SAMJ Vol 106, No 5 (2016) by HMPG

MAY 2016

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CME Acute viral bronchiolitis (part 2) IN PRACTICE A multifaceted approach to managing diabetes CASE REPORTS Haemotoxic snakebite in rural KwaZulu-Natal The case of the exploding egg REVIEW Maternal deaths from bleeding associated with caesarean delivery: A national emergency RESEARCH Trends in non-communicable disease mortality, 1997 - 2010 Costs of delivering HPV vaccination to schools in KwaZulu-Natal Publication trends in SA clinical trials

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MAY 2016

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FROM THE EDITOR

Chronic diseases in the Western world: Increasing incidence or increasing overdiagnosis? B Farham

GUEST EDITORIAL

Obstetric violence in South Africa R J Chadwick

EDITOR’S CHOICE

CORRESPONDENCE

Subacute sclerosing panencephalitis still occurring in South Africa: Clinicians need to remain vigilant S Pillay, R van Toorn, T Kilborn, A Ndondo, B Eley, J Wilmshurst

CEO AND PUBLISHER Hannah Kikaya | Email: hannahk@hmpg.co.za

Amoxicillin for the secondary prevention of rheumatic fever in children not allergic to penicillin K Sprenger, M Annamalai, J von Lobenstein, E G M Hoosen

MANAGING EDITORS Ingrid Nye Claudia Naidu

Kounis syndrome: Aspects of incidence and epidemiology N G Kounis, N Grapsas, D Lianas, G D Soufras, N Patsouras

Neuroimaging in migraine E Shevel

IZINDABA

18 18 21

Costly adult ADHD shunned by medical aids Drunk driving: Bring back the breathalyser – experts Health department selectively using NGO input – claim

21 21

ERRATA Kounis syndrome Consciously cutting to the bone of SA’s surgical/anaesthetic delivery

EDITORIALS

Maternal deaths from bleeding associated with caesarean delivery: A national emergency G J Hofmeyr

Persistent burden from non-communicable diseases in South Africa needs strong action B Nojilana, D Bradshaw, V Pillay-van Wyk, W Msemburi, N Somdyala, J D Joubert, P Groenewald, R Laubscher, R E Dorrington

A complementary model for medical subspecialty training in South Africa J P F Dalmeyer, M Struwig, T F Kruger

South African Guidelines Excellence (SAGE): Efficient, effective and unbiased clinical practice guideline teams K Grimmer, J M Dizon, Q Louw, T Kredo, T Young, S Machingaidze

HMPG

TECHNICAL EDITORS Emma Buchanan Paula van der Bijl NEWS EDITOR Chris Bateman | Email: chrisb@hmpg.co.za PRODUCTION MANAGER Emma Jane Couzens DTP AND DESIGN Carl Sampson

GUEST EDITORIAL

Acute viral bronchiolitis: Dawn of a new era for the prevention of respiratory syncytial virus infection through vaccination S A Madhi, R J Green

ARTICLES

Acute viral bronchiolitis in South Africa: Viral aetiology and clinical epidemiology

Acute viral bronchiolitis in South Africa: Intensive care management for severe disease

HEAD OF SALES AND MARKETING Diane Smith | Tel. 012 481 2069 Email: dianes@hmpg.co.za JOURNAL ADVERTISING Charles William Duke Benru de Jager Reneé van der Ryst Ladine van Heerden Azad Yusuf ONLINE SUPPORT Gertrude Fani FINANCE Tshepiso Mokoena HMPG BOARD OF DIRECTORS Prof. M Lukhele (Chair), Dr M R Abbas, Dr M J Grootboom, Mrs H Kikaya, Prof. E L Mazwai, Dr M Mbokota, Dr G Wolvaardt ISSN 0256-9574

EDITORS EMERITUS Daniel J Ncayiyana, MD (Groningen), FACOG, MD (Hon), FCM (Hon) JP de V van Niekerk, MD, FRCR ASSOCIATE EDITORS Q Abdool Karim, A Dhai, N Khumalo, R C Pattinson, A Rothberg, A A Stulting, J Surka, B Taylor, M Blockman

CME 28

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

D A White, S A Madhi, P Jeena, H J Zar, B M Morrow, R Masekela, S Risenga, R J Green B M Morrow, C Feldman, R J Green

IN PRACTICE

CLINICAL ALERT Emergence of plasmid-medicated colistin resistance (MRC-1) among Escherichia coli isolated from South African patients J Coetzee, C Corcoran, E Prentice, M Moodley, M Mendelson, L Poirel, P Nordmann, A J Brink

May 2016, Print edition

SAMA website: www.samedical.org Journal website: www.samj.org.za

A Lupin Group Company

For further product information contact PHARMA DYNAMICS P O Box 30958 Tokai Cape Town 7966 Tel 021 707 7000 Fax 021 701 5898 Email info@pharmadynamics.co.za CUSTOMER CARE LINE 0860 PHARMA (742 762) www.pharmadynamics.co.za Fedaloc SR 30 mg. Each slow release tablet contains 30 mg Nifedipine. Reg. No.: RSA S3 A37/7.1/0302. NAM NS2 10/7.1/0033. Fedaloc SR 60 mg. Each slow release tablet contains 60 mg Nifedipine. Reg. No.: RSA S3 A37/7.1/0303. NAM NS2 10/7.1/0034. For full prescribing information, refer to the package insert approved by the Medicines Control Council, 25 November 2011. 1) IMS Data, December 2015; Units sold in the period 1 January 2015 – 31 December 2015. 2) Department of Health website http://www.hoh.gov.za – Accessed 10/03/2016. * Calculated cost for 30 tablets. FCF293/04/2016

MEDICINE AND THE LAW HIV testing of children is not simple for health providers and researchers: Legal and policy frameworks guidance in South Africa H E van Rooyen, A E Strode, C M Slack

HEALTHCARE DELIVERY Advances in stroke treatment are within reach A Taylor, D le Feuvre, V Mngomezulu, D Royston, R Harrichandparsard, C de Vries, A Winter, F Potgieter

Introducing a multifaceted approach to the management of diabetes mellitus in resourcelimited settings S Pillay, C Aldous

CASE REPORTS Haemotoxic snakebite in rural KwaZulu-Natal, South Africa: A case presenting with haematemesis M Wagener

On your toes: Detecting mediastinal air on the chest radiograph in ecstasy abusers M Naidoo, M Govind

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) and cirrhosis of the liver: A case report and literature review M K Kgomo, A A Elnagar, C Jeske, J Nagel

Syphilitic lymphadenitis clinically and histologically mimicking lymphogranuloma venereum A Wessels, C Bamford, D A Lewis, M Martini, H C Wainwright

The case of the exploding egg C Brink, G McKay, H Rode

REVIEW Maternal deaths from bleeding associated with caesarean delivery: A national emergency S Fawcus, R C Pattinson, J Moodley, N F Moran, M G Schoon, R E Mhlanga, S Baloyi, E Bekker, G S Gebhardt, for the National Committee on Confidential Enquiries into Maternal Deaths

RESEARCH 58

Emerging trends in non-communicable disease mortality in South Africa, 1997 - 2010* B Nojilana, D Bradshaw, V Pillay-van Wyk, W Msemburi, R Laubscher, N I M Somdyala, J D Joubert, P Groenewald, R E Dorrington, on behalf of the South African National Burden of Disease team

National priorities for perioperative research in South Africa* B M Biccard, C S Alphonsus, D G Bishop, L Cronje, H-L Kluyts, B Kusel, S Maswime, R Oodit, A R Reed, A M Torborg, R Wise, on behalf of the South African Perioperative Research Group national research priority-setting working group

Active surveillance of hospital-acquired infections in South Africa: Implementation, impact and challenges* W Lowman

The costs of delivering human papillomavirus vaccination to Grade 4 learners in KwaZulu-Natal, South Africa* I Moodley, N Tathiah, B Sartorius

Intimate partner violence in early adolescence: The role of gender, socioeconomic factors and the school* A J Mason-Jones, P De Koker, S M Eggers, C Mathews, M Temmerman, E Leye, P J de Vries, H de Vries

Publication trends of clinical trials performed in South Africa* M Sibanda, R S Summers, J C Meyer

*Full article available online only.

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ONLINE CONTENTS LISTED IN Index Medicus (Medline) Excerpta Medica (EMBASE) Biological Abstracts (BIOSIS) Science Citation Index (SciSearch) Current Contents/Clinical Medicine SAMJ SUBSCRIPTION RATES Local subscriptions ZAR 1 368.00 p.a. Foreign subscriptions ZAR 3 108.00 p.a. Single copies ZAR114.00 local, ZAR 259.00 foreign Members of the South African Medical Association receive the SAMJ only on request, as part of their membership benefit. Subscriptions: Tel. 012 481 2071 Email: members@samedical.org The SAMJ is published monthly by the Health and Medical Publishing Group (Pty) Ltd, Co. registration 2004/0220 32/07, a subsidiary of SAMA. HEAD OFFICE Health and Medical Publishing Group (Pty) Ltd Block F, Castle Walk Corporate Park, Nossob Street, Erasmuskloof Ext. 3, Pretoria, 0181 Tel. 012 481 2069 Email: dianes@hmpg.co.za EDITORIAL OFFICE Suites 9 & 10, Lonsdale Building, Gardener Way, Pinelands, 7405 Tel. 021 532 1281 | Cell. 072 635 9825 Email: publishing@hmpg.co.za Please submit all letters and articles for publication online at www.samj.org.za © Copyright: Health and Medical Publishing Group (Pty) Ltd, a subsidiary of the South African Medical Association Use of editorial material is subject to the Creative Commons Attribution – Non-commercial Works Licence. http://creativecommons.org/licenses/by-nc/3.0 Printed by TANDYM PRINT

MAY 2016

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Additional content available in the full online issue, SAMJ Vol. 106 No. 5 CME Acute viral bronchiolitis (part 2)

May 2016, Print edition

IN PRACTICE A multifaceted approach to managing diabetes CASE REPORTS Haemotoxic snakebite in rural KwaZulu-Natal The case of the exploding egg REVIEW Maternal deaths from bleeding associated with caesarean delivery: A national emergency RESEARCH Trends in non-communicable disease mortality, 1997 - 2010 Costs of delivering HPV vaccination to schools in KwaZulu-Natal Publication trends in SA clinical trials

FROM THE EDITOR

Chronic diseases in the Western world: Increasing incidence or increasing overdiagnosis? This issue of the SAMJ carries an important paper for South Africa (SA), outlining the trends in non-communicable disease (NCD) mortality in this country over the 13 years 1997 - 2010.[1] In this largely resource-poor country, nearly 40% of deaths during this period were due to NCDs, and of these nearly 15% were regarded as premature deaths – i.e. before the age of 45. Another 21% were deaths between the ages of 45 and 59. This is a worrying trend in a country where we still have significant child mortality. However, commentators in the developed world are concerned, for different reasons, about an explosion of chronic disease. In a recent article in the BMJ, McGrail et al.[2] question whether this increase in chronic disease truly reflects worse health. They cite a recent paper from the Global Burden of Disease Study suggesting that only 4% of the world’s population is free of disease[3] – in other words, health is an anomaly. Chronic diseases are the conditions that contribute to this alarming ‘lack of health’, and multimorbidity – described as the ‘most common chronic condition’[4] – affects at least half of the population aged over 65.[5] Given that patients with chronic conditions now account for most consultations in primary care in the developed world,[6] and that the number of people with chronic conditions is rising faster than previously predicted,[7] we need to start to ask some hard questions about the reason why. This is exactly what McGrail et al.[2] are doing, remarking that this burden of disease is likely to bring the most challenges to healthcare systems in the developed world. They looked at figures on 11 chronic diseases from British Columbia, Canada, which were targeted for policy and practice change either because of their prevalence or their effect on healthcare expenditure, in 4-year windows. They found the expected increase in prevalence with age, but what struck them was the rate of increase in age-specific rates over time. For example, in 10 years the chronic disease burden in people aged ≥80 years rose from an average of 1.4 conditions to 2 conditions, and in the 70 - 79-year age group it rose from 1.2 to 1.5. The data showed that the increase in the age group ≥80 years results from both a smaller proportion of people having no diagnosed condition (only a fifth in 2012 - 2013) and a much higher proportion having three or more conditions (almost two-fifths in 2012 - 2013). McGrail et al.[2] suggest three possible explanations for the rapid increases in rates of chronic disease – a true pandemic, particularly bad in the elderly; earlier or more vigilant recording of existing and known diagnoses; or ‘diagnostic creep’ – people now diagnosed with chronic disease who would not have been a decade or so ago. We know that health declines with age, and populations in the developed world are ageing. With advances in healthcare, people are, for example, living through a heart attack that might previously have killed them – and are then left with a chronic disease label. This will account for at least some of the trend, although it is highly unlikely that this alone can explain the increase over such a short time. Population risk factors also change with time – the increased prevalence of diabetes is one such risk. There is also reason to believe that more vigilant recording of conditions accounts for at least some of this reported rise in chronic disease, particularly since

doctors in many of these countries are rewarded for the number of chronic diseases they diagnose and treat over a specific time. What was apparent from the Canadian data was that there was an apparent increase in diagnosis, with no change in underlying morbidity. However, what is really striking is that, parallel to this increase in the prevalence of chronic diseases, self-reported health status is improving – in other words, the people who are being diagnosed with multiple chronic diseases still feel pretty good. At the same time, governments – the UK is a good example – are trying to screen populations and catch disease at earlier stages. This should lead to faster increases in rates of chronic disease in younger age groups, but if anything, data show more rapid increases in diagnosis at older ages. The most likely candidate, according to this analysis, is redefining what constitutes illness, and there is plenty of evidence for this. Bone density testing has created a vast pool of new patients with osteoporosis. Lowering of clinical thresholds for hypertension and diabetes has among other things led to substantial increases in the number of people diagnosed.[8,9] In other words, there is overdiagnosis and hypermedicalisation.[9] The conclusion is that, although a single explanation is unlikely, changes in data capture and diagnostic practices are more important than actual changes in health status. While this is unlikely to be the case in SA yet – except possibly among the ‘worried well’ in the private health sector – these are important lessons to take forward as we enter the era of National Health Insurance. Be wary of screening for chronic disease, and be particularly wary of rewarding practitioners on the basis of cases of particular illnesses diagnosed. If your patient says she is feeling well, there is a good chance that she actually is healthy! Bridget Farham

Acting Editor ugqirha@iafrica.com 1. Nojilana B, Msemburi W, Laubscher R, et al., on behalf of the South African National Burden of Disease team. Emerging trends in non-communicable disease mortality in South Africa, 1997 - 2010. S Afr Med J 2016;106(5):477-484. DOI:10.7196/SAMJ.2016.v106i5.10674 2. McGrail K, Lavergne R, Lewis S, et al. The chronic disease explosion: Artificial bang or empirical whimper? BMJ 2016;352:i1312. DOI:10.1136/bmj.i1312 3. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;386(9995):743-800. DOI:10.1016/S0140-6736(15)60692-4 4. May C. Chronic illness and intractability: Professional-patient interactions in primary care. Chronic Illn 2005;1(1):15-20. DOI:10.1177/17423953050010011201 5. Fortin M, Stewart M, Poitras ME, Almirall J, Maddocks H. A systematic review of prevalence studies on multimorbidity: Toward a more uniform methodology. Ann Fam Med 2012;10(2):142-151. DOI:http://dx.doi.org/10.1370/afm.1337 6. Jayaraman G. Defining multimorbidity for public health surveillance and epidemiology. Presented at the Canadian Society for Epidemiology and Biostatistics Annual Conference, St John’s, Newfoundland, 25-27 June 2013:1-21. 7. Anderson G. Chronic care: Making the case for ongoing care. 2010. www.rwjf.org/content/dam/farm/ reports/reports/2010/rwjf54583 (accessed 8 April 2016). 8. Kaplan RM, Ong M. Rationale and public health implications of changing CHD risk factor definitions. Annu Rev Public Health 2007;28:321-344. DOI:10.1146/annurev.publhealth.28.021406.144141 9. Welch HG, Schwartz LM, Woloshin S. Overdiagnosed. Boston, MA: Beacon Press, 2011.

S Afr Med J 2016;106(5):422. DOI:10.7196/SAMJ.2016.v106i5.10875

May 2016, Print edition

GUEST EDITORIAL

Obstetric violence in South Africa Abusive practices in obstetric care settings have been reported in the USA since the 1950s. However, it is only since the 2000s that this issue has been identified as a worldwide health and social problem. [1] The mistreatment of women and girls during childbirth has been documented in a range of global contexts, including high-income countries[2-3] and middle- to low-income countries.[4-6] There has recently been growing international attention to this problem,[7,8] and it has been recognised that abusive treatment is connected to poor uptake of maternity services and poor maternal and infant health outcomes in some settings. For a long time, the importance of respectful and dignified care during labour and childbirth has been a ‘blind-spot’ in global health agendas,[7] but calls for action and accountability are now becoming difficult to ignore.[5,7,8] Current debates and global activism are increasingly drawing on the concept of ‘obstetric violence’ to contextualise and address patterns of mistreatment of women and girls during labour and childbirth. This editorial introduces this concept and explores its potential relevance in the South African (SA) context.

Introducing the concept of obstetric violence

A range of terms have been used to describe violence against women and girls during labour and birth, including childbirth abuse, ‘birth rape’, mistreatment, and most recently obstetric violence. A wide range of problematic practices have been associated with these terms, including neglect, verbal and emotional abuse, physical abuse, sexual abuse, lack of confidential and consensual care, and the inappropriate, non-evidence-based use of medical interventions, including routine episiotomies, routine inductions, preventing labour companions, and unnecessary caesarean sections.[9,10] The concept of obstetric violence emerged in the 2000s in Latin America and Spain as an extension of the activist struggle to humanise and demedicalise childbirth and empower women and girls during pregnancy, labour and birth. It emerged as a legal term in Venezuela in 2007 and was adopted by Argentina in 2009 and by Mexico in 2014. Perpetrators of acts of obstetric violence are subject to criminal liability in these countries, which usually amounts to a fine and a signed acknowledgement of wrongdoing on the part of the practitioner and/or the institution. In Venezuelan law, published in Article 15 of the ‘Organic Law on the Right of Women to a Life Free of Violence’, obstetric violence is included as one of 19 different forms of punishable violence against women and is defined as: ‘… the appropriation of the body and reproductive processes of women by health personnel, which is expressed as dehumanized treatment, an abuse of medication, and to convert the natural processes into pathological ones, bringing with it a loss of autonomy and the ability to decide freely about their bodies and sexuality, negatively impacting the quality of life of women’.[9] The use of the controversial term ‘obstetric violence’ over more neutral labels such as ‘mistreatment’ is part of a deliberate move to confront problematic practices, which have often been hidden, invisible and unacknowledged, as forms of violence. For activists and practitioners in Latin American contexts, aggressive, humiliating and disrespectful treatment of women and girls during labour and birth is part of broader and entrenched gender violence and social inequalities of race, class, age and ethnicity. Medical interventions (most notably routine episiotomies and unnecessary caesarean sections) that are used excessively are also defined as examples of ‘obstetric violence’.

Lack of accountability for abuses in the SA context

Not surprisingly, medical practitioners have been hostile to the concept of obstetric violence and its legal implications in the Latin American context, fearing that it potentially criminalises routine medical treatment.[5] The move to tackle abuse in maternal healthcare settings by adopting legal routes should, however, be recognised as partly the result of the failure of the medical establishment to confront these issues and hold healthcare professionals and institutions of care accountable for unacceptable practices. This is the case in Latin America and also increasingly in SA. As a result, calls for legal action and the criminalisation of abusive practices by healthcare professionals are now gaining ground in the SA context.[11] While it is true that the roots of abusive treatment (in SA and other contexts) are complex, including health system inadequacies, an insufficient emphasis on an ethics of care in midwifery training, poor working conditions, healthcare professional overload and historical legacies of inequalities, there is also no excuse for failure to hold individuals and institutions accountable for practices that dehumanise, degrade and cause harm to women and girls in some of their most vulnerable moments (i.e. labour and childbirth). Efforts to change institutional cultures that condone medicalised forms of violence and abuse need to be led by medical practitioners, professional associations and institutional boards.

A form of gender violence?

In the medical literature, debates about mistreatment are often predominantly framed in relation to quality-of-care issues and the failure of evidence-based obstetric practice. Often the assumption is that informing and training practitioners about evidence-based medicine (i.e. the benefits of labour companions) is enough to change practices on the ground. In the SA context in particular, achieving changes in practice has proved extremely difficult.[12] Reports of abusive mistreatment of women and girls in obstetric contexts date back to 1998,[13] yet little seems to have changed almost 20 years later, with recent research finding the same patterns of mistreatment in public sector facilities.[6] There is no doubt that there are significant structural impediments to changing practices (i.e. spatial configurations of obstetric facilities that discourage privacy and women’s right to a labour companion). At the same time, we need to acknowledge the abusive treatment of women and girls in maternity services as a form of gender violence[5,8,14] that reflects the broader societal devaluation of women and girls and the normalisation of violence against them (particularly marginalised and impoverished women and girls). Violence in obstetric contexts in SA is multilayered and complicated by the fact that it includes both individual acts of abuse and structural components such as degrading spatial configurations that lead to lack of privacy and impede the use of labour companions. We need to address both obvious forms of violence where there is a clear individual ‘perpetrator’ (i.e. physical abuse of patients and intentional emotional abuse) and structural forms of violence (demeaning attitudes towards poor women and girls, authoritative power of obstetric knowledge, infrastructural problems) that create the conditions for individual abuse. SA could learn a great deal from what is happening in Latin America and Spain, where activism and action against abusive treatment during labour and childbirth have been framed within

May 2016, Print edition

ADVERTORIAL

da Vinci Robotic Surgery in South Africa

Dr Gregory B Boustead, MMed, FCS (SA), FRCS (Urol) Specialist Urologist and Robotic Surgeon Netcare Waterfall City, Johannesburg and Christiaan Barnard Memorial, Cape Town, South Africa Introduction Introducing the latest cutting-edge medical technology into developing countries continues to pose moral and ethical dilemmas. Detractors cite high cost and restricted access and make a convincing argument that this investment would be better spent on other essential and more basic medical care. Proponents, on the other hand, argue that while all new technology is expensive initially, cost is driven down as this technology becomes more widely available and competition enters the marketplace. Improving patient outcomes remains the single most important factor by which these technologies should be judged, provided that the instruments used to measure these outcomes are robust, validated and reproducible. The introduction of the da Vinci Surgical Robotic master slave device has been a perfect example of the above. The technology was first introduced in the USA in 2002 and initially market penetration was poor, arguably due to applications in the wrong surgical disciplines and to significantly greater costs compared with open surgery. The timing of its introduction also coincided with widespread publication of comparative studies comparing open and standard laparoscopic techniques. Within certain surgical disciplines, such as urological surgery for example, procedures such as laparoscopic radical nephrectomy became the standard of care based on significantly superior outcomes, across almost every parameter measured. Therefore, showing any further benefit using expensive, robotically assisted laparoscopic surgery proved almost impossible. However, when this technology was applied to more complex renal surgery such as partial nephrectomy (PN), the enhanced vision and dexterity provided by the wristed instrumentation, allowed rapid excision of complex tumours with significantly reduced warm ischaemia times and reduced blood loss, transfusion and hospital stays. Robotic-assisted PN is now the gold standard.

da Vinci robotically assisted laparoscopic radical prostatectomy (RALP) The application of robotic technology to radical prostatectomy in treating organ-confined prostate cancer was a natural progression from standard laparoscopic radical prostatectomy. Once again, the superior vision afforded by 3D high-definition video and wristed instrumentation allowed significantly reduced learning curves. The introduction of training simulators made surgical training of novice surgeons faster and more reproducible, while improving safety. A recent UK HTA study demonstrated that robotic prostatectomy had lower peri-operative morbidity and a reduced risk of a positive surgical margin compared with laparoscopic prostatectomy.[1] The results of the UK randomised trial between surveillance, radical prostatectomy and radiation therapy are eagerly awaited (ProtecT trial) to determine the most effective form of therapy.[2]

Prostate cancer landscape in South Africa in the last decade Patterns of care studies from the USA and Europe have shown that radical prostatectomy has remained the most common form of therapy for early prostate cancer (>70%) across all three risk categories (low, intermediate and high-risk prostate cancer). In these countries, radiation techniques, specifically low-dose rate (LDR) brachytherapy, have represented <15% of treatments across all risk groups.[3,4] Until the introduction of robotic surgery, the treatment patterns in South Africa (SA) over the last decade are virtually precisely opposite to most other countries globally, with LDR brachytherapy (with or without external beam topup) representing >75% of therapy, while radical prostatectomy was <20%. As a consequence, few urologists have performed adequate surgical volumes to maintain skill levels, well documented to improve surgical outcomes. This dynamic is, however, changing, and to date nearly 20 signed-off robotic console surgeons are accredited, with further surgeons still under proctorship. While not every urologist will become robotically trained, the ideal situation would be to develop intermediate to highvolume centres of excellence

Robotic surgery in South Africa Robotic surgery was introduced in SA in October 2013 in a single specialty private urology facility, followed shortly after by two robotic platforms

simultaneously at multispecialty private facilities. Initially, only prostate cancer surgery was performed. More than 2 years on, there are now five robotic platforms installed and operational at centres in Johannesburg, Pretoria, two in Cape Town, with a fifth centre opened in Durban recently.

Training and credentialing in robotic surgery in South Africa The success of the robotic surgical programme in urological surgery to date is as a direct result of the strict selection, training and accreditation of urological surgeons. This has been facilitated by having a single distributor in SA and a single proctor for the vast majority of credentialing. Hospitals investing in robotic surgery need to understand the necessity for high-quality training and supervision as the technology is introduced. Implementation of an internationally agreed training pathway includes online modules, simulator training and equipment and cadaveric/animal laboratory training before moving to the live surgical environment under the mentorship of an expert proctor. Health funders have only approved funding for accredited robotic console surgeons or under an accredited proctor.[5]

Update on the da Vinci urological surgery programme in South Africa At the time of going to print 1 050 robotic procedures have been performed in four centres in SA in <3 years. Robotic-assisted laparoscopic radical prostatectomy has increased by about 70% over initial baseline levels. Audits of initial patient outcomes confirm excellent early cancer control outcomes, low urinary stress incontinence levels and acceptable preservation of sexual function. Complication rates remain low overall comparable with large international series of robotic-assisted and other approaches. Length of stay is significantly reduced with very low blood transfusion rates. Robotic-assisted partial nephrectomy has been introduced at two centres in Gauteng and one in Cape Town. The strong body of evidence supporting robotic PN will make this the gold standard, with the proviso that high-volume centres of excellence are developed. Robotic-assisted cystectomy and cysto-prostatectomy with continent or incontinent urinary diversion is an advanced robotic technique. Currently, there is only one internationally accredited surgeon in SA certified to carry out these procedures.

What does the future hold for robotic surgery in South Africa? Approximately six robotic centres in SA are likely to be the ideal number to optimise access and ensure excellent outcomes in urological surgery. Expansion of robotic surgery to other surgical disciplines will probably take place gradually over the next 2 - 3 years. These specialties may include colorectal surgery, ENT, thoracic surgery and gynaecology. Growth rates of robotic surgery will also depend on other factors, including expansion into the sub-Saharan market, as no other robotic centres exist in Africa. Other factors include entry of new competitor robotic platforms in the marketplace, which may eventually help to drive costs of robotic surgery down. References

1. Ramsay CPR, Robertson C, Close A, et al. Systematic review and economic modelling of the relative clinical benefit and cost-effectiveness of laparoscopic surgery and robotic surgery for removal of the prostate in men with localised prostate cancer. Health Technol Assess 2012;16(41). 2. Lane JA, Donovan JL, Davis M, et al. Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: Study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. Lancet Oncol 2014;15(10):1109-1118. 3. Cooperberg MR, Broering JM, Carroll PR. Time trends and local variation in primary treatment of localized prostate cancer. J Clin Oncol 2010;28(7):1117-1123. 4. Wallis CJD, Saskin R, Choo R, et al. Surgery versus radiotherapy for clinically-localized prostate cancer: A systematic review and meta-analysis. Eur Urol 2015. DOI:10.1016/j.eururo.2015.11.010 5. Vasdev N, Bishop C, Kass-Iliyya A, et al. Developing a robotic prostatectomy service and a robotic fellowship programme â&#x20AC;&#x201C; defining the learning curve. Curr Urol 2013;7(3):136-144.

Address for correspondence:

Suite 1020, Christiaan Barnard Memorial Hospital 181 Longmarket Street, Cape Town, 8001 Tel: +27 21 422 1050; Cell: 0818014363 email: greg@boustead.co.za

Surgical System

celebrates 2.5 successful years in South Africa

The revolutionary da Vinci surgical system,

2. Making difﬁcult operations routine

offered at five major SA hospitals, with the most

Robotic surgery allows surgeons to perform complex,

recent being at the Netcare Umhlanga Hospital.

minimally invasive procedures routinely, reproducibly and with conﬁdence.

1 100 robotic procedures have been undertaken in the last 2.5 years comprising of radical

3. Making new procedures possible

prostatectomy, partial nephrectomy and

Advanced features and the dexterity of da Vinci’s

cystectomy.

EndoWrist® instrumentation allow for a wider range of minimally invasive, multi-disciplinary procedures.

This sophisticated robotic system is designed to dramatically expand the surgeon’s capabilities and offer state-of-the-art, minimally invasive major surgery with improved outcomes. It is fundamentally changing surgery by: 1. Simplifying laparoscopic procedures

Patient beneﬁts from robotic surgery: • Excellent cancer control • Improved functional outcomes • Less blood loss and fewer transfusions

Standard laparoscopy uses small incisions to insert

• Shortened hospital stay

long-shafted instruments but has limitations. The

• Less pain

da Vinci surgery overcomes these with improved

• Lower risk of infection and complications

vision (a 3D high deﬁnition system) and precision

• Fast recovery and return to normal activities

through tiny wristed instruments that have seven

• Small incisions and less scarring

degrees of freedom and can rotate through 540 °.

da Vinci surgery is performed at the following SA hospitals: GAUTENG

WESTERN CAPE

The Urology Hospital, Pretoria

Netcare Christiaan Barnard Memorial Hospital, CPT

+27 12 423 4000

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GUEST EDITORIAL

a broader rhetoric of women’s rights to lives free from all forms of violence and abuse. In these contexts, high rates of medicalisation are also recognised as sources of abuse.[5,9] In the SA context, there has been a lack of attention to potential abuses in private sector facilities, with the predominant assumption that mistreatment and abuse is only a problem in public sector maternity services. This is surprising, given that the private sector in SA has one of the highest rates of caesarean section in the world, with estimates ranging between 40% and 82%.[15,16] Such estimates are far above the rate of 15% recommended by the World Health Organization and raise concerning questions about levels of unnecessary medical intervention in private sector obstetrics in SA. The silence on this issue is itself worrying, and the time is ripe for further investigation and debate regarding practices in the private sector.

Conclusions

Regardless of the roots of abusive treatment, it is important to strive for accountability on all levels – in respect of the state, medical institutions, training programmes and individual practitioners. The use of violence in the form of coercive practices, physical and emotional abuse, lack of consent, intentional humiliation, the withholding of medical attention and care during labour and childbirth as a form of punishment, and the unnecessary use of medical interventions are unacceptable and reflect entrenched systems of gender and class marginalisation in SA. The medical establishment needs to recognise forms of abuse during labour and childbirth as more than the actions of a few misinformed individuals and to address wider systemic sexism and classism in medical training, established protocols and attitudes towards childbearing women and girls.

Rachelle Joy Chadwick Gender Studies Section, School of African and Gender Studies, Anthropology and Linguistics, Faculty of Humanities, University of Cape Town, South Africa rachelle.chadwick@uct.ac.za 1. D’Oliveira A, Diniz S, Schraibe, L. Violence against women in health-care institutions: An emerging problem. Lancet 2002;359(9318):1681-1685. DOI:10.1016/S0140-6736(02)08592-6 2. Schroll, A, Kjaergaard, H, Midtgaard, J. Encountering abuse in health care: Lifetime experiences in postnatal women – a qualitative study. BMC Preg Childbirth 2013;13(74):1-11. DOI: 0.1186/1471-2393-13-74 3. Swahnberg K, Thapar-Bjőrkert S, Berterő C. Nullified: Women’s perceptions of being abused in health care. J Psychosom Obstet Gynaecol 2007;28(3):161-167. DOI:10.1080/01674820601143211 4. D’Ambruoso L, Abbey M, Hussain J. Please understand when I cry out in pain: Women’s accounts of maternity services during labour and birth in Ghana. BMC Public Health 2005;5(140):1-11. DOI:10.1186/1471-2458-5-140 5. Dixon L. Obstetrics in a time of violence: Mexican midwives critique routine hospital practices. Med Anthrop Quart 2015;29(4):437-454. 6. Chadwick R, Cooper D, Harries J. Narratives of distress about birth in South African public maternity settings: A qualitative study. Midwifery 2014;30(7):862-868. DOI:10.1016/j.midw.2013.12 7. Freedman L, Kruk M. Disrespect and abuse of women in childbirth: Challenging the global quality and accountability agendas. Lancet 2014;384(9948):e42-e44. DOI:10.1016/S0140-6736(14)60859-X 8. Jewkes R, Penn-Kekana L. Mistreatment of women in childbirth: Time for action on this important dimension of violence against women. PLoS Med 2015;12(6):e1001849. DOI:10:1371/journal/pmed.1001849 9. Pérez D’Gregorio R. Obstetric violence: A new legal term introduced in Venezuela. Int J Gynecol Obstet 2010;111(3):201-202. DOI:10.1016/j.ijgo.2010.09.002 10. Bohren M, Vogel J, Hunter E, et al. The mistreatment of women during childbirth in health facilities globally: A mixed-methods systematic review. PLoS Med 2015;12(6):e1001847. DOI:10.1371/journal. pmed.1001847 11. Pickles C. Eliminating abusive ‘care’: A criminal law response to obstetric violence in South Africa. SA Crime Quart 2015;54(1):5-16. DOI:10.4314/sacq.v5i1.1 12. Brown H, Hofmeyr J, Nikodem C, Smith H, Garner P. Promoting childbirth companions in South Africa: A randomised pilot study. BMC Med 2007;5(7):1-8. DOI:10.1186/1741-7015-5-7 13. Jewkes R, Abrahams N, Mvo Z. Why do nurses abuse patients? Reflections from South African obstetric services. Soc Sci Med 1998;47(11):1781-1795. DOI:10.1016/S0277-9536(98)00240-8 14. Smith-Oka V. Microagressions and the reproduction of social inequalities in medical encounters in Mexico. Soc Sci Med 2015;143:9-16. DOI:10.1016/j.socscimed.2015.08 15. Naidoo R, Moodley J. Rising rates of caesarean sections: An audit of caesarean sections in a specialist private practice. S Afr Fam Pract 2009;51(3):254-258. DOI:10.1080/20786204.2009.10873857 16. Rothberg A, Macleod H. Private-sector caesarean sections in perspective. S Afr Med J 2005;95(4):257-260.

S Afr Med J 2016;106(5):423-424. DOI:10.7196/SAMJ.2016.v106i5.10708

May 2016, Print edition

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EDITOR’S CHOICE

CME: Acute viral bronchiolitis

This issue of CME profiles acute viral bronchiolitis. This condition is very common, and while it is not often serious, a number of infants are admitted each year to hospital or even paediatric intensive care. This series of articles highlights the diagnostic principles involved and stresses the principles of management and prevention. Acute viral bronchiolitis occurs primarily in infants under a year of age. It is the first episode of a wheezing illness in children and this first episode is never asthma, even though it may lead to subsequent wheezing and even asthma in later life. The lower respiratory tract infection in bronchiolitis is always viral in aetiology and treatment does not require antibiotic management. It is distinguished from pneumonia by hyperinflation of the chest, which suggests airway involvement and not air-space disease. Part two of this CME series covers management in intensive care for severe disease and its epidemiology.

Maternal deaths from bleeding associated with caesarean delivery

Maternal deaths associated with caesarean deliveries (CDs) have been increasing in South Africa (SA) over the past decade.[1] The National Committee on Confidential Enquiries into Maternal Deaths (NCCEMD) is calling this an ‘epidemic’ – one that is increasing. Individual chart reviews of women who died from bleeding at or after CD show that 71% had avoidable factors such as surgical inexperience and poor skills, particularly in rural hospitals, poor postoperative clinical observations, and lack of administration of appropriate oxytocic agents. This appalling state of affairs was highlighted by the NCCEMD as long ago as 2011, when figures from 2005 to 2007 showed that bleeding associated with CD (BLDACD) was the most common causal subcategory of haemorrhage-related maternal death, unlike the pattern in other countries. It also showed that these deaths were increasing over time and were mainly occurring at district and regional hospitals, where most of the CDs were performed. Again, most of these deaths were clearly avoidable. Unforgivably, it would appear that the situation has deteriorated in the years following this initial report, in spite of publication of several reports and attempts at intervention since 2010. There is an urgent need for this epidemic of deaths due to BLDACD in SA to be dealt with. These are mostly young women and ‘mothers to be’ who die from preventable causes. New global goals are for every country to reduce its maternal mortality rate by two-thirds by 2030. This means that SA should reduce its maternal mortality rate from 140 to <50 deaths per 100 000 live births. This will not be achievable unless deaths from BLDACD are reduced.

A multifaceted approach to the management of diabetes mellitus (DM) in resource-limited settings

With the increasing incidence of diabetes mellitus and its conse quences in SA, we urgently need appropriate responses to managing this disease, particularly in resource-limited settings. Pillay and Aldous[2] describe the introduction of a multifaceted approach to this challenge through the introduction of several interventions at a clinic at Edendale Hospital, Pietermaritzburg, KwaZulu-Natal (KZN). These included a structured booking system, which allowed appropriate down-referral to local community healthcare clinics after stabilisation, reducing the numbers of patients seen each week in the Edendale Hospital clinic. A multidisciplinary team was established, which also took part in patient education. Staff were specially trained to deal with

patients with DM and new data collection tools were designed. All these are relatively simple measures that can and should be introduced elsewhere. It will be interesting to see how these measures affect disease outcomes among the patients in the Edendale Hospital clinic.

Emerging trends in noncommunicable disease mortality in SA, 1997 - 2010

This important article[3] reports on part of the second National Burden of Disease Study on behalf of the South African National Burden of Disease team between 1997 and 2010. This study focuses on trends in deaths and premature mortality from 140 causes of death. Of the estimated 594 071 deaths in 2010, 38.9% were due to non-communicable diseases (NCDs) (42.6% of females and 35.4% of males). A sizable proportion (14.7%) of these who died were aged <45 years and 21.5% were aged 45 - 59 years, indicating a considerable number of premature deaths. In 2010, the single leading cause of NCD deaths was stroke, followed by ischaemic heart disease, hypertensive heart disease and diabetes mellitus. For females, cervical and breast cancers ranked in the top 10 causes of death, while lung and prostate cancers were reported for males. Over the past 14 years, NCDs have continued to be a major cause of mortality in SA, despite the country’s profound AIDS epidemic. NCDs accounted for 39% of deaths in 2010 and for considerable premature mortality. Cardiovascular diseases were the major NCDs, and by 2010 stroke had become the second leading cause of death after HIV/AIDS. Of the approximately 230 000 South Africans who died from NCDs in 2010, 36% had not reached the average life expectancy of 60 years. This study shows that there has been a steady increase in deaths due to NCDs, driven by population growth and a shift in the age structure towards older ages. However, agestandardised death rates for NCDs declined by 0.4% per annum over this period, short of the recommended 2%. More work is needed on lifestyle changes to improve the rate of decline and decrease premature mortality.

Costs associated with delivery of HPV vaccination in KZN

High-income countries are introducing HPV vaccination for both males and females, but the World Health Organization recommends female-only vaccination in resource-limited countries such as our own. National policy is to roll out HPV vaccination nationally – two doses of Cervarix given 6 months apart – to all female Grade 4 learners at government schools, targeting approximately 500 000 learners. There needs to be a budget for vaccines and the costs of service delivery. This retrospective analysis[4] used data from the HPV vaccination demonstration project in KZN in 2011. The cost per learner amounted to ZAR510.28 (USD46.39). This translated to ZAR491 400 (USD44 673) for the 963 female learners in the Zululand District, in which the study was carried out. This provides the basis for estimating costs of including male and female learners in the provincial HPV vaccination programme. BF 1. Fawcus S, Pattinson RC, Moodley J, et al., for the National Committee on Confidential Enquiries into Maternal Deaths. Maternal deaths from bleeding associated with caesarean delivery: A national emergency. S Afr Med J 2016;106(5):472-476. DOI:10.7196/SAMJ.2016.v106i5.10821 2. Pillay S, Aldous C. Introducing a multifaceted approach to the management of diabetes mellitus in resource-limited settings. S Afr Med J 2016;106(5):456-458. DOI:10.7196/SAMJ.2016.v106i5.10409 3. Nojilana B, Pillay-van Wyk V, Msemburi W, et al., on behalf of the South African National Burden of Disease team. S Afr Med J 2016;106(5):477-484. DOI:10.7196/SAMJ.2016.v106i5.10674 4. Moodley I, Tathiah N, Sartorius B. The costs of delivering human papillomavirus vaccination to Grade 4 learners in KwaZulu-Natal, South Africa. S Afr Med J 2016;106(5):497-501. DOI:10.7196/ SAMJ.2016.v106i5.9988

May 2016, Print edition

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CORRESPONDENCE

Subacute sclerosing panencephalitis still occurring in South Africa: Clinicians need to remain vigilant

To the Editor: We report on another child with subacute sclerosing panencephalitis (SSPE), expanding the case series reported by Kija et al.[1] to six affected children from the Western Cape region of South Africa (SA) diagnosed in the past 18 months. The child presented to Red Cross War Memorial Children’s Hospital, Cape Town, at 6 years and 3 months of age. She had recently returned to SA after living for several years in Zimbabwe. Her caregivers in SA had not seen her regularly, but understood that her previous health and development had been normal. She was admitted with a reported 1-day history of suddenonset weakness and abnormal movements. She had no known history of toxin exposure or prodromal symptoms prior to her presentation. She had neurodevelopmental regression and demonstrated emotional lability with incoherent speech and disorientation. She was not independently mobile. Her tone and power were normal and symmetrical with brisk deep tendon reflexes. Her abnormal movements were noted to be myoclonic jerks and atonic seizures which manifested as ‘head nods’. She was systemically well with no evidence of sepsis, and while HIV-exposed she had tested negative. Cerebrospinal fluid (CSF) microscopy and chemistry results were normal. An electroencephalogram (EEG) was initially slow with no epileptiform activity correlating with the jerks. Owing to concern about her dramatic presentation and apparent acute-onset encephalopathy, an emergency magnetic resonance imaging (MRI) scan of the brain was performed. This showed high signal on T2 and fluid attenuation inversion recovery (FLAIR) in the posterosuperior putamina, seen to a greater extent on the left than the right (Fig. 1). On the basis of this finding and the unusual clinical phenotype, SSPE was suspected. The child’s CSF measles IgG was positive, while CSF measles polymerase chain reaction (PCR) tested negative. The history of prior measles infection was not initially elicited from the main caregiver, but on further questioning it emerged that the child had contracted measles during the epidemic of 2009 while in SA. The further history unfolded that she had returned from Zimbabwe several months previously but into the care of a different family member. At this point it was confirmed that her symptoms were more chronic and she had been managed at Tygerberg Children’s Hospital, where SSPE had been diagnosed previously. The caregiver at the time was counselled regarding

the diagnosis, but elected to remove the child and transferred her into the care of the current caregiver with no explanation of the preceding events – hence the precipitant presentation with the misleading history. A diagnosis of SSPE, stage two, was made and the child was initiated on carbamazepine and isoprinosine. Over the next 12 weeks her condition remained static with persistent myoclonic and atonic seizures. Serial EEGs, while detecting generalised epileptiform discharges, failed to correlate with the clinical events. Her level of awareness continued to fluctuate, but she has not regressed further. This case is similar to those reported by Kija et al.[1] in that the child contracted measles during the 2009 - 2011 epidemic, during the vulnerable period of infancy before her 9-month measles immunisation. While she was 2 years older at presentation than our previous cases, this is more in keeping with the internationally reported cases’ presenting age of 5 17 years.[2] Her MRI findings included changes affecting the deep greymatter region, which although unusual have been reported in SSPE.[3,4] To date her clinical deterioration has been slower than in the other cases. [1] It is not known whether this is because she was initiated on isoprinosine relatively early in her course, or because she presented at an older age than the other SA children. As in the other reported cases, her measles PCR was negative, with CSF measles antibody titres confirming the diagnosis. This additional case demonstrates that SSPE linked to the 2009 2011 measles epidemic continues to occur in the Western Cape region. It is unclear why it has not been reported from other provinces of SA. Clinicians should have a high index of suspicion when a child presents with acquired movement disorders, intractable seizures and cognitive decline, especially those who were infants during the epidemic of 2009 - 2011. Furthermore, the history of measles may not be forthcoming initially, and clinicians may need to pursue this clinical entity in their workup in order to confirm the diagnosis. Shakti Pillay

Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

Ronald van Toorn

Paediatric Neurology, Tygerberg Hospital, Cape Town, South Africa

Tracy Kilborn

Department of Radiology, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa

Alvin Ndondo

Paediatric Neurology Unit, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

Brian Eley

Paediatric Infectious Diseases Department, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

Jo Wilmshurst

Paediatric Neurology Unit, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital and Faculty of Health Sciences, University of Cape Town, South Africa jo.wilmshurst@uct.ac.za

Fig. 1. T2-weighted axial MRI scan of the brain at the level of the basal ganglia.

1. Kija E, Ndondo A, Spittal G, Hardie DR, Eley B, Wilmshurst JM. Subacute sclerosing panencephalitis in South African children following the measles outbreak between 2009 and 2011. S Afr Med J 2015;105(9):713-718. DOI:10.7196/SAMJnew.7788 2. Guler S, Kucukkoc M, Iscan A. Prognosis and demographic characteristics of SSPE patients in Istanbul, Turkey. Brain Dev 2015;37(6):612-617. DOI:10.1016/j.braindev.2014.09.006 3. Sawaishi Y, Yano T, Watanabe Y, Takada G. Migratory basal ganglia lesions in subacute sclerosing panencephalitis (SSPE): clinical implications of axonal spread. J Neurol Sci 1999;168(2):137-140. DOI:10.1016/S0022-510X(99)00177-X 4. Kim SJ, Kim JS, Lee DY. Neurologic outcome of acute measles encephalitis according to the MRI patterns. Pediatr Neurol 2003;28(4):281-284. DOI:10.1016/S0887-8994(02)00622-7

S Afr Med J 2016;106(5):425. DOI:10.7196/SAMJ.2016.v106i5.10630

May 2016, Print edition

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Exerted specific effects on the following tissues through its active metabolites: Brain, Genital tract and Bone2

Effectively relieved vasomotor symptoms in postmenopausal women3

Showed a better improvement on sexual function compared to combined HRT4

Had a minimal effect on breast tissue vs. combined HRT5 Showed a better vaginal bleeding pattern compared to combined HRT6

Showed beneficial effects on bone over a ten year treatment period7

HRT = hormone replacement therapy

Selected Safety Information: Contra-indications: Known or suspected hormone- dependent tumours; Known, past or suspected breast cancer – LIVIFEM® increased the risk of breast cancer recurrence in a placebo-controlled trial; Known or suspected oestrogen- dependent malignant tumours (e.g. endometrial cancer); Vaginal bleeding of unknown etiology; Untreated endometrial hyperplasia. Warnings: The use of LIVIFEM® should be avoided until 12 months after the last natural menstrual bleed. If LIVIFEM® is taken sooner than this, the frequency of irregular bleeding may be increased. Vaginal bleeding may occur during LIVIFEM® therapy, because of an apparently stimulated endometrium due to some estrogen production. Normally such bleeding is of short duration. Bleedings commencing after 3 months of treatment or recurrent or of longer duration should be investigated. Periodic examinations must be done for endometrial hyperplasia, as well as possible signs of virilisation. The risk of stroke, breast cancer and endometrial cancer (women with an intact uterus) for each women should be carefully assessed, in the light of her individual risk factors and bearing in mind the frequency and characteristics of both cancers and stroke, in terms of their response to treatment, morbidity and mortality. Conditions which need supervision: If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised. It should be taken into account that these conditions may recur or be aggravated during treatment with LIVIFEM®, in particular: leiomyoma (uterine fibroids) or endometriosis; risk factors for oestrogen dependent tumours, e.g. 1st degree for breast cancer; a history of endometrial hyperplasia.

For full prescribing information refer to the package insert approved by the medicines regulatory authority. Reference: 1. Nijland EA, Weijmar WCM, Davis SR. Effects of tibolone and raloxifene on health-related quality of life and sexual function. Maturitas 2007;58:164-173. 2. Data on file, MSD. 3. Hammar M, Christau S, Nathortst-Boos J, Rud T, Garre K. A double-blind, randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms. Br J Obstetr Gynecol 1998;105:904-911. 4. Nijland EA, Schultz WCM, Nathorst-Böös J et al. Tibolone and transdermal E2/NETA for the treatment of female sexual dysfunction in naturally menopausal women: Results of a randomized active-controlled trial. J Sex Med 2008;5(3):646-656. 5. Lundström E, Christow A, Kersemaekers W et al. Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density. Am J Obstet Gynecol 2002;186:717-722. 6. Hammar ML, van de Weijer P, Franke HR et al., on behalf of the TOTAL Study Investigators Group. Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability. BJOG 2007;114:1522-1529. 7. Rymer J, Robinson J, Fogelman I. Ten years of treatment with tibolone 2.5 mg daily: effects on bone loss in postmenopausal women. Climacteric 2002;5:390-398. S4 LIVIFEM® TABLETS. Each tablet contains 2,5 mg tibolone. Reg. No.: V/21.5.4/55. MSD (Pty) Ltd (Reg. No. 1996/003791/07), Private Bag 3, Halfway House 1685. Tel: 011 655 3000. Copyright© 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved. WOMN-1169777-0019 02/18

CORRESPONDENCE

Amoxicillin for the secondary prevention of rheumatic fever in children not allergic to penicillin

Ebrahim G M Hoosen

Paediatric Cardiologist, Unit Head Paediatric Cardiology, Inkosi Albert Luthuli Central Hospital, Honorary Lecturer University of KwaZulu-Natal, South Africa

To the Editor: In October 2014, a communication from the Department of Health substituted azithromycin for erythromycin for penicillin-allergic patients. This was for certain conditions including acute rheumatic fever and prophylaxis of rheumatic fever. It has recently been suggested that owing to the challenges with the availability of oral penicillin, azithromycin should be used as a penicillin substitute for patients who are not allergic to penicillin. In our opinion it is inappropriate to substitute a macrolide for another form of penicillin (amoxicillin) in this situation. The primary reason is that despite many decades of use, there is no significant group A beta-haemolytic streptococcal (GABHS) resistance to penicillin. There are, however, increasing reports of GABHS resistance to macrolides, and azithromycin in particular.[1-4] A previously reported randomised trial[5] of 125 mg phenoxy methylpenicillin (pen VK) or amoxicillin given three times a day for 10 days to children with GABHS pharyngitis demonstrated that the recurrence of the original GABHS within 21 days after the end of therapy was higher with pen VK (20%) than with amoxicillin (13%). The geometric mean minimum inhibitory concentrations for amoxicillin and pen VK against 88 isolates of GABHS were 0.008 and 0.009 μg/mL, respectively. The mean concentrations of amoxicillin and pen VK in sera after 125 mg doses were 3.86 µg/ mL and 1.74 μg/ mL, respectively. In this study, therefore, amoxicillin was active against Gram-positive organisms at an inhibitory level similar to that of pen VK, but had higher blood levels. This study suggests that amoxicillin is probably at least as good as pen VK for the treatment of GABHS pharyngitis. We therefore recommend, as per the South African Essential Drugs List, benzathine penicillin 600 000 units for children <30 kg and 1.2 million units for children ≥30 kg by intramuscular injection every 28 days for the secondary prevention of rheumatic fever. If it is not advisable to use an intramuscular form of penicillin (for example with a patient on warfarin), then in the absence of pen VK and in the absence of penicillin allergy, children weighing <20 kg should be given amoxicillin 125 mg twice daily, and children weighing ≥20 kg given 250 mg twice daily. There is no defined azithromycin paediatric dosage for the secondary prevention of rheumatic fever in penicillin allergy. Azithromycin has however been dosed long term in clinical trials in children with cystic fibrosis.[6-8] There is no consensus on the dosage, but there is some support[6-9] for 250 mg once daily (<40 kg) or 500 mg once daily (≥40 kg) three times a week (Monday, Wednesday and Friday). We recommend that azithromycin is used for the secondary prevention of rheumatic fever only in children who are allergic to penicillin and is dosed 250 mg (<40 kg) or 500 mg (≥40 kg), once a day three times a week (Monday, Wednesday and Friday). Ken Sprenger

Paediatric Cardiologist, Stanger Regional Hospital, KwaZulu-Natal, South Africa kensprenger@aol.com

Medeshni Annamalai

Paediatric Pulmonologist, Stanger Regional Hospital, KwaZulu-Natal, South Africa

Jeroen van Lobenstein

Paediatrician, HOD Department of Paediatrics and Child Health, Stanger Regional Hospital, KwaZulu-Natal, South Africa

1. Sayyahfar S, Fahimzad A, Naddaf A, Tavassoli S. Antibiotic susceptibility evaluation of group A streptococcus isolated from children with pharyngitis: A study from Iran. Infect Chemother 2015;47(4):225-230. DOI:10.3947/ic.2015.47.4.225. 2. Jain A, Shukla VK, Tiwari V, Kumar R. Antibiotic resistance pattern of group-a beta-hemolytic streptococci isolated from north Indian children. Indian J Med Sci 2008;62(10):392-396. DOI:10.4103/0019-5359.44018 3. Cocuzza C, Blandino G, Mattina R, Nicoletti F, Nicoletti G. Antibiotic susceptibility of group A Streptococci in 2 Italian cities: Milano and Catania. Microb Drug Resist 1997;3(4):379-384. 4. Gerber MA. Antibiotic resistance in group A streptococci. Pediatr Clin North Am 1995;42(3):539-551. 5. Stillerman M, Isenberg HD, Facklam RR. Treatment of pharyngitis associated with group A streptococcus: Comparison of amoxicillin and potassium phenoxymethyl penicillin. J Infect Dis 1974;129 (Suppl 2):S169-S177. 6. Clement A, Tamalet A, Leroux E, Ravilly S, Fauroux B, Jais J-P. Long term effects of azithromycin in patients with cystic fibrosis: A double blind, placebo controlled trial. Thorax 2006;61(10):895-902. DOI:10.1136/thx.2005.057950. 7. Baumann A, King M, App EM, et al. Long term azithromycin therapy in cystic fibrosis patients: A study on drug levels and sputum properties. Can Resp J 2004;11(2):151-155. 8. National Institute for Health and Care Excellence (NICE). Cystic fibrosis: long-term azithromycin. Evidence summary: Unlicensed or off-label medicine. 2014. http://www.nice.org.uk/guidance/ esuom37 (accessed 7 February 2016). 9. Royal Brompton & Harefield NHS Foundation Trust. Long term azithromycin. http://www.rbht.nhs. uk/healthprofessionals/clinical-departments/paediatrics/childrencf/respiratory-care/azithromycin/ (accessed 7 February 2016).

S Afr Med J 2016;106(4):317. DOI:10.7196/SAMJ.2016v106i4.10711

Kounis syndrome: Aspects of incidence and epidemiology

To the Editor: Kounis syndrome is a hypersensitivity coronary disorder induced by environmental factors, foods, drugs, conditions and stents. It manifests as coronary spasm, acute myocardial infarction and stent thrombosis, and affects the cerebral, mesenteric and coronary arteries. Allergic, hypersensitivity, anaphylactic and anaphylactoid reactions are associated with this syndrome. Kounis syndrome has been observed in every race, age group (2 - 90 years) and geographical location.[1] It is not a rare disease, but it is infrequently reported in clinical practice because of missed, unrecognised and/ or undiagnosed cases. Furthermore, there is a paucity of large prospective trials, determining its prevalence and exact incidence. In a very interesting report published in the SAMJ[2] a 39-year-old man with a previous history of exercise-induced asthma and allergy to cefixime developed type I Kounis syndrome following an allergic reaction to ciprofloxacin. The authors correctly commented on the paucity of data concerning the incidence and prevalence of Kounis syndrome in South Africa and elsewhere. We therefore consider the following aspects on its incidence and epidemiology to be of additional value: The incidence of anaphylaxis with circulatory symptoms is estimated at 7.9 - 9.6/100 000 inhabitants per year with a case fatality rate of 0.0001%.[3] In the only retrospective study published so far, the incidence of Kounis syndrome at emergency departments in 1 year among all admissions and allergy patients was 19.4/100 000 (27/138 911) and 3.4% (27/793), respectively.[4] Of the 51 cases of Kounis syndrome reported to the International Pharmacovigilance Agency (VigiBase) in the period 2010 - 2014, almost half (22 reports) were in 2014. Most cases occurred in the USA, and non-steroidal anti-inflammatories were the most frequent trigger drugs.[5] Kounis syndrome prevalence was estimated to be at 0.002% in the catheterisation laboratory of a tertiary hospital in Istanbul, Turkey.[6] The annual incidence of Kounis syndrome in the district of Achaia, Greece, with a population of 300 000 inhabitants, was estimated at 4.33 cases/100 000 inhabitants.[7] Troponin levels were found to be significantly raised in 31 patients admitted to the emergency department and suffering from anaphylaxis, angioedema, urticaria and urticaria-angioedema in comparison with 125 healthy controls. Systematic troponin

May 2016, Print edition

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CORRESPONDENCE

measurement in patients with acute allergic reactions is advisable in order to detect and treat potential myocardiac injury.[8] Finally, in 300 anaphylaxis cases, myocardial injury was present in 7.3% of patients. Various cardiomyopathies, including Kounis syndrome and Takotsubo cardiomyopathy, were also observed in patients with myocardial injury.[9] All the above denotes that the incidence of Kounis syndrome is higher that it has been estimated so far. Kounis syndrome has mostly been encountered in southern Europe, especially Turkey, Greece, Italy and Spain.[10] This geographical variation could be attributed to the increased awareness of physicians of the existence of Kounis syndrome, climate and environmental conditions that result in pollen cross-reactivities and hymenoptera exposures, overconsumption of medicines, or inadequacy of preventative measures. It is anticipated that with increased awareness of the existence of Kounis syndrome and the conducting of large prospective trials, the true estimation of its incidence will be achieved. Nicholas G Kounis

Department of Medical Sciences, Western Greece Highest Institute of Education and Technology, Patras, Achaia, Greece ngkounis@otenet.gr

Nicholas Grapsas, Dimitrios Lianas, George D Soufras

Department of Cardiology and Emergency Medicine, Saint Andrews State General Hospital, Patras, Achaia, Greece

Nicholas Patsouras

Department of Cardiology, University of Patras Medical School, Patras, Achaia, Greece 1. Kounis NG, Giannopoulos S, Soufras GD, Kounis GN, Goudevenos J. Foods, drugs and environmental factors: Novel Kounis syndrome offenders. Intern Med 2015;54(13):1577-1582. DOI:10.2169/ internalmedicine.54.3684 2. Ntuli PM, Makambwa E. Kounis syndrome. S Afr Med J 2015;105(10):878. DOI:10.7196/SAMJnew.8767 3. Helbling A, Hurni T, Mueller UR, Pichler WJ. Incidence of anaphylaxis with circulatory symptoms: A study over a 3‑year period comprising 940 000 inhabitants of the Swiss Canton Bern. Clin Exp Allergy 2004;34(2):285‑290. DOI:10.1111/j.1365-2222.2004.01882.x 4. Akoz A, Tanboga HI, Emet M, et al. A prospective study of Kounis syndrome: Clinical experience and cardiac magnetic resonance imaging findings for 21 patients. Acta Med Mediterraea 2013;29:811-816. 5. Renda F, Landoni G, Trotta F, et al. Kounis syndrome: An analysis of spontaneous reports from international pharmacovigilance database. Int J Cardiol 2016;203:217-220. DOI:10.1016/j.ijcard.2015.10.003 6. Biteker M. Current understanding of Kounis syndrome. Exp Rev Clin Immunol 2010;6(5):777-788. DOI:10.1586/eci.10.47 7. Kounis NG, Mazarakis A, Tsigkas G, Giannopoulos S, Goudevenos J. Kounis syndrome: A new twist on an old disease. Future Cardiol 2011;7(6):805-824. DOI:10.2217/fca.11.63 8. Lippi G, Buonocore R, Schirosa F, Cervellin G. Cardiac troponin I is increased in patients admitted to the emergency department with severe allergic reactions. A case-control study. Int J Cardiol 2015;194:6869. DOI:10.1016/j.ijcard.2015.05.093 9. Cha YS, Kim H, Bang MH, et al. Evaluation of myocardial injury through serum troponin I and echocardiography in anaphylaxis. Am J Emerg Med 2016;34(2):140-144. DOI:10.1016/j. ajem.2015.09.038 10. Kounis NG, Soufras GD, Davlouros P, Tsigkas G, Hahalis G. Combined etiology of anaphylactic cardiogenic shock: amiodarone, epinephrine, cardioverter defibrillator, left ventricular assist devices and the Kounis syndrome. Ann Card Anaesth 2015;18(2):261-264. DOI:10.4103/0971-9784.154498

S Afr Med J 2016;106(5):426. DOI:10.7196/SAMJ.2016.v106i5.10680

Neuroimaging in migraine

To the Editor: In a recent paper published in Cephalalgia, the official journal of the American Headache Society, Callaghan et al.[1] reported on information extracted from more than 50 million headache visits in the USA. This indicated that as many as 9.8% of patients

with a diagnosis of migraines underwent neuroimaging – either magnetic resonance angiography or computed tomography. After removing those patients with ‘red flags’ on neurological evaluation, the percentage undergoing neuroimaging decreased from 9.8% to 8.3%. This was contrary to the guidelines originally laid down by Frishberg,[2] and later confirmed in a number of studies. [3,4] These guidelines suggested that for migraines, there was no difference in the incidence of clinically meaningful pathology to the incidence in the general population, and that neuroimaging is unnecessary. [5] Exceptions to these recommendations are the presence of the following red flags: • new-onset or change in headache in patients who are >50 years old • thunderclap: rapid time to peak headache intensity (seconds to 5 minutes) • focal neurological symptoms (such as limb weakness, aura <5 minutes or >1 hour) • non-focal neurological symptoms (such as cognitive disturbance) • change in headache frequency, characteristics or associated symptoms • abnormal findings on neurological examination • headache that changes with posture • headache that wakes the patient up (migraine is the most frequent cause of morning headache) • headache precipitated by physical exertion or Valsalva manoeuvre (such as coughing, laughing and straining) • patients with risk factors for cerebral venous sinus thrombosis • jaw claudication or visual disturbance • neck stiffness • fever • new-onset headache in a patient with a history of HIV infection • new-onset headache in a patient with a history of cancer. Most headache specialists agree that neuroimaging in migraine is unnecessary, but in spite of this, many still continue to overuse neuroimaging because of the fear of litigation. All the evidence suggests that neuroimaging should only be used in migraine patients with red flags.[5] Elliot Shevel

Migraine Research Specialist, The Headache Clinic and Specialist Migraine Unit, Johannesburg, South Africa drshevel@headclin.com 1. Callaghan BC, Kerber KA, Pace RJ, Skolarus L, Cooper W, Burke JF. Headache neuroimaging: Routine testing when guidelines recommend against them. Cephalalgia 2015;35(13):1144-1152. DOI:10.1177/0333102415572918 2. Frishberg BM. The utility of neuroimaging in the evaluation of headache in patients with normal neurologic examinations. Neurology 1994;44(7):1191-1197. DOI:10.1212/WNL.44.7.1191 3. American Academy of Neurology. Evidence-based guidelines in the primary care setting: Neuroimaging in patients with nonacute headache. 1994. http://tools.aan.com/professionals/practice/pdfs/g10088.pdf (accessed 10 March 2016). 4. Loder E, Weizenbaum E, Frishberg B, Silberstein S. Choosing wisely in headache medicine: The American Headache Society’s list of five things physicians and patients should question. Headache 2013;53(10):1651-1659. DOI:10.1111/head.12233 5. Frishberg BM. Neuroimaging in headache: Lessons not learned. Cephalalgia 2015;35(13):1141-1143. DOI:10.1177/0333102415572919

S Afr J Med 2016;106(5):427. DOI:10.7196/SAMJ.2016.v106i5.10574

May 2016, Print edition

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IZINDABA

Costly adult ADHD shunned by medical aids Lack of clinical knowledge and financial support for adults with attention deficit hyperactive disorder (ADHD) are major barriers to treatment and diagnosis of a condition affecting an estimated one million South Africans aged 20 - 50 years. This is the finding of a thesis completed by Dr Renata Schoeman, a psychiatrist and Stellenbosch University Business School (SBC) top-of-class MBA student. It involved a triangulated study: a retrospective database analysis of all claims submitted to one of the country’s largest medical scheme administrators over a 2-year period, a survey of all registered psychiatrists (588, with 455 in private practice) treating adult ADHD patients, and a qualitative analysis of key local opinion leaders in the fields of psychiatry and neurology. She found that, left untreated or misdiagnosed, adult ADHD increased the risk of other psychiatric phenomena such as anxiety, mood disorder and substance abuse. At work, people with ADHD displayed poor time management, goal setting, stress management and organisational skills – which had a major impact on colleagues. While medical schemes routinely covered childhood ADHD, they seldom provided benefits for adults, who struggled to afford private treatment over and above their monthly medical aid costs. This led to huge undertreatment. ‘It’s a costly, chronic disorder,

with significant impact on the quality of life of patients and their families,’ she emphasises. She cites the condition’s disability-adjusted life-years (DALYs) at 424/100 000.

Primary care clinical knowledge poor

GPs routinely misdiagnosed or inappro priately diagnosed complex presenting symp toms. They and many psychiatrists (especially those who qualified before adult ADHD was recognised as a disorder) had limited knowledge about adult ADHD. ‘Also, you cannot assess properly in 15 minutes. It often presents with comorbidities. Those who primarily complain of ADHD symptoms are often students and professionals wanting the drugs for study purposes, so vigilance is needed.’ She described the longstanding student practice of misusing ADHD medication to improve concentration (without being diagnosed with the condition) as ‘irresponsible and potentially risky’. Schoeman has developed a new funding model. She’s confident that it will help medical aids come to grips with longterm patient needs, and improve access to diagnosis and treatment. She believes that medical aid funding reluctance may be due to a lack of knowledge, and the risk of overdiagnosis – which further strengthens the case for raising the diagnostic bar.

Dr Renata Schoeman, psychiatrist and top of her class at Stellenbosch University Business School.

Schoeman was judged SBC’s top MBA student for 2015. Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(5):431. DOI:10.7196/SAMJ.2016.v106i5.10910

Drunk driving: Bring back the breathalyser – experts Although mortuaries and trauma units around the country dealt with fewer dead and injured motorists this Easter (46% fewer fatalities than last year), a leading trauma surgeon and a high-profile forensic pathologist emerged to call for a return to legally competent breathalysers. Abandoned as a substandard primary prose cution tool after a precedent-setting drunkdriving case heard in the Cape Town High Court 3 years ago, the locally inaccurate and badly calibrated breathalyser had previously been the utilitarian weapon of choice. By this Easter there was no sign of its return. Prof. Ken Boffard,

Trauma Director at Netcare Milpark Hospital in Gauteng, a level 1-accredited trauma unit, sees 120 major trauma patients a month, half of whom are car occupants and 60% of whom are over the legal alcohol limit (0.05 g/dL). This equals the annual percentage of people over the legal alcohol limit whose bodies are brought to the State mortuary in Salt River, Cape Town – which sees the largest number of unnatural deaths in the country, according to Prof. Lorna Martin, Head of Forensic Medicine at the University of Cape Town and clinical department Head of Forensic Services for the Western Cape. Boffard, citing the average of

May 2016, Print edition

1 300 deaths per month on the road, said that the alternative to the breathalyser of securing convictions for alcohol abuse – blood alcohol tests – was ‘too much trouble’ for most police officers. ‘You have to find an appropriately registered doctor, then it takes days to get the tests back, and then you have to spend about 4 days, or more, in court. I’d venture to suggest that you could count on your hand the number of blood alcohols they take in one road block, let alone those drawn by a district surgeon. How do you deal with the problem when the bulk of law enforcers refuse to accept the effort required to deal with it?’ he asked.

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IZINDABA

Widespread incompet ence and lack of skills

Dr David Klatzow, independent forensic pathologist and pivotal expert witness in the case that brought about the breathalyser’s demise, said that ‘pure incompetence’ – from the roadside to the eventual laboratory testing of blood samples – was responsible for multiple court cases being thrown out. ‘Blood sampling is the gold standard when done properly by somebody qualified, but they seem incapable of maintaining the chain of evidence,’ he said. He explained that blood first had to drawn from a suspect by a registered nurse or a doctor, then put into a labelled bag and then into a ‘vacutainer’ (to keep it sterile), then handed to a policeman, who signed for it, and then transported to a laboratory, where it was again signed for. ‘There are usually four to five links in the chain which they seem incapable of getting right – and then it sits in the lab for weeks, if not several months.’ His contention is that the poor skills and low qualifications of staff at the national health department’s chemical laboratories are then responsible for wide variations in test results and delays – so much so that the bulk of samples are unreliable in court. Samples were supposed to be tested in duplicate at the same lab, with readings varying more by not more than 10%. His most recent experience in consulting for an insurer revealed that a client’s blood alcohol level read 0.08 and 0.16 g/dL in two tests at a state laboratory – which he said was ‘par for the course’. ‘I’d say that most of the samples they do are 134% apart,’ he added. Boffard says he can remember only one instance of a traffic officer requesting a legal blood alcohol sample from a patient in over 20 years at Milpark Hospital. The only record-breaking exception to the average (of illegally high) blood alcohol levels in 60% of his patients (0.171 g/dL) was a reading of 0.27 – the morning after the person concerned was admitted. ‘Last Christmas period we had three very high blood alcohols – and they were all police officers,’ he chuckled.

‘How do you deal with the problem when the bulk of law enforcers refuse to accept the effort required to deal with it?’ he asked. Klatzow’s claims on lack of capacity and skills seem strongly backed by figures released this year that show the direly needed drastic improvements in the backlog for drunk driving samples at state forensic labs across provinces to be patchy. In Pretoria, drunk driving test backlogs, after spiking from 11 890 on 31 January 2014 to 19 841 by 31 January

Prof. Ken Boffard, Trauma Director at Milpark Hospital in Johannesburg.

2015, dropped back in January this year to 6 074, a reduction of 49%. Cape Town’s drunk driving test backlog was 25 933 on 31 January 2014, 12 856 on 31 January 2015, and 2 360 in January 2016 – an impressive reduction of 90%. In Johannesburg, the backlog was 29 589 on 31 January 2014, down to 26 117 on 31 January 2015, and up again to 30 376 on mid-February, an increase of 3%.

Authorities turn down expert help

Klatzow says that he has repeatedly offered his expertise to state, provincial and municipal auth orities to help address the breathlyser shortcomings, but has been sullenly turned down. The state, however, reluctantly took his advice to use vacutainers to increase the integrity of blood samples. Turning to drug abuse, he said that the toxicology arm of state pathology services was ‘even worse, if that’s possible. You can wait 5 years for results – the other day a magistrate told me he’d waited 10 years – it’s the laughing stock of the professions.’ He accused government authorities of ‘never admitting that they could possibly be wrong – you cannot make science right by using smoke and mirrors’. An Izindaba check on trauma patient capacity in and around Bloemfontein, through which one of South Africa (SA)’s main highway routes passes, was somewhat less alarming, although Bloemfontein, Johannesburg and Pietermaritzburg emerged as isolated ‘islands of trauma care’ through which holiday travellers pass. Pelonomi Academic Hospital principal trauma surgeon Dr Andrew Laubser said that prehospital and in-hospital treatment in both the public and private sectors in and within 150 km of Bloemfontein were ‘pretty good’, with the private sector ‘well above average’. A

May 2016, Print edition

patient with severe complications in his trauma unit would be resuscitated and be in ‘good hands’. However, the problems began when they needed to be moved out of his trauma unit. Radiographers were either unavailable or not appointed, theatre support was often non-existent and computed tomography scanners stood for months in disrepair, while intensive care units were severely understaffed. ‘Sometimes we have two sisters attending to 80 patients during the night,’ he added. Both Pelanomi and Universitas hospitals had private healthcare hospitals physically attached to them, with patient care collaboration at Pelonomi more efficient. He said that both interpersonal violence and car crash admissions increased by about 30% over the festive seasons, with alcohol playing a major overall role. Boffard said that 88% of his severely injured Milpark patients had been involved in interpersonal violence.

Turning to drug abuse, Klatzow said that the toxicology arm of state pathology services was ‘even worse, if that’s possible. You can wait 5 years for results – the other day a magistrate told he’d waited 10 years – it’s the laughing stock of the professions.’ Boffard explained that the reason patients had both blood alcohol and toxicology testing on admission was because these affected how shock presented (and thus treatment), and could also be responsible for a reduced level of consciousness. He emphasised that unless a legally requested sample was taken, neither medical measurement could be used by police or insurance companies. All those interviewed for this article agreed that until SA society began viewing it as culturally unacceptable to drink and drive – and enforcement was backed up with legal accountability – the horrific death and injury statistics would remain. Transport-related injuries account for more than one-third of all external causes of death (33.8%) in SA. Road traffic age-specific mortality rates are about double the global rate in both sexes, peaking at 2.5 times the global rate in adult women aged 30 - 44.[1] Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(5):432-433. DOI:10.7196/SAMJ.2016.v106i5.10912 1. Norman R, Matzopoulos R, Groenewald P, Bradshaw D. The high burden of injuries in South Africa. Bull World Health Organ 2007;85(9):649-732. DOI:10.2471/BLT.06.037184

IZINDABA

Health department selectively using NGO input – claim Willing healthcare worker feedback to the unique Stop-Stock-Outs Coalition (SSC) stands to improve the quality and length of patients’ lives – but for thou sands, corrective action will take too long if government continues to ignore civil society input. That’s the message from SSC co-ordinator Sue Tafeni in response to last month’s findings by a National Department of Health (NDoH) task team after it reviewed reports on availability of medicines nationally. Consisting of local and international experts (but without any civil society coalition partners), the government task team studied reports from the Public Service Commission, the NDoH pharmaceutical team and the SSP. Tafeni described the recommendations as ‘news to us’, saying that the SSP was excluded from a subsequent stakeholder meeting held to discuss proposed interventions. The SSP consists of Médecins Sans Frontières, the Southern African HIV Clinicians Society, Section 27, the Rural Health Advocacy Project, the Rural Doctors Association of South Africa and the Treatment Action Campaign (TAC), all of whom have historically been well ahead of government

in initiating lifesaving public sector drug access and appropriate treatment. While welcoming the belated initiative and finance minister Pravin Gordhan’s allo cation of ZAR300 million for developing a national electronic medicine stock management system, Tafeni said there were huge logistic challenges. ‘It will take a lot of work and time. In the meantime they must put emergency distribution and reporting systems in place – and sort out drug depot issues in the provinces.’ The electronic medicine stock manage ment system is being piloted in two provinces. Tafeni finds it ‘ironical’ that the SSP, upon whose report many recommendations are based, is being ‘left out in the cold’, with attempts to engage with NDoH drug and policy chiefs allegedly proving futile. The SSP, with keen response from healthcare workers, called 79% of all primary healthcare facilities nationwide between July and October last year to find that 64% had experienced stockouts within the past 3 months and 44% were experiencing stock-outs on the day of their call. It found stock-outs of nine essential medicines, with more than half of all drug orders unplaced, insufficient or late.

Marcus Lowe, Head of Policy for the TAC, said that while they acknowledged that the government was taking steps to address stock-outs, it was not yet clear what the impact would be on patients and clinicians. ‘There’s a lack of transparency around exactly what they are doing and how they are measuring the impact of what they are doing. We think it’s unacceptable that we’ve been excluded from the current process to deal with stock-outs. Civic society organisations have a huge stake in how government responds to medicines stockouts. We’ve clearly done substantial work on this, and to be excluded is unacceptable. We suspect that things like medicines stock-outs are symptomatic of wider dysfunction in the healthcare system. In some cases it’s lack of management capacity and in some provinces it’s lack of political will. In others it’s just down to the politicisation of the healthcare system.’ Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(5):434. DOI:10.7196/SAMJ.2016.v106i5.10911

Errata Kounis syndrome

In the article entitled ‘Kounis syndrome’ by Ntuli and Makambwa, which appeared on p. 878 of the October 2015 SAMJ (Vol. 105, No. 10), Fig. 2 was mislabelled as ‘Unobstructed right coronary artery’ and Fig. 3 as ‘Unobstructed left coronary artery’. The legend for Fig. 2 should have read ‘Unobstructed left coronary artery’ and the legend for Fig. 3 ‘Unobstructed right coronary artery’. The online version of the article (http://dx.doi.org/10.7196/SAMJnew.8767) was corrected on 20 April 2016. S Afr Med J 2016;106(5):429. DOI:10.7196/SAMJ.2016.v106i5.10916

Consciously cutting to the bone of SA’s surgical/anasthetic delivery

In the Izindaba story entitled ‘Consciously cutting to the bone of SA’s surgical/anaesthetic delivery’ (http://dx.doi.org/10.7196/SAMJ.2016. v106i2.10526), which appeared in the February 2016 SAMJ (Vol. 106, No. 2, p. 134), Prof. Christina Lundgren, Clinical Head of Anaesthesia at Chris Hani Baragwanath Academic Hospital, cited the worldwide anaesthetic mortality rate as being 1%. The South African Society of Anaesthesiologists (SASA) has pointed out that such mortality rates vary widely owing to a number of factors, including the number of anaesthesiologists available, and are therefore dependent on the specific country conditions and too varied to be stated so specifically. SASA states that in South Africa the rate of deaths due to anaesthesia (including both obstetric and non-obstetric) is 1 in 10 000. S Afr Med J 2016;106(5):430. DOI:10.7196/SAMJ.2016.v106i5.10917

May 2016, Print edition

EDITORIAL

Maternal deaths from bleeding associated with caesarean delivery: A national emergency In this issue of the SAMJ, Fawcus et al.[1] draw attention to the epi demic of avoidable maternal deaths from caesarean-related haemorr hage in South Africa (SA). How can this epidemic be addressed? Firstly, the most effective and cost-effective way to reduce maternal mortality from all causes is by preventing unintended pregnancies. In SA we have proved our capacity to mainstream the largest HIV treatment programme in the world into all levels of our health services. We need to do the same for family planning. In particular, the copper intrauterine contraceptive device (IUCD) needs to be made more accessible as an option. Current limited evidence suggests that the IUCD is more effective than injectable progestogens.[2,3] Health workers need training in counselling and techniques of inserting the IUCD after pregnancy termination, after vaginal birth and at caesarean section, as well as in interval insertion. Secondly, we need to reduce unnecessary caesarean sections (CSs) by improving the quality of childbirth care. Drivers of the increasing CS rates include erosion of obstetric skills and confidence, and spiralling litigation, which leads to ‘defensive’, unscientific practices and reduces the funds available for public health services. Companionship during childbirth[4] has been shown to reduce CSs. In metropolitan areas, primary care, midwife-led childbirth services can be improved in terms of uptake, quality, safety and costeffectiveness by location on the premises of large hospitals.[5] Thirdly, we need to ensure that women undergoing CS receive adequate prophylactic uterotonics. Ironically, the availability of intravenous access at CS has led to a preference for intravenous rather than intramuscular oxytocin administration, but because of the risk of hypotension specific to the intravenous route, the initial dosage has been reduced from 10 to 2.5 IU, supplemented by an ongoing infusion that may or may not be remembered.[6] A case may be made for the simplicity and certainty of the intramuscular route. In addition, given the increased risk and danger of haemorrhage in the context of CS, addition of ergometrine for women without contraindications, and a second dose of oxytocin after 4 hours, have been recommended. As the authors point out,[1] the popularity of misoprostol has tended to distract attention from the more effective conventional uterotonics. Its formulation as a simple, inexpensive tablet may be assumed to be a less ‘invasive’ and therefore safer option than injectable uterotonics. On the contrary, misoprostol is a powerful

prostaglandin analogue with multiple side-effects. It has a modest effect on blood loss after childbirth, but has not yet been shown to reduce the overall risk of death.[7] What about future research? Oxytocin has the limitation of requiring a cold chain to maintain effectiveness. The World Health Organization is currently testing the effectiveness of a new, heatstable formulation of carbetocin.[8] More evidence is needed on the relative effectiveness of alternative strategies to treat haemorrhage when it occurs. No doubt our knowledge will increase. But to address the current crisis of avoidable maternal deaths, what is needed most are the health service infrastructure, education, workforce and political will to make the care already known to be effective, accessible to all women. G J Hofmeyr Walter Sisulu University, Mthatha, Eastern Cape, South Africa, University of Fort Hare, Alice, Eastern Cape, University of the Witwatersrand, Johannesburg, South Africa, and Eastern Cape Department of Health Corresponding author: G J Hofmeyr (justhof@gmail.com) 1. Fawcus S, Pattinson RC, Moodley J, et al., for the National Committee on Confidential Enquiries into Maternal Deaths (NCCEMD). Maternal deaths from bleeding associated with caesarean delivery: A national emergency. S Afr Med J 2016;106(5):472-476. DOI:10.7196/SAMJ.2016.v106i5.10821 2. Hofmeyr GJ, Singata M, Lawrie TA. Copper containing intra-uterine devices versus depot progestogens for contraception. Cochrane Database Syst Rev 2010; Issue 6. Art. No.: CD007043. DOI:10.1002/14651858.CD007043.pub2 3. Hofmeyr GJ, Singata-Madliki S, Lawrie TA, Bergel E, Temmerman M. Effects of the copper intrauterine device versus injectable progestin contraception on pregnancy rates and method discontinuation among women attending termination of pregnancy services in South Africa: A pragmatic randomised controlled trial. Reprod Health (in press). 4. Hodnett ED, Gates S, Hofmeyr GJ, Sakala C. Continuous support for women during childbirth. Cochrane Database Syst Rev 2012, Issue 10. Art. No.: CD003766. DOI:10.1002/14651858.CD003766. pub4 5. Hofmeyr G, Mancotywa T, Silwana-Kwadjo N, Mgudlwa B, Lawrie TA, Gülmezoglu A. Audit of a new model of birth care for women with low risk pregnancies in South Africa: The primary care onsite midwife-led birth unit (OMBU). BMC Pregnancy Childbirth 2014;14(1):417. DOI:10.1186/s12884014-0417-8 6. Farina Z, Fawcus S. Management of obstetric haemorrhage. Oxytocin ensuring appropriate use and balancing efficacy with safety. S Afr Med J 2015;105(4):271-274. DOI:10.7196/SAMJ.9179 7. Hofmeyr GJ, Gülmezoglu AM, Novikova N, Lawrie TA. Postpartum misoprostol for preventing maternal mortality and morbidity. Cochrane Database Syst Rev 2011, Issue 2. Art. No.: CD008982. DOI:10.1002/14651858.CD008982 8. Widmer M, Piaggio G, Abdel-Aleem H, et al. Room temperature stable carbetocin for the prevention of postpartum haemorrhage during the third stage of labour in women delivering vaginally: Study protocol for a randomized controlled trial. Trials 2016;17(1):143-152. DOI:10.1186/s13063-016-127-1

S Afr Med J 2016;106(5):435. DOI:10.7196/SAMJ.2016.v106i5.10822

May 2016, Print edition

EDITORIAL

Persistent burden from non-communicable diseases in South Africa needs strong action The number of deaths from non-communicable diseases (NCDs) has been rising globally, and NCDs are currently among the leading causes of death in many countries.[1] The mortality profile in the African region is currently dominated by communicable, maternal, nutritional and perinatal conditions. However, changes are taking place and the World Health Organization has projected that by 2030, NCDs will be the biggest cause of death in this region.[2] The Burden of Disease Research Unit at the South African Medical Research Council recently analysed mortality levels and trends for NCDs over a 14-year period as part of its second National Burden of Disease Study for South Africa (SA).[3] Our study shows that NCDs are already among the top causes of death in SA [3] By 2010, NCDs accounted for 39% of total deaths in the country. More than a third (36%) of these deaths occurred before the age of 60 years. In 2010, the number of deaths due to NCDs was similar to the number from HIV/AIDS and tuberculosis (TB) combined. However, the age-standardised death rates (ASDRs)

B. Females Deaths/100 000 population, n

160 140 120 100 80 60 40 20 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Deaths/100 000 population, n

Year

30 25 20 15 10 5 0

45 40 35

Colorectal Cervical Female breast Prostate

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Year Deaths/100 000 population, n

Year

70 60 50 40 30 20 20 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Deaths/100 000 population, n

Oesophagus Lung Stomach

30 25 20 15 10 5 0

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Deaths/100 000 population, n

Year 45 40 35

Cerebrovascular disease IHD Hypertensive heart disease Cardiomyopathy Diabetes mellitus Renal disease

Year

70 60 50 40 30 20 20

COPD Asthma Other respiratory disease

0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

160 140 120 100 80 60 40 20 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Deaths/100 000 population, n

A. Males

for NCDs were higher than those of other broad cause categories (namely HIV/AIDS and TB combined; and other communicable diseases, plus maternal, perinatal and nutritional conditions). We found that the overall NCD mortality rate decreased over time, but that there was a mix of increasing and decreasing trends for specific diseases (Fig. 1). This highlights the changing lifestyle and risk factor profiles of the SA population. The increase in mortality from diabetes mellitus, renal disease and endocrine/nutritional and blood disorders is concerning and is probably a result of lifestyle changes, urbanisation[4] and more South Africans falling into the overweight and obese category.[5] Effects of the tobacco control interventions[6] can be seen in the decrease in mortality rates from ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease and asthma. The substantial decrease in mortality from oesophageal cancer may be due to changing socioeconomic status, urbanisation and resultant dietary changes, including shifts from consuming home-grown to commercial maize.[7]

Year

Fig. 1. Trends in ASDRs for diabetes mellitus, cardiovascular diseases, cancers and chronic respiratory disease by specific cause by sex, SA 1997 - 2010.[3] (IHD = ischaemic heart disease; COPD = chronic obstructive pulmonary disease.)

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Cardiomyopathy

Hypertensive heart disease

Cerebrovascular disease

Diabetes mellitus

IHD

Renal disease

Other cardiovascular 250 Deaths/100 000 population, n

Cardiovascular diseases were the leading category of NCDs. However, population groups are in different stages of the cardiovascular transition,[8,9] as shown in Fig. 2. In 2010, Asians had distinctively high ASDRs for ischaemic heart disease (IHD) and renal disease. The ASDRs for IHD were almost twice as high as in the other population groups. In contrast, black Africans are in the midst of a cardiovascular epidemic with relatively high ASDRs from cerebrovascular disease, hypertensive heart disease, diabetes mellitus, IHD and cardiomyopathy. Marked declines were observed for cardiovascular disease and diabetes mellitus among coloureds and Asians, while there was an increase among black African males. Fig. 2 also reveals population group differences in diabetes and renal diseases, which may be associated with access to medical care. Our study showed that ASDRs from NCDs declined by 0.4% per annum over the 14-year period. However, this is much lower than the recommended goal of 2% per year. [10] The SA government has recognised the need to address NCDs and has developed a strategic plan with an ambitious goal to decrease premature mortality from cardiovascular disease, cancer, respiratory conditions and diabetes combined by 25% within a decade. [11] Our study estimated that in 2010, the premature mortality from these conditions was 26% (i.e. 26% of people who were 30 years old would die before the age of 70 years from these conditions if the 2010 mortality rates were to prevail). The NCD plan formulated by the National Department of Health balances populationbased strategies alongside individual-level strategies.[11] It promotes a multistakeholder national health commission that engages other sectors, including trade and industry, agriculture, education, sports, and arts and culture. Preventing and delaying the increase of NCDs is appreciably more effective and considerably less costly than treatment of those who become sick.[12] Policies for tobacco control and salt and fat reduction are in place, but aggressive efforts are needed to ensure their implementation. The government should be commended for the bold move on taxing sugar-sweetened drinks. This is expected to cut the number of obese people by 220 000 in 3 years.[13] However, policy development on alcohol harm reduction has been slow. NCD surveillance needs to be strength ened to provide reliable and robust infor mation for planning and monitoring health policy. There is a need to improve

215

200 140

150

107

100 50 0

76 26

119

108

79 49

Black African

30 23

Coloured

46 15

7 11

21 21

White

Asian

Population group

Fig. 2. ASDRs for cardiovascular diseases, diabetes mellitus and renal disease by population group, SA 2010.[3]

the completeness of death registration and the quality of cause-of-death information. Morbidity data and quality-of-care infor mation are not generally collected, and the national cancer register needs support. Importantly, risk factor monitoring through routine population-based surveys needs to be instituted at regular intervals. Monitoring is an essential step in meeting the goals of the NCD strategic plan. Continued effort and political will must be directed towards preventing, delaying the onset of or treating and managing these conditions. Acknowledgements. We thank Statistics South Africa for providing cause-of-death data and Ms Elize de Kock for administrative support on the SA National Burden of Disease Study. In addition, critical appraisal and input provided by Eric Bateman, Kirsty Bobrow, Alan Bryer, Krisela Steyn and Naomi Levitt are much appreciated.

Beatrice Nojilana, Debbie Bradshaw, Victoria Pillay-van Wyk, William Msemburi, Nontuthuzelo Somdyala, Jané D Joubert, Pam Groenewald Burden of Disease Research Unit, South African Medical Research Council, Cape Town, South Africa Ria Laubscher Biostatistics Unit, South African Medical Research Council, Cape Town, South Africa

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Rob E Dorrington Centre for Actuarial Research, Faculty of Commerce, University of Cape Town, South Africa Corresponding author: B Nojilana (beatrice. nojilana@mrc.ac.za) 1. Alwan A, MacLean DR, Riley LM, et al. Monitoring and surveillance of chronic non-communicable diseases: Progress and capacity in high-burden countries. Lancet 2010;376(9755):18611868. DOI:10.1016/S0140-6736(10)61853-3 2. Alwan A. Global Status Report on Non-communicable Diseases 2010. Geneva: World Health Organization, 2011. 3. Nojilana B, Bradshaw D, Pillay-van Wyk V, et al. Emerging trends in non-communicable disease mortality in South Africa, 1997-2010. S Afr Med J 2016;106(5):477-484. DOI:10.7196/SAMJ.2016.v106i4.10674 4. Reddy KS, Yusuf S. Emerging epidemic of cardiovascular disease in developing countries. Circulation 1998;97(6):596-601. DOI:10.1161/01.CIR.97.6.596 5. Peer N, Steyn K, Lombard C, et al. Alarming rise in prevalence of atherogenic dyslipidaemia in the black population of Cape Town: The Cardiovascular Risk in Black South Africans (CRIBSA) study. Eur J Prev Cardiol 2014;21(12):1549-1556. DOI:10.1177/2047487313497865 6. Peer N, Bradshaw D, Laubscher R, Steyn K. Trends in adult tobacco use from two South African demographic and health surveys conducted in 1998 and 2003. S Afr Med J 2009;99(10):744-749. 7. Somdyala NIM, Parkin MD, Sithole N, et al. Trends in cancer incidence in rural Eastern Cape Province, South Africa, 19982012. Int J Cancer 2014;136(5):E470-E474. DOI:10.1002/ijc.29224 8. Omran AR. Epidemiological transition: A theory of epidemi ology of population change. Millbank Memorial Fund Q 1971;49(4):509-538. DOI:10.2307/3349375 9. Yusuf D, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases Part 1: General considerations, the epidemiologic transition, risk factors and impact of urbanisation. Circulation 2001;104:2746-2753. DOI:10.1161/hc4601.099487 10. Strong K, Mathers C, Leeder S, et al. Preventing chronic diseases: How many lives can we save? Lancet 2005;366((9496):15781582. DOI:10.1016/s0140-6736(05)67341-2 11. National Department of Health. Strategic Plan for the Prevention and Control of Non-communicable Diseases 201317. Pretoria. National Department of Health, 2013. 12. Cecchini M, Sassi F, Lauer JA, et al. Tackling of unhealthy diets, physical inactivity, and obesity: Health effects and cost-effectiveness. Lancet 2010;376(9754):1775-1784. DOI:10.1016/S0140-6736(10)61514-0 13. Manyema M, Veerman LJ, Chola L, et al. The potential impact of a 20% tax on sugar-sweetened beverages on obesity in South African adults: A mathematical model. PLoS One 2014;9(8):e105287. DOI:10.1371/journal.pone.0105287

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EDITORIAL

A complementary model for medical subspecialty training in South Africa The shortage of healthcare workers and doctors in the developing world compared with the developed world is problematic, and will continue to be so, owing to the ongoing migration of qualified professionals and the inability of the state to remedy the shortfalls.[1-2] This will seriously hamper the governmentâ&#x20AC;&#x2122;s National Health Insurance (NHI) plan and the sustainability of South Africa (SA)â&#x20AC;&#x2122;s healthcare sector. Furthermore, it is well known that the duration of medical training in SA is exceptionally long, which discourages trainees.[3-6] Medical corporates have taken a limited initiative to fund education projects in collaboration with academic institutions. These projects have been unstructured, mostly ad hoc, and poorly co-ordinated. The private corporate medical sector has expressed a desire to become involved on a much larger scale by means of more formalised structures.[4] Given this background, the primary objective of our research was to develop a business model to complement the current academic medical subspecialty training. A pilot model for training subspecialists in reproductive medicine was developed as a first attempt to address the threatening shortage of subspecialists and the long duration of training. The programme was successful at all levels, from training subspecialists/fellows in reproductive medicine, embryology laboratory scientists, and three PhD candidates in the subspecialty. With this in mind, a research proposal was developed to scientifically confirm the viability of implementing the programme on a larger scale. A two-phased research process was used to collect the data. In phase 1, data were collected from stakeholder groups. The results of this phase assisted in generating variables to include in the measuring instrument used for the survey conducted in phase 2. In this latter phase, the perceptions and expectations of subspecialists with regard to subspecialty training were obtained. The results of the demographic variables confirm the ageing profile of subspecialists, particularly in reproductive medicine, and the dire need to ensure succession. The findings show that the expectations of reproductive specialists and cardiologists with regard to the training of subspecialists are very similar, except for their views on the duration of training. The reproductive subspecialist respondents were more in agreement than the cardiology respondents that the duration of training is too long. The greatest gap between perceptions and expectations was observed in the training factor. Based on these findings, a business model for the training of reproductive subspecialists was proposed. This model requires that role-players and stakeholders effect changes to accommodate larger-scale potential public-private partnerships (PPPs). The model could also be applied to other disciplines and where the need exists to complement other subspecialist education. The model envisages that all stakeholders in the training of subspecialists need to make a paradigm shift to facilitate changes to accommodate the complementary system, which will benefit both the private and the public sectors. The role-players, from the regulators to the DepartÂ ment of Health, via the Health Professions Council of South Africa (HPCSA), will need to undergo a change in their way of thinking, i.e. they do not need to be the sole decision-makers with regard to training numbers required for subspecialisation and they need to participate in the development of PPPs by collaborating with the subspecialist societies that are the closest to their members and their needs. They should play a more active role in the future of their members in much the same way that the HPCSA plays a role in decision-making with

regard to training numbers and institutional allocation. Furthermore, the subspecialist societies play an integral role in accreditation of distant learning sites with academic institutions. Private corporate funding for subspecialty training may be channelled directly to the Colleges of Medicine of South Africa (CMSA) or an independent administrative entity. This will avoid the intermediate step where social and corporate foundations make decisions on how funding is distributed. The CMSA or an administrative entity will ensure equitable decision-making and good governance in the distribution of funding, together with its academic responsibility, as laid down in its constitution. Academic institutions, where necessary, can make the required curriculum and logistic changes to enable training at a distant site. In an extended programme, negotiated agreements will be required to accommodate the development of PPPs, as the model does not foresee any input from the national fiscus. The private sector accepts that they are the greatest beneficiaries of the state-funded medical education system, and that they have a responsibility, in principle, to contribute to and participate in PPP medical training. The model will make an ideal point of departure towards such a joint venture. The academic institutions and CMSA should maintain their historical role of overseeing medical education, and assume an administrative financial role. The advantages of such a model are that it will provide for a complementary method of financing subspecialist training. It will address the declining numbers in both the private and public sectors. It will also ensure redistribution of subspecialists to smaller centres. Moreover, the model will allow a subspecialist to train in the subspecialty of their choice, in an area of their traditional practice, while earning a suitable income. The model has an innovative long-term financially sustainable funding initiative from a wide spectrum of corporate stakeholders and the private sector. It will allow much greater exposure to clinical practice, where currently there is disparity between the public and private sectors regarding pathology profiles and management protocols. The model will also bring tertiary professional medical education in line with the training of other professions, such as law and accounting. Lawyers and accountants are currently trained in the private sector, following completion of a basic degree, while medical training is done solely in the public sector. Academic institutions will continue to fulfil the role of educator, as they will provide, either distance, block-release or online training to subspecialists in collaboration with decentralised centres. The model also provides important guidelines on how to arrange a PPP or alternative special purpose vehicle. This model, on its own, may be an ideal model and provide an incentive for the developing NHI. The model is currently needed more than ever before, as we are now experiencing an enormous public outcry against tuition fees in tertiary educational institutions. With this model, we foresee that subspecialist education, the highest tier in medical education worldwide, can to a large extent be removed from the national medical budget and be absorbed by the private sector, which, as we know, is willing to do so. The model can also be applied to all subspecialties, and it is expected that both the public and private sectors will be able to benefit from it at the same time. The intention is to implement the model as a complementary system to the current public training system, and to thereby maintain numbers in both the public and private sectors.

May 2016, Print edition

EDITORIAL

This editorial is partly based on a PhD thesis in Business Management, Nelson Mandela Metropolitan University, Port Elizabeth, SA.[5]

J Paul F Dalmeyer, Miemie Struwig Department of Business Management, Faculty of Business and Economic Sciences, Nelson Mandela Metropolitan University, Port Elizabeth, South Africa Thinus F Kruger Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

Corresponding author: J P F Dalmeyer (paul@dalmeyer.co.za) 1. Benatar SR. Health care reform in the new South Africa. N Engl J Med 1997;35(1):81-85. DOI:10.1056/ NEJM199703203361224 2. Naicker S, Plange-Ruhle J, Tutt RC, Eastwood JB. Shortage of healthcare workers in developing countries – Africa. Ethn Dis 2009;19(1 Suppl 1):60-64. 3. Freed GL, Dunham KM, Switalski KE, Jones MD jun., McGuinness GA. Pediatric fellows: Perspectives on training and future scope of practice. Pediatrics 2009;123(Suppl 1):31-37. DOI:10.1542/peds.2008-1578I 4. Life Healthcare. Training and development – Life College of Learning. 2012. http://www.lifehealthcare. co.za (accessed 22 March 2016). 5. Dalmeyer JPF. A business model for medical subspecialty training in South Africa. PhD thesis. Port Elizabeth: Nelson Mandela Metropolitan University, 2015. 6. Van Niekerk JP. In favour of shorter medical training. S Afr Med J 2009;99(2):69.

S Afr Med J 2016;106(5):438-439. DOI:10.7196/SAMJ.2016.v106i5.10336

South African Guidelines Excellence (SAGE): Efficient, effective and unbiased clinical practice guideline teams There is increasing worldwide interest in clinical practice guide lines (CPGs). A range of different evidence-based methods for CPG activities have been established (e.g. Schünemann et al.,[1] Brouwers et al.,[2] Brouwers et al.,[3] Hillier et al.[4] and Guyatt et al.[5]), and there is common agreement in these that poorly conceived CPG team composition and management can jeopardise CPG integrity. Recognised CPG initiatives such as the Scottish Intercollegiate Guideline Network (SIGN) (http:// www.sign.ac.uk) and the National Institute of Health and Care Excellence (NICE) (https://www.nice.org.uk/guidance) therefore provide guidance on CPG team construction and management. This editorial is the third in a series produced by the South African Guidelines Excellence (SAGE) team. Project SAGE is funded by a South African Medical Research Council Flagship Grant (2014 - 2017). In our two previous editorials we discussed the critical components of a good-quality CPG[6] and the work being undertaken by Project SAGE to explore and better understand the development, implementation and use of CPGs in the South African (SA) primary care setting.[7] In this editorial we outline steps for effective, efficient and outcome-focused CPG team membership, roles and management. 1. Determine responsibilities and tasks. CPG team members may be asked to undertake a range of tasks. Efficient and effective CPG teams usually include methodologists (e.g. clinical epidemiologists, librarians, technical writers) who collate the evidence base, and experts who interpret the evidence base within local contexts. Team training requirements regarding best-practice CPG processes need to be identified and addressed prior to CPG commencement, so that standard processes are understood and undertaken by all team members. 2. Identify ‘experts’ and their ‘voices’. Weinstein[8] defined two types of experts – those who are expert because of what they know (epistemic expertise), and those who are expert because of what they do (performative expertise). Both have a place in CPG teams, and the relative merits of including one or both types should be considered early. What qualifies an individual to be nominated onto a CPG team as an expert remains unclear. Ideally, experts nominated by professional associations or organisations should be spokespeople for constituents, representing the collective rather than an individual view. The added value of an expert credibly presenting the ‘voice’ of an organisation is that this should assist with CPG endorsement and implementation.

3. I dentify a CPG team leader. Who chairs the CPG team is a critical decision, as the chair is responsible for the efficient and unbiased production of a CPG (World Health Organization (WHO)[9]). The chair may be identified by the CPG commissioning body, and he/she can be an independent appointment or determined from within the CPG team. He/she should be credible as a leader, and should have a sound understanding of CPG development, general knowledge of the CPG subject, and ideally CPG writing experience. He/she should have experience in efficient team management and resolution of conflicts. The WHO also recommends the appointment of a vice-chair.[9] 4. Determine and declare conflicts of interest (COIs). COIs arise when an individual’s private interests influence (or are perceived by others to influence) a public duty. When writing CPGs, COIs could influence which evidence is supported, which contexts are considered, or whether and how representative constituent feedback is obtained. Guidance regarding COI definitions, declara tion and management is provided by the International Committee of Medical Journal Editors (http://www.icmje.org)[10] and the American Thoracic Society Policy for Management of Financial Conflicts of Interest in the Development of ATS Clinical Practice Guidelines.[11] COIs should be determined when the CPG team is first convened and then reassessed regularly, as team members’ affiliations and activities may change over time. 5. Determine CPG team terms of reference. Terms of reference help CPG teams to clarify roles, responsibilities and workloads, including setting realistic time frames for obtaining constituent feedback. 6. Establish CPG time frames and tailored capacity develop ment. Many CPG team members work in voluntary capacities. Establishing clear time frames for activities occurring throughout the lifetime of the CPG allows team members to plan ahead. CPG team members often need to learn skills ‘on the job’, so it is important that training is provided and that team members’ activities are monitored, so that they do not ‘burn out’ through poorly managed processes.[12] 7. E stablish consensus. It is important that CPG team members agree on an equitable, respectful, efficient consensus process. There are established options for consensus that can be applied by CPG teams.[1] The CPG group may decide that it requires unanimity, or it may allow one or two dissenters whose contrary position is noted in minutes. A majority ruling may require a

May 2016, Print edition

EDITORIAL

super-majority (55 - 90%) or a simple majority (>50%). If there is divided opinion, the CPG team may accept rulings from the CPG team leader, or from an independent dispute resolution panel.

Conclusion

Writing CPGs can be time-consuming and expensive. Efforts therefore need to be underpinned by efficient, respectful and agreed processes. The integrity of CPG teams and activities should not be compromised by poor team composition or processes. Justifying CPG team membership, declaring COIs, identifying efficient ways of hearing constituent ‘voices’, defining and time-lining team tasks and roles, providing necessary training, and respecting individuals’ efforts and time should ensure that CPG team members enjoy their experiences. This will contribute to growing CPG expertise in SA and beyond. Karen Grimmer International Centre for Allied Health Evidence, City East Campus, University of South Australia, Adelaide, Australia, and Department of Physiotherapy, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa Janine Margarita Dizon Centre for Evidence-Based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa, and Center for Health Research and Movement Science, University of Santo Tomas, Manila, Philippines Quinette Louw Department of Physiotherapy and Centre for Evidence-Based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa Tamara Kredo Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa

Taryn Young Centre for Evidence-Based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa, and Cochrane South Africa, South African Medical Research Council, Cape Town Shingai Machingaidze Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa, and European and Developing Countries Clinical Trials Partnership (EDCTP), Cape Town Corresponding author: K Grimmer (karen.grimmer@unisa.edu.au) 1. Schünemann HJ, Wiercioch W, Etxeandia I, et al. Guidelines 2.0: Systematic development of a comprehensive checklist for a successful guideline enterprise. Can Med Assoc J 2014;186(3):E123-E142. DOI:10.1503/cmaj.131237 2. Brouwers MC, Kho ME, Browman GP, et al. Development of the AGREE II, part 1: Performance, usefulness and areas for improvement. Can Med Assoc J 2010a;182(10):1045-1052. DOI:10.1503/ cmaj.091714 3. Brouwers MC, Kho ME, Browman GP, et al. Development of the AGREE II, part 2: Assessment of validity of items and tools to support application. Can Med Assoc J 2010b;182(10):E472-E478. DOI:10.1503/cmaj.091716 4. Hillier S, Grimmer-Somers K, Merlin T, et al. FORM: An Australian method for grading recommen dations in evidence-based clinical guidelines. BMC Methodol 2011;11:23. DOI:10.1186/1471-228811-23 5. Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: A new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol 2011;64(4):380-382. DOI:10.1016/j. jclinepi.2010.09.011 6. Machingaidze S, Kredo T, Young T, Louw Q, Grimmer K. South African Guidelines Excellence (SAGE): Clinical practice guidelines – quality and credibility. S Afr Med J 2015;105(9):743-745. DOI:10.7196/ SAMJnew.7697 7. Kredo T, Machingaidze S, Young T, Louw Q, Grimmer K. South African Guidelines Excellence (SAGE): What’s in a name? S Afr Med J 2015;106(1):18-20. DOI:10.7196/SAMJ.2016.v106i1. 10286 8. Weinstein BD. What is an expert? Theor Med 1993;14(1):57-73. DOI:10.1007/BF00993988 9. World Health Organization. WHO Handbook for Guideline Development. Geneva: WHO, 2011. http:// apps.who.int/iris/bitstream/10665/75146/1/9789241548441_eng.pdf (accessed 11 February 2016). 10. International Committee of Medical Journal Editors. http://www.icmje.org/conflicts-of-interest/ (accessed 6 January 2016). 11. American Thoracic Society Policy for Management of Financial Conflicts of Interest in the Development of ATS Clinical Practice Guidelines as Approved by the Board of Directors, January 2015. https://www. thoracic.org/statements/document-development/resources/cpg-specific-coi-policy.pdf (accessed 29 February 2016). 12. Luban R. Keeping the Fire: From Burnout to Balance. Ruth Luban Audio & Books, 1996.

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GUEST EDITORIAL

Acute viral bronchiolitis: Dawn of a new era for the prevention of respiratory syncytial virus infection through vaccination Many cases of bronchiolitis are caused by the respiratory syncytial virus (RSV), which was first identified in 1956 as causing illness in humans. Despite ongoing efforts since the 1960s to develop an RSV vaccine, it has remained elusive. The RSV vaccine research agenda experienced a major setback after the increased susceptibility to severe RSV disease and death in children who received the first formalin-inactivated vaccine in the 1960s. Only in the mid-1980s was the search for an RSV vaccine re-ignited. Alternative approaches to developing this vaccine included attempts at attenuation of RSV, which generally resulted in vaccine candidates that were either too reactogenic or too attenuated. Furthermore, the targeted approach of using the conserved fusion protein (F-protein), although showing some promise in older persons with underlying medical conditions, was not developed into a potential candidate for young children, for whom the need is greatest. The F-protein target, however, was used to develop palivizumab, a humanised monocloncal antibody that has been shown – since the mid-1990s – to prevent RSV lower respiratory tract infection in young children with underlying risk factors. However, the widespread use of palivizumab has been impeded by the logistics to provide monthly intramuscular injections for 4 - 5 months of the year while the RSV circulates in temperate climates, and by its cost, which makes it unaffordable and not cost-effective in most countries. Also, as it is only targeted at high-risk children, it misses prevention of RSV in otherwise healthy children, who comprise 70% of all RSV hospitalisations. The prospect of more affordable and efficacious vaccines to prevent RSV illness in the majority of children has changed over the past 5 years. This includes the successful development of a re-engineered F-protein monoclonal antibody that has an extended half-life, which would allow for a single dose to provide protection against RSV illness for the duration of the RSV season (4 - 5 months). The first safety and antibody kinetics study of this monoclonal antibody was recently concluded. Moreover, a number of other RSV vaccine candidates (>20) are currently being researched in clinical trials.[1] These include the next generation of re-engineered live attenuated RSV vaccines, vector-based vaccines, F-protein-based subunit vaccines, including the use of nanoparticle technology or targeting the prefusion epitopes of the F-protein.[2,3] The strategy to optimise the protection of young infants, consi dering that the mean age for contracting RSV is usually 4 - 5 months and that these children might be too young to benefit from active vacci nation, has also recently undergone a paradigm shift. In particular, it has been accepted that pregnant women may potentially be vaccinated to protect their infants against illness during the first 3 - 4 months of life by enhancing transplacental acquisition of vac cine-induced maternal antibody. This strategy not only contributed to the control of neonatal tetanus globally, but has more recently been shown to prevent influenza and pertussis in young infants in whom the burden of severe disease is the greatest.[4,5] Accordingly, the first studies of the nanoparticle RSV F-protein vaccine candidate in pregnant women were recently completed, and a multicentre safety and efficacy trial is currently underway in pregnant women, also at multiple sites in South Africa. Furthermore, at least three other

vaccines, also targeted at the F-protein, are likely to enter into clinical trials in pregnant women during the next 5 years. Although vaccination of pregnant women is likely to benefit their young infants, this will probably need to be coupled with other vaccination strategies in children to provide protection until at least 12 - 24 months of age. Vaccination strategies specifically targeted at children are also being pursued over and above passive immunisation with a monoclonal antibody. This could include using the same vaccine candidates being evaluated in pregnant women and live attenuated vaccines, especially in older infants. Therefore, while RSV currently remains the leading cause of hospitalisation for lower respiratory tract infection globally (~30 40% of all cases), it is hoped that the next 10 years will see the face of paediatric practice change once again, if some of the current passive and active RSV vaccine candidates are licensed. The challenge for low- and middle-income countries would be to ensure that any such vaccines are affordable and timeously implemented into public immunisation programmes to reduce RSV-associated hospitalisation sequelae such as recurrent wheezing and death. S A Madhi Guest editor Vaccinology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg; South African Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Johannesburg; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, Johnnesburg; and National Institute for Communicable Diseases, Johannesburg, South Africa shabirm@nicd.ac.za

R J Green Guest editor Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Pretoria, and Steve Biko Academic Hospital, Pretoria, South Africa robin.green@up.ac.za 1. Mazur NI, Martinon-Torres F, Baraldi E, et al. Lower respiratory tract infection caused by respiratory syncytial virus: Current management and new therapeutics. Lancet Respir Med 2015;3(11):888-900. 2. Jaberolansar N, Toth I, Young PR, Skwarczynski M. Recent advances in the development of subunitbased RSV vaccines. Expert Rev Vaccines 2016;15(1):53-68. DOI:10.1586/14760584.2016.1105134 3. Morrison TG, Walsh EE. Subunit and virus-like particle vaccine approaches for respiratory syncytial virus. Curr Top Microbiol Immunol 2013;372:285-306. DOI:1007/978-3-642-38919-1_14 4. Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med 2014;371(10):918-931. DOI:10.1056/NEJMoa1401480 5. Amirthalingam G, Andrews N, Campbell H, et al. Effectiveness of maternal pertussis vaccination in England: An observational study. Lancet 2014;384(9953):1521-1528. DOI:10.1016/S01406736(14)60686-3

S Afr Med J 2016;106(5):442. DOI:10.7196/SAMJ.2016.v106i5.10735

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Acute viral bronchiolitis in South Africa: Viral aetiology and clinical epidemiology D A White,1 MB BCh, FC Paed (SA), MMed (Paed), Dip Allerg (SA), Cert Pulmonology (SA) Paed; S A Madhi,2 MB BCh, MMed (Paed), FC Paed (SA), PhD; P Jeena,3 MB ChB, FC Paed (SA), Cert Pulmonology (SA) Paed; H J Zar,4 MB BCh, FC Paed (SA), PhD; B M Morrow,5 PhD, BSc (Physio), PG Dipl (Health Research Ethics); R Masekela,3 MB BCh, MMed (Paed), Cert Pulmonology (SA) Paed, Dip Allerg (SA), FCCP, PhD; S Risenga,6 MB ChB, FC Paed (SA), Dip Allerg (SA), Cert Pulmonology (SA) Paed; R J Green,7 PhD, DSc epartment of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa D Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa 3 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of KwaZulu-Natal, Durban, South Africa 4 Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, and MRC Unit on Child and Adolescent Health, Faculty of Health Sciences, University of Cape Town, South Africa 5 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, South Africa 6 Department of Pulmonology, Faculty of Health Sciences, University of Limpopo, Polokwane, and Pietersburg Hospital, South Africa 7 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Pretoria, South Africa 1 2

Corresponding author: D A White (debbie.white@wits.ac.za)

Bronchiolitis is a viral-induced lower respiratory tract infection that occurs predominantly in children <2 years of age, particularly infants. Many viruses have been proven or attributed to cause bronchiolitis, including and most commonly the respiratory syncytial virus (RSV) and rhinovirus. RSV is responsible for more severe disease and complications (including hospitalisation) in bronchiolitis patients. Whereas bronchiolitis is exclusively due to respiratory viral infections, with little evidence of bacterial co-infection, the former could nevertheless predispose to superimposed bacterial infections. Although data support an interaction between RSV and pneumococcal superimposed infections, it should be noted that this specifically refers to children who are hospitalised with RSV-associated pneumonia, and not to children with bronchiolitis or milder outpatient RSV-associated illness. As such, empiric antibiotic treatment against pneumococcus in children with RSV-associated pneumonia is only warranted in cases of hospitalisation and when the clinical syndrome is more in keeping with pneumonia than uncomplicated bronchiolitis. In South Africa, the peak in the RSV season varies only slightly by province, with onset in February, and lasting until June. The important implication of these new seasonality findings is that where prophylaxis is possible, as in the case of RSV, it should be commenced in January of each year. S Afr Med J 2016;106(5):443-445. DOI:10.7196/SAMJ.2016.v106i5.10444

Definition

Bronchiolitis is a viral-induced lower respiratory tract infection (LRTI) that occurs predominantly in children <2 years of age, particularly infants.[1]

Causative organisms

The most frequent cause of severe bronchio litis is respiratory syncytial virus (RSV) infection, with other respiratory viruses (para-influenza virus (PIV), influenza virus, human metapneumovirus (hMPV) and measles virus) being less common or for which definitive attribution is yet to be established (e.g. rhinovirus (RV), bocavirus and coronavirus) (Table 1).

Epidemiology

Epidemiological studies on bronchiolitis often include all children presenting with physician-diagnosed LRTI, and may overesti mate the true incidence of bronchiolitis alone. In a prospective, hospital-based surveillance study of 8 723 children under-5 with physi

cian-diagnosed LRTI, from five sites in four provinces in South Africa (SA), from 2009 to 2012 (severe acute respiratory illness (SARI) programme), the overall prevalence of respiratory viruses was 78%. The viruses that were isolated included RV in 37%, RSV in 26%, adenovirus in 26%, influenza virus in 7% and hMPV in 5%.[2] In 2009 and 2010, this surveillance study evalua ted respiratory viruses by a 10-plex real-time reverse-trans

Table 1. Respiratory viruses associated with bronchiolitis Respiratory syncytial virus Rhinovirus Adenovirus Para-influenza virus (especially type 3) Influenza virus Human metapneumovirus Bocavirus Coronavirus Measles virus

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cription polymerase chain reaction (rRTPCR).[3] Respiratory viral co-infections among cases enrolled indicated 39.6% with single viral infections, while 17.4% had ≥2 viral co-infections.[3]

Many studies show RV to be associated with bronchiolitis; however, the high prevalence of RV in healthy asymptomatic children limits definitive attribution of its role in the pathogenesis of bronchiolitis. Early studies have suggested that oxygen saturation is generally not as low in children with RV- associated bronchiolitis as in those with RSV-associated bronchiolitis.[4] However, more recent studies suggest that RV may be more sinister.[5] All three types of RV have been identified in SA, although RV-A and RV-C are more common than RV-B. RV is associated with symptomatic respiratory illness; however, there is no association between RV type and disease severity.[6] RV-D has subsequently been identified.[7]

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RSV

The two major RSV subgroups are A (RSV-A) and B (RSV-B), which are further characterised into several genotypes, based on antigenic and genetic variability of the second hypervariable region of the G-protein. Several genotypes can co-circulate in a single epidemic season, and different genotypes can dominate in consecutive seasons. Over a 15-year study period in SA, RSV-A and RSV-B genotypes evolved, resulting in replacement of all genotypes over the study period.[8] Whereas genotype A virus, rather than RSV-B, has more frequently been associated with more severe disease, other studies have occasionally reported more severe disease with RSV-B than RSV-A. These differences could be related to the extent of community immunity to the specific genotype, with more severe disease observed in the presence of lower community immunity to that strain. RSV is the most common cause of moderate or severe bronchiolitis and a leading cause of LRTI among young children. RSV-associated bronchiolitis occurs most frequently in infancy, being 2 - 3 times higher than in children >5 years. Infection with RSV does not result in permanent or long-term immunity, as re-infections, albeit of lesser severity, are common and may be experienced throughout life.[9] An estimated 33.8 million new episodes of RSV-associated acute lower respiratory tract infection (ALRTI) occurred worldwide in 2005 in children under-5 (22% of episodes), with at least 3.4 (2.8 - 4.3) million episodes necessitating hospital admission. An estimated 66 000 199 000 children under-5 died from RSV-associated ALRTI in 2005, with 99% of these deaths occurring in developing countries.[10] In the SARI surveillance programme, the prevalence of RSV among 4 293 LRTI hospitalisations in under-5 children was 27%, including 863 of 1 157 (75%) <12 months of age, of whom 637 (74%) were <6 months old. Nine of 1 153 children with RSV-associated ALRTI died (case fatality proportion 1%), which was lower than the 2% (74 of 3 122) of children in whom RSV was not identified (p<0.001). Children admitted with RSV-associated ALRTI were younger than those who tested RSV negative (adjusted odds ratio (AOR) 2.8; 95% confidence interval (CI) 2.1 - 3.7 for age <6 months v. 23 - 59 months). Also, patients with RSV-associated ALRTI were more likely to present with cough (AOR 9.0; 95% CI 5.5 - 14.9) and lower-chest retractions (AOR 1.4; 95% CI 1.2 - 1.7) than children with non-RSV-associated ALRTI.[11] The incidence of RSV-associated severe ALRTI in children from developing and developed countries (5.5/1 000 v. 5.6/1 000) is equal, but the case fatality rate is higher in the former (2.1% v. 0.3 - 0.7%).[10] The case fatality rate for individual risk factors for RSV-associated disease among children with chronic lung disease is 3.5 - 23.0%, congenital heart defects (CHDs) 2 - 37%, nosocomial infection 0 - 12.2%, intensive care unit admission 1.1 - 8.8%, and prematurity 0.6 - 1.0%.[12] The risk of mortality with RSV disease increases threefold among haemodyna mically significant (complex disease with pulmonary hypertension) CHDs.[13] HIV is associated with a 2 - 3-fold greater risk of RSV disease and also with higher case fatality proportions (12% v. 2% in HIV-uninfected children).[11]

Bacterial-viral interactions

Whereas bronchiolitis is exclusively due to respiratory viral infections, with little evidence of bacterial co-infection,[14] the former could nevertheless predispose to superimposed bacterial infections.[15] These complicated cases of respiratory viral infections present with the more classic signs of pneumonia, including alveolar consolidation on chest radiographs, raised C-reactive protein (≥40 mg/dL), temperature ≥38°C, crepitations and bron chial breathing on chest auscultation. The role of bacterial co-

infections in children with a respiratory virus-associated pneumonia is frequently underemphasised owing to limited tools for diagnosing bacterial pneumonia, with blood culture sensitivity ranging from 3% to 18% for detecting pneumococcal pneumonia.[16] However, epidemiological studies have identified a strong temporal association between some respiratory viruses and invasive pneumococcal disease. Included among these are studies on the temporal association of the influenza virus and RSV epidemics and invasive pneumococcal disease.[17] Further evidence for this association was observed in an SA randomised controlled trial of an investigational 9-valent pneumo coccal conjugate vaccine (PCV), in which children vaccinated with PCV had a 32% lower risk of being hospitalised for a viral-associated pneumonia compared with placebo recipients.[18] This lower risk of respiratory virus-associated hospitalisation was evident for influenza virus, hMPV and RSV-associated pneumonia.[19] The biological rationale for the reduction in respiratory virus-associated pneumonia among the PCV-vaccinated children in this study, was attributed to vaccination having prevented the superimposed vaccine-serotype pneumococcal co-infection, which would have led to progression to more severe disease – culminating in hospitalisation among the placebo recipients. Notably, there was no reduction in hospitalisation for bronchiolitis among the PCV9 vaccinated children, corroborating that pneumococcal co-infection was unlikely to have played a role in the pathogenesis of bronchiolitis. The pathogenesis of increased susceptibility to pneumococcal infection following RSV infection in mice-model studies has been attri buted to RSV G glycoprotein-binding penicillin-binding protein 1a increasing pneumococcal virulence owing to up-regulation of viru lence genes, pneumococcal toxin and pneumolysin. This could lead to an increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures.[20,21] This again is corroborated by studies in children with alveolar pneumonia associated with RSV or RV infection, among whom higher pneumococcal bacterial load was observed in the nasopharynx than in children with RSV or RV in the absence of alveolar consolidation.[22] Observations from the SA study were recently corroborated by an ecological study in the USA, in which RSV and pneumococcal pneumonia were shown to share a distinctive spatiotemporal pattern, with RSV associated with a significant increase in the incidence of pneumococcal pneumonia in children <1 year of age (attributable percent (AP) 20.3%; 95% CI 17.4 - 25.1%) and among children aged 1 - 2 years (AP 10.1%; 95% CI 7.6 - 13.9%). Similarly, influenza was associated with an increase in pneumococcal pneumonia among children aged 1 - 2 years (AP 3.2%; 95% CI 1.7 - 4.7%). After the introduction of PCV7 into the USA immunisation programme examining physician-coded diagnosis, the authors observed a decline in RSV-coded hospitalisations for children <1 year old (AP −18.0%; 95% CI −22.6 to −13.1% for 2004/2005 - 2008/2009 v. 1997/1998 - 1999/2000).[23] Although the abovementioned data support an interaction between RSV and pneumococcal superimposed infections, these specifically refer to children who are hospitalised with RSV-associated pneu monia and not to those with bronchiolitis or milder outpatient RSV-associated illness. As such, empiric antibiotic treatment against pneumococcus with RSV-associated pneumonia is only warranted in a child who is hospitalised and whose clinical syndrome is more in keeping with pneumonia than uncomplicated bronchiolitis.

Seasonality

There are several factors responsible for an outbreak of RSV infection. These include geographical locations (latitude and altitude) and climatic factors (temperature, barometric pressure, relative humidity,

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vapour tension, hours of light, precipitation, dewpoint). In most temperate regions, such as the USA and Europe, RSV outbreaks last an average of 3 - 4 months, with a peak incidence during winter, although the exact timing of onset of the outbreak is uncertain. In tropical regions, RSV outbreaks are not distinctly related to season, but often occur during the hottest rainy season. In SA, the peak in RSV season varies slightly by province, with onset of the epidemic usually in KwaZulu-Natal in December - January, in Gauteng in February - March, and followed by the Western Cape in March.[24] In 2009 and 2010, the SARI programme reported seasonality for RSV, influenza A and B viruses, enterovirus, hMPV, and PIV type 3. RSV circulation was evident from February to June, before the influenza season, which occurred from May to September. Peak activity for hMPV was observed between July and August and for PIV type 3 between September and November. Adenovirus and RV were identified perennially without any obvious peaks, while PIV types 1 and 2 were detected sporadically throughout the 2 years.[3] The important implication of these new seasonality findings is that where prophylaxis is possible, as in the case of RSV, it should be commenced in January of each year.

RSV in HIV-infected children

RSV may be identified throughout the year in HIV-infected children because of prolonged shedding of the virus (up to 100 days post infection) compared with 5 - 7 days in HIV-uninfected children.[25] Although HIVinfected children with RSV-associated ALRTI are at increased risk of hospitalisation and death, this could be due to greater susceptibility to Pneumocystis jirovecii pneumonia and other co-infections. The increased risk of RSV-associated ALRTI hospitalisation in HIV-infected children is greatest during infancy, but remains high even in the second, third, and fourth years of life.[11]

Pathophysiology of RSV disease

The viral infection starts in the upper respiratory tract and spreads to the lower tract within a few days, resulting in inflammation of the bronchiolar epithelium and oedema of the submucosa and adventitia.[26] Plugs of sloughed, necrotic epithelium and fibrin and excessive mucus secretion add to airway obstruction, causing partial or total obstruction to airflow.[27] A ‘ball-valve’ mechanism can result in trapping of air distal to obstructed areas, with subsequent absorption, atelectasis, and a mismatch of pulmonary ventilation and perfusion that may lead to hypoxaemia. Smooth-muscle constriction seems to have a minor role in the pathological process, which may explain the limited benefit of bronchodilators observed in clinical studies.[26] Although these mechanisms are known for RSV bronchiolitis, it is assumed that other viruses produce similar pathological conditions.

References 1. Wohl MEB. Bronchiolitis. In: Chernick V, Boat TF, Wilmot RW, Bush A, eds. Kendig’s Disorders of the Respiratory Tract in Children. Philadelphia: Saunders, 2006:423-432. DOI:10.1016/B978-0-7216-3695-5.50029-8 2. Cohen C, Walaza S, Moyes J, et al. Epidemiology of viral-associated acute lower respiratory tract infection among children <5 years of age in a high HIV prevalence setting, South Africa, 2009 - 2012. Pediatr Infect Dis J 2015;34:66-72. DOI:10.1097/INF.0000000000000478 3. Pretorius MA, Madhi SA, Cohen C, et al. Respiratory viral coinfections identified by a 10-plex real-time reverse-transcription polymerase chain reaction assay in patients hospitalized with severe acute respiratory illness – South Africa, 2009 - 2010. J Infect Dis 2012;206(S1):S159-S165. DOI:10.1093/infdis/jis538 4. Matti K, Kotaniemi-Syrjänen A, Waris M, Vainionpää R, Reijonen TM. Rhinovirus-associated wheezing in infancy: Comparison with respiratory syncytial virus bronchiolitis. Pediatr Infect Dis J 2004;23:995-999. DOI:10.1097/01.inf.0000143642.72480.53 5. Morrow BM, Feldman C, Green RJ. Acute viral bronchiolitis in South Africa: Intensive care management for severe disease. S Afr Med J 2016;106(5):446-448. DOI:10.7196/SAMJ.2016.v106i5.10436 6. Pretorius MA, Tempia S, Treurnicht FK, et al. Genetic diversity and molecular epidemiology of human rhinoviruses in South Africa. Influenza Other Respir Virus 2014;8(5):567-573. DOI:10.1111/irv.12264 7. Palmenberg AC, Spiro D, Kuzmickas R, et al. Sequencing and analyses of all known human rhinovirus genomes reveal structure and evolution. Science 2009;324(5923):55-59. DOI:10.1126/science.1165557 8. Pretorius MA, van Niekerk S, Tempia S, et al. Replacement and positive evolution of subtype A and B respiratory syncytial virus G-protein genotypes from 1997 - 2012 in South Africa. J Infect Dis 2013;208(S3):S227-S237. DOI:10.1093/infdis/jit477 9. American Academy of Pediatrics, Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and Management of Bronchiolitis. Pediatrics 2006;118(4):1774-1793. DOI:10.1542/peds.2006-2223 10. Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: A systematic review and meta-analysis. Lancet 2010;375:1545-1555. DOI:10.1016/S0140-6736(10)60206-1 11. Moyes J, Cohen C, Pretorius M, et al. Epidemiology of respiratory syncytial virus-associated acute lower respiratory tract infection hospitalizations among HIV-infected and HIV-uninfected South African children, 2010 - 2011. J Infect Dis 2013;208(S3):S217-S226. DOI:10.1093/infdis/jit479 12. Welliver RC Sr, Checchia PA, Bauman JH, Fernandes AW, Mahadevia PJ, Hall CB. Fatality rates in published reports of RSV hospitalizations among high-risk and otherwise healthy children. Curr Med Res Opin 2010;26(9):2175-2181. DOI:10.1185/03007995.2010.505126 13. Altman CA, Englund JA, Demmler G, et al. Respiratory syncytial virus in patients with congenital heart disease: A contemporary look at epidemiology and success of preoperative screening. Pediatr Cardiol 2000;21(5):433-438. DOI:10.1007/s002460010103 14. Hall CB, Powell KR, Schnabel KC, Gala CL, Pincus PH. Risk of secondary bacterial infection in infants hospitalized with respiratory syncytial viral infection. J Pediatr 1988;113(2):266-271. DOI:10.1016/S0022-3476(88)80263-4 15. Moore DP, Dagan R, Madhi SA. Respiratory viral and pneumococcal coinfection of the respiratory tract: Implications of pneumococcal vaccination. Expert Rev Respir Med 2012;6(4):451-465. DOI:10.1586/ers.12.32 16. Madhi SA, Kuwanda L, Cutland C, Klugman KP. The impact of a 9-valent pneumococcal conjugate vaccine on the public health burden of pneumonia in HIV-infected and -uninfected children. Clin Infect Dis 2005;40(10):1511-1518. DOI:10.1086/429828 17. Talbot TR, Poehling KA, Hartert TV, et al. Seasonality of invasive pneumococcal disease: Temporal relation to documented influenza and respiratory syncytial viral circulation. Am J Med 2005;118(3):285-291. DOI:10.1016/j.amjmed.2004.09.016 18. Madhi SA, Klugman KP. A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med 2004;10(8):811-813. DOI:10.1038/nm1077 19. Madhi SA, Ludewick H, Kuwanda L, et al. Pneumococcal coinfection with human metapneumovirus. J Infect Dis 2006;193(9):1236-1243. DOI:10.1086/503053 20. Smith CM, Sandrini S, Datta S, et al. Respiratory syncytial virus increases the virulence of Streptococcus pneumoniae by binding to penicillin binding protein 1a. A new paradigm in respiratory infection. Am J Respir Crit Care Med 2014;190(2):196-207. DOI:10.1164/rccm.201311-2110OC 21. Hament JM, Aerts PC, Fleer A, et al. Enhanced adherence of Streptococcus pneumoniae to human epithelial cells infected with respiratory syncytial virus. Pediatr Res 2004;55(6):972-978. DOI:10.1203/01.PDR.0000127431.11750.D9 22. Esposito S, Marchese A, Tozzi AE, et al. DNA bacterial load in children with bacteremic pneumococcal community-acquired pneumonia. Eur J Clin Microbiol Infect Dis 2013;32(7):877-881. DOI:10.1007/ s10096-013-1821-0 23. Weinberger DM, Klugman KP, Steiner CA, Simonsen L, Viboud C. Association between respiratory syncytial virus activity and pneumococcal disease in infants: A time series analysis of US hospitalization data. PLoS Med 2015;12(1):e1001776. DOI:10.1371/journal.pmed.1001776 24. Green RJ, Zar HJ, Jeena PM, et al. South African guideline for the diagnosis, management and prevention of acute viral bronchiolitis in children. S Afr Med J 2010;100(5):320-325. DOI:10.7196/SAMJ.4016 25. King JC, Burke AR, Clemens JD, et al. Respiratory syncytial virus illnesses in human immunodeficiency virus- and non-infected children. Pediatr Infect Dis J 1993;12:733-739. DOI:10.1097/00006454-199309000-00006 26. Zorc JJ, Hall CB. Bronchiolitis: Recent evidence on diagnosis and management. Pediatrics 2010;125:342-349. DOI:10.1542/peds.2009-2092 27. McNamara PS, Smyth RL.The pathogenesis of respiratory syncytial virus disease in childhood. Br Med Bull 2002;61(1):13-28. DOI:10.1093/bmb/61.1.13

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Acute viral bronchiolitis in South Africa: Intensive care management for severe disease B M Morrow,1 PhD, BSc (Physio), PG Dipl (Health Research Ethics); C Feldman,2 MB BCh, FCP (SA), FRCP, PhD, DSc; R J Green,3 PhD, DSc epartment of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, South Africa D Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 3 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Pretoria, South Africa 1 2

Corresponding author: B M Morrow (brenda.morrow@uct.ac.za)

It is estimated that 2 - 3% of children will be hospitalised with viral bronchiolitis during their first year of life, and a small proportion of them will have a severe course of the disease, requiring intensive care and ventilatory support. In South Africa, 20% of children admitted to a paediatric intensive care unit (PICU) had positive respiratory viral isolates (especially respiratory syncytial virus), with symptomatic respiratory disease. Rapid laboratory-based diagnosis using multiplex polymerase chain reaction is recommended to reduce overall antibiotic use in the PICU and neonatal ICU (NICU) and improve the targeted use of antibiotics (antibiotic stewardship). The mainstay of bronchiolitis management in the PICU and NICU is supportive, comprising fluid management, oxygen supplementation and/or respiratory ventilatory support, and antipyretics if needed. Non-invasive nasal continuous positive airway pressure and high-flow nasal cannula oxygen therapy are increasingly being used in children with severe bronchiolitis, and may reduce the need for intubation. Infants with bronchiolitis may have a variety of clinical presentations, which may require different ventilatory approaches. Children may present predominantly with apnoeas, air trapping and wheeze, atelectasis and parenchymal disease (in acute respiratory distress syndrome), or a combination of these. Lung-protective ventilation, using a low tidal volume pressure-limited approach, is essential to limit ventilator-induced lung injury. S Afr Med J 2016;106(5):446-448. DOI:10.7196/SAMJ.v106i5.10436

It is estimated that 2 - 3% of children will be hospitalised with viral bronchiolitis during their first year of life, and a small proportion of them will have a severe course of the disease (Table 1), requiring intensive care and ventilatory support.[1-3] Risk factors for severe disease include a history of prematurity; underlying chronic conditions such as bron chopulmonary dysplasia, neuromuscular disease, and congenital heart diseases; lack of breastfeeding; poor socioeconomic circum stances; and immunosuppression, including HIV/AIDS.[4]

Aetiology and co-infection

In South Africa (SA), 20% of children admitted to a paediatric intensive care unit (PICU) were reported to have positive respiratory viral isolates, with symptomatic respiratory disease.[5] The most common viruses occurring in the PICU context in SA are human rhinovirus, respiratory syncytial virus (RSV), adenovirus, influenza and para-influenza viruses, and human metapneumovirus (hMPV).[5,6] The importance of human rhinovirus has previously been underestimated, but is now known to be a pathogen with the potential to cause severe disease in both PICU and neonatal ICU (NICU) populations, with a prevalence of up to 40% in emergency department and hospital settings.[7,8] In a case controlled study of children after cardiac surgery, human rhinovirus infection was associated with a twelvefold

Table 1. Assessment of bronchiolitis severity in infants[4] Observations

Mild bronchiolitis

Moderate bronchiolitis

Severe bronchiolitis

Feeding

Normal

Less than usual

Not interested

Respiratory rate, breaths/min

<2 mo, >60 >2 mo, >50

>60

>70

Chest wall recessions

Mild

Moderate

Severe

Nasal flare or grunting

Absent

Present

Oxygen saturation, %

>92

88 - 92

<88

General behaviour

Normal

Irritable

Lethargic

increase in the probability of extubation failure, a threefold increase in duration of PICU stay, and a twofold increase in length of hospital stay.[9] It has been suggested that when human rhinovirus is detected by polymerase chain reaction (PCR) in symptomatic individuals, it is likely to represent true infection.[10] hMPV has been reported in up to 19% of hospitalised SA children with respiratory tract infections (RTIs).[11,12] hMPV is associated with significant morbidity, with similar presentation and outcome to RSV infection.[12] In the PICU, co-infection with bacteria and other potential pathogens (e.g. fungi, Pneumocystis jirovecii) is common.[5] Recently, nosocomial acquisition of viral RTI has been highlighted as a potentially serious problem, particularly in the context of limited cohorting and isolation facilities in SA and other develop-

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ing countries.[5,6,13,14] The importance of infection control measures, including hand washing, surface cleaning, isolation, and cohorting must be emphasised to prevent nosocomial spread of respiratory viruses.[15] Rapid laboratory-based diagnosis using multiplex PCR is recommended to reduce overall antibiotic use in the PICU and NICU and to improve the targeted use of antibiotics (antibiotic stewardship), as well as early identification of potential outbreaks to ensure containment and limit nosocomial transmission.[16,17]

Management of bronchiolitis in the PICU and NICU

The mainstay of bronchiolitis management in the PICU and NICU is supportive, compris-

CME

ing fluid management, oxygen supplementation and/or respiratory ventilatory support, and antipyretics if needed.[17,18]

Ventilatory support

Mechanical ventilation for bronchiolitis was first described in the 1960s, when it markedly decreased mortality associated with respiratory failure.[19] However, numerous complications of intubation and mechanical ventilation are now described, including ventilator-induced lung injury, ventilator-associated pneumonia, and tracheal stenosis.[20] In a prospective observational multicentre study,[21] endotracheal intubation and mechanical ventilation were shown to cause a marked increase in pulmonary inflammation in infants with severe RSV bronchiolitis. The avoidance of intubation and invasive mechanical ventilation as far as possible is therefore optimal in terms of lung protection, but they may be necessary in severe disease. Non-invasive nasal continuous positive airway pressure (nCPAP) and high-flow nasal cannula (HFNC) oxygen therapy are increasingly being used in children with severe bronchiolitis, and may reduce the need for intubation.[22–24] Furthermore, these technologies may provide the only form of ventilatory support in areas where children with severe bronchiolitis cannot access mechanical ventilation.[23] nCPAP may reduce the work of breathing by preventing dynamic airway collapse, thereby potentially reducing air trapping and improving gaseous exchange, although there may also be a risk of overinflation.[25] HFNC has been shown to increase end-expiratory lung volumes and reduce respiratory rate in infants with bronchiolitis, and may be better tolerated than nCPAP.[26,27] However, systematic reviews have not yielded conclusive results as to whether either technique reduces intubation rates, largely due to a lack of prospective randomised controlled trials.[22,28] Even though there have been varying reports, there has been no consensus with regard to appropriate invasive mechanical ventilation strategies for infants with severe bronchiolitis. Pressure control or pressureregulated volume-controlled ventilation compared with volume-controlled ventila

tion, may deliver lower tidal volumes than those programmed in high resistance situations, leading to hypoventilation;[29] therefore, volume-controlled modes should be considered in children with bronchiolitis. Lung-protective ventilation, using a low tidal volume pressure-limited approach, is essential to limit ventilator-induced lung injury.[30] In an animal model of RSV RTI, low tidal volume mechanical ventilation caused less ventilation-induced cellular and cytokine influx into the bronchoalveolar space.[31] The key features of lung-protective ventilation are: • controlled oxygen exposure • permissive hypercapnia • low tidal volumes (4 - 6 mL/kg) • adequate (but not excessive) positive endexpiratory pressure • maintaining peak inspiratory pressures of <30 cmH2O. Infants with bronchiolitis may have a variety of clinical presentations, which may

require different ventilatory approaches (Fig. 1).[25,29,32] Children may predominantly present with apnoeas, air trapping and wheeze, atelectasis and parenchymal disease (in acute respiratory distress syndrome), or a combination of these.[25]

Other therapies

Recombinant human deoxyribonuclease (rhDNAse (Pulmozyme))[33] and glucocorticoids[34] are not recommended in the management of infants and children with bronchiolitis. Recommendations for the use of exogenous surfactant and heliox therapy are presented in Table 2.

Conclusion

Most cases of bronchiolitis in young infants and children are mild enough to manage conservatively at home or in general hospital wards. In exceptional cases, acute viral bronchiolitis may be so severe that it warrants admission of patients to the PICU for respiratory support and medical care.

Primary presentation

Atelectasis and parenchymal disease

Apnoeas

Use lung-protective ventilation (as mentioned above) to prevent lung injury

Manage as ARDS using lung-protective ventilation (as mentioned above) Consider high-frequency oscillatory ventilation if indicated

Air trapping/ hyperinflation

Manage as for asthma Perhaps some advantage of volume-targeted ventilation strategies with constant flow Minimise minute ventilation Increase expiratory time with adequate inspiration (I:E ratio >1:2) Slow respiratory rate to avoid air trapping Accept lower pH Allow permissive hypercapnia Watch intrinsic PEEP

Fig. 1. Invasive ventilation strategies for different presentations of severe bronchiolitis. (ARDS = acute respiratory distress syndrome; PEEP = positive end-expiratory pressure; I:E = inspiration:expiration.)

Table 2. Additional therapy in severe bronchiolitis Therapy

Effect

Practice recommendation

Exogenous surfactant

Reduces PICU length of stay Favourable effects on oxygenation and CO2 elimination

Exogenous surfactant may be useful in selected patients Larger trials needed before surfactant can be recommended as standard treatment

Heliox[35]

If delivered effectively (only with tightly fitted facemask or CPAP), heliox therapy significantly reduced length of hospital treatment at different points of care (wards, PICU) Nasal cannula heliox therapy is ineffective RSV-positive infants responded better to heliox therapy

Heliox therapy could be considered for hospitalised infants with bronchiolitis, hypoxaemia and/or respiratory distress If heliox therapy needs to be rationalised, it could be targeted to those who are RSV positive Heliox therapy should only be delivered via a tight-fitting non-rebreathing facemask or CPAP

[34]

May 2016, Print edition

CME

References 1. Deshpande SA, Northern V. The clinical and health economic burden of respiratory syncytial virus disease among children under 2 years of age in a defined geographical area. Arch Dis Child 2003;88(12):1065-1069. DOI:10.1136/adc.88.12.1065 2. Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009;360(6):588-598. DOI:10.1056/NEJMoa0804877 3. Hall CB, Weinberg GA, Blumkin AK, et al. Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age. Pediatrics 2013;132(2):e341-e348. DOI:10.1542/ peds.2013-0303 4. Oymar K, Skjerven HO, Mikalsen IB. Acute bronchiolitis in infants, a review. Scand J Trauma Resusc Emerg Med 2014;22:23. DOI:10.7241-22-23 5. Ghani AS, Morrow BM, Hardie DR, Argent AC. An investigation into the prevalence and outcome of patients admitted to a pediatric intensive care unit with viral respiratory tract infections in Cape Town, South Africa. Pediatr Crit Care Med 2012;13(5):e275-e281. DOI:10.1097/PCC.0b013e3182417848 6. Lonngren C, Morrow BM, Haynes S, Yusri T, Vyas H, Argent AC. North-South divide: Distribution and outcome of respiratory viral infections in paediatric intensive care units in Cape Town (South Africa) and Nottingham (United Kingdom). J Paediatr Child Health 2014;50(3):208-215. DOI:10.1111/jpc.12458 7. Hayden FG. Rhinovirus and the lower respiratory tract. Rev Med Virol 2004;14(1):17-31. DOI:10.1002/rmv.406 8. Louie JK, Roy-Burman A, Guardia-Labar L, et al. Rhinovirus associated with severe lower respiratory tract infections in children. Pediatr Infect Dis J 2009;28(4):337-339. DOI:10.1097/ INF.0b013e31818ffc1b 9. Delgado-Corcoran C, Witte MK, Ampofo K, Castillo R, Bodily S, Bratton SL. The impact of human rhinovirus infection in pediatric patients undergoing heart surgery. Pediatr Cardiol 2014;35(8):13871394. DOI:10.1007/s00246-014-0941-3 10. Jartti T, Korppi M. Rhinovirus-induced bronchiolitis and asthma development. Pediatr Allergy Immunol 2011;22(4):350-355. DOI:10.1111/j.1399-3038.2011.01170.x 11. Madhi SA, Ludewick H, Abed Y, Klugman KP, Boivin G. Human metapneumovirus-associated lower respiratory tract infections among hospitalized human immunodeficiency virus type 1 (HIV-1)-infected and HIV-1-uninfected African infants. Clin Infect Dis 2003;37(12):1705-1710. DOI:10.1086/37977112. 12. Morrow BM, Hatherill M, Smuts HE, Yeats J, Pitcher R, Argent AC. Clinical course of hospitalised children infected with human metapneumovirus and respiratory syncytial virus. J Paediatr Child Health 2006;42(4):174-178. DOI:10.1111/j.1440-1754.2006.00825.x 13. Hatherill M, Levin M, Lawrenson J, Hsiao NY, Reynolds L, Argent A. Evolution of an adenovirus outbreak in a multidisciplinary children’s hospital. J Paediatr Child Health 2004;40(8):449-454. DOI:10.1111/j.1440-1754.2004.00426.x 14. Madhi SA, Ismail K, O’Reilly C, Cutland C. Importance of nosocomial respiratory syncytial virus infections in an African setting. Trop Med Int Health 2004;9(4):491-498. DOI:10.1111/j.1365-3156.2004.01221.x 15. Aitken C, Jeffries DJ. Nosocomial spread of viral disease. Clin Microbiol Rev 2001;14(3):528-546. DOI:10.1128/CMR.14.3.528-546.2001 16. Vaideeswar P, Bavdekar SB, Biswas P, Sarangarajan R, Bhosale A. Viral ventilator-associated pneumonia: Uncovering tip of the iceberg. Indian J Pathol Microbiol 2011;54(2):339-343. DOI:10.4103/0377-4929.81633

17. Pavia AT. Viral infections of the lower respiratory tract: Old viruses, new viruses, and the role of diagnosis. Clin Infect Dis 2011;52(Suppl 4):S284-S289. DOI:10.1093/cid/cir043 18. Nagakumar P, Doull I. Current therapy for bronchiolitis. Arch Dis Child 2012;97(9):827-830. DOI:10.1136/archdischild-2011-301579 19. Downes JJ, Wood DW, Striker TW, Haddad C. Acute respiratory failure in infants with bronchiolitis. Anesthesiology 1968;29(3):426-434. DOI:10.1097/00000542-196805000-00008 20. Principi T, Fraser DD, Morrison GC, et al. Complications of mechanical ventilation in the pediatric population. Pediatr Pulmonol 2010;46(5):452-457. DOI:10.1002/ppul.21389 21. Hennus MP, van Vught AJ, Brabander M, Brus F, Jansen NJ, Bont LJ. Mechanical ventilation drives inflammation in severe viral bronchiolitis. PLoS One 2013;8(12):e83035. DOI:10.1371/journal.pone.0083035 22. Donlan M, Fontela PS, Puligandla PS. Use of continuous positive airway pressure (CPAP) in acute viral bronchiolitis: A systematic review. Pediatr Pulmonol 2011;46(8):736-746. DOI:10.1002/ppul.21483 23. Argent AC, Biban P. What’s new on NIV in the PICU: Does everyone in respiratory failure require endotracheal intubation? Intensive Care Med 2014;40(6):880-884. DOI:10.1007/s00134-014-3274-z 24. Lazner MR, Basu AP, Klonin H. Non-invasive ventilation for severe bronchiolitis: Analysis and evidence. Pediatr Pulmonol 2012;47(9):909-916. DOI:10.1002/ppul.22513 25. Greenough A. Role of ventilation in RSV disease: CPAP, ventilation, HFO, ECMO. Paediatr Respir Rev 2009;10(Suppl 1):26-28. DOI:10.1016/S1526-0542(09)70012-0 26. Hough JL, Pham TM, Schibler A. Physiologic effect of high-flow nasal cannula in infants with bronchiolitis. Pediatr Crit Care Med 2014;15(5):e214-e219. DOI:10.1097/PCC.0000000000000112 27. Abboud PA, Roth PJ, Skiles CL, Stolfi A, Rowin ME. Predictors of failure in infants with viral bronchiolitis treated with high-flow, high-humidity nasal cannula therapy. Pediatr Crit Care Med 2012;13(6):e343-e349. DOI:10.1097/PCC.0b013e31825b546f 28. Beggs S, Wong ZH, Kaul S, Ogden KJ, Walters JA. High-flow nasal cannula therapy for infants with bronchiolitis. Cochrane Database Syst Rev 2014;1:CD009609. DOI:10.1002/14651858.cd009609.pub2 29. Medina A, Modesto-Alapont V, Lobete C, et al. Is pressure-regulated volume control mode appropriate for severely obstructed patients? J Crit Care 2014;29(6):1041-1045. DOI:10.1016/j.jcrc.2014.07.006 30. Turner DA, Arnold JH. Insights in pediatric ventilation: Timing of intubation, ventilatory strategies, and weaning. Curr Opin Crit Care 2007;13(1):57-63. DOI:10.1097/MCC.0b013e32801297f9 31. Hennus MP, Bont LJ, Jansen NJ, van Vught AJ. Tidal volume drives inflammation during mechanical ventilation for viral respiratory infection. Pediatr Crit Care Med 2014;15(1):e27-e31. DOI:10.1097/01. pcc.0000436197.07713.30 32. Rose L. Clinical application of ventilator modes: Ventilatory strategies for lung protection. Aust Crit Care 2010;23(2):71-80. DOI:10.1016/j.aucc.2010.03.003 33. Enriquez A, Chu IW, Mellis C, Lin WY. Nebulised deoxyribonuclease for viral bronchiolitis in children younger than 24 months. Cochrane Database Syst Rev 2012;11:CD008395. DOI:10.1002/14651858.cd008395.pub2 34. Jat KR, Chawla D. Surfactant therapy for bronchiolitis in critically ill infants. Cochrane Database Syst Rev 2012;9:CD009194. DOI:10.1002/14651858.cd009194.pub2 35. Chowdhury MM, McKenzie SA, Pearson CC, et al. Heliox therapy in bronchiolitis: Phase III multicenter double-blind randomized controlled trial. Pediatrics 2013;131(4):661-669. DOI:10.1542/ peds.2012-1317

Doctors Without Borders (MSF) cordially invites SAMJ readers to attend

MSF Scientific Day Southern Africa 2016 UNIVERSITY OF WITWATERSRAND MEDICAL CAMPUS, JOHANNESBURG 9 JUNE 2016 | 9.00 – 16.30 MSF Scientific Days present peer-reviewed research from MSF’s medical humanitarian operations around the world. Through this we aim to connect audiences - across countries, organisations, and disciplines - to enable critical analysis and debate on medical research and innovation around issues of access to health care. Linked events will be held in London (20 & 21 May) and New Delhi (28 May) Lunch will be provided Attendance is free Posters & exhibits will be on display E: sciday@joburg.msf.org T: +27 11 403 4440 Full agenda & registration: www.msf.org.za/msf-scientific-day

‘A M E D I CA L C O N F E R E N C E W I T H O U T B O R D E R S ’

IN PRACTICE

CLINICAL ALERT

Emergence of plasmid-mediated colistin resistance (MCR-1) among Escherichia coli isolated from South African patients J Coetzee, C Corcoran, E Prentice, M Moodley, M Mendelson, L Poirel, P Nordmann, A J Brink Jennifer Coetzee, Craig Corcoran and Elizabeth Prentice are all specialists in the Departments of Clinical Microbiology and Molecular Sciences at the Ampath Reference Laboratory, Centurion, Pretoria, South Africa. Mischka Moodley is a clinical microbiologist at the Ampath National Laboratory Services, Cape Town, South Africa. Marc Mendelson is an infectious diseases specialist and Head of Infectious Diseases and HIV Medicine at the Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa. Laurent Poirel and Patricia Nordmann are microbiologists in the Emerging Antibiotic Resistance Unit, Department of Medical and Molecular Microbiology, Department of Medicine, Faculty of Science, University of Fribourg, Switzerland. Adrian Brink is a clinical microbiologist at Ampath National Laboratory Services, Milpark Hospital, Johannesburg. Corresponding author: J Coetzee (coetzeej@ampath.co.za)

The polymyxin antibiotic colistin is an antibiotic of last resort for the treatment of extensively drug-resistant Gram-negative bacteria, including carbapenemase-producing Enterobacteriaceae. The State of the World’s Antibiotics report in 2015 highlighted South Africa (SA)’s increasing incidence of these ‘superbugs’ (3.2% of Klebsiella pneumoniae reported from SA were carbapenemase producers), and in doing so, underscored SA’s increasing reliance on colistin as a last line of defence. Colistin resistance effectively renders such increasingly common infections untreatable. S Afr Med J 2016;106(5):449-450. DOI:10.7196/SAMJ.2016.v106i5.10710

Current global concerns

In the 2015 State of the World’s Antibiotics[1] report, an increasing incidence of extensively drug-resistant Gram-negative bacteria was highlighted for South Africa (SA), underscoring SA’s increasing reliance on colistin as a last line of defence. Although colistin resistance was first reported in the Czech Republic in 1999 and was subsequently only reported sporadically, recent reports of increasing colistin resistance among clinical isolates, including from SA, are cause for alarm.[2,3] Of particular concern is the emergence of colistin resistance among commonly encountered Enterobacteriaceae such as Klebsiella pneumoniae. Up to now, the mechanism of colistin resistance in SA isolates was due to changes in genes associated with complex alterations in the bacterial regulatory systems.[4] These genes were not readily transferrable between species. Recent routine surveillance of antibiotic resistance in commen sal Escherichia coli from food animals in China documented a major increase of colistin resistance due to a highly mobile, transferrable, plasmid-mediated colistin-resistance gene designated mcr-1.[5] They observed mcr-1 in E. coli isolates collected from 15% (78/523) of raw retail meat samples (chicken and pork) and 21% (166/804) of animals (pigs) during 2011 - 2014. Of note, 1% (16/1 322) of clinical isolates from infected, hospitalised Chinese patients harboured mcr-1. The authors demonstrated transfer of mcr-1 between E. coli strains, including strains with known epi demic potential, such as ST131. Furthermore, the plasmid could be passed to K. pneumoniae and even Pseudomonas aeruginosa strains. Globally, the dissemination of mcr-1 among E. coli strains from feed animals and asymptomatic humans has now been reported from at least 17 countries. Recently, Dutch travellers to Asia (China, Thailand, Vietnam, Cambodia and Laos), North Africa

(Tunisia) and South America (Peru, Bolivia and Colombia) were reported, after their travels, to have gastrointestinal colonisation with mcr-1-containing E. coli.[6] mcr-1 has also been detected among Salmonella spp. collected in 2012 - 2013 from the French agricultural food sector and has been confirmed in Salmonella enterica serotype typhimurium cultured from food samples in Portugal. In addition, the mcr-1 gene has been identified in clinical isolates of K. pneumoniae and in association with carbapenemase genes.[7]

Current situation in SA

A countrywide surveillance programme of poultry operations revealed that colistin resistance in E. coli strains increased substantially in 2015, predominantly in the second half of the year. [8] It was surmised that this sudden increase was likely due to the selection of mcr-1-containing strains where colistin was being used. Subsequent analysis detected mcr-1 in 19/24 (79%) colistin-resistant cultures from the last quarter of 2015. Of critical importance, mcr-1 has now been detected in clinical isolates of colistin-resistant E. coli from hospitalised (n=3) and outpatient-based (n=6) patients in SA. This has been confirmed by a specialised antibiotic resistance unit in Switzerland that performed confirmatory molecular studies including plasmid characterisation (submitted for publication). As depicted in Table 1, mcr-1-positive, colistin-resistant E. coli was cultured from patients in two SA provinces. Except for one patient with an abscess, all the community-acquired cases presented to primary care with urinary tract infections. None was previously exposed to colistin. mcr-1 leads to raised colistin minimum inhibitory concentrations of 4 - 8 mg/L. Four of the isolates coproduced an extended-spectrum β-lactamase (data not shown).

May 2016, Print edition

IN PRACTICE

Table 1. Demographics of clinical isolates of mcr-1-containing E. coli Age (years), sex

Source

Admission date

Culture date

Colistin MIC (mg/L)

Clinical diagnosis

Prior colistin

City

Additional comments

54, M

Blood

23 March 2014

Stem cell transplant

Pretoria

Prior carbapenem and fluoroquinolone treatment

60, F

Wound (bedsore)

9 February 2015 (ICU)

12 March 2015

AIDS, TB, P. jirovecii pneumonia

Johannesburg

On antiretrovirals, TB and P. jirovecii treatment

73, F

Urine

17 November 2015 (ward)

21 November 2015

UTI

Johannesburg

Admitted for hip replacement

48, F

Pus

Outpatient

23 March 2014

Perianal abscess

Johannesburg

No prior antibiotics

60, F

Urine

Outpatient

7 October 2014

UTI

Johannesburg

No prior antibiotics

63, F

Urine

Outpatient

11 May 2015

UTI

Johannesburg

Chronic UTIs. Previously treated with nitrofurantoin and fosfomycin

68, F

Urine

28 May 2015

UTI

Johannesburg

Admitted for hip replacement, diabetic

36, F

Urine

Outpatient

29 May 2015

UTI

Pretoria

Previous hospitaliÂsation (>6 months) for renal transplant

19, F

Urine

Outpatient

24 January 2016

UTI

Cape Town

No prior antibiotics

M = male; F = female; NR = not recorded; PCR = polymerase chain reaction; ICU = intensive care unit; MIC = minimum inhibitory concentration; TB = tuberculosis; UTIs = urinary tract infections. *Outpatient managed by primary care physician.

Implications for public health

The national and global significance of the sudden spread of MCR-1 and the attendant loss of colistin has profound public health implications, and confirms the continuum between colistin use in feed animals and colistin resistance in slaughtered animals, food for human consumption, colonised humans and infected patients. We join the international community in calling for tighter control of colistin use in animal health, including a ban on use for animal growth promotion and the need for an urgent review of its use in metaphylaxis in feed animals and directed therapy in companion animals. We also call for increased restriction of colistin use in patients. In this regard, redefined considerations for empirical and directed use of colistin are urgently warranted. Strict antibiotic stewardship is essential, including a mandatory loading dose of 12 million units, and use only in combination with at least one other agent.

1. The Center for Disease Dynamics, Economics and Policy. The State of the Worldâ&#x20AC;&#x2122;s Antibiotics, 2015. Washington DC: The Centre for Disease Dynamics, Economics and Policy, 2015. http:// cddep.org/publications/state_worlds_antibiotics_2015#sthash.S3a3ME0o.dpbs (accessed 19 February 2016). 2. Brink AJ, Coetzee J, Corcoran C, et al. Emergence of OXA-48 and OXA-181 carbapenemases among Enterobacteriaceae in South Africa and evidence of in vivo selection of colistin resistance as a consequence of selective decontamination of the gastrointestinal tract. J Clin Micro 2013;51(1):369372. DOI:10.1128/JCM.02234-12 3. Mendelson M, Matsoso MB. A global call for action to combat antimicrobial resistance: Can we get it right this time? S Afr Med J 2014;104(7):478-479. DOI:10.7196/SAMJ.8534 4. Jayol A, Nordmann P, Brink AJ, et al. Heteroresistance to colistin in Klebsiella pneumoniae associated with alterations in the PhoPQ regulatory system. Antimicrob Agents Chemother 2015;59(5):27802784. DOI:10.1128/AAC.05055-14 5. Liu Y-Y, Wang T, Walsh TR, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study. Lancet Infect Dis 2016;16(2):161-168. DOI:10.1016/S1473-3099(15)00424-7 6. Arcilla MS, van Hattem JM, Matamoros S, et al. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis 2016;16(2):147-149. DOI:10.1016/S1473-3099(15)00541-1 7. Poirel L, Kieffer N, Liassine N, et al. Plasmid-mediated carbapenem and colistin resistance in a clinical isolate of Escherichia coli. Lancet Infect Dis 2016, in press. 8. Gerber D. Colistin resistance in E. coli in broiler operations in South Africa. In: V-Tech Report, 11 January 2016. Johannesburg: V-Tech Pty (Ltd), 2016.

Accepted 24 February 2016.

May 2016, Print edition

IN PRACTICE

MEDICINE AND THE LAW

HIV testing of children is not simple for health providers and researchers: Legal and policy frameworks guidance in South Africa H E van Rooyen, A E Strode, C M Slack Heidi van Rooyen, PhD, is an Executive Director in the Human and Social Development Programme at the Human Sciences Research Council, Durban, South Africa. A social scientist with a PhD in psychology, she has worked in the HIV field for the past 24 years in various capacities from counselling, training, clinical and academic supervision, mentoring and community-based research to policy development. Ann Strode, PhD, is a lawyer and Catherine Slack, PhD, a clinical psychologist. They have worked with the HIV/AIDS Vaccines Ethics Group (HAVEG) in the School of Applied Health Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa, since 2000 to explore and strengthen the ethical-legal framework for the conduct of HIV vaccine trials. Both have a special interest in the participation of children and adolescents in research. Corresponding author: H van Rooyen (hvanrooyen@hsrc.ac.za)

Antiretroviral treatment coverage for children and adolescents is significantly lower than that for adults. A first step in improving this situation is ensuring increased access to HIV counselling and testing services. Current legal and policy frameworks outline four norms that should inform HIV testing of children in South Africa: limiting HIV testing to defined circumstances, and ensuring that consent is obtained, counselling is provided and confidentiality is maintained. Implementing these norms is not simple, and we discuss the challenges and opportunities they present for children, their families, health providers and researchers working in this area. Better alignment between evolving public health approaches and the HIV counselling and testing legal/policy frameworks (and the internal coherence of domestic frameworks) would better serve children, their parents and those who work with them. S Afr Med J 2016;106(5):451-453. DOI:10.7196/SAMJ.2016.v106i5.10484

Less than 30% of HIV-infected children are currently accessing antiretroviral therapy (ART) in South Africa (SA), with ART coverage for children and adolescents significantly lower than for adults.[1] Ensuring better ART coverage requires improving access to and providing better HIV counselling and testing (HCT) services for children. This could lead to earlier diagnosis of HIV-positive children, more effective care, and reduced mortality.[2,3] HIV testing of children is no simple matter, raising complexities for parents, caregivers and children and for the health professionals and researchers who work with them. We outline the four legal norms governing HCT of children in SA, and discuss the challenges and opportunities these present for children, their families, and practitioners and researchers working in this area.

The four norms

HIV testing is regulated through four key norms in the Children’s Act 38 of 2005.[4] Additional direction is provided in the National HIV Counselling and Testing Policy Guidelines[5] and the 2012 Implementation Guidelines, which provide legal, ethical and counselling guidance for testing children and adolescents.[6,7] The four norms that pertain to HIV testing of children are: (i) limiting HIV testing to defined circumstances; (ii) ensuring that consent is obtained; (iii) ensuring that counselling is provided; and (iv) ensuring that confidentiality is maintained.

Limiting HIV testing to defined circumstances

The Children’s Act states that children may only be tested for HIV if it is in their best interests.[4] Most HIV testing will be in the child’s best interests, as knowledge of their HIV status will facilitate access to HIV prevention services and ART. This means that for HIV testing (unlike most other health interventions, where a procedure may be undergone for any reason) it must be demonstrated that it is in the child’s best interests.[8] Determining ‘best interests’ involves the practitioner assessing

whether the testing will promote the child’s physical, moral, emotional and spiritual welfare.[9-11] Examples of when testing is in the child’s best interests include testing babies born to HIV-positive mothers and testing child survivors of sexual assault. In HIV prevention trials, it is possible that enrolled participants may falsely believe that they are assigned the experimental product or that the product will protect them, and therefore increase risky behaviours; it is also important to identify HIV infections in order to take participants ‘off-product’. In this context, testing would be in the best interests of the child if it was accompanied by risk reduction counselling tailored to their circumstances.[12] In these instances, and many others, children can benefit from HIV testing, especially where it enables them to access to HIV treatment and care. The second circumstance in which testing of children can take place is in the case of potential occupational exposure where a healthcare worker or a third party may have been exposed to HIV from contact with the child’s body fluids.[4] Testing children under this circumstance is likely to occur less frequently.

Consent

Any child aged >12 years may consent independently to an HIV test according to the Children’s Act,[4,8] which means that if such a child requests an HIV test they should be assisted to access one. Children aged <12 years may only consent independently to HIV testing if they have ‘sufficient maturity to understand the benefits, risks and social implications of such a test’.[4,8] A child must be offered the test provided they meet the age or maturity standard. A maturity assessment requires that the conductor of the test be satisfied that the child understands the benefits (e.g. assessing ART and knowledge of prevention), the risks (e.g. stress from receiving a positive diagnosis) and the social implications (e.g. possible stigma or parental disapproval) that may accompany an HIV test. The

May 2016, Print edition

IN PRACTICE

child’s circumstances at the time (i.e. their age, knowledge, experience and judgement) should also be taken into account.[6,7] If a third party may have been exposed to HIV from contact with a child’s body fluids, consent should be obtained from the child or their proxy to conduct the HIV test. If consent is refused and a healthcare worker has potentially been exposed to HIV, the test may be done without consent.[4] If a third party who is not a healthcare worker may have been exposed to HIV and the child or their caregiver refuses to give consent to the test, a court order for the non-consensual testing will have to be obtained.[4] HIV testing may be initiated by a service provider, guardian or caregiver or by the child themselves. However, even if testing is parent or provider initiated, the child aged >12 years must freely consent to the process, and the caregiver must consent if the child is aged <12 years. In the latter instance, the provincial head of the Department of Social Development can in exceptional circumstances be approached to provide consent to HIV testing of orphans and vulnerable children. [5] As children can be easily persuaded, or feel they must comply with a request from a more powerful adult, the reasons why the child wishes to know their HIV status should always be explored. In HIV prevention trials, adolescents may be invited to consent to research exploring safety, efficacy or acceptability of HIV prevention products for this age group. Such research may involve specific components such as regular HCT. In this context, HCT is one of many trial procedures and is initiated by researchers. We have argued[8,13] that adolescents aged ≥12 years should self-consent to HIV testing in the trial despite their parents or guardians having provided consent to their participation.

Counselling

The Children’s Act and the national HCT policy direct that HIV testing of children must be accompanied by proper pre- and posttest counselling by an appropriately trained person.[4,5] This training should equip providers with the communication and counselling skills to work with the different developmental stages of childhood and adolescence.[6] If the child’s parent or caregiver is aware of the testing, he or she should also be involved in counselling.[4] Counselling after testing enables the child (and parents) to be informed about the implications of the test result and referred for treatment, care and psychosocial services when needed.[5] Healthcare providers should be aware that during the counselling children may disclose matters that trigger mandatory reporting, e.g. incidents of consensual but underage sex.[13,14] Currently, there is no need to report consensual underage sex between 12 - 15-year-olds, or between those in this age group who have a partner aged 16 or 17 years, provided the gap between their ages is not >2 years.[13,14] However, if there is a larger age gap, if one partner is an adult or if the child having sex is aged <12 years, reporting is still mandatory.[13,14] Institutions providing HIV testing services to young people should ensure that staff are aware of when and how they should make such reports.

Confidentiality

The Children’s Act and HCT policy hold that children who are capable of consent can decide who should know their HIV status. The national HCT policy recommends disclosure of a child’s HIV positive status to a least one other person as being beneficial for psychosocial support and for adherence. We have argued[13] that adolescents aged ≥12 years who participate in research should be encouraged to disclose to a trusted adult within a reasonable timeframe.

Discussion

The increased availability of ART provides a compelling benefit to HIV testing of children. Despite this public health imperative, policy

and guidelines for managing children at risk of and infected with HIV have often lagged behind those for adults. The current legal and policy guidelines provide much-needed guidance to practitioners and health researchers offering HCT services to children.[15] While we hope that these norms will encourage greater testing of children, they have several constraints that may limit scale-up of testing services for children. These barriers must be addressed so that children have better access to HIV prevention and treatment services.

The complexities for children and parents

There are several reasons why offering HCT to children is complex. Firstly, testing children highlights the possibility of perinatal trans mission of HIV. Testing children often raises serious implications for the child’s mother and her own HIV status. Parents are often apprehensive about subjecting their children to HIV tests, especially when they are unsure of their own status.[16] Parents may also fear being stigmatised and discriminated against if their child is HIV-positive and his or her status becomes known. These issues should be explored during counselling and appropriate coping strategies discussed. Secondly, if the child did not consent to the test (either because they were perinatally infected or aged <12), disclosure to the child of his or her HIV status is required. Many parents and caregivers find it difficult to disclose a child’s HIV positive status to them.[16] Providers should respect parental wishes and views regarding disclosure of a child’s HIV-positive status, but involvement of the child in this discussion should be encouraged and supported with appropriate disclosure strategies as the child develops. [6,7] For all children, their extent of knowledge and understanding, emo tional responses and stage of development will generally serve as a guide to when their status should be disclosed to them.[6,7,17-19] Providers working with children and adolescents need appropriate training and support to facilitate these counselling conversations with parents, caregivers and other trusted adults, where appropriate,[13] and with children. Disclosure by adolescents to others may also be complex. The policies provide that children aged ≥12 years may consent to and access HCT independently (without parental knowledge or permission). HIV infection at this age has usually been acquired through sex[20] and these children may deny sexual activity, especially if counselled in the presence of a parent or guardian. Such children may have concerns that testing will inadvertently reveal their at-risk behaviours to parents, and about facing family or social disapproval for having engaged in underage sexual activity leading to HIV infection.[20] However, many adolescents do not have the basic knowledge and skills to protect themselves from exposure to HIV, and have insufficient access to information, HCT, condoms, and treatment and care for sexually transmitted infections.[1] All participants in HIV prevention trials, including adolescents, must be assured of access to a high standard of prevention, including these components.[12] In the adolescent age group, the extent of parental involvement in decisions to test, and disclosure of test results, therefore merit careful consideration during counselling.

Implications for healthcare providers

The current ethical and legal frameworks recommend that children can consent independently to an HIV test from the age of 12 years. This acknowledges the right of a child to participate in decisions related to their own healthcare.[8,21] However, requiring HIV testing to be in the best interests of the child means that healthcare providers need to determine the reason why the child wants to be tested for HIV.[8,21] This may over-protect children because: (i) it inappropriately limits the autonomy of older adolescents in electing to undergo HIV testing; (ii) it exceptionalises HIV testing by treating it differently to other sexual and reproductive services where this is not a requirement; and (iii) it is out of step with international best practice on HIV testing, which aims at normalising and integrating HIV testing into other health services.[2]

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Acknowledging that children have a right to participate in matters that affect them creates a high standard for all who work with children. It may also place a burden on under-resourced, overstretched and often untrained lay workers who interface with children in health, social and welfare systems. Such providers may have to assess the child’s best interests (for all children) and maturity to test (for children aged <12 years) based on limited information and within a short space of time. In HIV prevention trials, there may be fewer of these constraints.[10,13] Scale-up of HIV testing for children in accordance with these norms requires investment in training, skills building and support of providers and should address the reluctance of healthcare providers to test children and ensure adequately trained staff to counsel children. Other obstacles are the divergent approaches to the sexual and reproductive rights of children taken by the criminal law and the Children’s Act.[13,14,21,23,24] The Children’s Act provides that children aged ≥12 years can access a range of sexual and reproductive health services including contraceptives, HIV testing and treatment for sexually transmitted infections. Until recently, the Criminal Law (Sexual Offences and Related Matters) Amendment Act 32 of 2007[25] made it an offence to have consensual sex under the age of 16 years, and knowledge of this crime had to be reported ‘immediately’ to the police. This placed an obligation on all service providers, including healthcare providers and researchers, to report consensual underage sex or sexual activity to the police.[13,14,21,23] The Constitutional Court found that the criminalisation of consensual sex between adolescents violated the constitutional rights of children to privacy and bodily integrity.[14,26] Although the scope of criminalised consensual sex has been narrowed, reporting requirements remain in place.[14] The lack of a common vision of when and how children should be offered HCT also hinders implementation of testing services to children. Confusion has been created about aspects of the recent Integrated School Health Policy (ISHP).[27] The policy addresses the provision of comprehensive services for schoolgoing children and youth – including HCT for sexually active learners. However, it requires learners aged under 18 years to obtain the written consent of their parent or caregiver in order to access HCT. Furthermore, when consenting to individual services learners must be at least 14 years of age. This approach represents a disconnect between the positions taken in policy and in law. It is out of step with the Children’s Act and the national HCT policy, and represents a disconnect in internal domestic policy that will cause confusion for service providers and children. Empirical research with stakeholders that explores: (i) their awareness of this disconnect in policy; and (ii) how they are responding to the incoherence is recommended. Furthermore, obtaining written consent from parents or caregivers to HCT may be an obstacle to some children accessing such services.

Implications for researchers

The ISHP policy for testing clashes with current recommendations governing children’s participation in HIV prevention research. Generally, children aged <18 years require consent from a parent or legal guardian to participate in clinical trials, including HIV prevention trials (unless there are exceptional circumstances),[28] but they should consent independently to various health procedures such as HCT from the age of 12 years.[8,13,21] Obtaining parental consent for adolescent enrolment in HIV prevention trials requires a sound understanding of exactly what information parents will and will not have access to, and makes the consent process for both parents and children demanding but feasible.[13,21]

Conclusion

We are able to treat HIV as a chronic, long-term condition and must do more to increase access to HCT services and treatment for

children. The legal and policy frameworks governing testing in SA children provide some guidance on how to proceed, but also create several complexities for children and parents, and those who work with them in various contexts. Better alignment between evolving public health approaches and the HCT legal/policy frameworks (and the internal coherence of domestic frameworks) would better serve children, their parents and those who work with them. Acknowledgements and disclaimer. The work described here was supported by award number 1RO1 A1094586 from the National Institutes of Health (NIH) entitled CHAMPS (Choices for Adolescent Methods of Prevention in South Africa). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The views of the authors are also not necessarily the views of any committee or council with which the authors are affiliated. Many thanks to Amin Matola for assistance with the referencing and manuscript preparation. 1. UNAIDS. Report on the Global AIDS Epidemic. Geneva: UNAIDS, 2012. http://www.unaids.org/ sites/default/files/media_asset/20121120_UNAIDS_Global_Report_2012_with_annexes_en_1.pdf (accessed 17 December 2015). 2. World Health Organization. HIV and Adolescents: HIV Testing and Counselling, Treatment and Care for Adolescents Living with HIV. Policy Brief. Geneva: WHO, 2013. http://apps.who.int/iris/ bitstream/10665/94561/1/9789241506526_eng.pdf (accessed 17 December 2015). 3. Kellerman S, Essajee S. HIV testing for children in resource-limited settings: What are we waiting for? PloS Med 2010;7:285-285. DOI:10.1371/journal.pmed.1000285 4. Government of South Africa. Children’s Act: No. 38 of 2005. Pretoria: Government Printer, 2006. http://www.plusto.com/uploads/5780/docs/Childrens-Act.pdf (accessed 17 December 2015). 5. National Department of Health. National HIV Counselling and Testing (HCT) Policy Guidelines. Pretoria: NDoH, 2015. http://www.health-e.org.za/wp-content/uploads/2015/07/HCT-Guidelines-2015.pdf (accessed 17 December 2015). 6. Grant K, Lazarus R, Strode A, van Rooyen H, Vujovic M. HIV Counselling and Testing of Children: Implementation Guidelines, 2012. http://www.hsrc.ac.za/uploads/pageContent/3181/HIVcounselling andtestingofchildren-implementationguidelinesWEB.pdf (accessed 17 December 2015). 7. Grant K, Lazarus R, Strode A, van Rooyen H, Vujovic, M. HIV Testing of Children: Legal Guidelines for Implementers, 2012. http://www.hsrc.ac.za/uploads/pageContent/3181/ LegalGuidelinesforHIVTestingofChildrenWEB.pdf (accessed 17 December 2015). 8. Strode A, Slack C, Essack Z. Child consent in South African law: Implications for researchers, service providers and policy-makers. S Afr Med J 2010;100(4):247-249. 9. McCall v McCall 1994 (3) SA 201 (C). 10. Strode A, Slack C. Child research in South Africa: How do the new regulations help? S Afr Med J 2015;105(11):899-900. DOI:10.7196/SAMJ.2015.v105i11.9838 11. Stobie M, Strode AE, Slack CM. The dilemma of enrolling children in HIV vaccine research in South Africa: What is in ‘the child’s best interests’? In: Van Niekerk A, Kopelman L, eds. Ethics and AIDS in Africa. Cape Town: David Philip Publishers, 2005:190-207. 12. Essack Z. Ensuring access to HIV prevention services in South African HIV vaccine trials: Correspondence between guidelines and practices. Public Health Ethics 2014;7(2):195-206. DOI:10.1093/phe/phu010 13. Strode A, Slack C. Selected Ethical-legal Norms in Child and Adolescent HIV Prevention Research: Consent, Confidentiality and Mandatory Reporting [revised]. Pietermaritzburg: HIV AIDS Vaccines Ethics Group (HAVEG), 2014:1-8. 14. Bhamjee S, Essack Z, Strode A. Amendments to the Sexual Offences Act dealing with underage sex: Implications for doctors and researchers. S Afr Med J 2016;106(3):256-259. DOI:10.7196/SAMJ.2016.v106i3.9877 15. Editorial. Giving children a chance. Lancet 2013;381(9866):507. DOI:10.1016/S0140-6736(13)60261-5 16. Rwemisisi J, Wolff B, Coutinho A, Grosskurth H, Whitworth J. ‘What if they ask how I got it?’ Dilemmas of disclosing parental HIV status and testing children for HIV in Uganda. Health Policy Plan 2008;23(1):36-42. DOI:10.1093/heapol/czm040 17. Lesch A, Swartz L, Kagee A, et al. Paediatric HIV/AIDS disclosure: Towards a developmental and process-oriented approach. AIDS Care 2007;19(6):811-816. DOI:10.1080/09540120601129301 18. Rochat TJ, Mkwanazi N, Bland R. Maternal HIV disclosure to HIV-uninfected children in rural South Africa: A pilot study of a family-based intervention. BMC Public Health 2013;13(147):1-16. DOI:10.1186/1471-2458-13-147 19. Vaz LM, Eng E, Maman S, Tshikandu T, Behets F. Telling children they have HIV: Lessons learned from findings of a qualitative study in sub-Saharan Africa. AIDS Patient Care STDs 2010;24(4):247-256. DOI:10.1089/apc.2009.0217 20. Shisana O, Rehle T, Simbayi LC, et al. South African National HIV Prevalence Incidence Behaviour and Communication Survey 2008: A Turning Tide among Teenagers? Cape Town: HSRC Press, 2009. 21. Strode A, Richter M, Wallace M, Toohey J, Technau K. Failing the vulnerable: Three new consent norms that will undermine health research with children. South Afr J HIV Med 2014;15(2):46-49. DOI:10.4102/hivmed.v15i2.18 22. Gwandure R, Ross E, Gardner, J. Parents perceptions of HIV counselling and testing in schools: Ethical, legal and social implications. S Afr Med J 2014;104(1):40-42. DOI:10.7196/SAMJ.6645 23. Strode A, Toohey J, Slack C, Bhamjee, S. Reporting underage consensual sex after the Teddy Bear case: A different perspective. S Afr J Bioeth Law 2013;6(2):45-47. DOI:10.7196/SAJBL.289 24. Strode A, Slack C. Sex, lies and disclosures: Researchers and the reporting of under-age sex. South Afr J HIV Med 2009;10(2):8-10. 25. Government of South Africa. Criminal Law (Sexual Offences and Related Matters) Amendment Act: No. 32 of 2007. Pretoria: Government Printer, 2007. 26. Teddy Bear Clinic for Abused Children, and Resources Aimed at the Prevention of Child Abuse and Neglect (RAPCAN) v. Minister of Justice and Constitutional Development Case, 2014 (1) SACR 327 (CC). 27. National Departments of Health and Basic Education. Integrated School Health Policy. Pretoria, 2012. http://www. health-e.org.za/wp-content/uploads/2013/10/Integrated_School_Health_Policy.pdf (accessed 17 December 2015). 28. Department of Health. Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa. Pretoria: Department of Health, 2006. http://www.kznhealth.gov.za/ research/guideline2.pdf (accessed 17 December 2015).

Accepted 7 January 2016.

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Advances in stroke treatment are within reach A Taylor, D le Feuvre, V Mngomezulu, D Royston, R Harrichandparsard, C de Vries, A Winter, F Potgieter Allan Taylor and David le Feuvre are neurosurgeons working in the Division of Neurosurgery, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa. Victor Mngomezulu is a radiologist and Head of the Department of Radiology in the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Duncan Royston is a radiologist and partner at Lake, Smit Partners in Durban, South Africa. Rohen Harrichandparsard is a neurosurgeon working at Inkosi Albert Luthuli Hospital and the Division of Neurosurgery, School of Clinical Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. Coert de Vries is a radiologist and head of the Department of Radiology in the Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa. Arthur Winter and Francois Potgieter are radiologists and partners at Burger Radiologists in Pretoria, South Africa. Corresponding author: A Taylor (allan.taylor@uct.ac.za)

Five recent trials have shown that mechanical removal of clot from cerebral arteries after a stroke can achieve a functional independent outcome in up to 60% of patients. This was an absolute benefit of between 13.5% and 31% for patients who had clot removal initiated within 6 hours of symptoms over those who had best medical treatment. Coupled with this, there is a strong drive to develop stroke units internationally and in South Africa. As a starting point, more primary stroke care centres that can administer intravenous thrombolysis are needed. Comprehensive stroke centres that can offer mechanical thrombectomy are available, but more will be required as referral of patients increases. Collaboration of all role-players will ensure that we can deliver training and care at the best level for stroke patients. S Afr Med J 2016;106(5):454-455. DOI:10.7196/SAMJ.2016.v106i5.10355

Stroke is no longer regarded as an untreatable condition with inevitable long-term morbidity. The current drive to establish more stroke units in South African (SA) public and private hospitals is to be commended.[1] There is robust evidence in the medical literature to indicate that treating stroke patients in a multidisciplinary stroke unit significantly reduces death and dependency.[2] The components of care that are probably responsible for this improved outcome include good nursing care, protocol-driven care with attention to swallowing, hydration, nutrition, early detection of complications of stroke and early rehabilitation. Intravenous thrombolysis with tissue plasminogen activator (tPA) has become the standard of care in specialised stroke units for selected patients who can be treated within 4.5 hours of onset of symptoms. Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, intravenous tPA significantly improves the overall odds of a good stroke outcome when delivered within 4.5 hours of stroke onset, with earlier treatment associated with bigger proportional benefits.[3] This treatment should only be provided in stroke centres, where the staff are trained to administer thrombolysis for stroke using a clear protocol with access to early brain imaging, laboratory facilities and neurosurgical advice.

Emerging treatment – mechanical thrombectomy

Until recently, intravenous tPA has been the only reperfusion therapy proven to reduce disability after acute ischaemic stroke. Although intravenous tPA is effective at recanalising more distal thrombi, it is less successful in dissolving larger more proximal thrombi.[4] Randomised trials published in the past year have shown significant benefit of mechanical thrombectomy within 6 hours of onset over best medical treatment in patients with acute ischaemic stroke due to proximal large-vessel occlusion (terminal internal carotid, middle cerebral and anterior cerebral arteries), with an absolute benefit (modified Rankin score 0 - 2 at 90 days) for functional outcome

ranging from 13.5% to 31% for thrombectomy over best medical treatment.[5-9] The development of more effective devices has allowed reopening of vessels in up to 84.5% of patients.[10] Currently the most effective option is the use of retrievable stents, which are deployed into the thrombus and then pulled out together with the clot that is occluding the affected vessel. The results of these recently published trials for acute ischaemic stroke herald the beginning of a new era in the treatment of patients with large-vessel occlusion amenable to endovascular intervention. Mechanical thrombectomy is not without risk. Vessels can be damaged, resulting in rupture and intracranial bleeding, and clot can be fragmented and occlude more distal vessels. Fortunately these complications are infrequent when the procedure is performed by trained interventionists.[5] Guidelines and consensus documents in both Europe and the USA recommend this form of treatment in the context of comprehensive stroke centres, where patients with largevessel occlusion of the anterior circulation presenting within 6 hours after symptom onset can be considered for mechanical thrombectomy. For those arriving within 4.5 hours, intravenous thrombolysis is also recommended prior to thrombectomy, unless contraindicated. [11,12] Careful selection of patients by stroke neurologists/physicians in the setting of a stroke centre, optimising time to reperfusion by appropriately trained interventionists, and performance of the procedure in a ‘high-volume centre’ with regular audit will be critical to providing benefit to patients.

Patient selection

Re-establishing cerebral perfusion is only of benefit if brain tissue is not completely infarcted. Identifying patients who have ischaemic but still viable tissue, the penumbra, is important, as is not selecting patients with large established infarcts. Patients with large infarcts have an increased risk of reperfusion bleeding. Various computed tomography and magnetic resonance imaging techniques are currently used in conjunction with clinical findings when selecting patients.[6,9] This triage process requires expertise in image

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interpretation and clinical evaluation and must be done in organised stroke centres with stroke physicians.

Neurointerventional training

Unlike specialties and subspecialties registered with the Health Professions Council of South Africa and examined via the Colleges of Medicine, the training requirements for new disciplines such as neurointervention are not yet well defined. Training standards aligned with international norms have been adopted by the academic teaching units in this country and form the basis for peer recognition for proficiency as a neurointerventionist.[13] Such candidates are expected to undergo practical training at an established unit for 1 - 2 years, depending on prior clinical experience and exposure to diagnostic neuroradiology and clinical neurosciences. Training should include a logbook with a minimum number of supervised procedures. The South African Neurointervention Society expects its members to participate in annual peer review meetings, and adherence to evidence-based practice is strongly encouraged. Assuming that any doctor working in the endovascular field is able to do an intracranial intervention effectively and safely without the recommended training is flawed. Participation in short courses, workshops and industrydriven programmes that are typically focused on use of a particular device, together with attendance at live case demonstrations, does not replace the requirement for supervised structured teaching. Stroke is a far more common problem than other neurovascular conditions such as cerebral aneurysm, and the need to train doctors only to do stroke thrombectomy rather than all neurointervention procedures, in order to provide sufficient cover, is currently being reviewed by international societies. It is likely, however, that training of stroke interventionists will need to take place in established neurointervention centres.

Mechanical thrombectomy for stroke in SA

The new era of endovascular therapy for large-vessel ischaemic stroke is likely to present many challenges in SA. For the trial results to be replicated and patients with acute stroke to reap the benefits of endovascular management, it is important that

mechanical thrombectomy starts on a firm foundation. This includes identification and support of comprehensive stroke units with appropriate referral pathways of selected patients from primary stroke centres. One of the distinguishing features of a comprehensive stroke centre is the availability of a qualified neurointerventionist with protocols for thrombectomy. In the private sector, primary stroke units are rapidly being established in response to the advantage offered by new treatments. This is a positive development that should result in better care and improved patient access and includes the effective use of intravenous thrombolytics. However, for the additional benefit of neurointerventional procedures to be realised, we need to ensure that patients have access to comprehensive stroke centres, and that there are sufficient trained stroke interventionists to cover these services. This is certainly possible with the collaboration of all role-players and if established guidelines are followed. 1. Mystroke. http://www.mystroke.co.za (accessed 2 September 2015). 2. Stroke Unit Trialists’ Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev 2013, Issue 9. Art. No.: CD000197. DOI:10.1002/14651858.CD000197.pub3 3. Enberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: A meta-analysis of individual patient data from randomized trials. Lancet 2014;384(9958):1929-1935. DOI:10.1016/S0140-6736(14)60584-5 4. Bhatia R, Hill MD, Shobha N, et al. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke. Stroke 2010;41:2254-2258. DOI:10.1161/ STROKEAHA.110.592535 5. Berkhemer OA, Fransen PSS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372(1):11-20. DOI:10.1056/NEJMoa1411587 6. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusionimaging selection. N Engl J Med 2015;372(11):1009-1018. DOI:10.1056/NEJMoa1414792 7. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372(11):1019-1030. DOI:10.1056/NEJMoa1414905 8. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs t-PA alone in stroke. N Engl J Med 2015;372(24):2285-2295. DOI:10.1056/NEJMoa1415061 9. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptoms onset in ischemic stroke. N Engl J Med 2015;372(24):2296-306. DOI:10.1056/NEJMoa1503780 10. Grech R, Mizzi A, Pullicino R, et al. Functional outcomes and recanalization rates of stent retrievers in acute ischaemic stroke: A systematic review and meta-analysis. Neuroradiol J 2015;28(2):152-171. DOI:10.1177/1971400915576678 11. Powers WJ, Derdeyn CP, Biller J, et al. 2015 AHA/ASA focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015;46(10):3020-3035. DOI:10.1161/STR.0000000000000074 12. Consensus statement on mechanical thrombectomy in acute ischemic stroke – ESO-Karolinska Stroke Update 2014 in collaboration with ESMINT and ESNR. http://2014.strokeupdate.org/consensusstatement-mechanical-thrombectomy-acute-ischemic-stroke (accessed 18 August 2015). 13. Guidelines for training in interventional neuroradiology in South Africa. http://www.sanis.co.za/ Resources/Interventional%20neuroradiology%20training%20doc%20draft%203.pdf (accessed 13 November 2015).

Accepted 2 December 2015.

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Introducing a multifaceted approach to the management of diabetes mellitus in resource-limited settings S Pillay, C Aldous Somasundram Pillay is a specialist physician working at Edendale Hospital, Pietermaritzburg, South Africa, and involved in both undergraduate and postgraduate teaching and supervision. Upon completion of his fellowship exams, his research focus has centred around improving diabetes care at a regional level hospital. He has completed his MMed and is now working on his PhD dissertation. His main interest lies in diabetes and endocrinology. Colleen Aldous is Associate Professor and Academic Leader for Research in the School of Clinical Medicine at the University of KwaZulu-Natal, Durban, South Africa. She is a medical scientist with a PhD in science education and is involved in postgraduate research mentorship across several medical disciplines including surgery, orthopaedics, dermatology, paediatrics, ophthalmology, general medicine and psychology. Her own research interest is human genetics. Corresponding author: S Pillay (drspillay@iafrica.com)

Globally diabetes mellitus (DM) and its complications are placing an enormous burden on individual patients and countries alike. South Africa is a developing country already under enormous pressure from communicable diseases such as HIV and tuberculosis. Added to this is DM, which serves to fuel the interactions between communicable and non-communicable diseases. Data from KwaZulu-Natal Province (KZN) have demonstrated that the majority of patients with DM in the public healthcare sector are diagnosed and started on treatment at their local resource-limited healthcare clinics. This article describes introduction of a multifaceted approach to the management of DM in a resource-limited clinic at Edendale Hospital, Pietermaritzburg, KZN. Strategies like this may help provide a blueprint for other resourcelimited healthcare facilities in developing countries. S Afr Med J 2016;106(5):456-458. DOI:10.7196/SAMJ.2016.v106i5.10409

Diabetes mellitus (DM) and its complications remain a health threat to individual patients and a burden to the health economies of countries all over the world, particularly developing countries that are already overburdened with communicable diseases (CDs) such as HIV and tuberculosis (TB). South Africa (SA) is one such developing country, where DM can serve to fuel the interactions between CDs and non-communicable diseases (NCDs). HIV infection increases the risk of developing type 2 DM two-fold, while DM increases the risk of contracting TB three-fold.[1] SA has the third-highest prevalence of TB globally.[2] Improving diabetes control may provide a means of breaking this interaction between CDs and NCDs. The factors impeding attainment of optimal diabetes control include obesity and healthcare worker compliance with clinical guidelines. The prevalence of type 2 DM is being fuelled by the obesity pandemic, with SA having the highest rate of obesity among females in sub-Saharan Africa. [3] Optimal control of DM is not being achieved in either the private or the public sector in SA.[4-5] Healthcare worker compliance with clinical guidelines has been shown to be suboptimal both in SA and globally.[6-8] The following interventions have demonstrated improvements in diabetes care: • Electronic patient registries have been shown to improve glycaemic and low-density lipoprotein and total cholesterol control in resource-limited settings.[9] • A study by Ricci-Cabello et al.[10] suggests that multiple intervention strategies directed at both clinicians and patients can improve diabetes control in resource-limited clinics. We have shown[11] that the majority of patients with DM attending public sector healthcare facilities in KwaZulu-Natal Province (KZN), SA, over the period 2010 - 2014 were diagnosed and initiated on

diabetes treatment at their clinics rather than at hospital level. Multifaceted strategies targeted at clinic level could therefore provide an ideal approach. With most diabetes clinics in developing countries being resource-limited, use of the scarce resources available needs to be maximised to achieve some degree of control of this pandemic.

As things were …

Edendale Hospital is a busy regional hospital in Pietermaritzburg, the capital of KZN, which provides district as well as regional services. The diabetes clinic in this resource-limited hospital originally mirrored what exists in many other developing countries. Problems at the clinic included an unstructured booking system, which meant that a large number of patients seen did not in fact require specialist care at that point, clinician understaffing, poor or no patient education and staff in-service training, lack of the equipment necessary for appropriate examination of the patient with DM, an incomplete multidisciplinary team (lacking podiatrist, dietician and regular ophthalmological assessments), limited access to selfmonitoring of blood glucose (SMBG), and no means of collecting and auditing patient data.

Changes made at the Edendale Hospital diabetes clinic

Acknowledging the shortage of resources and having assessed the deficits, the following changes were made.

Organisation of the clinic

• A structured booking system was introduced in the clinic. Once patients had been appropriately down-referred to their local community healthcare clinics after being stabilised, the number of patients seen at the Edendale clinic decreased from 60 - 70 a week to a more manageable 30 - 40.

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IN PRACTICE

Staffing and patient education • A multidisciplinary team was established that included the following members: • specialist physician • family physician • medical officers/interns • nursing staff • diabetes nurse-educator • dieticians • podiatrist • ophthalmologist for annual eye assessments. All the members of this team were involved in intensive patient education. Patient diabetes educational material was acquired and displayed strategically in waiting areas. • A diabetes nurse-educator was employed to oversee all clinic bookings and the general weekly running of the clinic. All the other members of the team were employed at Edendale Hospital and allocated to the clinic weekly.

Staff training on all aspects of the care and needs of the patient with DM

• Nursing staff working at the clinic were trained on all aspects of diabetes care by the specialist physicians. • All clinicians working at the clinic were re-trained on the management of diabetes using the 2012 South African diabetes guidelines.[12] Laminated copies of these guidelines were affixed to the walls of each consulting room.

Data collection tools

Two data collection tools were designed and introduced into the clinic. • An ink-based stamp was used to stamp outpatient (OP) files of all patients visiting the clinic. It ensured that the clinical variables listed below were routinely measured for every patient and entered directly into the patient’s OP folder. This decreased the risk of these values being written on loose pieces of paper, which are easily mislaid. The vital examinations that needed to be completed by the nursing staff before the patient’s consultation with the clinician were listed on the stamp as follows: • sitting and standing blood pressure (mmHg) • resting pulse rate (/min) • height (cm) • weight (kg) • body mass index (BMI) (kg/m2) • waist circumference (cm) • urine dipstick findings (all patients visiting the clinic now had a urine dipstick examination performed on every visit) • random blood glucose (RBG) (mmol/L). • A specialised comprehensive datasheet was completed in triplicate by the attending clinician and served the following purposes: • To ensure standardisation in the evaluation and management of all patients seen at the clinic • To enable communication between the clinic and other healthcare facilities and personnel that the patient might consult at a later stage • To ensure that commonly forgotten areas of diabetes management are reinforced (e.g. the need for regular ophthalmological and foot care and dietician reviews) • To facilitate auditing and reporting. A computer program that matched the datasheet was designed for the clinic, and all the data from the datasheets were captured on it. This program was written using Visual Basic Studio 2010 and

.NET Framework 4 technologies (Microsoft, USA) Reports were then generated via Crystal Reports (version 13, USA). These were used for auditing purposes.

Additions to physical resources

• Equipment for the clinic was obtained mostly through donations. We ensured that all rooms had tuning forks, patellar hammers and monofilament for testing the feet. A BMI scale was acquired. All consulting rooms had a functional ophthalmoscope, enabling accurate fundoscopy to be performed.

The multidisciplinary team

• Foot care is an integral part of diabetes management, as individuals with DM are 20 times more prone to lower limb amputations than non-diabetics.[13] The podiatrist working at the local tertiary hospital was recruited to provide group patient education at the clinic while patients waited to see the clinicians, and also to consult individual patients with specific foot problems identified by the clinicians. • Dietary changes are an important lifestyle modification that needs to be started as soon as a patient is diagnosed with DM and continued for life thereafter.[14] Dietary patterns of patients of different ethnic groups need to be considered when dietary education is being given. After consultation with the dietetics department at Edendale Hospital it was agreed that dieticians would attend the clinic to provide group dietary education, and that all patients attending the clinic would be consulted individually at least once a year. Dietary education pamphlets in various languages were issued to patients as well. • Patients were referred to the eye clinic for annual diabetes eye screening as per local diabetes guidelines. This screening is essential, as diabetic retinopathy is responsible for most cases of new-onset blindness in adults aged 20 - 74 years.[15]

Issuing of glucometers to patients

• SMBG has been shown to improve metabolic control in patients with DM.[16] The majority (71.2%) of the patients at our clinic had previously had no access to glucometers.[4] An ongoing donation of glucometers was secured. All patients on any form of insulin therapy were given one, with education on its use and instructions on what to do in the event of hypo- or hyperglycaemia.

Conclusions

Patient education disseminated from all members of the multi disciplinary team and coupled with ongoing in-service training of clinicians and nurses is an integral component of this multifaceted approach to diabetes care. The ink-based stamp at the nurses’ station ensures that every patient has vital clinical information measured and entered into the OP file. This information allows the clinician to assess for RBG, postural hypotension, urine dipstick findings such as proteinuria and evidence of urinary tract infections, raised BMI and waist-to-height ratios indicating obesity. The creation of the datasheet and its incorporation into the clinic ensures comprehensive and standardised management of all patients seen. The datasheet helps direct clinicians in approaching the complex entity of diabetes assessment and management. The computer program enables us to evaluate the baseline state of diabetes control in the clinic, and we will also be able to monitor trends in diabetes control there over future years. With improved clinic booking systems and referral criteria, the number of patients seen has been brought down to a manageable 30 40 a week. This allows clinicians to spend more time with patients, conducting a thorough diabetes history and clinical examination.

May 2016, Print edition

IN PRACTICE

The changes we have made in this resource-limited clinic could be adapted to other similar clinics in developing countries, as well as to district and regional hospitals. If necessary, datasheets could be completed at other health institutions and sent to a central regional hospital for capturing onto a customised computer program. Reports generated in this way could provide important information regarding diabetes control in these healthcare facilities. DM is a complex disease entity that requires a holistic and multifaceted approach to ensure adequate control with minimal complications. Strategies like ours may help provide a blueprint for other healthcare facilities in developing countries to tackle the global pandemic of DM. 1. Galli L, Salpietro S, Pellicciotta G, et al. Risk of type 2 diabetes among HIV-infected and healthy subjects in Italy. Eur J Epidemiol 2012;27(8):657-665, DOI:10.1007/s10654-012-9707-5 2. Department of Health, South Africa. Annual Performance Plan 2012/13 - 2014/15. http://www.tbfacts. org/wp-content/uploads/2015/06/App2012-2014.pdf (accessed 1 November 2015). 3. 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. DOI:10.1016/S0140-6736(14)60460-8 4. Pillay S, Aldous C, Mahomed F. Diabetic patients served at a regional level hospital: What is their clinical picture? J Endocrinol Metab Diabetes S Afr 2015;20(1):60-66. DOI:10.1080/16089677.2015.1030856 5. Amod A, Riback W. Diabetes guidelines and clinical practice: Is there a gap? The South African cohort of the International Diabetes Management Practices Study. J Endocrinol Metab Diabetes S Afr 2012;17(2):85-90. DOI:10.1080/22201009.2012.10872282

6. Igbojiaku OJ, Harbor OC, Ross A. Compliance with diabetes guidelines at a regional hospital in KwaZulu-Natal, South Africa. Afr J Prim Health Care Fam Med 2013;5(1). DOI:10.4102/phcfm. v5i1.447 7. Kirkman MS, Williams S, Caffrey H, et al. Impact of a program to improve adherence to diabetes guidelines by primary care physicians. Diabetes Care 2002;25(11):1946-1951. DOI:10.2337/ diacare.25.11.1946 8. Hetlevik I, Holmen J, Midthjell K. Treatment of diabetes mellitus - physicians’ adherence to clinical guideline in Norway. Scand J Prim Health Care 1997;15(4):193-197. DOI:10.3109/02813439709035027 9. Pollard C, Bailey KA, Petitte T, et al. Electronic patient registries improve diabetes care and clinical outcomes in rural community health centers. J Rural Health 2009;25(1):77-84. DOI:10.1111/j.17480361.2009.00202.x 10. Ricci-Cabello I, Ruiz-Perez I, Rojas-Garcia A, Pastor G, Goncalves DC. Improving diabetes care in rural areas: A systematic review and meta-analysis of quality improvement interventions in OECD countries. PLoS One 2013;8(12):e84464. DOI:10.1371/journal.pone.0084464 11. Pillay S, Lutge E, Aldous C. The burden of diabetes mellitus in KwaZulu-Natal’s public sector: A 5-year perspective. S Afr Med J 2016;106(4):384-388. DOI:10.7196/SAMJ. 2016.v106i4.9920 12. Amod A, Motala A, Levitt N, et al. The 2012 SEMDSA guidelines for the management of type 2 diabetes. J Endocrinol Metab Diabetes S Afr 2012;17(1):S1-S94. DOI:10.1080/22201009.2012.10872277 13. Van Houtm WH, Lavery LA, Harkless LB. The impact of diabetes-related lower-extremity amputations in the Netherlands. J Diabetes Complications 1996;10(6):325-33. DOI:10.1016/1056-8727(95)00088-7 14. Andrews RC, Cooper AR, Montgomery AA, et al. Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: The Early ACTID randomised controlled trial. Lancet 2011;378(9786):129-139. DOI:10.1016/S0140-6736(11)60442-X 15. Fong DS, Aiello L, Gardner TW, et al. Retinopathy in diabetes. Diabetes Care 2004;27(1):S84-S87. DOI:10.2337/diacare.27.2007.S84 16. Guerci B, Drouin P, Grange V, et al. Self-monitoring of blood glucose significantly improves metabolic control in patients with type 2 diabetes mellitus: The Auto-Surveillance Intervention Active (ASIA) study. Diabetes Metab 2003;29(6):587-594. DOI:10.1016/S1262-3636(07)70073-3

Accepted 30 November 2015.

CASE REPORT

Haemotoxic snakebite in rural KwaZulu-Natal, South Africa: A case presenting with haematemesis M Wagener Mark Wagener, MB ChB (University of Cape Town), is a medical officer grade 1 in General Surgery at Ngwelezane Hospital, Empangeni, KwaZulu-Natal, South Africa. Corresponding author: M Wagener (mark.wagener2@gmail.com)

A 36-year-old man who had been bitten on the left index finger by a snake identified as a boomslang (Dispholidus typus) presented with haematemesis and hypovolaemic shock. Coagulopathy was presumed, and the platelet count was 2 × 10⁹/L. Findings on upper endoscopy included oesophageal petechial haemorrhages, severe haemorrhagic gastritis and an antral ulcer. The patient was successfully managed using freeze-dried plasma, packed red blood cells, isotonic crystalloids and polyvalent antivenom. S Afr Med J 2016;106(5):459-460. DOI:10.7196/SAMJ.2016.v106i5.9124

Case report

A 36-year-old man sustained a snakebite on the left index finger at 17h00. The snake was caught and identified as a boomslang (Dispholidus typus) according to the referring doctor. He presented to his local district hospital at midnight, was referred to Ngwelezane Hospital (Empangeni, KwaZulu-Natal, South Africa) and arrived there at 07h00 the next day. The patient had developed haematemesis from 01h00 while at the base hospital, active haematemesis being witnessed by medical staff. He also had painful progressive swelling of the left arm. There was no past medical history of note, and his HIV status was unknown. He had no history of non-steroidal anti-inflammatory use, but admitted to excessive alcohol intake. On examination at the base hospital, the patient’s pulse rate was 100/min and his blood pressure 86/50 mmHg. He was dehydrated

and pale, was not jaundiced and had no signs of chronic liver disease. There was swelling of the left arm from the fingertips to above the elbow. The compartments were not tense and there was no area of skin necrosis. Examination of the respiratory and cardiovascular systems revealed no other abnormalities, and the patient was alert and orientated. Details of resuscitation initiated at the base hospital were as follows. The patient’s airway was self-maintained before, during and after administration of antivenom, the lungs had equal air entry, and he did not develop bronchospasm before, during or after administration of antivenom. Because circulatory changes showed evidence of hypovolaemic shock on presentation, two 18-gauge intravenous (IV) cannulas were inserted and he was given a total of 3 L normal saline, 3 × 500 mL units of fresh-dried plasma (FDP) given empirically for presumed coagulopathy, and a 40 mg IV bolus of pantoprozole.

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Discussion

Fig. 1. Endoscopic view of the oesophagus of a patient with haemotoxic snakebite, demonstrating diffuse petechial haemorrhages.

Fig. 3. The gastric antrum. Gastritis is evident, and there is a prepyloric ulcer (arrow).

Fig. 2. View of the stomach looking towards the antrum, showing severe gastritis.

Fig. 4. Prepyloric ulcer (arrow). It shows no signs of recent haemorrhage and has a fibrin-covered base.

Polyvalent antivenom (four 10 mL ampoules, i.e. 40 mL) in 200 mL normal saline was administered over 15 minutes, preceded by 0.5 mL 1:1 000 adrenaline as an intramuscular injection (IMI), 25 mg promethazine as an IMI, and 200 mg hydrocortisone as an IMI. The patient did not develop any evidence of anaphylaxis after administration of antivenom. He was also given one unit of packed red blood cells. The results of testing of blood samples taken before resuscitation and referral were as follows: sodium 127 mmol/L, potassium 3.6 mmol/L, chloride 100 mmol/L, urea 7.5 mmol/L, creatinine 111 mmol/L, haemo globin (Hb) 11.1 g/dL, platelets 2 × 10⁹/L and international normalised ratio (INR) 0.96. On arrival at Ngwelezane Hospital, the patient was still alert and orientated. His pulse rate was 94/min and his blood pressure 142/72 mmHg. The swelling of the left arm from fingertips to above the elbow had not progressed beyond where it had been marked by the doctor at the base hospital.

The patient underwent gastroscopy at Ngwelezane Hospital at 09h00, performed by the author. The findings were as follows: oesophagus – diffuse petechial haemorrhages (Fig. 1); stomach – severe diffuse gastritis (Fig. 2) and a prepyloric ulcer with overlying slough (Figs 3 and 4); and duodenum – D1 and D2 duodenitis. During his stay in hospital the patient experienced no further haematemesis. Melaena was noted for 2 days after admission and then resolved. The left arm swelling resolved, and he remained haemodynamically stable. The results of blood tests on arrival at Ngwelezane Hospital at 07h00 were as follows: Hb 6.8 g/dL, white cell count 15.58 × 10⁹/L, platelets 205 × 10⁹/L, sodium 136 mmol/L, potassium 4.4 mmol/L, urea 6.9 mmol/L and INR 1.19. Liver function was normal. The patient received two further units of packed red blood cells and oral omeprazole. He was discharged from hospital after 3 days with an Hb of 8.6 g/dL.

May 2016, Print edition

This case illustrates a number of interesting aspects of the management of snakebite. Firstly, it is a dramatic presentation of a haematoxic snakebite. A bite from a boomslang produces a consumptive coagulopathy with onset between [1] 6 and 36 hours after envenom ation. In particular, a profound drop in fibrinogen levels develops. [1,2] This is one of the indications for the use of cryoprecipitate.[2] Since this product was not available at the base hospital, and it was not possible to measure the fibrinogen level there, FDP was a good choice. Of note is that the use of polyvalent antivenom is not indicated in boomslang bite; instead boomslang antivenom should [1,3] be used. Since this was not available, polyvalent antivenom was given. The patient nevertheless experienced a remark able reversal of bleeding symptoms and thrombocytopenia, the platelet count climbing from 2 to 205 × 10⁹/L in less than 24 hours. It could be argued that the initial platelet count was spurious, but the presence of diffuse oesophageal petechiae would contradict this. It is also possible that the snake was wrongly identified. Puff adder (Bitis arietans) bites are far more common than boomslang bites, and may also result in bleeding.[3] In support of this was the amount of swelling, which was more than would be expected from a boomslang bite,[1-3] and the fact that the polyvalent antivenom was so effective. Also of note is that the patient had another risk factor for the development of an upper gastro intestinal (GI) bleed, namely chronic heavy alcohol consumption. This is likely to have contributed to his gastric ulcer, and possibly his gastritis as well. The actual source of his upper GI bleed was probably the severe haemorrhagic gastritis, since petechial haemorrhages do not bleed and the gastric ulcer showed no evidence of a recent bleed (Forrest III). 1. Müller GJ, Modler H, Wium CA, Veale DJH, Marks CJ. Snake bite in southern Africa: Diagnosis and management. CME 2012;30(10):362-381. 2. Ashe S, Blaylock R, Chisale MGP, et al. Guidelines for the Prevention and Clinical Management of Snakebite in Africa. Brazzaville: World Health Organization, Regional Office for Africa, 2010. 3. Blaylock RS. The identification and syndromic management of snakebite in South Africa. S Afr Fam Pract 2005;47(9):48-53.

Accepted 19 January 2016.

IN PRACTICE

CASE REPORT

On your toes: Detecting mediastinal air on the chest radiograph in ecstasy abusers M Naidoo, M Govind Dr Mergan Naidoo is a family physician working as a head of clinical unit/lecturer for the Department of Family Medicine in the School of Nursing and Public Health, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa, and the KZN Department of Health. His special interests include primary emergency care, and he has been involved with emergency care outreach using simulation-based teaching in the province of KZN for a number of years. Dr Mayuri Govind is a radiologist working as an MMed co-ordinator in the Department of Academic Clinical and Professional Practice in the School of Clinical Medicine at UKZN. She has an interest in medical education. Corresponding author: M Naidoo (naidoom@ukzn.ac.za)

Abnormal mediastinal air may be caused by inhalational illicit drug use subsequent to barotrauma resulting from coughing after deep inhalation and breath holding. It may also arise from oesophageal rupture due to retching after ingestion of the illicit drug. The history can alert the practitioner to this cause of chest pain. As chest radiographs are widely accessible and mediastinal air is easily recognisable, the chest radiograph should be included and carefully scrutinised in the diagnostic workup of chest pain in the recreational drug abuser. It is prudent to exclude oesophageal rupture, particularly in the setting of retching, before deciding on conservative and expectant management. S Afr Med J 2016;106(5):461-462. DOI:10.7196/SAMJ.2016.v106i5.9867

The ‘club drug’ known as ecstasy (3,4-methylene dioxy meth amphetamine (MDMA)) has been reported to be involved in 1% of primary and 3% of secondary drug abuse in patients presenting to treatment facilities in Durban, South Africa.[1] The emergency room (ER) presentation of patients suffering from the effects of this drug poses a particular challenge, as ecstasy is often abused in conjunction with other agents.[1] We report the case of a 19-year-old man who presented with acute chest pain following drug ingestion.

A 19-year-old man presented to the ER at Wentworth Hospital, Durban, late at night. He reported central chest pain for 22 hours following the ingestion of alcohol and seven tablets of a drug called ‘Mercedes’ (a form of MDMA). There was no history of retching or vomiting. The patient was clinically stable on admission with a pulse of 95/min, a blood pressure of 138/98 mmHg and a respiratory rate of 20/min. He was alert but needed assistance with mobilising. Blood tests revealed a marginally elevated creatinine kinase cardiac fraction, but troponin-T levels were normal. Findings on electrocardiography were normal. A chest radiograph (CXR) was done and misinterpreted as normal. There was no known underlying lung pathology. The patient was admitted to a general ward for observation. During the ward round the next day a pericardial friction rub was noted, but neck crepitus was not present. The initial CXR (Fig. 1) was reviewed and revealed mediastinal air (pneumomediastinum and pneumopericardium). On day 2 he remained stable but was referred to the cardiothoracic surgeons as a precaution. The CXR was repeated and an echocardiogram and contrast swallow were recommended. The repeat CXR demonstrated reduction in mediastinal air, and the echocardiogram was normal. The patient was returned to a general ward in the hospital for observation. He was counselled by the social workers and made a full recovery within the week.

for mediastinal air in ecstasy abuse is barotrauma rather than a direct pharmacological mechanism.[3] Drug inhalation is associated with valsalva manoeuvres such as prolonged breath holding, coughing and physical exertion. These manoeuvres increase the intra-alveolar pressure causing spontaneous rupture of the alveoli, particularly in the scenario of airway inflammation, i.e. weakened alveolar integrity. As the interstitial pressure is relatively lower, the alveolar air tracks along the peribronchovascular spaces to reach the hilum and mediastinum.[4] In contrast, retching following drug ingestion can lead to rupture of the oesophagus and the direct introduction of air into the tissue planes of the mediastinum. Interstitial air can give rise to further complications by dissecting through tissue planes to extend into the potential spaces, causing secondary pneumopericardium and pneumothorax.[4] Careful examination of the CXR would assist in detecting mediastinal air and its complications. Importantly, the mechanism of drug consumption may indicate the causation of mediastinal air and therefore determine subsequent diagnostic workup. Bakhos et al. [5] in their report on spontaneous pneumomediastinum noted that illicit drug use accounted for 24% of cases, and that 41% of all presentations of spontaneous pneumomediastinum occurred in individuals with no underlying lung pathology. They suggested a conservative approach to investigation and management, as the condition is usually benign and self-limiting. In an earlier case report, Levine et al.[6] recommended that rupture of the oesophagus be excluded before proceeding with conservative management. Similarly, Newcomb and Clark[7] recommended that a non-invasive contrasted computed tomography scan of the chest and water-soluble contrast swallow examination be included in the diagnostic work-up if there is a suspicion of oesophageal rupture. Two cases of spontaneous pneumomediastinum following ecstasy ingestion have been reported by Rezvani et al.,[8] but the pathophysiology was not described. We could not assign either mechanism of barotrauma to our case, as there was no history of deep inhalation, excessive coughing or retching.

Discussion

The CXR

Case report

Ecstasy may be inhaled as a powder or ingested as a tablet. Despite the two different modes of consumption, the underlying pathophysiology

The CXR is an easily accessible imaging tool, and despite its limitations it can demonstrate mediastinal emphysema (pneumo

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mediastinum and pneumopericardium) clearly as air contrasts well with the soft tissue of the mediastinum. Some of the pathognomonic features of mediastinal air on a plain CXR are shown in Fig. 1. Pneumomediastinum is seen as discontinuous hypodense streaks of air in the hyperdense mediastinal tissue. The air lies in the interstitial spaces and can streak upwards into the neck and the subcutaneous soft tissue of the axilla and chest, inferiorly into the retroperitoneum and beyond the anatomical attachments of the pericardium.[9] This air does not shift with change in patient positioning, as opposed to air in pericardial space, which alters with gravity.[9] Other signs that suggest mediastinal air on the CXR include the ‘continuous diaphragm sign’ (air trapped posterior to the peri cardium), ‘Naclerio’s V sign’, which is formed by the junction of mediastinal air in the left lower mediastinum and extrapleural air adjacent to the left hemidiaphragm, the ‘V sign’ that is formed by the confluence of the superior margins of the brachiocephalic veins, the ‘ring around artery sign’ that results from air outlining the pulmonary artery and the main branches, the ‘double bronchial wall sign’ formed by air outlining the bronchi, air in the pulmonary ligament and irregular bilateral apical extrapleural air.[9] However, mediastinal air may be appreciated only on a lateral CXR as the hypolucent outline of the right pulmonary artery, aortic arch, ascending aorta, trachea and proximal bronchi. A more easily recognisable feature on the lateral CXR is the presence of retrosternal extrapleural air.[9]

Conclusion

Pneumomediastinum following MDMA use has been described as a fairly rare cause of chest pain. It is often associated with normal vital signs, and the air can be detected on the standard CXR. With the global and in particular the national trend of increasing drug abuse among teenagers and young adults, ER physicians need to be aware of this diagnosis as a complication, albeit rare, of inhalational illicit drug abuse and recognise its signs on the CXR. The management of uncomplicated non-surgical mediastinal air is expectant observation. During this time the patient should be monitored for acute complications such as tension pneumopericardium and tension pneumothorax. Sometimes, as in the case described, the history may not suggest the diagnosis. Nevertheless, when there is a history of illicit drug use it is prudent to include the correct interpretation of a CXR in the diagnostic work-up. 1. Dada S, Pluddemann A, Parry C, et al. Monitoring alcohol and drug abuse trends in South Africa. SACENDU Res Br 2012;15(1):1-15. 2. Van Loggerenberg CJ. Emergency management of drug abuse in South Africa: Drug abuse remains both a global scourge and a significant social and medical problem in South Africa. CME 2012;30(11):409-413.

Fig. 1. Posteroanterior erect CXR demonstrating features of mediastinal air. Pericardial air is noted as a radiolucent line marginated by the hyperdense pericardial sac and pericardial recess (A: adjacent to the right atrium; B: outlining the right heart border behind the anterior aspect of the right diaphragm; C: outlining the left hemidiaphragm; D: adjacent to the left ventricle; E: within the pericardial recesses beyond the proximal left pulmonary artery). Hypodense streaks of air extend beyond the pericardial attachments (F: superiorly into the anterior neck; G: outlining the aortic arch; H: superior vena cava above the azygos vein; I: outlining the sternal insertion of the left diaphragm). 3. Harris R, Joseph A. Spontaneous pneumomediastinum? ‘Ecstasy’: A hard pill to swallow. Aust N Z J Med 2000;30(3):401-403. DOI:10.1111/j.1445-5994.2000.tb00848.x 4. Macklin MT, Macklin CC. Malignant interstitial emphysema of the lungs and mediastinum as an important occult complication in many respiratory diseases and other conditions: An interpretation of the clinical literature in the light of laboratory experiment. Medicine 1944;23(4):281-358. 5. Bakhos CT, Pupovac SS, Ata A, Fantauzzi JP, Fabian T. Spontaneous pneumomediastinum: An extensive workup is not required. J Am Coll Surg 2014;219(4):713-717. DOI:10.1016/j.jamcollsurg.2014.06.001 6. Levine AJ, Drew S, Rees GM. ‘Ecstasy’ induced pneumomediastinum. J R Soc Med 1993;86(4):232-233. 7. Newcomb AE, Clarke CP. Spontaneous pneumomediastinum: A benign curiosity or a significant problem? Chest J 2005;128(5):3298-3302. DOI:10.1378/chest.128.5.3298 8. Rezvani K, Kurbaan A, Brenton D. Ecstasy induced pneumomediastinum. Thorax 1996;51(9):960-961. 9. Bejvan SM, Godwin JD. Pneumomediastinum: Old signs and new signs. AJR Am J Roentgenol 1996;166(5):1041-1048. DOI:10.2214/ajr.166.5.8615238

Accepted 7 March 2016.

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CASE REPORT

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) and cirrhosis of the liver: A case report and literature review M K Kgomo, A A Elnagar, C Jeske, J Nagel Dr Mpho Kgomo is a gastroenterologist and heads the Gastroenterology Division of Internal Medicine at Steve Biko Academic Hospital and the School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa. He has an interest in oesophageal cancer research. Working in the same division is Dr Ali Elnagar, a gastroenterologist with an interest in viral hepatitis. Dr Christian Jeske is a gastroenterologist in the Gastroenterology Division of Surgery at Steve Biko Academic Hospital and the School of Medicine, Faculty of Health Sciences, University of Pretoria. He has an interest in hepatobiliary diseases. Dr Jackoo Nagel is a specialist physician and a trainee gastroenterologist in the Gastroenterology Division of Internal Medicine. Corresponding author: M K Kgomo (kgomomk@worldonline.co.za)

Patients with cirrhosis of the liver usually present with a small, shrunken liver and a large spleen. The presence of an unusually huge liver should prompt the treating doctor to look for another cause, as this may be treatable and improve the patientâ&#x20AC;&#x2122;s outcome. In South Africa tuberculosis and lymphoma in the presence of HIV infection should be excluded. Sinus histiocytosis with massive lymphadenopathy and cirrhosis is a rare combination and has not been reported before in the literature. This case is intended to make clinicians aware of this rare combination of diseases. S Afr Med J 2016;106(5):463-464. DOI:10.7196/SAMJ.2016.v106i5.9614

Case report

A 62-year-old woman was known to have cirrhosis of the liver of unknown causation, confirmed histologically, with a micronodular pattern and regeneration. On previous investigation she was found to have ascites, and no varices on upper endoscopy. An autoimmune screen was positive for antinuclear factor (ANF) with a titre of 160 and a homogeneous pattern, but all other markers for autoimmune hepatitis were negative. Hepatitis B and C screening were also negative, iron status was normal, and copper and ceruloplasmin levels were normal. The patient now presented to the liver clinic at Steve Biko Academic Hospital, Pretoria, South Africa, with massive hepatosplenomegaly. A computed tomography (CT) scan of the abdomen showed extensive adenopathy at the porta hepatis area (Fig. 1). Liver function tests showed an infiltrative pattern. The erythrocyte sedimentation rate (ESR) was elevated at 89 mm/h. Differential diagnoses of tuberculosis and lymphoma were considered. A chest radiograph was normal, and laparoscopic lymph node biopsy was negative for both tuberculosis and lymphoma. However, it revealed prominent sinus histiocytosis, with the lymph node showing retained architecture and polarity. The patient was continued on diuretics for cirrhosis. A search for other autoimmune diseases such as rheumatoid arthritis was negative. She will be continued on this treatment until the condition poses the risk of spleen rupture or threatens her life.

Discussion

As far as we could establish from a PubMed search, no other case of sinus histiocytosis and liver cirrhosis has been reported. The closest case is one of chronic hepatitis B viral infection and lymphoma with sinus histiocytosis reported by Melikyan et al.[1] Sasaki et al.[2] reported a case of sinus histiocytosis with massive lymphadenopathy complicated by pathological fractures, kidney failure and liver

Fig. 1. CT scan of the abdomen of a patient with sinus histiocytosis and massive lymphadenopathy and cirrhosis of the liver showing lymph nodes in the porta hepatis area (arrow).

cirrhosis, treated with cladribine. In our case screening for both hepatitis B and C was negative, and apart from a positive test for ANF, no other explanation for the cirrhosis could be found. Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare and benign source of lymphadenopathy of unknown aetiology, first described in 1969 by Rosai and Dorfman (cited by Moore et al.[3]), that can mimic neoplastic processes.[3] It is a self-limiting

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disease that characteristically manifests as painless bilateral cervical adenopathy accompanied by fever, leucocytosis, an elevated ESR and hypergammaglobulinaemia.[4] The most common sites for extra足nodal disease are the skin,[5] upper respiratory tract and bone, followed by the genitourinary and lower respiratory tracts, oral cavity and soft tissues.[6] The disease commonly presents in children and young adults, with supradiaphragmatic lymphadenopathy or extranodal lesions consisting of tissue infiltrates composed of a polyclonal population of sinus histiocytes.[3] The disease involves overproduction of a type of white blood cell called non-Langerhans sinus histiocytes. These cells occur in lymph nodes, but can exist in other areas of the body and can lead to organ damage. The reason for the overproduction of these cells is not known, but several possibilities have been considered, including viral, bacterial, infective, environmental and genetic causes. Treatment of SHML is unnecessary unless the disorder becomes life or organ threatening, since the disease will resolve spontaneously in most cases.[3] SHML has been found to occur concomitantly with other diseases such as diffuse large B-cell lymphoma,[1] HIV infection,[2] varicella zoster infection and autoimmune lymphoproliferative syndrome.[7]

Delacretaz et al.[8] reported the first case of sinus histiocytosis and HIV, in a 31-year-old black woman with HIV infection who presented with symptomatic generalised lymphadenopathy. Since then a few other such cases have been reported, including that by Perry et al.[9] in 1998. Other agents to treat the condition are still being researched, and case reports continue to appear, though at a slow rate. Because this disease is so rare, there have been no large-scale studies. 1. Melikyan AC, Kovringina AM, Gilyazildinova EA, Gittis MK. A case of sinus histiocytosis with massive lymphadenopathy in a patient with diffuse large cell lymphoma and chronic hepatitis B virus infection. Ter Arkh 2012;84(11):66-70. 2. Sasaki K, Pemmaraju N, Westin JR, et al. A single case of Rosai-Dorfman disease marked by pathological fractures, kidney failure, and liver cirrhosis treated by a single agent cladribine. Front Oncol 2014;29(4):297. DOI:103389/fonc.2014.00297 3. Moore JC, Zhao X, Nelson EL. Concomitant sinus histiocytosis with massive lymphadenopathy and diffuse large cell lymphoma: A case report. J Med Case Rep 2008;2:70. DOI:10.1186/1752-1947-2-70 4. Park YK, Kim YW, Choi WS, Lim YJ. Sinus histiocytosis with massive lymphadenopathy, multiple skull involvement. J Korean Med Sci 1998;13(4):423-427. 5. Faucar E, Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy: Current status and future directions. Arch Dermatol 1988;124(6):1211-1214. 6. Faucar E, Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy: Review of the entity. Semin Diagn Pathol 1990;7(1):19-73. 7. Silvers AR, Som PM, Meyer RJ. Egg shell nodal calcification in a patient with sinus histiocytosis with massive lymphadenopathy treated with interferon. Am J Neuroradiol 1996;17(2):361-363. 8. Delacretaz F, Meuge-Moraw C, Anwar D. Sinus histiocytosis with massive lymphadenopathy in a human immune deficiency virus-positive patient. Virchows Arch A 1991;419(3):251-254. 9. Perry BP, Gregg CM, Myers S, et al. Rosai-Dorman disease (extranodal sinus histiocytosis) in a patient with HIV. Ear Nose Throat J 1998;77(10):855-858.

Accepted 26 March 2016.

CASE REPORT

Syphilitic lymphadenitis clinically and histologically mimicking lymphogranuloma venereum A Wessels, C Bamford, D A Lewis, M Martini, H C Wainwright Dr Annesu Wessels is a senior registrar in anatomical pathology working at Groote Schuur Hospital, Cape Town, South Africa. Dr Colleen Bamford is a senior pathologist in the Division of Microbiology, Faculty of Health Sciences, University of Cape Town. She is actively involved in research and education regarding the rational use of antibiotics and appropriate use of microbiological investigations. Prof. David Lewis is a sexual health physician currently working as Director of the Western Sydney Sexual Health Centre, Australia, with conjoint professorial appointment at the University of Sydney. He also serves as President of the International Union against Sexually Transmitted Infections, and was formerly Head of the Centre for HIV and Sexually Transmitted Infections at the National Institute for Communicable Diseases in South Africa. He has an interest in sexual health and has published more than 100 scientific articles. Dr Markus Martini is a medical officer in the Department of Surgery at Victoria Hospital, Wynberg, Cape Town. He has a special interest in laparoscopic surgery. Prof. Helen Wainwright is a principal pathologist and associate professor in the Department of Anatomical Pathology at the University of Cape Town. She has special interests in neonatal, hepatic and pulmonary pathology. Corresponding author: A Wessels (wssann003@myuct.ac.za)

An inguinal lymph node was discovered incidentally during surgery for a suspected strangulated inguinal hernia. The patient had recently been treated for candidal balanoposthitis and was known to have a paraphimosis. A new foreskin ulcer was discovered when he was admitted for the hernia surgery. The lymph node histology showed stellate abscesses suggestive of lymphogranuloma venereum (LGV). Chlamydial serologic tests were negative. As the histological appearance and clinical details provided were thought to suggest LGV, tissue was also sent for a real-time quadriplex polymerase chain reaction assay. This was used to screen for Chlamydia trachomatis in conjunction with other genital ulcer-related pathogens. The assay was negative for C. trachomatis, but positive for Treponema pallidum. Further histochemical staining of the histological specimen confirmed the presence of spirochaetes. S Afr Med J 2016;106(5):465-467. DOI:10.7196/SAMJ.2016v106i5.8723

A 56-year-old non-insulin dependent diabetic man initially presented with paraphimosis and candidal balanoposthitis. The treatment was successful and circumcision was planned, but the patient failed to

return for surgery. Seven months later he presented acutely with a 2-day history of severe abdominal pain, nausea and constipation, and a 6-week history of increasing swelling in his right groin. These clinical

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features were indicative of a strangulated inguinal or femoral hernia. A small ulcer on his foreskin was also noted, while the phimosis was still present. A small uncomplicated direct inguinal hernia and a firm enlarged inguinal lymph node were found in surgery. The lymph node was excised for histology and microbiological culture, while a routine open mesh repair of the hernia and a circumcision were performed. The foreskin was not submitted for histology. The patient recovered well after surgery. On gross examination, the lymph node measured 35 × 25 × 20 mm, and showed well-circumscribed pale areas on the cut section. The tissue was fixed and embedded in paraffin. Sections were stained routinely with haematoxylin and eosin, and examined using light microscopy. Microscopically, the sections showed a diffusely enlarged lymph node and adjacent fibroadipose tissue. The nodal architecture was effaced by necrotising inflammation producing stellate and serpiginous abscesses containing macrophages, neutrophils and nuclear debris without giant cells or granulomas (Fig. 1). No organ isms were demonstrated on histochemical stains (Ziehl-Neelsen ± modification, PAS, Grocott). Bacterial and mycobacterial cultures of the lymph node tissue yielded no growth. Chlamydial serology was requested and a complement fixation test (CFT) showed low-level positive antibody titres of 1 in 32 for the chlamydia-specific panel, which includes Chlamydia trachomatis (serovars A-K and L1-L3), Chlamydophila psittaci and Chlamydophila pneumoniae. This low-level positivity can be seen as a result of previous exposure to chlamydial infection, and cross-reactivity between antigens is frequently encountered. A subsequent C. trachomatis microimmunofluorescence test was negative for antibodies against lymphogranuloma venereum (LGV)specific serovars, essentially ruling out LGV as a diagnosis. As the histological appearance and the clinical details provided were thought to be suspicious for LGV, residual inguinal lymph node tissue was sent to the Centre for HIV and Sexually Transmitted Infections at the National Institute for Communicable Diseases in Johannesburg, South Africa (SA) for confirmation and further testing. A validated in-house, real-time quadriplex polymerase chain reaction (PCR) assay was used to screen for C. trachomatis in conjunction with other genital ulcer-related pathogens, specifically herpes simplex virus (HSV), Treponema pallidum and Haemophilus ducreyi. The assay was negative for C. trachomatis, HSV and H. ducreyi, but positive for T. pallidum. We were unable to test the genital ulcer for the presence of T. pallidum with the same molecular assay as the foreskin had been discarded post circumcision. Given the positive PCR assay result, a Warthin-Starry stain was requested on the histologically processed tissue biopsy and found to be positive for spirochaetes (Fig. 2). In addition, rapid plasma reagin (RPR) and a T. pallidum haemagglutination assay were performed retrospectively. Both were reactive, with titres of 1:16 and 1:1 280, respectively. A combination of molecular, histological and serological diagnostic strategies confirmed a clinically unexpected diagnosis of syphilis in the patient.

Discussion

The presence of a mass in the groin area, especially of short duration, would prompt the clinician to investigate the patient for an incarcerated inguinal hernia, among other things. Finding enlarged lymph nodes and adjacent fibroadipose tissue in such cases is not uncommon. Pathological changes in the aforementioned lymph nodes are also not unusual as this is frequently the reason for the incarceration. Necrotising lymphadenitis can be a nonspecific finding accom panying many benign and malignant processes involving lymph

Fig. 1. Haematoxylin and eosin-stained section of the lymph node showing a stellate-shaped abscess (arrow).

Fig. 2. Warthin-Starry histochemical stain showing a coiled spirochaete (arrow) morphologically consistent with T. pallidum.

nodes at any site. Acute nonspecific lymphadenitis, which is rarely biopsied, shows dilation of sinuses, neutrophilic infiltrates, vascular ectasia and oedema. Suppurative lymphadenitis may be due to a Staphylococcus aureus infection, mesenteric lymphadenitis, LGV and cat-scratch disease. Necrotising lymphadenitis may be seen in bubonic plague, tularaemia, anthrax, typhoid fever, melioidosis and Kikuchi’s lymphadenitis.[1] The presence of stellate micro-abscesses is a more specific finding, with a differential diagnosis of cat-scratch disease, LGV, and less likely tularaemia and atypical mycobacterial infection.[2] The histological findings in this case represent a very unusual lymph node response to syphilis. Typical features of syphilis, such as endarteritis and phlebitis, were not easy to see in this particular case due to extensive necrosis. The famous physician Sir William Osler is quoted as saying ‘he who knows syphilis knows medicine’.[3] Our case is another good example of the clinical and pathological mimicry that characterises infection with T. pallidum. Before the introduction of penicillin, which led to a marked reduction in syphilitic infections, every clinician was well attuned to the myriad clinical presentations of this important infectious disease. These days, however, syphilis may be misdiagnosed and mistreated if the condition itself is not considered in the differential diagnosis.[3] Key to making a correct diagnosis is the taking of an adequate sexual history which tends to be poorly undertaken in many medical and surgical specialities. The risk of

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syphilis is increased in patients with multiple sexual partners, among men who have sex with sex workers, among sex workers themselves, and importantly among those men who have sex with men (MSM) who are engaged in high-risk sexual practices.[4-6] Syphilis may be easily transmitted through vaginal, anal and, of note, oral sexual intercourse.[3] Untreated syphilis evolves through several stages. Localised lymph node enlargement can be seen in primary or tertiary syphilis, whereas secondary syphilis commonly shows generalised lymphadenopathy in keeping with the generalised dissemination of treponemes that accompanies this stage of the disease. The primary ulcers may be painless and may thus go unnoticed by the patient.[5] The associated inflammation that accompanies many primary lesions may cause tissue swelling and occasionally phimosis, which interferes with clear visualisation of the ulcer. Histologically, primary nodal syphilis usually presents with capsular and pericapsular inflammation and extensive fibrosis. A diffuse plasmacytic infiltrate, proliferation of blood vessels with endothelial swelling and phlebitis/endarteritis are commonly seen, in a background of follicular hyperplasia.[1,2] Rarely, non-caseating granulomas and abscesses can be found.[1] As with this case, T. pallidum can be demonstrated by histochemical stains (Warthin-Starry, Levaditi), immunohistochemistry or immunofluorescence. [2] Detection in fineneedle biopsies of lymph nodes using Southern blotting and PCR is also possible.[2] If available, molecular assays are the diagnostic test of choice for primary syphilis.[5] It is important to note that sera from up to a third of patients with primary syphilis will be non-reactive when tested with non-treponemal (such as RPR) and treponemalspecific serological assays. Therefore, negative syphilis serology in the presence of a genital ulcer does not exclude syphilis as a diagnosis and blood should be retested after a further 10 - 14 days. In the secondary stage, all serological tests should be positive for syphilis and the diagnosis is therefore easy to confirm as long as the clinician considers the diagnosis. LGV is a less common sexually transmitted disease and is caused by the lymphotropic serovars of C. trachomatis (L1, L2, L3 and their variants).[7] A small, painless genital vesicle or ulcer may be the presenting sign (primary stage) although this is often missed.[1] Most patients in SA present with inguinal lymphadenopathy and bubo formation (the secondary phase, also termed the inguinal syndrome). In addition, proctitis and haemorrhagic procto-colitis (the anorectal syndrome) has been described in women and MSM who practise receptive anal intercourse. Currently, an outbreak of ano-rectal LGV is ongoing among MSM in Western Europe and, to a lesser extent, North America.[8] The outbreak is associated with the newly described L2b variant of C. trachomatis.[9] Many of these MSM are co-infected with HIV and it has been hypothesised that pathogenic C. trachomatis L2b strains may be passed between MSM on sex toys and other fomites. Ano-rectal LGV may also mimic inflammatory bowel disease, particularly Crohn’s disease, on both clinical and histological grounds.[8] Several reports exist of LGV in MSM who have been initially treated by gastroenterologists for inflammatory

bowel disease.[10] The diagnosis of LGV may be missed in such cases due to poor or non-existent sexual history taking by the attending physician. In terms of LGV-associated lymph node histopathology, the presence of tiny necrotic foci with infiltrating neutrophils may be an early finding. These foci enlarge and coalesce to form the typical abscesses of LGV.[2] Epithelioid cells and Langhans-type giant cells line the abscess walls in later stages, and confluence of abscesses with sinus-formation can follow.[1,2] Diagnosis of LGV is best undertaken using specific molecular DNA amplification assays and/or microimmunofluorescence serology. These diagnostic techniques are often only available in specialised reference laboratories. Most peripheral laboratories offer a CFT, but this assay lacks specificity. The CFT titres reported in this case are consistent with previous exposure to chlamydial infection and should not be regarded as indicative of a recent LGV infection. It should be appreciated that, as with syphilis, serology may be negative in the ulcerative stage and it is only a useful diagnostic tool in the context of patients presenting with the inguinal and ano-rectal syndromes.

Conclusion

Taking a detailed medical history is an important part of medical practice, including an adequate sexual history, particularly when a patient has a genital ulcer and inguinal lymphadenopathy. An adequate and relevant history can assist in directed special investigations and treatment. It is also important to remember that sexually transmitted diseases are best considered as a group, rather than individual entities, as they often occur together. The histological findings of the lymph node in the current case prompted the pathologist to request chlamydial serology. If relevant serologic tests had been included initially the diagnosis of syphilis could have been suspected and confirmed on Warthin-Starry stain. Histology of the foreskin ulcer would also have been beneficial in this case. This case highlights the value of a multidisciplinary approach in the management of such cases. Solving complicated cases such as these teaches us valuable lessons that can be used in managing patients in the future. 1. Rosai J. Chapter 21: Rosai and Ackerman’s surgical pathology. In: Lymph Nodes Vol. 2. 10th ed. Elsevier, 2011:1785-1793. 2. Ioachim HL, Medeiros LJ. Chapters 17, 19 and 20. In: Ioachim’s Lymph Node Pathology. 4th ed. Philadelphia. Wolters Kluwer/Lippincott Williams & Wilkins, 2009:110-114, 119-126. 3. Singh AE, Romanowski B. Syphilis: Review with emphasis on clinical, epidemiologic, and some biologic features. Clin Microbiol Rev 1999;12(2):187-209. 4. Fenton KA. A multilevel approach to understanding the resurgence and evolution of infectious syphilis in Western Europe. Euro Surveill 2004;9(12):3-4. 5. French P. Syphilis. BMJ 2007:334(7585):143-147. DOI:10.1136/bmj.39085.518148.BE 6. Heffelfinger JD, Swint EB, Berman SM, et al. Trends in primary and secondary syphilis among men who have sex with men in the United States. Am J Public Health 2007;97(6):1076-1083. DOI:10.2105/AJPH.2005.070417 7. Mabey D, Peeling RW. Lymphogranuloma venereum. Sex Transm Infect 2002;78(2):90-92. DOI:10.1136/sti.78.2.90 8. De Vrieze NH, de Vries HJ. Lymphogranuloma venereum among men who have sex with men. An epidemiological and clinical review. Expert Rev Anti Infect Ther 2014;12(6):697-704. DOI:10.1586/ 14787210.2014.901169 9. Spaargaren J, Fennema HS, Morre SA, et al. New lymphogranuloma venereum Chlamydia trachomatis variant, Amsterdam. Emerg Infect Dis 2005;11(7):1090-1092. 10. Soni S, Srirajaskanthan R, Lucas SB, et al. Lymphogranuloma venereum proctitis masquerading as inflammatory bowel disease in 12 homosexual men. Aliment Pharmacol Ther 2010;32(1):59-65. DOI:10.1111/j.1365-2036.2010.04313.x

Accepted 13 October 2014.

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CASE REPORT

The case of the exploding egg C Brink, G McKay, H Rode Dr Christie Brink is a community-service doctor currently working in the Department of Paediatric Surgery, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa. At the time of the study Ms Gillian McKay was an elective final-year medical student from Lakehead University, Ontario, Canada. Emeritus Professor Heinz Rode is attached to the Department of Paediatric Surgery, Red Cross War Memorial Children’s Hospital. Corresponding author: H Rode (heinz.rode@uct.ac.za)

The vast majority of paediatric burns occur in developing countries, and many of these injuries are entirely preventable. In general, four paediatric injury patterns have been identified in toddlers and infants, who are at a significantly increased risk of burn injuries. Children <2 years of age are often innocent bystanders, but as they grow older physical mobility, social independence and gender-specific high-risk activities come into play. S Afr Med J 2016;106(5):468. DOI:10.7196/SAMJ.2016.v106i5.10662

Microwave ovens provide an efficient method of defrosting, cooking and reheating foods. However, owing to the different properties of food components and microwave ovens, their use leads to differential energy distribution. This results in varying cooking times, differential heating and, in the case of enclosed foods, explosion. Vollmer et al.[1] studied the mechanics of microwave technology and the heating of different components. They particularly observed the heating of 100 fresh and boiled eggs in standard microwave ovens. In most of the eggs only the shell surface cracked, but one of the eggs generated enough energy to cause an explosion and destroy the entire container. The differing thermodynamics of heating an egg can be explained by the high water content of the egg white compared with the more fatty egg yolk. During heating, the water vaporises rapidly, increasing pressure within the egg. On removal from the heat source, expansion of the yolk continues, overcoming the pressure exerted from the egg shell, and finally resulting in an explosion. There have been cases in the literature of exploding microwaved eggs causing corneal laceration and facial burns.[2,3] The Burns Unit at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa has had two such documented burns patients. The first was a 5-year-old child who sustained 4% partial thickness burns to the

lower face and neck. The second was a 4-year-old child who sustained 6% partial thickness burns to the face. Neither child sustained corneal injuries. Both had attempted to microwave eggs, which exploded after removing them from the microwave oven. These burns healed with conservative therapy, but have left the children with depigmented facial scars. These cases highlight the differing thermodynamic reactions that can occur when eggs are heated in microwave ovens. To prevent this from happening, eggshells should be pierced to avoid rapid pressure changes when prepared in such ovens. The eggs should also be allowed time to stand before consumption. Fortunately, the facial injuries are usually relatively constant and mild, but some patients may suffer ocular disturbances and long-term decrease in visual acuity.[4] 1. Vollmer M, Mollmann K-P, Karstadt D. More experiments with microwave ovens. Phys Educ 2004;39(4):346-351. DOI:10.1088/0031-9120/39/4/003 2. Bagrithan S, Rao K, Al-Benna S, O’Boyle CP. Facial burns from exploding microwaved foods: Case series and review. Burns 2015;15:S0305. DOI:10.1016/j.burns.2015.02.014 3. Berestizshevsky S, Goldenberg-Cohen N, Friling R, Weinberger D, Snir M. Ocular injury in children from exploding microwaved eggs. Am J Ophthalmol 2005;139(4):718-719. 4. Wolf Y, Adler N, Hauben DJ. Exploding microwaved eggs – revisited. Burns 2001;27(8):53-55. DOI:10.1016/S0305-4170(01)00041-9

Accepted 24 February 2016.

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REVIEW

Maternal deaths from bleeding associated with caesarean delivery: A national emergency S Fawcus,1 MB BCh, FRCOG; R C Pattinson,2 BSc, MB BCh, FRCOG, MD, FCOG (SA), MMed (O&G); J Moodley,3 MB ChB, FCOG, FRCOG, MD; N F Moran,3,4 MB BCh, MA, FCOG; M G Schoon,5 MMed (O&G), PhD; R E Mhlanga,6 MB ChB, DMCH, FCOG (SA), MPH; S Baloyi,7 MB ChB, CML (Law), CRIA (Theology), Dip Obst, FMAS, Dip MAS, PG Dip Fam Med, MMed (O et G), FCOG (SA); E Bekker,8 BSocSc (Nursing), Dip Nursing Education, MSocSc (Advanced Midwifery and Neonatology); G S Gebhardt,9 MB ChB, MSc (Med Sci), MMed (O&G), FCOG (SA); for the National Committee on Confidential Enquiries into Maternal Deaths epartment of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Cape Town, South Africa, and Deputy Chairperson, D National Committee on Confidential Enquiries into Maternal Deaths, South Africa 2 South African Medical Research Council Maternal and Infant Health Care Strategies Unit and Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, South Africa 3 Department of Obstetrics and Gynaecology, School of Clinical Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa 4 Department of Health, KwaZulu-Natal, South Africa 5 Department of Health, Free State, South Africa 6 Department of Health, Mpumalanga, South Africa 7 Department of Health, Limpopo, South Africa 8 School of Nursing, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa, and Society of Midwives of South Africa 9 Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Tygerberg, Cape Town, South Africa 1

Corresponding author: J Moodley (jmog@ukzn.ac.za)

Maternal deaths associated with caesarean deliveries (CDs) have been increasing in South Africa over the past decade. The objective of this report is to bring national attention to this increasing epidemic of maternal deaths due to bleeding associated with CD in the majority of provinces of the country. Individual chart reviews of women who died from bleeding at or after CD show that 71% had avoidable factors. Among the steps we can take are to improve surgical skills and experience, especially in rural hospitals; to improve clinical observations in the immediate postoperative period and in the postnatal wards; and to ensure that appropriate oxytocic agents are given to prevent postpartum haemorrhage. CEOs and medical managers of health facilities, district clinical specialists, heads of obstetrics and gynaecology, and midwifery training institutions must show leadership and accountability in providing an appropriate environment to ensure that women who require CD receive the procedure for the correct indications and in a safe manner to minimise risks. S Afr Med J 2016;106(5):472-476. DOI:10.7196/SAMJ.2016.v106i5.10821

As early as 2011, the National Committee on Confidential Enquiries into Maternal Deaths (NCCEMD) highlighted the concern of haemorrhage associated with caesarean delivery (CD) in an article published in the SAMJ entitled ‘Haemorrhage associated with caesarean section in South Africa – be aware’.[1] This article drew attention to the findings of the fourth triennial Saving Mothers report for 2005 - 2007,[2] which showed that bleeding associated with caesarean delivery (BLDACD) was the most common causal subcategory of haemorrhage-related maternal death, unlike the pattern in other countries. It also showed that these deaths were increasing over time and were mainly occurring at district and regional hospitals, where most of the CDs were performed. Of most concern, 85% were ‘clearly avoidable’. Multiple instances of health system failure and substandard care were identified as contributing to these preventable deaths from BLDACD. Practical algorithms for the clinical management of haemorrhage at and after CD were presented. The article exhorted the medical and obstetric community to pay attention to this serious problem. Since 2010, there have been several publications and interventions directed to this problem: • The next two triennial reports (2008 - 2010[3] and 2011 - 2013[4]) of the NCCEMD showed further increases in the problem of deaths from BLDACD and described associated avoidable factors.

472

• Since 2008, the Essential Steps in Managing Obstetric Emergencies (ESMOE) training programme[5] has taught practical modules on managing bleeding at CD. This was recently updated with the inclusion of training videos on the surgical management of postpartum haemorrhage (PPH). • Two monographs (guideline pocketbooks) were produced by the NCCEMD on: (i) the management of PPH (2010), with algorithms for its prevention and management;[6] and (ii) caesarean section (CS) (2013), aimed at promoting safer CD.[7] • A PPH training programme, including a lecture, accompanied dissemination of the PPH monograph throughout the country in 2011. • A CME publication on this problem by the NCCEMD appeared in 2012.[8] • A DVD lecture on PPH was developed by the Health Systems Trust in 2014 and circulated to district clinical specialist teams to use for teaching in all health districts.[9] • Publications on maternal mortality and CD in SA[10] and controversies around the use of uterotonics at CD in SA[11] appeared in the SAMJ in 2015. • Obstetrics & Gynaecology Forum published a special edition with all the articles on the theme of safe CD, including an NCCEMD statement on setting minimum standards for safe CD.[12]

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The sixth Saving Mothers report on maternal deaths in SA for 2011 2013 identified 221 deaths due to BLDACD.[4] Fig. 1 shows that this is an increase from 180 during 2008 - 2010, 141 in 2005 - 2007 and 78 in 2002 - 2004. In the two earlier triennia (2002 - 2004 and 2005 - 2007) these numbers may be overestimates, since for those two reports BLDACD deaths were included in a category of ‘uterine trauma’ that included cervical and vaginal trauma in addition to BLDACD. The overall increase in numbers of BLDACD deaths may therefore be even greater. The majority of these deaths (98%) were in the public sector. Fig. 2 gives a yearly breakdown of deaths due to BLDACD from 2008 to 2014 and divides them into those specified to be due to bleeding at CD and to bleeding after CD. These numbers of deaths due to BLDACD over the years obviously need to be viewed in the context of total numbers of CDs performed in SA over the same period (Tables 1 and 2). Total numbers of CDs in the public sector (according to District Health Information System statistics) have shown a steady increase from 372 590 (2002 - 2004) to 655 705 (2011 - 2013). This corresponds to an increase in the CD rate (CDR) from 16.1% to 23.2% between 2002 and 2013. In a recent publication, based on a review of country trends in maternal/newborn mortality rates and CDRs,[13] the World Health Organization (WHO) stated that CDRs above 10 - 15% did not confer benefit in terms of reduction in mortality.[14] However, in the same publication the WHO stated that ‘every effort should be made to provide caesarean sections to women in need, rather than striving to achieve a specific rate’ and ‘Caesarean sections should ideally only be undertaken when medically necessary’. The publication also cited the problem of CD-associated complications. This was quantified in the results of an earlier WHO global survey on maternal and perinatal health which showed that maternal mortality after CD without medical indications is three times higher than after vaginal delivery.[15] If consideration is given to the role of CD in reducing maternal and newborn morbidity (as well as mortality), population CD rates approaching 20 - 25% may be acceptable. The CDR in the private sector in SA is >67%, a level far above that which is necessary to reduce morbidity and mortality.[4] Although numbers of CDs and the CDR have increased in SA, the increase in BLDACD deaths is not merely explained by the increase

250 200 Deaths, n

Trends in maternal mortality due to BLDACD in SA

in the CDR. Table 1 shows that there has been an increase in the case fatality rate (CFR) for CD (maternal deaths from BLDACD × 100 000/total number of CDs performed) from 20.9/100 000 CDs in 2002 - 2004 to 33.6/100 000 in 2011 - 2013. The CFR for CD increased by one-third between 2002 and 2013. This is a finding of major concern, showing that the risk of dying from BLDACD has shown a real increase in SA. This serious finding is illustrated graphically in Fig. 3. Table 2 sets out annual trends of deaths due to BLDACD and CFRs for CDs since 2008. These data come from the two most recent triennial reports[3,4] and the interim report for 2014.[16] It is possible

150 100 50 0

2002 - 2004

2005 - 2007

2008 - 2010

2011 - 2013

Triennium

Fig. 1. Total numbers of maternal deaths due to BLDACD, 2002 - 2013.

Deaths, n

However, despite the above attempts to raise awareness of the problem, the distribution of training materials and the training programmes, the situation has deteriorated. This is in the context of an overall 12.6% reduction in the institutional maternal mortality rate (MMR) in SA in 2011 - 2013 compared with 2008 - 2010, mostly due to a marked reduction in HIV-related mortality, as shown in the sixth triennial Saving Mothers report.[4]

100

At CD

After CD Total

60 40 20 0

2008

2009

2010

2011 Year

2012

2013

2014

Fig. 2. Deaths from bleeding at v. after CD, 2008 - 2014.

Table 1. Comparison between the CD rate for SA and the CFR for bleeding at or after CD Triennium 2002 - 2004 2005 - 2007 2008 - 2010 2011 - 2013 Deaths, n

141

180

221

Total CDs, n

372 590

483 944

563 508

655 705

CFR/100 000 CDs 20.9

29.1

31.8

33.6

SA CD rate, %

17.8

20.0

23.2

16.1

Table 2. Details of deaths due to BLDACD per year, 2008 - 2014 Year Deaths at CD, n

2008

2009

2010

2011

2012

2013

2014

Deaths after CD, n

Total deaths, n

Total CDs, n

181 405

186 438

195 665

209 060

217 871

228 774

236 149

CFR/100 000 CDs

23.7

32.2

38.8

30.1

40.4

30.6

29.6

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40 35

40 35 CFR/100 000 CDs

30 CFR/100 000 CDs

2002 - 2004 2005 - 2007 2008 - 2010 2011 - 2013

25 20 15

30 25 20 15 10

0 10

CD rate (%)

that both indices have stabilised, and that they may have fallen from 2013, but the numbers and rates are still above acceptable levels. Fig. 4 shows CFRs graphically by year from 2008 to 2014. The sixth Saving Mothers report for 2011 - 2013[4] showed that CFRs for CD were higher in provinces where CDs were less frequently done. When the CD rate for each province is compared with its CFR from BLDACD, it is quite striking that more mothers died from BLDACD in the provinces where there was a low overall CD rate. The provinces with a CD rate >23% (e.g. Western Cape, KwaZulu-Natal) had a BLDACD CFR of <20, and those with a CD rate of <17% (e.g. Mpumulanga, Limpopo) had CFRs of >30. This could be due to a variety of reasons, including lack of easy access to safe CD in some provinces, and better retention of skills when a reasonable CD rate is maintained.

Why are deaths from BLDACD occurring and increasing?

There are two aspects to this question: (i) what are the causes of the excessive BLDACD that leads to death? and (ii) why are women dying from BLDACD?

Near-miss audits or monitoring of severe maternal morbidity in SA, although done in a few tertiary centres, is not widespread in SA. This means that accurate statistics on rates of severe morbidity from BLDACD, or the mortality index from this condition, are not available for SA or for different settings and levels of care. Excessive blood loss at CD is defined as blood loss in excess of 1 000 mL. Routine estimation of blood loss at CD is inaccurate and is done by weighing swabs and measuring blood in suction bottles. However, soaking of theatre/bedlinen and contamination with amniotic fluid makes this inaccurate, and it is well known that blood loss at CD is frequently underestimated. Women who die from BLDACD would be expected to have lost more than 2 500 mL blood. Loss of less blood can be fatal if the woman has severe or moderately severe anaemia at the start of the procedure. With blood loss over 2 000 mL, adjunctive coagulopathy occurs to compound the bleeding problem. At the pathological level, the causes of excessive bleeding at CD are uterine atony (commonly after prolonged labour), uterine trauma (excessive bleeding from uterine incision or additional tears laterally into the broad ligament or vertically down the lower segment) and placental site bleeding (associated with placenta praevia, previous CD

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2009

2010

2011

2012

2013

2014

Year

Fig. 3. Association between the CFR for BLDACD and the CD rate between the triennia 2002 - 2004 and 2011 - 2013.

What are the causes of the excessive BLDACD that leads to death?

2008

Fig. 4. CFRs for BLDACD, 2008 - 2014.

and/or morbidly adherent placenta). A rare but frequently fatal cause of mortality due to BLDACD is amniotic fluid embolus-induced coagulopathy. The NCCEMD process involves provincial assessors and the specific topic chapter writer analysing all maternal deaths in SA to determine both the cause and avoidable factors. This means that a detailed folder review has been done for all maternal deaths due to BLDACD. The analysis in the sixth Saving Mothers report,[4] also illustrated in Fig. 2 and Table 2 in this article, found that the majority of deaths were reported as due to BLDACD after CD (179 deaths, 81%) as opposed to at CD (42 deaths, 19%). Unfortunately, in many cases these retrospective folder reviews of deaths could not identify the underlying reason why the woman had BLDACD. The doctor’s theatre notes on the CD were frequently of such poor quality that it was not possible to ascertain estimated blood loss, whether the surgeon had found uterine atony, uterine tears or placental site bleeding, what uterotonics were given, whether vaginal bleeding from uterine atony was looked for before wound closure, or the skill of the operator. In many cases the CD was documented as ‘uneventful’ and had been done very quickly. Nevertheless, it is likely that some pathological event at the operation was responsible for bleeding after the CD, e.g. uterine atony not recognised, uterine angle bleeding not recognised, or bleeding not recognised intraoperatively because of spinal anaesthesia-related hypotension. However, the folder review identified some concerning factors related to BLDACD: • In several cases the CD was not indicated (only early decelerations on the cardiotocograph) or actually contraindicated (abruptio placentae with intrauterine death). • In several cases the CD was done in the second stage of labour because there was insufficient skill to perform assisted vaginal delivery, and in some hospitals assisted deliveries were ‘not done’. A second-stage CD is known to have an increased PPH complication rate. • In several cases the CD was done too late, when labour was obstructed and sepsis had developed.

Why are women dying from BLDACD?

BLDACD is a serious problem, but there are definitive medical and surgical treatments for it, so these women need not die. Whereas the NCCEMD folder review cannot answer question (i) above very well because of insufficient notes about the CD, it can provide better answers for question (ii), which relates to the quality of management of the BLDACD. The following themes emerged from

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folder review of deaths due to BLDACD in the sixth Saving Mothers report:[4] • Seventy-one percent of the deaths were possibly or probably avoidable. • Use of uterotonics was inadequate and poorly documented. It is essential that oxytocin is given at CD for prevention of PPH, and there are clear national guidelines both for the dosages required for its use in prophylaxis and for therapeutic use of oxytocin and other uterotonic agents such as ergometrine, syntometrine, misoprostol and prostaglandin F2-alpha.[6,7,11] Owing to fear of hypotension caused by large intravenous boluses of oxytocin, the doctors providing the anaesthetics appear to be reluctant to give sufficient uterotonics at CD, and this could have contributed to the increasing mortality from BLDACD. In addition, maintaining an oxytocin infusion for 4 - 6 hours after delivery can ensure sustained uterine contraction. If an intravenous infusion cannot be maintained, intramuscular syntometrine or ergometrine can be given postoperatively, provided there are no contraindications. Research on the use of carbetocin as a long-acting oxytocin is awaited, as is research on the use of prophylactic tranexamic acid for the reduction of blood loss at CD. • Surgical skills and experience for CD were insufficient, especially in rural district hospitals. • There was delay in calling for any help in the event of ongoing bleeding (telephonic or consultant on call). • There was insufficient recourse to additional surgical measures such as uterine compression sutures, and balloon tamponade, which can be therapeutic and obviate the need for hysterectomy; delay in performing hysterectomy where skill was available; and failure to use a uterine tourniquet as a temporising measure during patient transfer. • There was delay in and insufficient resuscitation, and lack of skill of the doctor providing the anaesthetic. • Patients were inappropriately discharged from the theatre recovery area while still in hypovolaemic shock. • Poor monitoring in the postnatal ward resulted in late detection of haemorrhage, or delayed action in response to deteriorating vital signs. • There was failure to recognise internal post-CD bleeding. • Doctors at district hospitals were reluctant to reoperate when bleeding was detected after CD, patients instead being transferred to the regional hospital in an unstable condition and dying en route. • Staffing/supplies issues included emergency blood not available, freeze-dried plasma not stocked, and insufficient staff available for monitoring or to cope with a catastrophic emergency such as massive PPH. NB: Underlying health system factors related to lack of leadership, lack of clinical governance and inequitable distribution of human resources (doctors/midwives) are likely to be important determinants of the above problems.

Solutions

There is an urgent need for this epidemic of deaths due to BLDACD in SA to be dealt with. These are mostly young women and ‘mothers to be’ who die from preventable causes. New global goals are for every country to reduce its MMR by twothirds by 2030. This means that SA should reduce its MMR from 140 to <50 deaths per 100 000 live births. This will not be achievable unless deaths from BLDACD are reduced. The solutions are multifactorial and must address the following aspects: • Health systems issues: ensuring safety of CD in appropriately designated sites according to the document on setting minimum standards for safe CD.[12]

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Description of a maternal death from bleeding associated with CD at a district hospital

• Emergency CD in para 1 for cephalopelvic disproprtion. No documentation of prophylactic oxytocin. • PPH in recovery, sent to postnatal ward (PNW) despite low blood pressure and tachycardia. PPH in PNW. Low BP and tachycardia >120/min continued. • Well monitored but no response by nurse to signs of shock. • After 2 hours, doctor was called and gave telephonic advice to give oxytocin 20 IU as an intravenous bolus and 30 IU as an infusion. • Doctor called again when no improvement, and came to see patient. Decided to refer rather than do relaparotomy. • Patient died in lift on way to ambulance. Comment Oxytocin prophylaxis should always be given at CD. The patient should not have been allowed to leave the recovery area with signs of hypovolaemic shock. Despite good monitoring there was a delayed response by the nurse in calling the doctor. The doctor did not assess the patient, and telephonically prescribed an incorrect dose of oxytocin. On subsequent assessment, the doctor decided to refer the patient without performing any definitive treatment. Immediate administration of further uterotonics and a relook laparotomy should have been done before the patient left the recovery area.

• Ensuring access to surgical or anaesthetic skills through reliable and timeous interfacility transport.[17] • Ensuring equitable distribution of appropriately skilled staff to all levels of care, districts and provinces. • Clinical governance and outreach mechanisms to support district doctors and midwives. • Training and skills development to be ongoing for midwives and doctors with the continuation of regular ESMOE/Emergency Obstetric Simulation Training (EOST). This has resulted in a 30% reduction of deaths from obstetric haemorrhage in eight priority districts.[18] • Improved training of health professionals in assisted vaginal delivery. • Surgical skills for CD/complicated CD need to be taught by ESMOE and by ‘hands-on’ supervision. Surgical competence of junior doctors needs to accredited by a senior doctor before they are allowed to operate independently.[12] • Adherence to protocols and algorithms.[5,8] • Monitoring of BLDACD in all facilities conducting CDs needs to be routinely performed, with monthly review of data by senior staff including CEOs and district clinical specialist teams (DCSTs). Charts that monitor trends in BLDACD should be posted on all obstetric theatre noticeboards to ensure a team approach to reducing it and to ensure accountability. (This also requires improved documentation of surgical details at CD.) • Obstetricians in the private sector to be requested to assist the public sector, performing CD lists and assisting with CD skills training. These same recommendations have been listed before in previous publications and guidelines.[1-11] Now is the time for more focused implementation, leadership and accountability. Involvement of CEOs, DCSTs, heads of obstetrics and gynaecology and midwifery at training institutions, and clinical managers is essential for this.

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The paradox in SA is that there is an over 67% CD rate in private facilities. These procedures, many without medical indications, are done in well-resourced facilities by skilled surgeons, whereas in the public sector the CD rate is 23%, the majority of CSs are performed for medical indications only, and most are done in district hospitals with limited human resources, skills and other essential resources. This paradox in our health system today is well illustrated by a comment by Julian Tudor-Hart in 1971[19] suggesting the ‘inverse care law’ for healthcare provision: ‘The inverse care law is the principle that the availability of good medical or social care tends to vary inversely with the need of the population served.’

Urgent activities needed to reduce deaths from bleeding at CD

• Prevention. Ensure that CDs are only done for appropriate indications. Indications for CD should be discussed at district meetings or with senior doctors, and audited using Robson’s classification as recommended in the WHO Statement on Caesarean Section.[14] Improve skills of doctors and midwives in assisted vaginal delivery. • Early recognition. Ensure routine post-CD monitoring with early warning charts, and immediate assessment when BLDACD is suspected. • Immediate resuscitation. Implement algorithms for resuscitation, and ensure availability of fluids, giving sets, blood and freeze-dried plasma. • Immediate medical and surgical treatment to stop the bleeding. Ensure that skills are available, display PPH posters, follow protocols, strengthen teamwork and perform EOST drills. • Emergency transport. Ensure that on-site transport for interfacility transfer is available from level 1 after applying temporary measures to deal with the BLDACD. • Leadership. CEOs and clinical managers to take responsibility for the above activities by ensuring accountability, supplies and staffing, functioning referral systems, regular auditing of BLDACD, and compliance with protocols. To achieve the above, facilities and provinces need to prioritise maternal care and step up their governance and accountability processes and prioritise to ensure CD safety.

Suggested key actions to be implemented immediately

• All hospitals conducting CDs must ensure that they comply with the minimum standards for safe CD in SA. Hospitals that currently do not comply must be supported by their provincial health departments to make the necessary changes to ensure compliance as a matter of urgency. • All hospitals conducting CDs must have on-site ESMOE trainers, who run a regular programme of ESMOE training for all doctors at the hospital involved in CDs (this includes sessional doctors and

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midwives working in the maternity section). The ESMOE training must cover the management of obstetric haemorrhage and surgical skills, incorporating EOST (emergency drills) training • District clinical specialist teams and specialists at regional or tertiary centres should prioritise training in CD technique (through direct supervision in theatre) for medical officers, registrars and interns, ensuring that it is a regular key activity in their monthly schedule. • Every facility performing CD must monitor and audit BLDACD by recording the numbers of women who bleed more than 1 000 mL at CD and/or require additional surgical measures/ blood transfusion after CD. Findings to be discussed at facility maternal mortality and morbidity meetings. Caesarean sections were introduced in obstetrics to save lives, not to cause additional mortality. They need to be done for appropriate indications and safely for all women, including those who are poor. Women’s lives matter! References 1. Fawcus S, Moodley J, for the National Committee on Confidential Enquiries into Maternal Deaths. Haemorrhage associated with caesarean section in South Africa – be aware. S Afr Med J 2011;101(5):306-309. 2. Pattinson RC, ed. Saving Mothers: Fourth Report on Confidential Enquiries into Maternal Deaths in South Africa, 2005-2007. Pretoria: National Department of Health, 2010. 3. Pattinson RC, ed. Saving Mothers: Fifth report on Confidential Enquiries into Maternal Deaths in South Africa 2008-2010. Pretoria: National Department of Health, 2012. 4. Pattinson RC, ed. Saving Mothers 2011-2013: The Sixth Report of the National Committee for Confidential Enquiries into Maternal Deaths in South Africa. Pretoria: Government Printer, 2014. 5. Pattinson RC, ed. Essential Steps in Managing Obstetric Emergencies (ESMOE) training policy. January 2009. ww.ESMOE.co.za (accessed 8 April 2016). 6. National Committee on Confidential Enquiries into Maternal Deaths. A Monograph of the Management of Postpartum Haemorrhage. Pretoria: National Department of Health, 2010. 7. National Committee on Confidential Enquiries into Maternal Deaths. A Monograph on Caesarean Section. Pretoria: National Department of Health, 2013. 8. Fawcus S, Moodley J, for the National Committee on Confidential Enquiries into Maternal Deaths. Prevention and management of blood loss at caesarean section. CME 2012;30(4):138-142. 9. Health Systems Trust. Management of postpartum haemorrhage training videos, Part I and Part II, 2014. http://www.hst.org.za/projects/reducing-maternal-and-child-mortality-through-strengtheningprimary-healthcare-rmch (accessed 22 March 2016). 10. Gebhardt GS, Fawcus S, Moodley J, Farina Z. Maternal death and caesarean section in South Africa: Results from the 2011 - 2013 Saving Mothers Report of the National Committee for Confidential Enquiries into Maternal Deaths. S Afr Med J 2015;105(4):287-291. DOI:10.7196/SAMJ.9531 11. Farina Z, Fawcus S. Management of obstetric haemorrhage. Oxytocin ensuring appropriate use and balancing efficacy with safety. S Afr Med J 2015;105(4):271-274. DOI:10.7196/SAMJ.9179 12. Moran N, for the NCCEMD. Setting minimum standards for caesarean delivery in South Africa. Obstetrics & Gynaecology Forum 2015;25(3):41-44. 13. Ye J, Betran AP, Velo MG, Souza JP, Zhang J. Searching for the optimal rate of medically necessary caesarean delivery. Birth 2014;41(3):237-244. DOI:10.1186%2Fs12978-015-0043-6 14. World Health Organization. WHO Statement on Caesarean Section: Executive Summary. Geneva: WHO, 2015. http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/csstatement/en/ (accessed 22 March 2016). 15. Souza JP, Gulmezoglu AM, Lumbiganon P, et al., for the WHO Global Survey on Maternal and Perinatal Health Research Group. Caesarean section without medical indication is associated with an increased risk of adverse short-term maternal outcomes: The 2004-2008 WHO Global Survey on Maternal and Perinatal Health. BMC Med 2010;8:71. 16. National Committee on Confidential Enquiries into Maternal Deaths. Saving Mothers, 2014: Interim Report. Pretoria: Department of Health, 2014. 17. Schoon MG. Impact of inter-facility transport on maternal mortality in the Free State Province. S Afr Med J 2013;103(8):534-537. DOI:10.7196/SAMJ.6828 18. Pattinson RC. ESMOE-EOST scale up programme: Interim report on impact. Presented at the 35th Priorities in Perinatal Care Conference, Bela Bela, South Africa, 8 - 11 March 2016. 19. Tudor-Hart J. The inverse care law. Lancet 1971;297(7696):405-412. DOI:10.1016/S01406736(71)92410-X

Accepted 31 March 2016.

May 2016, Vol. 106, No. 5

RESEARCH

Emerging trends in non-communicable disease mortality in South Africa, 1997 - 2010 B Nojilana,1 MPH; D Bradshaw,1 DPhil, MSc; V Pillay-van Wyk,1 PhD (Paediatrics), MPH (Epidemiology and Biostatistics); W Msemburi,1 MPhil (Demography), BSc Hons (Statistics); R Laubscher,2 BCom (Maths); N I M Somdyala,1 MDS, BCur; J D Joubert,1 PhD, MA (Socio-linguistics); MA (Demography); P Groenewald,1 MB ChB, MPH; R E Dorrington,3 MPhil (FASSA), BCom, BA, BSc Hons; on behalf of the South African National Burden of Disease team urden of Disease Research Unit, South African Medical Research Council, Cape Town, South Africa B Biostatistics Unit, South African Medical Research Council, Cape Town, South Africa 3 Centre for Actuarial Research, Faculty of Commerce, University of Cape Town, South Africa 1 2

Corresponding author: B Nojilana (beatrice.nojilana@mrc.ac.za)

Objectives. National trends in age-standardised death rates (ASDRs) for non-communicable diseases (NCDs) in South Africa (SA) were identified between 1997 and 2010. Methods. As part of the second National Burden of Disease Study, vital registration data were used after validity checks, proportional redistribution of missing age, sex and population group, demographic adjustments for registration incompleteness, and identification of misclassified AIDS deaths. Garbage codes were redistributed proportionally to specified codes by age, sex and population group. ASDRs were calculated using mid-year population estimates and the World Health Organization world standard. Results. Of 594 071 deaths in 2010, 38.9% were due to NCDs (42.6% females). ASDRs were 287/100 000 for cardiovascular diseases (CVDs), 114/100 000 for cancers (malignant neoplasms), 58/100 000 for chronic respiratory conditions and 52/100 000 for diabetes mellitus. An overall annual decrease of 0.4% was observed resulting from declines in stroke, ischaemic heart disease, oesophageal and lung cancer, asthma and chronic respiratory disease, while increases were observed for diabetes mellitus, renal disease, endocrine and nutritional disorders, and breast and prostate cancers. Stroke was the leading NCD cause of death, accounting for 17.5% of total NCD deaths. Compared with those for whites, NCD mortality rates for other population groups were higher at 1.3 for black Africans, 1.4 for Indians and 1.4 for coloureds, but varied by condition. Conclusions. NCDs contribute to premature mortality in SA, threatening socioeconomic development. While NCD mortality rates have decreased slightly, it is necessary to strengthen prevention and healthcare provision and monitor emerging trends in cause-specific mortality to inform these strategies if the target of 2% annual decline is to be achieved. S Afr Med J 2016;106(5):477-484. DOI:10.7196/SAMJ.2016.v106i5.10674

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i5.10674

National priorities for perioperative research in South Africa B M Biccard,1,2 PhD; C S Alphonsus,2 FCA (SA); D G Bishop,2 FCA (SA); L Cronje,2 FCA (SA); H-L Kluyts,3 MMed (Anaes); B Kusel,2 FCA (SA), MMed; S Maswime,4 FCOG (SA), MMed; R Oodit,5 FCS (SA); A R Reed,1 FRCA, MMed (Anaes); A M Torborg,2 FCA (SA); R Wise,2 FCA (SA), MMed (Anaes), Cert Crit Care (SA); on behalf of the South African Perioperative Research Group national research priority-setting working group epartment of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, D South Africa 2 Perioperative Research Group, Discipline of Anaesthesiology and Critical Care, School of Clinical Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa 3 Department of Anaesthesiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa 4 Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 5 Discipline of General Surgery, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa, and Matley and Partners, Cape Town 1

Corresponding author: B M Biccard (bruce.biccard@uct.ac.za)

May 2016, Print edition

RESEARCH

Background. Perioperative research is currently unco-ordinated in South Africa (SA), with no clear research agenda. Objective. To determine the top ten national research priorities for perioperative research in SA. Methods. A Delphi technique was used to establish consensus on the top ten research priorities. Results. The top ten research priorities were as follows: (i) establishment of a national database of (a) critical care outcomes, and (b) critical care resources; (ii) a randomised controlled trial of preoperative B-type natriuretic peptide-guided medical therapy to decrease major adverse cardiac events following non-cardiac surgery; (iii) a national prospective observational study of the outcomes associated with paediatric surgical cases; (iv) a national observational study of maternal and fetal outcomes following operative delivery in SA; (v) a steppedwedge trial of an enhanced recovery after surgery programme for (a) surgery, (b) obstetrics, (c) emergency surgery, and (d) trauma surgery; (vi) a stepped-wedge trial of a surgical safety checklist on patient outcomes in SA; (vii) a prospective observational study of perioperative outcomes after surgery in district general hospitals in SA; (viii) short-course interventions to improve anaesthetic skills in rural doctors; (ix) studies of the efficacy of simulation training to improve (a) patient outcomes, (b) team dynamics, and (c) leadership; and (x) development and validation of a risk stratification tool for SA surgery based on the South African Surgical Outcomes Study (SASOS) data. Conclusions. These research priorities provide the structure for an intermediate-term research agenda. S Afr Med J 2016;106(5):485-488. DOI:10.7196/SAMJ.2016.v106i5.10269

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i5.10269

Active surveillance of hospital-acquired infections in South Africa: Implementation, impact and challenges W Lowman, MB BCh, MMed, FC Path (SA) Vermaak and Partners Pathologists, Wits Donald Gordon Medical Centre, Johannesburg, South Africa, and Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg Corresponding author: W Lowman (warren.lowman@wits.ac.za)

Background. Hospital-acquired infections (HAIs) are a significant although unquantified burden in South Africa. Lack of adequate surveillance compounds this problem. Objective. To report on the establishment and outcomes of a unit-specific surveillance system for hospital-acquired infections, based on international standards, in a private academic hospital. Methods. Active unit-specific surveillance of device-associated infections (DAIs) was introduced over a 2-year period. The surveillance system was based on the US National Healthcare Safety Network (NHSN) utilising standardised definitions. Analysis of DAI rates and device utilisation was done according to Centers for Disease Control and Prevention methods. Comparative analysis using study-derived annualised data and existing NHSN data was done. Results. Surveillance results of DAI rates showed significant reductions in intensive care unit-related ventilator-associated pneumonia (42%) and central line-associated bloodstream infections (100%) over a 3-year period. Substantial variations in DAI rates and utilisation ratios between wards highlight the importance of unit-specific surveillance. Conclusions. Active surveillance requires a significant investment in resources and is a sustained operational challenge, although equally significant benefits are derived from a better understanding of HAIs with more targeted interventions and efficient use of resources. A robust surveillance system is an essential component of any healthcare infection prevention and control programme and is a prerequisite to contextualising the HAI burden of hospitals. S Afr Med J 2016;106(5):489-493. DOI:10.7196/SAMJ.2016.v106i5.10783

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i5.10783

May 2016, Print edition

RESEARCH

The costs of delivering human papillomavirus vaccination to Grade 4 learners in KwaZulu-Natal, South Africa I Moodley,1 PhD; N Tathiah,2 BSc Hons, MB ChB, Dip HIV Man (SA), MS (Epi), FCPHM, MMed; B Sartorius,3 PhD ealth Outcomes Research Unit, Discipline of Public Health Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, H University of KwaZulu-Natal, Durban, South Africa 2 School of Nursing and Public Health, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa 3 Discipline of Public Health Medicine, School of Nursing and Public Health, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa 1

Corresponding author: I Moodley (moodleyi15@ukzn.ac.za)

Background. The national human papillomavirus (HPV) vaccination roll-out in South Africa provides two doses of Cervarix to all female Grade 4 learners in state schools. This study estimated the costs of vaccinating all learners in KwaZulu-Natal Province (females or males and females) using either the two- or three-dose strategies for both the bivalent and quadrivalent vaccines. Objective. To determine costs of the HPV vaccination programme in KwaZulu-Natal. Methods. Costs were determined adapting World Health Organization vaccination costing guidelines. Results. The 2014 current cost of delivering three doses of Gardasil was ZAR510 per learner. The projected cost of delivering Cervarix to female learners at two or three doses over the period 2014 - 2018, adjusted for inflation, was ZAR172 717 342 and ZAR250 048 426, respectively. Similarly, the cost for Gardasil at these doses was ZAR197 482 200 and ZAR287 194 361, respectively. For male and female learners the cost for Cervarix over this period at two or three doses was ZAR337 101 132 and ZAR540 150 713, respectively. Similarly, the cost for Gardasil at these doses was ZAR426 597 971 and ZAR620 392 784, respectively. Accounting for population variation for females over 5 years, the cost of two doses of Cervarix ranged from ZAR168 888 677 to ZAR 176 545 977 at the lower and upper 95% confidence intervals (CIs), respectively. For three doses the cost ranged from ZAR244 505 544 to ZAR255 591 263 at the lower and upper 95% CIs, respectively. Similarly, the cost for two doses of Gardasil ranged from ZAR193 104 566 to ZAR201 859 798. For three doses the cost ranged from ZAR280 828 057 to ZAR293 560 614. Conclusion. This study gives decision makers a basis for structured planning and cost apportionment to ensure effective roll-out of the HPV vaccination programme. S Afr Med J 2016;106(5):497-501. DOI:10.7196/SAMJ.2016.v106i5.9988

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i5.9988

Intimate partner violence in early adolescence: The role of gender, socioeconomic factors and the school A J Mason-Jones,1,2 PhD, MPH, MSc, RGN, RHV; P De Koker,2,3 MA; S M Eggers,4 MSc; C Mathews,5,2 PhD; M Temmerman,3,6 MB ChB, PhD; E Leye,3 PhD; P J de Vries,2 MB ChB, MRCPsych, PhD; H de Vries,4 PhD epartment of Health Sciences, University of York, UK D Adolescent Health Research Unit, Division of Child and Adolescent Psychiatry, Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, South Africa 3 International Centre for Reproductive Health, Faculty of Medicine and Health Sciences, Ghent University, Belgium 4 Department of Health Promotion, School for Public Health and Primary Care (CAPHRI), Maastricht University, Netherlands 5 Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa 6 Center of Excellence for Women and Child Health, Aga Khan University, Nairobi, Kenya 1 2

Corresponding author: A J Mason-Jones (amanda.mason-jones@york.ac.uk)

Background. Intimate partner violence (IPV) among adolescents is common worldwide, but our understanding of perpetration, gender differences and the role of social-ecological factors remains limited.

May 2016, Print edition

RESEARCH

Objectives. To explore the prevalence of physical and sexual IPV perpetration and victimisation by gender, and associated risk and protective factors. Methods. Young adolescents (N=2 839) from 41 randomly selected public high schools in the Western Cape region of South Africa (SA), participating in the PREPARE study, completed a self-administered questionnaire. Results. The participants’ mean age was 13.65 years (standard deviation 1.01), with 19.1% (541/2 839) reporting being victims/survivors of IPV and 13.0% (370/2 839) reporting perpetrating IPV. Girls were less likely to report being a victim/survivor of physical IPV (odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57 - 0.92) and less likely to be a perpetrator of sexual IPV than boys (OR 0.33; 95% CI 0.21 - 0.52). Factors associated with perpetration of physical and sexual IPV were similar and included being a victim/survivor (physical IPV: OR 12.42; 95% CI 8.89 - 17.36, sexual IPV: OR 20.76; 95% CI 11.67 - 36.93), being older (physical IPV: OR 1.26; 95% CI 1.08 - 1.47, sexual IPV: OR 1.36; 95% CI 1.14 - 1.62 ), having lower scores on school connectedness (physical IPV: OR 0.59; 95% CI 0.46 - 0.75, sexual IPV: OR 0.56; 95% CI 0.42 - 0.76) and scoring lower on feelings of school safety (physical IPV: OR 0.66; 95% CI 0.57 - 0.77, sexual IPV: OR 0.50; 95% CI 0.40 - 0.62). Conclusions. Physical and sexual IPV was commonly reported among young adolescents in SA. Further qualitative exploration of the role of reciprocal violence by gender is needed, and the role of ‘school climate’-related factors should be taken into account when developing preventive interventions. S Afr Med J 2016;106(5):502-509. DOI:10.7196/SAMJ.2016.v106i5.9770

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i5.9770

Publication trends of clinical trials performed in South Africa M Sibanda,1,2 BPharm Hons; R S Summers,1 BPharm, MSc, PhD; J C Meyer,1 BPharm, MSc (Med), PhD 1 2

Department of Pharmacy, Sefako Makgatho Health Sciences University, Ga-Rankuwa, Pretoria, South Africa Inqaba Biotechnical Industries (Pty) Ltd, Pretoria, South Africa

Corresponding author: M Sibanda (mncengelis@gmail.com)

Background. Investigators and sponsors of clinical trials have an ethical obligation to disseminate clinical trial results, whether positive or negative, in a timely manner. Objectives. To determine the publication rate and average time to reporting for clinical trials carried out in South Africa (SA) and to explore factors indicating whether a study is published or not. Methods. A registry-based quantitative retrospective analysis of 79 SA clinical trials for new medicines registered between January 2008 and December 2010 was performed. The relevant trial identification number in the register was used to track all peer-reviewed publications subsequent to registration. Tracking of clinical trials was done through a systematic literature search of the electronic journal databases of the South African Medical Journal (SAMJ), the Cochrane Library, Public Library of Science Medical Journal (PLoS Medicine) and BioMed Central, all of which are indexed on MEDLINE via PubMed. In addition, a manual search of the Open Access Journal of Clinical Trials databases and reference lists on articles related to the trial medicine was performed. Results. Of the 79 clinical trials surveyed, 72 were concluded by December 2014. Only 35 (48.6%) of them had the results published in a peer-reviewed journal, the current benchmark for dissemination of trial results. The majority (82.9%) of those published had a positive outcome. Of the 35 trials that were published, 77.1% were published within 2 years. The average time from completion to initial reporting was 22 months. Fewer than half (40.5%) of the clinical trials surveyed were placebo controlled. Conclusion. The absence of complete outcomes data from SA clinical trials warrants utmost attention. The study puts forward a case to the regulatory body and research ethics committees to compel all data from clinical trials to be made accessible to clinicians and the public in general by being published in an easily accessible form and in a timely manner. S Afr Med J 2016;106(5):519-523. DOI:10.7196/SAMJ.2016.v106i5.9952

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i5.9952

May 2016, Print edition

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GP Locum/ AssistantJohannesburg North

At Wynberg Pharmacy In Cape Town General Practitioner Required An onsite GP required for a busy pharmacy in Wynberg, Cape Town. Consulting hours: Mon-Fri 5pm-9pm Saturdays 1pm-6pm

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Fluency in French is recommended

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Anatomical Pathologist: We are looking for a colleague to join us in our growing private practice. We are a well established, dynamic, independent laboratory in Cape Town offering specialised Anatomical Pathology services. Please contact Dr Roger James for more information: email roger@jdwpathology.co.za, phone 0765907766.

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CLINICAL PATHOLOGISTS / CLINICAL MICROBIOLOGISTS KLERKSDORP/POTCHEFSTROOM/WELKOM/EAST LONDON/VEREENIGING/NAMIBIA We are a dynamic, cutting edge, purpose driven and values based Pathology and Diagnostic laboratory, caring for the health of patients, while offering support and expertise to medical professionals. We are seeking appropriate individuals to assist us in our next phases of growth. We have an opportunity for an Anatomical Pathologist to work at PathCare Namibia and a Clinical Pathologist to work at our East London branch, as well as a vacancy for a Clinical Pathologist to work at our Welkom branch and a Clinical Microbiologist for our Vereeniging branch. We have further vacancies for a Clinical Microbiologist/Clinical Pathologist to work at our Klerksdorp and Potchefstroom branch. If you are a creative, dynamic and passionate professional who adopts a customer-centric approach, is respectful and accountable and possesses a welldeveloped work ethic, while working with diverse groups of people and excelling within a multi-cultural environment then this opportunity could be what you are looking for. Requirements: • • • •

M. Med or FC Pathology (SA) Current registration with the HPCSA as a Pathologist Relevant working experience High level of ethics and integrity

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True (A) or false (B): SAMJ Maternal deaths from bleeding associated with caesarean delivery (CD) 1. The majority of deaths from bleeding associated with CD in South Africa (SA) were in the public sector. 2. Women who die from bleeding associated with CD would be expected to have lost more than 2 500 L of blood. Emerging trends in non-communicable disease (NCD) mortality in SA, 1997 - 2010 3. Stroke was the leading NCD cause of death, accounting for 17.5% of total NCD deaths. Active surveillance of hospital-acquired infections in SA 4. SA has no standardised surveillance system for hospital-acquired infections. 5. The majority of surveillance activities in both the public and private sectors are laboratory based. The costs of delivering human papillomavirus vaccination to grade 4 learners in KwaZulu-Natal, SA 6. Cervical cancer is the second most common cancer after breast cancer in SA women. 7. The World Health Organization has recommended that both males and females are vaccinated against HPV in all economic settings. Intimate partner violence in early adolescence 8. Sexual violence is the most common form of intimate partner violence. Identity (ID) tags: A vector for cross-infection? (online only) 9. White coats, neckties and stethoscopes have all been implicated in cross-infection in hospitals. 10. Lanyards were found not to be as contaminated as ID tags.

CME Acute viral bronchiolitis in SA: Viral aetiology and clinical epi demiology 11. Bronchiolitis is a viral-induced lower respiratory tract infection (LRTI) that occurs predominantly in children <2 years of age, particularly infants. 12. Epidemiological studies on bronchiolitis often include all children presenting with physician-diagnosed LRTI and may overestimate the true incidence of bronchiolitis alone. 13. Many studies currently show rhinovirus to be associated with bronchiolitis. 14. Respiratory syncytial virus is the most common cause of moderate or severe bronchiolitis and is a leading cause of LRTI among young children. 15. Epidemiological studies have identified a strong temporal associa tion between some respiratory viruses and invasive pneumococcal disease. Acute viral bronchiolitis in SA: Intensive care management for severe disease 16. Most admissions for bronchiolitis require intensive care manage ment. 17. Risk factors for severe disease include prematurity and immuno suppression. 18. In South Africa, 20% of children admitted to a paediatric intensive care unit (PICU) had positive respiratory viral isolates, with symptomatic respiratory disease. 19. The mainstay of bronchiolitis management in the PICU and neo natal ICU is supportive. 20. Intubation and mechanical ventilation are recommended for all patients with bronchiolitis admitted to the ICU.

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May 2016, Print edition

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References: 1. Kalaitzakis E, Björnsson E. A review of esomeprazole in the treatment of gastroesophageal reflux disease (GERD). Therapeut & Clin Risk Management 2007;3(4):653-663. 2. Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of Ulcers by Esomeprazole in At-Risk Patients Using Non-Selective NSAIDs and COX-2 Inhibitors. Am J Gastroenterol 2006;101:701-710. 3. Data on File: Ranbaxy (SA) (Pty) Ltd. S4 Nexipraz® 20 Gastro-resistant tablets. Reg. No. 45/11.4.3/0125. Each gastro-resistant tablet contains esomeprazole magnesium 20,7 mg equivalent to esomeprazole 20 mg. Contains sugar. S4 Nexipraz® 40 Gastro-resistant tablets.Reg. No. 45/11.4.3/0126. Each gastro-resistant tablet contains esomeprazole magnesium 41,4 mg equivalent to esomeprazole 40 mg. Contains sugar. For full prescribing information please refer to the package insert approved by the medicines regulatory authority. Applicant: Ranbaxy (SA) (Pty) Ltd, a SUN PHARMA company, Ground Floor, Tugela House, Riverside Office Park, 1303 Heuwel Avenue, Centurion, 0046.Tel: +27 12 643 2000. Fax: +27 12 643 2001. www.sunpharma.com.

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