoniazid preventive therapy, regardless of the tuberculin skin test result.

Diagnosis and management of drug-resistant tuberculosis (DRTB) in South African adults 13. The majority of new DR-TB cases diagnosed in SA are due to transmission of already resistant strains.

14. All cases of presumptive TB should ideally be screened for at least rifampicin resistance at initial clinical presentation.

Diagnosis and medical management of tuberculous meningitis in adults 15. The diagnostic yield of cerebrospinal fluid (CSF) in tuberculous meningitis may be improved by analysing large volumes of CSF and performing repeated lumbar punctures.

16.

A normal CSF white cell count may be present in severely immunosuppressed HIV-infected patients with tuberculous meningitis.

Management of HIV-associated cryptococcal disease in SA 17. Cryptococcus neoformans is the most common cause of adult meningitis in southern Africa, because of its association with HIV. 18.

The safe approach that is now accepted is that ART can be introduced 4 - 6 weeks after antifungal therapy is started.

Focus on adolescents with HIV and AIDS 19.

Disclosure of HIV status to HIV-infected adolescents should ideally occur by 15 years of age, as recommended by the World Health Organization.

Antiretroviral therapy for the management of HIV in children 20. Despite access to ART, 7% of African children given ART die in the first year in programmatic settings.

CPD questions include articles from CME. The full versions of each article can be found on the SAMJ website (http://www.samj.org.za)

A maximum of 3 CEUs will be awarded per correctly completed test.

INSTRUCTIONS 1. Read the journal. All the answers will be found there.

2. Go to www.mpconsulting.co.za to answer the questions.

Accreditation number: MDB001/007/01/2014 (Clinical)

December 2014, Vol. 104, No. 7

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