SAMJ Vol 108, No 7 (2018) by HMPG

JULY 2018

PRINT EDITION

CME Paediatric asthma in South Africa (part 1) IN PRACTICE Antimicrobial stewardship in a rural regional hospital Curbing tobacco use: Not working yet CASE REPORT Rapunzel syndrome RESEARCH Forecasting monthly malaria cases in KwaZulu-Natal Increasing incidence of infective endocarditis with recreational drug abuse Hepatitis C in men who have sex with men Hypertension in elective surgery patients

JULY 2018 PRINT EDITION

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

FROM THE EDITOR 4

… while Rome burns B Farham

EDITOR’S CHOICE

EDITORS EMERITUS Daniel J Ncayiyana, MD (Groningen), FACOG, MD (Hon), FCM (Hon) JP de V van Niekerk, MD, FRCR

CORRESPONDENCE 8

Contribution of congenital disorders to neonatal mortality in South Africa H L Malherbe, A L Christianson, D Woods, C Aldous

Post-pulmonary tuberculosis complications in South Africa and a potential link with pulmonary hypertension: Premise for clinical and scientific investigations B W Allwood, G J Maarman, C G Kyriakakis, A F Doubell

Completing laboratory request forms diligently – when did it become optional? C J Opperman

IZINDABA 14

16 18

30 days in medicine B Farham BOOK REVIEWS High Performance in Hospital Management: A Guideline for Developing and Developed Countries I Woolard

HMPG CEO AND PUBLISHER Hannah Kikaya Email: hannahk@hmpg.co.za MANAGING EDITORS Claudia Naidu Naadia van der Bergh TECHNICAL EDITORS Emma Buchanan Kirsten Morreira Paula van der Bijl PRODUCTION MANAGER Emma Jane Couzens

Beyond Evolutionary Psychology: How and Why Neuropsychological Modules Arise A S Mall

SENIOR DESIGNER Clinton Griffin

EDITORIAL

CHIEF OPERATING OFFICER Diane Smith | Tel. 012 481 2069 Email: dianes@hmpg.co.za

National coverage of reflex cryptococcal antigen screening: A milestone achievement in the care of persons with advanced HIV disease N P Govender, D K Glencross

CONTINUING MEDICAL EDUCATION 21

ASSOCIATE EDITORS Q Abdool Karim, A Dhai, R C Pattinson, A Rothberg, A A Stulting, J Surka, B Taylor, M Blockman, J M Pettifor, W Edridge, R P Abratt, D L Clarke

GUEST EDITORIAL Paediatric asthma in South Africa: A case of hunger in times of plenty R Masekela ARTICLES The increasing burden of asthma in South African children: A call to action R Masekela, C L Gray, R J Green, A I Manjra, F E Kritzinger, M Levin, H Zar, on behalf of the South African Childhood Asthma Working Group (SACAWG) The diagnosis of asthma in children: An evidence-based approach to a common clinical dilemma R Masekela, S M Risenga, O P Kitchin, D A White, G Davis, P Goussard, A I Manjra, F E Kritzinger, M Levin, H Zar, R J Green, on behalf of the South African Childhood Asthma Working Group (SACAWG)

IN PRACTICE 32

ISSUES IN MEDICINE Antimicrobial stewardship in a rural regional hospital – growing a positive culture E Junaid, L Jenkins, H Swanepoel, Z North, T Gould

ISSUES IN PUBLIC HEALTH Current strategies are inadequate to curb the rise of tobacco use in Africa N Peer

MEDICINE AND THE LAW Obtaining informed consent for a sterilisation in the light of recent case law C J Badul, A Strode, P P Singh

CASE REPORT Rapunzel syndrome: A South African variety J Plaskett, G Chinnery, D Thomson, S Thomson, B Dedekind, E Jonas

July 2018, Print edition

SALES MANAGER (CAPE TOWN) Azad Yusuf JOURNAL ADVERTISING Reneé Hinze Ladine van Heerden Makhadzi Mulaudzi Charmalin Comalie ONLINE SUPPORT Gertrude Fani FINANCE Tshepiso Mokoena HMPG BOARD OF DIRECTORS Prof. M Lukhele (Chair), Dr M R Abbas, Mrs H Kikaya, Dr M Mbokota, Dr G Wolvaardt ISSN 0256-9574 HMPG website: www.hmpg.co.za SAMA website: www.samedical.org Journal website: www.samj.org.za

RESEARCH

ONLINE CONTENTS LISTED IN Index Medicus (Medline) Excerpta Medica (EMBASE) Biological Abstracts (BIOSIS) Science Citation Index (SciSearch) Directory of Open Access Journals (DOAJ) Current Contents/Clinical Medicine

Hepatitis C prevalence in HIV-infected heterosexual men and men who have sex with men N A Gogela, M W Sonderup, K Rebe, T Chivese, C W Spearman

A Seasonal Autoregressive Integrated Moving Average (SARIMA) forecasting model to predict monthly malaria cases in KwaZulu-Natal, South Africa* O Ebhuoma, M Gebreslasie, L Magubane

SAMJ SUBSCRIPTION RATES Local subscriptions ZAR1 632.00 p.a. Foreign subscriptions ZAR3 744.00 p.a. Single copies ZAR136.00 local, ZAR312.00 foreign

Describing key performance indicators for waiting times in emergency centres in the Western Cape Province, South Africa, between 2013 and 2014* K Cohen, S Bruijns

Members of the South African Medical Association receive the SAMJ only on request, as part of their membership benefit.

Striking increase in the incidence of infective endocarditis associated with recreational drug abuse in urban South Africa* R Meel, M R Essop

A multicentre, cross-sectional study investigating the prevalence of hypertensive disease in patients presenting for elective surgery in the Western Cape Province, South Africa* K van der Spuy, M Crowther, M Nejthardt, F Roodt, J Davids, J Roos, E Cloete, T Pretorius, G Davies, J van der Walt, C van der Westhuizen, M Flint, J Swanevelder, B Biccard

Quality of counselling and support provided by the South African National AIDS Helpline: Content analysis of mystery client interviews* N Arullapan, M F Chersich, N Mashabane, M Richter, N Geffen, J Vearey, L Jankelowitz, F Scorgie, W D F Venter

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 Suite 11, Lonsdale Building, Lonsdale Way, Pinelands, 7405 Tel. 021 532 1281 | Cell. 072 635 9825 Email: publishing@hmpg.co.za

*Abstract only, full article available online. CAREERS AND CLASSIFIEDS CPD QUESTIONS

Please submit all letters and articles for publication online at http://www.editorialmanager.com/samj © 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. https://creativecommons.org/licenses/bync/4.0 Printed by TANDYM PRINT

JULY 2018

PRINT EDITION

CME Paediatric asthma in South Africa (part 1) IN PRACTICE Antimicrobial stewardship in a rural regional hospital

Background photo: Theatre team | Shaun Swingler

Curbing tobacco use: Not working yet CASE REPORT Rapunzel syndrome

Box photos: Poster designed to help make nurses aware of antibiotic stewardship (detail) | George Hospital; Cigarette smoking | Shutterstock; Rapunzel syndrome | Plaskett et al.

July 2018, Print edition

RESEARCH Forecasting monthly malaria cases in KwaZulu-Natal Increasing incidence of infective endocarditis with recreational drug abuse Hepatitis C in men who have sex with men Hypertension in elective surgery patients

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

FROM THE EDITOR

… while Rome burns Trawling the news these days is becoming a depressing affair if you care about healthcare in South Africa (SA). A headline in Bizcommunity.com, ‘Is Motsoaledi fiddling while healthcare is burning?’,[1] ‘Tygerberg Hospital must “be shut down and replaced”’,[2] and in the midst of all this, ‘NHI open for public comment soon’[3] – these news stories have flooded the media in response to the recent tabling of a report by the Office of Health Standards Compliance (OHSC) to Parliament. In this report, only five of the 696 hospital and clinics that were inspected in 2016 - 2017 complied with the Department of Health’s norms and standards to achieve an 80% ‘pass mark’. And these inspections covered only one-fifth of SA’s 3 816 public health facilities. Parliament’s Portfolio Committee on Health was told on Wednesday 6 June 2018 that Tygerberg Hospital, the Western Cape’s largest hospital, is in such a bad state that it needs to be shut down and replaced. Dr Beth Engelbrecht, Head of the Western Cape Department of Health, told the committee that it would cost an estimated ZAR10 billion to replace the hospital. At the same time Health-e News reports that ‘Limpopo health system is on the verge of collapse’,[4] citing the results of a surprise visit paid to Polokwane Provincial Hospital by the South African Human Rights Commission, who found that expired food and medicines were being given to patients. Filing systems are in such chaos that new files are opened each time a patient visits the hospital because old files are lost. Hundreds of patients are transferred from underperforming regional hospitals, and a shortage of consulting rooms means that consultations are held in corridors, with scant regard for privacy or confidentiality. As all this is hitting the news, our Minister of Health, Aaron Motsoaledi, is telling anyone who will listen that it is all an exaggeration and that he does not ‘know the yardstick that was used to arrive at a conclusion of collapse. Surely healthcare systems

are measured on some form of scientific yardstick to arrive at any conclusion’, apparently discounting the methods used by the OHSC – the statutory body charged with assessing the quality of hospitals and clinics. This same body will be responsible for determining whether public health facilities are adequate for accreditation under the National Health Insurance (NHI) programme. The Minister does concede that overcrowding is a problem, but went on to point out the merits of the decentralised medication pick-up points, strangely disregarding the frequently reported stock-outs of medication at these facilities. And he waxed lyrical about our TB and HIV medication programmes, pointing out their sheer scale, in itself something of an indication of failures elsewhere in the public healthcare system. We need a functioning public healthcare system in SA. Introducing NHI while our public facilities are in this parlous state is an enormous mistake. First fix what is broken – hopefully not broken beyond repair – and then perhaps think about changing the system under which it is administered. Bridget Farham Editor ugqirha@iafrica.com 1. Bizcommunity.com. http://www.bizcommunity.com/Article/196/330/177967.html#topstory (accessed 12 June 2018). 2. IOL. https://www.iol.co.za/capeargus/news/tygerberg-hospital-must-be-shut-down-andreplaced-15357136 (accessed 12 June 2018). 3. Bizcommunity.com. http://www.bizcommunity.com/Article/196/330/178100.html (accessed 12 June 2018). 4. Health-e News. https://www.health-e.org.za/2018/06/12/limpopo-health-system-on-the-verge-ofcollapse/ (accessed 12 June 2018).

S Afr Med J 2018;108(7):526. DOI:10.7196/SAMJ.2018.v108i7.13469

July 2018, Print edition

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2018/03/23 4:33 PM

EDITOR’S CHOICE

CME: Paediatric asthma in South Africa (part 1)

Asthma is a heterogeneous chronic inflammatory condition with variable airflow limitation and characterised by airway reversibility. Globally, asthma is among the top five most common respiratory noncommunicable diseases, with an estimated >300 million sufferers. The 2015 Global Burden of Disease Study found that worldwide 4 million deaths are due to chronic respiratory disease, with 80 - 90% occurring in low- and middle-income countries, including South Africa (SA). In a modelling study, asthma prevalence was found to be increasing in adults and children in Africa; asthma rates almost tripled over 20 years, from 40 million in 1990 to 119 million in 2010. In the International Study of Asthma and Allergies in Childhood (ISAAC), SA children were found to have the highest prevalence of asthma symptoms: >20% in 13 - 14-year-olds and >50% with severe asthma symptoms, reflecting a high morbidity due to asthma. An increasing prevalence of asthma has also been linked to increased rates of urbanisation. The following are risk factors for the development of asthma and more severe asthma symptoms: urbanisation, which is associated with increased exposure to air pollution due to traffic, poor ventilation of houses in periurban areas, high levels of violence, psychosocial stressors and little physical activity. Despite SA having an excellent package of medications for asthma care in the Standard Treatment Guidelines and Essential Medicines List for South Africa, the number of asthma deaths remains high, with SA being among the top 10 countries in the world in terms of asthma deaths. The key to improving asthma-related outcomes is linked to three key pillars: access to a diagnosis being made, appropriate access to medication, and education to improve adherence and achieve asthma control. In this issue of CME, the South African Childhood Asthma Working Group (SACAWG)[1,2] reviews the epidemiology and diagnosis and control of asthma in children.

Quality of counselling and support provided by the SA National AIDS Helpline: Content analysis of mystery client interviews

Telephone helplines can facilitate referral, education and support for patients living with HIV or those concerned about the infection. The anonymity of helplines facilitates discussion of sensitive issues that are difficult to raise face to face. These services could support the expansion of HIV self-testing. However, maintaining quality and standardising messages in rapidly evolving fields such as HIV is challenging. The objective of this study by Arullapan et al.[3] was to evaluate the quality of the SA National AIDS Helpline. Mystery clients posing as members of the public made 200 calls to the service in 2014. They presented several scenarios, including having received HIV-positive results from a doctor’s secretary or through self-testing. Following the call, ‘clients’ completed a semistructured questionnaire on the information received and the caller-counsellor interaction. Calls were answered within a median of 5 seconds (interquartile range (IQR) 2 - 14). Conversations took place in 8 of the 11 SA official languages, though mainly in English. Overall, 75% of callers felt that with the information they received they could locate a nearby clinic for further services. Counsellors expressed appropriate levels of concern about inadequate counselling callers had received and confidentiality breaches in some scenarios. Eight counsellors incorrectly mentioned the need for a waiting period to confirm a positive result. Consistent with policy, almost all said that being foreign would not affect HIV treatment access. About 90% explained the need for CD4+ testing and antiretroviral therapy, but only 78%

discussed HIV prevention. Counsellors were mostly empathetic (83%), though some adopted a neutral tone (10%) or were brusque (6%) or unhelpful (2%). Overall, helpline counsellors were proficient at providing information about local clinics, HIV testing and steps needed for initiating ART. Dissatisfaction with the caller-counsellor interactions, instances of incorrect information and the relatively low attention accorded to HIV prevention are worrying, however. Training for both refreshing and updating knowledge, and supervision and monitoring of calls, could target these areas.

A Seasonal Autoregressive Integrated Moving Average (SARIMA) forecasting model to predict monthly malaria cases in KwaZulu-Natal, SA

SA in general, and KwaZulu-Natal (KZN) Province in particular, have stepped up efforts to eliminate malaria. To strengthen malaria control in KZN, a relevant malaria forecasting model is important. The objective of this study by Ebhuoma et al.[4] was to develop a forecasting model to predict malaria cases in KZN using the Seasonal Autoregressive Integrated Moving Average (SARIMA) time series approach. The study was carried out retrospectively using a clinically confirmed monthly malaria case dataset that was split into two. The first dataset (January 2005 - December 2013) was used to construct a SARIMA model by adopting the Box-Jenkins approach, while the second dataset (January - December 2014) was used to validate the forecast generated from the best-fit model. Three plausible models were identified, and the SARIMA (0,1,1) (0,1,1)12 model was selected as the best-fit model. This model was used to forecast malaria cases during 2014, and it was observed to fit closely with malaria cases reported in 2014. The SARIMA (0,1,1)(0,1,1)12 model could serve as a useful tool for modelling and forecasting monthly malaria cases in KZN. It could therefore play a key role in shaping malaria control and elimination efforts in the province.

Hepatitis C prevalence in HIV-infected heterosexual men and men who have sex with men

Globally 1% of individuals are infected with hepatitis C virus (HCV). In SA the prevalence ranges between 0.3% and 1%, with few prospective screening data available. Similarly, local data on transmission modes of HCV are limited, but probably include parenteral routes and pre-1992 blood or blood products. The risk of heterosexual transmission of HCV is low but is increased in men who have sex with men (MSM), with co-transmission risk of both HIV and HCV. Given few local data, Gogela et al.[5] sought to better understand HCV characteristics and prevalence in two groups of HIV-infected men. HIV-positive men in the greater Cape Town metropolitan area were recruited. Sexual orientation was self-identified and demographic and other personal data were obtained via a confidential questionnaire. Participants were screened for HCV after a blood draw. Those with positive HCV tests had further HCV RNA confirmation. Univariate and multivariate modelling were used to determine factors associated with HCV seropositivity. Five hundred HIV-positive men were recruited, 285 (57.0%) MSM and 215 (43.0%) non-MSM, median age 36 years (IQR 20 - 64) and 37 years (IQR 21 - 56), respectively (p=NS). Overall, 3.4% (n=17) screened HCV-positive, 5.6% MSM (n=16) and 0.5% non-MSM

July 2018, Print edition

EDITOR’S CHOICE

(n=1); 82.4% were viraemic for HCV RNA. In respect of genotype distribution, 50.0% were infected with genotype 1a, 14.3% with genotype 4 and 35.7% with genotype 2. In terms of risk, MSM were more likely to have used drugs (54.4% v. 30.2%; p<0.001) and to have used all five modes of drug administration (13.0% MSM v. 0.5% non-MSM for injected drugs, 36.1% v. 2.3% for inhaled, 10.0% v. 0% for rectal, 48.1% v. 28.8% for smoked and 27.4% v. 2.3% for oral). More MSM than non-MSM (46.3% v. 16.7%) reported having sex while using recreational drugs, and similarly more MSM (21.4% v. 14%) reported having sex with a sex worker (SW). With multivariate modelling, intravenous drug use (odds ratio (OR) 30.0, 95% confidence interval (CI) 1.52 - 591.26; p<0.020), hepatitis B surface antigen (OR 7.71, 95% CI 1.05 - 56.72; p=0.045) and sex with an SW (OR 14.17, 95% CI 1.86 - 108; p<0.01) were associated with HCV infection risk. HCV prevalence in HIV-positive MSM is higher than previously appreciated or documented in SA. Risk factors include injection drug

use, hepatitis B infection and sex with SWs. Targeted interventions are required to address this emerging challenge to achieve the viral hepatitis elimination ideal by 2030. BF 1. Masekela R, Gray CL, Green RJ, et al., on behalf of the South African Childhood Asthma Working Group (SACAWG). The increasing burden of asthma in South African children: A call to action. S Afr Med J 2018;108(7):537-539. https://doi.org/10.7196/SAMJ.2018.v108i7.13162 2. Masekela R, Risenga SM, Kitchin OP, et al., on behalf of the South African Childhood Asthma Working Group (SACAWG). The diagnosis of asthma in children: An evidence-based approach to a common clinical dilemma. S Afr Med J 2018;108(7):540-545. https://doi.org/10.7196/SAMJ.2018. v108i7.13165 3. Arullapan N, Chersich MF, Mashabane N, et al. Quality of counselling and support provided by the South African National AIDS Helpline: Content analysis of mystery client interviews. S Afr Med J 2018;108(7):596-602. https://doi.org/10.7196/SAMJ.2018.v108i7.12543 4. Ebhuoma O, Gebreslasie M, Magubane L. A Seasonal Autoregressive Integrated Moving Average (SARIMA) forecasting model to predict monthly malaria cases in KwaZulu-Natal, South Africa. S Afr Med J 2018;108(7):573-578. https://doi.org/10.7196/SAMJ.2018.v108i7.12885 5. Gogela NA, Sonderup MW, Rebe K, Chivese T, Spearman CW. Hepatitis C prevalence in HIVinfected heterosexual men and men who have sex with men. S Afr Med J 2018;108(7):568-572. https://doi.org/10.7196/SAMJ.2018.v108i7.13041

July 2018, Print edition

These open-access articles are distributed under Creative Commons licence CC-BY-NC 4.0.

CORRESPONDENCE

Contribution of congenital disorders to neonatal mortality in South Africa

To the Editor: The article ‘Reducing neonatal deaths in South Africa: Progress and challenges’[1] in the March 2018 SAMJ Maternal and Child Health Supplement reviews recent neonatal estimates, causes and ways of reducing preventable deaths in this age category in the context of the Sustainable Development Goals.[2] While the article acknowledges the increasing contribution of ‘congenital anomalies’ as a cause of neonatal death, it fails to acknowledge the proportion of ‘congenital disorders’ (CDs) as a collective. No definition is included, but the literature defines congenital anomalies as macroscopic morphological anomalies present at birth,[3,4] referring to clinically obvious structural abnormalities as classified in Chapter XVII: ‘Congenital malformations, deformations and chromosomal abnormalities’ of the International Statistical Classification of Diseases and Related Health Problems (ICD-10).[5] This excludes ‘nonsyndromic congenital disability (intellectual, physical, visual and auditory disability and epilepsy), common single gene disorders such as the haemoglobin disorders, glucose-6 phosphate dehydrogenase deficiency, cystic fibrosis, oculocutaneous albinism, spinal muscular atrophy and inborn errors of metabolism’[4] and teratogens. These are distributed throughout the ICD-10 system, accounting for a third of CDs globally.[6] Presenting only a subset of CDs to represent the totality of CDs has implications, particularly for cause-of-death rankings and planning of services and interventions. While the role of congenital anomalies is indicated as a notable cause of death in neonates in South Africa (SA), ranking fourth after prematurity, intrapartum-related events and infection, CDs may rank higher as a cause of death. CDs are internationally defined as abnormalities in structure or function present from birth, including inborn errors in metabolism.[4] This classification disparity is further evidenced by the average baseline birth prevalence rates of congenital anomalies of 20 per 1 000 live births[7] v. that of CDs at >39.7 per 1 000 live births.[6,8] Interestingly, contrary to the article text, data in Fig. 5 showing causes of neonatal deaths per level of care indicate that congenital anomalies rank third as a cause of neonatal death at an overall 8.8%, ahead of infection at 7.7%, with the greatest disparity between these two causes of death at district hospitals.[1] Non-diagnosis or misdiagnosis resulting in the cause of death being incorrectly attributed also contributes to underreporting of CDs as a cause of death. Honein et al.[9] report CDs as being twice as common in preterm infants (24 - 36 weeks) as in term infants, and five times more likely in very preterm infants (24 - 31 weeks), with 16% of very preterm births having a CD. Similarly, a portion of deaths assigned to intrapartum-related events may be due to severe congenital cerebral palsy (CP). The Centers for Disease Control and Prevention indicates that 85 - 90% of CP is congenital,[10] of which an estimated 30 - 40% has a genetic aetiology, with birth asphyxia only accounting for 10 - 15% of all CP cases.[11-16] Congenital syphilis, a CD by definition, contributes a minimum of 3% of neonatal deaths[17] and together with other congenital (TORCH) infections (which include toxoplasmosis, other (syphilis, varicella-zoster, parvovirus b19), rubella, cytomegalovirus and herpes) may also be allocated to the infections cause of death category.[8] This proportion is probably an underestimate, since diagnosis of congenital syphilis in neonates is more difficult than in pregnant women, with adverse pregnancy outcomes in 38% of cases of maternal infection, including neonatal death in 7% of cases.[18] Neonates born with a CD have an increased susceptibility to infection in certain instances, with the infection being more ‘obvious’ and more likely to be diagnosed and assigned as the cause of death

than the underlying CD in cases of comorbidity.[19,20] The lack of a newborn screening policy and top-to-toe examination of the infant prior to discharge further contributes to non-diagnosis and the inaccurate assessment of the contribution of CDs to the burden of disease.[8,19,21,22] With a significant proportion of under-5 deaths occurring during the neonatal period, comprehensively addressing CDs as a cause of neonatal deaths in SA is now an imperative. World Health Assembly (WHA) Resolution 63.17 of 2010[23] recognised the importance of CDs as a cause of stillbirths and neonatal mortality and their contribution to the failure in attaining Millennium Development Goal 4. The same WHA recommendations must now be heeded if the SGD targets set for 2030 to end preventable deaths in this age group are to be met.[2,23] Author contributions: All authors were involved in the conceptualisation of this letter and all provided input and technical contributions on the draft produced by the main author (HLM). All authors signed off on the final version prior to submission. Funding. Thanks to the School of Clinical Medicine, University of KwaZulu-Natal, Durban, SA, for their ongoing support of this research via a post-doctoral research scholarship.

Helen L Malherbe School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa helen@hmconsult.co.za

Arnold L Christianson Wits Centre for Ethics (WiCE), Department of Philosophy, Faculty of Humanities, University of the Witwatersrand, Johannesburg, South Africa

David Woods Newborn Care, School of Child and Adolescent Health, Faculty of Health Sciences, University of Cape Town, South Africa

Colleen Aldous Emerging Academics Research Support, School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa

1. Rhoda N, Velaphi S, Gebhardt G, Kauchali S, Barron P. Reducing neonatal deaths in South Africa: Progress and challenges. S Afr Med J 2018;108(Suppl 1):S9-S16. https://doi.org/10.7196/SAMJ.2017. v108i3b.12804 2. United Nations. Sustainable Development Goal 3: Ensure Healthy Lives and Promote Well-being for All and at All Ages. Geneva: UN, 2015. http://www.un.org/sustainabledevelopment/health/ (accessed 13 January 2016). 3. World Health Organization. Guidelines for the Development of National Programmes for Monitoring Birth Defects. Geneva: WHO, 1993:33. 4. World Health Organization. Management of Birth Defects and Haemoglobin Disorders. Report of a Joint WHO-March of Dimes Meeting, Geneva, Switzerland, 17 - 19 May 2006. Geneva: WHO, 2006:27. 5. World Health Organization. International Statistical Classification of Diseases and Related Health Problems. 10th revision. Geneva: WHO, 1992. http://apps.who.int/classifications/icd10/browse/2015/ (accessed 1 June 2016). 6. Modell B, Darlison M, Moorthie S, et al. Epidemiological Methods in Community Genetics and the Modell Global Database of Congenital Disorders (MGDb). London: University College London, 2016. http://discovery.ucl.ac.uk/1532179/ (accessed 16 July 2017). 7. Czeizel A, Sankaranarayanan K. The load of genetic and partially genetic disorders in man I. Congenital anomalies: Estimates of detriment in terms of years of life lost and years of impaired life. Mutat Res 1984;128(1):73-103. https://doi.org/10.1016/0027-5107(84)90049-6 8. Christianson A, Howson C, Modell B. March of Dimes: Global Report on Birth Defects, the Hidden Toll of Dying and Disabled Children. New York: March of Dimes, 2006:84. 9. Honein MA, Kirby RS, Meyer RE, et al. The association between major birth defects and preterm birth. Matern Child Health J 2009;13(2):164-175. https://doi.org/10.1007/s10995-008-0348-y 10. Centers for Disease Control and Prevention. Causes and Risk Factors of Cerebral Palsy. Atlanta: CDC, 2017. https://www.cdc.gov/ncbddd/cp/causes.html (accessed 30 April 2018). 11. Costeff H. Estimated frequency of genetic and nongenetic causes of congenital idiopathic cerebral palsy in west Sweden. Ann Hum Genet 2004;68(5):515-520. https://doi.org/10.1046/j.15298817.2004.00105.x 12. Moreno-De-Luca A, Ledbetter DH, Martin CL. Genetic insights into the causes and classification of the cerebral palsies. Lancet Neurol 2012;11(3):283-292. https://doi.org/10.1016/s1474-4422(11)70287-3

July 2018, Print edition

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Sadia Murray is a medical doctor working in general paediatrics at Tygerberg Hospital. She chose USB’s MBA stream in Health Care Leadership to expand her business skillset in order to lead positive change in her industry.

CORRESPONDENCE

13. MacLennan AH, Thompson SC, Gecz J. Cerebral palsy: Causes, pathways, and the role of genetic variants. Am J Obstet Gynecol 2015;213(6):779-788. https://doi.org/10.1016/j.ajog.2015.05.034 14. Fahey MC, Maclennan AH, Kretzschmar D, Gecz J, Kruer MC. The genetic basis of cerebral palsy. Dev Med Child Neurol 2017;59(5):462-469. https://doi.org/10.1111/dmcn.13363 15. Nelson KB. What proportion of cerebral palsy is related to birth asphyxia? J Pediatr 1988;112(4):572574. https://doi.org/10.1016/s0022-3476(88)80169-0 16. Graham EM, Ruis KA, Hartman AL, Northington FJ, Fox HE. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008;199(6):587-595. https://doi.org/10.1016/j.ajog.2008.06.094 17. Reid AE, Hendricks MK, Groenewald P, Bradshaw D. Where do children die and what are the causes? Under-5 deaths in the Metro West geographical service area of the Western Cape, South Africa, 2011. SÂ Afr Med J 2016;106(4):359-364. https://doi.org/10.7196/SAMJ.2016.v106i4.10521 18. Wijesooriya NS, Rochat RW, Kamb ML, et al. Global burden of maternal and congenital syphilis in 2008 and 2012: A health systems modelling study. Lancet Glob Health 2016;4(8):e525-e533. https:// doi.org/10.1016/S2214-109X(16)30135-8 19. Christianson A, Modell B. Medical genetics in developing countries. Ann Rev Genomics Hum Genet 2004;5:219-265. https://doi.org/10.1146/annurev.genom.5.061903.175935 20. World Health Organization. Services for the Prevention and Management of Genetic Disorders and Birth Defects in Developing Countries. Report of a Joint WHO/WAOPBD Meeting, The Hague, 5 - 7 January 1999. Geneva: WHO,1999:100. 21. Nippert I, Christianson A, Gribaldo L, et al. Genetic Testing in Emerging Economies (GenTEE): Summary Report. Italy: Publications Office of the European Union, 2013:194. 22. Malherbe H, Aldous C, Woods D, Christianson A. The contribution of congenital disorders to child mortality in South Africa. In: Padarath A, King J, Mackie E, Casciola J, eds. South African Health Review 2016. 19th ed. Durban: Health Systems Trust, 2016:137-152. 23. World Health Assembly. Sixty-Third World Health Assembly Resolution 63.17. Birth Defects. 2010. http://apps.who.int/gb/ebwha/pdf_files/WHA63/A63_R17-en.pdf (accessed 10 December 2012).

S Afr Med J 2018;108(7):527-528. DOI:10.7196/SAMJ.2018.v108i7.13393

Post-pulmonary tuberculosis complications in South Africa and a potential link with pulmonary hypertension: Premise for clinical and scientific investigations

To the Editor: The magnitude of the pulmonary tuberculosis (TB) epidemic in South Africa (SA) and globally[1] has received increased attention. Efforts have been made to explore new and improved diagnostic[2] and treatment strategies,[3] but the story does not end with treatment, and TB frequently results in long-term lung damage. This may include chronic airflow obstruction, reduced lung function (forced vital capacity) and destruction of the pulmonary vascular bed in cases of advanced lung disease.[4,5] This destruction of the vascular bed is attributed to parenchymal abnormalities that lead to reduced cross-sectional area of the pulmonary vasculature.[6] We highlight the fact that long-term consequences of advanced destruction of the pulmonary vasculature may occur in the absence of significant parenchymal damage, and that this is another post-TB complication that remains largely unexplored. Few previous reports[7-9] and our clinical experience suggest that there is an association between post-TB lung disease and pulmonary hypertension (PHT). Although a proportion of patients with current TB do present with PHT,[7,8,10] the strength of this association remains largely undefined. [9,10] In addition, the prevalence of PHT among individuals who have been treated for pulmonary TB but who have minimal fibrotic parenchymal disease is also not known. We have noticed a paucity of literature listing TB as a potential cause of pulmonary vascular disease, or demonstrating an association between TB and PHT. Furthermore, the literature and PHT guideline documents rarely mention TB among the list of causes of group 3 PHT.[11] We therefore propose that a discordance may exist between our clinical reality and the literature on post-TB pulmonary vascular disease and PHT. This discordance is difficult to explain, and may in part be due to a low TB incidence in countries currently researching PHT. It is possible that in their setting they do not frequently observe patients with TB progressing to advanced lung destruction, like we do here in SA. This highlights many important

unanswered questions, that include: What is the strength of the association between pulmonary TB and PHT, across the spectrum of parenchymal abnormality in TB patients? Why does the degree of right heart failure correlate so poorly with the degree of radiological changes?[8] Does the degree of right heart failure correlate with the degree of airway obstruction/restriction regardless of the degree of radiological changes? What is the time of onset of PHT in patients who were successfully treated for TB? Lastly, do other co-factors, such as smoking, drug use or HIV, have a modifying role in the development of PHT? Considering that in SA there were an estimated 438 000 cases of tuberculosis in 2016 alone,[1] we highlight that further clinical investigation and research into this disease association is important. This research is essential if we are to design treatment strategies for these patients. Without sufficient data, management decisions appear to be largely informed by anecdotes. Moreover, management algorithms are usually extrapolated from those of other group 3 PHT-related diseases (e.g. chronic obstructive pulmonary disease and pulmonary fibrosis),[11] where the mechanism of pathology is likely to be entirely different. In our clinical experience, it is clear that TB does not end with cessation of treatment, and long after the current epidemic is over we may be left with a generation of individuals still suffering long-term consequences, one of which is PHT. B W Allwood Division of Pulmonology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa brianallwood@gmail.com

G J Maarman Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

C G Kyriakakis, A F Doubell Division of Cardiology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

1. World Health Organization. Global Tuberculosis Report 2017. Geneva: WHO, 2017. 2. Datta S, Saunders MJ, Tovar MA, Evans CA. Improving tuberculosis diagnosis: Better tests or better healthcare? PLoS Med 2017;14(10):e1002406. https://doi.org/10.1371/journal.pmed.1002406 3. Marx FM, Yaesoubi R, Menzies NA, et al. Tuberculosis control interventions targeted to previously treated people in a high-incidence setting: A modelling study. Lancet Glob Health 2018;6(4):e426-e435. https://doi.org/10.1016/S2214-109X(18)30022-6 4. Amaral AFS, Coton S, Kato B, et al. Tuberculosis associates with both airflow obstruction and low lung function: BOLD results. Eur Respir J 2015;46(4):1104-1112. https://doi.org/10.1183/13993003.02325-2014 5. Harries AD, Ade S, Burney P, Hoa NB, Schluger NW, Castro JL. Successfully treated but not fit for purpose: Paying attention to chronic lung impairment after TB treatment. Int J Tuberc Lung Dis 2016;20(8):1010-1014. https://doi.org/10.5588/ijtld.16.0277 6. Verma AK. Tuberculosis and pulmonary hypertension: Commentary. Lung India. 2016;33(2):232-233. https://doi.org/10.4103/0970-2113.177455 7. Ahmed AE, Ibrahim AS, Elshafie SM. Pulmonary hypertension in patients with treated pulmonary tuberculosis: Analysis of 14 consecutive cases. Clin Med Insights Circ Respir Pulm Med 2011;5:1-5. https://doi.org/10.4137/CCRPM.S6437 8. Bhattacharyya P, Saha D, Bhattacherjee PD, Das SK, Bhattacharyya PP, Dey R. Tuberculosis associated pulmonary hypertension: The revelation of a clinical observation. Lung India 2016;33(2):135-139. https://doi.org/10.4103/0970-2113.177433 9. Thienemann F, Dzudie A, Mocumbi AO, et al. The causes, treatment, and outcome of pulmonary hypertension in Africa: Insights from the Pan African Pulmonary Hypertension Cohort (PAPUCO) Registry. Int J Cardiol 2016;221:205-211. https://doi.org/10.1016/j.ijcard.2016.06.242 10. Ivanov AK. [Echocardiographic evaluation of pulmonary tuberculosis in adolescent and young patients]. Probl Tuberk 1995;(5):32-34. 11. Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 2015;46(4):903-975. https://doi.org/10.1183/13993003.01032-2015

S Afr Med J 2018;108(7):529. DOI:10.7196/SAMJ.2018.v108i7.13359

July 2018, Print edition

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Tel: +27(0)87 813 0335. Cell: +27(0)74 288 9400. Fax: +27(0)86 270 6755. e-Mail: info@genesispharma.co.za Web: www.genesispharma.co.za P.O.Box 429, Kelvin, 2054

Location

Clinical/specimen details

Contact details of responsible practitioner

Specimen site

Signature

Contact information

Persal or practice number

Name

Taken by

Time taken

Date taken

Type of specimen

Medication/antibiotics received

Diagnosis/reason for request

Ward

Hospital/clinic

To the Editor: Working in a microbiology laboratory has given me a new perspective on completing laboratory forms thoroughly. Diligent completion of these forms shows care and conscientiousness in one’s duties and ensures the correct processing of a hard-earned biopsy taken by the surgeon in theatre. Unfortunately, we as laboratory personnel see poorly completed forms daily and have to phone out unlabelled specimens to senior doctors routinely. Fig. 1 tells the story of these uncompleted forms. These data were captured from 621 National Health Laboratory Service request forms, which include all specimen types received in one day. Only 37% of the practitioners included their contact information, making it very difficult to communicate critical results. Furthermore, only 25% of the laboratory request forms had a specimen site indicated, an important factor to consider when selecting the conditions and media to culture samples. The diagnosis and reason for the investigation were not entered by almost a third of the responsible practitioners, which makes it difficult to place preliminary results into context. Not one of the laboratory forms was completed with all the requested sections filled in. Only 14 samples were rejected by our laboratory (6 leaked, 3 were unsuitable for the test requested, 3 were unlabelled, 1 sample was placed in the wrong container, and in 1 case information on the form did not match that of the sample). The

100 90 80 70 60 50 40 30 20 10 0 Patient name and number

Completing laboratory request forms diligently – when did it become optional?

Sections completed, %

CORRESPONDENCE

Microbiology

Fig. 1. Completed sections of the NHLS request form. Data include samples from urine, stool, pus, tissue, blood culture, cerebrospinal fluid, sputum, mycology and tuberculosis specimens. Laboratory forms that have sections omitted (mauve bars) may be rejected, as stipulated on the NHLS request form. (NHLS = National Health Laboratory Service.)

problem is not so much the lack of completeness, but that samples are rejected when a sample cannot be correctly attributed. It is the patient who must carry the burden of lost samples and our health system that must carry the financial strain. On the other hand, accepting specimens with unknown collection dates or no specimen type indicated may result in non-conformance when undergoing external laboratory accreditation processes. This can jeopardise the soundness of these results if processed and sent out by our laboratory. If we were to reject all samples with incomplete forms, this would mean rejecting at least 56% of the request

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forms, as no persal or practice number was entered for those samples. This issue needs to be addressed at medical school and intern level, so that completing the forms correctly is second nature. C J Opperman Division of Medical Microbiology, National Health Laboratory Service, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa stefanopperman1@gmail.com S Afr Med J 2018;108(7):530. DOI:10.7196/SAMJ.2018.v108i7.13363

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These open-access articles are distributed under Creative Commons licence CC-BY-NC 4.0.

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30 days in medicine Childhood leukaemia possibly preventable by early exposure to infections

Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer in developed countries, affecting one in 2 000 children up to the age of 15 years, and is growing in incidence at 1% a year. Because of its epidemiology there has been a suspicion that infection, or an abnormal response to infection, plays a causal role. Now research has shown that the disease is caused by a two-stage process of genetic mutation and may be preventable. It appears that two genetic changes, the first of which occurs in the womb, are responsible. The first change, found in 5% of newborns, makes the immune system more susceptible to react to routine infections after birth with a poorly regulated inflammatory response, causing a second genetic change, which in turn causes the disease. This second change only causes disease in children who have been raised in environments relatively free of bacteria. When these children are later faced with a pathogen such as the flu virus, the second change takes place, which leads to ALL. The absence of exposure to infections before the age of 1 year prevents the immune system from functioning correctly later, explaining why ALL is a disease of affluence and almost unknown in poorer countries, why it is usually seen in firstborns and why cases arise in clusters. Greaves M. A causal mechanism for childhood acute lymphoblastic leukaemia. Nat Rev Cancer 2018 (epub 21 May 2018). https://doi.org/10.1038/s41568-018-0015-6

Seven in 10 women with breast cancer do not need chemotherapy

Most women with early-stage hormone receptor-positive breast cancer do not need chemotherapy as well as endocrine therapy after surgery if tests with a 21 tumour gene expression assay (Oncotype DX) are in the mid-range for risk of recurrence. This is the finding of a large randomised trial published recently in the New England Journal of Medicine. The study, from the US National Cancer Institute, included 10 273 women with hormone receptor-positive, HER2-negative, axillary node-negative early-stage breast cancer. Of the 9 719 patients with follow-up information, >69% had a mid-range score when tested with

Oncotype DX. These women were randomised to treatment with chemotherapy plus endocrine therapy or to endocrine therapy alone. At 9 years, 83.3% of patients treated with endocrine therapy alone were free from breast cancer compared with 84.3% of those treated with chemotherapy and endocrine therapy. In addition, both groups had similar rates of freedom from distant site recurrence. Further analysis showed that women aged ≤50 years and with a risk score of 16 - 25 were more likely than others to benefit from the addition of chemotherapy. Sparano JA, Gray RJ, Makower F, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med 2018 (epub 3 June 2018). https://doi.org/10.1056/NEJMoa1804710

Years of education linked to risk of myopia

The prevalence of myopia is increasing rapidly, and it is one of the leading causes of visual disability worldwide. Currently, 30 - 50% of adults in the USA and Europe are myopic, with levels of 80 - 90% reported in school leavers aged 17 or 18 years in Singapore, South Korea, China and other high-income Eastern and Southeast Asian countries. A recent study published in the British Medical Journal suggests that exposure to more years in education contributes to the rising prevalence of the condition. Using a mendelian randomisation study, the researchers looked at 67 798 men and women from England, Scotland and Wales with the UK Biobank cohort, for whom information on years of completed education and refractive error was available. They found that every additional year of education was associated with a more myopic refractive error of –0.18 dioptres per year. The cumulative effect of more years in education on refractive error means that a university graduate in the UK with 17 years of education would, on average, be at least –1 dioptre more myopic than someone who left school at age 16 (with 12 years of education). This is enough to need glasses for driving. Mountjoy E, Davies NM, Plotnikov D, et al. Education and myopia: Assessing the direction of causality by medelian randomisation. BMJ 2018;361:k2022. https://doi.org/10.1136/bmj.k2022

B Farham Editor ugqirha@iafrica.com

July 2018, Print edition

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BOOK REVIEWS

High Performance in Hospital Management: A Guideline for Developing and Developed Countries.

By Edda Weimann and Peter Weimann. Berlin: Springer Publishing Company, 2017. ISBN: 978-3-662-49658-9 ISBN (e-book): 978-3-662-49660-2 I recently had the pleasure of reading Prof. Edda and Prof. Peter Weimann’s excellent book High Performance in Hospital Management: A Guideline for Developing and Developed Countries, which makes a very important contribution to management practice. The book covers an incredibly wide range of topics in an accessible and highly readable way. It is an exceptionally useful resource, even for those of us who have no direct involvement in healthcare. Let me briefly discuss just six of the ways in which the book contributes to the wider debates within our society. Specifically, I will focus on what the book contributes to the discussion in South Africa (SA) and other developing countries

about the need to work towards universal healthcare. First, the book articulates cogent arguments around universal health coverage as a basic right towards which we need to strive. Universal health coverage improves health, but it also reduces poverty, creates jobs, drives economic growth and promotes gender equality. It takes vision, commitment and long-term thinking. Second, healthcare is an investment rather than a consumption good. The authors estimate that National Health Insurance (NHI) in SA could reduce the burden of disease by 14.2 million disabilityadjusted life years and save 184 085 lives (by avoiding premature death), but then – rightly – qualify that by saying that this will only happen if service provision, equity and efficiency are improved. This book fills a much-needed gap in terms of setting out in a clear way how those efficiencies can be achieved. Third, an NHI scheme will fail if the country’s public hospitals continue to function as badly as many of them currently do. Mismanagement and poor services are the norm at many of SA’s government medical facilities. The country’s beleaguered public health system will have to improve drastically for NHI to be properly implemented. It is evident that we currently have public health expenditure with bad outcomes; raising more money for healthcare will not guarantee that health outcomes will improve. The real problem is the administration of that service. This is, of course, exactly what makes the contribution so important – the whole book is about how to improve the management of health services. Fourth, the book emphasises the critical importance of accountability and good governance. It is clear that the present lack of accountability for the mismanagement of state medical facilities is a huge problem. The book sets out ways to increase accountability, such as through hospital trusts with a board of directors that consists of members of

July 2018, Print edition

the public. The board holds the hospital accountable for its services, which can make a huge difference in the efficiency of hospitals. Fifth, there is currently a lack of autonomy among state hospital chiefs, especially with regard to managing staff and supplies. The heads of large state hospitals have little authority to make real decisions over critical management issues. Because of this, government health institutions are not being run as efficiently as they could be. State hospital chief executives have little say in the hiring and firing of staff or the purchasing of new equipment. Something as small as allowing state hospital chief executives to directly manage repairs could significantly improve service delivery. Sixth, there is a great need to collect data on the management of patients at state hospitals. These data would tell us how successfully, or unsuccessfully, a hospital handles its patients and what could be done differently. At present the system does not keep track of a patient’s journey through a hospital, and we do not even know how many patients are transferred between hospital departments. This is where the innovations of those with expertise in information systems can play a critical role in helping to design management information systems. It is clear that delivering high-quality healthcare is not an issue that healthcare professionals can address on their own. The contributions of economists, accountants, organisational psychologists and management consultants are critical to the design of health systems, the financing of the healthcare system and the delivery of highquality, efficient services. This book sets out myriad ways in which all disciplines can start to contribute. I highly recommend it. Ingrid Woolard Dean of the Faculty of Economic and Management Sciences, Stellenbosch University, South Africa ingridw@sun.ac.za

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Beyond Evolutionary Psychology: How and Why Neuropsychological Modules Arise By George Ellis and Mark Solms. Cambridge: Cambridge University Press, 2018. ISBN: 978-1-107-66141-7

Evolutionary psychologists can be divided into two broad groups: nativists, who regard the mind as a product of essentially genetically innately specified, domain-specific structures and processes, and empiricists, who consider the mind

(specifically the neocortex), as a ‘soft-wired’ arrangement of neurons designed by genes and continually sculpted by experience and developmental processes under the influence of ascending neural pathways from the limbic (emotional) brain, which asserts its influence globally in the neocortex by neuromodulators (the evo-devo theory). It was Noam Chomsky who first formulated the idea of an innate grammar module in the brain’s neocortex, which Steven Pinker developed into a ‘language instinct’. Innate modules, it was argued, were necessary to equip the neonate to survive in a world with a ‘poverty of stimulus’, despite the richness of the mother-child bond in the vulnerable period of the newborn’s life. Profs George Ellis and Mark Solms of the University of Cape Town are among a long list of researchers who have challenged this idea in their very recent book of seven chapters and 177 pages, with a comprehensive reference list and illustrations. The modular theorists suggest that the evolved mind is adapted to survive in the context of the African savannah of the hunter-gatherers, which empiricists feel discounts the ability to respond to changes in the environment, for example, the modern way of life. New environments, with the variety of stimuli they generate, could be very unpredictable, demanding of the mind a characteristic plasticity, an ability to adapt to new experiences, which a modular brain with its innate specificity may be unable to cope with. Brain plasticity would allow for

July 2018, Print edition

rewiring of the brain to suit new needs as the neurons, with their ‘softer’ synapses, break old connections and make new ones, to adapt to new environmental circumstances. Gene expression in neurons certainly plays a role here, with epigenetic mechanisms working through gene-regulated networks. This is the manner in which we learn about our unpredictable environments, which require this flexibility rather than a restrictive instinctive response that would make adaptation difficult. Interaction with our environments enables us to survive and reproduce, thus helping us to fulfil the Darwinian imperative! Of course there are innate instinctive modules in the brain, performing affective rather than cognitive functions, largely in the limbic system, the subcortical sensory and motor systems, and the autonomic and peripheral nervous systems, well described by the authors. No matter which side of the debate the reader is on, this book is a worthwhile read for the layperson and specialist alike, leaving much to mull over. The book has a section on how we learn, how we read and the importance of the narrative, all very useful in the context of illiteracy and a failing educational system in South Africa. Anwar Suleman Mall Emeritus Professor and Senior Scholar, Division of General Surgery, Faculty of Health Sciences, University of Cape Town, South Africa anwar.mall@uct.ac.za

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

EDITORIAL

National coverage of reflex cryptococcal antigen screening: A milestone achievement in the care of persons with advanced HIV disease HIV/AIDS-related mortality accounts for almost one-third of deaths in South Africa (SA), and globally ~15% of AIDS-related mortality is associated with cryptococcal disease.[1,2] The burden of cryptococcal meningitis has remained high in SA among severely immunosuppressed HIV-positive patients, despite substantial improvements in antiretroviral treatment (ART) coverage over the past decade.[3] Approximately one-third of patients entering HIV care in the SA public sector in 2016 had advanced HIV disease (defined as a CD4+ T-lymphocyte count <200 cells/µL), and 17% had a CD4+ count <100 cells/µL.[4] In 2011, the World Health Organization (WHO) recommended that countries consider integrating cryptococcal antigen (CrAg) screening into HIV programmes to detect cryptococcal disease at an earlier point in its trajectory, followed by pre-emptive antifungal treatment to reduce AIDS deaths. [5] The CrAg screen-and-treat intervention therefore aligns with the Joint United Nations Programme on HIV/AIDS (UNAIDS) over-arching goal to reduce global AIDS deaths to >500 000 by 2020, and has been included in a new WHO-recommended package of care for managing advanced HIV disease.[6] Since it was first included in SA’s national strategic plan for HIV/AIDS, tuberculosis and STIs in 2012, evidence has mounted in favour of the CrAg screen-andtreat intervention. A randomised controlled trial from Zambia and Tanzania revealed that pre-ART CrAg screening with pre-emptive antifungal treatment for patients with a CD4+ count <200 cells/µL, coupled with 4 weeks of community-based ART adherence support, resulted in a 28% reduction in all-cause mortality at 12 months.[7] In the light of these data, on 1 October 2016 the National Health Laboratory Service (NHLS) implemented a ground-breaking service to provide the world’s first and largest national laboratory-based CrAg screening programme aimed at detecting early cryptococcal disease before progression to meningitis in all HIV-seropositive patients with a CD4+ count <100 cells/µL across SA. The launch of the programme was the culmination of a long, successful, nationally co-ordinated effort by the National Institute for Communicable Diseases (NICD), the National Department of Health (NDoH), the NHLS and other local and international partners. Several activities preceded this important milestone. Following a circular (circular no. H116/2012) from the Western Cape provincial government to screen all patients whose CD4+ count was <100 cells/ µL, a provider-initiated CrAg screening initiative was implemented in the Western Cape in mid-2012. No clinical training was offered, and no feedback was provided to clinicians in terms of the proportion of eligible patients screened at their clinics. A retrospective evaluation showed that just over a quarter of eligible patients were screened under this initiative; compared with those who were screened, those who were not screened were almost twice as likely to develop disseminated cryptococcal disease.[8] In contrast, a simpler laboratory-based approach using remnant CD4+ samples reflexively tested for CrAg if the CD4+ count was <100 cells/µL was simultaneously piloted in four districts in Gauteng and Free State provinces from 2012 through to 2015.[9,10] This initiative was paired with intensive clinician training on how to appropriately manage CrAg-positive patients identified through reflexed testing. In this scenario, almost 100% of eligible patients were screened for cryptococcal antigenaemia. Implementation of these two contrasting approaches offered a valuable opportunity for parallel evaluation. A detailed costeffectiveness model demonstrated that laboratory-based reflex CrAg

screening was simpler and more cost-effective than a clinicianinitiated approach, allowed for almost universal screening coverage, and potentially saved more lives.[11] In 2014, the NDoH adopted a detailed screen-and-treat clinical algorithm for seamless integration into the HIV care cascade. This algorithm has subsequently been included in the Standard Treatment Guidelines/Essential Medicines List at all healthcare levels.[12,13] Several skills-based training workshops for management of cryptococcal disease were developed and cascaded downwards to healthcare workers at facility level. On the NHLS side, the initiative facilitated the evaluation of several CrAg assays and workflow analyses for scaling up state laboratory services. [14-17] The NHLS also undertook intensive training of laboratory personnel based on standard operating procedures and on-site assessment of laboratory work flow, enabling integration into existing CD4+ services. The development of a national laboratory proficiency testing scheme (PTS) by the NICD/NHLS completed the final phase of service delivery implementation; the first batch of PTS samples was distributed to NHLS CD4+ laboratories in November 2016. On the NDoH side, a public health planning and resource allocation exercise was conducted, specifically to ensure that fluconazole was procured and made available at all healthcare levels. A laboratory dashboard for CrAg has been integrated into a broader SA HIV programme dashboard, with two key indicators: CrAg screening coverage and prevalence of cryptococcal antigenaemia. Good linkage to laboratory CrAg results is the cornerstone of this programme. Several methods are being implemented to ensure that CrAg-positive patients return for clinical evaluation and begin appropriate antifungal treatment. Weekly CrAg results for action (RFA) reports are emailed to registered end-users (currently including district/facility managers or registered healthcare workers at 220 facilities in 32 districts). RFA reports are formatted as line-lists of patients with a positive CrAg result who need urgent follow-up. Looking ahead, the impact of the CrAg screen-and-treat programme on patient outcomes will be evaluated by clinic-based field surveys over the next 5 years through the NICD’s CAST-NET project. Several interventions will also be explored to optimise implementation of CrAg screen-and-treat, including intensive refresher healthcare worker training with novel methods of delivery, patient education, enhanced delivery of laboratory results to clinicians, and risk stratification of patients by piloting semi-quantitative CrAg testing on reflexively tested blood specimens.[18] Through this national CrAg screening initiative, 276 125 patients were screened during the first year (October 2016 through to September 2017) with 95% coverage, and 15 757 (5.7%) were identified with cryptococcal antigenaemia,[19-21] highlighting both the large burden of advanced HIV disease and opportunistic infections in SA and the urgent need to recruit these very ill patients into care. Acknowledgements. We acknowledge NHLS personnel and National Priority Programme co-ordinator Dr L M Coetzee who graciously took on the CrAg screening workload to enable this programme to be rolled out within the existing state CD4+ service, reducing implementation costs. Our group is also grateful for the important groundwork that was laid for this programme and the support received from our collaborators, funders and the NDoH. Pilot work for the CrAg screen-and-treat programme was supported by a Centers for Disease Control and Prevention (CDC)

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EDITORIAL

and NHLS co-operative agreement (CDC-RFA-GH15-1575; project PI, NPG). NPG is partially supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) under award no. R01AI118511. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the CDC.

Nelesh P Govender National Institute for Communicable Diseases (Centre for HealthcareAssociated Infections, Antimicrobial Resistance and Mycoses), a Division of the National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa neleshg@nicd.ac.za Deborah K Glencross National Priority Programme Unit, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 1. Pillay-van Wyk V, Msemburi W, Laubscher R, et al. Mortality trends and differentials in South Africa from 1997 to 2012: Second National Burden of Disease Study. Lancet Glob Health 2016;4(9):e642-e653. https://doi.org/10.1016/S2214-109X(16)30113-9 2. Rajasingham R, Smith RM, Park BJ, et al. Global burden of disease of HIV-associated cryptococcal meningitis: An updated analysis. Lancet Infect Dis 2017;17(8):873-881. https://doi.org/10.1016/S14733099(17)30243-8 3. Britz E, Perovic O, von Mollendorf C, et al. The epidemiology of meningitis among adults in a South African province with a high HIV prevalence, 2009 - 2012. PLoS One 2016;11(9):e0163036. https://doi. org/10.1371/journal.pone.0163036 4. Carmona S, Bor J, Nattey C, et al. Persistent high burden of advanced HIV disease among patients seeking care in South Africa’s national HIV programme: Data from a nationwide laboratory cohort. Clin Infect Dis 2018;66(Suppl 2):S111-S117. https://doi.org/10.1093/cid/ciy045 5. World Health Organization. Rapid Advice: Diagnosis, Prevention and Management of Cryptococcal Disease in HIV-infected Adults, Adolescents and Children. Geneva: WHO, 2011. www.who.int/hiv/ pub/cryptococcal_disease2011/en/ (accessed 3 January 2018). 6. World Health Organization. Guidelines for Managing Advanced HIV Disease and Rapid Initiation of Antiretroviral Therapy. Geneva: WHO, 2017. www.who.int/hiv/pub/guidelines/advanced-HIVdisease/en/ (accessed 3 January 2018). 7. Mfinanga S, Chanda D, Kivuyo SL, et al. Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: An open-label, randomised controlled trial. Lancet 2015;385(9983):2173-2182. https://doi.org/10.1016/S0140-6736(15)60164-7

8. Vallabhaneni S, Longley N, Smith M, et al. Evaluation of a public-sector, provider-initiated cryptococcal antigen screening and treatment program, Western Cape, South Africa. J Acquir Immune Defic Syndr 20161;72(2):e37-e42. https://doi.org/10.1097/QAI.0000000000000976 9. Govender NP, Chetty V, Roy M, et al. Phased implementation of screening for cryptococcal disease in South Africa. S Afr Med J 2012;102(12):914-917. https://doi.org/10.7196/SAMJ.6228 10. Govender NP, Chetty V, Spencer D, et al. Cryptococcal screen-and-treat in Gauteng Province, South Africa: Update from the first 2 years of implementation, 2012 - 2014. S Afr J HIV Med 2014;15(4):156159. https://doi.org/10.7196/SAJHIVMED.1124 11. Larson BA, Rockers PC, Bonawitz R, et al. Screening HIV-infected patients with low CD4 counts for cryptococcal antigenemia prior to initiation of antiretroviral therapy: Cost effectiveness of alternative screening strategies in South Africa. PLoS One 2016;11(7):24. https://doi.org/10.1371/journal. pone.0158986 12. Govender NP, Meintjes G, Bicanic T, et al. Guideline for prevention, diagnosis and management of cryptococcal meningitis among HIV-infected persons: 2013 update. S Afr J HIV Med 2013;14(2):7686. https://doi.org/10.7196/SAJHIVMED.930 13. National Department of Health, South Africa. Essential Drugs Programme: Primary Healthcare Standard Treatment Guidelines and Essential Medicines List. 5th ed. Pretoria: NDoH, 2014. www. health.gov.za/index.php/component/phocadownload/category/285-phc (accessed 13 February 2018). 14. Coetzee LM, Cassim N, Glencross DK. Laboratory diagnosis of early cryptococcal antigenaemia detection. Presented at the 2nd African Society for Laboratory Medicine Conference, Cape Town International Convention Centre, Cape Town, South Africa, 30 November - 4 December 2014. http:// aslm2014.org/programme/conference-books/ (accessed 8 June 2018). 15. Coetzee LM, Cassim N, Moodley K, Glencross D. Roadmap for implementing a national early detection programme for reflexed CrAg screening in national health CD4 laboratories in South Africa. Presented at the 7th SA AIDS Conference, International Conference Centre, Durban, South Africa, 9 - 12 June 2014. 16. Cassim N, Schnippel K, Coetzee LM, Glencross DK. Establishing a cost-per-result of laboratory-based, reflex cryptococcal antigenaemia screening (CrAg) in HIV+ patients with CD4 counts less than 100 cells/μl using a lateral flow assay (LFA) at a typical busy CD4 laboratory in South Africa. PLoS One 2017;12(2):e0171675. https://doi.org/10.1371/journal.pone.0171675 17. Cassim N, Schnippel K, Coetzee LM, Glencross DK. Estimating the cost-per-result of a national reflexed cryptococcal antigenaemia screening program: Forecasting the impact of potential HIV guideline changes and treatment goals. PLoS One 2017;12(8):e0182154. https://doi.org/10.1371/ journal.pone.0182154 18. Wake RM, Britz E, Sriruttan C, et al. High cryptococcal antigen titers in blood are predictive of subclinical cryptococcal meningitis among HIV-infected patients. Clin Infect Dis 2017;66(5):686-692. https://doi.org/10.1093/cid/cix872 19. Coetzee LM, Cassim N, Sriruttan C, Govender NP, Glencross DK. Cryptococcal prevalence rates in patients with CD4 counts <100 cells/μl in a national screening programme identifies advanced disease burden in districts for intensified programmatic support and fast tracking of patients into care. PLoS One 2018;13(6):e0198993. https://doi.org/10.1371/journal.pone.0198993 20. Coetzee LM, Cassim N, Glencross DK. Analysis of HIV disease burden by calculating the percentages of patients with CD4 counts <100 cells/µL across 52 districts reveals hot spots for intensified commitment to programmatic support. S Afr Med J 2017;107(6):507-513. https://doi.org/10.7196/ SAMJ.2017.v107i6.1131 21. Coetzee LM, Cassim N, Govender NP, Glencross D. CrAg positivity rates reported from a national CD4 reflexed screening programme identify high-risk regions of co-existent HIV/cryptococcal disease, requiring urgent programmatic focus into care. Presented at the XXII International AIDS Conference, Le Palais des Congres de Paris, Paris, France, 23 - 26 July 2017. https://www.ias2017.org/ (accessed 8 June 2018).

S Afr Med J 2018;108(7):534-535. DOI:10.7196/SAMJ.2018.v108i7.13094

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GUEST EDITORIAL

Paediatric asthma in South Africa: A case of hunger in times of plenty Asthma is a heterogeneous chronic inflammatory condition with variable airflow limitation and characterised by airway reversibility.[1] Globally, asthma is among the top five most common respiratory non-communicable diseases, with an estimate of >300 million sufferers.[2] The 2015 Global Burden of Disease Study found that worldwide 4 million deaths are due to chronic respiratory disease, with 80 - 90% occurring in low- and middle-income countries, including South Africa (SA).[3,4] In a modelling study, asthma prevalence was found to be increasing in adults and children in Africa. Asthma rates almost tripled over 20 years – from 40 million in 1990 to 119 million in 2010.[5] In the International Study of Asthma and Allergies in Childhood (ISAAC), SA children were found to have the highest prevalence of asthma symptoms: >20% in 13 - 14-year-olds and >50% with severe asthma symptoms, reflecting a high morbidity due to asthma.[6,7] An increasing prevalence of asthma has also been linked to increased rates of urbanisation. The following are risk factors for the development of asthma and more severe asthma symptoms: urbanisation, which is associated with increased exposure to air pollution due to traffic, poor ventilation of houses in peri-urban areas, high levels of violence, psychosocial stressors and little physical activity. Despite SA having an excellent package of medications for asthma care in the Standard Treatment Guidelines and Essential Medicines List for South Africa,[8] the number of asthma deaths remains high, with SA being among the top 10 countries in the world in terms of such deaths.[9] The key to improving asthma-related outcomes is linked to three main pillars: access to a diagnosis being made, appropriate access to medication, and education to improve adherence and achieve asthma control. In this issue of CME, the South African Childhood Asthma Working Group (SACAWG)[10,11] reviews the epidemiology, diagnosis and control of asthma in children. Diagnosis of paediatric asthma is particularly challenging, especially in preschool children ˂5 years of age. Although this age group has a low mortality risk, there is significant morbidity owing to over-utilisation of healthcare resources, e.g. multiple visits to healthcare providers, use of unnecessary and sometimes harmful medications and the need for repeated admissions. Primary-level healthcare providers do not feel confident to make the diagnosis of asthma in young children. Consequently, recurrent wheezing in a preschool child is not documented or is attributed to conditions other than asthma. Furthermore, the current traditional diagnostic tools for asthma in children >6 years old to demonstrate airways reversibility are difficult to use in preschool children. Noting these diagnostic challenges, a key change to the recommendations in confirming the presence of asthma in this age group is the concept of a 6 - 8-week trial of medication, followed by a period of cessation of

treatment to confirm the diagnosis of asthma. Should the symptoms recur with discontinuation of therapy, a diagnosis of asthma can then confidently be made. Achieving asthma control is one of the goals of asthma treatment. Poor asthma control is linked to a diminished quality of life and escalation of direct and indirect costs with regard to the condition. While an assessment of asthma control should be done during each follow-up visit, the new recommendations have been adapted to include the assessment of future risk for poor asthma outcomes, in line with the Global Initiative for Asthma recommendations.[1] A diagnosis of asthma and access to treatment are achievable goals in SA, even in young children, as long as healthcare providers perform a simple risk assessment and initiate a therapeutic trial of medications, thereby reversing the current status quo of poor access to diagnosis and therefore appropriate accessible treatment. Refiloe Masekela Inkosi Albert Luthuli Central Hospital and Department of Paediatrics and Child Health, College of Health Sciences, School of Clinical Medicine, University of KwaZuluNatal, Durban, South Africa masekelar@ukzn.ac.za 1. Global Initiative for Asthma. www.ginasthma.org (accessed 22 January 2017). 2. Global Asthma Report. 2014. http://globalasthmareport.org/ (accessed 5 May 2018). 3. Beran D, Zar HJ, Perrin C, Menezes AM, Burney P, for the Forum of International Respiratory Societies Working Group Collaboration. Burden of asthma and chronic obstructive pulmonary disease and access to essential medicines in low-income and middle-income countries. Lancet Respir Med 2015;3(2):159-170. https://doi.org/10.1016/S2213-2600(15)00004-1 4. GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980 - 2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388(10053):1459-1544. https://doi. org/10.1016/S0140-6736(16)31012-1 5. Adeloye D, Chan KY, Rudan I, Campbell H. An estimate of asthma prevalence in Africa: A systematic analysis. Croat Med J 2013;54(6):519-531. 6. Pearce N, Aït-Khaled N, Beasley R, et al., and the ISAAC Phase Three Study Group. Worldwide trends in the prevalence of asthma symptoms: Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2007;62(9):757-765. https://doi.org/10.1136/thx.2006.070169 7. Zar HJ, Ehrlich RI, Workman L, Weinberg EG. The changing prevalence of asthma from 1995 to 2002. Pediatr Allergy Immunol 2007;18(7):560-565. https://doi.org/10.1111/j.1399-3038.2007.00554.x 8. National Department of Health. Standard Treatment Guidelines and Essential Medicines List for South Africa: Hospital Level Paediatrics. Pretoria: NDoH, 2017. 9. Zar HJ, Stickells D, Toerien A, Wilson D, Klein M, Bateman ED. Changes in fatal and near fatal asthma in an urban area of South Africa from 1980 - 1997. Eur Respir J 2001;18:33-37. https://doi.org/10.11 83/09031936.01.00081801 10. Masekela R, Gray CL, Green RJ, et al., on behalf of the South African Childhood Asthma Working Group (SACAWG). The increasing burden of asthma in South African children: A call to action. S Afr Med J 2018;108(7):537-539. https://doi.org/10.7196/SAMJ.2018.v108i7.13162 11. Masekela R, Risenga SM, Kitchin OP, et al., on behalf of the South African Childhood Asthma Working Group (SACAWG). The diagnosis of asthma in children: An evidence-based approach to a common clinical dilemma. S Afr Med J 2018;108(7):540-545. https://doi.org/10.7196/SAMJ.2018.v108i7.13165

S Afr Med J 2018;108(7):536. DOI:10.7196/SAMJ.2018.v108i7.13387

July 2018, Print edition

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CME

The increasing burden of asthma in South African children: A call to action R Masekela,1 PhD; C L Gray,2 PhD; R J Green,3 PhD, DSc; A I Manjra,4 FCPaed (SA), M Clin Pharm; F E Kritzinger,5 Cert Pulmonology (SA) Paed; M Levin,2 PhD; H Zar,2 PhD; on behalf of the South African Childhood Asthma Working Group Inkosi Albert Luthuli Central Hospital and Department of Paediatrics and Child Health, School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa 2 Department of Paediatrics and Adolescent Health, Red Cross War Memorial Children’s Hospital and Faculty of Health Sciences, University of Cape Town, South Africa 3 Steve Biko Academic Hospital and Department of Paediatrics and Child Health, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa 4 Private Practice, Life Westville Hospital, Durban, South Africa 5 Netcare Christiaan Barnard Memorial Hospital, Cape Town; and Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa 1

Corresponding author: R Masekela (masekelar@ukzn.ac.za) Background. Asthma is a heterogeneous condition characterised by chronic inflammation and variable expiratory airflow limitation, as well as airway reversibility. The burden of asthma in children is increasing in low- and middle-income countries and remains underrecognised and poorly managed. Objectives. To quantify the burden of asthma in the South African (SA) population and identify the risk factors associated with disease severity in the local context. Methods. The SA Childhood Asthma Working Group (SACAWG) convened in January 2017 with task groups, each headed by a section leader, constituting the editorial committee on assessment of asthma epidemiology, diagnosis, control, treatments, novel treatments and self-management plans. The epidemiology task group reviewed the available scientific literature and assigned evidence according to the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. Conclusions. Asthma in children remains a common condition, which has shown an increasing prevalence in urban and rural populations of SA. Of concern is that almost half of children in urban communities experience severe asthma symptoms, and many asthmatics lack a formal diagnosis and thus access to treatment. Exposure to tobacco smoke and living in highly polluted areas increase the severity of wheezing in young children. S Afr Med J 2018;108(7):537-539. DOI:10.7196/SAMJ.2018.v108i7.13162

Asthma is a heterogeneous condition characterised by chronic inflammation and variable expiratory airflow limitation,[1] as well as airway reversibility. Worldwide, asthma is the most common chronic non-communicable disease in children. The most recent global estimate of asthma in adults and children (2008 - 2010) suggests that as many as 334 million people have asthma.[2] The historical view of asthma being a disease of high-income countries no longer holds. Most people affected reside in low- and middle-income countries, where asthma prevalence is estimated to be increasing fastest, while plateauing in high-income countries. Asthma carries a high economic cost to society and the healthcare system, with costs being both direct (hospitalisation, medications and outpatient visits) and indirect (related to absenteeism and loss of productivity). Improving access to care and medications, coupled with use of and adherence to evidence-based treatments, can reduce the economic burden of asthma. Accurate diagnosis of childhood asthma may be especially challenging in African settings, where respiratory infectious diseases predominate. In non-English-speaking populations, asthma terminology may not be easily translated into local languages. In resource-constrained areas, poor access to healthcare and lack of availability of lung function testing to confirm the diagnosis also contribute to delayed diagnosis.[3] Questionnaire-based studies must

be interpreted with caution, as these often rely on literate populations who understand the meaning of words such as ‘wheezing’ and ‘asthma’; this group of individuals may be prone to recall bias.[3] Despite these limitations, the International Study of Asthma and Allergies in Childhood (ISAAC) has provided the most reliable global, comparative data on the prevalence of asthma and other allergic conditions in children, using standard written and video questionnaires, enabling comparison of asthma prevalence between different parts of the world.

Objectives

We reviewed the current literature on the burden of asthma in South Africa (SA) in the context of other low- and middle-income countries and on rural and urban differences in prevalence and severity of asthma.

Methods

The SA Childhood Asthma Working Group (SACAWG) convened in January 2017 with six task groups, each headed by a leader (Appendix A), constituting the editorial committee on assessment of asthma epidemiology, diagnosis, control, treatments, novel treatments and self-management plans. The task groups reviewed the available scientific literature on the burden of asthma from high-quality datasets and any local data on asthma prevalence and severity in

July 2018, Print edition

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CME

children, and graded the level of evidence and recommendations based on the current evidence.

Asthma prevalence

Worldwide asthma prevalence

ISAAC phase I and phase III studies, using identical questionnaires, were performed ~7 years apart and enabled the investigation of time trends with regard to the symptoms of asthma. Studies were carried out in two age groups: children aged 6 - 7 years and adolescents aged 13 - 14 years.[4-6] The large number of children surveyed (>1 million), centres (N=233) and countries (N=98) that participated in ISAAC phase III, made this the most comprehensive global survey of childhood asthma to date.[7] The current overall worldwide prevalence of asthma (ISAAC phase III), measured by reported symptoms in children aged 6 - 7 years and 13 - 14 years, was 11.5% and 14.1%, respectively.[8] There was a significant variation in the prevalence of asthma between countries (Table 1). The prevalence of asthma in 13 - 14-year-old black African children was 15.3%, which was higher than the global average.[6] Moreover, the prevalence of childhood asthma in African countries is increasing, compared with that in many high-income settings, where it has stabilised or is decreasing.[3,4] Only two African centres in addition to SA centres included the younger age group of 6 - 7-yearolds. In these centres in Nigeria and Mozambique, the 12-month prevalence of wheeze was 5.6% and 13.3%, respectively.[9] Overall, in Africa, the 12-month prevalence of wheeze was 10.0% in the 6 7-years age group. Globally, the current prevalence of wheeze in this age group is 11.5% and that of severe wheeze 4.9%. The high, increasing prevalence of childhood asthma in Africa reported by ISAAC has been supported by studies measuring bronchial hyper-responsiveness (BHR) for diagnosing asthma. Such studies have shown a consistent increase in asthma prevalence in rural and urban settings in African countries.[10-14] Furthermore, black African children with asthma have been reported to have more severe

symptoms than those in high-income countries, which may relate to factors such as lack of diagnosis, access to care, affordability of therapy, as well as environmental irritants and genetic susceptibility to more severe disease, or a combination of these.[15]

Asthma prevalence in South Africa

The prevalence of asthma in SA children was measured using the ISAAC methodology in Cape Town in 1995 (phase I) and repeated 7 years later in 2002 (phase III). Children aged 13 - 14 years, from all population groups, were included in the study.[8] In 1995, a total of 5 178 children completed the questionnaire and in 2002, 5 037 children responded. The prevalence of lifetime and 12-month wheezing increased between phase I and phase III from 27.7% to 33.1% and 16.0% to 20.3%, respectively (Table 2).[8] Similarly, the 12-month prevalence of night waking with wheeze, severe wheeze, exercise-induced wheeze and nocturnal cough all increased significantly from 1995 to 2002. Worryingly, approximately half of all children with asthma had severe, uncontrolled symptoms.[7,8] ISAAC phase III was conducted in a rural population in Polokwane, Limpopo, in 4 660 children aged 13 - 14 years. The 12-month prevalence of asthma was 18%, while the prevalence of severe asthma symptoms in Cape Town was less (6.6%).[6] Using the ISAAC phase III methodology in a younger cohort (N=2Â 437) of 6 - 7-year-old black African children in Polokwane, the 12-month prevalence of wheeze and severe wheeze was 11.2% and 5.7%, respectively.[9] In this cohort, various potential risk factors and asthma symptoms were investigated. Living in a rural area was protective, which significantly decreased the likelihood of wheeze by 31%. Risk factors for the increased likelihood of wheeze included: exposure to environmental tobacco smoke (77%), eczema (104%) and rhinoconjunctivitis (226%) symptoms. The presence of rhinoconjunctivitis increased the likelihood of severe wheeze by 107%.[9] Studies in SA children measuring BHR confirmed the increase in asthma prevalence. In 1979, the first study of asthma prevalence in SA

Table 1. Current prevalence of asthma symptoms by world region in 6 - 7-year and 13 - 14-year age groups as measured in ISAAC phase III* Region Africa Asia-Pacific Eastern Mediterranean Indian subcontinent Latin America North America Northern and Eastern Europe Oceania Western Europe Global total

N 5 865 59 979 40 573 50 092 93 774 4 012 42 548 13 888 77 722 388 811

6 - 7 years n 589 5 719 3 824 3 392 16 256 767 3 715 3 020 7 487 44 799

13 - 14 years n 10 168 8 731 4 801 3 884 26 350 30 427 7 009 6 301 15 483 112 630

N 66 308 99 634 51 705 55 783 165 900 141 009 72 057 36 299 107 673 798 685

% 10.0 9.5 9.4 6.7 17.3 19.1 8.7 21.7 9.6 11.5

% 15.3 8.7 9.2 6.9 15.9 21.6 9.7 17.4 14.4 14.1

ISAAC = International Study of Asthma and Allergies in Childhood; n = number of participants with a positive asthma-screening questionnaire. *Adapted from AĂŻt-Khaled et al.[6]

Table 2. Current prevalence of asthma symptoms (12-month prevalence rate of wheeze) by region in South Africa in 6 - 7-year and 13 - 14-year age groups as measured in ISAAC phase I and phase III 6 - 7 years Region Cape Town (ISAAC I) Cape Town (ISAAC III)

N -

% -

N 5 178 5 037

Polokwane (ISAAC III)

2 437

11.2

4 660

ISAAC = International Study of Asthma and Allergies in Childhood.

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13 - 14 years % 16.0 20.3 18.0

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children found a 30-fold higher prevalence in urban (3.1%) compared with rural (0.01%) Xhosa children aged 7 - 9 years.[10] A follow-up study in 2003 reported an increase in asthma prevalence in urban and rural children, with a reduction in the urban-rural gradient.[13] Increased BHR was associated with rural children adopting an urban lifestyle. A later study measuring BHR also confirmed an increase in asthma prevalence in urban (15%) and rural (9%) Xhosa children, with a reduction in the urban-rural gradient.[14] Obesity was identified as a risk factor for an increase in BHR. The most recent study showed BHR in 16% of peri-urban black African teenagers, with high rates of allergen sensitisation in individuals with BHR.[15]

Risk factors for asthma

Eczema is an important risk factor for asthma, and longitudinal studies have shown that from one-third to one-half of children with eczema develop asthma.[17] In a SA study of 100 children with atopic dermatitis, 39% described symptoms of asthma according to the ISAAC questionnaire, and in 29% asthma was diagnosed by a doctor.[18] Asthma prevalence increased with age: at the time of the study asthma symptoms were present in 22% of children <2 years old, 43% of 2 - 4-year-olds and 50% of children >4 years old.[18] Industrial pollution is a further risk factor associated with a higher prevalence of asthma. A study in Durban questioned 422 learners (average age 10.5 years) on symptoms of asthma. In this cohort, the presence of symptoms that were consistent with asthma of any severity was 32%, and the prevalence of doctor-diagnosed asthma was 13.0 - 16.5%, depending on the area surveyed. Children from areas with higher levels of industrial pollution had a higher prevalence of respiratory health problems.[19] In a separate study in a highly polluted area in the south of Durban, which included 248 school-aged participants from grades 3 to 7, 52% had asthma of any severity, 11% had moderate-to-severe persistent asthma, and 21% had marked airways hyperreactivity on methacholine challenge testing.[20]

Asthma morbidity and mortality

Almost half of children in Cape Town who reported asthma in ISAAC phase III had severe symptoms.[8] Furthermore, >30% of children with severe asthma symptoms had never been formally diagnosed with asthma.[7,14] In addition to morbidity from childhood asthma, SA has a very high rate of asthma-related deaths, suggesting that lack of appropriate diagnosis, treatment or access to care may be important considerations.[16-18] Although SA was ranked 25th worldwide for the prevalence of asthma, it ranked 4th in asthma mortality in the 5 34-year-old age group and 5th for asthma case fatality rates, with an estimated 18.5 per 100 000 asthmatics.[17,18]

Conclusion

Childhood asthma remains a common condition, which has shown an increasing prevalence in urban and rural populations in SA. Of concern is that almost half of children in urban communities experience severe asthma symptoms, and many asthmatics lack a formal diagnosis and thus access to treatment. Exposure to tobacco smoke and living in highly polluted areas increase the severity of wheezing in young children. Acknowledgements. We acknowledge the hard work and contribution of the South African Childhood Asthma Working Group (SACAWG) members. We also acknowledge the huge contribution of the late Prof. Cas Motala, who was convener of the past three SACAWG guidelines. Author contributions. RM: review, write-up and manuscript editing; HZ, CLG: conceptualisation, methodology, write-up and manuscript editing; and ML, RJG, AIM, FEK: write-up and manuscript editing.

Funding. SACAWG conducted a workshop that received an unconditional educational grant from the Allergy Society of South Africa – funded by Novartis. Conflicts of interest. None. 1. Global Initiative for Asthma. www.ginasthma.org (accessed 22 January 2017). 2. The Global Asthma Report. www.globalasthmareport.org (accessed 22 January 2017). 3. Zar HJ, Levin ME. Challenges in treating paediatric asthma in developing countries. Pediatr Drugs 2012;14(6):1-7. 4. Asher MI, Montefort S, Bjorksten B, et al., and the ISAAC Phase Three Study Group. Worldwide trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006;368(9537):733-737. https://doi.org/10.1016/S0140-6736(6)69283-0 5. Pearce N, Aït-Khaled N, Beasley R, et al., and the ISAAC Phase Three Study Group. Worldwide trends in the prevalence of asthma symptoms: Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2007;62(9):757-765. https://doi.org/10.1136/thx.2006.070169 6. Aït-Khaled N, Odhiambo J, Pearce N, et al. Prevalence of symptoms of asthma, rhinitis and eczema in 13- to 14-year-old children in Africa: The International Study of Asthma and Allergies in Childhood Phase III. Allergy 2007;62(3):247-258. https://doi.org/10.1111/j.1398-9995.2007.01325.x 7. Mallol J, Crane J, von Mutius E, Odhiambo J, Keil U, Stewart A, the ISAAC Phase Three Study Group. The International Study of Asthma and Allergies in Childhood (ISAAC) phase three: A global synthesis. Allergol Immunopathol (Madr) 2013;41(2):73-85. https://doi.org/10.1016/j.aller.2012.03.001 8. Zar HJ, Ehrlich RI, Workman L, Weinberg EG. The changing prevalence of asthma from 1995 to 2002. Pediatr Allergy Immunol 2007;18(7):560-565. https://doi.org/10.1111/j.1399-3038.2007.00554.x 9. Wichmann J, Wolvaardt J, Maritz C, Voyi K. Household conditions, eczema symptoms and rhinitis symptoms: Relationship with wheeze and severe wheeze in children living in the Polokwane area, South Africa. Matern Child Health J 2009;13(1):107-118. https://doi.org/10.1007/s10995-007-0309-x 10. Van Niekerk CH, Weinberg EG, Shore SC, et al. Prevalence of asthma: A comparative study of urban and rural Xhosa Children. Clin Allergy 1979;9(4):319-324. https://doi.org/10.1111/j.1365-2222.1979.tb02489.x 11. Keeley D, Neil P, Gallivan S. Comparison of the prevalence of reversible airway obstruct in rural and urban Zimbabwean children. Thorax 1991;46(8):549-553. https://doi.org/10.1136/thx.46.8.549 12. Addo Yobo E, Custovic A, Taggard SC, et al. Exercise-induced bronchospasm in Ghana: Differences in prevalence between urban and rural school-children. Thorax 1997;52(2):161-165. https://doi. org/10.1136/thx.52.2.161 13. Steinman HA, Donson H, Kawalski M, et al. Bronchial hyper-responsiveness and atopy in urban, periurban and rural South African children. Paediatr Allergy Immunol 2003;14(5):383-393. https://doi. org/10.1034/j.1399-3038.2003.00062.x 14. Calvert J, Burney P. Effect of body mass on exercise-induced bronchospasm and atopy in African children. J Allergy Clin Immunol 2005;116(4):773-779. https://doi.org/10.1016/j.jaci.2005.05.025 15. Levin ME, Muloiwa R, Motala C. Associations between asthma and bronchial hyper-responsiveness with allergy and atopy phenotypes in urban black South African teenagers. S Afr Med J 2011;101(7):472-476. 16. Lai CK, Beasley R, Crane J, Foliaki S, Shah J, Weiland S, the ISAAC Phase Three Study Group. Global variation in the prevalence and severity of asthma symptoms: Phase three of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2009;64(6):476-483. https://doi.org/10.1136/thx.2008.106609 17. Van der Hulst AE, Klip H, Brand PL. Risk of developing asthma in young children with atopic eczema: A systematic review. J Allergy Clin Immunol 2007;120(3):565-569. https://doi.org/10.1016/j.jaci.2007.05.042 18. Gray CL, Levin ME, Zar HJ, et al. Food allergy in South African children with atopic dermatitis. Pediatr Allergy Immunol 2014;25(6):572-579. https://doi.org/10.1111/pai.12270 19. Naidoo RN, Robins TG, Batterman S, Mentz G, Jack C. Ambient pollution and respiratory outcomes among schoolchildren in Durban, South Africa. S Afr J Child Health 2013;7(4):127-134. https://doi. org/10.7196/SAJCH.598 20. Kistnasamy EJ, Robins TG, Naidoo R, Batterman S, Mentz GB, Jack C. The relationship between asthma and ambient air pollutants among primary school students in Durban, South Africa. Int J Environ Health 2008;2(3-4):365. https://doi.org/10.1504/IJENVH.2008.020929 21. Masoli M, Fabian D, Holt S, Beasley R, Global Initiative for Asthma (GINA) Program. The global burden of asthma: Executive summary of the GINA Dissemination Committee report. Allergy 2004;59(5):469-478. https://doi.org/10.1111/j.1398-9995.2004.00526.x 22. Zar HJ, Stickells D, Toerien A, Wilson D, Klein M, Bateman ED. Changes in fatal and near fatal asthma in an urban area of South Africa from 1980 - 1997. Eur Respir J 2001;18(1):33-37. https://doi.org/10. 1183/09031936.01.00081801 23. Beran D, Zar HJ, Perrin C, Menezes AM, Burney P, for the Forum of International Respiratory Societies Working Group Collaboration. Burden of asthma and chronic obstructive pulmonary disease and access to essential medicines in low-income and middle-income countries. Lancet Respir Med 2015;3(2):159-170. https://doi.org/10.1016/S2213-2600(15)00004-1

Accepted 7 May 2018.

Appendix A. The SA Childhood Asthma Working Group (SACAWG)

Epidemiology: H Zar (leader), Western Cape; C Gray, Western Cape. Diagnosis of asthma: R Masekela (leader), KwaZulu-Natal; S M Risenga, Limpopo; O P Kitchin, Gauteng; P Goussard, Western Cape. Assessment of asthma control: R J Green (leader), Gauteng; D White, Gauteng; G Davis, Gauteng. Pharmacotherapy: F E Kritzinger (leader), Western Cape; A Jeevanathrum, Gauteng; P de Waal, Free State; S Kling, Western Cape; A Vanker, Western Cape; T C Gray, Western Cape; J Morrison, Western Cape; A Puterman, Western Cape; E Zollner, Western Cape; D Rhode, Western Cape. Pharmacotherapy – other therapies: A I Manjra (leader), KwaZulu-Natal; P M Jeena, KwaZulu-Natal; V Naidoo, KwaZulu-Natal; M Annamalai, KwaZulu-Natal; A van Niekerk, Gauteng. Self-management plans: M Levin (leader), Western Cape; S Emanuel, Western Cape; D Hawarden, Western Cape; H Katz, Gauteng.

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The diagnosis of asthma in children: An evidencebased approach to a common clinical dilemma R Masekela,1 PhD; S M Risenga,2 Cert Pulmonology (SA) Paed; O P Kitchin,3 Cert Pulmonology (SA) Paed; D A White,4 Cert Pulmonology (SA) Paed; G Davis,5 MB ChB; P Goussard,6 PhD; A I Manjra,7 FCPaed (SA), M Clin Pharm; F E Kritzinger,6,8 Cert Pulmonology (SA) Paed; M Levin,9 PhD; H Zar,9 PhD; R J Green,10 PhD, DSc; on behalf of the South African Childhood Asthma Working Group (SACAWG) Inkosi Albert Luthuli Central Hospital and Department of Paediatrics and Child Health, School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa 2 Department of Pulmonology and Allergy, Faculty of Health Sciences, Polokwane/Mankweng Campus, University of Limpopo, Polokwane, South Africa 3 Private Practice, Netcare Waterfall City Hospital, Johannesburg, South Africa 4 Charlotte Maxeke Academic Hospital and Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 5 Private Practice, Greenside, Johannesburg, South Africa 6 Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa 7 Private Practice, Life Westville Hospital, Durban, South Africa 8 Netcare Christiaan Barnard Memorial Hospital, Cape Town, South Africa 9 Department of Paediatrics and Adolescent Health, Red Cross War Memorial Childrenâ&#x20AC;&#x2122;s Hospital and Faculty of Health Sciences, University of Cape Town, South Africa 10 Steve Biko Academic Hospital and Department of Paediatrics and Child Health, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa 1

Corresponding author: R Masekela (masekelar@ukzn.ac.za) Background. Asthma is a heterogeneous condition characterised by chronic inflammation and variable expiratory airflow limitation, as well as airway reversibility. The diagnosis of asthma in young children is limited by the inability to perform objective lung function testing in this group of patients and the wide variety of conditions that can phenotypically present with asthma-like symptoms. Objectives. To provide an evidence-based approach for clinicians to accurately diagnose asthma in young children and to assess the level of control to guide therapeutic decisions. Methods. The South African Childhood Asthma Working Group (SACAWG) convened in January 2017 with task groups, each headed by a section leader, constituting the editorial committee on assessment of asthma epidemiology, diagnosis, control, treatments, novel treatments and self-management plans. The asthma diagnosis and control task groups reviewed the available scientific literature and assigned evidence according to the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system, providing recommendations based on current evidence. Conclusions. Asthma in young children should only be diagnosed if all other causes of wheezing have been considered and excluded, and if there is a response to a therapeutic trial and worsening with withdrawal of asthma medication. Asthma control should be assessed at each visit to guide therapeutic decisions. S Afr Med J 2018;108(7):540-545. DOI:10.7196/SAMJ.2018.v108i7.13165

On a global scale, asthma is the most common chronic non-communicable disease in children. It is a heterogeneous condition characterised by chronic inflammation and variable expiratory airflow limitation,[1] as well as airway reversibility (evidence level C). Airway inflammation and airway obstruction are features of asthma and are usually not measured in young children, except in research settings. The term asthma, therefore, should not be used to describe preschool wheezing illness.[2] The child should demonstrate clinical improvement during 2 - 3 months of controller treatment, with worsening of symptoms after treatment cessation.[3] A history of other allergic disease (eczema or allergic rhinitis) or asthma in firstdegree relatives is useful in some instances (evidence level B).

Objectives

We reviewed the current literature on the diagnosis of asthma in children, with particular emphasis on young children and the

available evidence. We also examined the assessment of asthma control in children and the current evidence basis for the importance of these assessments.

Methods

The South African Childhood Asthma Working Group (SACAWG) convened in January 2017 with six task groups, each assigned to a section leader (Appendix A), who constituted the editorial committee on assessment of asthma epidemiology, diagnosis, control, treatments, novel treatments and self-management plans. The task groups reviewed the available scientific literature on the diagnosis of asthma and assessment of asthma control in young children according to high-quality evidence, graded the level of evidence, and made recommendations based on the literature (Appendix B).

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Asthma in children

The presentation and differential diagnosis of asthma differ significantly as the child matures. For the purpose of this review and in line with the current literature, children are categorised as preschoolers (<5 years of age) and older children.

Children <5 years of age

One-third of all children wheeze at least once before their third birthday. Children <5 years old are prone to frequently recurring viral upper-respiratory tract infections, which may be associated with wheeze. Although wheeze commonly occurs, most children are asymptomatic by school-going age, with only one-quarter having persistent symptoms and later developing asthma[2] (evidence level B). In South Africa (SA), wheeze and asthma need to be distinguished from other causes of pneumonia, e.g. tuberculosis and other bacterial pneumonias (Table 1). Predictive indices for asthma As asthma in infancy and preschoolers has nonspecific symptoms, making it difficult to determine who has or will have asthma, predictive models have been developed.[4] These models have been proposed to improve early diagnosis, and therefore early access to treatment.[5] Some of the predictive models are the modified asthma predictive index (mAPI) and the prevention and incidence of asthma and mite allergy (PIAMA) risk score (evidence level C).[5,6] Use of these scores has not been validated in the African setting, where the atopy levels are lower (evidence level C), and should therefore not be used in the SA context. History History-taking alone is often all that is needed to diagnose a preschool wheezing disorder. Rather than categorising the wheezy ‘phenotype’ of the child, the decision to initiate an asthma therapeutic trial should primarily be determined by the following: • Severity of wheezy episodes (presence of dyspnoea, increased respiratory rate and need for oxygen therapy during the episode).

• Frequency of wheezy episodes (the child is symptomatic for >10 days during upper-respiratory tract infections or has >3 wheezy episodes per year). • Temporal pattern of symptoms (presence of wheezing not only with viral colds (infections), but triggered by allergens, irritants (pollution), exercise and sudden emotional changes (crying or laughing) between episodes (evidence level C) or worsening of symptoms on most days and nights). • Reversibility of wheezy episodes (bronchodilator response test (evidence level D)). • A positive family history of eczema (allergic dermatitis), allergic rhinitis, allergic conjunctivitis and/or food allergy (evidence level B). • History of an individual child’s allergic problems, as mentioned above. Clinical examination This may be unhelpful in the young child, especially where there are no other atopic manifestations, but it must be remembered that ‘not all that wheezes is asthma’. Therapeutic trial The current evidence based on symptoms and their relationship to asthma diagnosis in under-5 children are set out in Table 2. The principle when starting treatment for a child with a wheezing disorder is that treatment should be viewed as a therapeutic trial, i.e. therapy should be initiated and the child followed up after 6 - 8 weeks (Fig. 1).[1,7,8] If there is no clinical response to therapy, it should be discontinued and a differential diagnosis considered as the cause of wheezing (Table 1). Should the child respond to therapy after the trial, medication should be discontinued. The reasons for a therapeutic response may be owing to the child being asthmatic or the natural history of improvement in the case of viral infections. Should symptoms recur after withdrawal of therapy, the child can be placed on maintenance therapy.[7,8] Early use of inhaled corticosteroids (ICSs) in preschool children with wheeze, reduces symptoms and prevents or delays the onset of

Table 1. Differential diagnosis of wheeze in children <5 years of age* Category Congenital upper airway

Disease entity Complete tracheal rings Tracheomalacia Laryngomalacia Vocal cord palsy/paresis Subglottic stenosis/post-intubation/ congenital Vascular rings/slings Bronchomalacia Gastroesophageal reflux disease Swallowing inco-ordination Laryngeal cleft Tracheo-oesophageal fistula Cystic fibrosis Primary ciliary dyskinesia Persistent bacterial bronchitis Primary immunodeficiency HIV Foreign body Tuberculosis granuloma Malignancies Enlarged heart Congenital heart disease (left-to-right shunts)

Congenital lower airway Aspiration

Bronchiectasis

Endobronchial lesions

Cardiac *Adapted from White et al.[3]

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Table 2. Diagnostic characteristics of asthma in children <5 years of age and grade of recommendation* Characteristics Exercise-/activity-induced symptoms Nocturnal coughing (problematic, with awakening) Symptoms persisting in children >3 years old Response to a bronchodilator (short-acting beta-agonist) No seasonal variation in symptoms Viral colds with accompanying chest involvement Symptoms with specific trigger exposure, including emotional upsets (e.g. crying and laughing) Response to a short course of oral corticosteroids during acute exacerbation of symptoms Comorbid allergic rhinitis, proven food allergy and atopic dermatitis Absence of seasonal variation Wheezing lasting >1 month A positive modified bronchodilator test

Grade A

C D

*Adapted from Global Initiative for Asthma.[1]

Table 3. Differential diagnosis of asthma in children 6 - 11 years of age* Condition Chronic upper-airway cough syndrome Inhaled foreign body Bronchiectasis Primary ciliary dyskinesia Congenital heart disease Bronchopulmonary dysplasia Cystic fibrosis

Symptoms Sneezing, itching, blocked nose, throat clearing Sudden onset of symptoms, unilateral wheeze Recurrent infections, productive cough Recurrent infections, productive cough, sinusitis Cardiac murmurs Preterm delivery, symptoms since birth Excessive cough and mucus production, gastrointestinal symptoms

*Adapted from Global Initiative for Asthma.[1]

Box 1. Clinical signs in children <5 years of age, suggesting an alternative diagnosis and a need for specialist referral

Therapeutic trial

Failure to thrive Continuous wheezing without a clear history of exacerbation Digital clubbing Failure to respond to 2 - 3 months’ optimal asthma treatment (e.g. correct technique, compliance) Vomiting associated with respiratory symptoms Very young age of onset of respiratory symptoms (often during the first month of life) Severe hypoxaemia at clinical presentation Focal/segmental lung signs Cardiovascular signs

6 - 8 weeks

STOP

No change

Worsening

Children 6 - 11 years of age

Stop asthma therapy

Restart chronic asthma treatment and review 3 - 4-monthly

Fig. 1. Therapeutic trial and review protocol for young children with suspected asthma.

asthma in children (evidence level A).[9-11] Therefore, early institution of therapy will not improve lung function of those who do not have asthma. There are specific clinical pointers, which should guide the healthcare practitioner to seek another diagnosis in children with persistent wheezing (Box 1).

For children ≥6 years of age, besides the presenting symptoms, variable airflow limitation can be demonstrated by objective testing on peak flow measurements or by spirometry (Box 2) – ideally before commencement of controller medication. Normal lung function tests do not exclude the diagnosis of asthma (evidence level B).[12] Where the history is suggestive of asthma with normal spirometry, other specialised tests, such as methacholine challenge and exercise challenge tests, may be done by a pulmonologist to confirm the diagnosis (Appendix C). If the respiratory symptoms are suggestive of asthma, but not confirmed by variable airflow limitation or resolution with commencement of therapy, an alternative diagnosis is usually sought and may include those listed in Table 3. Some of these conditions may coexist with asthma. Investigations that are not helpful in diagnosing asthma include chest radiography, which may be normal or show evidence of air trapping with hyperinflation.

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Box 2. Confirmation of variable airflow limitation and grade of recommendation Pulmonary function test Reduced FEV1/FVC (normal >0.9) when FEV1 is low Positive bronchodilator reversibility test with an increase in FEV1 of >12% predicted Positive exercise challenge test with a fall in FEV1 of >12% predicted or PEF >15%, target heart rate (0.8 × 220 - age in years) and noting that target heart rate can be reached earlier in children PEF variability 2 weeks twice a day, with an average daily diurnal PEF variability of >13% Excessive variation of pulmonary function between outpatient visits with variability of FEV1 >12% or PEF >15% (using the same peak flow meter during each visit) with or without respiratory tract infections

Grade A A A A A

FEV1 = forced expiratory volume in 1 second; PEF = peak expiratory flow.

Box 3. Recommendations to achieve asthma control and level of evidence Recommendations Once an asthmatic is on controller therapy, regular assessment of control is critical. Of equal importance is regular assessment of future risk (exacerbations and side-effects) Control must be formally measured at every visit and not fewer than 6-monthly Formal tools for assessing control include symptom assessments, scores (such as the cACT and ACQ) and spirometry For uncontrolled asthma in children >5 years old using a low-dose ICS, doubling the dose of ICS is as beneficial as adding a LABA Where ICSs cause local or systemic side-effects or there is a risk of such side-effects, LABA addition is preferred for poorly controlled asthma in children >5 years of age In more severe asthma, before the dose of ICS is increased or a new drug is added, it is critical to assess the reasons for poor control thoroughly, including reconsidering the diagnosis, educating patients and treating comorbidities LABA use has not been well studied in preschool children and efficacy and safety are not established. LABAs should not be used in these children LTRA use has been poorly studied in preschool children. LTRAs’ relatively clean safety profile makes them preferred addon options for poorly controlled preschool asthmatics

Level of evidence A B B A C B C B

cACT = childhood Asthma Control Test; ACQ = Asthma Control Questionnaire; ICSs = inhaled corticosteroids; LTRAs = leukotriene receptor antagonists; LABAs = long-acting beta agonists.

Table 4. Assessment of asthma control and future risk in children <5 years of age (evidence level B)* Symptom control Well controlled Partly controlled Uncontrolled In the past week, has the patient had: None 1-2 3-4 • Daytime asthma symptoms more than twice per week • Any night-time awakening due to asthma • Reliever use more than twice per week • Limitation of activity Risk factors for poor asthma outcomes Assess the patient’s risk for Exacerbations Uncontrolled asthma symptoms One or more exacerbations in the previous year Start of the child’s usual ‘flare-up’ season (especially if autumn) Exposures: tobacco smoke, indoor or outdoor air pollution, indoor allergens (e.g. house-dust mite, cockroaches, pets, mould), especially in combination with viral infection Major psychological or socioeconomic problems for child or family Poor adherence with controller medication or incorrect inhaler technique Fixed airflow obstruction Severe asthma with several hospitalisations History of bronchiolitis Medication side-effects Systemic: frequent courses of OCSs, high-dose and/or potent ICSs Local: moderate-/high-dose or potent ICSs, incorrect inhaler technique, failure to protect skin or eyes when using ICS by nebuliser or spacer with face mask ICSs = inhaled corticosteroids; OCSs = oral corticosteroids. *Adapted from Global Initiative for Asthma.[1]

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Predictors of asthma in childhood Factors that independently predict asthma in late childhood are male sex, post-term delivery, medium or low parental education, family history of asthma and/or other atopic diseases, frequency of wheeze and wheezing dyspnoea (not associated with a cold).[5]

Asthma control

Asthma control is the extent to which asthma symptoms can be observed in a patient or have been reduced or eliminated by treatment.[1] The recent Global Initiative for Asthma (GINA) guidelines suggest that the monitoring of asthma control is essential in all asthmatics.[1] Assessment of control should evaluate symptoms (over the past week and month) and quality of life. The risk of future exacerbations (as measured by spirometry and, possibly, exhaled nitric oxide) and medication side-effects (as a result of steroid use and, particularly, growth in children) must be assessed regularly. Optimal formal tools for assessing control offer the best insight into asthma control.[13] No test is a gold standard and all tests must be used in conjunction to assess control (evidence level B).[14] Every practitioner and all children >6 years of age should have access to a peak flow meter to assess changes in lung function. Asthma control is significantly more likely in patients or parents/ caregivers who are educated (know their disease), are regularly taught to use the inhaler device, have a written action plan and educational material (www.asthmasa.co.za) and are encouraged to use controller medication regularly (level I evidence). If control is suboptimal, determine the reasons and educate the patient. A small number of patients need adjustment of their treatment (Box 3). The child should demonstrate clinical improvement during the 2 3 months of controller treatment, with worsening of symptoms after treatment cessation (Fig. 1). Thereafter, assessment of asthma control and future risk can be determined at each visit (Table 4).

Conclusion

Asthma in young children should only be diagnosed when all other causes of wheezing have been considered and excluded, more so in younger children. A therapeutic trial should be performed in uncertain cases, with follow-up and withdrawal of therapy to confirm or exclude the diagnosis of asthma. Asthma control should be assessed at each visit to guide therapeutic decisions. Acknowledgements. We acknowledge the hard work and contribution of the South African Childhood Asthma Working Group (SACAWG) members. We also acknowledge the huge contribution of the late Prof. Cas Motala, who was convener of the past three SACAWG guidelines. Author contributions. RM: methodology, review, write-up and manuscript editing; SMR: conceptualisation, write-up and manuscript editing; OPK, DA, HZ, GD: conceptualisation, methodology, write-up and manuscript editing; ML, RJG, AIM, FEK: write-up and manuscript editing; and PG: conceptualisation, methodology, write-up. Funding. SACAWG conducted a workshop that received an unconditional educational grant from the Allergy Society of South Africa – funded by Novartis. Conflicts of interest. None.

1. Global Initiative for Asthma. 2017. www.ginasthma.org (accessed 22 January 2017). 2. Brand PLP, Baraldi E, Bisgaard H, et al. Definition, assessment and treatment of wheezing disorders in preschool children: An evidence-based approach. Eur Respir J 2008;32:1096-1110. https://doi. org/10.1183/09031936.00002108 3. White D, Masekela R. Recurrent wheeze in a child under five year of age. In: Manjra A, Levin M, Gray C, eds. ALLSA Handbook of Practical Allergy. 4th ed. Cape Town: ALLSA, 2018. 4. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. N Engl J Med 1995;332(3):133-138. https://doi.org/10.1056/NEJM199501193320301 5. Castro-Rodriguez JA. The asthma predictive index: A very useful tool for predicting asthma in young children. J Allergy Clin Immunol 2010;126(2):212-216. https://doi.org/10.1016/j.jaci.2010.06.032 6. Hafkamp-de Groen E, Lingsma HF, Caudri D, et al. Predicting asthma in preschool children with asthma-like symptoms: Validating and updating the PIAMA risk score. J Allergy Clin Immunol 2013;132:1303-1310. https://doi.org/10.1016/j.jaci.2013.07.007 7. Brand PLP, Caudri D, Eber E, et al. Classification and pharmacological treatment of preschool wheezing: Changes since 2008. Eur Respir J 2014;43(4):1172-1177. https://doi.org/10.1183/09031936.00199913 8. Bush A, Ngakumar P. Preschool wheezing phenotypes. Eur Med J 2016;1(1):93-101. 9. Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med 2006;354(19):1998-2005. https://doi.org/10.1056/ NEJMoa054692 10. Guilbert T, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med 2006;354(19):1985-1997. https://doi.org/10.1056/NEJMoa051378 11. The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000;343(15):1054-1063. https://doi.org/10.1056/ NEJM200010123431501 12. Galant SP, Morphew T, Newcomb RL, Hioe K, Guijon O, Liao O. The relationship of the bronchodilator response to poor asthma control in children with normal spirometry. J Pediatr 2011;158(6):953-958. https://doi.org/10.1016/j.jpeds.2010.11.029 13. Deschildre A, Pin I, El Abd K, et al. Asthma control assessment in a pediatric population: Comparison between GINA/NAEPP guidelines, childhood asthma control test (C-ACT), and physician’s rating. Allergy 2014;69(6):784-790. https://doi.org/10.1111/all.12402 14. Green RJ, Klein M, Becker P, et al. Disagreement between common measures of asthma control. CHEST 2013;143:117-122. https://doi.org/10.1378/chest.12-1070

Accepted 7 May 2018.

Appendix A. The SA Childhood Asthma Working Group (SACAWG)

Epidemiology: H Zar (leader), Western Cape; C Gray, Western Cape. Diagnosis of asthma: R Masekela (leader), KwaZulu-Natal; S M Risenga, Limpopo; O P Kitchin, Gauteng; P Goussard, Western Cape. Assessment of asthma control: R J Green (leader), Gauteng; D White, Gauteng; G Davis, Gauteng. Pharmacotherapy: F E Kritzinger (leader), Western Cape; A Jeevanathrum, Gauteng; P de Waal, Free State; S Kling, Western Cape; A Vanker, Western Cape; T C Gray, Western Cape; J Morrison, Western Cape; A Puterman, Western Cape; E Zollner, Western Cape; D Rhode, Western Cape. Pharmacotherapy – other therapies: A I Manjra (leader), KwaZuluNatal; P M Jeena, KwaZulu-Natal; V Naidoo, KwaZulu-Natal; M Annamalai, KwaZulu-Natal; A van Niekerk, Gauteng. Self-management plans: M Levin (leader), Western Cape; S Emanuel, Western Cape; D Hawarden, Western Cape; H Katz, Gauteng.

Appendix B. Level of evidence

IA Evidence from meta-analysis and randomised controlled trials IB Evidence from at least one randomised controlled trial IIA Evidence from at least one controlled trial without randomisation IIB Evidence from at least one or other quasi-experimental study III Evidence from non-experimental descriptive studies, such as comparative studies, correlation studies and case-controlled studies IV Evidence from expert committee reports, opinions or clinical experience of respected authorities

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Appendix B. Grades of Recommendation Assessment, Development and Evaluation (GRADE) Level of recommendation Quality of evidence A High B

Moderate

Low

Very low

Definition High-quality research very unlikely to change our confidence in the estimate effect based on level I evidence Moderate-quality evidence, where future research is likely to have an important impact on our confidence in the estimate effect. Based on level II evidence or extrapolated from recommendations from level I evidence Low-quality evidence, where future research is likely to have an important impact on our confidence in the estimate effect. Based on level III evidence or recommendations from level I and II evidence Very-low-quality evidence, where the estimate effect is uncertain. Based on level IV evidence or recommendations from level I, II and III evidence

Appendix C. Lung function testing in children >5 years of age and level of evidence[12] Lung function test Peak flow

Spirometry

Bronchial responsiveness

Advantages Cheap Easy-to-teach technique Pre-diagnosis and disease monitoring for older patients Computer incentive-based devices can obtain reliable tests in 2 - 6-year-olds Available at most centres Assess reversibility to bronchodilator

Successful in preschoolers and differentiates between chronic asthma and chronic coughing Facilitates diagnosis of asthma

Disadvantages Not reliable in young children

Level of evidence II

I FEV1 0.5 and FEV1 0.75 may be more reliable in preschoolers FEV1 0.5 an FEV1 0.75 (not validated for clinical application) Needs active co-operation and breath control Currently no recommendations for II cold air challenge testing

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Antimicrobial stewardship in a rural regional hospital – growing a positive culture E Junaid,1 MB ChB, BSc; L Jenkins,2 MB ChB, MFamMed, FCFP (SA), PhD; H Swanepoel,3 MB ChB, FC Path Clin (SA), MMed (Clin Path); Z North,4 MB ChB, MPH; T Gould,5 MB ChB, MMed (Int Med), FCP (SA) University of Manchester, UK; and Improving Global Health, NHS Thames Valley and Wessex Leadership Academy, UK Head of Clinical Unit: Family and Emergency Medicine, George Regional Hospital, Department of Health, Western Cape, South Africa; and Department of Family and Emergency Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa 3 Clinical pathologist, National Health Laboratory Service, George Regional Hospital, Department of Health, Western Cape, South Africa 4 Medical Manager, George Regional Hospital, Department of Health, Western Cape, South Africa 5 Head of Clinical Unit: Internal Medicine, George Regional Hospital, Department of Health, Western Cape, South Africa 1 2

Corresponding author: L Jenkins (louis.jenkins@westerncape.gov.za)

Antimicrobial stewardship programmes have been introduced worldwide in response to the rise in antimicrobial resistance. The World Health Organization has mandated each Member State to produce a plan to address this problem. We report on the organic development of an antibiotic stewardship programme in a rural regional hospital in a resource-limited setting in South Africa. This has resulted in organisational change with increased awareness, participation, monitoring and education in antibiotic stewardship throughout the hospital. S Afr Med J 2018;108(7):546-550. DOI:10.7196/SAMJ.2018.v108i7.13149

Antimicrobials are used to treat various infections caused by bacteria, viruses, fungi, protozoa and parasites. Of these, antibiotics specifically are used to treat various bacterial infections. Before Alexander Fleming’s revolutionary discovery of penicillin, millions of people died of now treatable infectious diseases. However, as he predicted with his discovery, the ability of microbes to develop resistance posed a threat to antibiotic treatment in the future. Fleming stated: ‘… there is the danger that the ignorant man may easily under dose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant’.[1] Consequently, microbes have become increasingly ‘resistant’ and survive against the antimicrobials that were once effective to treat infections. One driver of developing resistance is the inappropriate use of antimicrobials. Antimicrobial resistance is a growing problem worldwide. The increase in antimicrobial resistance, together with the insufficient numbers of new antimicrobials being produced, have triggered global concern about the future of treating infectious diseases. There is a worldwide fear that since the last major class of antibiotics was released in 1987, a post-antibiotic era is coming where there will not be enough agents to treat resistant infections.[2,3] Consequently, the World Health Organization (WHO) introduced the Global Action Plan on Antimicrobial Resistance at the 2015 World Health Assembly, with a focus on antimicrobial stewardship. Antimicrobial stewardship programmes include the appropriate use of antimicrobials, aiming to reduce resistance to antimicrobials and prevent the spread of infection. It was mandated that each Member State of the WHO should produce its own plan.[3] This article describes the development of an institutional antibiotic stewardship programme, with a focus on bacterial infection, based on the national plan and conceptual framework of the National Department of Health and implemented over 3 years in a rural regional hospital in South Africa (SA).

National context

SA has a high burden of morbidity and mortality from infectious diseases.[4] One study in 2003 (National Department of Health, South Africa, ‘Impact of the Essential Drugs Programme at primary health care level in South Africa’, described in the 2017 South African Health Review[5]) showed that the percentage of encounters in which an antibiotic was prescribed increased from 36% to 47% between 1998 and 2003. In view of the global strategies for antimicrobial stewardship and the mandate from the WHO, a national plan for antimicrobial stewardship in SA was developed, together with a conceptual framework (Fig. 1).[5]

Local context

George Hospital is a level 2 regional referral hospital with primary, secondary and tertiary services, located in the Western Cape Province of SA. This 272-bed facility has specialists in most clinical departments, operating theatres, outpatient departments, critical care and a robust outreach and support programme to the 10 outlying district hospitals. The pharmacy department consists of six non-ward pharmacists. The on-site National Health Laboratory Service (NHLS) laboratory has a clinical pathologist trained in microbiology, and the hospital has a nursing-based infection prevention and control (IPC) clinical programme co-ordinator. There is a strong commitment to the training of undergraduate and postgraduate students from the universities of Cape Town and Stellenbosch, interns, international students, and students and interns in the nursing, allied health and pharmacy professions. The hospital serves the communities of Eden and Central Karoo districts, which have a combined population of ~685 000 people, with a literacy rate of 82.6% and 73.4%, respectively. [7,8] The main languages spoken are Afrikaans, English and Xhosa. Antibiotic stewardship was first introduced in the Western Cape at Groote Schuur Hospital (GSH), which is the referral hospital for

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George, in 2012.[9] In the initial phase of its antibiotic stewardship programme, the GSH Department of Internal Medicine introduced dedicated antibiotic stewardship ward rounds and a dedicated prescription chart.[10] Subsequently, during outreach from the Department of Internal Medicine at GSH to George Hospital, the hospital became sensitised to antibiotic stewardship and started to develop its own local antimicrobial stewardship programme.

The antibiotic stewardship programme Early days – incubating the concepts

In February 2015, the Department of Internal Medicine at George Hospital started creating awareness around antibiotic stewardship.

Impact: Rational antimicrobial use and improved patient outcome

Antimicrobial resistance governance

Enhance surveillance

Antimicrobial stewardship

Prevention including IPC and vaccination

Education and communication/public awareness

Health systems strengthening, research, education and communication Fig. 1. Pillars of the South African antimicrobial stewardship strategy framework.[6] (IPC = infection prevention and control.)

As part of a collaborative leadership development initiative between the Western Cape Department of Health and the Improving Global Health (IGH) through Leadership Development Programme in the UK, the hospital has been allocated a dedicated young doctor or other health professional for 6-month periods, to partake in a local systems improvement project. Three ‘fellows’ at a time have been rotating for 6-month periods at George Hospital since 2014, each addressing a specific quality improvement project in the George subdistrict. These fellows are supervised by local senior health professionals, who act as mentors to help the fellows develop leadership skills in a health management environment. With each 6-month period, a fellow is allocated to quality improvement of the antibiotic stewardship programme. This has ensured continued local leadership by a dedicated champion for antibiotic stewardship improvement over 3 years, with each subsequent fellow continuing where the previous fellow left off. We utilised project management principles from the quality improvement model used by Brink et al.[11] in an antibiotic stewardship implementation study in 47 SA hospitals, which ran over 5 years. At the start of this collaboration, there was no formal antimicrobial stewardship programme. Antibiotic stewardship ward rounds were being held in three departments, namely General Surgery, Paediatrics and Internal Medicine. With ongoing outreach support from the tertiary hospital (GSH), and learning from their programme, George Hospital introduced an antibiotic stewardship programme in February 2015. This included several components, namely: • Weekly dedicated antibiotic stewardship ward rounds, attended by multi-professional teams of doctors, pharmacists and nurses and the clinical pathologist from the on-site NHLS laboratory • A dedicated prescription chart • Audit tools for pharmacy, IPC and ward rounds • Regular multi-professional reviews with doctors, pharmacists, nurses, the clinical pathologist, management and the IGH fellow • A hospital-wide education programme incorporating current principles of antibiotic stewardship, with small-group discussions, posters, flash cards, and an e-training module for staff (Table 1)[10] • Infection prevention and control programme monitoring.

Standards were set for 6-monthly audits and were adjusted upon Figure 1. Pillars of the South African review during each successive phase of the programme, relevant to and integrated with the performance of the hospital at the time. Implementation data were collected by the antibiotic stewardship audit team consisting of the current IGH fellow, the IPC nurse, the pharmacy and the clinical pathologist. Data included uptake of the antibiotic stewardship ward rounds in each clinical department, antibiotic consumption, quality of prescribing, use of laboratory tests and antibiotic chart compliance.

Table 1. Checklist for optimal antibiotic prescribing[12] 1. Drug – which is the narrowest-spectrum antibiotic that I can use to treat this bacterial infection? 2. Dose – many antibiotics require weight-based dosing and their dosing depends on renal and/or hepatic function. 3. Dose frequency – dependent on the half-life of the drug and whether the action of the antibiotic depends on the time above the MIC or the area under the concentration/time curve. Calculation of the dosing frequency may require therapeutic drug monitoring, such as for vancomycin or aminoglycosides 4. Duration – should be dictated by evidence from randomised controlled trials whenever possible. Expert opinion from national and international guidelines should be consulted where evidence is weak. 5. Route – most antibiotics have good oral bioavailability, but some infections will require intravenous therapy either for the whole or part of the course. 6. De-escalation – applies to the spectrum of antibiotic use and route of administration. All attempts to convert early from parenteral to oral use should be made. MIC = minimum inhibitory concentration.

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Results â&#x20AC;&#x201C; growing the culture

The main findings of the programme so far have been the following: Increased awareness among staff of antibiotic stewardship principles This has been achieved through various media, including posters that explain correct infection prevention and control practices and address issues of hand washing and isolation procedures for the different indications, as well as posters on principles for antibiotic prescribing. While only the Department of Internal Medicine engaged with the programme in 2015, roll-out and uptake of the programme across all clinical departments has resulted in a changed institutional culture over 3 years; for example, the newly introduced antibiotic prescription charts are now integrated into the general prescription charts across the hospital. Institution-wide uptake of antibiotic stewardship ward rounds Dedicated weekly multi-professional ward rounds are taking place in the departments of General Surgery, Internal Medicine, Family Medicine, Paediatrics, Emergency Medicine, Orthopaedics, Neonatology and Obstetrics and Gynaecology. The number of ward rounds has increased; for example, in February 2017 there were only four rounds, which increased to 25 in November 2017.

DDSs/100 patient days

Increased tracking and reporting in antibiotic stewardship process measurements Since the start of the programme, antibiotic prescription chart auditing has been ongoing and continually evolving, as has the production of data on antibiotic consumption, antibiotic stewardship ward round quality, intravenous line and trans-urethral catheter use, and healthcare-associated infections. These data are now being reported to staff at all levels through email, via a dedicated noticeboard and an electronic communication system and at the Hospital Antimicrobial Stewardship Committee meetings. Antibiotic consumption data are collected and analysed provincially through a system of defined daily doses (DDDs)/100 days and sent through to the hospital on a periodic basis (Fig. 2). Comprehensive completion of the prescription chart, including patient weight, allergies, renal function and proof of culture, is a way to show that there has been consideration of all parameters related to antibiotic prescribing. It also allows for pharmacists to assess the chart when it is reviewed by them. An antibiotic prescription chart audit in November 2017 showed that dosing considerations filled in on the chart have improved for weight and estimated glomerular filtration rate (eGFR); however, allergy entries decreased compared with January 2017 (weight 88%, allergy 72%, eGFR 83% v. weight 71%, allergy 86%, eGFR 65%, respectively). This has led to increased

489.65 469.42 461.15

460.56 441.71

Financial quarter 2016/17

Fig. 2. DDDs/100 patient days at George Hospital between April 2016 and June 2017. (DDDs = defined daily doses.)

staff training by the stewardship teams during ward rounds as well as performance reporting at antibiotic stewardship board feedback meetings. Education on sending of cultures prior to antibiotic commencement has resulted in an observed increase in awareness of the principle. Regular, iterative, patient-centred bedside educational meetings during ward rounds on antibiotic stewardship These occur between members of the team and are multi-professional in teaching and learning roles. Members of the rounds report increased knowledge on stewardship principles because of these learning opportunities (reports from other staff members). Emergence of the multi-professional team during the dedicated ward rounds Ward rounds now regularly include the ward doctors, the ward nurses, a pharmacist, the clinical pathologist and the institutional infection control nurse, as well as the IGH fellow. Dedication of resources towards the programme Resources include providing training opportunities in antibiotic stewardship and the allocation of dedicated IGH fellows.

Discussion

The implementation of the antibiotic stewardship programme at George Hospital has been multifaceted, with various interventions being introduced to strengthen it. The main results have been an increase in awareness of antibiotic stewardship principles and an increase in dedicated ward rounds. These can be attributed to the various components of the programme as described in the National Quality Partners Playbook: Antibiotic Stewardship in Acute Care:[13] leadership commitment, health worker accountability, drug expertise, action, tracking, reporting and education. Implementing a stewardship programme requires dedicated staff to champion the programme at various levels and in multiple health professions. Antimicrobial stewardship has been championed by the senior management staff at George Hospital, including the provision of four dedicated IGH fellows to the programme, specifically focusing on quality improvement in health systems, the presence of the medical manager on the board of the Hospital Antimicrobial Stewardship Committee, promoting regular training and education opportunities in antibiotic stewardship, and dedicated weekly time allocation to encourage staff to participate in antibiotic stewardship ward rounds. Overall leadership of the programme itself has been owned by the resident clinical pathologist. The importance of leadership accountability been shown through co-ordination and championing of antibiotic stewardship ward rounds, ensuring that they take place, and education on antibiotic stewardship as an expert in the area. Actively encouraging staff to engage with the rounds on a ward-to-ward basis has been a driving force in increasing buy-in from staff and is now established practice, even in the absence of the IGH fellows. A number of other quality improvement projects formed part of the programme. For example, an audit was conducted on the appropriate use of surgical prophylaxis. In the orthopaedic ward, intravenous cefazolin was being used as ward stock with little discretionary control.[14] As a result, it was removed as ward stock to enable review of antibiotics prior to dispensing, leading to improved quality of prescriptions in that ward. In addition, auditing of ward round compliance and quality occurred, leading to improvements. Tracking of metrics in antibiotic stewardship has been produced locally and provincially in the form of a facility antibiogram and

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Cefuroxime (parenteral) Cefuroxime (oral) Ceftriaxone (nonCNS infection) Ceftriaxone (CNS infection) Ceftazidime Cefoxitin Cefotaxime/ceftriaxone Cefepime Ampicillin/ amoxicillin

88 92 77 100 43 87 100 47 0 80 100 100 0 0 100 77 0 22 91 96 100 88 100 80 100 89 0 100 100 100 4 13 86 100 100 97 48 100 0 0 20 0 0 0 0 100 100 100 100 100 100 100 100 100 100 100 100 0 100 100 100 100 100 100 0 100 100 100 0 92 100 100 96 90 96 96 100 94 100 80 100 100 89 0 0 0 0 91 50 100 86 100 100 100 100 100 100 100 100 100 100 100 100 93 63 88 91 100 94 100 100 100 100 89 100 0 0 0

Isolates, n

Organism Gram positives Staphylococcus aureus Coagulase-neg. staphylococci Streptococcus pneumoniae Viridans group streptococci S. pyogenes S. agalactiae Enterococcus faecalis E. faecium Gram negatives Escherichia coli Klebsiella pneumoniae K. oxytoca Proteus mirabilis P. vulgaris Enterobacter cloacae E. aerogenes Serratia marcescens Pseudomonas aeruginosa Acinetobacter baumannii Stenotrophomonas maltophilia Salmonella (non-typhi) S. typhi Shigella spp.

Amikacin

56 27 15 8 16 1 0 0 99 23 1 17 1 5 2 1 9 1 1 13 1 9

Amoxicillinclavulanic acid

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CNS = central nervous system; neg. = negative.

Ciprofloxacin

95 79 100 100 100 0

Clindamycin

93 90 100 88 96 100 94 100 100 100 100 89 0 100 100 100

Cloxacillin

91 87 0 100 0 0 100 0 0 0 0 0 0

Ertapenem

87 87 0 100 0 0 100 0 0 0 0 0 0

Antibiotic, % of organisms sensitive

Erythromycin/ azithromycin

100

Gentamicin

100

Imipenem

94 87 100 100 100 80 100 100 89 0 100 100 100

Meropenem

95 100 100 100 100 0 0 0 0 0 0 0 0

Nitrofurantoin

94 87 100 100 100 80 100 100 0 0 100 100 100

Penicillin/ ampicillin

94 87 100 100 100 80 100 100 89 0 100 100 100

Piperacillintazobactam

100 26 0 0 47 0 0 0 77 0 44

Trimethoprimsulfamethoxazole

77 83 100 100 100 0 0 0 0 0 92 100 44

Vancomycin

Table 2. George facility antibiogram – emergency centre

DDDs, respectively. Local resistance patterns of organisms to antibiotics are collected and presented to the clinical and management staff by the clinical pathologist (Table 2). These are produced according to guidelines as set out by the Clinical and Laboratory Standards Institute, USA. There may be numerous reasons for the lack of change in the DDDs, one of which could simply be the early nature of the programme. It is postulated that the DDDs should have decreased on review in a year’s time. Reporting the hospital’s performance in metrics for antibiotic stewardship has been a strong focus. The platforms for reporting have included the Hospital Antimicrobial Stewardship Committee meetings held on a quarterly basis, where data are presented, feedback is given and areas for improvement are proposed. This information is made available to all hospital staff through the hospital’s online enterprise content management platform. The information is also displayed through a dedicated noticeboard in antibiotic stewardship. These platforms all provide ways to raise awareness of what is being done for stewardship in the hospital and why it is being done, and encourage staff to identify areas for improvement and formulate recommendations. Education in antibiotic stewardship principles has also been a key component of the programme. This has included face-to-face training of pharmacy staff, doctors and nurses at the patient bedside during ward rounds, as well as a George Hospitalspecific online learning module for annual training to be completed during the induction programme by new medical staff. Posters have also been distributed around the hospital to educate the wider nonclinical medical staff and the public, particularly in conjunction with the annual World Antibiotic Awareness Week. The development of signage for infection prevention and control processes, which includes isolation of patients with communicable diseases, particularly tuberculosis, and handhygiene instruction posters, has helped to educate the public and other non-medical staff.

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The commencement of the multi-professional stewardship rounds across all departments and the strengthening of the previously commenced ward rounds have added a new level of patientcentred care around evidence-based medicine, with the various team members discussing and learning together, which we have observed to encourage communication between disciplines, checking the Essential Drugs List, the provincial coding list and the South African Antibiotic Stewardship Programme mobile application for accurate and appropriate prescriptions.[14,15]

Future growth

Antibiotic stewardship is continually evolving worldwide. Before 2015, George Hospital had no explicit awareness of or structured approach to antibiotic stewardship. While the hospital is situated in a public, rural, resource-limited setting, a robust quality improvement programme in antibiotic stewardship has been initiated and is continually being improved. This article attempts to share this local experience with a wider audience. Future goals include producing antibiograms for the six surrounding subdistricts to engage and increase the understanding of staff in the referring hospitals around antibiotic stewardship, and recognising the effect of micro-organism resistance in referring hospitals in Eden and Central Karoo. Other goals include the introduction of a dedicated pharmacist who is trained in and has expertise in antibiotic stewardship. Local prescription guidelines based on local resistance patterns will also be developed. Auditing and reporting should continue to improve and expand, considering the further use of information technologies in antibiotic stewardship metrics. Similarly, online resources and other media forums for the local communities for antibiotic education could be of benefit. The key, as described by Mendelson,[12] is for ‘… every prescriber to become an antibiotic steward’. Acknowledgements. The authors are grateful for the support of all the staff at George Hospital who are still participating in the programme. Support for the programme from the CEO, Mr M Vonk, the nursing head, Ms E Sellars, the head of pharmacy, Ms S Brits, and Eden District Office is also acknowledged.

Author contributions. EJ conceptualised the original manuscript. LJ and HS contributed extensively to the subsequent drafts. All authors added to and approved the final draft. Funding. None. Conflicts of interest. None.

1. Fleming A. Fleming Lecture. Nobel Prize. 11 December 1945. https://www.nobelprize.org/nobel_prizes/ medicine/laureates/1945/fleming-lecture.pdf (accessed 27 January 2018). 2. World Health Organization. Global Action Plan on Antimicrobial Resistance. 2015. http://apps.who.int/ iris/bitstream/10665/193736/1/9789241509763_eng.pdf?ua=1 (accessed 27 January 2018). 3. O’Neill J. Review on Antimicrobial Resistance. Tackling drug-resistant infections globally: Final report and recommendations. May 2016. https://amr-review.org/sites/default/files/160518_Final%20paper_ with%20cover.pdf (accessed 27 January 2018). 4. Statistics South Africa. Mortality and causes of death in South Africa, 2015: Findings from death notification. http://www.statssa.gov.za/publications/P03093/P030932015.pdf (accessed 27 January 2018). 5. Padarath A, Barron P, eds. South African Health Review 2017. Durban: Health Systems Trust:53. http://www.hst.org.za/publications/South%20African%20Health%20Reviews/HST%20SAHR%20 2017%20Web%20Version.pdf (accessed 6 June 2018). 6. National Department of Health, South Africa. Antimicrobial Resistance National Strategy Framework 2014 - 2024. Pretoria: NDoH, 2014. http://www.health.gov.za (accessed 27 January 2018). 7. Western Cape Government. Socio-economic Profile Central Karoo District Municipality. Cape Town: Western Cape Government, 2016. https://www.westerncape.gov.za/assets/departments/ treasury/Documents/Socio-economic-profiles/2016/Central-Karoo-District/dc05_central_karoo_ district_2016_socio-economic_profile_sep-lg.pdf (accessed 27 January 2018). 8. Western Cape Government. Socio-economic Profile Eden District Municipality. Cape Town: Western Cape Government, 2016. https://www.westerncape.gov.za/assets/departments/treasury/Documents/ Socio-economic-profiles/2016/Eden-District/dc04_eden_district_municipality_2016_socioeconomic_profile_sep-lg.pdf (accessed 27 January 2018). 9. Boyles TH, Whitelaw A, Bamford C, Moodley M, Bonorchis K. Antibiotic stewardship ward rounds and a dedicated prescription chart reduce antibiotic consumption and pharmacy costs without affecting inpatient mortality or re-admission rates. PLoS One 2013;8(12). https://doi.org/10.1371/ journal.pone.0079747 10. Federation of Infectious Diseases Societies of Southern Africa. About SAASP: Mission Statement of the South African Antibiotic Stewardship Programme. 2017. http://www.fidssa.co.za/SAASP (accessed 14 December 2017). 11. Brink AJ, Messina AP, Feldman C, et al. Antimicrobial stewardship across 47 South African hospitals: An implementation study. Lancet Infect Dis 2016;16(9):1017-1025. https://doi.org/10.1016/S14733099(16)30012-3 12. Mendelson M. Role of antibiotic stewardship in extending the age of modern medicine. S Afr Med J 2015;105(5):414-418. https://doi.org/10.7196/SAMJ.9635 13. National Quality Forum. Antibiotic Stewardship in Acute Care. Washington, DC: The Joint Commission, 2016. https://www.jointcommission.org/assets/1/6/New_Antimicrobial_Stewardship_ Standard.pdf (accessed 27 January 2018). 14. National Department of Health, South Africa. Standard Treatment Guidelines and Essential Medicines List for South Africa. 2015. http://www.kznhealth.gov.za/pharmacy/hospitallevel_adult2015.pdf (accessed 27 January 2018). 15. Wasserman S, Boyles T, Mendelson M. South African Antibiotic Stewardship Programme – a Pocket Guide to Antibiotic Prescribing for Adults in South Africa. https://www.fidssa.co.za/Content/ Documents/SAASP_Antibiotic_Guidelines_2015.pdf (accessed 27 January 2018).

Accepted 10 May 2018.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

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Current strategies are inadequate to curb the rise of tobacco use in Africa N Peer, MB ChB, MBA, MPH, PhD Non-communicable Diseases Research Unit, South African Medical Research Council, Durban, South Africa Corresponding author: N Peer (nasheeta.peer@mrc.ac.za)

Recently, there have been significant advances in the battle against tobacco use in Africa, with achievements including ratification of the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) and the passing of tobacco control legislation in several countries. Many African countries have achieved measured success, while Uganda, South Africa and Mauritius have accomplished significantly more in their efforts to curb tobacco use. Nevertheless, few African countries meet the standards of the individual WHO FCTC articles with regard to comprehensive implementation. Africa has lower rates of tobacco taxation, weaker smoke-free policies and fewer restrictions on tobacco advertising compared with other world regions. These shortcomings have enabled the tobacco industry to expand its markets on the continent by capitalising on economic growth, changing social norms and population demographics. Consequently, tobacco use is increasing in Africa, with smoking prevalence having risen 57% between 1990 and 2009 compared with western Europe, where it decreased substantially during the same period. Rapid smoking uptake in Africa has led to tobacco-related conditions emerging as increasingly important public health problems. African nations are unlikely to meet the 2025 goal of a 30% relative reduction in tobacco use, as advocated by the World Health Assembly in 2013 and identified as the ‘most urgent and immediate priority’ intervention to reduce non-communicable diseases (NCDs). While there has been some progress, the current commitment of most African countries to the WHO FCTC has not translated into effective delivery of tobacco control policies and programmes. Strong tobacco control policies, which are among the most effective population-based strategies for NCD prevention, are needed. These include introducing higher tobacco excise taxes, stronger smoke-free policies, graphic warnings on cigarette packages, bans on tobacco advertising, promotion and sponsorship, and anti-smoking mass media campaigns. Furthermore, tobacco industry interference needs to be actively addressed by monitoring its activities and exposing misconducts, thereby changing attitudes to the industry. Technical support, capacity building and adequate financing are needed in Africa to enable countries to competently manage legal challenges to tobacco control and deal with the subversive tactics of the industry. Civil society and the media – major players in holding governments accountable for responsible stewardship – need to educate and pressurise African politicians and governments to implement and enforce effective tobacco control policies. Otherwise, if unchecked, the widespread uptake of tobacco use will be a threat not only to health but also to sustainable human development in Africa. S Afr Med J 2018;108(7):551-556. DOI:10.7196/SAMJ.2018.v108i7.12978

Tobacco use has become a huge and growing public health burden worldwide, with the threat to global health greater today than ever before.[1] Even in Africa, where smoking prevalence has increased only recently, lung cancer is now the most common cause of cancerattributable mortality in men.[2] This underscores the rapidity of smoking uptake in Africa that has led to tobacco-related conditions emerging as an increasingly important public health problem on the continent.[3] Although Africa had the lowest smoking prevalence (12%) compared with other world regions,[4] it has increased by 57% between 1990 and 2009.[5] This contrasts with western Europe, the area with the highest smoking prevalence, which witnessed a decrease of ~26% in tobacco use during the same period.[5] Of further concern is the smoking prevalence in African youth, as it was not significantly lower than that in all other World Health Organization (WHO) regions, unlike in adults. It is also a reflection of the tobacco industry’s success in promoting tobacco uptake in the region.[6] Current trends predict that African nations are unlikely to meet the 2025 World Health Assembly 2013 goal of a 30% relative reduction in tobacco use, which was identified as the ‘most urgent and immediate priority’ intervention to reduce non-communicable diseases (NCDs).[7] Although it is projected that global tobacco smoking prevalence will decrease, it is expected to be 3.5 percentage

points above target. This represents a 14% relative reduction compared with the desired 30% relative reduction in smoking prevalence. Disconcertingly, however, in Africa and the Eastern Mediterranean WHO regions, smoking prevalence is expected to increase between 2010 and 2025. In Africa, smoking prevalence is predicted to increase by 41% – from 12.8% in 2010 to 18.1% in 2025, compared with the prediction of 26% for the Eastern Mediterranean.[7] Therefore, although global targets for smoking reduction will not be achieved, in the latter two regions there is a trend towards increased smoking prevalence, which warrants an appraisal of the situation. Tobacco-related morbidity and mortality in Africa will not only have a devastating impact on health but also on development and economic growth of the continent. In addition to the suffering and loss of life, there are far-reaching social and financial repercussions as breadwinners succumb to tobacco-related illnesses, thereby perpetuating the vicious cycle of poverty.[3] In low-resource settings, healthcare costs for these conditions, including prolonged and expensive treatment, together with the loss of breadwinners, rapidly drain household incomes and force families into poverty. Therefore, it is crucial that African countries urgently target tobacco use, implement measures to curb its uptake and halt the use of tobacco products. This article discusses the current tobacco

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control strategies in Africa, highlighting the difficulties associated with the implementation of such initiatives, and deliberates on the way forward.

Tobacco control strategies: WHO Framework Convention on Tobacco Control

The WHO Framework Convention on Tobacco Control (WHO FCTC), adopted by the World Health Assembly in May 2003, requires state parties to adopt and implement tobacco control measures, and guides governments with regard to suggested policies and programmes for reducing tobacco use.[8] Among the key strategies advocated are banning tobacco advertising, promotion and sponsorship, introducing smoke-free policies by prohibiting smoking in public and workplaces, imposing high taxes on tobacco products, introducing health warnings on cigarette packages, implementing anti-tobacco media campaigns and promoting smoking cessation. All of these approaches are effective, involve minimal costs and should be easy to execute.[9] Nevertheless, numerous obstacles exist worldwide, particularly in Africa and other developing regions. Consequently, what should be a simple endeavour, becomes rather difficult to achieve.

Tobacco control strategies in Africa

Recently, there have been significant advances in the battle against tobacco use in Africa, with achievements including ratification of the WHO FCTC and passing of tobacco control legislation in several countries. In the WHO African Region, 44 of the 47 countries have ratified the WHO FCTC.[10,11] However, the implementation of the WHO FCTC in Africa has been variable, as illustrated by Husain et al.[12] They described the status of tobacco control and prevention efforts in 23 African countries and reported that implementation rates of the WHO FCTC ranged from 9% in Sierra Leone to 78% in Kenya.[12] Notably, the overall implementation rate of 43% in the WHO African Region was lower than the 53% in the remaining five WHO regions, which comprised data from 107 countries.[12] This highlights that although the majority of African countries have ratified the treaty, they have not optimally fulfilled their obligations under the WHO FCTC provisions[12] and lag behind other world regions. Bilano et al.,[13] who analysed global trends in tobacco use, concur. Of the 178 countries for which projections were made in their analysis, the outlook for African countries, together with those in the Eastern Mediterranean Region, was among the worst for achieving tobacco control targets by 2025.[13] There was modest progress in the WHO FCTC implementation in many African countries with legislation or policies covering some aspects of the treaty. However, only a few countries meet the standards of the individual WHO FCTC articles with regard to comprehensive implementation; no African country complies with best practice guidelines across all key areas. The focus of tobacco control strategies in Africa includes raising tobacco taxes, protection from exposure to tobacco smoke with smoking restriction in certain venues, packaging and labelling of tobacco products with the introduction of warning messages on cigarette packaging, and restricting or banning tobacco advertising, promotion and sponsorship.[14] The lack of compliance with best practice guidelines for tobacco control strategies will possibly lead to their ineffective or suboptimal implementation. For example, in Kenya, smoke-free laws comply only partially with the WHO FCTC recommendations; consequently, measures are ineffective to protect non-smokers from tobacco smoke

exposure in bars and restaurants.[15] Brathwaite et al.[16] questioned the effectiveness of current taxation policies in curbing tobacco use in African countries. Although taxation policies of any kind to reduce tobacco consumption were present in 8 of the 9 African countries they surveyed in 2014, taxes on tobacco products were <70% in most of the countries.[16] According to a WHO analysis, in 2014 Madagascar and Seychelles were the only nations in Africa with a sufficiently high tax of >75% of the retail price of cigarettes.[17] That tobacco taxes are one of the most effective ways to reduce or stop tobacco use among current users or to prevent the uptake among non-smokers, has been shown in South Africa (SA), where total taxes on cigarettes increased from 32% to 52% of the retail price between 1993 and 2009.[17] This led to a sizeable reduction in tobacco use; a 10% increase in the real price of cigarettes led to a 6 - 8% decrease in consumption.[18] Also, government tobacco tax revenues increased ninefold.[17] In contrast, Sierra Leone, which has no policy on taxation, an absence of comprehensive bans on tobacco advertising, promotion and sponsorship,[16] and a low WHO FCTC implementation rate (9%),[12] had the highest prevalence of smoking among men in sub-Saharan Africa (33.3%).[4] Of the countries examined, Brathwaite et al.[16] found that cigarette prices increased only in Congo and Nigeria, but declined in Senegal and SA, while remaining the same in 4 other African countries (Ghana, Kenya, Togo and Uganda) for about 2 years. Cigarettes may become more affordable if their price decreases or remains steady, while simultaneous economic growth results in greater disposable incomes. The WHO confirmed this supposition, reporting that SA and Botswana were among the countries where income and purchasing power had grown rapidly to the extent that tobacco had become increasingly affordable.[17] This resulted in an escalation in consumption, despite rises in tobacco taxes, because the resultant price increases were not large enough to counter growth in real incomes. Therefore, it is not only important to introduce tobacco excise taxes but also to ensure that they are sufficiently high to be optimally effective.

The tobacco industry in Africa

A major obstacle that African countries face in their efforts to implement tobacco control policies, is strong obstruction from the tobacco industry, which is vocal and relentless in its opposition to effective policies globally.[19] Tactics employed include lobbying policymakers to prevent future policies by presenting misleading economic arguments, rebranding political activities as corporate social responsibility, drafting weak laws and using litigation to weaken, postpone or prevent strong tobacco control legislation.[14,20] For example, the tobacco industry succeeded in preventing advertising bans in Sierra Leone and Uganda.[20] In Kenya, their challenge of the Tobacco Control Act led to the suspension of the public smoking ban and their lobbying of policymakers resulted in weak tobacco control legislation.[14] Furthermore, British American Tobacco (BAT) succeeded in delaying regulations aimed at restricting the promotion and sale of cigarettes in Kenya for 15 years.[21] Bribery and corruption are widespread and BAT is currently under formal investigation over claims of bribing officials in east Africa to subvert anti-smoking legislation.[22] In Mauritius, the industry used delay tactics to undermine the law for implementing graphic health warnings on packaging.[14] Tobacco industry interference delayed the ratification of the WHO FCTC in Namibia; this is a key step in tobacco control, which provides support to governments and enables the strengthening of tobacco control legislation.[23] When this eventually failed, BAT used intimidation tactics and threatened

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to take the Namibian government to court if the Tobacco Products Control Act was implemented. BAT cited violations of their ‘rights to property’ and ‘rights to freedom of expression’, as provided by the Namibian constitution.[23] The tobacco conglomerates increasingly use litigation to intimidate African nations from implementing effective policies,[20] and it was recently reported that they have threatened at least 8 African governments.[21] However, in Uganda, BAT unsuccessfully appealed against the ban on public smoking, and in SA, the tobacco industry went to court on grounds that the ban on tobacco advertising and promotion was unconstitutional, but their application was dismissed.[14] The tobacco industry further encourages ineffectual tobacco control policies in Africa, such as promoting voluntary regulation of smoke-free zones to avert strict regulation through legislation.[14] Consequently, the tobacco industry’s unremitting efforts on multiple fronts to undermine tobacco control measures have led to slow and uneven implementation of the WHO FCTC.[20] These tactics highlight that tobacco industry interference with tobacco control initiatives of governments remains one of the greatest challenges to curbing this epidemic in Africa. Tobacco companies falsely convince African governments that tobacco production leads to economic development.[24] They have agricultural lobbies, such as the International Tobacco Growers Association (ITGA), which promote tobacco farming as a lucrative income source. However, in-depth scrutiny reveals a negative environmental impact, exploitive contracting practices and negative health effects[24] that present an economic threat. As an example, tobacco farmers, including their children who work in the fields, may absorb nicotine each day, with the amount as high as that found in 50 cigarettes.[25] This leads to nicotine poisoning, known as green tobacco sickness; children are particularly vulnerable because of their smaller size compared with the amount of nicotine absorbed. In Malawi, ~80 000 children work in tobacco farming, which has a devastating effect on their health and their ability to receive adequate schooling.[25] The cycle of poverty is perpetuated, and it is not surprising that African countries dependent on tobacco farming are among the world’s poorest nations.[24] While legislation restricts tobacco-promoting activities in highincome countries,[2] in Africa, unfortunately, tobacco companies are able to use aggressive marketing tactics to promote smoking in previously underexploited markets. They successfully target potential growth markets such as women and the youth, who are vulnerable groups with traditionally low tobacco use.[20] The tobacco industry exploits the economic growth, changing social norms and population demographics in Africa to maximally expand its consumer base.[16] The pivotal role that it plays in escalating the worldwide use of tobacco has, unsurprisingly, led to it being appropriately labelled the vector of the tobacco epidemic.[20] The tobacco industry undermines the usefulness of tobacco excise taxes to curb smoking by introducing cheaper brands in response to higher taxes.[26] Furthermore, they under-report their product pricing for tax valuation, thereby maintaining the affordability of cigarettes.

Civil society, other stakeholders and tobacco control in Africa

Civil society has a major role to play in holding governments accountable for responsible stewardship, and their influence and importance should not be underestimated. Advocacy efforts aim to de-normalise smoking, increase awareness of the harmful effects of tobacco use and overall promote the anti-tobacco agenda.

In Uganda, for example, where there was no comprehensive national tobacco control legislation, smoke-free legislation was introduced as a result of public interest litigation.[14] This was possible because of the country’s favourable legal system, which allows an individual or organisation to bring an action against the violation of the human rights of another individual or group. Unfortunately, these smoke-free regulations were poorly enforced, and underlined the need for continued public awareness campaigns to gain public support and become self-enforcing.[14] Nevertheless, great advances have been made in Uganda after the efforts of several stakeholders, including the Ministry of Health and civil society organisations, despite strong resistance from the tobacco industry.[27,28] The Ugandan parliament introduced the Tobacco Control Act 2015, which is in keeping with the strongest tobacco control policies globally, and positioned the country as a leading example of tobacco control in the region. Another illustration of the importance of the role played by civil society is in Niger, where tobacco control legislation allows tobacco control organisations to initiate action against violators of the law. A non-governmental tobacco control organisation successfully sued two tobacco companies for violating the advertising ban.[14] Furthermore, the media may exert pressure on governments to promote tobacco control legislation, and in resource-constrained African nations serve as government ‘watchdogs’.[23] For example, the Cancer Association of Namibia engaged with the media to follow up with government on the pending tobacco control legislation. This pressure from news media that frequently highlighted the issue might have contributed to the introduction of Namibia’s Tobacco Products Control Act in 2010. Civil society organisations also serve as gatekeepers and collaborating platforms. For instance, Vision for Alternative Livelihood Development in Ghana increases awareness of the harmful effects of tobacco use among the public.[24] They also build capacity to ensure effective implementation and enforcement of national tobacco control policies. Bloomberg Philanthropies, the Bill and Melinda Gates Foundation and the Canadian International Development Research Centre are the largest international development partners to offer financial and technical support for tobacco prevention and control in Africa.[24] The former two partnered in 2008 to commit USD500 million to tobacco control initiatives in developing countries. They also assist, among other initiatives, in implementing effective tobacco control policies, with a specific goal to prevent a tobacco epidemic from ‘taking root’ in Africa. The Centre for Tobacco Control in Africa (CTCA), established in 2011, is funded by the Bill and Melinda Gates Foundation and supported by the WHO. Its mandate is to support African governments with advancing tobacco control policies and legislation through the provision of technical support and creation of a platform for dialogue, among other measures.[29] The CTCA has provided technical and financial resources to develop comprehensive tobacco control policies and has played a significant role in promoting the anti-tobacco agenda in Africa.

Use of tobacco products apart from cigarettes

The use of smokeless tobacco products that may be sniffed, chewed, sucked or applied to teeth and gums, is common in some African countries. There is limited information on the prevalence of their use, but it varies widely across countries – from as high as 28.3% in Mauritanian women and 22.6% in Madagascan men to as low as 0.5% in Nigerian and Zimbabwean women and 0.2% in Zambian men.[30]

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Smokeless tobacco products are generally cheaper than cigarettes and consequently used more widely by poorer populations, as well as by older compared with younger adults. In some regions, tobacco companies are using these factors to market the use of smokeless tobacco products to specific target groups, such as women and young individuals, as an alternative to cigarette smoking and as ‘starter’ products.[30] Most African countries have not extended their tobacco control legislation to encompass the use of smokeless tobacco products, and there is generally an absence of public health education or cessation programmes. For example, in SA, excise taxes apply to cigarettes but not to smokeless tobacco products, making the latter cheaper than cigarettes.[30] Smokeless tobacco products are not harmless; therefore, their regulation needs to be integrated into tobacco control policies.[2] This is essential to manage the harm caused by these products, as well as the need for Africa-specific research to inform future policy action on smokeless tobacco. Nevertheless, the WHO FCTC should guide the development of policies for smokeless tobacco products. These may include graphic health warnings covering 50% of the package display area, banning the use of flavourings in these products to reduce their appeal to the youth, prohibiting advertisements, promoting cessation and increasing public awareness and education campaigns.[30] Another tobacco product, once confined to India, North Africa and the Middle East, which has spread beyond these regions and become integrated into the global tobacco market, is the smoking of water pipes.[2] Its use is popular and rising in adolescents and young adults.[2] In SA, almost two-thirds of university students in the Western Cape reported having ever smoked a hookah pipe.[31] Knowledge of the dangers of water-pipe smoking was poor among students,[32] and water-pipe smokers are frequently under the false impression that their form of tobacco use is safer than smoking cigarettes.[2] Considering that the tobacco industry intentionally misrepresents the harmful health effects of smoking water-pipe tobacco, comprehensive and aggressive awareness campaigns and educational efforts are necessary to dispel these false beliefs. Otherwise, individuals who explicitly refuse to smoke cigarettes, are likely to continue to use water pipes.[2] Strict tobacco control policies, predominantly tailored for cigarette use, have allowed water-pipe smoking to thrive.[2] Exemptions on water-pipe smoking in public places have led to its increase in popularity as a social practice.[2,32] Therefore, there is an urgent need to regulate water-pipe use in the same way as cigarette smoking; use of the former in public should not be exempt from smoke-free laws.[2] Research quantifying the harmful health effects of waterpipe smoking is needed to increase awareness and thereby curb the rise in its use. Nonetheless, based on the current scientific evidence, a number of African countries, including Rwanda, Tanzania and Kenya, have banned the use of water pipes.[33] The introduction of and rise in uptake of the electronic cigarette (e-cigarettes) have created a conundrum on the harmful or beneficial effects of this product in the absence of adequate research. While the long-term effect of e-cigarettes is not yet known, evidence from limited short-term studies found that their use is less harmful than smoking.[34] Although the efficacy of e-cigarettes as a smoking cessation aid has not been proven, Nansseu and Bigna[35] propose that the use of e-cigarettes may contribute to smoking reduction or cessation in sub-Saharan Africa.[35] Importantly, the use of e-cigarettes should be strictly limited to current and/or ex-smokers to assist them to quit smoking or prevent relapse; never-smokers should not use these devices. Further research is urgently needed to aid governments globally, including in Africa, to decide how to regulate e-cigarettes.[2] In SA,

the minister of health is keen to include the use of e-cigarettes in smoking legislation, similar to the US Food and Drug Administration (FDA), which has classified e-cigarettes under ‘tobacco products’.[36] There is also a need to regulate the production of e-cigarettes and ensure that safety guidelines are met, as these contain varying ingredients, some of which may be toxic.[37] The tobacco industry is investing heavily in the e-cigarette trade to ensure their share of this growing market, which is expected to surpass traditional cigarettes by 2024.[2] In September 2017, Philip Morris established the Foundation for a Smoke-Free World, with annual funding of ~USD80 million for 12 years, and a previous WHO official, Dr Derek Yach, as the Foundation’s president.[38] In response, the WHO reiterated the United Nations’ stand of a ‘fundamental conflict of interest between the tobacco industry and public health’ and recommended that governments and the public health community ‘not accept financial or other contributions from the tobacco industry or those working to further its interests, such as this Foundation’. Philip Morris, together with other players in the tobacco industry, subvert every tobacco control effort and have a history of misleading the public with regard to the risks associated with tobacco products. Their interests are contradictory to those of tobacco control initiatives and, therefore, their research and advocacy cannot be accepted at face value.[38]

The way forward for Africa

Despite the huge obstacles that African nations face in their quest to introduce comprehensive tobacco control policies, many countries have achieved measured success, while others such as Uganda, SA and Mauritius have accomplished significantly more in their efforts to curb tobacco use. Nevertheless, Africa still needs to urgently intensify efforts to implement effective tobacco control policies that are fully compliant with the WHO FCTC.[12,14] Otherwise, the current tobacco trends will continue, with potential devastating consequences. The overall smoking prevalence in Africa will increase by more than a third (37.5%) over 2 decades, i.e. from 16% in 2010 to 22% in 2030, and the number of smokers will triple by the end of this century.[2] The American Cancer Society reported that by 2100, ‘without action, Africa will grow from being the fly on the wall to the elephant in the room’.[6] The powerful tobacco industry, with its vast resources and predatory practices, is irrefutably the driving force behind the global tobacco pandemic and the major barrier to WHO FCTC implementation in Africa.[14] Therefore, in the battle against rising rates of tobacco use on the continent, a prerequisite is to actively address tobacco industry interference by monitoring its activities and exposing its misconducts, thereby changing attitudes to this industry.[20] It is no coincidence that countries with the most successful tobacco control policies across all income categories are those that most rigorously monitor industry activities. The tobacco industry frequently encourages the opposition of certain government ministries to the introduction of comprehensive tobacco control legislation. These may include the agricultural and trade and industry departments, which might have competing priorities to that of the health ministry, and consequently influence the drafting of ineffective tobacco control legislation. A whole-of-government approach is required, with tobacco control integrated in all government programmes, including the taxation and commerce sectors.[39] Considering that the tobacco industry generally exerts more power and influence at national than sub-national levels, it may be prudent and perhaps more feasible to introduce tobacco legislation at sub-national levels.[14] Although this may not offer protection to the

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entire population, enacting and enforcing tobacco legislation at local, state, provincial or municipal levels may be easier and more effective. Whether the enforcement of current sub-national legislation in Africa is effective, has yet to be determined.[14] Technical support and capacity building are needed in Africa to enable countries to competently manage legal challenges to tobacco control and deal with the subversive tactics of the industry.[20] Further, African nations need to prioritise resources to build capacity for drafting comprehensive WHO FCTC-compliant legislation.[14] As demonstrated in Namibia, key obstacles to the introduction of tobacco control legislation, together with competing priorities and administrative delays, were insufficient staff and legal capacity.[23] The lack of legal expertise within the ministry to challenge the false information that BAT provided to the Namibian health ministry, i.e. that it could not ratify the WHO FCTC prior to passing national tobacco control legislation, possibly also delayed its ratification. Consequently, it took nearly 20 years for the country to pass the Tobacco Products Control Act. Resources are also needed to generate locally relevant research on tobacco use.[14,40] Importantly, economic studies should be undertaken to conclusively refute the negative impact of tobacco control policies in Africa. Tobacco is grown in >125 countries globally, including Africa, and the role it plays in employment, tax-revenue generation and trade balances in some countries is highly promoted by the tobacco industry.[41] However, independent studies demonstrated that, even with very strong tobacco-control policies, there will be a minimal negative impact on economic growth, employment, tax revenues and foreign trade balances over the medium and long term in most countries. Tobacco control should be integrated in the implementation of the Sustainable Development Goals. There is a need to switch from tobacco farming to other crops, which has been successfully achieved in a programme in Brazil with a change to fruit or vegetable cultivation.[25] A government programme that encourages the use of locally grown fruit and vegetables for school lunches ensures a market for their produce. In this way a countryâ&#x20AC;&#x2122;s economic dependence on tobacco farming and the negative health consequences of tobacco are reduced, and the cycle of poverty is broken. Financial resources for tobacco control in Africa are challenging in the face of competing priorities. Nevertheless, by failing to fully implement the WHO FCTC, many African countries that signed the treaty breach their legal obligations under international law to implement it in good faith.[14] More concerted and innovative approaches, together with a strong will, are needed for governments to invest in tobacco control measures. For example, governments need to ensure efficient collection of tobacco-related taxes and direct such revenue to tobacco-control initiatives. Kenya is one of a few countries globally that is able to monitor local cigarette production and collect related taxes.[42] Consequently, there has been a substantial increase in tax revenue from local tobacco manufacturers and a marked decrease in illicit tobacco trade. The use of tax revenue for tobacco control activities, if framed as an economic problem v. a health concern only, is likely to garner more support, as shown in Thailand.[26] Tobacco control advocates in Thailand presented evidence to cabinet that a small investment in health promotion would translate into a reduced financial burden for the treatment of NCDs. Furthermore, the health promotion bill required that tobacco and alcohol companies fund the health promotion programme, which was enacted into law in 2001. Such changes are only possible with well-planned advocacy and lobbying by non-governmental organisations (NGOs).[26] Therefore, the role

played by NGOs in Africa, such as Bloomberg Philanthropies, the Bill and Melinda Gates Foundation and the Canadian International Development Research Centre, mentioned above, is critical for accelerating the tobacco control agenda on the continent. Relevant research from Africa will inform policies and may increase political will by generating vital political attention for tobacco control. Moreover, tobacco control measures based on locally garnered evidence are likely to be more effective, with such research also potentially refuting tobacco industry myths. Highquality research in all sub-Saharan African countries, of which there is currently a dearth, should also include data on the incidence, prevalence, trends and uptake facilitating factors of cigarette smoking and other tobacco products, including e-cigarettes, water pipes and smokeless tobacco products, and evidence of the implementation and effectiveness of tobacco control policies.[16] Such data will demonstrate the degree of success of strategies implemented with regard to tobacco use patterns and underscore shortcomings in existing policies. Civil society, NGOs and researchers need to educate and pressurise African politicians and governments to implement and enforce effective tobacco control policies. Expecting African countries to implement comprehensive and effective tobacco control policies with efficient monitoring and enforcement of such activities, is not unrealistic. Some countries on the continent have already shown that they not only have the ability to implement effective tobacco control strategies but are also able to be at the forefront of global tobacco control initiatives. SA and Mauritius, together with Bahrain, are the worldâ&#x20AC;&#x2122;s first three countries to ban smoking in vehicles carrying children.[2] Furthermore, when Mauritius introduced graphic health warning labels on packaging, their warnings were the third largest in the world, covering 60% of the front and 70% of the back package display areas.[14] At that time, Mauritius was the only African country with graphic health warning labels on packaging;[14] there are now 8.[43] Chadâ&#x20AC;&#x2122;s health warnings cover 70% of the main display areas and are now the largest in Africa.[43] Therefore, with sufficient political will, African nations have the potential to meet their commitment to the WHO FCTC and prevent a full-scale escalation of the tobacco epidemic.[20]

Conclusions

The lower rates of tobacco taxation, weaker smoke-free policies and fewer restrictions on tobacco advertising in Africa compared with high-income countries are key factors driving the tobacco epidemic on the continent.[16] These shortcomings, enabled by the tobacco industry thwarting anti-tobacco initiatives, have allowed it to expand its markets in the region by capitalising on economic growth, changing social norms and population demographics. Consequently, while there has been progress, the current commitment of most African countries to the WHO FCTC has not translated into effective delivery of meeting the WHO Global NCD Action Plan goal of a 30% relative reduction in tobacco use by 2025 compared with 2010.[9] This is of great concern, as tobacco use is not only a threat to health but also to sustainable human development. The rapid expansion of tobacco use in Africa needs to be counteracted by strong tobacco control policies, which is one of the most effective population-based strategies for NCD prevention. African countries need to intensify efforts to implement effective tobacco control policies that are fully compliant with the WHO FCTC.[14] These should include higher tobacco excise taxes, stronger smoke-free policies, bans on tobacco advertising, promotion and sponsorship, graphic warnings on cigarette packages and antismoking mass media campaigns.[40] Otherwise, the recent increases

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in economic development and population growth will spur the widespread uptake of tobacco use and lead to the loss of hundreds of millions of lives in this century owing to tobacco smoking.[2] Acknowledgements. None. Author contributions. Sole author. Funding. None. Conflicts of interest. None. 1. Pampel F. Tobacco use in sub-Sahara Africa: Estimates from the demographic health surveys. Soc Sci Med 2008;66(8):1772-1783. https://doi.org/10.1016/j.socscimed.2007.12.003 2. Eriksen MP, Mackay J, Schluger N, Islami F, Drope J. The Tobacco Atlas. 5th ed. Atlanta, GA: American Cancer Society, 2015. 3. Madu EC, Richardson KD, Ozigbo OH, Baugh DS. Improving cardiovascular disease prevention and management in Africa: Issues to consider for the 21st century. Ethn Dis 2003;13(2 Suppl 2):S71-S76. 4. World Health Organizaton. Global Status Report on Noncommunicable Diseases 2014. Geneva: WHO, 2014. 5. Eriksen M, Mackay J, Ross H. The Tobacco Atlas. 4th ed. Atlanta, GA: World Lung Foundation/ American Cancer Society, 2011. 6. Bletcher E, Ross H, American Cancer Society. Tobacco Use in Africa: Tobacco Control Through Prevention. Atlanta, GA: American Cancer Society, 2013. 7. World Health Organization. Global Report on Trends in Tobacco Smoking 2000 - 2025. Geneva: WHO, 2017. 8. World Health Organization. Framework Convention on Tobacco Control. Geneva: WHO, 2003. 9. Britton J. Progress with the global tobacco epidemic. Lancet 2015;385(9972):924-926. https://doi. org/10.1016/S0140-6736(15)60498-6 10. World Health Organization. Tobacco Control – Overview. Geneva: WHO, 2015. 11. United Nations Treaty Collection. United Nations, Treaty Series: WHO Framework Convention on Tobacco Control. New York: UN, 2017. 12. Husain MJ, English LM, Ramanandraibe N. An overview of tobacco control and prevention policy status in Africa. Prev Med 2016;91:S16-S22. https://doi.org/10.1016/j.ypmed.2016.02.017 13. Bilano V, Gilmour S, Moffiet T, et al. Global trends and projections for tobacco use, 1990 - 2025: An analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control. Lancet 2015;385(9972):966-976. https://doi.org/10.1016/S0140-6736(15)60264-1 14. Tumwine J. Implementation of the framework convention on tobacco control in Africa: Current status of legislation. Int J Environ Res Public Health 2011;8(11):4312-4331. https://doi.org/10.3390/ijerph8114312 15. Karimi KJ, Ayah R, Olewe T. Adherence to the Tobacco Control Act, 2007: Presence of a workplace policy on tobacco use in bars and restaurants in Nairobi, Kenya. BMJ Open 2016;6(9):e012526. https:// doi.org/10.1136/bmjopen-2016-012526 16. Brathwaite R, Addo J, Smeeth L, Lock K. A systematic review of tobacco smoking prevalence and description of tobacco control strategies in sub-Saharan African countries; 2007 to 2014. PLOS ONE 2015;10(7):e0132401. https://doi.org/10.1371/journal.pone.0132401 17. World Health Organization. Report on the Global Tobacco Epidemic, 2015: Raising Taxes on Tobacco. Geneva: WHO, 2015. 18. Van Walbeek C. [Tobacco control in South Africa]. Promot Educ 2005;(Suppl 4):25-28,57. 19. Beaglehole R, Bonita R, Yach D, Mackay J, Reddy KS. A tobacco-free world: A call to action to phase out the sale of tobacco products by 2040. Lancet 2015;385(9972):1011-1018. https://doi.org/10.1016/S01406736(15)60133-7 20. Gilmore AB, Fooks G, Drope J, Bialous SA, Jackson RR. Exposing and addressing tobacco industry conduct in low-income and middle-income countries. Lancet 2015;385(9972):1029-1043. https://doi. org/10.1016/S0140-6736(15)60312-9 21. Boseley S. Threats, bullying, lawsuits: Tobacco industry’s dirty war for the African market. The Guardian, 12 July 2017. https://www.theguardian.com/world/2017/jul/12/big-tobacco-dirty-war-africa-market (accessed 15 December 2017).

22. Sullivan C. BAT investigated by serious fraud office over bribery allegations. Financial Times, 1 August 2017. https://www.ft.com/content/fd6eb592-7682-11e7-90c0-90a9d1bc9691 (accessed 15 December 2017). 23. Tam J, van Walbeek C. Tobacco control in Namibia: The importance of government capacity, media coverage and industry interference. Tobac Control 2014;23(6):518-523. https://doi.org/10.1136/ tobaccocontrol-2012-050725 24. Academy of Science of South Africa. Preventing a tobacco epidemic in Africa. Consensus study report. 2014. http://hdl.handle.net/20.500.11911/57 (accessed 28 May 2018). 25. Kulik MC, Bialous SA, Munthali S, Max W. Tobacco growing and the sustainable development goals, Malawi. Bull World Health Organ 2017;95(5):362-367. https://doi.org/10.2471/BLT.16.175596 26. Vathesatogkit P, Charoenca N. Tobacco control: Lessons learnt in Thailand. Ind J Public Health 2011;55(3):228-233. https://doi.org/10.4103/0019-557X.89938 27. The Union. Uganda passes tobacco control law in line with the world’s most stringent policies. The Union, 15 June 2015. http://www.theunion.org/news-centre/news/uganda-passes-tobacco-control-law-in-linewith-the-worlds-most-stringent-policies (accessed 15 June 2017). 28. TTC Mobile. Tobacco control law passed in Uganda. 2015. https://ttcmobile.com/tobacco-control-lawpassed-in-uganda/ (accessed 15 June 2017). 29. Kellen N. CTCA: A resource centre for advancing tobacco control in Africa. 2014. https://www.phasa.org. za/ctca-resource-centre-advancing-tobacco-control-africa/ (accessed 28 May 2018). 30. National Cancer Institute and Centers for Disease Control and Prevention. Smokeless Tobacco and Public Health: A Global Perspective. Bethesda, MD: US Department of Health and Human Services, CDC, National Institutes of Health, NCI, 2014. 31. Kruger L, van Walbeek C, Vellios N. Waterpipe and cigarette smoking among university students in the Western Cape, South Africa. Am J Health Behav 2016;40(4):416-426. https://doi.org/10.5993/ AJHB.40.4.3 32. Van der Merwe N, Banoobhai T, Gqweta A, et al. Hookah pipe smoking among health sciences students. S Afr Med J 2013;103(11):847-849. https://doi.org/10.7196/samj.7448 33. Merab E. Kenya joins Rwanda, Tanzania in shisha ban. The East African, 30 December 2017. http:// www.theeastafrican.co.ke/scienceandhealth/Kenya-bans-shisha/3073694-4244126-lmlqswz/index.html (accessed 15 January 2018). 34. Zborovskaya Y. E-cigarettes and smoking cessation: A primer for oncology clinicians. Clin J Oncol Nurs 2017;21(1):54-63. https://doi.org/10.1188/17.CJON.54-63 35. Nansseu JR, Bigna JJ. Electronic cigarettes for curbing the tobacco-induced burden of noncommunicable diseases: Evidence revisited with emphasis on challenges in sub-Saharan Africa. Pulm Med 2016;2016:4894352. https://doi.org/10.1155/2016/4894352 36. National Occupational Safety Association (South Africa). Where does the law lie with vaping? 2017. http://blog.nosa.co.za/blog/where-does-the-law-lie-with-vaping (accessed 28 May 2017). 37. Varga P. Is South Africa’s strong stance on smoking set to cover e-cigarettes, too? News24, 11 August 2016. https://www.news24.com/MyNews24/is-south-africas-strong-stance-on-smoking-set-to-cover-ecigarettes-too-20160811 (accessed 28 May 2018). 38. World Health Organization. Statement on Philip Morris Funded Foundation for a Smoke-Free World. Geneva: WHO, 2017. http://www.who.int/mediacentre/news/statements/2017/philip-morrisfoundation/en/ (accessed 15 December 2017). 39. Munzer A. The WHO FCTC: The challenge of implementation. Lancet Respir Med 2013;1(3):182-184. https://doi.org/10.1016/S2213-2600(13)70048-1 40. Jha P. Deaths and taxes: Stronger global tobacco control by 2025. Lancet 2015;385(9972):918-920. https:// doi.org/10.1016/S0140-6736(15)60464-0 41. Wipfli H, Samet JM. Global economic and health benefits of tobacco control: Part 1. Clin Pharmacol Ther 2009;86(3):263-271. https://doi.org/10.1038/clpt.2009.93 42. Ntiabang T. Africa Moves to Improve the Tobacco Control Fight. Pretoria: Africa Centre for Tobacco Industry Monitoring and Policy Research, 2016. https://www.atim.co.za/contacts/ (accessed 15 December 2017). 43. World Health Organization. Pictorial Health Warnings Gain Ground in Africa. Geneva: WHO, 2017. http://www.who.int/fctc/mediacentre/news/2015/africapictorial/en/ (accessed 15 December 2017).

Accepted 15 January 2018.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

IN PRACTICE

MEDICINE AND THE LAW

Obtaining informed consent for a sterilisation in the light of recent case law C J Badul,1,2 BA, LLB, LLM; A Strode,2 BA, LLB, LLM, PhD; P P Singh,2 BCom, LLB, LLM Law Clinic, Pietermaritzburg Campus, School of Law, College of Law and Management Studies, University of KwaZulu-Natal, Durban, South Africa 2 School of Law, College of Law and Management Studies, University of KwaZulu-Natal, Durban, South Africa 1

Corresponding author: P P Singh (singhpp@ukzn.ac.za)

The need to obtain informed consent prior to any sterilisation is a very well-established ethical and legal obligation. South African law, however, does not specifically state who is responsible for obtaining informed consent before performing a sterilisation. This has implications for the liability of a surgeon or gynaecologist in circumstances where the informed consent is defective. Due to the vagueness of the applicable law, a surgeon or gynaecologist might be held liable, even in situations where he/she did not obtain the consent and relied on a nurse or assistant to procure the relevant informed consent. This article explores the relevant statutory law and canvasses two legal cases that came before the court regarding defective informed consent and the resultant liability for damages. We also make recommendations for proposed amendments to the current law to provide further clarity. S Afr Med J 2018;108(7):557-558. DOI:10.7196/SAMJ.2018.v108i7.13141

The ethical-legal obligation to obtain informed consent from patients before any medical procedure or operation is undertaken is a wellestablished principle in legislation[1] and the common law.[2] In this article, the authors, however, focus specifically on the unsettled issue of obtaining informed consent for a sterilisation (this article is based partially on the PhD thesis of C J Badul – refer to author contributions below). Informed consent is a positive right in terms of the right to bodily integrity[3] and a defence for doctors facing civil claims for damages (volenti non fit injuria [there can be no injury to a person who has voluntarily consented]).[4,5] Even though the ethicallegal framework for consent is well established, one of the unresolved complexities is the question of who bears the legal duty to obtain the consent or ensure that consent has been obtained for a sterilisation. This is a broad issue involving the potential liability of a surgeon for failing to personally obtain and record the consent of a patient, and it has come before the courts in relation to two sterilisation cases.[6,7] In Pandie v Isaacs[6] the court grappled with this point, but failed to make a definitive finding on whether the surgeon or the nurse had to take responsibility to ensure that consent had been properly obtained and documented. However, in the Government of Namibia v LM and Others[7] case, the court held that the duty lay with the medical practitioner to procure written informed consent. This article explores the relevant legislation, case law and guidelines with regard to sterilisation to ascertain on whom the duty rests to obtain informed consent.

Consent to a sterilisation – the South African ethical-legal framework

The Sterilisation Act No. 44 of 1998[8] (the Act) provides that the patient requesting the sterilisation must be >18 years of age and capable of consenting in writing to the procedure. The Act[8] specifies that consent must be free from coercion and must be provided after an unambiguous explanation of the proposed procedure, including information on its permanency or reversibility. Finally, the Act[8] states that the patient must be advised that their consent may be withdrawn at any time before the sterilisation is performed.

Although the Act[8] is silent on who is responsible for providing this information and obtaining written consent, there are ethical guidelines dealing with this point, which have been issued by the Health Professions Council of South Africa (HPCSA).[9] The guidelines state that it is the duty of the healthcare practitioner to obtain the patient’s informed consent before any treatment is given.[10] Nevertheless, the guidelines allow a practitioner to delegate the task of obtaining informed consent, provided the final responsibility remains with the healthcare practitioner.[10] Furthermore, where a patient’s informed consent was obtained by a third party, the healthcare practitioner must nevertheless ascertain from the patient how well they understood the proposed procedure and its attendant risks.[10] Ensuring that the signed copy of the consent form is in the file, is inadequate.[7]

Recent case law on consent to a sterilisation Pandie v Isaacs

Pandie v Isaacs[6] related to a civil claim for damages by a woman who argued that she had been sterilised without her full and informed consent. Isaacs alleged that she was offered the opportunity to be sterilised when she undergoes her caesarean section, but declined. When she was admitted to hospital, she was presented with a pre-drafted consent form that was prepared based on her doctor’s admission letter. It indicated that she was to have a caesarean section and be sterilised. Isaacs refused to sign the consent form, indicating that she only wished to undergo a caesarean section and not a sterilisation. The nurse advised her to inform the surgeon of this change regarding the procedures, which she did not do. Isaacs only became aware that she had been sterilised when the theatre nurse held up a jar and showed her the severed portion of the fallopian tubes. The court held that, in terms of the Act,[8] written consent was required, which had not been obtained in this case. Nevertheless, obtaining written consent was, in practice, the function of the nurse and Dr Pandie could not be held liable for negligence for failing to confirm the contents of the consent document with Isaacs. The

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IN PRACTICE

court further held that in the event of the patient changing her mind, there would be a duty on the nurse to bring this to the attention of the gynaecologist. In coming to this conclusion, the court relied on expert evidence that it was not a common practice among surgeons to personally check written consent forms before operating.

Government of Namibia v LM and Others

In the LM[7] case, 3 HIV-positive women claimed that they had been sterilised, without their voluntary consent, while undergoing caesarean sections in state hospitals in Namibia. The Namibian Supreme Court found that the written consent taken from the women did not mean that there was informed consent.[7] If practitioners are to rely on the volenti non fit injuria defence, they must be able to prove that all elements of the defence as set out in Castell v de Greef[2] are present, including: disclosure of all material risks and voluntariness.[7] In this case, the court held that an obligation was placed on healthcare professionals to obtain consent from a patient: ‘… sterilisation allows time for informed and considered decisions … health professionals are under an obligation to assess the patient and point out the risks involved in particular procedures so as to enable the patient to make an informed decision and give informed consent.’[7]

Discussion

Although the Act[8] is silent as to who ought to obtain informed consent from the patient wishing to be sterilised, we submit that the court in the Pandie[6] case erred in suggesting that a surgeon may delegate this task to a nurse. We have five reasons for adopting this approach. Firstly, although the Act[8] does not specify where the legal obligation to obtain consent lies, the HPCSA guidelines are clear on this point. In Jansen van Vuuren and Another NNO v Kruger,[11] the then Appellate Division, when dealing with an HIV-positive patient’s right to confidentiality, held that patients have a right to expect that their medical practitioner complies with the professional guidelines. Given that the ethical guidelines require the surgeon to take responsibility for obtaining consent, regardless of whether they delegate part of this task, it was inappropriate of the court to suggest that liability could potentially be placed at the feet of the nurse. Secondly, in defending a civil claim, a surgeon is able to rely on the defence of volenti non fit injuria. It would, however, be very difficult for them to prove all elements of the defence if they did not themselves obtain the consent. Thirdly, the court only gave one rationale for the nurse rather than the surgeon being responsible for obtaining consent, i.e. because it was an accepted practice within the profession.[6] It is submitted that this is insufficient. Expert evidence that this is a practice in hospitals is not a justification for failing to comply with professional ethical guidelines. The court in this instance ought to have found the conduct wrongful, as based on the approach in the Jansen van Vuuren[11] case. Surgeons are duty-bound to ensure that consent is obtained properly. Fourthly, the complexity of transferring the task of consent obligation to a nurse would be: which nurse would be liable? There may be several nurses who are involved in the consent process, such as the ward and theatre nurses. Finally, the Pandie[6] case is out of step with the approach taken in other similar jurisdictions, such as in Namibia.

Conclusion

come before the courts.[8] We submit that despite the silence in the Act[8] on this issue, there is an express duty on the surgeon, given the HPCSA guidelines. The Namibian courts have gone further by requiring that surgeons obtain and document consent before a sterilisation.[7] We submit that this is the correct approach. We make two recommendations. Firstly, we suggest an amendment to the Act[8] to ensure that there cannot be any misunderstanding regarding the consent obligations and that involuntary sterilisations do not occur in the future. It must be clarified who has to take consent from the patient. This change will be broadly beneficial, as it will protect all persons considering sterilisation as a form of birth control. In this regard, the proposed recommendations in italics and underlined, as set out below, are an addition to section 4 of the Sterilisation Act.[8] ‘Consent 4. For the purposes of this Act, “consent” means consent given freely and voluntarily without any inducement and may only be given if the person giving it has – (a) been given a clear explanation and adequate description of the – (i) proposed plan of the procedure; and (ii) consequences, risks and the reversible or irreversible nature of the sterilisation procedure; (b) been given advice that the consent may be withdrawn any time before the treatment; (c) signed the prescribed consent form and (d) written consent may only be obtained before the onset of labour by a surgeon or gynaecologist performing the procedure.’ Secondly, we recommend that hospitals develop standard operating procedures that ensure that there is space on the consent form for the surgeon to sign and make any notes they deem necessary regarding the consent procedure. This will ensure that the surgeon is aware of whether consent has been obtained in every case prior to the procedure being performed. Acknowledgements. None. Author contributions. This article is based in part on work contained in C J Badul’s PhD thesis, ‘The coerced and forced sterilisation of women living with HIV in South Africa: A critical review of existing legal remedies’. The thesis is currently in the process of being examined (1 June 2018); A E Strode and P P Singh are C J Badul’s supervisors. Funding. None. Conflicts of interest. None. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

The duty to obtain informed consent before a sterilisation is clear – both in terms of the Act[8] and common law. However, the Act[8] does not deal with on whom this consent rests, and it has only recently

South Africa. National Health Act No. 61 of 2003. Castell v de Greef 1994 (4) SA 408 (C). South Africa. Constitution of the Republic of South Africa Act No. 108 of 1996. McDonald v Wroe 2006 (3) All SA 565 (C). Christian Lawyers’ Association v National Minister of Health (Reproductive Health Alliance as Amicus Curiae) 2005 (1) SA 509 (T). Pandie v Isaacs (A135/2013, 1221/2007) [2013] ZA WCHC123. The Government of the Republic of Namibia v LM and Others (SA 49/2012) [2014] NASC 19 (3 November 2014). South Africa. Sterilisation Act No. 44 of 1998. Health Professions Council of South Africa. Guidelines for Good Practice in the Health Care Professions. General Ethical Guidelines for Reproductive Health. Booklet 13. Pretoria: HPCSA, 2008. http://www.hpcsa.co.za (accessed 1 December 2017). Health Professions Council of South Africa. Guidelines for Good Practice in the Health Care Professions. Seeking Patients’ Informed Consent: The Ethical Considerations. Booklet 9. Pretoria: HPCSA, 2008. http://www.hpcsa.co.za (accessed 1 December 2017). Jansen van Vuuren and Another NNO v Kruger (675/91) [1993] ZA SCA 1450; 1993 (4) SA 842 (AD); [1993] 2 All SA 619 (A) (28 September 1993).

Accepted 31 January 2018.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

IN PRACTICE

CASE REPORT

Rapunzel syndrome: A South African variety J Plaskett,1 MB ChB, FCS (SA), MMed; G Chinnery,1 MB ChB, FCS (SA), Cert Gastroenterology (SA) Surg; D Thomson,1 MB ChB, FCS (SA), Cert Crit Care (SA) Surg; S Thomson,1 ChM, FRCS (Eng & Edin), FRCP (Edin); B Dedekind,2 MB ChB, FCS (SA); E Jonas,1 MB ChB, MMed, FCS (SA), PhD 1 2

Department of Surgery, Faculty of Health Sciences, Groote Schuur Hospital and University of Cape Town, South Africa Netcare Christiaan Barnard Memorial Hospital, Cape Town, South Africa

Corresponding author: E Jonas (eduard.jonas@uct.ac.za)

Trichobezoars are intraluminal accretions of ingested hair. Rapunzel syndrome is a rare and extreme presentation, with the trichobezoar extending into the small intestine. It is most frequently reported in children and psychiatric patients. We report a South African series of 5 patients who presented with trichobezoars. Each patient was retrospectively reviewed and analysed with regard to background, demographics, clinical presentation, diagnosis, surgical management and complications. Five female patients with a median age of 19 (range 12 - 27) years presented with clinical symptoms, including early satiety, intermittent vomiting with gastric outlet obstruction, abdominal pain and weight loss. The diagnosis was made by endoscopy, abdominal computed tomography (CT) imaging, barium meal examination or plain abdominal radiography. Two patients presented with sealed/contained gastric perforations, and 1 patient with a smallbowel perforation. All 5 bezoars, 2 of which consisted entirely of artificial hair extensions, extended into the jejunum, the longest measuring 1.4 m. All were removed by laparotomy. While trichobezoars are a rare entity, they may present with significant complications, such as obstructions and perforations. In view of the infection risk and considerable size of many of these bezoars, an open removal is probably safer than any minimally invasive attempt. S Afr Med J 2018;108(7):559-562. DOI:10.7196/SAMJ.2018.v108i7.13115

Trichotillomania (a compulsive desire to pull out oneâ&#x20AC;&#x2122;s own hair) was first described by Hallopeau in 1889, while the first case of trichobezoar was described by Baudamant in 1779.[1] Rapunzel syndrome is a rare form of trichobezoar, reported by Vaughan et al.[2] in 1968, and characterised by extension into the small intestine. To date, Ë&#x201A;30 cases have been reported in the literature.[1] Rapunzel syndrome commonly occurs in young females, who usually have an underlying psychiatric disorder, with only a single reported male patient who ate the hair of his sisters.[3,4] Approximately 10% of patients with trichotillomania also demonstrate trichophagia.[5] The name Rapunzel originates from the Brothers Grimm fairy tale of a 12-year-old princess locked inside a tower, who uses her long, golden hair to permit her young prince to climb up to her window and rescue her.[6] The term bezoar is believed to be derived from the Arabic badzehr or the Persian panzehr, meaning antidote. In ancient times, bezoars were believed to have medicinal and magical properties and considered as antidotes to a variety of poisons and diseases.[7] Bezoars are typically either phytobezoars (composed of indigestible vegetable or fruit fibres), trichobezoars (composed of accretions of ingested hair), lactobezoars (composed of milk protein), or pharmacobezoars (composed of concretions of various medications).[8] Trichobezoars form when ingested hair strands become retained in the folds of the gastric mucosa, escaping peristaltic propulsion owing to their slippery surface. More hair becomes enmeshed by peristalsis, forming a ball too large to exit the stomach and causing gastric atony owing to its large size.[9,10] The significant size of a bezoar may eventually reduce the mucosal blood supply to the stomach and proximal small bowel, causing ulceration and perforation. Various criteria have been used in the literature to define Rapunzel syndrome: a gastric trichobezoar with a tail extending up to the ileocaecal junction,[11] a simple trichobezoar with a long tail extending beyond the pylorus,[2]

or a bezoar of any size causing obstruction.[1] For the purpose of our case series, Rapunzel syndrome was defined as a symptomatic gastric trichobezoar, with its tail extending into the jejunum for a variable distance, as originally described by Vaughan et al.[2] Risk factors for the formation of gastric bezoars are impaired gastric motility (previous vagotomy or gastroparesis), previous gastric surgery, gastric outlet obstruction, high-fibre diet (especially in the case of phytobezoars) and impaired chewing. Common presenting complaints include abdominal pain, nausea and vomiting, and gastric outlet obstruction. Patients may remain asymptomatic for many years.[1] Less commonly, patients may present with weight loss, anorexia, haematemesis and intussusception.[12,13] Complications include gastric ulceration, perforation with peritonitis,[14-16] obstructive jaundice,[12] acute pancreatitis[17,18] and even death.[19] We describe a retrospective series of 5 patients with trichobezoar, who presented to our unit over a 5-year period.

Patients and methods

Patients with trichobezoars, who presented to the Upper Gastrointestinal Unit, Groote Schuur Hospital, Cape Town, South Africa, were identified from a prospective registry. The patientsâ&#x20AC;&#x2122; demographic profiles, presenting symptoms, diagnostic findings, treatment and outcomes are reported. The registry has been approved (ref. no. HREC 488/2017) by the Human Research Ethics Committee of the University of Cape Town.

Results

During the study period, 5 patients presented to our unit with trichobezoar (Table 1). All patients were female, with a median age of 19 (range 12 - 27) years. Three patients were of Indian and 2 of African ethnicity. Four individuals were highly functional (3 high-school

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Cerebral palsy patient

F = female; CT = computed tomography.

University student

High-school learner High-school learner

Sex F

Age, years 27

Patient Clerk

Table 1. Patient information

Plain abdominal radiographs

Method of diagnosis Endoscopy and CT of the abdomen Endoscopy and barium meal CT of the abdomen

Epigastric mass, anorexia Endoscopy and CT of the abdomen

Abdominal distention, abdominal pain

Abdominal pain, early satiety, epigastric mass Abdominal pain

Presentation Vomiting, weight loss

Intra-operative finding Sealed prepyloric perforation, large trichobezoar extending into the jejunum Large trichobezoar extending 1.4 m into the jejunum Contained gastric perforation with massive gastric trichobezoar Small-bowel obstruction and perforation from gastric trichobezoar extending into the small bowel Large trichobezoar extending into the jejunum Natural

Laparotomy and gastrotomy

None

Natural

None

Complications None

Synthetic

Hair Synthetic

Laparotomy and gastrotomy

Laparotomy and gastrotomy Laparotomy and gastrotomy

Removal technique Laparotomy and gastrotomy

Patient knew she had trichotillomania and trichophagia

Patient acknowledged trichophagia in times of stress

Evaluation Patient denied trichophagia, despite psychiatric intervention Patient acknowledged 4 years of trichophagia Patient acknowledged trichophagia in times of stress

IN PRACTICE

graduates/students and 1 university student), while the 5th patient was a 12-year-old cerebral palsy child with known trichotillomania. Presenting symptoms included: anorexia and early satiety (n=2), intermittent vomiting with features of gastric outlet obstruction (n=1), abdominal pain (n=3) and weight loss (n=1). Four of the patients had a history of trichotillomania and trichophagia. Diagnosis was made by upper-gastrointestinal (GI) endoscopy in 3 cases (complemented by abdominal computed tomography (CT) and a barium meal), abdominal CT alone in 1 case, and plain abdominal radiography in 1 case (Figs 1 - 3). All patients were managed by laparotomy, gastrotomy and open removal of the bezoar (Figs 4 and 5). In 2 patients there was an intraoperative finding of a sealed,

Fig. 1. Endoscopic examination, indicating a trichobezoar.

Fig. 2. Barium meal examination, showing a gastric trichobezoar with extension into the duodenum.

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Fig. 3. (A) Computed tomography scan of the abdomen, showing a gastric trichobezoar.

Fig. 4. Removal of a bezoar via open gastrotomy.

Fig. 3. (B) Computed tomography scan of the abdomen, showing a gastric trichobezoar extending into the jejunum.

contained gastric perforation, and a jejunal perforation was found in 1 patient. All 5 bezoars extended into the jejunum, the longest measuring 1.4 m; 2 consisted entirely of artificial hair extensions. All patients had an uncomplicated postoperative course and 4 were referred for psychiatric evaluation.

Discussion

We present the joint largest series of patients with Rapunzel syndrome. Fallon et al.[20] described a series of 7 trichobezoars, 5 of which had features of Rapunzel syndrome. Our series also includes 2 patients in whom the bezoar consisted entirely of artificial hair extensions. Only 2 other cases of trichobezoar composed of synthetic hair have been described.[21,22] Trichobezoar and Rapunzel syndrome should be considered as a differential diagnosis in young females who present with nonspecific symptoms, such as epigastric pain, fatigue and weight loss, and an epigastric mass. A thorough history regarding any psychiatric comorbidity, as well as a history of trichotillomania/ trichophagia, should be sought, although most patients deny this, even when specifically asked.[1] Severe halitosis or patchy alopecia may be an indication of the condition. Physical examination may occasionally reveal a palpable abdominal mass. Plain abdominal radiographs often serve as the initial imaging modality, showing either an inhomogeneous mass or filling defect in the region of the stomach. A diagnosis based solely on plain radiography can be made in 50 - 75% of patients with small-bowel obstruction,[23] while only

Fig. 5. Removal of a 1.4 m trichobezoar.

10 - 18% of bezoars are recognised on radiographic features alone.[24,25] A barium meal may demonstrate a filling defect in the stomach and confirm the diagnosis. Both ultrasound and CT scans have been shown to be reliable methods for diagnosing trichobezoars and distinguishing them from other possible causes, particularly when an abdominal mass is palpated. Abdominal ultrasound scanning might demonstrate increased echogenicity, with a marked acoustic shadow due to intermixed hair and food, and CT imaging might show a low attenuating heterogenous mass containing trapped air, with oral contrast most prominent at its margins.[26,27] In a retrospective analysis of 17 patients with GI bezoars by RipollĂŠs et al.,[24] sonography detected only 25% of gastric bezoars, while CT imaging indicated the preoperative diagnosis in all patients. Upper GI endoscopy, however, remains the gold standard for diagnosis and also allows for treatment options in selected cases of small trichobezoars.[28,29] As the literature comprises small series and case studies, and there is a paucity of randomised data, it is difficult to draw conclusions regarding the optimal management of this rare group of patients.

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IN PRACTICE

The goals of bezoar treatment are the removal of the bezoar and the prevention of recurrence by addressing the underlying psychiatric/ emotional cause.[29] Unlike phytobezoars, trichobezoars are often resistant to enzymatic dissolution.[8] Endoscopic management of the trichobezoar is rarely a definitive treatment, as the bezoars are usually too large for dissolution and retrieval, and fragmentation is often impossible owing to size, density and hardness, even with specialised bezotomes and bezotriptors.[28,30] Endoscopic fragmentation can also lead to distal migration and small-bowel obstruction.[20] In the case of Rapunzel syndrome, complete removal without breakage and distal migration emphasise the importance of adequate exposure, as well as the limitations of endoscopic management. Furthermore, a recent review by Gorter et al.[30] showed that only 5% of trichobezoars were amenable to complete endoscopic removal. Endoscopic management was not attempted in any of our patients because of the large size of the bezoar and anticipated difficulty with complete removal. The optimal surgical management of trichobezoar remains controversial and divided between laparoscopic and open approaches, most often dictated by local expertise and the size of the bezoar.[30] The first laparoscopic removal of a trichobezoar was reported by Nirasawa et al.[31] in 1998. Since then, fewer than 10 other reports of attempted laparoscopic removal have been published, usually restricted to trichobezoars without extension. A novel laparoscopicassisted technique using a wound retractor has also been described to improve access and reduce operative time and complications.[32] The laparoscopic approach remains an attractive option, warranting further consideration with regard to its appropriate use in managing this rare pathological condition. The surgical management of Rapunzel syndrome, however, appears more clearly defined, as the bezoar extends beyond the pylorus and because of the risk of incomplete removal. Careful manipulation of the jejunum, to ensure complete removal of the tail without perforation or breakage, further highlights the limitations of the laparoscopic approach. Increased operative time, risk of intra-abdominal spillage and necessity of extended incisions (for bezoar removal) are additional arguments made by opponents of this approach.[30] All of our patients were successfully treated with a laparotomy. This is comparable with the findings of Fallon et al.[20] and Gorter et al.,[30] demonstrating a 99% and 100% success rate with laparotomy, respectively,. Our complete lack of postoperative complications is also in line with the benign postoperative course reported in the series by Fallon et al.[20] However, there have recently been 3 reports of successful laparoscopic removal of trichobezoars in paediatric patients, 2 of whom had post-pyloric extension.[33-35] Psychiatric assessment and long-term behavioural therapy should be considered a standard component of treatment.[30,36]

Conclusion

Although Rapunzel syndrome is a very rare entity, our series suggests that its occurrence could be higher than expected among patients with trichobezoars. The finding of a contained perforation in 60% of patients emphasises the potential for serious complications. Preoperative diagnosis requires a thorough history, complemented by radiological and endoscopic investigations. Laparotomy and open removal by gastrotomy and/or enterotomy seem to be the most frequently reported approaches, with the highest success rate and lowest complication rate. The case for laparoscopic surgical management remains compelling in appropriate cases, where it can achieve complete removal. Further experience in the form of larger series, however, is required to establish its precise role. Psychiatric consultation should be considered in all patients to prevent recurrence.

Acknowledgements. None. Author contributions. JP and GC conceived the idea and performed the analysis; JP, GC, DT, ST and BD collected the data; JP, GC, ST and EJ performed the analysis; JP wrote the article (with proofreading and corrections by GC and EJ); and GC formulated the tables. Funding. None. Conflicts of interest. None. 1. Naik S, Gupta V, Naik S, et al. Rapunzel syndrome reviewed and redefined. Dig Surg 2007;24(3):157161. https://doi.org/10.1159/000102098 2. Vaughan ED Jr, Sawyers JL, Scott HW Jr. The Rapunzel syndrome. An unusual complication of intestinal bezoar. Surgery 1968;63(2):339-343. https://doi.org/10.1016/0022-3468(68)90155-3 3. Phillips MR, Zaheer S, Drugas GT. Gastric trichobezoar: Case report and literature review. Mayo Clin Proc 1998;73(7):653-656. https://doi.org/10.1016/S0025-6196(11)64889-1 4. Hirugade S, Talpallikar M, Deshpande A, Gavali J, Borwankar S. Rapunzel syndrome with a long tail. Ind J Pediatr 2001;68(9):895-896. https://doi.org/10.1007/BF02762123 5. Schlosser S, Black DW, Blum N, Goldstein MPH. The demography, phenomenology, and family history of 22 persons with compulsive hair pulling. Ann Clin Psych 1994;6(3):147-152. https://doi. org/10.3109/10401239409148996 6. Grimm Brothers. Rapunzel. [Translated by J R Godwin.] Richmond, VA: Commonwealth University Department of Foreign Languages, 1999. 7. Williams RS. The fascinating history of bezoars. Med J Aust 1986;145(11-12):613-614. 8. Sanders MK. Bezoars: From mystical charms to medical and nutritional management. Pract Gastroenterol 2004;28:37-50. 9. Pace A, Fearne C. Trichobezoar in a 13 year old male: A case report and review of literature. Malta Med J 2003;15:39-40. 10. Deslypere J, Praet M, Verdonk G. An unusual case of trichobezoar: The Rapunzel syndrome. Am J Gastroenterol 1982;77(7):467-470. 11. Kaspar A, Deeg KH, Schmidt K, Meister R. Rapunzel syndrome, a rare form of intestinal trichobezoars. Klin Padiatr 1999;211(5):420-422. https://doi.org/10.1055/s-2008-1043825 12. Hollaar L. The Rapunzel syndrome (trichobezoar) causing atypical intussusception in a child: A case report. J Pediatr Surg 1999;34(3):479-480. https://doi.org/10.1016/S0022-3468(99)90504-3 13. Yik Y, How A. Stomach trichobezoar (Rapunzel syndrome) with iatrogenic intussusception. Med J Malaysia 2016;71(2):74-76. 14. Parakh JS, McAvoy A, Corless DJ. Rapunzel syndrome resulting in gastric perforation. Ann R Coll Surg Engl 2016;98(1):6-7. https://doi.org/ 10.1308/rcsann.2016.0008 15. Marique L, Wirtz M, Henkens A, et al. Gastric perforation due to giant trichobezoar in a 13-year-old child. J Gastrointest Surg 2017;21(6):1093-1094. https://doi.org/10.1007/s11605-016-3272-2 16. Jiledar Singh G, Mitra SK. Gastric perforation secondary to recurrent trichobezoar. Ind J Pediatr 1996;63(5):689-691. 17. Jones GC, Coutinho K, Anjaria D, Hussain N, Dholakia R. Treatment of recurrent Rapunzel syndrome and trichotillomania: Case report and literature review. Psychosomatics 2010;51(5):443-446. https:// doi.org/ 10.1176/appi.psy.51.5.443 18. Shawis R, Doig C. Gastric trichobezoar with transient pancreatitis. Arch Dis Child 1984;59(10):994995. https://doi.org/10.1136/adc.59.10.994 19. Ventura D, Herbella F, Schettini S, Delmonte C. Rapunzel syndrome with a fatal outcome in a neglected child. J Pediatr Surg 2005;40:1665-1667. https://doi.org/10.1016/j.jpedsurg.2005.06.038 20. Fallon SC, Slater BJ, Larimer EL, Brandt ML, Lopez ME. The surgical management of Rapunzel syndrome: A case series and literature review. J Pediatr Surg 2013;48(4):830-834. https://doi. org/10.1016/j.jpedsurg.2012.07.046 21. Kwong W, Kalmaz D. A modern form of Rapunzel syndrome: Trichobezoar composed of synthetic hair extensions. Clin Gastroenterol Hepatol 2014;12(5):A33-A34. https://doi.org/10.1016/j.cgh.2014.01.036 22. Flaherty DC, Aguilar F, Pradhan B, Grewal H. Rapunzel syndrome due to ingested hair extensions: Surgical and psychiatric considerations. Int J Surg Case Rep 2015;17:155-157. https://doi.org/10.1016/j. ijscr.2015.11.009 23. Erzurumlu K, Malazgirt Z, Bektas A, et al. Gastrointestinal bezoars: A retrospective analysis of 34 cases. World J Gastroenterol 2005;11(12):1813-1817. https://doi.org/10.3748/wjg.v11.i12.1813 24. Ripollés T, García-Aguayo J, Martínez MJ, Gil P. Gastrointestinal bezoars: Sonographic and CT characteristics. Am J Roentgenol 2001;177(1):65-69. https://doi.org/10.2214/ajr.177.1.1770065 25. Verstandig AG, Klin B, Bloom RA, Hadas I, Libson E. Small bowel phytobezoars: Detection with radiography. Radiology 1989;172(3):705-707. https://doi.org/10.1148/radiology.172.3.2772176 26. Newman B, Girdany B. Gastric trichobezoars – sonographic and computed tomographic appearance. Pediatr Radiol 1990;20(7):526-527. https://doi.org/10.1016/0022-3468(91)90741-B 27. West W, Duncan N. CT appearances of the Rapunzel syndrome: An unusual form of bezoar and gastrointestinal obstruction. Pediatr Radiol 1998;28(5):315-316. https://doi.org/10.1007/s002470050362 28. Wang YG, Seitz U, Li ZL, Soehendra N, Qiao XA. Endoscopic management of huge bezoars. Endoscopy 1998;30(4):371-374. https://doi.org/10.1055/s-2007-1001285 29. Gonuguntla V, Joshi DD. Rapunzel syndrome: A comprehensive review of an unusual case of trichobezoar. Clin Med Res 2009;7(3):99-102. https://doi.org/10.3121/cmr.2009.822 30. Gorter RR, Kneepkens CMF, Mattens ECJL, Aronson DC, Heij HA. Management of trichobezoar: Case report and literature review. Pediatr Surg Int 2010;26(5):457-463. https://doi.org/10.1007/s00383010-2570-0 31. Nirasawa Y, Mori T, Ito Y, Tanaka H, Seki N, Atomi Y. Laparoscopic removal of a large gastric trichobezoar. J Pediatr Surg 1998;33(4):663-665. https://doi.org/10.1016/S0022-3468(98)90342-6 32. Tudor ECG, Clark MC. Laparoscopic-assisted removal of gastric trichobezoar: A novel technique to reduce operative complications and time. J Pediatr Surg 2013;48(3):13-15. https://doi.org/10.1016/j.jpedsurg.2012.12.028 33. Fraser J, Leys C. Laparoscopic removal of a gastric trichobezoar in a pediatric patient. J Laparoendosc Adv Surg Tech A 2009;19(6):835-837. https://doi.org/10.1089/lap.2008.0367 34. Cintolo J, Telem D, Divino C. Laparoscopic removal of a large gastric trichobezoar in a 4-year-old girl. J Soc Laparosc Surgeons 2009;13(4):608-611. https://doi.org/10.4293/108680809X12589999538110 35. Dorn HF, Gillick JL, Stringel G. Laparoscopic intragastric removal of giant trichobezoar. J Soc Laparosc Surgeons 2010;14(2):259-262. https://doi.org/10.4293/108680810X12785289144520 36. Franklin ME, Edson AL, Ledley DA, Cahill SP. Behavior therapy for pediatric trichotillomania: A randomized controlled trial. J Am Acad Child Adolesc Psychiatry 2011;50(8):763-771. https:// doi.org/10.1016/j.jaac.2011.05.009

Accepted 15 March 2018.

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Incidence of Hodgkin lymphoma in HIV-positive and HIV-negative patients at a tertiary hospital in South Africa (2005 - 2016) and comparison with other African countries N Naidoo,1 MB BCh, MPH; A Abayomi,1 MBBS, MRCP, FCPath, MPhil, DHSM; C Locketz,2 MB ChB, FC Path (Anat), MMed (Anat Path); F Musaigwa,1 MPath (Haem Path); R Grewal,1 MB ChB, FC Path (Haem), MMed (Haem Path) 1 2

Division of Haematopathology, Department of Pathology, National Health Laboratory Service and Stellenbosch University, Cape Town, South Africa Division of Anatomical Pathology, Department of Pathology, National Health Laboratory Service and Stellenbosch University, Cape Town, South Africa

Corresponding author: N Naidoo (nasheen.naidoo@nhls.ac.za) Background. Hodgkin lymphoma (HL) is the most common non-AIDS-defining cancer in HIV-positive patients. Studies on South African (SA) populations have described the prevalence as 7 - 17% of all lymphomas, 8 - 27% of head and neck lymphomas, 9% of lymph node biopsies and 4% of HIV-related malignancies. Objectives. To describe the incidence of HL at our centre between 2005 and 2016 by year, gender, HIV status, histological subclassification and bone marrow involvement, and compare these findings with similar SA and African studies. Methods. This was a retrospective study of all incident HL cases diagnosed in the Department of Pathology, National Health Laboratory Service, Tygerberg Academic Hospital, Cape Town. Follow-up, relapsed and referral cases were excluded. A positive diagnosis of HL was confirmed by either lymph node or bone marrow biopsy and was based on morphological and immunohistochemical findings in accordance with the World Health Organization classification. Results. There were 303 incident cases of HL diagnosed. The incidence increased from 2005 to 2011, with a spike in cases in 2008 and a subsequent decline overall after 2011. The highest proportion of cases was in the 25 - 49-year-old age category (51.1%). There were 77 HIV-positive patients (25.4%), of whom 53 (68.8%) had CD4+ counts <500 cells/µL. In keeping with other African studies, the main subtypes were nodular sclerosis HL (49.8%) and mixed-cellularity HL (23.1%). Bone marrow biopsy following lymph node diagnosis of HL confirmed involvement in 23.7% of patients. Conclusions. Absolute numbers of cases of HL at our centre have increased since the roll-out of antiretroviral therapy (ART) to the public sector. The recent change in policy to make ART available to all HIV-positive patients independent of CD4+ count suggests that patients will survive longer and are therefore at increased risk of developing HL. We anticipate that numbers of HL cases will increase or remain high in the coming years, and we need to prepare for this. S Afr Med J 2018;108(7):563-567. DOI:10.7196/SAMJ.2018.v108i7.12844

It has been shown in the past 30 years that Hodgkin lymphoma (HL) comprises two different B-cell disease entities, namely classic HL (CHL) and nodular lymphocyte-predominant HL. Although gene expression profiling shows that these two types of HL have similarities, they differ considerably in their morphology, immunophenotype and clinical course. CHL comprises ~95% of all lymphomas and is further subclassified into four different histological variants, namely nodular sclerosis HL (CHL-NS), mixed-cellularity HL (CHL-MC), lymphocyterich HL (CHL-LR) and lymphocyte-deplete HL (CHL-LD).[1] HL is the most common non-AIDS-defining cancer in HIVpositive patients, who are at 8 - 10 times higher risk than HIVnegative individuals. In 2016, it was estimated that 12.7% (7.03 million) of the population aged 15 - 49 years in South Africa (SA) was HIV-positive, compared with 10.8% (5.1 million) in 2005. The global incidence of HL increased by 12.9% between 2005 and 2015.[2] This rise in incidence largely seems to be linked to HIV infection. Several studies conducted at SA tertiary hospitals have described the prevalence of HL as 7 - 17% of all lymphomas,[3-6] 8 - 27% of head and neck lymphomas,[7,8] 9% of lymph node biopsies and 4% of HIV-related malignancies[9] presenting at the respective hospitals. HIV seropositivity in these cases ranged between 8% and

67%.[3-6,8] The most common subtypes documented were CHL-MC and CHL-NS.[6,8] There are few epidemiological studies of HL in other African countries, with previous studies showing prevalences of HL between 0.5% and 2% of all malignancies,[10,11] 7 - 12.5% of all lymphomas[12] and 7 - 11% of all lymph node biopsies[13] investigated. HIV seropositivity ranged between 0% and 16%,[10-14] with some studies not testing for HIV owing to lack of availability of the means to do so.[10,11,13] A multi-African study[14] (n=52 cases) and a Nigerian study[11] (n=80) described CHL-MC and CHL-NS as the most common subtypes, whereas studies in Nigeria[13] (n=56) and Malawi[12] (n=31) recorded a predominance of CHL-MC and CHL-LD. It is reported that HIV-positive patients on antiretroviral therapy (ART) with a higher CD4+ count are at higher risk of developing CHL than patients with a lower CD4+ count. The risk of developing HL is highest when the CD4+ count is between 150 and 199 cells/µL. There are several theories regarding the role of ART. One is that ART increases the CD4+ count, which the Hodgkin Reed-Sternberg (HRS) cells are dependent on for their growth. A second theory is that the HRS cell is a crippled B-cell and therefore not directly affected by HIV. As these HRS cells are B-cells they attract CD4+ T-cells, and the

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increase in CD4+ T-cells is therefore a consequence of the tumour cell. A third theory is that there are competing risks, in that patients with lower CD4+ counts are more likely to suffer from AIDs-defining illnesses.[1] As CHL has previously been shown to be dependent on CD4+ counts in HIV-positive patients, it is vital that we establish the baseline incidence and the impact of ART rollout on the incidence of HL in our institution over the past decade. Initiation of ART in the public sector in SA was implemented in patients with a CD4+ count of <200 cells/µL in 2004. This changed to <350 cells/µL in 2013 and then to <500 cells/µL in 2015. The 2017 Adult Antiretroviral Therapy Guideline recommendation is to treat HIV-positive patients independent of the baseline CD4+ count.

Objectives

The prevalence of HL at our centre, Tygerberg Academic Hospital (TAH) in the Western Cape Province of SA, was 17% of all lymphomas diagnosed between 2002 and 2009 (n=187 cases); 8% of HL patients were HIV-positive.[5] The objective of this study was to expand on this previous prevalence study of all lymphomas conducted at our centre[5] by describing in more detail the incidence of HL between 2005 and 2016 by year, gender, HIV status, histological subclassification and bone marrow involvement, and to compare these findings with other SA and African studies describing HL.

Methods

A retrospective study of HL cases diagnosed in the Division of Anatomical Pathology and the Division of Haematopathology, Department of Pathology, National Health Laboratory Service (NHLS), TAH, was conducted. TAH is a 1 380-bed tertiary referral academic hospital affiliated to Stellenbosch University and services approximately half of the population of the Western Cape (total population ~6.3 million). Cases were collected from 1 January 2005 to 31 December 2016 and form part of the ongoing Tygerberg Lymphoma Study Group database (Human Research Ethics Committee ref. no. N07/03/068) established in 2007 in the Division of Haematopathology with the aim of documenting all lymphoma cases presenting at TAH.[5] Patient demographic, HIV test, CD4+ count, lymph node and bone marrow biopsy data for this database were extracted from the DisaLab version 04.16.04.373 (Laboratory System Technology (Pty) Ltd, South Africa) (up to August 2015) and TrakCare v6.10 (InterSystems, Australia) laboratory information systems. Ethical approval of the study was granted by the Health Research Ethics Committee, Stellenbosch University (ref. no. S15/09/206).

Case definition

A positive diagnosis of HL was confirmed either by lymph node biopsy assessment reported by the Division of Anatomical Pathology or by bone marrow biopsy assessment reported by the Division of Haematopathology. A staging bone marrow biopsy was routinely performed on all lymph node biopsy-positive lymphoma patients at our centre. The lymph node and bone marrow biopsy diagnoses were based on morphological and immunohistochemical findings in accordance with the 2008 World Health Organization classification of tumours of haematopoietic and lymphoid tissues. The bone marrow biopsy procedure and reporting format followed the International Council for Standardisation in Haematology guidelines.

Inclusion and exclusion criteria

All incident cases of HL of all ages presenting between 1 January 2005 and 31 December 2016 were included in the study. Follow-up, relapsed and referral cases of HL were excluded.

Patient variables

Demographic characteristics (age and gender), date of diagnosis, HIV status (using enzyme-linked immunosorbent assay HIV serology testing), CD4+ count (using flow cytometry pan-leucocyte gating techniques), HIV viral load (measured by quantitative RNA-based testing using the Amplicor HIV-1 Monitor Test (Roche Diagnostics, USA)), HL subclassification and presence of bone marrow involvement of HL (stage 4 disease) were collected. Age ranges for analysis were selected as per the 2012 South African National HIV Prevalence, Incidence and Behavioural Survey for comparability.

Data analysis

Statistical analysis of all data was performed using Excel 2016 (Microsoft, USA) and SPSS v20 (SPSS, USA). Results were summarised and presented by year, gender and HIV status using descriptive statistical methods. As HL is an HIV-related tumour, all variables were analysed by HIV status.

Results

There were 303 incident cases of HL (56.4% male and 43.6% female) diagnosed between 2005 and 2016 (Table 1).

Year

There was an increasing trend in incidence of cases in both HIV-positive and HIV-negative patients from 2005 to 2011, with a spike in cases in 2008. There was a subsequent overall decline after 2011 (Fig. 1).

Age

The mean (standard deviation (SD)) age at diagnosis of HL, independent of HIV status, was 33.4 (15.9) years. There was no significant difference in the mean age at diagnosis of HL between the HIV-positive and HIV-negative groups (Table 1). The highest number of cases was found in the 25 - 49-year age range category (n=155, 51.1%) (Table 1 and Fig. 2).

Gender

There was no statistically significant difference in gender between the HIV-positive and HIV-negative groups (p=0.14).

HIV status and CD4+ count

Only 81.2% (n=246) of our sample had confirmation of HIV testing. There were 77 HIV-positive patients (25.4%), of whom 64 (21.1%) had CD4+ counts reported. There were 169 HIV-negative patients (55.8%) and 57 patients with unknown HIV status (18.8%). In the HIV-positive group, 43 patients (55.8%) had a CD4+ count of <350 cells/µL at the time of diagnosis, whereas 53 patients (71.4%) had a count of <500 cells/µL. Only 30 patients (39.0%) had a count of <200 cells/µl (Table 2). The 2015 SA HIV management guidelines recommended changing initiation of treatment in all HIV-positive patients from CD4+ <350 cells/µL to <500 cells/µL. The mean (SD) CD4+ count at the time of diagnosis for those tested was 225 (173) cells/µL).

Histological subtype

There were 280 cases of HL (92.4%) diagnosed by lymph node biopsy. The most frequent subtypes identified were CHL-NS (151 cases, 49.8% of all subtypes identified) and CHL-MC (70 cases, 23.1%) (Fig. 3). Of those patients tested for HIV, more were HIV-negative in these two subtypes (72.2% v. 67.6%) (Table 1 and Fig. 3).

Bone marrow involvement (stage 4 disease)

Bone marrow biopsy following lymph node diagnosis of HL con-

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Table 1. Selected characteristics of all HL cases by HIV status, 2005 - 2016 HIV status (N=303) HIV-negative Unknown (n=169, 55.8%) (n=57, 18.8%) 32.2 (16.7) 35.6 (19.1) 21 (12.4) 8 (14.0) 41 (24.3) 8 (14.0) 71 (42.0) 25 (43.9) 25 (14.8) 8 (14.0) 11 (6.5) 8 (14.8)

Total 31 (10.2) 59 (19.5) 155 (51.1) 38 (12.5) 20 (6.6)

p-value 0.24

0.14 38 (49.4) 39 (50.6)

101 (59.8) 68 (40.2)

32 (56.7) 25 (43.9)

171 (56.4) 132 (43.6)

7 (9.1) 32 (41.6) 20 (26.0) 3 (3.9) 3 (3.9) 0 12 (15.6)

20 (11.8) 88 (52.1) 34 (20.1) 6 (3.6) 3 (1.8) 8 (4.7) 10 (5.9)

4 (7.0) 31 (54.4) 15 (26.3) 0 3 (5.3) 2 (3.5) 2 (3.5)

31 (10.2) 151 (49.8) 69 (22.7) 9 (3.0) 9 (3.0) 10 (3.3) 24 (7.9)

33 (19.5) 5 (2.9) 121 (71.6) 13 (7.7) 2 (1.2)

4 (7.0) 1 (1.8) 18 (31.6) 35 (61.4) 0

72 (23.7) 14 (4.6) 168 (55.4) 60 (19.8) 3 (1.0)

35 (45.5) 8 (10.3) 29 (37.7) 12 (15.6) 1 (1.3)

Cases, n

Characteristics Age (yr), mean (SD) Age (yr), n (%) 0 - 14 15 - 24 25 - 49 50 - 59 ≥60 Gender, n (%) Male Female Histological subtype (based on lymph node diagnosis), n (%) CHL (no subclassification) CHL-NS CHL-MC CHL-LR CHL-LD NLPHL Inconclusive Bone marrow involvement, n (%) Yes Bone marrow diagnosis No Not done Inadequate bone marrow

HIV-positive (n=77, 25.4%) 34.4 (10.5) 2 (2.6) 10 (13.0) 59 (76.6) 5 (6.5) 1 (1.3)

45 40 35 30 25 20

Unknown HIV-negative HIV-positive

HL = Hodgkin lymphoma; CHL = classic HL; CHL-NS = nodular sclerosis CHL; CHL-MC = mixed-cellularity CHL; CHL-LR = lymphocyte-rich CHL; CHL-LD = lymphocyte-depleted CHL; 15 NLPHL = nodular lymphocyte-predominant CHL.

10 5

Table 2. Number and percentage of patients in CD4+ categories, 2005 - 2016 0

Patients, n (%)

<50 10 (13.0)

51 - 149 12 (15.6)

CD4+ cell count (cells/µL) 2005 2006 2007 Unknown 2008 2009 2010 2011Total 2012 2013 2014 2015 2016 150 - 199 >200 Year 77 8 (10.4) 34 (44.2) 13 (16.8)

Unknown HIV-negative HIV-positive

45 40 35

Cases, n

30 25 20 15 10 5

Unknown HIV-negative HIV-positive

180 160 140 120 100 80 60 40 20 0 0 - 14

Year

Unknown 72 patients (23.7%), HIV-negative marrowHIV-positive involvement

Cases, n

180involvement of the bone marrow in firmed while160 168 patients (55.4%) did not have bone 140 (Table 1 and Fig. 4). Of patients with bone marrow involvement, 120 roughly equal numbers were HIV-positive (48.6%) and HIV-negative 100 80 60 40 20 0

51 25 - 49

50 - 59

≥60

Fig. 2. Age distribution of Hodgkin lymphoma cases by HIV status, 2005 - 2016.

Fig. 1. Number of incident Hodgkin lymphoma cases by year and HIV status, 2005 - 2016.

15 - 24

25 - 49

Age range (years)

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

0 - 14

15 - 24

50 - 59

(45.8%). There were 29 HIV-positive HL patients who did not have bone marrow involvement. There were 14 cases of HL that were initially diagnosed from incidental bone marrow biopsies for investigation of pancytopenia or bicytopenia. Subtyping of HL is currently not performed on bone marrow biopsy specimens.

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CHL CHL-NS Subtype

CHL-MC CHL-LR Unknown HIV-negative

CHL CHL-LD CHL-NS

NLPHL

HIV-positive

CHL-MC

Subtype

Inconclusive

CHL-LR

CHL-LD 0 NLPHL

100 Unknown 120 140

Cases, n

HIV-negative

160

HIV-positive

Inconclusive

Fig. 3. Hodgkin lymphoma subtype by HIV status (based on lymph node 0 20 (CHL 40 =60classic 80 Hodgkin 100 120lymphoma; 140 160CHL-NS = diagnosis), 2005 - 2016. Cases, n nodular sclerosis CHL; CHL-MC = mixed-cellularity CHL; CHL-LR = lymphocyte-rich CHL; CHL-LD = lymphocyte-depleted CHL; NLPHL = nodular lymphocyte-predominant CHL.) Bone marrow involved

Combined ART has been shown to improve survival in HL patients. The total number of patients receiving ART in SA increased from 47 500 in mid-2004 to 1.79 million in mid-2011, with ~85% of these patients receiving ART through the public health sector.[15] There were 5 000 patients on ART in the Western Cape in 2004, the figure increasing to 107 000 by 2011 in the public, private and nongovernmental organisation sectors combined. The percentage of new patients on ART ranged between 34% and 64% each year. From 2004 to 2011, there were twice as many women than men on ART.[15] These increases in ART coverage would be likely to affect the epidemiology of HIV-related lymphomas presenting at our institution. Early epidemiological studies have suggested a possible association between ART and the incidence of HL. The risk of HL increased by 68% in HIV-positive patients since ART was introduced in the USA (1996 - 2002) compared with the previous period of no ART (1990 - 1995).[16]

HIV status and CD4+ count

A higher proportion of cases in our study population were HIVnegative (55.8%) than HIV-positive (25.4%). Of the HIV-positive Bone marrow involved patients, 54.6% had a CD4+ count >150 cells/µL, which is consistent Bone marrow not involved with a US population study of HL from 1980 to 2002 that showed significantly more patients with CD4+ counts of 150 - 199 cells/µL Bone marrow not involved Unknown compared with <50 cells/µL.[17] None of the studies on HL in African Unknown populations reviewed had documented CD4+ counts. Unknown Unknown HIV-negative A study of several US states linking HIV/AIDS and cancer registry HIV-negative Inconclusive HIV-positive data in patients to identify HL cases (1980 - 2002, n=173 cases) Inconclusive HIV-positive concluded that patients with moderate levels of immunodeficiency 80 120 100 140120 180 count 150 - 199 cells/µL) were at higher risk of developing 00 2020 40 40 60 6080 100 160 140 180 160 (CD4+ HL than those with more severe levels of immunodeficiency (CD4+ Cases, Cases, n n count <50 cells/µL). Furthermore, in another study the mean CD4+ count at diagnosis of HL was 210 cells/µL, which was found to be Fig. 4. Bone marrow involvement by HIV status, 2005 - 2016. relatively high compared with other HIV-associated non-HL.[18] Our study found that ~55% of HIV-positive HL patients had a CD4+ Discussion count >150 cells/µL, in keeping with the US study. This finding Our study identified 303 new cases of HL at Tygerberg Hospital further supports the hypothesis that the tumour microenvironment between 2005 and 2016 by lymph node biopsy diagnosis (93.4%) or (non-neoplastic reactive cells) releases feedback cytokines and bone marrow biopsy diagnosis (4.6%). HL was not identified in any chemokines that stimulate the proliferation or inhibition of apoptosis other extranodal sites. of HRS cells.[18] Increasing trend in HL incidence from 2005 to 2011 However, a subsequent Swiss cohort of HIV-positive patients followed up for 20 years (n=14 606) concluded there was no evidence The global incidence of HL increased by 12.9% between 2005 and of increased HL risk with ART and improved immunity. A study in 2015.[2] Similarly, a previous study at our institution between 2002 Uganda (1999 - 2008) evaluated the effect of ART on HIV-related and 2009 showed an increased incidence of all lymphomas, including cancer incidence and further concluded that there was no association more rare types such as Burkitt lymphoma and plasmablastic between increased ART coverage and incidence of HL (n=153 cases).[19] lymphoma, in both HIV-positive and HIV-negative patients.[5] The increasing trend in the incidence of HL in our population between 2005 and 2011 is influenced by multifactorial causes. Age and gender Firstly, ART rollout for HIV-positive patients in the public health HIV seroprevalence in this study population was highest in the 25 sector commenced in 2004. Secondly, urbanisation with migration 49-year age group (76.6%), which is also the age group most affected of people to the Western Cape from other areas of SA and other by HIV in SA. There was no difference between male and female African countries may have contributed to the increase. International patients in our study, which is in keeping with a previous study in guidelines for the diagnosis and treatment of HL suggest HIV testing several sub-Saharan African countries[14] and in Western populations. as part of risk stratification. Unfortunately, testing for HIV in SA carried a social stigma during the early rise of HIV disease. This Decreasing trend from 2012 to 2016 resulted in fewer suspected lymphoma patients being tested and Although the trend from 2012 to 2016 differs from that for 2005 to therefore could have influenced our data. This is possibly evidenced 2011, absolute numbers of HL have increased since 2005. Further by the 18.8% of patients of unknown HIV status in our data, with investigation is necessary to identify the underlying causes for these the majority of these cases before 2012 (66.7%). Although our study differences during this period. showed that overall more incident cases of HL were HIV-negative, the proportion of patients who were HIV-positive was noted to be Histological subtype on the rise. The predominant subtypes (CHL-MC and CHL-NS) in HIV-

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positive patients are in keeping with previous SA studies[6-8] and with two African studies.[11,14] Two other African studies showed a predominance of CHL-MC and CHL-LD.[12,13] In contrast, the most common HL subtypes in Western populations are CHL-MC and CHL-LD.

Bone marrow involvement (stage 4 disease)

Our HL population included 72 cases (23.7%) with bone marrow involvement, compared with 6 cases (50%) in a recent Malawian study.[12] Of these 72 patients, 14 (19.4%) were initially diagnosed by bone marrow biopsy. This finding supports clinical observations that HIV-positive patients with lymphoma may present atypically. In our setting, the diagnosis of lymphoma may be delayed owing to the increase of concomitant TB and HIV, as the clinical presentations overlap. HIV patients may therefore present with extensive disease. This is an important finding, and we recommend that clinicians have a high index of suspicion when HIV-positive patients present with suggestive clinical features, namely B-cell symptoms.

Study strengths and limitations

A strength of our study was the long period of observation and the comprehensive laboratory information management systems at TAH. Limitations include the retrospective study design and incomplete data on the HIV status of 18.8% of the cohort. Further, we did not have data on ART use in this cohort. We also did not have data on patients diagnosed at other centres/departments or in the private health sector and then subsequently referred to TBH for treatment.

Conclusions

Our study showed that the absolute numbers of HL at our centre increased over the 10 years after roll-out of ART to the public sector. The change in recent policy of ART availability to all HIV-positive patients independent of CD4+ count suggests that patients will survive longer and are therefore at increased risk of developing HL. Based on the study findings, we anticipate that numbers of HL cases will increase or remain high in the coming years, and we need to increase awareness and to prepare for this. Finally, our findings highlight the value of a regional and national cancer registry linked to an HIV test result database for the monitoring of HIV-related malignancies such as HL. Acknowledgements. We thank the NHLS at Tygerberg Hospital for use of their database and Mr W Kleynhans (IT Department) for data access and retrieval.

Author contributions. NN contributed to the study design, analysis and manuscript writing. RG contributed to conceptualisation, study design and manuscript writing. AA and CL contributed to critical review. FM contributed to data collection and analysis. Funding. We thank the Cancer Association of South Africa for their financial contribution towards this study. Conflicts of interest. None. The views expressed in this article are the authors’ own and not the official position of the NHLS and Stellenbosch University. 1. Martis N, Mounier N. Hodgkin lymphoma in patients with HIV infection: A review. Curr Hematol Malig Rep 2012;7(3):228-234. https://doi.org/10.1007/s11899-012-0125-2 2. Fitzmaurice C, Allen C, Barber RM, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the Global Burden of Disease Study. JAMA Oncol 2017;3(4):524-548. https://doi.org/10.1001/jamaoncol.2016.5688 3. Patel M, Philip V, Omar T, et al. The impact of human immunodeficiency virus infection (HIV) on lymphoma in South Africa. J Cancer Ther 2015;6(6):527-535. https://doi.org/10.4236/jct.2015.66057 4. Wiggill TM, Mantina H, Willem P, et al. Changing pattern of lymphoma subgroups at a tertiary academic complex in a high-prevalence HIV setting: A South African perspective. J Acquir Immune Defic Syndr 2011;56(5):460-466. https://doi.org/10.1097/QAI.0b013e31820bb06a 5. Abayomi EA, Somers A, Grewal R, et al. Impact of the HIV epidemic and anti-retroviral treatment policy on lymphoma incidence and subtypes seen in the Western Cape of South Africa, 2002 - 2009: Preliminary findings of the Tygerberg Lymphoma Study Group. Transfus Apher Sci 2011;44(2):161166. https://doi.org/10.1016/j.transci.2011.01.007 6. Mantina H, Wiggill TM, Carmona S, et al. Characterization of lymphomas in a high prevalence HIV setting. J Acquir Immune Defic Syndr 2010;53(5):656-660. https://insights.ovid.com/ pubmed?pmid=20160652 (accessed 28 May 2018). 7. Alli N, Meer S. Head and neck lymphomas: A 20-year review in an oral pathology unit, Johannesburg, South Africa, a country with the highest global incidence of HIV/AIDS. Oral Oncol 2017;67(4):17-23. https://doi.org/10.1016/j.oraloncology.2017.01.011 8. Chetty M, Sudi S, Abayomi EA. Prevalence and spectrum of head and neck lymphomas at Tygerberg Hospital, South Africa, 2003 to 2007. J S Afr Dent Assoc 2012;67(6):270-277. http://journals.co.za/ content/sada/67/6/EJC143694 (accessed 28 May 2018). 9. Reddy DL, Venter WD, Pather S. Patterns of lymph node pathology; fine needle aspiration biopsy as an evaluation tool for lymphadenopathy: A retrospective descriptive study conducted at the largest hospital in Africa. PloS One 2015;10(6):1-10. https://doi.org/10.1371/journal.pone.0130148 10. Chokunonga E, Borok MZ, Chirenje ZM, et al. Trends in the incidence of cancer in the black population of Harare, Zimbabwe 1991 - 2010. Int J Cancer 2013;133(3):721-729. https://doi.org/10.1002/ijc.28063 11. Oluwasola AO, Olaniyi JA, Otegbayo JA, et al. A fifteen-year review of lymphomas in a Nigerian tertiary healthcare centre. J Health Popul Nutr 2011;29(4):310-316. https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3190361/ 12. Westmoreland KD, Stanley CC, Montgomery ND, et al. Hodgkin lymphoma, HIV, and Epstein-Barr virus in Malawi: Longitudinal results from the Kamuzu Central Hospital Lymphoma study. Pediatr Blood Cancer 2017;64(5):e26302. https://doi.org/10.1002/pbc.26302 13. Olu-Eddo AN, Omoti CE. Hodgkin lymphoma: Clinicopathologic features in Benin City, Nigeria and update on its biology and classification. Niger J Clin Pract 2011;14(4):440-444. https://doi. org/10.4103/1119-3077.91752 14. Naresh KN, Raphael M, Ayers L, et al. Lymphomas in sub-Saharan Africa – what can we learn and how can we help in improving diagnosis, managing patients and fostering translational research? Br J Haematol 2011;154(6):696-703. https://doi.org/10.1111/j.1365-2141.2011.08772.x 15. Johnson LF. Access to antiretroviral treatment in South Africa, 2004 - 2011. South Afr J HIV Med 2012;13(1):22-27. https://doi.org/10.1080/09540121.2014.994471 16. Engels EA, Pfeiffer RM, Goedert JJ, et al. Trends in cancer risk among people with AIDS in the United States 1980 - 2002. AIDS 2006;20(12):1645-1654. https://doi.org/10.1097/01.aids.0000238411.75324.59 17. Biggar RJ, Jaffe ES, Goedert JJ, et al. Hodgkin lymphoma and immunodeficiency in persons with HIV/ AIDS. Blood 2006;108(12):3786-3791. https://doi.org/10.1182/blood-2006-05-024109 18. Carbone A, Vaccher E, Gloghini A, et al. Diagnosis and management of lymphomas and other cancers in HIV-infected patients. Nat Rev Clin Oncol 2014;11(4):223-238. https://doi.org/10.1038/ nrclinonc.2014.31 19. Mutyaba I, Phipps W, Krantz EM, et al. A population-level evaluation of the effect of antiretroviral therapy on cancer incidence in Kyadondo County, Uganda, 1999 - 2008. J Acquir Immune Defic Syndr 2015;69(4):481-486. https://doi.org/10.1097/QAI.0000000000000620

Accepted 13 February 2018.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

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Hepatitis C prevalence in HIV-infected heterosexual men and men who have sex with men N A Gogela,1 FCP (SA); M W Sonderup,1 FCP (SA), MMed; K Rebe,2,3 FCP (SA); T Chivese,3,4 MSc; C W Spearman,1 FCP (SA), PhD Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa 2 ANOVA Health Institute, Johannesburg and Cape Town, South Africa 3 Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 4 Biostats Unit, Centre for Evidence Based Health Care, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa 1

Corresponding author: M W Sonderup (mark.sonderup@uct.ac.za) Background. Globally 1% of individuals are infected with hepatitis C virus (HCV). In South Africa (SA) the prevalence ranges between 0.3% and 1%, with few prospective screening data available. Similarly, local data on transmission modes of HCV are limited, but probably include parenteral routes and pre-1992 blood or blood products. The risk of heterosexual transmission of HCV is low but is increased in men who have sex with men (MSM), with co-transmission risk of both HIV and HCV. Objectives. Given few local data, we sought to better understand HCV characteristics and prevalence in two groups of HIV-infected men. Methods. HIV-positive men in the greater Cape Town metropolitan area were recruited. Sexual orientation was self-identified and demographic and other personal data were obtained via a confidential questionnaire. Participants were screened for HCV after a blood draw. Those with positive HCV tests had further HCV RNA confirmation. Risk factors associated with HCV seropositivity were determined. Results. Five hundred HIV-positive men were recruited, 285 (57.0%) MSM and 215 (43.0%) non-MSM, median age 36 years (interquartile range (IQR) 20 - 64) and 37 years (IQR 21 - 56), respectively (p=NS). Overall, 3.4% (n=17) screened HCV-positive, 5.6% MSM (n=16) and 0.5% non-MSM (n=1); 82.4% were viraemic for HCV RNA. In respect of genotype distribution, 50.0% were infected with genotype 1a, 14.3% with genotype 4 and 35.7% with genotype 2. In terms of risk, MSM were more likely to have used drugs (54.4% v. 30.2%; p<0.001) and to have used all five modes of drug administration (13.0% MSM v. 0.5% non-MSM for injected drugs, 36.1% v. 2.3% for inhaled, 10.0% v. 0% for rectal, 48.1% v. 28.8% for smoked and 27.4% v. 2.3% for oral). More MSM than non-MSM (46.3% v. 16.7%) reported having sex while using recreational drugs, and similarly more MSM (21.4% v. 14%) reported having sex with a sex worker (SW). Risk factors for HCV seropositivity included drug use history (odds ratio (OR) 6.28, 95% confidence interval (CI) 1.78 - 22.12; p=0.004) and in MSM, sex with an SW (OR 5.5, 95% CI 2.06 - 14.68; p=0.001) or use of recreational drugs with sex (OR 6.88, 95% CI 2.21 - 21.44; p=0.001). Conclusions. HCV prevalence in HIV-positive MSM is higher than previously appreciated or documented in SA. Risk factors include injection drug use, use of recreational drugs with sex, and sex with SWs. Targeted interventions are required to address this emerging challenge to achieve the viral hepatitis elimination ideal by 2030. S Afr Med J 2018;108(7):568-572. DOI:10.7196/SAMJ.2018.v108i7.13041

In 2017 an estimated 71 million people globally were hepatitis C virus (HCV) viraemic, while 2.3 million were HIV co-infected.[1] HCV is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide.[2] Traditionally HCV transmission has mostly been parenteral, typically in people who inject drugs (PWID), but recent data have demonstrated that HCV prevalence increased by 15 - 20% in HIVinfected men who have sex with men (MSM) between 2007 and 2008.[3] Supporting these findings are reports from the USA, Australia and Eastern Europe of HCV emerging as a sexually transmitted infection among MSM. Data from the UK Public Health Service in 2012 noted HIV notifications increasing by 24% among MSM, of whom 13% were HCV co-infected.[4] In 2015, HCV accounted for almost 38 000 deaths in sub-Saharan Africa.[5] However, there are few data for high-risk groups, with accurate data collection complicated by potential cultural bias and laws against PWID and MSM. Approximately 8% of the global PWID population resides in sub-Saharan Africa, and hepatitis C is incompletely characterised in this key population.[6] The genotype distribution of HCV in a population is informative, and the finding of predominantly genotypes 1 and 4 in non-PWID

MSM and genotype 3a in PWID suggests possible intra-network modes of transmission.[7] South Africa (SA) is an epicentre of the HIV pandemic, with an estimated 12.2% HIV prevalence equating to some 7.1 million HIVinfected people.[8] There are very few data on HCV and HCV-HIV co-infection prevalence in SA. Data from blood transfusion services indicate donor HCV viraemic rates of ≤0.3% and random clinicbased screening data reporting 1% seroprevalence rates. Of note, in a 1997 antiretroviral therapy study with mandatory HCV screening that included SA as a site, HCV antibody prevalence in HIV-positive patients was 2%, much higher than would have been anticipated.[9] Local HIV management guidelines do not include routine screening for HCV. A concern with HIV/HCV co-infection is that it can accelerate the progression of liver disease and HCC risk.[10]

Objectives

Given the need for the better understanding of our local HCV epidemiology, we elected to determine local HCV prevalence in an at-risk group, viz. HIV-positive men, by comparing heterosexual men

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and MSM, to better characterise modes of transmission and HCV genotype distribution.

Methods

Study design

Serologically confirmed HIV-positive men aged >18 years were prospectively recruited between 2011 and 2014 from healthcare centres in the greater Cape Town metropolitan area, including a dedicated clinic serving MSM. Following informed consent, participants self-identified their sexual orientation as heterosexual or MSM. A confidential questionnaire was administered during a face-to-face interview. Blood samples were obtained for testing and storage at –80oC within an hour of collection. Serum was tested for the presence of hepatitis C IgG antibody using the ARCHITECT II system (Abbott Diagnostics Division, USA). Samples positive for hepatitis C IgG antibody were analysed for the presence of hepatitis C RNA by means of an in-house polymerase chain reaction (PCR) technique after amplifying the 5’NCR region of the virus. HCV genotype was determined using the Versant HCV Genotype v2.0 Line Probe Assay (Siemens AG, Germany) and viral loads using the COBAS Ampliprep/Cobas TaqMan v2.0 (Roche Diagnostics, Switzerland). All participants identified as viraemic for HCV were referred to the Liver Clinic at Groote Schuur Hospital, Cape Town. The Human Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town, approved the study (ref. no. 355/ 2009). The study complied with the Declaration of Helsinki (2007).

Data collection

A standardised structured questionnaire that included demographic data was confidentially administered to all participants to capture information on age, self-identified ethnicity/race and sexual orientation, and other risk factors for HCV acquisition, e.g. blood transfusion/blood products received prior to 1992. A detailed history of past or current substance use was obtained, including cannabis, MDMA (methylenedioxymethamphetamine), GHB (gamma-hydroxybutyrate), crystal methamphetamine, cocaine, CAT (methcathinone), liquid MDMA (liquid E), heroin and methaqualone. The mode of substance use administration was recorded as oral, sniffing/insufflation, injection, smoking or rectal, and the quantity of alcohol consumed (g/d) was also documented. Information on the use of these substances at times of sexual intercourse and on the use of commercial sex worker (SW) services was also recorded. Additional data including possible needlestick injury (especially for healthcare workers) and known hepatitis B surface antigen status and CD4+ counts were documented.

Statistical analysis

The non-MSM and MSM groups were compared and statistical significance was tested at a level of 0.05 with 95% confidence intervals (CIs). Medians and interquartile ranges (IQRs) were reported for measured data (age and CD4+ count) as they were not normally distributed, while frequencies and percentages were used to describe categorical data. The χ2 test was used to compare categorical outcomes and the Wilcoxon rank-sum test to compare measured data. HCV prevalence as reported by antibody and viraemia was calculated as a simple proportion of HCV-positives divided by the whole sample. Exploratory univariate analysis for factors associated with acquiring HCV infection was performed. The use of individual drugs (cannabis, MDMA, GHB/liquid E, crystal meth, cocaine, CAT, heroin and methaqualone) and drug administration modes (oral, sniffing, injection, smoking and rectal) were also explored for

association with acquiring HCV. Other variables considered were previous parenteral injury for former or current healthcare workers, sexual history variables such as whether the individual was in a current relationship or not, current sex partner, MSM v. non-MSM, drug use before or during sex, and sex with a commercial SW. Odds ratios (ORs) and their 95% CIs were reported. Statistical analysis was performed using Stata 15 (StataCorp, USA).

Results

Demographic characteristics

Table 1 provides a summary of the demographics of the study participants. Of the 500 HIV-positive men recruited, 285 (57.0%) were MSM and 215 (43.0%) non-MSM. The median ages of the MSM and the non-MSM were 36 years (IQR 20 - 64) and 37 years (IQR 21 - 56) (p=NS). The median CD4+ T-cell count of the MSM was significantly higher than that of the non-MSM, 413 cells/µL (IQR 78 - 989) and 283 cells/µL (IQR 7 - 727), respectively; p<0.001. Most non-MSM participants (88.8%) were black African, while most MSM (48.1%) were white. There were no differences in pre-1992 blood/blood product exposure between MSM and non-MSM. MSM were more likely to have used drugs (54.4% v. 30.2%, p<0.001). Furthermore, MSM were more likely than non-MSM to have used all five modes of drug administration (p<0.001). MSM were also more likely to have used cannabis, GHB, MDMA, crystal meth, cocaine, CAT or heroin. No participant gave a history of a needlestick injury. Non-MSM were more likely than MSM to be in a monogamous relationship (76.3% v. 42.1%; p<0.001). A small component of MSM (2.3%) reported women as their predominant sexual partners, while 7.8% reported having both males and females as their normal sexual partners. Of the MSM, 46.3% reported having sex under the influence of recreational drugs, compared with 16.7% of non-MSM (p<0.001), while 21.4% of MSM reported having sex with a commercial SW, compared with 14.0% of non-MSM (p=0.033). Significantly more non-MSM than MSM, 26.1% and 18.3%, respectively, reported alcohol consumption of ≥40 g/day (p=0.036). Hepatitis B surface antigen status did not differ significantly between MSM and non-MSM (p=0.064).

HCV prevalence

In total, 3.4% (n=17) were HCV IgG antibody-positive at screening (Table 2), the majority in the MSM group (5.6% of MSM (n=16) and 0.5% of non-MSM (n=1)). Non-MSM who screened HCV antibodypositive reported only inhaled heroin use and no other drug use. Of the MSM who screened positive, 14 were HCV PCR-positive and 3 negative, yielding a viraemia rate of 2.8%. In respect of genotype distribution, 50.0% were genotype 1a, 14.3% genotype 4 (subtype 4d) and 35.7% genotype 2 (subtypes 2b or 2c). The median HCV viral load was 538 500 IU/mL (range 19 000 - 1 400 000). Of those who screened HCV-positive, a single participant reported using a significant amount of alcohol (≥40 g/d).

Risk factors for HCV

Factors associated with an increased risk of acquiring HCV infection are listed in Table 3. White race, low CD4+ count and use of drugs were strongly associated with risk. This was irrespective of the type of drug used or route of administration. Use of drugs with sex and sex with an SW were associated with equal risks of being HCV-positive.

Discussion

The overall HCV seroprevalence in HIV-positive men was 3.4%, notably higher than previously reported in SA. However, MSM constituted the overwhelming majority of those who screened

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Table 1. Characteristics of MSM and non-MSM participants Variable Age (years), median (IQR) CD4+ count (cells/ÂľL), median (IQR) Ethnicity, n (%) Mixed ancestry Black African White Asian Blood transfusion (pre-1992), % Drug history (yes), % Drug routes, % Injected Oral Smoked Inhaled Rectal Drug use, % Cannabis MDMA GHB/liquid E Crystal meth Cocaine CAT Heroin Mandrax In a current relationship (yes), % Had sex under influence of drugs (yes), % Had sex with commercial sex worker (yes), % Normal sex partner Men Women Both Alcohol intake â&#x2030;Ľ40 g/d (yes), % Hepatitis B surface antigen Positive Negative Unknown

MSM (N=285) 36 (20 - 64) 413 (78 - 989)

Non-MSM (N=215) 37 (21 - 57) 283 (7 - 727)

66 (23.2) 79 (27.7) 137 (48.1) 3 (1.1) 2.8 54.4

18 (8.4) 191 (88.8) 5 (2.3) 1 (0.5) 0.9 30.7

13.3 27.4 48.1 36.1 10.2

0.5 2.3 28.8 2.3 0

39.7 29.8 17.9 31.9 30.9 39.7 7.0 6.7 42.1 46.3 21.4

27.4 2.8 0.9 4.2 3.7 27.4 2.8 6.5 76.3 16.7 14.0

90.1 2.1 7.8 18.3

0 100 0 26.1

4.9 67.4 27.7

2.8 47.9 49.3

p-value 0.627 <0.001 <0.001

0.138 <0.001 <0.001

0.004 <0.001 <0.001 <0.001 <0.001 <0.001 0.035 0.945 <0.001 <0.001 0.033 <0.001

0.036 0.064

MSM = men who have sex with men; IQR = interquartile range; MDMA = methylenedioxymethamphetamine; GHB = gamma-hydroxybutyrate; CAT = methcathinone.

Table 2. Hepatitis C infection prevalence

All participants (N=500) MSM (N=285) Non-MSM (N=215)

Screened positive, n 17 16 1

Prevalence, % (95% CI) 3.4 (2.1 - 5.4) 5.6 (3.5 - 9.0) 0.5 (0.06 - 3.3)

CI = confidence interval; MSM = men who have sex with men.

HCV-positive. This is in keeping with data supporting MSM as an emerging at-risk population. Our study is the first prospective screening study of its kind in SA specifically looking at this key demographic. A recent systematic review of HCV seroprevalence in the sub-Saharan Africa region suggested a pooled HCV seroprevalence rate of 2.98%. When subcategorised, the HCV seroprevalence rate was 5.7% among HIV-infected individuals.[5,11] Our findings are not dissimilar. Two studies in Nigeria, based on hepatitis C antibody seroprevalence in different centres, 3 years apart

and performed in heterogeneous groups of HIV-positive cohorts, demonstrated even higher seroprevalence rates of 10.8% and 15%, respectively.[12,13] Interestingly, more women tested HCV antibodypositive. In one of the studies there was no significant correlation between injected drug use and HCV infection.[13] This possibly suggests that HIV poses a signficant risk for HCV acquisition regardless of gender. In this cohort, it is unclear whether the women were asked about their sexual risks, or whether they were screened for other sexually transmitted infections. In those who were HCV antibody-positive, 82% confirmed HCV RNA-positive, yielding an overall viraemic rate of 2.8%. All our viraemic patients were in the MSM cohort. We observed that MSM were more likely to use drugs and significantly more used an injection route. Existing data support the fact that injecting drug use is associated with increased risks of both HIV and HCV acquisition.[14] All participants in the MSM group who tested HCV antibody-positive had a history of injecting drug use, among other routes. The single non-MSM participant denied injecting drug use.

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of HCV transmission.[21] These behaviours include lack of lubricant use, possibly douching before anal sex, multiple partners and sex in the context of crystal methamphetamine use. We did not record information on specific sexual practices of MSM in our study, other than determination of anal sex. We do, however, note that in our local experience we have observed several HCV-positive MSM without any reported substance use or behaviours likely to cause trauma to anorectal tissue, suggesting ordinary unprotected penile-anal sexual activity as the only risk factor for HCV transmission in often concomitantly HIV-positive MSM.[22] An unexpected finding was the genotype distribution in our cohort. Genotype 1a predominated (50.0%), followed by genotype 2 (35.7%) and genotype 4 (14.3%), with no genotype 3 or 5 reported. This contrasts with a study in the general SA population, where even though genotype 1 was a predominant genotype among blood donors (34%), genotype 5 was the most prevalent overall.[5] However, a very recent seroprevalence survey of key populations in SA demonstrated genotypes 1, 3 and 4 in MSM, PWID and SWs.[23] This suggests that selected genotypes are circulating in SA MSM and other key populations. Furthermore, given that Cape Town is a popular international destination, the possibility of sex tourism by MSM introduces the potential that dominant genotypes, e.g. genotype 2c, from European origins may explain this genotype predominating in our MSM population. Phylogenetic linkage analyses of patients with similar, yet uncommon genotype subtypes would suggest a network spread of virus. Seven of the 14 viraemic patients have been linked to care. They were all treated successfully, one with pegylated interferon/ribavirin-based therapy and all the others with the more recent direct-acting antiviral therapies for hepatitis C. Despite proper counselling during the recruiting period, 50% of HCV-viraemic individuals were lost to follow-up and appropriate linkage to care. This has serious implications, as these are high-risk individuals who are likely to onwardly transmit the infection. Hepatitis C is invariably an asymptomatic infection, and if high-risk individuals are not screened periodically, we will fail to identify and treat HCV-infected individuals and prevent onward transmission. Elimination of viral hepatitis in the high-risk groups of MSM and PWID requires active harm reduction practices including hepatitis B vaccination, condom use and needle-syringe and opiate substitution programmes.

Table 3. Risk factors for HCV infection Variable Demographics Age Ethnicity Black African Mixed ancestry White CD4+ <200 cells/ÂľL Drug use Drug use history Cannabis use MDMA use GHB use Crystal meth use Cocaine use CAT use Heroin use Mandrax use Drug use routes Smoking Injection Nasal Oral Rectal Alcohol â&#x2030;Ľ40 g/d Sexual history In a current relationship Current partner (male) MSM (v. non-MSM) Sex after drugs Sex with CSW Normal sex partner Hepatitis B surface antigen (positive v. negative)

Univariate analysis OR (95% CI) p-value 1.04 (0.995 - 1.09)

0.078

1 (base) 3.24 (0.20 - 52.38) 31.77 (4.15 - 243.18) 1.003 (1.001 - 1.005)

0.408 0.001 <0.001

6.28 (1.78 - 22.12) 3.67 (1.33 - 10.09) 4.28 (1.61 - 11.43) 6.65 (2.42 - 18.30) 10.77 (3.70 - 31.36) 3.99 (1.50 - 10.63) 7.64 (2.84 - 20.54) 9.17 (2.96 - 28.41) 3.24 (0.88 - 11.88)

0.004 0.012 0.004 <0.001 <0.001 0.006 <0.001 <0.001 0.077

5.19 (1.67 - 16.15) 22.35 (7.93 - 63.04) 7.30 (2.63 - 20.22) 6.22 (2.32 - 16.63) 7.97 (2.60 - 24.45) 0.22 (0.29 - 1.68)

0.004 <0.001 <0.001 <0.001 <0.001 0.144

0.40 (0.14 - 1.11) 1.07 (0.38 - 2.97) 12.73 (1.67 - 96.75) 6.88 (2.21 - 21.44) 5.50 (2.06 - 14.68) 0.23 (0.07 - 0.77) 1.53 (0.56 - 4.17)

0.077 0.897 0.014 0.001 0.001 0.018 0.405

OR = odds ratio; CI = confidence interval; MDMA = methylenedioxymethamphetamine; GHB = gamma-hydroxybutyrate; CAT = methcathinone; MSM = men who have sex with men; CSW = commercial sex worker.

Study limitations

An important factor associated with HCV acquisition was high-risk sexual behaviour. There were significant differences in numbers of MSM who engaged in such behaviour, namely having unprotected sex with commercial SWs and having sex with the use of recreational drugs. Several studies have shown that HCV is increasing as a sexually transmitted infection among MSM who do not inject drugs.[16,17] Several observational studies comparing injecting with non-injecting MSM have noted that non-injecting patients had different viral phylogenetic profiles compared with injectors.[18-20] The conclusion from this observation suggested a permucosal route of transmission, especially among HIV-positive MSM who had multiple sexual partners, MSM who tested positive for other sexually transmitted disease, namely syphilis, and MSM who engaged in sexual practices that could cause mucosal trauma, such as fisting and use of objects. Similarly, we observed an association between sex with SWs and HCV seropositivity. We observed that injecting drug users were seven times more likely than non-injecting drug users to acquire HCV infection. It is, however, thought that sexual behaviours that are likely to cause mucosal trauma increase the risk

This was a small select group that lacked heterogeneity. A larger number more representative of SA, including provinces more affected by HIV infection, may yield different HCV seroprevalence rates.

Conclusions

This study alone raises concerns that HCV seroprevalence is indeed underestimated in SA in at-risk populations. Key populations, and particularly those who are HIV-infected, should access HCV screening. Furthermore, all patients with the risk profiles described above should be tested for HCV and be linked to care. Without addressing infections in key populations, attainment of the elimination ideal for hepatitis C will not be achieved. Acknowledgements. The participants, who willingly gave of their time, are acknowledged, They have deepened our understanding of the challenges we face. Author contributions. MWS conceived the study. NAG and TC executed the fieldwork for the study in participant recruitment and prepared the draft manuscript. All authors contributed to the development of the manuscript and final submission.

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Funding. A Gastroenterology Foundation of South Africa (GFSA) grant funded the study. Conflicts of interest. None. 1. Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015;61(1):77-87. https://doi.org/10.1002/hep.27259 2. Razavi H, Elkhoury AC, Elbasha E, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology 2013;57(6):2164-2170. https://doi.org/10.1002/hep.26218 3. Van de Laar TJ, van der Bij AK, Prins M, et al. Increase in HCV incidence among men who have sex with men in Amsterdam most likely caused by sexual transmission. J Infect Dis 2007;196(2):230-238. https://doi.org/10.1086/518796 4. Daskalopoulou M, Rodger A, Thornton A, et al. Sexual behaviour, recreational drug use and hepatitis C co-infection in HIV-diagnosed men who have sex with men in the United Kingdom: Results from the ASTRA study. J Int AIDS Soc 2014;17(4 Suppl 3):19630. https://doi.org/10.7448/IAS.17.4.19630 5. Polaris Observatory HCVC. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: A modelling study. Lancet Gastroenterol Hepatol 2017;2(3):161-176. https://doi.org/10.1016/ S2468-1253(16)30181-9 6. Nelson PK, Mathers BM, Cowie B, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: Results of systematic reviews. Lancet 2011;378(9791):571-583. https://doi. org/10.1016/S0140-6736(11)61097-0 7. Urbanus AT, van de Laar TJ, Geskus R, et al. Trends in hepatitis C virus infections among MSM attending a sexually transmitted infection clinic; 1995 - 2010. AIDS 2014;28(5):781-790. https://doi. org/10.1097/QAD.0000000000000126 8. Zuma K, Shisana O, Rehle TM, et al. New insights into HIV epidemic in South Africa: Key findings from the National HIV Prevalence, Incidence and Behaviour Survey, 2012. Afr J AIDS Res 2016;15(1):67-75. https://doi.org/10.2989/16085906.2016.1153491 9. Amin J, Kaye M, Skidmore S, Pillay D, Cooper DA, Dore GJ. HIV and hepatitis C coinfection within the CAESAR study. HIV Med 2004;5(3):174-179. https://doi.org/10.1111/j.1468-1293.2004.00207.x 10. Gjaerde LI, Shepherd L, Jablonowska E, et al. Trends in incidences and risk factors for hepatocellular carcinoma and other liver events in HIV and hepatitis C virus-coinfected individuals from 2001 to 2014: A multicohort study. Clin Infect Dis 2016;63(6):821-829. https://doi.org/10.1093/cid/ciw380 11. Rao VB, Johari N, du Cros P, Messina J, Ford N, Cooke GS. Hepatitis C seroprevalence and HIV co-infection in sub-Saharan Africa: A systematic review and meta-analysis. Lancet Infect Dis 2015;15(7):819-824. https://doi.org/10.1016/S1473-3099(15)00006-7 12. Tremeau-Bravard A, Ogbukagu IC, Ticao CJ, Abubakar JJ. Seroprevalence of hepatitis B and C infection among the HIV-positive population in Abuja, Nigeria. Afr Health Sci 2012;12(3):312-317. https://doi.org/10.4314/ahs.v12i3.10

13. Newton OE, Oghene OA, Okonko IO. Anti-HCV antibody among newly diagnosed HIV patients in Ughelli, a suburban area of Delta State Nigeria. Afr Health Sci 2015;15(3):728-736. https://doi. org/10.4314/ahs.v15i3.5 14. Zhuang X, Wang Y, Chow EP, Liang Y, Wilson DP, Zhang L. HIV and HCV prevalence among entrants to methadone maintenance treatment clinics in China: A systematic review and metaanalysis. BMC Infect Dis 2012;8(12):130. https://doi.org/10.1186/1471-2334-12-130 15. Centers for Disease C, Prevention. Sexual transmission of hepatitis C virus among HIV-infected men who have sex with men – New York City, 2005 - 2010. MMWR Morb Mortal Wkly Rep 2011;60(28):945-950. 16. Fierer DS. Epidemic of sexually transmitted hepatitis C virus infection among HIV-infected men. Curr Infect Dis Rep 2010;12(2):118-125. https://doi.org/10.1007/s11908-010-0088-1 17. Breskin A, Drobnik A, Pathela P, et al. Factors associated with hepatitis C infection among HIVinfected men who have sex with men with no reported injection drug use in New York City, 2000 2010. Sex Transm Dis 2015;42(7):382-386. https://doi.org/10.1097/OLQ.0000000000000293 18. Urbanus AT, van de Laar TJ, Stolte IG, et al. Hepatitis C virus infections among HIV-infected men who have sex with men: An expanding epidemic. AIDS 2009;23(12):F1-F7. https://doi.org/10.1097/ QAD.0b013e32832e5631 19. Van de Laar TJ, Matthews GV, Prins M, Danta M. Acute hepatitis C in HIV-infected men who have sex with men: An emerging sexually transmitted infection. AIDS 2010;24(12):1799-1812. https:// doi.org/10.1097/QAD.0b013e32833c11a5 20. Chan DP, Lin AW, Wong KH, Wong NS, Lee SS. Diverse origins of hepatitis C virus in HIV coinfected men who have sex with men in Hong Kong. Virol J 2015;12:120. https://doi.org/10.1186/ s12985-015-0355-8 21. Tohme RA, Holmberg SD. Is sexual contact a major mode of hepatitis C virus transmission? Hepatology 2010;52(4):1497-1505. https://doi.org/10.1002/hep.23808 22. Semugoma NP, Rebe K, Sonderup MW, et al. Hepatitis C: A South African literature review and results from a burden of disease study among a cohort of drug-using men who have sex with men in Cape Town, South Africa. S Afr Med J 2017;107(12):1116-1120. https://doi.org/10.7196/SAMJ.2017. v107i12.12623 23. Sonderup MW, Prabdial-Singh N, Manamela MJ, et al. Characteristics of hepatitis B and C prevalence in key populations in South Africa. Hepatology 2017;66(S1):561A-562A. https://doi. org/10.1002/hep.29501

Accepted 26 January 2018.

July 2018, Print edition

These open-access articles are distributed under Creative Commons licence CC-BY-NC 4.0.

RESEARCH

A Seasonal Autoregressive Integrated Moving Average (SARIMA) forecasting model to predict monthly malaria cases in KwaZulu-Natal, South Africa O Ebhuoma, BSc Hons, NEBOSH Enviro Dip, MSc, PhD; M Gebreslasie, BA, MSc, PhD; L Magubane, BSc Hons School of Agricultural, Earth and Environmental Sciences, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Durban, South Africa Corresponding author: O Ebhuoma (osadolorebhuoma@gmail.com) Background. South Africa (SA) in general, and KwaZulu-Natal (KZN) Province in particular, have stepped up efforts to eliminate malaria. To strengthen malaria control in KZN, a relevant malaria forecasting model is important. Objectives. To develop a forecasting model to predict malaria cases in KZN using the Seasonal Autoregressive Integrated Moving Average (SARIMA) time series approach. Methods. The study was carried out retrospectively using a clinically confirmed monthly malaria case dataset that was split into two. The first dataset (January 2005 - December 2013) was used to construct a SARIMA model by adopting the Box-Jenkins approach, while the second dataset (January - December 2014) was used to validate the forecast generated from the best-fit model. Results. Three plausible models were identified, and the SARIMA (0,1,1)(0,1,1)12 model was selected as the best-fit model. This model was used to forecast malaria cases during 2014, and it was observed to fit closely with malaria cases reported in 2014. Conclusions. The SARIMA (0,1,1)(0,1,1)12 model could serve as a useful tool for modelling and forecasting monthly malaria cases in KZN. It could therefore play a key role in shaping malaria control and elimination efforts in the province. S Afr Med J 2018;108(7):573-578. DOI:10.7196/SAMJ.2018.v108i7.12844

Full article available online at https://doi.org/10.7196/SAMJ.2018.v108i7.12844

Describing key performance indicators for waiting times in emergency centres in the Western Cape Province, South Africa, between 2013 and 2014 K Cohen, MB ChB, MMed, MPhil; S Bruijns, MB ChB, DipPEC, MPhil, FRCEM, PhD Division of Emergency Medicine, Faculty of Health Sciences, University of Cape Town, South Africa Corresponding author: K Cohen (kirstenlcohen@gmail.com) Background. Data measured as key performance indicators (KPIs) are used internationally in emergency medicine to measure and monitor quality of care. The Department of Health in the Western Cape Province, South Africa, introduced time-based KPIs for emergency centres (ECs) in 2012. Objectives. To describe the most recently processed results of the audits conducted in Western Cape ECs between 2013 and 2014. Methods. A retrospective, descriptive study was conducted on data collected in the 6-monthly Western Cape EC triage and waiting time audits for 2013 - 2014. Time variables were analysed overall and per triage category. ECs in hospitals were compared with ECs in community health centres (CHCs). A descriptive analysis of the sample was undertaken. Proportions for categorical data are presented throughout. The continuous variable time was described using means and standard deviations. The Ď&#x2021;2 test and Fisherâ&#x20AC;&#x2122;s exact test were used to describe associations. The level of significance was p<0.05, with the 95% confidence interval where appropriate. Results. There was no significant difference in triage acuity proportions between hospital and CHC ECs. Waiting times were longer than recommended for the South African Triage Scale, but higher-acuity patients were seen faster than lower-acuity patients. Waiting times were significantly longer at hospitals than at CHCs. A red priority patient presenting to a CHC would take 6.1 times longer to reach definitive care than if the patient had presented to a hospital EC.

July 2018, Print edition

RESEARCH

Conclusions. The triage process appears to improve waiting times for the sickest patients, although it is protracted throughout. Acutely ill patient journeys starting at CHC ECs suggested significant delays in care. Models need to be explored that allow appropriate care at the first point of contact and rapid transfer if needed. To improve waiting times, resource allocation in the emergency care system will need to be reconsidered. S Afr Med J 2018;108(7):579-584. DOI:10.7196/SAMJ.2018.v108i7.12969

Full article available online at https://doi.org/10.7196/SAMJ.2018.v108i7.12969

Striking increase in the incidence of infective endocarditis associated with recreational drug abuse in urban South Africa R Meel, PhD; M R Essop, MD Division of Cardiology, Department of Internal Medicine, Chris Hani Baragwanath Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand and Milpark Hospital, Johannesburg, South Africa Corresponding author: R Meel (ruchikameel@gmail.com) Background. We have recently noted a dramatic rise in the number of patients with infective endocarditis (IE) related to intravenous (IV) nyaope (a mixture of heroin, cocaine and antiretroviral drugs) presenting to Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa. Objectives. To document the clinical and echocardiographic characteristics of these patients. Methods. Clinical and echocardiographic characteristics of all patients (N=68) with IE due to IV nyaope use were retrospectively extracted from hospital records (December 2014 - February 2017). Results. The mean (standard deviation) age of the patients was 25.8 (4.5) years (97.1% were male). Withdrawal symptoms were noted in 25.1% of cases, fever in 58.8%, dyspnoea in 86.7% and right ventricular failure in 42.6%. Most patients were HIV-positive (76.1%), with CD4+ cell counts of <200 cells/ÂľL in 8.8% of the total, 58.1% had hepatitis C infection, and only three were on antiretrovirals. Septic pulmonary emboli were noted in 61.8%. Blood cultures revealed Staphylococcus aureus in 61.2%, Enterococcus faecalis in 8.8% and Pseudomonas aeruginosa in 1 patient; 29.2% had sterile cultures and 8.8% polymicrobial infection. Severe right ventricular systolic dysfunction (RVS' Doppler velocity <10 cm/s) and pulmonary hypertension were noted in 19.1% and 62.2% of patients, respectively. Pericardial effusion was noted in 37.8%. The most commonly involved valve was the tricuspid (60.1%), followed by the mitral (17.2%), aortic (2.9%) and pulmonary (1 patient) valves. Combined valve lesions were noted in 19.1% of patients. Ten patients (14.7%) died. The main predictor of in-hospital mortality was S. aureus infection (odds ratio 5.0; p=0.042). Conclusions. We have documented the common clinical and echocardiographic characteristics of patients with IE secondary to IV nyaope use. IE due to IV drug use is responsible for considerable morbidity and mortality in a predominantly young male population. S Afr Med J 2018;108(7):585-589. DOI:10.7196/SAMJ.2018.v108i7.13007

Full article available online at https://doi.org/10.7196/SAMJ.2018.v108i7.13007

July 2018, Print edition

RESEARCH

A multicentre, cross-sectional study investigating the prevalence of hypertensive disease in patients presenting for elective surgery in the Western Cape Province, South Africa K van der Spuy,1 BSc Hons (Physiotherapy), MB ChB; M Crowther,1 MB ChB; M Nejthardt,2 BSc Hons (Physiology), MB BCh, DA (SA), FCA (SA); F Roodt,2 MB ChB, FCA (SA); J Davids,3 MB ChB, DA (SA), MMed, FCA (SA); J Roos,4 MB ChB, DA (SA), FCA (SA); E Cloete,5 MB ChB, DA (SA), FCA (SA); T Pretorius,6 MB ChB, DA (SA), FCA (SA), MMed; G Davies,6 MB ChB, FCA (SA); J van der Walt,7 MB ChB, DCh (SA), DA (SA), FCA (SA), MMed; C van der Westhuizen,8 MB ChB, DA (SA), FCA (SA), MMed; M Flint,1 BSc (Medical Physiology), HSc, MSc, PhD; J Swanevelder,1 MB ChB, DA (SA), FCA (SA), MMed, FRCA; B Biccard,1 MB ChB, MMedSci, FCA (SA), PhD Department of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa Department of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital, Red Cross War Memorial Children’s Hospital and Faculty of Health Sciences, University of Cape Town, South Africa 3 Department of Anaesthesiology, George Regional Hospital, Western Cape, South Africa 4 Department of Anaesthesiology, Mitchell’s Plain Hospital, Cape Town, South Africa 5 Department of Anaesthesiology, New Somerset Hospital, Cape Town, South Africa 6 Department of Anaesthesiology, Paarl Provincial Hospital, Western Cape, South Africa 7 Department of Anaesthesiology, Victoria Hospital, Cape Town, South Africa 8 Department of Anaesthesiology, Worcester Hospital, Western Cape, South Africa

1 2

Corresponding author: K van der Spuy (karenvdspuy@gmail.com) Background. Hypertension is common, affecting over one billion people worldwide. In sub-Saharan Africa, hypertensive disease not only affects the older population but is becoming increasingly prevalent in younger individuals. In South Africa (SA), >30% of the adult population has hypertension, making it the single most common cardiovascular risk factor and the predominant contributor to cardiovascular disease and mortality. Elevated blood pressure is the most common perioperative comorbidity encountered in non-cardiac surgical patients, with an overall prevalence of 20 - 25%, and it remains poorly controlled in low- and middle-income countries. Hypertension in the perioperative setting may adversely affect patient outcome. It therefore not only flags possible perioperative challenges to anaesthesiologists, but also identifies patients at risk of long-term morbidity and mortality. Objectives. To determine the prevalence and severity of hypertension in elective adult surgical patients in the Western Cape Province, SA. Results. The study population included all elective surgical patients from seven hospitals in the Western Cape during a 1-week period. Hypertension, defined as having had a previous diagnosis of hypertension or meeting the blood pressure criteria of >140/90 mmHg, was identified in 51.8% of patients during preoperative assessment. Significantly, newly diagnosed hypertension was present in 9.9% of all patients presenting for elective surgery. Although 98.1% of the known hypertensive patients were on antihypertensive therapy, 36.9% were inadequately controlled. There are numerous reasons for this, but notably 32.1% of patients admitted to forgetting to take their medication, making patient factors the most common reason for treatment non-compliance. Conclusions. The perioperative period may be an important opportunity to identify undiagnosed hypertensive patients. The perioperative encounter may have a significant public health implication in facilitating appropriate referral and treatment of patients with hypertension to decrease long-term cardiovascular complications in SA. S Afr Med J 2018;108(7):590-595. DOI:10.7196/SAMJ.2018.v108i7.13022

Full article available online at https://doi.org/10.7196/SAMJ.2018.v108i7.13022

July 2018, Print edition

RESEARCH

Quality of counselling and support provided by the South African National AIDS Helpline: Content analysis of mystery client interviews N Arullapan,1 National Diploma; M F Chersich,1 MB BCh, PhD; N Mashabane,1 B Pharm; M Richter,2,3,4 BA Hons, MA, LLM, PhD; N Geffen,5 MSc, PhD; J Vearey,4,6 MSc, PhD; L Jankelowitz,1 BA Hons, MBA; F Scorgie,1 MA, PhD; W D F Venter,1 FCP, MMed Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Sonke Gender Justice, South Africa 3 School of Family Medicine and Public Health, Faculty of Health Sciences, University of Cape Town, South Africa 4 African Centre for Migration and Society, School of Social Sciences, University of the Witwatersrand, Johannesburg, South Africa 5 Centre for Social Science Research, Faculty of Humanities, University of Cape Town, South Africa 6 Centre for African Studies, University of Edinburgh, UK 1 2

Corresponding author: W D F Venter (fventer@wrhi.co.za) Background. Telephone helplines can facilitate referral, education and support for patients living with HIV or those concerned about the infection. The anonymity of helplines facilitates discussion of sensitive issues that are difficult to raise face to face. These services could support the expansion of HIV self-testing. However, maintaining quality and standardising messages in rapidly evolving fields such as HIV is challenging. Objectives. To evaluate the quality of the South African (SA) National AIDS Helpline. Methods. Mystery clients posing as members of the public made 200 calls to the service in 2014. They presented several scenarios, including having received HIV-positive results from a doctor’s secretary or through self-testing. Following the call, ‘clients’ completed a semistructured questionnaire on the information received and the caller-counsellor interaction. Results. Calls were answered within a median of 5 seconds (interquartile range 2 - 14). Conversations took place in 8 of the 11 SA official languages, though mainly in English. Overall, 75% of callers felt that with the information they received they could locate a nearby clinic for further services. Counsellors expressed appropriate levels of concern about inadequate counselling that callers had received and confidentiality breaches in some scenarios. Eight counsellors incorrectly mentioned the need for a waiting period to confirm a positive result. Consistent with policy, almost all said that being foreign would not affect HIV treatment access. About 90% explained the need for CD4+ testing and antiretroviral therapy, but only 78% discussed HIV prevention. Counsellors were mostly empathetic (83%), though some adopted a neutral tone (10%) or were brusque (6%) or unhelpful (2%). Conclusions. Overall, helpline counsellors were proficient at providing information about local clinics, HIV testing and steps needed for initiating ART. Dissatisfaction with the caller-counsellor interactions, instances of incorrect information and the relatively low attention accorded to HIV prevention are worrying, however. Training for both refreshing and updating knowledge, and supervision and monitoring of calls, could target these areas. S Afr Med J 2018;108(7):596-602. DOI:10.7196/SAMJ.2018.v108i7.12543

Full article available online at https://doi.org/10.7196/SAMJ.2018.v108i7.12543

July 2018, Print edition

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True (A) or false (B): SAMJ Incidence of Hodgkin lymphoma (HL) in HIV-positive and HIV-negative patients at a tertiary hospital in South Africa (SA) (2005Â - 2016) and comparison with other African countries 1. HL is the most common non-AIDS-defining cancer in HIVpositive patients. 2. The global incidence of HL increased by 12.9% between 2005 and 2015, largely linked to HIV infection. Hepatitis C prevalence in HIV-infected heterosexual men and men who have sex with men 3. Globally 1% of individuals are infected with hepatitis C virus (HCV). 4. Risk factors for acquisition of HCV infection include injection drug use, use of recreational drugs with sex and sex with sex workers. Striking increase in the incidence of infective endocarditis (IE) associated with recreational drug abuse in urban SA 5. In developed countries, IE infrequently complicates intravenous drug use and HIV infection. 6. Nyaope is exclusive to SA and its use is common among young and unemployed black people from poor socioeconomic backgrounds. A multicentre, cross-sectional study investigating the prevalence of hypertensive disease in patients presenting for elective surgery in the Western Cape Province, SA 7. In sub-Saharan Africa, hypertensive disease not only affects the older population but is becoming increasingly prevalent in younger individuals. 8. In SA, >30% of the adult population have hypertension, and it remains the single most common cardiovascular risk factor and the predominant contributor to cardiovascular disease and mortality. 9. Hypertension is most frequently diagnosed and treatment initiated in the primary healthcare setting. 10. Five out of every 10 patients presenting for elective surgery in the Western Cape are hypertensive. Of these, 20% are undiagnosed and 40% are inadequately controlled.

CME The increasing burden of asthma in SA children: A call to action 11. Most people with asthma live in low- and middle-income countries, where asthma prevalence is increasing fastest. 12. The prevalence of asthma in 13 - 14-year-old black children is lower than the global average. 13. Black African children with asthma are reported to have more severe symptoms than those in high-income countries. 14. Obesity has been identified as a risk factor for bronchial hyperresponsiveness. 15. Eczema is an important risk factor for asthma. The diagnosis of asthma in children: An evidence-based approach to a common clinical dilemma 16. The presentation and differential diagnosis of asthma differ significantly as the child matures. 17. One-third of all children wheeze at least once before their third birthday. 18. History-taking alone is often all that is needed to diagnose a preschool wheezing disorder. 19. Clinical examination may be unhelpful in the young child, particularly where there are no other atopic manifestations. 20. Early use of inhaled corticosteroids in preschool children with wheeze reduces symptoms and prevents or delays the onset of asthma.

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BUHLE WASTE (PTY) LTD. IS A 100% BLACK-OWNED AND MANAGED WASTE SERVICE COMPANY THAT WAS STARTED IN 1997 ON THE DUSTY STREETS OF KATLEHONG. We are a holistic waste company providing on-site waste management and integrated services throughout the various waste streams:

MEDICAL WASTE | GENERAL WASTE | HAZARDOUS WASTE | CHEMICAL WASTE SANITATION & HYGIENE WASTE | CONSTRUCTION RUBBLE We are a market leader in the management of waste in South Africa with over 350 staff and 70 trucks collecting, transporting, treating and assisting you with your waste. We are committed to ensuring that, as our client, your waste is handled with the utmost love and respect so that your waste compliance becomes a thing of beauty. Become part of our Buhle Waste family; take on the Buhle Waste vision; find the beauty, love and respect in all that we do.

1634 Canon Crescent

POSTAL ADDRESS:

011 866 2316

Roodekop

P.O. Box 13091, Katlehong

info@buhlewaste.co.za

1401

1432

www.buhlewaste.co.za

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