SAMJ Vol 107, No 12 (2017) by HMPG

DECEMBER 2017

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GUEST EDITORIAL Celebrating the 50th anniversary of the worldâ&#x20AC;&#x2122;s first human heart transplant IN PRACTICE Using GIS to support UNAIDS 90-90-90 targets Berg adder bite: An unusual case of acute poisoning RESEARCH Impact of Xpert MTB/RIF rollout on TB management When is surgical intervention needed after a snakebite? Mortality trends in Cape Town (2001 - 2013): Reducing inequities Comparison of private and public sector ICU infrastructure

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DECEMBER 2017 PRINT EDITION

GUEST EDITORIAL 4

The world’s first human-to-human heart transplant at Groote Schuur Hospital: 50 years later J Brink, T Pennel, K Seele, P Zilla

REPRINTS FROM THE SAMJ OF 30 DECEMBER 1967 7

Members of the heart transplant team, Groote Schuur Hospital, 3 December 1967

Cardiac transplantation – the anaesthetist’s view: A case report J Ozinsky

The operation: A human cardiac transplant: An interim report of a successful operation performed at Groote Schuur Hospital, Cape Town C N Barnard

FROM THE EDITOR

EDITOR Bridget Farham, BSc (Hons), PhD, MB ChB EDITORS EMERITUS Daniel J Ncayiyana, MD (Groningen), FACOG, MD (Hon), FCM (Hon) JP de V van Niekerk, MD, FRCR ASSOCIATE EDITORS Q Abdool Karim, A Dhai, 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 HMPG CEO AND PUBLISHER Hannah Kikaya Email: hannahk@hmpg.co.za

Thank you from HMPG and the editors B Farham

MANAGING EDITORS Claudia Naidu Naadia van der Bergh

EDITOR’S CHOICE

TECHNICAL EDITORS Emma Buchanan Kirsten Morreira Paula van der Bijl

CORRESPONDENCE 20

Acute high-altitude illness B Basnyat; response from R Hofmeyr, G Tölken, R De Decker

Development of the MB ChB curriculum map at the University of KwaZulu-Natal, South Africa S Ramklass, M Matthews

Human dignity and the future of the voluntary active euthanasia debate in South Africa D W Jordaan

IZINDABA 23

OBITUARIES Joseph (Ozzie) Ozinsky P Gordon

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CHIEF OPERATING OFFICER Diane Smith | Tel. 012 481 2069 Email: dianes@hmpg.co.za SALES MANAGER (CAPE TOWN) Azad Yusuf

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PRODUCTION MANAGER Emma Jane Couzens

ISSUES IN MEDICINE Lamivudine monotherapy in children and adolescents: The devil is in the detail L Fairlie, J Bernheimer, N Sipambo, C Fick, L Kuhn ISSUES IN PUBLIC HEALTH Prevalence and predictors of late presentation for HIV care in South Africa H N Fomundam, A R Tesfay, S A Mushipe, M B Mosina, C T Boshielo, H T Nyambi, A Larsen, M Cheyip, A Getahun, Y Pillay Application opportunities of geographic information systems analysis to support achievement of the UNAIDS 90-90-90 targets in South Africa R R Lilian, C J Grobbelaar, T Hurter, J A McIntyre, H E Struthers, R P H Peters MEDICINE AND THE LAW Disclosing details about the medical treatment of a deceased public figure in a book: Who should have consented to the disclosures in Mandela’s Last Days? D J McQuoid-Mason CASE REPORT Berg adder (Bitis atropos): An unusual case of acute poisoning C A Wium, C J Marks, C E du Plessis, G J Müller

December 2017, Print edition

HMPG BOARD OF DIRECTORS Prof. M Lukhele (Chair), Dr M R Abbas, Mrs H Kikaya, Dr M Mbokota, Dr G Wolvaardt ISSN 0256-9574 SAMA website: www.samedical.org Journal website: www.samj.org.za

RESEARCH 48

Impact of Xpert MTB/RIF rollout on management of tuberculosis in a South African community B-M Schmidt, H Geldenhuys, M Tameris, A Luabeya, H Mulenga, E Bunyasi, T Scriba, M Hatherill

A comparison of private and public sector intensive care unit infrastructure in South Africa* S Mahomed, A W Sturm, P Moodley

Mortality trends in the City of Cape Town between 2001 and 2013: Reducing inequities in health* P Groenewald, I Neethling, J Evans, V Azevedo, T Naledi, R Matzopoulos, N Nannan, J Daniels, D Bradshaw

Geographical maldistribution of surgical resources in South Africa: A review of the number of hospitals, hospital beds and surgical beds* A J Dell, D Kahn

Acne in South African blacks: A retrospective study in the private sector* T P Zulu, A Mosam, Y Balakrishna, N C Dlova

Multimorbidity in a large district hospital: A descriptive cross-sectional study* S Roche, E de Vries

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* N P Semugoma, K Rebe, M W Sonderup, M Kamkeumah, G de Swardt, H Struthers, H Eksen, J McIntyre

Auditing stillbirths at Lower Umfolozi War Memorial Regional Hospital: A 12-month review* I Govender

Obstetric spinal hypotension: Preoperative risk factors and the development of a preliminary risk score – the PRAM score* D G Bishop, C Cairns, M Grobbelaar, R N Rodseth

Gendered risk factors associated with self-harm mortality among youth in South Africa, 2006 - 2014* N de Wet

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 SAMJ SUBSCRIPTION RATES Local subscriptions ZAR1 488.00 p.a. Foreign subscriptions ZAR3 408.00 p.a. Single copies ZAR124.00 local, ZAR284.00 foreign Members of the South African Medical Association receive the SAMJ only on request, as part of their membership benefit. Subscriptions: Tel. 012 481 2071 Email: members@samedical.org The SAMJ is published monthly by the Health and Medical Publishing Group (Pty) Ltd, Co. registration 2004/0220 32/07, a subsidiary of SAMA. HEAD OFFICE Health and Medical Publishing Group (Pty) Ltd Block F, Castle Walk Corporate Park, Nossob Street, Erasmuskloof Ext. 3, Pretoria, 0181 Tel. 012 481 2069 Email: dianes@hmpg.co.za EDITORIAL OFFICE Suite 11, Lonsdale Building, Lonsdale Way, Pinelands, 7405 Tel. 021 532 1281 | Cell. 072 635 9825 Email: publishing@hmpg.co.za Please submit all letters and articles for publication online at 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

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

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Background photo: Louis Washkansky shakes hands with surgeon Chris Barnard a few days after the historic heart transplant on 3 December 1967 | First Heart Transplant Museum, Groote Schuur Hospital, Cape Town; Defibrillation of the transplanted donor heart | Ozinsky Box photos: Geographic information system analyses can generate maps that community health workers can use to perform home visits (patient residences are fictional and do not resemble any real disease distribution) | Lilian et al.; Berg adder (Bitis atropos) | Wium et al. (photo J Marais); Intensive care unit | Shutterstock

December 2017, Print edition

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GUEST EDITORIAL Celebrating the 50th anniversary of the world’s first human heart transplant IN PRACTICE Using GIS to support UNAIDS 90-90-90 targets Berg adder bite: An unusual case of acute poisoning RESEARCH Impact of Xpert MTB/RIF rollout on TB management When is surgical intervention needed after a snakebite? Mortality trends in Cape Town (2001 - 2013): Reducing inequities Comparison of private and public sector ICU infrastructure

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

GUEST EDITORIAL

The world’s first human-to-human heart transplant at Groote Schuur Hospital: 50 years later Fifty years ago, on 3 December 1967, the world’s first human-tohuman heart transplant was performed by Dr Christiaan Barnard at Groote Schuur Hospital in Cape Town. This was, and probably will remain, the most publicised medical event of all time, making headlines in nearly every international newspaper, magazine and tabloid within days of the event. The idea of transplanting a heart from one human to another captured the minds and imaginations of the public like no other medical event before or since. The only other iconic event in that era that was equally well publicised was man’s first landing on the moon 18 months later. This medical breakthrough was published in the SAMJ 3 weeks later, towards the end of December 1967, and is one of the most cited articles in this journal. The first heart transplant placed Groote Schuur Hospital, the University of Cape Town and South Africa (SA) firmly on the international medical map. A heart transplant was seen by the public as transplanting the very soul of an individual from one person into another. It provoked tremendous debate, some of it very emotional, around the ethics of transplantation and spurred on the international medical and philosophy community to develop the concept of brain death into law. Many countries took decades to adopt such laws – most notably Japan, which took another 30 years (until 1997) to allow organ transplantation from brain-dead donors. Even today many countries do not accept brain death, preventing organ transplantation as a therapeutic option for end-stage heart failure. This tremendous publicity generated by the first heart transplant occurred despite kidney and liver transplantation having preceded heart transplantation by many years. These prior surgical innovations were instrumental in paving the way for immunosuppression, vital for modifying the recipient immune response and preventing rejection from a genetically non-identical donor. The suppression of host rejection as well as the prevention and treatment of subsequent side-effects remains the biggest challenge in organ transplantation. Ultimately, the goal of a transplant is to improve both length and quality of life when medication and conventional cardiac surgery will not adequately alleviate symptoms of heart failure. As far as possible, transplant teams strive to help the recipient lead a life similar in quality to that of his or her peers, unconstrained by the limitations of heart failure. The operation itself as performed today has changed very little since Dr Norman Shumway of Stanford University in the USA first described the technique in animals in the early 1960s. Small technical variations, the use of heart-preservation solutions (cardioplegia), and improvements in the heart-lung machine have optimised this procedure through the decades. The lack of donors has also been offset by the use of implantable mechanical assist devices (miniature pumps that help the heart), and even a totally artificial heart, as a bridge to transplantation, as well as the recent use of donors whose hearts have stopped (donation after circulatory death: DCD), which would previously have been deemed unsuitable for transplantation. The expensive equipment required to resuscitate these DCD hearts is not available in SA at present, however, and mechanical assist devices are currently only accessible to patients with excellent health insurance. In those developed countries that can afford their extended use, mechanical assist devices are increasingly being used as

The cover of the SAMJ of 30 December 1976, signed by some of the members of the heart transplant team. From the top in a clockwise direction, the signatures are those of Prof. Chris Barnard, Prof. Val Schrire (cardiologist and head of the cardiac clinic at Groote Schuur Hospital/University of Cape Town), Dr M C Botha (haematologist/immunologist), Dr Terry O’Donovan (surgeon), Dr S C Bosman (surgeon), Dr Joe (Oz) Ozinsky (anaesthetist), Dr Rodney Hewitson (senior surgeon), and Dr Coert Venter (junior surgeon in training). Two key articles from the issue are reprinted in the following pages.

permanent treatment for heart failure, so-called destination therapy, because of the dearth of donor organs. Progress in postoperative critical care has significantly improved early outcomes of heart transplantation, and patients without complications are discharged from the intensive care unit in 4 days or less. In the past year Groote Schuur Hospital has instituted a longterm extracorporeal membrane oxygenation (ECMO) service, which brings the unit in line with international standards for postoperative care in complicated cases. Approximately 15 years after the first heart transplant, in the early 1980s a ‘miracle’ drug called cyclosporine was discovered by Jean Borel, earning him a Nobel Prize. This drug was a significant breakthrough in the management of donor organ rejection, and transformed transplantation from an experimental operation in leading academic medical centres to standard medical treatment for end-stage organ failure with reproducible results that could be applied more widely. The numbers of all organ transplants rapidly escalated in the early 1980s, reaching a plateau a decade later when the availability of donor organs became the major constraint. Cyclosporine is a member of the class of drugs called calcineurin

December 2017, Print edition

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GUEST EDITORIAL

inhibitors (Sandimmun and Neoral are the commercial formulations of the drug), and the other commonly used drug in this class is tacrolimus (Prograft or Advagraft). Calcineurin inhibitors are still the mainstay of treatment in organ transplantation, and their use has led to significantly fewer rejection episodes and longer life expectancy. However, unwanted sideeffects are a concern with this more effective immunosuppression. Increased incidences of infection, hypertension, nephrotoxicity and in some instances long-term renal failure, diabetes, high cholesterol and cancers are some of the side-effects of immunosuppression. The newer immunosuppressive drugs show promise of a reduction in some of these side-effects with or without some calcineurin inhibition, and provide physicians with a larger armamentarium to treat patients. The medical management of heart transplant recipients remains an ongoing challenge during the period immediately after the transplant, as well as in the long term. Following the significant milestone 50 years ago, the Christiaan Barnard Division of Cardiothoracic Surgery at the University of Cape Town and Groote Schuur and Red Cross War Memorial Children’s hospitals has transplanted 537 hearts and remains the only heart transplant facility for both indigent and insured patients in SA. Despite the challenges that exist with heart transplantation, the outcome has improved significantly over the past 20 years. The functional status of the recipient after the procedure is generally excellent, depending on his or her motivation, with an expected 85% survival rate at 1 year, decreasing to 75% at 5 years. The Christiaan Barnard Division of Cardiothoracic Surgery is the proud host of an international celebration to commemorate the 50th anniversary of the world’s first heart transplant, ‘50 years of Heart Transplantation: Courage and Innovation’, on 2 - 4 December 2017 at Groote Schuur Hospital. We hope that the celebration of this courageous and innovative event will not only encourage further innovations in the management of heart failure, which constitutes a major burden of disease, but also inspire young academics to follow in the footsteps of Christiaan Barnard and his team five decades later.

Johan Brink Christiaan Barnard Division of Cardiothoracic Surgery, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa johan.brink@uct.ac.za

Tim Pennel Christiaan Barnard Division of Cardiothoracic Surgery, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

Karen Seele Christiaan Barnard Division of Cardiothoracic Surgery, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

Peter Zilla Christiaan Barnard Division of Cardiothoracic Surgery, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa S Afr Med J 2017;107(12):1035-1036. DOI:10.7196/SAMJ.2017.v107i12.12960

Some of the members of the team that performed the first heart transplant, photographed on 3 December 1967 (photo: First Heart Transplant Museum, Groote Schuur Hospital). The full team is listed opposite.

December 2017, Print edition

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

FROM THE EDITOR

Thank you from HMPG and the editors The SAMJ reviewers

HMPG and the editors of SAMJ would like to thank all who participated in the peer review process during this past year. We are grateful for the expertise, insight and thoughtful critiques shared with our authors through the review process, and without which maintaining the high standard of our journal would be impossible. We apologise if any individual reviewer has inadvertently been excluded, and to those reviewers who were recruited after this issue was published. Fareed Abdullah, South African Medical Research Council Sumaiya Adam, University of Pretoria Yasmin Adams, Chris Hani Baragwanath Academic Hospital/ University of the Witwatersrand Miriam Adhikari, University of KwaZulu-Natal Riedwaan Ally, University of the Witwatersrand Elize Archer, Stellenbosch University Márcio Araújo, International Integration of the Lusophone AfroBrazillian (Unilab) Andrew Argent, University of Cape Town/Red Cross War Memorial Children’s Hospital Affirul Ariffin, Universiti Sains Islam Malaysia Akwi Asombang, Beth Israel Deaconess Medical Center, Harvard Medical School Marina Aucamp, Private Daynia Ballot, University of the Witwatersrand Peter Barron, University of the Witwatersrand Wanda Bekker, University of KwaZulu-Natal Michael Berry, Imperial School of Anaesthesia Arvin Bhana, South African Medical Research Council Rajendra Bhimma, University of KwaZulu-Natal Jack Biko, University of Pretoria Evan Blecher, University of Illinois at Chicago Marc Blockman, University of Cape Town Lucille Blumberg, National Institute for Communicable Diseases Martin Both, Stellenbosch University Adrian Brink, Ampath National Laboratory Services Hanneke Brits, University of the Free State Russell Britz, University of the Witwatersrand Stevan Bruijns, University of Cape Town Piotr Brezinski, Military Support Unit Eckhart Buchmann, University of the Witwatersrand Alex Butchart, World Health Organization Neil Cameron, Stellenbosch University Alain Chichom-Mefire, University of Buea Chitalu Chama-Chiliba, University of Zambia Lawrence Chauke, University of the Witwatersrand Kathryn Chu, Médecins Sans Frontières Damian Clarke, University of KwaZulu-Natal Peter Cleaton-Jones, University of the Witwatersrand Philip Cloete, University of Cape Town Marius Coetzee, National Health Laboratory Service/University of the Free State Diane Cooper, University of the Western Cape Mark Cotton, Stellenbosch University Herbert Cubasch, Chris Hani Baragwanath Academic Hospital/ University of the Witwatersrand Christina Cutter, University of Michigan Aqiel Dalvie, University of Cape Town Alan Davidson, University of Cape Town Victor Davies, University of the Witwatersrand

Halima Dawood, Grey’s Hospital Renee de Waal, University of Cape Town Wilma deWitt, University of Pretoria Wim Delva, Stellenbosch University Daan den Hollander, University of KwaZulu-Natal Greta Dryer, University of Pretoria Karen du Preez, Stellenbosch University Jacques du Toit, Stellenbosch University David Durrheim, University of Newcastle Robin Dyers, Western Cape Government Ian Edelstein, Human Sciences Research Council Jennifer Edge, Private Brian Eley, Red Cross War Memorial Children’s Hospital Denise Evans, University of the Witwatersrand June Fabian, University of the Witwatersrand Lee Fairlie, University of the Witwatersrand Shinga Feresu, University of Pretoria Nando Ferreira, University of Pretoria Pierre Foex, University of Oxford Sasha Frade, University of the Witwatersrand Jennifer Geel, University of the Witwatersrand Stefan Gerbhart, Stellenbosch University Brian Goemans, EMERGO, Underwriters Laboratories David Greenfield, University of Cape Town Andrew Grieve, University of the Witwatersrand Larry Hadley, University of KwaZulu-Natal Timothy Hardcastle, University of KwaZulu-Natal Haly Holmes, University of the Western Cape Muhammad Hoque, University of Limpopo (Medunsa Campus) Johan Hugo, Anova Health Institute Francis Hyera, University of Limpopo Eduard Jonas, University of Cape Town John Joska, University of Cape Town Ben Jugmohan, University of the Witwatersrand Sharon Kling, Stellenbosch University Karen Koch, University of the Witwatersrand/Donald Gordon Hospital Jake Krige, University of Cape Town Carl-Heinz Kruse, Grey’s Hospital Suresh Kumar, Jawaharlal Institute of Postgraduate Medical Education and Research Yves Lafort, Ghent University Sanjay Lala, University of the Witwatersrand James Leckman, Yale School of Medicine Richard Lessells, London School of Hygiene and Tropical Medicine Cecil Levy, Charlotte Maxeke Academic Hospital Jeffrey Lipman, University of the Witwatersrand Jerome Loveland, University of the Witwatersrand Irene Lubbe, University of Pretoria Christina Lundgren, University of the Witwatersrand Johnny Mahlangu, University of the Witwatersrand Hassan Mahomed, Stellenbosch University/Western Cape Government: Health Ozayr Mahomed, University of KwaZulu-Natal Johan Marais, African Snakebite Institute Cathy Mathews, South Africa Medical Research Council Richard Matzopoulos, South African Medical Research Council/ University of Cape Town/University of the Witwatersrand David McQuoid-Mason, University of KwaZulu-Natal Graeme Meintjies, University of Cape Town Mervyn Mer, University of the Witwatersrand Fraukje Mevissen, Maastricht University

December 2017, Print edition

FROM THE EDITOR

Johanna Meyer, Sefako Makgatho Health Sciences University Peter Millard, University of New England Malcolm Miller, Groote Schuur Hospital Jacqui Miot, University of the Witwatersrand Zainab Mohamed, Groote Schuur Hospital Elizabeth Molyneux, University of Malawi Daya Moodley, University of KwaZulu-Natal Anisa Mosam, University of KwaZulu-Natal Susan Msadabwe, Cancer Diseases Hospital, Ministry of Health David Muckart, University of KwaZulu-Natal Elmi Muller, University of Cape Town Landon Myer, University of Cape Town Saloshini Naidoo, University of KwaZulu-Natal Pradeep Navsaria, University of Cape Town/Groote Schuur Hospital Jabulani Ncayiyana, University of the Witwatersrand Charles Ngwena, University of Pretoria Nicolas Novitsky, University of Cape Town Duduzile Nsibande, Medical Research Council Ntobeko Ntusi, University of Cape Town Julian Oettle, University of the Witwatersrand Okechukwu Ogah, University College Hospital, Ibadan Emmy Okello, Uganda Heart Institute/Makerere University Steve Olorunju, Medical Research Council Andy Parrish, Walter Sisulu University/Cecilia Makiwane Hospital Mososa Patel, University of the Witwatersrand Robert Pattinson, University of Pretoria Olga Perovic, National Institute for Communicable Diseases Velisha Perumal, University of KwaZulu-Natal Kubendran Pillay, Private Fraser Pirie, University of KwaZulu-Natal Frances Priddy, International AIDS Vaccine Initiative Helena Rabie, Stellenbosch University Arthur Rantloane, University of Pretoria Bernardo Rapoport, Medical Oncology Centre of Rosebank Mpho Ratshikana-Moloko, University of the Witwatersrand Sarah Rayne, University of the Witwatersrand Brian Rayner, University of Cape Town Kate Rees, Anova Health Institute Jürgen Rehm, Centre for Addiction and Mental Health (CAMH) Gina Rencken, University of KwaZulu-Natal Helmuth Reuter, Stellenbosch University Anne Robertson, University of Limpopo Reitze Rodseth, University of KwaZulu-Natal. Susanne Roley, Collaborative for Leadership in Ayres Sensory Integration Charl Roux, University of Johannesburg Paul Ruff, University of the Witwatersrand Haroon Saloojee, University of the Witwatersrand Yusuf Saloojee, National Council Against Smoking Helen Schneider, University of the Western Cape Kathryn Schnippel, University of Cape Town Motshedisi Sebitloane, University of KwaZulu-Natal Mohammed Seedat, University of South Africa Sherona Seetharam, University of the Witwatersrand/Lancet Laboratories Hannah Simonds, Tygerberg Academic Hospital Elvira Singh, National Health Laboratory Service Kevin Spicer, Kentucky Department for Public Health Egilius Spierings, MedVadis Research Vanessa Steenkamp, University of Pretoria Victoria Stephen, Thelle Mogoerane Regional Hospital Ramudungoane Tabana, University of South Africa Allan Taylor, University of Cape Town Gerhard Theron, Stellenbosch University

Ciprian Tomuleasa, Oncology Institute ‘Prof. Dr. Ion Chiricuţă’ Joyce Tsoka-Gwegweni, University of KwaZulu-Natal Richard van-Zyl Smit, University of Cape Town Arnaud Vincent, Erasmus University Medical Center Linda Visser, University of KwaZulu-Natal Mari Viviers, Sefako Makgatho Health Sciences University Tim Walker, University of Rwanda/Butare University Teaching Hospital Cathy Ward, University of Cape Town Nicola Wearne, University of Cape Town Andrew Whitelaw, Stellenbosch University Janine Wichman, University of Pretoria Margaret Williams, Nelson Mandela Metropolitan University Charles Wiysonge, Stellenbosch University Darryl Wood, Queen’s Hospital Emergency Department/Queen Mary University Caradee Wright, South African Medical Research Council Michelle Youngleson, Institute for Healthcare, Boston/University of Cape Town Virginia Zweigenthal, University of Cape Town

The CME guest editors and authors

As editor of CME and SAMJ, I would like to thank all the guest editors and authors for their truly outstanding contributions to CME during 2017. This is much appreciated, particularly in the face of increasingly heavy clinical and teaching loads. Anaemia (parts 1 and 2) Guest editor: N Alli Authors: N Alli, J Vaughan, M Patel Prevention of childhood injuries (parts 1 and 2) Guest editors: A B van As, A van Niekerk Authors: M Arnold, A B van As, A Numanoglu, A van Niekerk, R Govender, R Jacobs, D K Kimemia, Y Ferreira Tuberous sclerosis complex Guest editor: P J de Vries Authors: P J de Vries, L Leclezio, J M Wilmshurst, G Fieggen, E Gottlich, L Jacklin, I P Naiker, R Newaj, D Shamley, B Schlegel, A Venter Wilderness medicine (parts 1 and 2) Guest editors: R Hofmeyr, J Matthew, R De Decker, S Buchanan, G Tölken Authors: R Hofmeyr, G Tölken, R De Decker, J Matthew, C Robertson, S Buchanan, C D’Alton, J Roos Chronic kidney disease Guest editor: A M Meyers Authors: A M Meyers, M Davies Contraceptive implants (parts 1 and 2) Guest editors: S Mullick, M F Chersich, Y Pillay, H Rees Authors: D Pillay, M F Chersich, C Morroni, M Pleaner, O A Adeagbo, N Naidoo, S Mullick, H Rees, J Smit, N Lince-Deroche, M Makua, Y Pillay Bridget Farham Editor ugqirha@iafrica.com

S Afr Med J 2017;107(12):1045-1046. DOI:10.7196/SAMJ.2017.v107i12.12985

December 2017, Print edition

EDITORâ&#x20AC;&#x2122;S CHOICE

Impact of Xpert MTB/RIF rollout on management of tuberculosis in a South African (SA) community

The Xpert MTB/RIF test shortens the time to microbiological confirmation of pulmonary tuberculosis (TB) under research conditions, and this study by Schmidt et al.[1] evaluated the field impact of Xpert MTB/RIF rollout on TB diagnostic yield and time to treatment in an SA community. The authors compared TB investigation outcomes for 6-month calendar periods before and after Xpert MTB/RIF rollout in a semirural area of SA. The proportion of adult patients who tested positive by sputum smear microscopy, liquid culture or Xpert MTB/RIF and the proportion of positive sputum smear, liquid culture or Xpert MTB/RIF tests were compared. Secondary outcomes included time to laboratory diagnosis and treatment initiation. Data were collected from the National Health Laboratory Service database and from the Western Cape Provincial Department of Health TB register. Regional rollout of Xpert MTB/RIF testing occurred in 2013. Of the 15 629 patients investigated in the post-rollout period, 7.9% tested positive on GeneXpert, compared with 6.4% of the 10 741 investigated in the pre-rollout period who tested positive by sputum smear microscopy (p<0.001). Median laboratory processing time was <1 day for Xpert MTB/RIF (interquartile range (IQR) 0 - 1) compared with 1 day (IQR 0 - 16) for sputum smear microscopy (p=0.001). The median time to TB treatment initiation was 4 days (IQR 2 - 8) after rollout compared with 5 days (IQR 2 - 14) before (p=0.001). Patients investigated for suspected pulmonary TB were more likely to be diagnosed after rollout of Xpert MTB/RIF testing, although the benefit to diagnostic yield was modest, and Xpert MTB/RIF testing was associated with a marginal improvement in time to treatment initiation.

Mortality trends in the City of Cape Town between 2001 and 2013: Reducing inequities in health

The City of Cape Town (CoCT), SA, has collected cause-of-death data from death certificates for many years to monitor population health. In 2000, the CoCT and collaborators set up a local mortality surveillance system to provide timeous mortality data at subdistrict level. Initial analyses revealed large disparities in health across subdistricts and directed the implementation of public health interventions aimed at reducing these disparities. Groenewald et al.[2] describe the changes in mortality in health subdistricts in the CoCT between 2001 and 2013, using pooled mortality data for the periods 2001 - 2004 and 2010 - 2013 from a local mortality surveillance system in the CoCT. These data were analysed by age, gender, cause of death and health subdistrict. Age-specific mortality rates for each period were calculated and age-standardised using the world standard population, and then compared across subdistricts. All-cause mortality in the CoCT declined by 8% from 938 to 863 per 100 000 between 2001 - 2004 and 2010 - 2013. Mortality in males declined more than that in females owing to a large reduction in male injury mortality, particularly firearm-related homicide. HIV/AIDS and tuberculosis (TB) mortality dropped by ~10% in both males and females, but there was a marked shift to older ages. Mortality in children aged <5 years dropped markedly, mostly owing to reductions in HIV/AIDS and TB mortality. Health inequities between subdistricts were reduced, with the highest-burden subdistricts achieving the largest reductions in mortality. Local mortality surveillance provides important data for planning, implementing and evaluating targeted health interventions at small-

area level. Trends in mortality over the past decade indicate some gains in health and equity, but highlight the need for multisectoral interventions to focus on HIV and TB and homicide and the emerging epidemic of non-communicable diseases.

Hepatitis C: A South African literature review and results from a burden of disease study among a cohort of drugusing men who have sex with men in Cape Town, SA

Hepatitis C virus (HCV) is a chronic infection of increasing importance, especially among people living with HIV/AIDS. Co-infection with HIV can accelerate progression of HCV liver disease to cirrhosis and end-stage liver failure and elevate the risk of hepatocellular carcinoma. Globally, men who have sex with men (MSM) and people who inject drugs are at an increased risk of HCV infection compared with the general population. Few studies on HCV in these key populations have been done in SA. Semugoma et al.[3] describe the disease burden of HCV in drug-using MSM attending harm-reduction services at the Anova Health Instituteâ&#x20AC;&#x2122;s Health4Men clinic in Cape Town, SA. In 2012 2014, attendees of an MSM-focused harm-reduction programme were invited to participate in the study. After informed consent, participants completed a brief demographic questionnaire and underwent phlebotomy for anti-HCV antibody, hepatitis B virus (HBV) surface antigen and surface antibody testing. Participants received counselling and education with regard to their results. HIV status was extracted from the case notes of participants who had previously been tested at the study site. Data were analysed using standard statistical techniques. Of 41 MSM enrolled, 11 (27.0%) tested anti-HCV antibodypositive, indicating prior exposure to HCV or chronic infection; 10/11 (91.0%) were positive for HBV surface antibodies, suggesting previous HBV exposure or vaccination; and 1 (2.0%) screened positive for HBV. HIV status was known in 8 of the 11 HCVseropositive individuals; 3/8 (37.5%) were HIV-positive. This study demonstrated a high burden of HCV exposure or infection in a small urban cohort of MSM who inject drugs. The authors recommend active screening of MSM (especially those who report drug use) for HCV, and the development of referral networks for access to treatment.

A comparison of private and public sector intensive care unit infrastructure in SA

Intensive care units (ICUs) are designed to care for patients who are often at increased risk of acquiring healthcare-associated infections. The structure of ICUs should be optimally designed to facilitate the care of these critically ill patients, and minimise their risk of infection. National regulations (R158) were developed to govern the building and registration of private hospitals, and until recently equivalent regulations were not available for public hospitals. Mahomed et al.[4] used a cross-sectional study design to assess the infrastructure of 25 private sector and 6 public sector ICUs in eThekwini Health District, KwaZulu-Natal Province, SA. The authors used the R158 checklist, which was developed by the KwaZuluNatal Department of Health Private Licensing Unit and Infection Prevention and Control Unit. The aspects covered in the R158 checklist were categorised into the design, general safety and patient services of the ICUs. Most of the ICUs in both sectors met the general safety requirements. There were varying levels of compliance with the

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EDITORâ&#x20AC;&#x2122;S CHOICE

design criteria. Only 7 (28.0%) and 1 (16.7%) of the private and public ICUs, respectively, had sufficient space around the beds. Twenty-two private ICUs (88.0%) and 4 public ICUs (66.7%) had isolation rooms, but only some of these isolation rooms (15 private and 2 public) had appropriate mechanical ventilation. None of the ICUs had clinical hand-wash basins in the nurse stations and dirty utility rooms. The majority of the ICUs had the required number of oxygen and electric outlets at the bedside. None of the public ICUs met the light intensity requirement over the bed area. Adequate spacing in ICUs was an issue in many cases. Interventions need to be put in place to ensure that ICUs meet the relevant design standards. There is an urgent need to revise the R158 regulations to reflect current best practices, particularly with regard to infection

control. The same standards should be applied to ICUs in the private and public health sectors to maintain quality of care to patients. BF 1. Schmidt B-M, Geldenhuys H, Tameris M, et al. Impact of Xpert MTB/RIF rollout on management of tuberculosis in a South African community. S Afr Med J 2017;108(12):1078-1081. https://doi. org/10.7196/SAMJ.2017.v107i12.12502 2. Groenewald P, Neethling I, Evans J, et al. Mortality trends in the City of Cape Town between 2001 and 2013: Reducing inequities in health. S Afr Med J 2017;108(12):1091-1098. https://doi.org/10.7196/ SAMJ.2017.v107i12.12458 3. 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;108(12):1116-1120. https://doi.org/10.7196/SAMJ.2017. v107i12.12623 4. Mahomed S, Sturm AW, Moodley P. A comparison of private and public sector intensive care unit infrastructure in South Africa. S Afr Med J 2017;108(12):1086-1090. https://doi.org/10.7196/ SAMJ.2017.v107i12.12631

MC Botha, Bertie Bosman and Chris Barnard (photo: First Heart Transplant Museum, Groote Schuur Hospital).

December 2017, Print edition

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CORRESPONDENCE

Acute high-altitude illness

To the Editor: It was delightful to see an article[1] about altitude illness in a recent issue of SAMJ, especially in view of the fact that over the years there have been many unnecessary deaths on Kilimanjaro due to climbers going up too high too fast. For this reason, prevention of altitude illness is indeed a very relevant topic for your local readership in Africa. The authors have rightly pointed out that ascending gradually is the best away to acclimatise to high altitude and not suffer from acute mountain sickness (AMS) and lifethreatening high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE). Unfortunately there are several misperceptions in the article, and I would like to focus on the use of acetazolamide. The authors do not seem to be clear about the fact that there is strong evidence for the role of acetazolamide in the prevention of AMS. In fact, the guideline[2] that they cite mentions this in no uncertain terms. Clearly for most trekkers it may be best not to take any drugs and trek up the mountain gradually, but in certain circumstances (for example in a trekker with a prior history of AMS) acetazolamide is certainly very useful chemoprophylaxis. This important fact about the usefulness of acetazolamide when necessary is not emphasised. In fact, the authors promptly note the uncommon side-effects of acetazolamide, including blurred vision, and later lump the most common side-effect (by far), which is a tingling and burning sensation in the fingers and toes, together with the relatively rare side-effects. In addition, in the treatment of moderate AMS, where acetazolamide is clearly indicated with strong evidence for its effectiveness,[2] the authors bring up acetazolamide treatment almost as an afterthought. They suggest acetazolamide for established HAPE, but in the setting of HAPE this diuretic may in fact cause more dehydration and hyperventilation and complicate the problem, and is not indicated. [2] In addition they suggest treatment of HAPE with dexamethasone, when there is no proof in the literature for this, and they also suggest simultaneously administering both nifedipine and sildenafil for HAPE, which many high-altitude doctors would frown upon. Finally, it is probably true to say that if knowledgeable guides were to carry acetazolamide and dexamethasone on Kilimanjaro trips, lives could potentially be saved. Buddha Basnyat Medical Director, Oxford University Clinical Research Unit-Nepal, Centre for

peaks (such as Kilimanjaro, Kenya, Stanley and Toubkal) very frequently feature short approaches with increased potential for high-risk ascent profiles.[3] The non-technical nature of many of these peaks allows many trekkers and climbers to ascend and descend rapidly enough to have returned to lower elevations before altitude illness has fully manifested. This practice has led to the true risks being underestimated, and (in our opinion) to an over-reliance on chemoprophylaxis to compensate for high-risk ascent profiles (see Table 2 of our article, adapted from Wilderness Medical Society guidelines[1,4]) rather than risk reduction through profile adjustment.[5] This increasing use of and/or reliance on chemoprophylaxis has also been described elsewhere, such as in Himalayan trekkers.[6] Furthermore, while there is good evidence that acetazolamide undoubtedly hastens acclimatisation (numbers needed to treat in the range of 3 - 8, depending on circumstance[6-8]), it cannot compensate for excessively rapid ascent.[9-12] For this reason, we have placed great emphasis on prevention, but wholeheartedly agree that acetazolamide has a strong role in moderate- to high-risk cases where acclimatisation alone is insufficient.[6,13] We reiterate our recommendation for first-time users to take a few test doses of acetazolamide prior to departure; while (as Dr Basnyat notes) the most common side-effect is severe paraesthesia/tingling/burning of the digits, it does help the user to identify the less common side-effects, which may be confused with AMS at altitude.[6] With regard to treatment (as opposed to prophylaxis), it is worth noting that while acetazolamide is widely accepted and used, there are remarkably few examples of robust randomised studies supporting this practice.[4,14] However, we would re-emphasise our recommendation to follow the existing guidelines and initiate treatment in moderate to severe AMS.[4] For management of HAPE alone, acetazolamide and dexamethasone are indeed of questionable value, although the latter has been the subject of significant debate and appears in various guidelines.[4,15,16] While the brevity of our text and the accompanying cognitive aid may give the mistaken impression of a ‘shotgun’ approach, treatment must of course be selected in the context of the patient’s clinical condition, which may or may not include isolated AMS, HACE, HAPE, or any combination thereof. Dr Basnyat’s closing remark is apt: Lives could certainly be saved on Kilimanjaro by knowledgeable administration of acetazolamide, dexamethasone and other drugs. However, an ounce of prevention through conscientious mountaineering and adhering to safe ascent profiles is worth a pound of cure.

Tropical Medicine and Global Health, Nuffield Department of Medicine, University

R Hofmeyr

of Oxford, UK

Department of Anaesthesia and Perioperative Medicine, Faculty of Health Sciences,

buddha.basnyat@ndm.ox.ac.uk

University of Cape Town; and WildMedix, Cape Town, South Africa ross.hofmeyr@uct.ac.za

1. Hofmeyr R, Tölken G, De Decker R. Acute high-altitude illness. S Afr J Med 2017;107(7):556-561. https://doi.org/10.7196/SAMJ.2017.v107i7.12612 2. Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2014 update. Wilderness Environ Med 2014;25(Suppl 4):S4-S14. https://doi.org/10.1016/j.wem.2014.06.017

Dr R Hofmeyr et al. respond: We note with pleasure that our recent article on acute high-altitude illness[1] has drawn significant attention, and are greatly encouraged by the discourse it has generated. We are grateful to Dr Basnyat for his expert engagement and acknowledgement of the challenges of managing acute altituderelated illnesses (such as AMS, HACE and HAPE) in Africa. We regret, therefore, if the brevity of our article and its strong emphasis on safe acclimatisation practices and basic field management of altitude illness have left the misapprehension that we do not advocate the use of acetazolamide where indicated. Rapid ascent to high altitudes by relative novices is not a uniquely African problem, nor is it limited to mountaineers.[2] However, African

G Tölken WildMedix, Cape Town; and Mountain Rescue, Hottentots-Holland Section – Mountain Club of South Africa, Cape Town, South Africa

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

1. Hofmeyr R, Tölken G, De Decker R. Acute high-altitude illness. S Afr Med J 2017;107(7):556-561. https://doi.org/10.7196/SAMJ.2017.v107i7.12612 2. Basnyat B. High altitude pilgrimage medicine. High Alt Med Biol 2014;15(4):434-439. https://doi. org/10.1089/ham.2014.1088 3. Hofmeyr R, Meyer W, James M, et al. Recognising and mitigating the risk of altitude-related illness. S Afr Med J 2016;106(9):834-835. https://doi.org/10.7196/SAMJ.2016.v106i9.11389 4. Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2014 update. Wilderness Environ Med 2014;25(4 Suppl):S4-S14. https://doi.org/10.1016/j.wem.2014.06.017 5. De Decker R, Tölken G, Roos J. Human factors: Predictors of avoidable wilderness accidents? S Afr Med J 2017;107(8):669-673. https://doi.org/10.7196/SAMJ.2017.v107i8.12677

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6. Kayser B, Dumont L, Lysakowski C, et al. Reappraisal of acetazolamide for the prevention of acute mountain sickness: A systematic review and meta-analysis. High Alt Med Biol 2012;13(2):82-92. https://doi.org/10.1089/ham.2011.1084 7. Basnyat B, Gertsch JH, Johnson EW, et al. Efficacy of low-dose acetazolamide (125 mg BID) for the prophylaxis of acute mountain sickness: A prospective, double-blind, randomized, placebo-controlled trial. High Alt Med Biol 2003;4(1):45-52. https://doi.org/10.1089/152702903321488979 8. Ritchie ND, Baggott AV, Todd WTA. Acetazolamide for the prevention of acute mountain sickness – a systematic review and meta-analysis. J Travel Med 2012;19(5):298-307. https://doi.org/10.1111/j.17088305.2012.00629.x 9. Gallagher SA, Hackett PH. High-altitude illness. Emerg Med Clin North Am 2004;22(2):329-355, viii. https://doi.org/10.1016/j.emc.2004.02.001 10. Küpper T, Gieseler U, Angeline C, et al., UIAA MedCom (Union Internationale des Associations d’Alpinisme Medical Commission). Consensus Statement of the UIAA Medical Commission. Vol. 2: Emergency Field Management of Acute Mountain Sickness, High Altitude Pulmonary Edema, and High Altitude Cerebral Edema. 2012. http://theuiaa.org/documents/mountainmedicine/English_ UIAA_MedCom_Rec_No_2_AMS_HAPE_HACE_2012_V3-2.pdf (accessed 31 October 2017). 11. Davies AJ, Kalson NS, Stokes S, et al. Determinants of summiting success and acute mountain sickness on Mt Kilimanjaro (5895 m). Wilderness Environ Med 2009;20(4):311-317. https://doi. org/10.1580/1080-6032-020.004.0311 12. Jackson SJ, Varley J, Sellers C, et al. Incidence and predictors of acute mountain sickness among trekkers on Mount Kilimanjaro. High Alt Med Biol 2010;11(3):217-222. https://doi.org/10.1089/ ham.2010.1003 13. Basnyat B. Acclimatizing with acetazolamide. J Travel Med 2012;19(5):281-283. https://doi. org/10.1111/j.1708-8305.2012.00646.x 14. Grissom CK, Roach RC, Sarnquist FH, et al. Acetazolamide in the treatment of acute mountain sickness: Clinical efficacy and effect on gas exchange. Ann Intern Med 1992;116(6):461-465. https:// doi.org/10.7326/0003-4819-116-6-461 15. Richalet J-P. Pro: Corticosteroids are useful in the management of HAPE. High Alt Med Biol 2015;16(3):186-189. https://doi.org/10.1089/ham.2015.0035 16. Mairbäurl H, Baloglu E. Con: Corticosteroids are useful in the management of HAPE. High Alt Med Biol 2015;16(3):190-192. https://doi.org/10.1089/ham.2015.0071

S Afr Med J 2017;107(12):1047-1048. DOI:10.7196/SAMJ.2017.v107i12.12863

workshops were hosted for academic staff by the platform developer from Charité, the LOOOP representative from Sefako Makgatho University, and relevant academics. Academics were motivated to engage with the process through a variety of forums such as school teaching and learning committees, school boards, departmental meetings and meetings with module co-ordinators. This mapping exercise has been a developmental process and a formative exercise for academic staff. Stakeholders have access to LOOOP to enable a comprehensive paperless view of the curriculum. This allows educators to interrogate and clarify their own content and understand how this articulates with other content in achieving the desired learning outcomes. It has identified redundancies and gaps, particularly with regard to inter- and transprofessional learning. It has clarified the vertical and horizontal integration and learning spirals essential for curriculum development with relevance to context. Curriculum mapping is an integral step for aligning curriculum content with outcomes in a competency-based curriculum. The experience in the MB ChB programme will be shared, and recommendations will be made to support the process of curriculum mapping across other health professions programmes in this and other institutions. Serela Ramklass, Margaret Matthews School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal,

Development of the MB ChB curriculum map at the University of KwaZulu-Natal, South Africa

Durban, South Africa matthewsm@ukzn.ac.za

To the Editor: With reference to the article by Van Heerden aimed at addressing the health needs of South Africa (SA)’s population through competency-based health professions curricula, we share our experience of developing the MB ChB curriculum map at the University of KwaZulu-Natal (UKZN) as a first step towards curriculum review. The map is intended to evaluate the current curriculum against the five key elements referred to in the article as necessary to inform the training of health professionals for the SA context. This communication will describe the process of mapping the curriculum in under a year using LOOOP (Learning Opportunities, Objectives and Outcome Platform), a web-based platform developed at Charité University in Germany.[2] On LOOOP, the learning events in every module or discipline are linked to learning objectives, the seven Health Professions Council of South Africa meta-competencies, Medical Subject Headings (MeSH), the National Qualification Framework, and UKZN-specific exit level/yearly outcomes. Teaching methods and resources are defined, and every objective is linked to assessment methods. Fragmentation of the medical curriculum across three schools in the College of Health Sciences has presented challenges, evidenced by a lack of cohesiveness in curriculum content, delivery and assessment methods. To make the different components and interconnections in a competency-based programme transparent, we embarked on this project to improve curriculum access for students, teachers and curriculum planners across the schools and disciplines. Various factors influenced participation, and strategies were developed to mobilise academic staff to recognise the benefits of the process and understand its requirements. A process of information sharing was project-managed by the dean and office of teaching and learning in the School of Clinical Medicine and led by key academics across the schools. Implementation of the project required a range of resources to support co-ordinated and integrated processes among leadership, academic staff, support staff, organisational structure, technical support and communication networks. To increase participation in the project, multiple training

[1]

1. Van Heerden B. Effectively addressing the health needs of South Africa’s population: The role of health professions education in the 21st century. S Afr Med J 2013;103(1):21-22. https://doi.org/10.7196/ SAMJ.6463 2. Balzer F, Hautz WE, Spies C, et al. Development and alignment of undergraduate medical curricula in a web-based, dynamic Learning Opportunities, Objectives and Outcome Platform (LOOOP). Med Teach 2016;38(4):369-377. https://doi.org/10.3109/0142159X.2015.1035054

S Afr Med J 2017;107(12):1049. DOI:10.7196/SAMJ.2017.v107i12.12859

Human dignity and the future of the voluntary active euthanasia debate in South Africa

To the Editor: In this letter, I reply to Dr Donkin’s[1] response to my article ‘Human dignity and the future of the voluntary active euthanasia debate in South Africa’,[2] published in the May 2017 edition of the SAMJ. I start with the question of whether individual autonomy is central to the definition of human dignity. Although the concept of human dignity has near-universal appeal, internationally several conceptions of its meaning exist. In South Africa (SA), our Constitutional Court has over the past generation often grappled with the concept in its jurisprudence. In the case of Barkhuizen v Napier,[3] the Constitutional Court explicitly held that ‘Self-autonomy, or the ability to regulate one’s own affairs, even to one’s own detriment, is the very essence of freedom and a vital part of dignity.’ This position was echoed in MEC for Education: Kwazulu-Natal v Pillay,[4] where the majority of the Constitutional Court held that an ‘entitlement to respect for the unique set of ends that the individual pursues’ – which approximates to autonomy – is a ‘necessary element of freedom and of dignity of any individual’. Furthermore, the Supreme Court of Appeal held as follows in British American Tobacco South Africa (Pty) Ltd v Minister of Health:[5] ‘Recognising the role of freedom of expression in asserting the moral autonomy of individuals demonstrates the close links between freedom of expression and other constitutional rights such as human dignity, privacy and freedom. Underlying all these constitutional rights is the constitutional celebration of the

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CORRESPONDENCE

possibility of morally autonomous human beings independently able to form opinions and act on them.’ Accordingly, there is solid authority for my proposition that, in SA law, individual autonomy is central to human dignity. Dr Donkin’s accusation that so-called ‘pro-euthanasia activists’ frequently ‘hijack’ dignity and use it as a ‘euphemism’ for autonomy is therefore without merit. In our law, autonomy needs no euphemism – it is explicitly celebrated as a vital part of human dignity. This is the reality that will have to be confronted in any subsequent litigation about voluntary active euthanasia. Next, Dr Donkin states that ‘Jordaan failed to mention that individual autonomy can never be absolute.’ This is not correct. I clearly stated in my article that human dignity, and per implication therefore individual autonomy, are not the only relevant considerations in the voluntary active euthanasia debate. In fact, I concluded my article by stating that ‘It bears repetition that human dignity is not the only right that is relevant to this complex discourse. The question of whether or not voluntary active euthanasia is required by SA’s human rights system must be answered by carefully balancing all rights that are relevant to the subject.’ The balancing of rights is a standard principle of our law that goes without saying. The term ‘autonomy’ is used, with somewhat different meanings, in fields as diverse as law and psychology, and one must be careful to avoid conflating these different uses. In particular, questions of free will must be distinguished from the legal meaning of autonomy. John Stuart Mill refers to this very distinction in the first sentence of On Liberty[6] (in somewhat old-fashioned language): ‘The subject of this Essay is not the so-called Liberty of the Will, so unfortunately

opposed to the misnamed doctrine of Philosophical Necessity; but Civil, or Social Liberty: the nature and limits of the power which can be legitimately exercised by society over the individual.’ As such, when I propose that autonomy is a central component of human dignity, I am making a legal claim that the constitutional right to dignity entails the right of individuals to self-determination. On a practical level, Dr Donkin mentions the possibility of abuse of sick persons. The possibility for abuse exists in many areas of the law, but does not constitute a good reason for blanket prohibitions. The proper way to address foreseeable abuse in the context of voluntary active euthanasia is by putting legal safeguards in place. In surrogacy, for instance, the legal safeguards against abuse include, among others, that any surrogacy agreement must be approved by the High Court before it is put into effect. Lastly, Dr Donkin contends that I lose sight of the ‘human consequences’ of euthanasia. Is the vindication – or violation! – of a person’s dignity not a ‘human consequence’? Donrich W Jordaan School of Law, Howard College, University of KwaZulu-Natal, Durban, South Africa jordaand@ukzn.ac.za 1. Donkin A. Human dignity and the future of the voluntary active euthanasia debate in South Africa. S Afr Med J 2017;107(8):647. https://doi.org/10.7196/SAMJ.2017.v107i8.12599 2. Jordaan DW. Human dignity and the future of the voluntary active euthanasia debate in South Africa. S Afr Med J 2017;107(5):383-385. https://doi.org/10.7196/SAMJ.2017.v107i5.12339 3. Barkhuizen v Napier [2007] ZACC 5. 4. MEC for Education: Kwazulu-Natal v Pillay [2007] ZACC 21. 5. British American Tobacco South Africa (Pty) Ltd v Minister of Health [2012] ZASCA 107. 6. Mill JS. On Liberty. 1859. http://www.econlib.org/library/Mill/mlLbty1.html (accessed 4 November 2017).

S Afr Med J 2017;107(12):1050. DOI:10.7196/SAMJ.2017.v107i12.12932

Louis Washkansky having his chest auscultated by Chris Barnard, with an ICU nurse in attendance (photo: First Heart Transplant Museum, Groote Schuur Hospital).

December 2017, Print edition

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

IZINDABA

30 days in medicine Weather-related disasters increasing

An international team reporting in The Lancet say that climate change is already having a significant effect on health. This because of an increase in the number of weather-related disasters, greater exposure to heatwaves and an increased risk of dengue fever because conditions are more favourable for mosquitoes. A key underpinning assumption is that the rise in temperatures where people live is much higher than the average increase in global temperature as a whole, because land warms to a greater extent than do oceans. This means that the number of people exposed to heatwaves rose by 125 million between 2000 and 2016. Between 2007 and 2016, weather-related disasters increased by 46% compared with the 1990 - 1999 average, with most deaths occurring in resource-poor countries. Watts N, Amann M, Ayeb-Karlsson S, et al. The Lancet countdown on health and climate change: from 25 years of inaction to a global transformation for public health. Lancet 2017 (epub 30 October 2017). http:// dx.doi.org/10.1016/S0140-6736(17)32464-9

Still gaps in yellow fever vaccination cover

Recent large outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. A study published in the The Lancet Infectious Diseases estimated global yellow fever vaccination coverage from 1970 through to 2016 to calculate the number of individuals still needing vaccination in order to reach the thresholds for outbreak prevention. The authors found major increases in vaccine coverage since 1970, but with notable gaps within yellow fever risk zones, with an estimated 393.7 million to 472.9 million people who still need vaccination in yellow fever risk zones to reach the 80% coverage recommended by the World Health Organization. Shearer FM, Moyes CL, Pigott DM, et al. Global yellow fever vaccination coverage from 1970 to 2016: An adjusted retrospective analysis. Lancet Infect Dis 2017;17(11):1209-1217. https://doi.org/10.1016/S14733099(17)30419-X

Stents for stable angina of no benefit

Percutaneous coronary intervention (PCI) is not significantly better than a placebo procedure in improving exercise capacity

or symptoms, even in patients with severe coronary stenosis, according to the ORBITA study published in The Lancet. This is the first double-blind randomised controlled trial to directly compare stenting with placebo in patients with angina who are receiving the correct drug treatment. Exercise tests were carried out before the procedure and 6 weeks later in 200 patients with severe (≥70%) single-vessel stenosis, who had been given 6 weeks of intensive medical treatment and were then randomly assigned to PCI (105 patients) or a placebo group (95 patients). The placebo group only had an angiogram. There was no statistically significant difference in overall exercise time or symptom alleviation before and after the procedure between the two groups. Al-Lamee R, Thompson D, Dehbi H, et al. Percutaneous coronary intervention in stable angina (ORBITA): A double blind, randomised controlled trial. Lancet 2017 (epub 2 November 2017). https://doi.org/10.1016/ S0140-6736(17)32714-9

Misdiagnosis of type 3 diabetes

A large primary care study in the UK has found that type 3 diabetes, or diabetes of the exocrine pancreas, is commonly misdiagnosed as type 2 diabetes in most patients. Researchers used routinely collected primary care records for more than 2 million patients in England for incident cases of adult-onset diabetes between 1 January 2005 and 31 March 2016. In results reported in Diabetes Care, they identified 31 789 new diagnoses of adult-onset diabetes. They found 559 cases of diabetes that occurred after pancreatic disease. Doctors treating these cases generally classified them as type 2 diabetes (87.8%), with only 2.7% of cases being classified as diabetes of the exocrine pancreas. Compared with patients with type 2 diabetes, patients with diabetes occurring after pancreatic disease were nearly twice as likely to have poor glycaemic control and much more likely to need insulin within 5 years of diagnosis. Woodmansey C, McGovern AP, McCullough KA, et al. Incidence, demographics, and clinical characteristics of diabetes of the exocrine pancreas (type 3c): A retrospective cohort study. Diabetes Care 2017;40(11):14861493. https://doi.org/10.2337/dc17-0542

B Farham Editor ugqirha@iafrica.com

December 2017, Print edition

IZINDABA

OBITUARIES Joseph (Ozzie) Ozinsky

Dr Joseph Ozinsky, doyen of cardiac anaesthesiologists in South Africa and mentor to generations of anaesthetic trainees in the University of Cape Town Department of Anaesthesia, passed away in Cape Town on 15 August 2017 at the age of 90. Born of Polish parents in 1927, he was educated as a Queen Victoria Scholar at SACS, where he matriculated at age 15. He then studied medicine as a SACS Memorial Scholar at UCT, graduating MB ChB in 1949. He trained in anaesthesia at Groote Schuur Hospital in Cape Town and King Edward

VII Hospital in Durban. In 1955 he travelled to the UK, where he worked as a registrar at Barnet General Hospital in London and passed both the DA (RCP&S) and the DA (Ire). He returned to Cape Town to the newly opened Red Cross War Memorial Children’s Hospital and then to Groote Schuur Hospital, where he progressed from specialist to chief specialist in the Department of Anaesthesia. In 1990 UCT honoured him by making him an associate professor. Oz was in charge of cardiothoracic anaesthesia at Groote Schuur for over 40 years and is probably best known for being the lead anaesthetist in Christiaan Barnard’s heart transplant team. His unflappable temperament and dry sense of humour enabled him to control prima donna surgeons and defuse tense situations. He was also able to ‘defend his space’ on the anaesthetist’s side of the ‘blood–brain’ barrier, as many visiting surgeons discovered. During an academic meeting in 1977 he suffered the first of several strokes that were to plague him in later life, and woke with temporary aphasia and a hemiparesis. This led to Prof. Bull penning the following: He died not in church He died not in Shul He died whilst listening To Professor Bull.

To which Oz replied: He listened with patience He listened in pain To things he had heard Again and again. Then sleep overcame him Completely besotted He relaxed his neck And kinked his carotid. Oz was appointed head of clinical services in the UCT Department of Anaesthesia and administered the day-to-day running of the department for many years. One of his lasting legacies was the advisory role he played in the layout of theatres, and the purchase of ‘state-of-the-art’ theatre equipment, in the move to the new Groote Schuur Hospital in 1989. Oz retired in 1992, but continued his interest in cardiothoracic anaesthesia in the department until the end of December 2001. His wife Maria (‘Poppy’, née Rautenbach) passed away in 2011. He is survived by his sons Max and Adrian, and their families. Peter Gordon Archivist, South African Society of Anaesthesiologists Cape Town, South Africa peter.gordon@uct.ac.za

Cecil Moss

Anaesthetist Dr Cecil Moss died in Cape Town on 27 October 2017, at the age of 92. He was born in Riversdale in February 1925,

to parents of Lithuanian extraction. His grandfather served as Rabbi in Riversdale. Determined to provide their sons with a good education, Cecil’s parents moved to Muizenberg and enrolled them at SACS, from where Cecil matriculated at the age of 15 in 1940. An excellent all-round sportsman, he never played for the school’s first rugby team because of his young age. The following year he enrolled to study medicine at the University of Cape Town, and played for their first XV in 1943. In 1944 he broke his studies and enlisted in the armed forces together with fifteen other UCT students. He became a medical corporal in the Special Service Battalion of the 6th Division, serving in Egypt and Italy. After the war he returned to UCT, graduating MB ChB in 1948, at the age of 23. During his internship year at Durban’s King Edward VIII Hospital Cecil captained the Natal rugby team and was vice-captain

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of the 1949 Springbok rugby team that trounced the All Blacks 4-0. In November 1950, Cecil married University of Natal science student Jill Kalf. The couple moved to Cape Town, where Cecil went into general practice. He developed an interest in anaesthesia, and in 1954 they relocated to England, where he specialised at the University of Liverpool under Prof. Cecil Gray, and then at London Hospital, obtaining the DA (Ire) in 1955, the DA (Eng) in 1956 and the FFA RCS (Eng) in 1957. After returning to Cape Town in 1959, Cecil became a founder partner of Dr Basil Solomon and Partners (forerunner of the Cape Anaesthetic Clinic), with part-time sessions at Groote Schuur Hospital. In 1961 he returned to full-time practice at Groote Schuur. As the anaesthetist on call on 3 December 1967, he was part of the team led by Chris Barnard that performed the world’s first human-to-human heart

IZINDABA

transplant operation, during which he cared for the donor during the explantation procedure before assisting senior anaesthetist Dr Joseph Ozinsky. In 1989 he returned to private practice with Dr Clive Nussbaum. Cecil is probably best known for his success on the rugby field as player, coach and administrator. He coached the UCT rugby team for nine years, during which time they won the Grand Challenge, Town

Challenge and Ted Sceales trophies. He also coached Western Province from 1972 to 1992, winning several Currie Cups, and during the isolation years he coached the Springboks, winning ten out of twelve ‘unofficial tests’. Cecil’s colleagues and friends will remember him for his modesty, thoughtfulness, attention to detail and intellect. A few weeks ago, he paid a fascinating off-the-cuff tribute

to Ozinsky at the memorial service held for him at GSH. Cecil is survived by his wife Jill, their son Jaime and daughter Tessa, and four grandchildren. Peter Gordon Archivist, South African Society of Anaesthesiologists Cape Town, South Africa peter.gordon@uct.ac.za

Donald (Don) Leonard Fisher-Jeffes

Dr Donald (Don) Fisher-Jeffes passed away in Cape Town on 5 September 2017 at the age of 98. Born in Sydney, Australia, on 3 June 1919, he emigrated to South Africa with his family in 1930, when his father Norman opened South Africa’s first WeetBix factory in Cape Town. Don matriculated

at Wynberg Boys’ High School and studied medicine at the University of Cape Town, graduating MB ChB in 1944. Don’s interest in anaesthesia developed while he was an intern at Nokuphila Mission Hospital on the Witwatersrand. He then transferred to the newly opened Coronation Hospital, where after obtaining the Diploma in Public Health in 1946, he continued his training in anaesthesia under the tutelage of Dr Molly Barlow. In 1949 Don was one of the first group of three graduates to pass the University of the Witwatersrand’s Diploma in Anaesthesia, South Africa’s first specialist anaesthetic examination. He continued his association with the Johannesburg group of teaching hospitals, initially as a full-time specialist and after 1955 as a part-timer at Coronation Hospital. For 14 years he was in practice with Dr Cyril Frost. Don developed a special interest in the fledgling subspecialty of cardiothoracic anaesthesia and was involved in many of the early repairs of congenital tracheo-oesophageal fistulas performed in Johannesburg. He

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provided anaesthesia for the pioneering cardiac catheterisation procedures performed by Drs Morris McGregor and Bernard van Lingen at Johannesburg Hospital in the 1950s. A long-time servant of the South African Society of Anaesthesiologists (SASA), Don was a member of the SASA Council for 43 years. During this time he served two terms as secretary and two terms as president. During his second term as president he developed unstable angina and underwent successful coronary artery bypass surgery. In 1970 he was awarded SASA’s highest honour, that of honorary life vice-president. Don is survived by his second wife Suzanne and his three children from his marriage to his first wife, Doreen, who passed away in 1982. His son Norman is a neurosurgeon in Cape Town. Peter Gordon Archivist, South African Society of Anaesthesiologists Cape Town, South Africa peter.gordon@uct.ac.za

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ISSUES IN MEDICINE

Lamivudine monotherapy in children and adolescents: The devil is in the detail L Fairlie,1 MB ChB, FCPaed (SA), MMed; J Bernheimer,2 MD, MSc, DTM&H; N Sipambo,3 MB BCh, FCPaed (SA); C Fick,1,4 MB BCh; L Kuhn,5 PhD Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa MĂŠdecins Sans FrontiĂ¨res (Doctors Without Borders), Khayelitsha, South Africa 3 Chris Hani Baragwanath Academic Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 4 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 5 Gertrude H Sergievsky Center, College of Physicians and Surgeons; and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA 1 2

Corresponding author: L Fairlie (lfairlie@wrhi.ac.za)

Although expanded access to antiretroviral therapy (ART), and starting lifelong ART as soon as possible after diagnosis of HIV, have dramatically improved survival and reduced morbidity in HIV-infected children and adolescents, ~20% of children will develop virological failure (VF). Children and adolescents may be at higher risk of VF and drug resistance for a number of reasons, including prevention of mother-to-child exposure, reliance on a caregiver to administer ART, poor palatability of paediatric drugs, tuberculosis/HIV co-treatment in protease inhibitor (PI) (mainly lopinavir/ritonavir)-based regimens, and adolescence being associated with poor adherence. In children with VF, if adherence issues are addressed and re-suppression is not achieved, a switch to second- or third-line drugs may be indicated, which is the gold standard in management. However, in the face of ongoing adherence challenges, with potential accumulation of resistance mutations, limited treatment options due to extensive resistance and limited approved paediatric formulations, other strategies have been used. These include continuing a failing PI regimen, switching to a holding regimen (one or more nucleoside reverse transcriptase inhibitors) or discontinuing ART. Lamivudine monotherapy is a common choice when holding regimens are used, on the premise that the lamivudineassociated M184V resistance mutation reduces viral replication and may maintain clinical and immunological stability compared with discontinuing treatment altogether. However, this strategy is generally associated with immunological, and in some cases clinical, decline after starting lamivudine monotherapy. We discuss the pros and cons of using this therapy in children. We also propose guidance for using lamivudine monotherapy, suggesting clinical and immunological criteria for its use. Close monitoring and adherence support are required with this approach. Given many new emerging ART drugs and strategies, lamivudine monotherapy should be administered temporarily, while efforts to improve adherence are implemented. It should not be considered a default option in children with VF. S Afr Med J 2017;107(12):1055-1057. DOI:10.7196/SAMJ.2017.v107i12.12776

Success with prevention of mother-to-child transmission (PMTCT) has resulted in a substantial reduction in the number of HIV-infected children.[1] Expanded access to antiretroviral therapy (ART), and recommendations to start lifelong ART as soon as possible after diagnosis, have dramatically improved survival and reduced morbidity in HIVinfected children and adolescents.[2] Current HIV treatment guidelines for children recommend a protease inhibitor (PI)-based regimen (lopinavir/ ritonavir (LPV/r)) in those Ë&#x201A;3 years of age and a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in those >3 years old, combined with 2 nucleoside reverse transcriptase inhibitors (NRTIs).[3,4] In longitudinal follow-up studies, ~20% of children develop virological failure (VF) 3 years after ART initiation.[5] In these children, associated drug resistance mutations (RMs) may occur in up to 90%. The most common mutations are associated with NNRTIs, lamivudine and thymidine analogues, with the lamivudine-associated mutation, M184V, occurring frequently.[6] In children on first-line PI regimens, detected NNRTI RMs would have been selected by PMTCT. In children, unique factors may result in poor adherence and/ or VF. These include exposure to nevirapine or efavirenz for PMTCT, with expected universal selection of NNRTI mutations in the exposed, and even modest rates of RMs in the unexposed (a

reported rate of 24% in a PMTCT-unexposed population in South Africa (SA)).[7-9] Children are also caregiver dependent, and thus completely reliant on an adult for ART administration. Any social or financial instability or change threatens the sustainability of their treatment. Furthermore, there is poor palatability of certain paediatric antiretrovirals, particularly LPV/r, and in some cases lack of availability of paediatric formulations, which requires adaptation of adult formulations. Tuberculosis (TB) co-treatment is common, raising complexities of drug-drug interactions between rifampicin and LPV/r, which is used as first-line treatment in children. Failure to boost LPV/r, ideally with the addition of ritonavir, or worse still, in early HIV/TB a switch to ritonavir as a single PI with rifampicinbased co-treatment (recommended by treatment guidelines at the time) has resulted in PI-associated RMs.[10,11] Adolescence is also a challenging time for adherence. The abovementioned factors possibly conspire to increase the risks of VF and resistance in children and adolescents compared with their adult counterparts.

Virological failure in children

In children with VF, if issues related to poor adherence can be addressed, and re-suppression is not achieved while on the current

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IN PRACTICE

regimen, a switch to a second- or third-line regimen may be indicated. Currently, children failing a first-line NNRTI-based regimen are switched to a PI-based regimen, which is fairly straightforward. More complicated is the scenario when children fail a first- or second-line PI-based regimen. Generally, PI-based regimens may allow lower adherence compared with an NNRTI-based regimen, as several mutations are required to confer resistance and rarely are selected, i.e. there is a high genetic barrier to resistance. The World Health Organization (WHO) recommends a switch from failing PI-based to NNRTI-based ART.[3] However, this alternative has not been studied well and should be further investigated. Resistance testing may be helpful to guide the further management and to select drugs that can be included in the next regimen. The clinical use of resistance testing depends on which drugs were included in the initial regimen and the availability of other agents. These second- or third-line regimens following PI-based ART usually include integrase strand transfer inhibitors (INSTIs), a PI (older or new generation) and possibly an NNRTI (new generation). In SA, atazanavir is routinely available for children >12 years of age and darunavir on a special application basis for children >3 years old. Children able to access these options generally do well clinically and virologically on third-line regimens.[3,12-14] Switching to a new susceptible regimen is the gold standard in managing children with VF. However, in the face of ongoing adherence challenges with potential accumulation of RMs, and limited treatment options due to extensive resistance and limited approved paediatric formulations, other strategies, such as continuing a failing PI regimen, switching to a holding regimen or discontinuing ART, have been used.[15,16] In comparative studies in the USA and SA, switching to a definitive regimen has been shown to have preferable virological and immunological outcomes than when children remain on their failing regimen, switch to a holding regimen or discontinue ART.[15,16]

Holding regimens

In cases where ongoing poor adherence is expected and there is concern regarding increased accumulation of RMs, or where few new drugs are available, strategies to ‘buy time’ while improving adherence have been employed. Holding regimens are defined as a switch to one or more NRTIs to provide some clinical and immunological benefit without the expectation of full viral suppression until adherence can be achieved and/or an alternative regimen can be obtained. Most commonly, lamivudine monotherapy is used as a holding regimen in children with known lamivudine resistance, on the premise that the lamivudine-associated M184V mutation reduces viral replication.[17] While this may be an option in certain situations, it should be used with caution and not as a default regimen in children who fail ART. Few data exist on the safety and efficacy of this holding regimen. Studies generally show immunological and sometimes clinical deterioration when this strategy is used. Studies from Johannesburg, the Eastern Cape and the multicentre International epidemiology Databases to Evaluate AIDS (IeDEA) cohort, reported a ≤25% decline in CD4+ count compared with time of switch after 6 months of lamivudine monotherapy in up to 72% of children, while in another study 8% of children deteriorated to WHO stage 3 or 4 disease.[18-20] The only randomised controlled study comparing lamivudine monotherapy with continuation of a failing PI-based regimen, IMPAACT P1094, enrolled 33 children and adolescents; it was discontinued owing to lack of accrual and delays in approval by ethics committees.[21] This study reported a >30% decline in CD4+ count in those receiving lamivudine monotherapy compared with those continuing a failing PI without clinical deterioration, leading to a recommendation by some guideline bodies that this strategy should not be routinely

recommended.[21,22] Using additional NRTIs does not appear to mitigate CD4+ count decline. A study from New York, where children failing a PI-based regimen continued with ≥2 NRTIs, showed that at 48 weeks, there was a statistically significant decline in CD4+ count compared with baseline; however, there was no control group.[23] An additional concern with holding regimens that allow continuing viraemia is the possibility of increased risks of neurocognitive decline in children. HIV-infected children, even those who receive ART, have significant neurocognitive delay compared with their HIVunexposed and HIV-exposed uninfected counterparts.[24] In the context of planned treatment interruption in the Children with HIV Early Antiretroviral Therapy (CHER) trial, motor development was affected.[25] Nevertheless, with close observation and re-initiation of ART, recovery was possible (B Laughton – personal communication). The Paediatric European Network for Treatment of AIDS 11 (PENTA 11) study found no neurocognitive deterioration with ART interruption.[26] In adults, treatment interruption is discouraged, largely based on the Strategies for Management of Antiretroviral Therapy (SMART) study, which found poorer outcomes in those who discontinued ART than in those who continued while being suppressed, attributable to unchecked inflammation and increased risk of cardiovascular disease.[27] In contrast, in children, no adverse clinical effects of short-term treatment interruptions have been observed. The reasons for halting the treatment interruption studies in children, such as in the OHP-03, have not been because of safety, but owing to low treatment interruption durability, i.e. futility of their intended purpose to lead to remission.[25,28,29] One of the motivations for the use of a holding regimen is to allow children and adolescents to practise adherence to their ART regimen. This may be advantageous, but may also introduce new adherence challenges and misunderstandings. For instance, children may misinterpret lamivudine monotherapy as a safe and easy regimen and may prefer it to ART. This could make it difficult to switch back to a suppressive regimen when necessary, based on immunological or clinical criteria. Children who receive lamivudine monotherapy also require intense clinical and adherence follow-up, including at least 3-monthly CD4+ count monitoring. This may be problematic for children who have socioeconomic problems at the heart of their poor adherence, where increased visits are simply not affordable. Ongoing enhanced adherence support is essential in these children and their families to enable an eventual switch back to a definitive ART regimen. An additional factor is that lamivudine monotherapy administered by less experienced clinicians may result in children and adolescents only accessing suppressive ART after severe clinical and immunological deterioration. Therefore, construing this option as safe for children may be misleading for clinicians and caregivers and should not be a default option in all children who fail ART, especially those failing second-line regimens.

Recommendations for lamivudine monotherapy in children

There are, however, specific situations where it may be necessary to consider a holding regimen. We propose the following inclusion criteria for recommending lamivudine monotherapy or holding regimens: • Clinically well child (growth stable along centiles, no current or recent clinical disease expected to recur or re verse remission with immunological deterioration, including most WHO stage 4 conditions, such as extrapulmonary TB, cryptococcal disease, Mycobacterium avium complex, lymphoma, Kaposi sarcoma and HIV-associated neurological disease). Children with proven previous pulmonary TB should be excluded.

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• CD4+ count >30% and >500 cells/µL – to be checked 3-monthly. • Able to attend the clinic for monthly follow-up. • Able to conduct adherence counselling and support at each clinic visit. • Child should be >5 years old, unless there are no other options for treatment. • Success of lamivudine treatment should be measured by a switch to a definitive ART regimen.

New regimens for children/adolescents

There are problems with constructing new regimens for children with extensive resistance, which include challenges with regard to dosing and safety data for new ARVs, TB co-treatment, cost and availability. However, it is anticipated that newer drugs, such as dolutegravir, with a reduced side-effect and improved resistance profile, will be available in the next few years. It is hoped that these drugs will reduce the need for regimen switches in children with VF. Other new INSTIs, NNRTIs and PIs are currently being evaluated in phase I/II studies, as are improved formulations for delivery, such as injectable ARVs, including cabotegravir and rilpivirine. Research is also being done on therapeutic HIV vaccines and neutralising antibodies as treatment adjuvants. Investigation of new drugs in children is often delayed compared with that in adolescents and adults; often these studies do not include formulations palatable and easy to administer in children. However, over recent years there has been substantial progress in drug development, with numerous studies evaluating new ART in newborns, children and adolescents, making it likely that in the near future improved variety and efficacy of therapeutic options will be available for children.

Conclusion

The management of VF in children is challenging. Improving adherence is the most important component. Key management points to consider are: minimising the accumulation of resistance mutations, ensuring that the child’s clinical condition remains stable, preventing new opportunistic infections or reversing remission of latent infections, and optimising growth and neurocognitive and educational development. Alternative options to fully suppressive ART should be used only in special circumstances, with substantial support, rather than as a default option. Acknowledgements. We acknowledge all the children and their families whom we have the privilege of caring for. Author contributions. All authors were involved in conceiving the manuscript and developing its content. All authors reviewed the manuscript and approved the final version. Funding. LF and CF are supported by the President’s Emergency Plan for AIDS Relief (PEPFAR)/United States Agency for International Development (USAID) funding (ref. no. IU0IGH002094_01). Conflicts of interest. None. 1. United States Agency for International Development. Get on the Fast-Track. Finding Solutions for Everyone at Every Stage of Life. Washington, DC: USAID, 2016. 2. Violari A, Cotton MF, Gibb DM, et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 2008;359(21):2233-2244. https://doi.org/10.1056/NEJMoa0800971

3. World Health Organization. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. Geneva: WHO, 2013. 4. National Department of Health. National Consolidated Guidelines for the Prevention of Mother-toChild Transmission of HIV (PMTCT) and the Management of HIV in Children, Adolescents and Adults. Pretoria: NDoH, 2015. 5. Davies MA, Moultrie H, Eley B, et al. Virologic failure and second-line antiretroviral therapy in children in South Africa – the IeDEA southern Africa collaboration. J Acquir Immune Defic Syndr 2011;56(3):270-288. https://doi.org/10.1097/QAI.0b013e3182060610 6. Muri L, Gamell A, Ntamatungiro AJ, et al. Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: An emerging public health concern. AIDS 2017;31(1):61-70. https://doi.org/10.1097/qad.0000000000001273 7. Church JD, Mwatha A, Bagenda D, et al. In utero HIV infection is associated with an increased risk of nevirapine resistance in Ugandan infants who were exposed to perinatal single dose nevirapine. AIDS Res Human Retrovirus 2009;25(7):673-677. https://doi.org/10.1089/aid.2009.0003 8. Martinson NA, Morris L, Gray G, et al. Selection and persistence of viral resistance in HIV-infected children after exposure to single-dose nevirapine. J Acquir Immune Defic Syndr 2007;44(2):148-153. https://doi.org/10.1097/QAI.0b013e31802b920e 9. Kuhn L, Hunt G, Technau KG, et al. Drug resistance among newly diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis. AIDS 2014;28(11):1673-1678. https://doi. org/10.1097/qad.0000000000000261 10. Rossouw TM, Feucht UD, Melikian G, et al. Factors associated with the development of drug resistance mutations in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy in South Africa. PLoS ONE 2015;10(7):e0133452. https://doi.org/10.1371/journal.pone.0133452 11. Van Zyl GU, van der Merwe L, Claassen M, et al. Protease inhibitor resistance in South African children with virologic failure. Pediatr Infect Dis J 2009;28(12):1125-1127. https://doi.org/10.1097/ INF.0b013e3181af829d 12. Kindra G, Sipambo N, Moultrie H, Fairlie L. Outcomes in treatment with darunavir/ritonavir in ARTexperienced paediatric patients. S Afr Med J 2015;105(5):330-331. https://doi.org/10.7196/samj.9211 13. Dehority W, Abadi J, Wiznia A, Viani RM. Use of integrase inhibitors in HIV-infected children and adolescents. Drugs 2015;75(13):1483-1497. https://doi.org/10.1007/s40265-015-0446-2 14. Lazarus E, Nicol S, Frigati L, et al. Second- and third-line antiretroviral therapy for children and adolescents: A scoping review. Pediatr Infect Dis J 2017;36(5):492-499. https://doi.org/10.1097/inf.0000000000001481 15. Fairlie L, Karalius B, Patel K, et al. CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States. AIDS 2015;29(16):2109-2119. https://doi.org/10.1097/qad.0000000000000809 16. Patten G, Schomaker M, Davies M-A, et al., eds. What Should We do when HIV-positive Children Fail First-line Combination Anti-retroviral Therapy? A Comparison of 4 ART Management Strategies. Paris: International AIDS Society, 2017. 17. Gallant JE, Gerondelis PZ, Wainberg MA, et al. Nucleoside and nucleotide analogue reverse transcriptase inhibitors: A clinical review of antiretroviral resistance. Antiviral Ther 2003;8(6):489-506. 18. Linder V, Goldswain C, Adler H, et al. Lamivudine monotherapy: Experience of medium-term outcomes in HIV-infected children unable to adhere to triple therapy. Pediatr Infect Dis J 2016;35(7):e199-e205. https://doi.org/10.1097/inf.0000000000001156 19. Patten GEM, Bernheimer J, Cox V, et al. Outcomes in HIV-positive children on lamivudine monotherapy as a holding regimen in the IeDEA southern African cohorts. 8th International Workshop on HIV Pediatrics, 15 - 16 July 2016, Durban, South Africa. http://www.virology-education. com/event/previous/hiv-pediatrics-workshop-2016/ (accessed 6 November 2017). 20. Lazarus EM, Otwombe K, Fairlie L, et al. Lamivudine monotherapy as a holding strategy in HIV-infected children in South Africa. J AIDS Clin Res 2013;4(10):246-251. https://doi.org/10.4172/2155-6113.1000246 21. Agwu AL, Warshaw M, McFarland E, et al. Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial. PLoS ONE 2017;12(6):e0178075. https://doi.org/10.1371/journal.pone.0178075. 22. Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 2017. https://aidsinfo.nih.gov/guidelines/ html/2/pediatric-arv/0 (accessed 6 November 2017). 23. Abadi J, Sprecher E, Rosenberg MG, et al. Partial treatment interruption of protease inhibitor-based highly active antiretroviral therapy regimens in HIV-infected children. J Acquir Immune Defic Syndr 2006;41(3):298-303. https://doi.org/10.1097/01.qai.0000197078.41150.0d 24. Boivin M, Chernoff M, Zimmer B, et al. Neuropsychological performance in African children with HIV enrolled in a multi-site anti-retroviral clinical trial is poorer than non-infected children at those study sites. 8th International Workshop on HIV Pediatrics, 15 - 16 July 2016, Durban, South Africa. http://www.virology-education.com/event/previous/hiv-pediatrics-workshop-2016/ (accessed 6 November 2017). 25. Cotton MF, Violari A, Otwombe K, et al. Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: Results from the children with HIV early antiretroviral (CHER) randomised trial. Lancet 2013;382(9904):1555-1563. https://doi.org/10.1016/ s0140-6736(13)61409-9 26. Ananworanich J, Melvin D, Amador JT, et al. Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption. AIDS 2016;30(7):10751081. https://doi.org/10.1097/qad.0000000000001011 27. El-Sadr WM, Lundgren J, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006;355(22):2283-2296. https://doi.org/10.1056/NEJMoa062360 28. Wamalwa D, Benki-Nugent S, Langat A, et al. Treatment interruption after 2-year antiretroviral treatment initiated during acute/early HIV in infancy. AIDS 2016;30(15):2303-2313. https://doi.org/10.1097/ qad.0000000000001158 29. Klein N, Sefe D, Mosconi I, et al. The immunological and virological consequences of planned treatment interruptions in children with HIV infection. PLoS ONE 2013;8(10):e76582. https://doi. org/10.1371/journal.pone.0076582

Accepted 28 September 2017.

December 2017, Print edition

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

IN PRACTICE

ISSUES IN PUBLIC HEALTH

Prevalence and predictors of late presentation for HIV care in South Africa H N Fomundam,1 PharmD; A R Tesfay,1 MSc (Med); S A Mushipe,1 MPH; M B Mosina,1 BSc; C T Boshielo,1 MPH; H T Nyambi,1 BA; A Larsen,2 MPH; M Cheyip,2 MSc (Med); A Getahun,2 MD, MPH; Y Pillay,3 PhD Howard University Global Initiative South Africa, Howard University, Pretoria, South Africa Division of Global HIV/AIDS and Tuberculosis, Centers for Disease Control and Prevention, Pretoria, South Africa 3 Strategic Health Programmes, National Department of Health, Pretoria, South Africa 1 2

Corresponding author: A R Tesfay (abrahamrezene@yahoo.com) Background. Many people living with HIV in South Africa (SA) are not aware of their seropositive status and are diagnosed late during the course of HIV infection. These individuals do not obtain the full benefit from available HIV care and treatment services. Objectives. To describe the prevalence of late presentation for HIV care among newly diagnosed HIV-positive individuals and evaluate sociodemographic variables associated with late presentation for HIV care in three high-burden districts of SA. Methods. We used data abstracted from records of 8 138 newly diagnosed HIV-positive individuals in 35 clinics between 1 June 2014 and 31 March 2015 to determine the prevalence of late presentation among newly diagnosed HIV-positive individuals in selected highprevalence health districts. Individuals were categorised as ‘moderately late’, ‘very late’ or ‘extremely late’ presenters based on specified criteria. Descriptive analysis was performed to measure the prevalence of late presentation, and multivariate regression analysis was conducted to identify variables independently associated with extremely late presentation. Results. Overall, 79% of the newly diagnosed cases presented for HIV care late in the course of HIV infection (CD4+ count ≤500 cells/ µL and/or AIDS-defining illness in World Health Organization (WHO) stage III/IV), 19% presented moderately late (CD4+ count 351 500 cells/µL and WHO clinical stage I or II), 27% presented very late (CD4+ count 201 - 350 cells/µL or WHO clinical stage III), and 33% presented extremely late (CD4+ count ≤200 cells/µL and/or WHO clinical stage IV) for HIV care. Multivariate regression analysis indicated that males, non-pregnant women, individuals aged >30 years, and those accessing care in facilities located in townships and inner cities were more likely to present late for HIV care. Conclusions. The majority of newly diagnosed HIV-positive individuals in the three high-burden districts (Gert Sibande, uThukela and City of Johannesburg) presented for HIV care late in the course of HIV infection. Interventions that encourage early presentation for HIV care should be prioritised in SA and should target males, non-pregnant women, individuals aged >30 years and those accessing care in facilities located in inner cities and urban townships. S Afr Med J 2017;107(12):1058-1064. DOI:10.7196/SAMJ.2017.v107i12.12358

More than 6.4 million people are currently living with HIV infection in South Africa (SA), and ~400 000 new HIV infections occur each year.[1] With the adoption of policies such as nurse-initiated management of antiretroviral therapy (ART) services and the re-engineering of primary healthcare, SA has managed to rapidly expand ART services to people living with HIV.[1] Massive HIV counselling and testing (HCT) campaigns have been conducted since 2010 to hasten diagnosis and facilitate early presentation to care, but a significant number of people living with HIV are still diagnosed late during the course of HIV infection.[2] Universal HIV therapy leading to viral suppression is critical to ending the HIV epidemic in SA and other parts of the world.[3] People living with HIV can derive maximum benefit from ART if they are diagnosed and receive treatment early in the course of HIV infection.[4] The SA government has adopted the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 strategy: diagnosing 90% of people living with HIV, putting 90% of people with diagnosed HIV on treatment, and achieving viral suppression in 90% of people receiving ART services by 2020.[3] Despite effective treatment services, data from the 2014 national population-based HIV survey in SA indicated that 62% of men and 45% of women living with HIV infection had yet to be diagnosed and

were not aware of their seropositive status.[1] The prevalence of late presentation for HIV care ranges from 30% in developed countries to >70% in African countries.[5-7] A study conducted in Brazil showed that ~40% of HIV-infected individuals presented late for HIV care, 70% of the late presenters had severe clinical and immunological impairment, and ~30% were diagnosed only at death.[8] People living with HIV infection can achieve viral suppression if they receive sustained combination ART.[9,10] HIV-infected individuals on ART are less likely to transmit HIV infection to their sexual partners than those who are not on ART, as ART can lead to viral suppression and significantly reduce the risk of sexual transmission of HIV infection.[11,12] Early initiation of ART during the asymptomatic phase of the HIV infection can also greatly reduce the risk of progression to symptomatic HIV disease and death.[13] Late presentation for HIV care is associated with an increased likelihood of progression to AIDS. HIV-positive individuals who present late for HIV care also experience an increased risk of mortality.[14-18] It has been reported that premature death due to late presentation for HIV care accounts for ~40% of all AIDS-related deaths.[19] Management of individuals living with HIV who present late for care with advanced clinical manifestations of AIDS and severely compromised immune systems

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is extremely expensive, as they suffer more morbidity and utilise more medical care resources than similar patients who present early. [20] Epidemiological data indicate that ART significantly reduces the risk of HIV transmission in heterosexual serodiscordant couples. [11,21] The incidence of HIV infection decreased over time in locations where a high level of ART coverage was achieved through successful scale-up of HIV treatment services.[10,22,23]

Objectives

To describe late presentation for HIV care among newly diagnosed HIV-positive individuals based on disease progression and to identify potential predictors of late presentation for HIV care.

Methods

This study was conducted in 35 purposefully selected primary healthcare (PHC) clinics. The clinics were selected from three high HIV burden districts of SA (Gert Sibande, uThukela and City of Johannesburg). PHCs that could generate quality clinical data (phase 6) for newly diagnosed HIV-positive individuals were identified in each district. PHC clinics were selected based on the prevalence of HIV, the HIV positivity rate and the quality of clinical data available in the clinics. All newly diagnosed HIV-positive individuals aged ≥12 years who received their first positive test result for HIV between 1 June 2014 and 31 March 2015 were included in this study, in line with the HCT guideline of SA.[24] Newly diagnosed HIV-positive individuals with missing CD4+ measurements in their clinical records were excluded from the analysis. Data on sociodemographic and clinical variables of newly diagnosed HIV cases were collected. Facilities were classified into rural, urban township, urban suburb or urban inner city, based on the location of the facility. Facilities in rural settlements away from cities and towns where agriculture is the mainstay of the economic activities were classified as ‘rural’. Facilities located in a central business district of an urban setting were classified as ‘urban inner city’. Statistics South Africa classification of household income was used to classify urban facilities further into ‘urban township’ and ‘urban suburb’.[25] Facilities located in a formal settlement of middle-income communities were classified as ‘urban

township’. Facilities located in a suburb of upper-income communities were classified as ‘urban suburb’. Other sociodemographic data such as education, employment and income are not routinely documented in clinical records, so were not included in this study. Clinical data related to HCT and clinical screening and laboratory monitoring services provided to newly diagnosed HIV-positive individuals were collected from various clinical registers and records through clinical record review using a standardised case record form. Computerised data quality verification was performed using STATA version 14.1 software (StataCorp, USA) to detect and correct data entry errors. The dataset was analysed to determine the prevalence and predictors of late presentation for HIV care. Late presentation for HIV care was largely defined based on the 2014 HIV treatment guideline of SA.[26] Cues were also taken from historical SA ART guidelines to determine the cut-off point when classifying late presenters into three subcategories based on CD4+ measurement and World Health Organization (WHO) clinical staging. The 2014 ART guideline suggests that people living with HIV who enter care with a CD4+ count of ≤500 cells/µL are unable to benefit fully from ART, so are considered late presenters. WHO clinical staging and CD4+ measurement are both independent parameters that assist clinicians to determine ART eligibility of newly diagnosed HIV cases.[26] For the purpose of this analysis, late presentation for HIV care refers to an HIV-positive individual whose HIV diagnosis was done when the CD4+ cell count had dropped to ≤500 cells/µL and/or who had clinical manifestations of AIDS at the time of diagnosis.[24,26] Fig. 1 shows the matrix used to classify late presenters further into ‘moderately late presentation’, ‘very late presentation’ and ‘extremely late presentation’, based on level of disease progression measured by CD4+ count and WHO clinical staging. Newly diagnosed HIVpositive individuals with a baseline CD4+ count of 351 - 500 cells/ µL, excluding those presenting with clinical manifestations of AIDS in WHO stage III or IV, were classified as having moderately late presentation for HIV care. Newly diagnosed HIV-positive individuals with clinical manifestations of AIDS in WHO clinical stage III irrespective of CD4+ count, and/or with a CD4+ count

Fig. 1. Classification matrix for late presenters. (WHO = World Health Organization.)

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of 201 - 350 cells/µL, excluding those presenting in WHO stage IV, were classified as having very late presentation for HIV care. Newly diagnosed HIV-positive individuals presenting with clinical manifestations of AIDS in WHO clinical stage IV irrespective of CD4+ count, and/or with a CD4+ count ≤200 cells/µL irrespective of WHO staging, were classified as having extremely late presentation for HIV care. Individuals whose CD4+ count was missing were excluded from the analysis. Those who were not clinically staged according to WHO staging were classified based on CD4+ count criteria alone. A cross-sectional analysis to determine the proportion of newly diagnosed HIV-positive individuals presenting late for HIV care was computed using the definitions outlined above. The distribution of late presentation was examined by sex, age group, pregnancy status, health facility, district and facility location using χ2 tests. Special emphasis was given to the ‘extremely late presentation’ outcome, and further analysis was carried out to identify variables associated with this outcome. Univariate regression analysis was performed to examine associations between extremely late presentation for HIV care and sociodemographic variables. Multivariate logistic regression analysis was conducted to identify variables independently associated with extremely late presentation for HIV care. Variables were included in the regression model using a backward elimination approach. A p-value of >0.05 was used to eliminate variables that did not show significant effect from the model. Individuals with missing CD4+ counts were excluded from the analysis. The protocol for the pre-ART surveillance project was approved by the Associate Director of Science at the US Centers for Disease Control

and Prevention, Division of Global HIV/AIDS and Tuberculosis (ref. no. 00000891) and by the Research Ethics Committee at the School of Health Sciences and Public Health at the University of Pretoria (ref. no. 169/2013). Howard University also obtained relevant permissions from the national and the respective provincial departments of health of SA.

Results

We identified 12 413 newly diagnosed HIV-positive individuals in 35 PHC facilities who were eligible for inclusion in the analysis based on the criteria outlined under ‘Methods’. About 34% of these individuals were excluded from the analysis owing to missing CD4+ counts in their clinical records. Generally, the sex distribution of individuals who were excluded from the study was similar to that of those who were included, with the majority of newly diagnosed HIV-positive individuals being women (69%). There was also no major difference between individuals included in the study and individuals excluded in terms of age distribution, pregnancy status and district. Most (73%) of the newly diagnosed individuals were between the ages of 21 and 40 years (Table 1). WHO clinical staging information was available for 47% of the study subjects, of whom <1% were classified as stage IV and 6% as stage III. About 32% of study subjects had a recorded baseline CD4+ count ≤200 cells/µL and 22% a CD4+ count >500 cells/µL. About three-quarters of newly diagnosed individuals were known to be eligible for ART initiation at the date of diagnosis based on the national ART eligibility guideline.[24] Overall, more than three-

Table 1. Characteristics of newly diagnosed HIV-positive cases presenting late for HIV care in three high-burden districts of South Africa, June 2014 - March 2015 Presentation categories Total HIV cases, N

Early presentation, n (%)

Moderately late presentation, n (%)

Very late presentation, n (%)

Extremely late presentation, n (%)

Female

5 601

1 411 (25.2)

1 189 (21.2)

1 506 (26.9)

1 495 (26.7)

Male

2 533

350 (13.8)

367 (14.5)

663 (26.2)

1 153 (45.5)

12 - 20

665

193 (29.0)

159 (23.9)

192 (28.9)

121 (18.2)

21 - 30

3 421

890 (26.0)

730 (21.3)

937 (27.4)

864 (25.3)

31 - 40

2 484

422 (17.0)

432 (17.4)

675 (27.2)

955 (38.4)

41 - 50

1 073

184 (17.1)

169 (15.8)

236 (22.0)

484 (45.1)

>50

467

67 (14.3)

61 (13.1)

116 (24.8)

223 (47.8)

Yes

1 640

446 (27.2)

448 (27.3)

472 (28.8)

274 (16.7)

3 374

789 (23.4)

611 (18.1)

914 (27.1)

1 060 (31.4)

Gert Sibande

3 145

635 (20.2)

595 (18.9)

924 (29.4)

991 (31.5)

Johannesburg

2 306

401 (17.4)

455 (19.7)

584 (25.3)

866 (37.6)

uThukela

2 687

726 (27.0)

507 (18.9)

664 (24.7)

790 (29.4)

Rural

1 388

380 (27.4)

266 (19.2)

334 (24.1)

408 (29.4)

Urban suburb

1 478

364 (24.6)

251 (17.0)

387 (26.2)

476 (32.2)

Urban township

4 983

959 (19.2)

987 (19.8)

1 393 (28.0)

1 644 (33.0)

Urban inner city

289

59 (20.4)

53 (18.3)

58 (20.1)

119 (41.2)

8 138

1 762 (21.7)

1 557 (19.1)

2 172 (26.7)

2 648 (32.5)

Sociodemographic variables Sex

Age category (yr)

Pregnancy

District

Location of facilities

Total HIV cases

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Table 2. Proportions of newly diagnosed HIV-positive individuals presenting extremely late HIV care in three high-burden districts in South Africa, disaggregated by age and sex, June 2014 - March 2015 Total newly diagnosed HIV cases, N

Extremely late presenters, n (%)

Age category (yr)

Female

Male

Female

Male

12 - 20

586

90 (15.4)

31 (39.2)

21 - 30

2 663

750

587 (22.0)

272 (36.3)

31 - 40

1 465

1 012

483 (33.0)

466 (46.0)

41 - 50

613

460

228 (37.2)

256 (55.7)

>50

245

221

100 (40.8)

123 (55.7)

Total

5 572

2 522

1 488 (26.7)

1 148 (45.5)

quarters of the study cases presented late for HIV care, with 19% presenting moderately late (CD4+ count 351 - 500 cells/µL and/ or WHO clinical stage I or II), 27% presenting very late (CD4+ count 201 - 350 cells/µL and/or WHO clinical stage III), and 33% presenting extremely late (CD4+ count ≤200 cells/µL and/or WHO clinical stage IV). A subanalysis was conducted to describe extremely late presentation among newly diagnosed HIV-positive individuals by gender and age. Generally, the proportion of males presenting extremely late for HIV care was much higher than that of females across all age categories. More than half of males aged ≥40 years presented for HIV care extremely late with a CD4+ count ≤200 cells/µL and/or WHO clinical stage IV. The widest gap between the proportion of males and females presenting extremely late for HIV care was observed in the age category 12 - 20 years, in which the proportion of males exceeded the proportion of females by 24% (Table 2). Multivariate logistic regression analysis was conducted to determine the likelihood of extremely late presentation for HIV care at each level v. the likelihood of early presentation. Males were far more likely than their female counterparts to present extremely late (adjusted odds ratio (AOR) 2.7, 95% confidence interval (CI) 1.5 - 4.9) v. early. The analysis showed a strong association between age at diagnosis and extremely late presentation. Newly diagnosed HIV-positive individuals aged ≥51 years were more likely to present extremely late for HIV care compared with individuals in the age group 12 - 20 years (AOR 3.4, 95% CI 2.4 - 4.9). Similarly, individuals aged 30 - 50 years were at least 2.6 times more likely to present extremely late for HIV care compared with individuals in the age group 12 - 20 years. Pregnant women were less likely to present extremely late for HIV care compared with women who were not pregnant (AOR 0.53, 95% CI 0.44 - 0.64). Newly diagnosed HIV-positive individuals accessing care in facilities located in urban townships (AOR 1.6, 95% CI 1.4 - 1.5) and inner cities (AOR 1.5, 95% CI 1.1 - 2.2) were more likely to present extremely late for HIV care compared with HIV-positive individuals accessing care in rural facilities (Table 3).

Discussion

The current analysis shows that a third of newly diagnosed HIV-positive individuals were not effectively linked to HIV care and/or did not have a documented CD4+ result. There are two possible explanations for the observed gap in the clinical data. Most newly diagnosed HIVpositive individuals with missing or incomplete clinical records may be considered early losses to follow-up. This may represent a real gap in clinical service delivery. The current data show that a third of newly diagnosed HIV-positive individuals did not gain immediate benefit from available healthcare services. Similar rates of loss to follow-up have been reported among newly diagnosed HIV-positive individuals

Table 3. Sociodemographic variables and the likelihood of extremely late presentation for HIV care among newly diagnosed HIV-positive individuals in three high-burden districts of South Africa, June 2014 - March 2015 Early presenters, n

Extremely late presenters

Female

1 411

1 503

Male

350

1 153

2.73 (1.50 - 4.94)

Sociodemographic variables

AOR (95% CI)

Sex

Age (yr)

12 - 20

193

121

21 - 30

890

864

1.34 (1.04 - 1.73)

31 - 40

422

955

2.6 (1.99 - 3.39)

41 - 50

184

486

2.72 (2.02 - 3.66)

>50

223

3.4 (2.35 - 4.92)

446

274

Yes

789

1 060

0.53 (0.44 - 0.64)

Pregnancy

Location of facilities

Rural

380

408

Urban inner city

364

476

1.52 (1.06 - 2.20)

Urban suburb

959

1 644

1.16 (0.94 - 1.43)

Urban township

119

1.59 (1.34 - 1.90)

AOR = adjusted odds ratio; CI = confidence interval.

in other studies.[27,28] Recording and transcription errors may also result in crucial clinical data being missed. Substandard clinical data can compromise the ability to research and understand the provision of quality healthcare.[29] Clinical record systems need continuous improvement to reflect the state of the healthcare system accurately and assist in rational decision-making. More than three-quarters of the 8 138 newly diagnosed HIVpositive individuals in this study presented late for HIV care with a CD4+ count ≤500 cells/µL and/or WHO clinical stage III/IV disease, and one-third presented extremely late for HIV care with a CD4+ count of ≤200 cells/µL and/or WHO clinical stage IV disease. Sex, age and pregnancy status were independently associated with the likelihood of late presentation for HIV care. Late presentation for HIV care tended to be more prevalent among males, older people, non-pregnant women and individuals accessing care in facilities located in inner cities and urban townships compared with females, younger people, pregnant women and individuals accessing care

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in rural facilities. These findings are consistent with what has been observed in other studies, taking into account differences in the definition of the term ‘late presentation’.[5-7,30] An attempt was made to provide a more detailed description of presentation to care by looking into the full spectrum spanning from early presentation to extremely late presentation and analysing the subcategories across sociodemographic groups. The present study found that the prevalence of late presentation for HIV care was exceptionally high among males in general, and older males in particular, compared with their female or younger counterparts. This finding is consistent with similar studies from SA[28] and elsewhere in the sub-Saharan African region.[30-33] While the national scale-up of ART in SA has resulted in gains in life expectancy for both men and women, the gains have disproportionately benefited women, further confirming that men are failing to interact with the health system early enough to improve their health outcomes.[34,35] These studies collectively highlight an urgent need to target men, and in particular older men, to encourage uptake of HIV testing with the ultimate goal of reducing late presentation for HIV care. The differential in late presentation by sex and age has been explained in prior studies as the combined effects of social norms,[31-37] health knowledge,[32,38] age-specific progression of disease[34-38] and the policy environment.[39] Social constructs of masculinity were cited as a barrier to health-seeking in Zimbabwe,[36] while a study conducted across sub-Saharan Africa found that men aged >50 years exhibited a disproportionately low level of knowledge of HIV.[38] Previous studies note evidence that seroconversion at older ages is associated with more aggressive disease progression, so that individuals infected later in life are more likely than those infected at a younger age to present for HIV care with lower CD4+ counts. Other factors that may also play a role in delaying HIV testing among older males include fear and stigma associated with HIV infection, alcohol and drug abuse, traditional beliefs associated with HIV, language and cultural obstacles.[40] Some barriers are modifiable, and a combination of strategies directed at both individual and social levels can ameliorate the observed late presentation of older men to HIV care. It is important to note that younger males in the age group 12 20 years experienced a disproportionately higher prevalence of extremely late presentation for HIV care compared with their female counterparts in the same age group. Women in their teens are more likely than males to interact with the healthcare system as they seek reproductive healthcare. Survey data indicate that ~30% of teenage women in SA reported ever having been pregnant.[41] Pregnancy can facilitate early diagnosis of HIV, as HCT services are routinely offered to all pregnant women during antenatal care.[42] Teenage males do not benefit from similar interventions that can hasten HIV diagnosis. An innovative strategy is therefore needed to facilitate access to healthcare services for young males. The current analysis also shows that the rate of late presentation for HIV care is higher in facilities located in inner cities and urban townships than in facilities in rural areas. Migration patterns and several barriers to care may explain the observed findings. Workrelated internal migration is common in SA, especially among older males. People migrate from their rural homes to urban centres in search of work and better living conditions.[43] This phenomenon has increased the burden of care in urban health facilities, resulting in congestion and long waiting hours.[44] Most health facilities do not cater for the specific needs of migrants, which include extending operational hours during weekdays and opening for service over the weekend.[45] These factors may compromise access to care for people in inner cities and townships and discourage them from seeking HIV testing early, resulting in late presentation for HIV care.

Several other barriers have been reported to contribute to a high prevalence of late presentation for HIV care. Fear can be a significant barrier to early presentation, including fear of the disease itself, fear of disclosure and fear of subsequent social stigma, discrimination and criminalisation of risk behaviours.[46] A study in Uganda suggested that close relatives of individuals who were assumed to be infected with HIV were less likely to seek HIV testing.[47] Some beliefs and cultural norms associated with HIV, such as ‘AIDS is caused by witchcraft’, discourage people from seeking HIV testing and presenting to care early.[48] It has been reported that premature death due to late presentation for HIV care accounts for ~40% of all AIDS-related deaths.[49] The results of this study highlight a profile of individuals that should be targeted by policies and programmes as a matter of urgency to encourage early presentation to HIV care and timely initiation of treatment, and ultimately to reduce viral load and prevent death from HIV/AIDS.

Study limitations

This study has some limitations that could have influenced the observed findings. The sample was not selected based on a probability sampling strategy. As such, the sample population may not be representative of the total population of newly diagnosed HIVpositive individuals in SA. Diverse facilities from urban, periurban and rural settings are represented in this analysis, which generated a large sample size. The results may be a reflection of presentation to care in SA. However, it may not be possible to extrapolate the findings to newly diagnosed individuals not included in the study. Presentation to care could not be determined for a third of newly diagnosed HIV-positive individuals owing to missing CD4+ counts. Exclusion of these individuals from the analysis could have influenced the observed outcome in either direction, depending on the distribution of missing data in the study population. This analysis was based on secondary data generated during routine clinical management of newly diagnosed HIV-positive individuals at participating facilities. The investigators could not independently ascertain the provision of services provided to HIV-positive individuals, or the lack thereof. An assumption was made that clinical records reflected service delivery. About half of the study participants did not have documented WHO staging and their presentation to HIV care was classified on the basis of CD4+ measurement alone, which may have resulted in misclassification of some cases. A study design that involved a statistically representative sample of newly diagnosed HIV-positive individuals and active collection of primary data instead of passively relying on clinical records could have improved the validity of this study and addressed the issue of missing data. We used CD4+ counts and WHO staging as markers to measure the time between HIV infection and HIV diagnosis, and a scale of presentation to care from early presentation to extremely late presentation was developed based on these markers. This could have introduced measuring bias, as the markers may not be accurate indicators of duration of HIV infection. Sociodemographic variables such as level of education, income and employment were not considered, as they are not generally reported in clinical records.

Conclusions and recommendations

Although this study used a purposeful sample, which is prone to selection bias, the researchers found no major differences in the independent variables between individuals included and those excluded from the study and decided to proceed with analysis. The findings of this study could be an indication of presentation to care in other high HIV-volume PHC facilities in SA.

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The majority of newly diagnosed HIV-positive individuals in the 35 clinics presented for HIV care late in the course of HIV infection. Extremely late presentation for HIV care is disproportionately prevalent among older males. Facilities in townships and inner cities have a high prevalence of extremely late presentation. These findings are major impediments to reaching the targets set in the 90-90-90 strategy, achieving universal viral suppression, and significantly changing the trajectory of the HIV epidemic. There is a need to focus policy and programmatic efforts towards realigning the strategies of the HCT services so that they specifically target individuals and geographical locations that exhibit a high likelihood of late presentation to HIV care. Policies should be developed to incentivise men towards early engagement with the health system. Until late presentation to HIV care is urgently prioritised and drastically reduced in SA, efforts to avert numerous preventable deaths and slow the HIV/AIDS epidemic may continue to be less effective. Acknowledgements. None. Author contributions. HNF conceptualised the research approach and provided leadership and guidance during development of this manuscript. ART compiled the literature review, developed the analysis plan, carried out multiple statistical analysis, developed the description of the statistical output and composed the discussion and recommendation sections of the manuscript. YP, AL, MC and AG made extensive input to the study approach, literature review, analysis plan, presentation of data and recommendations during the development of the manuscript. SAM, MBM, CTB and NTH reviewed the manuscript and made input into and organised the reference list. Funding. This research work was made possible through the support provided by the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention (CDC) under a cooperative agreement (grant no. 5U2GGH000391). The funder provided technical oversight during the development of the study design, the data analysis and the preparation of the manuscript. The opinions expressed are those of the authors and do not necessarily reflect the views of the CDC. Conflicts of interest. None.

1. Human Sciences Research Council. South African National HIV Prevalence, Incidence and Behaviour Survey. Pretoria: HSRC, 2014. http://www.hsrc.ac.za/en/research-data/view/6871 (accessed 20 June 2016). 2. South African National AIDS Council. The National HIV Counselling and Testing Campaign Strategy. Pretoria: SANAC, 2010. https://www.westerncape.gov.za/Other/2010/6/hct_campaign_ strategy_2_3_10_final.pdf (accessed 10 December 2016). 3. Joint United Nations Programme on HIV/AIDS. 90-90-90 – an Ambitious Treatment Target to Help End the AIDS Epidemic. Geneva: UNAIDS, 2014. http://www.unaids.org/en/resources/ documents/2014/90-90-90 (accessed 15 January 2016). 4. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011;356(6):493-505. https://doi. org/10.1056/NEJMoa1105243 5. Fleishman JA, Yehia BR, Moore RD, Gebo KA. The economic burden of late entry into medical care for patients with HIV infection. Med Care 2010;48(12):1071-1079. https://doi.org/10.1097/ MLR.0b013e3181f81c4a 6. Nadiaye B, Salleron J, Vincent A, et al. Factors associated with presentation to care with advanced HIV disease in Brussels and Northern France. BMC Infect Dis 2011;11:11. https://doi.org/10.1186/14712334-11-11 7. Dickson NP, McAllister S, Sharples K, Paul C. Late presentation of HIV infection among adults in New Zealand 2005 - 2010. HIV Med 2011;13(3):182-189. https://doi.org/10.1111/j.1468-1293.2011.00959.x 8. Grangeiro A, Escuder MM, Pereira JCR. Late entry into HIV care: Lessons from Brazil, 2003 to 2006. BMC Infect Dis 2012;12:99. https://doi.org/10.1186/1471-2334-12-99 9. Gill VS, Lima VD, Zhang W, et al. Improved virological outcomes in British Columbia concomitant with decreasing incidence of HIV type 1 drug resistance detection. Clin Infect Dis 2010;50(1):98-105. https://doi.org/10.1086/648729 10. Moupali DM, Chu PL, Santos G-M, et al. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS One 2010;5(6):e11068. https://doi. org/10.1371/journal.pone.0011068 11. Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: A prospective cohort analysis. Lancet 2010;375(9731):2092-2098. https://doi.org/10.1016/ S0140-6736(10)60705-2 12. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011;356(6):493-505. https://doi.org/10.1056/NEJMoa1105243

13. Anglemyer A, Rutherford GW, Easterbrook PJ, et al. Early initiation of antiretroviral therapy in HIV-infected adults and adolescents: A systematic review. AIDS 2014;28(2):S105-S118. https://doi. org/10.1097/QAD.0000000000000232 14. Tuboi SH, Schechter M, McGowan CC, et al. Mortality during the first year of potent antiretroviral therapy in HIV-1-infected patients in 7 sites throughout Latin America and the Caribbean. J Acquir Immune Defic Syndr 2009;51(5):615-623. https://doi.org/10.1097/QAI.0b013e3181a44f0a 15. Harrison KM, Song R, Zhang X. Life expectancy after HIV diagnosis based on national HIV surveillance data from 25 states, United States. J Acquir Immune Defic Syndr 2007;53(1):124 -130. https://doi.org/10.1097/QAI.0b013e3181b563e7 16. Lawn SD, Little F, Bekker LG, et al. Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa. N Engl J Med 2009;23(3):335-342. https://doi.org/10.1097/ QAD.0b013e328321823f 17. Egger M, May M, Chêne G, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: A collaborative analysis of prospective studies. Lancet 2002;360(9327):119-129. https://doi.org/10.1016/S0140-6736(02)09411-4 18. Chasombat S, McConnell MS, Siangphoe U, et al. National expansion of antiretroviral treatment in Thailand, 2000 - 2007: Program scale-up and patient outcomes. J Acquir Immune Defic Syndr 2009;50(5):506-512. https://doi.org/10.1097/QAI.0b013e3181967602 19. Grangeiro A, Escuder MM, Menezes PR, Alencar R. Late entry into HIV care: Estimated impact on AIDS mortality rates in Brazil, 2003 - 2007. PLoS One 2011;6(1):e14585. https://doi.org/10.1371/ journal.pone.0014585 20. Leisegang R, Cleary S, Hislop M, Early and late direct costs in a Southern African antiretroviral treatment programme: A retrospective cohort analysis. PLoS Med 2009;6(12):e1000189. https://doi. org/10.1371/journal.pmed.1000189 21. Attia S, Egger M, Müller M, Zwahlen M, Low N. Sexual transmission of HIV according to viral load and antiretroviral therapy: Systematic review and meta-analysis. AIDS 2009;23(11):1397-1404. https:// doi.org/10.1097/QAD.0b013e32832b7dca 22. Wood E, Kerr T, Marshall BDL. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: Prospective cohort study. BMJ 2009;338:b1649. https://doi.org/10.1136/bmj.b1649 23. Fang CT, Hsu HM, Twu SJ, et al. Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan. J Infect Dis 2004;190(5):879-885. https://doi. org/10.1086/422601 24. National Department of Health, South Africa. National HIV Counselling and Testing Policy Guideline. Pretoria: NDoH, 2015. https://www.health-e.org.za/wp-content/uploads/2015/07/HCTGuidelines-2015.pdf (accessed 12 March 2016). 25. Statistics South Africa. Census 2011: Income dynamics and poverty status of households in South Africa. http://www.statssa.gov.za/publications/Report-03-10-10/Report-03-10-102014.pdf (accessed 4 July 2017). 26. National Department of Health, South Africa. National Consolidated Guidelines for the Prevention of Mother-to-child Transmission of HIV (PMTCT) and the Management of HIV in Children, Adolescents and Adults. Pretoria: NDoH, 2014. http://www.health.gov.za/index.php/2014-03-17-0909-38/policies-and-guidelines/category/230-2015.pdf (accessed 10 June 2016). 27. Hassan AS, Fielding KL, Thuo NM, Nabwera HM, Sanders EJ, Berkley JA. Early loss to follow-up of recently diagnosed HIV-infected adults from routine pre-ART care in a rural district hospital in Kenya: A cohort study. Trop Med Int Health 2012;17(1):82-93. https://doi.org/10.1111/j.13653156.2011.02889.x 28. Evangeli M, Newell M-L, McGrath N. Factors associated with pre-ART loss-to-follow up in adults in rural KwaZulu-Natal, South Africa: A prospective cohort study. BMC Public Health 2016;16:358. https://doi.org/10.1186/s12889-016-3025-x 29. European Medicines Agency. Guideline on Missing Data in Confirmatory Clinical Trials. London: EMA, 2010. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/09/ WC500096793.pdf (accessed 15 June 2017). 30. National Department of Health, South Africa. Operational Plan for Comprehensive HIV and AIDS Care, Management and Treatment for South Africa. Pretoria: NDoH, 2003. http://www.gov.za/sites/ www.gov.za/files/aidsoperationalplan1_0.pdf (accessed 20 July 2016). 31. Kigozi IM, Dobkin LM, Martin JN, et al. Late disease stage at presentation to an HIV clinic in the era of free antiretroviral therapy in sub-Saharan Africa. J Acquir Immune Defic Syndr 2009;52(2):280-289. https://doi.org/10.1097/QAI.0b013e3181ab6eab 32. Drain PK, Elena LE, Parker G, et al. Risk factors for late-stage HIV disease presentation at initial HIV diagnosis in Durban, South Africa. PLoS One 2013;8(1):e55305. https://doi.org/10.1371/journal. pone.0055305 33. Wanyenze RK, Kamya MR, Fatch R, et al. Missed opportunities for HIV testing and late-stage diagnosis among HIV-infected patients in Uganda. PLoS One 2011;6(7):e21794. https://doi.org/10.1371/journal. pone.0021794 34. Lahuerta M, Wu Y, Hoffman S, et al. Advanced HIV disease at entry into HIV care and initiation of antiretroviral therapy during 2006 - 2011: Findings from four sub-Saharan African countries. Clin Infect Dis 2014;58(3):432-441. https://doi.org/10.1093/cid/cit724 35. Bor J, Rosen S, Chimbindi N, et al. Mass HIV treatment and sex disparities in life expectancy: Demographic surveillance in rural South Africa. PLoS Med 2015;12(11):e1001905. https://doi. org/10.1371/journal.pmed.1001905 36. Cornell M, Schomaker M, Belen GD, et al. Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: A multicentre cohort study. PLoS Med 2012;9(9):e1001304. https://doi.org/10.1371/journal.pmed.1001304 37. Skovdal M, Campbell C, Madanhire C, et al. Masculinity as a barrier to men’s use of HIV services in Zimbabwe. Global Health 2011;7:13. https://doi.org/10.1186/1744-8603-7-13 38. Gelaw YA, Senbete GH, Adane AA, Alene KA. Determinants of late presentation to HIV/AIDS care in Southern Tigray Zone, Northern Ethiopia: An institution based case-control study. AIDS Res Ther 2015;12:40. https://doi.org/10.1186/s12981-015-0079-2 39. Negin J, Cumming RG. HIV infection in older adults in sub-Saharan Africa: Extrapolating prevalence from existing data. Bull World Health Organ 2010;88(11):847-853. https://doi.org/10.2471/ BLT.10.076349 40. Lahuerta M, Ue F, Hoffman S, et al. The problem of late ART initiation in sub-Saharan Africa: A transient aspect of scale-up or a long-term phenomenon? J Health Care Poor Underserved 2013;24(1):359-383. https://doi.org/10.1353/hpu.2013.0014 41. Yazdanpanah Y, Lange J, Gerstoft J, Cairns G. Earlier testing for HIV – how do we prevent late presentation? Antivir Ther 2010;15(1):17-24. https://doi.org/10.3851/IMP1526 42. Partners in Sexual Health. A Review of Teenage Pregnancy in South Africa – Experiences of Schooling, and Knowledge and Access to Sexual & Reproductive Health Services. Cape Town: PSH, 2013. http:// www.hst.org.za/publications/NonHST%20Publications/Teenage%20Pregnancy%20in%20South%20 Africa%20Final%2010%20May%202013.pdf (accessed 26 July 2016). 43. National Department of Health, South Africa. National HIV Counselling and Testing Policy Guideline. Pretoria: NDoH, 2015. https://www.health-e.org.za/wp-content/uploads/2015/07/HCTGuidelines-2015.pdf (accessed 12 March 2016). 44. International Institute for Environment and Development. Urbanization and Development in South Africa: Economic Imperatives, Spatial Distortions and Strategic Responses. London: IIED, 2012. http://www.delog.org/cms/upload/pdf-africa/Urbanisation_and_Development_in_South_Africa_-_ Economic_Imperatives_Spatial_Distortions_and_Strategic_Responses.pdf (accessed 8 May 2016).

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45. University of the Witwatersrand. Health Care Usersâ&#x20AC;&#x2122; Experiences and Perceptions of Waiting Time at a Diabetes Clinic in an Academic Hospital. Johannesburg: University of the Witwatersrand, 2012. http://wiredspace.wits.ac.za/xmlui/bitstream/handle/10539/14496/Health%20Care%20User's%20 Experiences%20and%20Perceptions%20of%20Waiting%20Ti.pdf ?sequence=1&isAllowed=y (accessed 16 December 2016). 46. Fomundam HN, Wutoh A, Tesfay A, et al. Surveillance of HIV-positive Pre-ART Persons in South Africa: Gap Analysis Report. Pretoria: Howard University, 2013. 47. Deblonde J, De Koker P, Hamers FF, Fontaine J, Luchters S, Temmerman M. Barriers to HIV testing in Europe: A systematic review. Eur J Public Health 2010;20(4):422-432. https://doi. org/10.1093/eurpub/ckp231

48. Netsanet F, Dessie A. Acceptance of referral for partners by clients testing positive for human immunodeficiency virus. HIV/AIDS Res Palliat Care 2013;5:19-28. https://doi.org/10.2147/HIV.S39250 49. Sovran S. Understanding culture and HIV/AIDS in sub-Saharan Africa. SAHARA J 2013;10(1):32-41. https://doi.org/10.1080/17290376.2013.807071

Accepted 29 August 2017.

Louis Washkansky being wheeled to post-transplant radiation therapy as part of the immunosuppressive regimen (photo: First Heart Transplant Museum, Groote Schuur Hospital).

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

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ISSUES IN PUBLIC HEALTH

Application opportunities of geographic information systems analysis to support achievement of the UNAIDS 90-90-90 targets in South Africa R R Lilian,1 MSc (Med); C J Grobbelaar,1 MB ChB, MFamMed; T Hurter,1 MPH; J A McIntyre,1,2 MB ChB, FRCOG; H E Struthers,1,3 PhD; R P H Peters,1 MD, PhD, DLSHTM, Dip HIV Man (SA) Anova Health Institute, Johannesburg and Cape Winelands, South Africa School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 3 Division of Infectious Diseases and HIV Medicine, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 1 2

Corresponding author: R P H Peters (peters@anovahealth.co.za)

In an effort to achieve control of the HIV epidemic, 90-90-90 targets have been proposed whereby 90% of the HIV-infected population should know their status, 90% of those diagnosed should be receiving antiretroviral therapy, and 90% of those on treatment should be virologically suppressed. In this article we present approaches for using relatively simple geographic information systems (GIS) analyses of routinely available data to support HIV programme management towards achieving the 90-90-90 targets, with a focus on South Africa (SA) and other high-prevalence settings in low- and middle-income countries. We present programme-level GIS applications to map aggregated health data and individual-level applications to track distinct patients. We illustrate these applications using data from City of Johannesburg Region D, demonstrating that GIS has great potential to guide HIV programme operations and assist in achieving the 90-90-90 targets in SA. S Afr Med J 2017;107(12):1065-1071. DOI:10.7196/SAMJ.2017.v107i12.12666

Geographic information systems (GIS) analysis refers to the capture, management, evaluation and visualisation of geographically referenced data, although the term can generally be applied to any investigation that incorporates a location variable.[1] This can range from simple maps that provide information about point locations, for example facilities, to complex spatial statistical analyses.[2] GIS is an important tool to advance public health, as many aspects of health and illness have a geographical or spatial component.[2] GIS applications may include mapping of disease distribution, assessing patterns of health interventions such as immunisations, investigating spatial and temporal trends, mapping variations in risk factors and forecasting epidemics.[2] One of the major health challenges facing South Africa (SA) and other low- and middle-income countries (LMICs), particularly in sub-Saharan Africa, is the HIV epidemic. In an effort to achieve epidemic control, the Joint United Nations Programme on HIV/ AIDS (UNAIDS) has proposed ambitious 90-90-90 targets to be achieved by 2020, whereby 90% of people infected with HIV will have received a diagnosis, 90% of those diagnosed will be receiving sustained antiretroviral therapy (ART), and 90% of those on treatment will be virally suppressed.[3] GIS analyses, often involving complex spatial statistics, have been used to investigate various aspects of the HIV epidemic in a number of countries including SA, for example to examine the distribution of HIV infection, including hot-spots or clusters of high or low prevalence;[4-17] to assess the spatial distribution of factors contributing to HIV infection;[4,14,18] to describe the spatial distribution of the HIV care continuum (HIV testing, uptake of ART, viral suppression) and the factors that affect provision of this care, including location of services;[19-27] to investigate HIV infection, prevention services and location/density of key populations, including injection drug users, men who have sex

with men and sex workers;[28-33] to guide or map prevention efforts such as male circumcision or condom distribution;[34,35] to understand patterns of HIV knowledge;[36] and to examine distribution of funding for HIV services.[37] Although some of these applications can inform efforts towards achieving the 90-90-90 objectives, to our knowledge no systematic approach has been presented to define the role of GIS in achieving these targets. Furthermore, GIS analyses may be of limited use in LMICs if complex analyses are performed that require highly skilled personnel or if the analyses primarily draw on research data, with no link to routine, programme data that can be used to inform programme implementation. In this article we present approaches for using relatively simple GIS analyses of routinely available data to support HIV programme management towards achieving the 90-90-90 targets, with a focus on SA and other high-prevalence settings in LMICs. Using data from City of Johannesburg (CoJ) Region D, we present applications at a programme level to map aggregated health data and at an individual level to track distinct patients, both of which can guide efforts towards achieving the 90-90-90 targets.

The first 90: Diagnosis of 90% of people infected with HIV

GIS can be used to guide progress towards the first 90 by mapping population groups that require improved access to HIV testing services (HTS). For example, since a high number of HIV-infected males in SA remain undiagnosed, with low HTS uptake also recorded among men in other LMICs,[38,39] visualising male population density by ward would be useful to identify specific areas with high concentrations of men. These areas, identified as wards 27, 30 and 45 in CoJ Region D (Fig. 1, A), could then be targeted for testing, for example, mobilising community health workers (CHWs) or mobile

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testing units to perform community-based testing after hours or over weekends when men, most of whom would be at work during routine clinic hours, would more likely be available for testing. Uptake of HIV testing has been shown to be particularly low among adolescent and young males aged 12 - 24 years,[40,41] and a similar map showing population density of this target group can be generated to further focus testing in areas where this specific age group is more likely to be found (Fig. 1, B). A further use of GIS to guide progress towards the first 90 is mapping of high-risk populations to direct testing for higher yield. Explanatory variables associated with HIV prevalence, many of which have been mapped in SA and LMICs,[4,12,14,18] can be simply visualised with pie charts to identify locations with populations at high risk of contracting HIV (Fig. 2).[14] This may include populations with low socioeconomic status, multiple sexual partners or high rates of intergenerational sex.[14] HTS resources could then be directed to these areas for potentially high-yield testing. Interestingly, in CoJ Region D, ward 40 appears to be a target area based on socioeconomic status (Fig. 2) as well as population density of adolescent and young males (Fig. 1, B), suggesting that focused efforts to provide HTS to this area may well assist in supporting progress toward the first 90 target. In addition, more complex GIS techniques have been used in several African settings to identify clusters or hotspots where HIV prevalence is significantly higher than in surrounding areas,[8,13,15] which may also direct testing for higher yield by identifying locations where there are likely to be higher numbers of individuals living with HIV. The application of GIS in the context of the first 90 would be largely at a programme level. Applications using individual-level data, for example plotting individuals who have undergone HIV testing, would only be of value with specific populations in small geographical areas and would therefore be of limited use in the context of the first 90, which focuses on higher-level population screening.

The second 90: 90% of people with diagnosed HIV infection on ART

Achieving the second 90% target by 2020 is likely to be a challenge in SA,[42] and closing the treatment gap will require implementation of well-considered and innovative strategies. A compelling example of how GIS can guide this process is presented in Fig. 3, where GIS analysis of routine data is used to identify geographical areas with large gaps in ART

Male population density (population/area in km2), total 443 - 2 170 2 171 - 3 897 3 898 - 5 623 5 624 - 7 350 7 351 - 9 077

Male population density (population/area in km2), 12 - 24 years 101 - 490 491 - 879 880 - 1 267 1 268 - 1 656 1 657 - 2 044

Fig. 1. Identifying the male target population for HIV testing in City of Johannesburg Region D. Population density (population/area in km2) by ward for (A) the total male population and (B) male adolescents and youth aged 12 - 24 years (Census 2011 data[43]) (the numbers on the figure are the ward numbers). Wards 27, 30 and 45 have a high density of total males and male youth. Four additional wards (15, 40, 51 and 52) also have a high density of younger males and can be targeted for HIV testing services to reach this target group.

coverage. The first step in this process is to estimate the HIV-infected population by age and gender. This is performed by multiplying population data, available from Statistics South Africa,[43] by HIV prevalence data, which are publicly available from data sources such as the Thembisa model[44] or, in the case of other LMICs, from antenatal surveillance or demographic and health surveys. The number of HIV-infected individuals receiving ART by age and gender, obtained from routine monitoring and evaluation (M&E) data, can then be subtracted from the estimated HIV-infected population to calculate the programme gap, namely the number of HIV-infected individuals who are not receiving ART. By triangulating population and M&E data in this way, the specific age and gender group with the greatest programme gap can be identified. Population and ART data for the target group in individual wards can then be overlaid and mapped to visualise wardlevel profiles (Fig. 3, B). These maps can be

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used to identify where the highest numbers of individuals who are missing from the ART programme are likely to be located, which in the case of CoJ Region D is wards 16, 33 and 37 for the male target group aged 30 - 39 years. Programme planners can thus strategically focus efforts to improve ART coverage in areas with the greatest need, including initiating communitybased awareness campaigns and expanding clinic-based services into the community through mobile clinics and alternative ART distribution points. Spatial patterns of ART coverage can be monitored over time by updating ART data in the heat maps on an ongoing basis, thereby tracking progress of interventions. In view of the recommendation for universal test and treat,[45] it is important to assess the proportion of the total HIVinfected population who are not receiving ART. This programme gap % can be calculated by dividing the programme gap by the estimated HIV-infected population.

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initiation can be mapped so that CHWs can perform home visits to link these individuals to care (sample map presented in Fig. 5; locations have been modified to protect patient confidentiality). This would not only be of clinical value for the individual patients, but would also serve to streamline CHW work and would inform programme planning by identifying areas with high numbers of individuals who are lost to initiation where communitydispensing points may be of benefit. In addition, maps can be used to identify HIVinfected individuals who live furthest from HIV clinics so that CHWs can proactively perform home visits to these high-risk individuals, as the odds of timeous ART access decrease with increasing distance from an HIV clinic, particularly for clinics located further from transportation hubs.[19,23] The distance between patient locations and HIV clinics can be calculated using Google Earth, precluding the need for advanced computer skills or expensive software,[23] and this approach would therefore be relatively easy to implement in LMICs.

Flush toilet Other toilet No toilet

The third 90: 90% of people on ART virally suppressed

Piped water in dwelling or yard Piped water on community stand No piped water

Fig. 2. Identifying potentially high-yield areas for HIV testing in City of Johannesburg Region D. Household access to (A) toilet facilities and (B) piped water by ward (Census 2011 data[43]). Wards 19, 24 and 40 (indicated by black arrows) have a lower proportion of households with flush toilets and in-dwelling or in-yard piped water and may be of lower socioeconomic status. Since low socioeconomic status is associated with an increased prevalence of HIV,[14] HIV testing services can be directed to these areas for potentially high-yield testing.

When overlaid with a heat map of the HIVinfected population, conclusions can be drawn regarding programme achievements in high-burden areas (Fig. 4). For example, in CoJ Region D, ward 11 has a large HIVinfected population among males aged 30 39 years with a very small programme gap %, indicating that only a small proportion of the HIV-infected population is missing from the ART programme. This suggests that the programme has been well managed and supported in this area. In contrast, other wards with large numbers of HIVinfected individuals have a large programme gap %, suggesting that these high-burden areas may benefit from further support. This GIS approach, which entails overlaying variables such as population estimates and programme performance, enables a nuanced approach to understanding performance of the ART programme in different areas. GIS can further assist in supporting progress to the second 90% target by generating maps of population groups at high

risk of attrition prior to ART initiation, such as males, adolescents and young adults. [46] Interventions targeting these groups for ART initiation, such as community-based adherence clubs or services over the weekend or after work and school hours, can then be planned in areas with high proportions of these populations where there is a large gap in ART initiation. In addition, geographical barriers to uptake of treatment that may contribute to poor ART coverage can be identified using GIS by visualising service utilisation together with geographical variables such as location of roads, villages and healthcare facilities. Identifying geographical barriers to uptake of services allows deployment of innovative alternatives, for example motorbikes in remote areas[47] or boats in island communities.[48] In addition to programme-level applications, individual-level GIS analyses can also assist in guiding progress towards the second 90. Residences of individuals who test HIV-positive but are lost to treatment

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The third 90 refers to viral suppression rates in individuals receiving ART. However, in line with a ‘cascade approach’ to treatment targets, this objective should encompass wider efforts to improve longterm retention in care, with sustained HIV treatment, ongoing viral load monitoring and interventions to promote treatment adherence.[3] Both retention in care and viral suppression rates can be calculated from routine M&E data and the spatial distributions visualised with heat maps (as in Fig. 3, B) to identify areas that require targeted interventions. Using GIS one can visualise whether geographical areas of poor retention overlap with areas of poor viral suppression, which interestingly has not been found to be the case, suggesting that different factors may be responsible for poor outcomes at different steps of the HIV care cascade.[21] GIS can also be used to visualise performance of individual healthcare facilities. In CoJ Region D, there are a number of facilities, located in the outer wards of the region, with viral suppression rates <90% (Fig. 6). Targeting poor viral suppression rates in these areas may involve campaigns for viral load testing and addressing factors underlying poor ART adherence – for example, running public information campaigns addressing beliefs in divine healing, preference for traditional

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medicine and doubts regarding the benefits and safety of ART, while providing clinical training to address poor patient-provider relationships.[49-51] It is also important for programme planning to identify areas with high rates of viral suppression, as individuals in these areas can be treated in the community to ease the burden on healthcare facilities. In addition to monitoring patterns of retention in care and viral suppression, GIS can be used to identify geographical barriers that may affect ART adherence, including infrastructure barriers such as inadequate transport.[52] Poor access to healthcare facilities as a result of transport challenges highlights areas for communitybased interventions such as adherence clubs, alternative ART distribution points and deployment of mobile clinics. Individual-level GIS analyses are highly beneficial in the context of the third 90. Mapping households of individuals with poor adherence or those who have defaulted from ART care would enable CHWs to perform home visits to provide intensified adherence counselling and linkage back to care (Fig. 5). Using these maps, clusters of defaulters can then be identified. Where clusters are located near healthcare facilities, possible problems with facility services should be investigated and addressed. In addition, households with high-risk individuals can be mapped for pre-emptive home visits by CHWs. High-risk individuals for poor viral suppression include those who are economically deprived,[26] while individuals living further from HIV clinics are at risk of poor adherence, as clinic distance is associated with missed clinic visits[27] and transportation costs compromise access to care.[53] CHWs can also use area maps to talk to individuals about where best to locate alternative points for ART distribution that may facilitate improved adherence.

Region D population Data source 1: Statistics South Africa[43]

HIV prevalence Data source 2: Thembisa model[44] Data source 1×2

ART data Data source 3: Routine monitoring and evaluation data

Number of HIV-infected individuals active on ART in Region D by age and gender group

Estimated HIV-infected population in Region D by age and gender group Triangulate

Estimated ART programme gap (HIV-infected individuals not in care) by age and gender group: HIV-infected population minus on ART Determine the target group for each gender – the age group with the largest programme gap: Region D males aged 30 - 39 years

Map the programme gap in the target group by ward to determine where the target group can be found

ART programme gap, males 30 - 39 years ≤300 301 - 600 601 - 900 ≤300 901 - 1 200 1 201 - 1 500

Fig. 3. Identifying wards with the highest gap in ART coverage in City of Johannesburg Region D. (A) Approach to calculating the ART programme gap in the HIV-infected population by ward. (B) Visual output of the ART programme gap by ward for the male target group aged 30 - 39 years clearly highlights that wards 16, 33 and 37 (in red) have the greatest gap in service coverage (the numbers on the figure are the ward numbers). (ART = antiretroviral therapy.)

Considerations for implementing GIS in routine settings

As illustrated above for CoJ Region D and summarised in Table 1, GIS has many practical applications in support of programme operations working towards achieving the 90-90-90 targets. When implementing this technology in routine settings, it is firstly important to consider the choice of GIS software. Open-source, webbased GIS systems can reduce obstacles to end-user access and display a high degree of learnability,[54] with web-based software that does not require specialised GIS skill having demonstrated potential for public health applications in LMICs.[55] Affordability has

Programme gap %, males 30 - 39 years ≤0.30 0.31 - 0.50 0.51 - 0.70 0.71 - 0.90 0.91 - 1.00

HIV-positive population, males 30 - 39 years (n) 415 - 481 482 - 538 539 - 565 566 - 619 620 - 1 217

Fig. 4. Programme gap % (proportion of the HIV-infected population not in care) and the HIV-infected population by ward among males aged 30 - 39 years in City of Johannesburg Region D. Ward 11 (indicated by a green arrow) has a large HIV-infected population with a very small programme gap %, suggesting that the HIV programme has been well managed and supported in this high-burden area. In contrast, other wards in dark red with large numbers of HIV-infected individuals have a large programme gap % and may benefit from further support.

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Table 1. Summary of potential applications of GIS to support achievement of the 90-90-90 targets Programme-level support applications

Individual-level support applications

First 90: diagnosis of 90% of people infected with HIV

• Map population density of target groups that require • Limited use – can map individuals who have undergone improved access to HTS to identify areas with a high HIV testing to assess patterns of HTS uptake, but only density of these individuals for focussed HTS in small geographical areas for specific populations • Map high-risk populations and/or risk factors associated with HIV infection to identify potentially high-yield areas for delivery of focused HTS • Map clusters or hotspots of HIV prevalence to identify areas where there are likely to be higher numbers of HIV-infected individuals who can be identified through HTS

Second 90: 90% of people with diagnosed HIV-infection on ART

• Visualise the spatial pattern of ART uptake to identify areas with the greatest gap in care for targeted interventions. Overlay data from the ART programme with population data to provide a nuanced approach to understanding performance of the ART programme in high-burden areas • Monitor spatial patterns of ART coverage over time to assess progress of programme implementation and impact of interventions • Generate maps of population groups at high risk of attrition prior to ART initiation so that interventions can be planned in areas with a high proportion of these populations • Visualise geographical barriers to ART coverage that may contribute to poor treatment uptake, such as inadequate roads and long distances to clinics

• Track patients who test HIV-positive but do not link to care – map residences of these individuals to facilitate home visits by CHWs • Streamline CHW work by grouping visits to individuals who live in the same area • Inform programme planning by identifying areas with high numbers of individuals lost to initiation where community-based dispensing points may be of benefit • Plan proactive household visits by CHWs to HIVinfected individuals who live furthest from clinics to increase the likelihood of these high-risk individuals linking to care

Third 90: 90% of people on ART virally suppressed

• Visualise the spatial distribution of retention in ART care and viral suppression to identify areas with poor retention and/or suppression rates that require targeted interventions, such as viral load testing campaigns or addressing factors underlying poor ART adherence • Identify areas with high rates of viral suppression where patients can be treated in the community to ease the burden on healthcare facilities • Visualise facility-level viral suppression rates and assess whether facilities with poor performance cluster in certain areas • Identify geographical barriers that may affect ART adherence, including infrastructure barriers

• Track patients who have defaulted from ART care or those with poor adherence – map residences of these individuals so that CHWs can perform home visits to provide intensified adherence counselling and re-linkage to ART care • Identify ART facilities with potential service problems by identifying facilities around which there are clusters of individuals who have defaulted from care • Plan pre-emptive home visits by CHWs to high-risk individuals who are likely to have compromised ART adherence or viral suppression • Plan locations for alternative ART distribution points by using area maps to talk to individuals about where best to locate these services, thus facilitating improved adherence

GIS = geographic information systems; HTS = HIV testing service; ART = antiretroviral therapy; CHW = community health worker.

become less problematic over time, with the availability of free or inexpensive GIS software and easy mapping of point locations with inexpensive global positioning systems and/or mobile phones. [56,57] Secondly, the poor quality of routine M&E data, lack of unique patient identifiers and deficit of GIS data in some LMICs must be considered, in particular the availability of patient addresses for individual-level GIS applications. It is important to bear in mind that the definition of a patient address is multifaceted, as locations of work, sleep and family residence may vary, and that there may be no street names in rural settings for reporting patient addresses. Thirdly, it is essential to ensure confidentiality of individual-level patient data, particularly when using free web-based software.[34,58] Finally, stakeholders may prove challenging if there is a lack of understanding regarding what GIS can deliver and how to interpret the outputs. Obtaining buy-in from stakeholders may also be difficult where there

are concerns regarding transition from paper-based systems, misuse of information or political interference.[54,58] It is important to address buy-in from the start and to provide adequate training for capacity development of local staff to ensure sustainable systems.[56]

Conclusions

GIS has great potential to assist in achieving the 90-90-90 targets in SA and other LMICs and is currently being under-utilised for this purpose. This article demonstrates opportunities for using easily accessible resources to generate GIS visualisations and underlines the important benefits GIS can have in guiding HIV programme operations, the principles of which can be applied to any infectious disease. GIS can be incorporated into routine programme planning by visualising the spatial distribution of programme implementation gaps and impact of interventions. Individual-level analyses are of clinical value for

December 2017, Print edition

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Funding. This study was made possible by the generous support of the American people through the US President’s Emergency Plan for AIDS Relief (PEPFAR) through the United States Agency for International Development (USAID) under co-operative agreement no. 674A-12-00015 to the Anova Health Institute. The contents are the responsibility of Anova Health Institute and do not necessarily reflect the views of USAID or the United States Government. Conflicts of interest. None.

Households for CHW tracing Healthcare facility Fig. 5. Residences of HIV-infected individuals living in City of Johannesburg Region D who require home visits by CHWs (locations have been modified to protect patient confidentiality). Residences of HIV-infected individuals who are lost to treatment initiation or lost to follow-up from care can be georeferenced to generate maps that CHWs can use to perform home visits. (CHW = community health worker.)

Facility viral suppression Facility with lowest viral suppression rate (71%)

Facility with highest viral suppression rate (95%)

Fig. 6. Viral suppression rates at primary healthcare facilities in City of Johannesburg Region D. Facilities in red and orange with lower viral suppression rates, located around the outside of the region, should receive targeted interventions to improve progress towards the third 90% target.

patients and can also guide programme-level decisions. Interactive, dynamic systems using inexpensive GIS software may therefore prove a valuable tool to support control of the HIV epidemic in SA. Acknowledgements. None. Author contributions. RRL and RPHP con-

ceptualised the article, and JAM and HES supervised the project. CJG, TH and RRL managed the data to create the visualisations. All the authors reflected on and interpreted the visualisations. RRL wrote the manuscript, which was critically revised by all the authors. All the authors read and approved the final manuscript.

December 2017, Print edition

1. Simms I, Gibin M, Petersen J. Location, location, location: What can geographic information science (GIS) offer sexual health research? Sex Transm Infect 2014;90(6):442-443. https://doi. org/10.1136/sextrans-2014-051695 2. Kandwal R, Garg PK, Garg RD. Health GIS and HIV/AIDS studies: Perspective and retrospective. J Biomed Inform 2009;42(4):748-755. https://doi.org/10.1016/j.jbi.2009.04.008 3. Joint United Nations Programme on HIV/AIDS. 90-90-90: An Ambitious Treatment Target to Help End the AIDS Epidemic. Geneva: UNAIDS, 2014. 4. Zulu LC, Kalipeni E, Johannes E. Analyzing spatial clustering and the spatiotemporal nature and trends of HIV/AIDS prevalence using GIS: The case of Malawi, 1994 - 2010. BMC Infect Dis 2014;14:285. https://doi.org/10.1186/1471-2334-14-285 5. Carrel M, Janko M, Mwandagalirwa MK, et al. Changing spatial patterns and increasing rurality of HIV prevalence in the Democratic Republic of the Congo between 2007 and 2013. Health Place 2016;39:79-85. https://doi.org/10.1016/j. healthplace.2016.02.009 6. Tanser F, Barnighausen T, Cooke GS, Newell ML. Localized spatial clustering of HIV infections in a widely disseminated rural South African epidemic. Int J Epidemiol 2009;38(4):10081016. https://doi.org/10.1093/ije/dyp148 7. Messina JP, Emch M, Muwonga J, et al. Spatial and sociobehavioral patterns of HIV prevalence in the Democratic Republic of Congo. Soc Sci Med 2010;71(8):1428-1435. https:// doi.org/10.1016/j.socscimed.2010.07.025 8. Barankanira E, Molinari N, Niyongabo T, Laurent C. Spatial analysis of HIV infection and associated individual characteristics in Burundi: Indications for effective prevention. BMC Public Health 2016;16:118. https://doi.org/10.1186/ s12889-016-2760-3 9. Goswami ND, Hecker EJ, Vickery C, et al. Geographic information system-based screening for TB, HIV, and syphilis (GIS-THIS): A cross-sectional study. PLoS One 2012;7(10):e46029. https://doi. org/10.1371/journal.pone.0046029 10. Wand H, Ramjee G. Targeting the hotspots: Investigating spatial and demographic variations in HIV infection in small communities in South Africa. J Int AIDS Soc 2010;13(1):41. https://doi.org/10.1186/1758-2652-13-41 11. Wand H, Whitaker C, Ramjee G. Geoadditive models to assess spatial variation of HIV infections among women in local communities of Durban, South Africa. Int J Health Geogr 2011;10:28. https://doi.org/10.1186/1476-072X-10-28 12. Tanser F, Lesueur D, Solarsh G, Wilkinson D. HIV heterogeneity and proximity of homestead to roads in rural South Africa: An exploration using a geographical information system. Trop Med Int Health 2000;5(1):40-46. https://doi.org/10.1046/j.13653156.2000.00513.x 13. Cuadros DF, Awad SF, Abu-Raddad LJ. Mapping HIV clustering: A strategy for identifying populations at high risk of HIV infection in sub-Saharan Africa. Int J Health Geogr 2013;12:28. https://doi.org/10.1186/1476-072X-12-28 14. Wabiri N, Shisana O, Zuma K, Freeman J. Assessing the spatial nonstationarity in relationship between local patterns of HIV infections and the covariates in South Africa: A geographically weighted regression analysis. Spat Spatiotemporal Epidemiol 2016;16:88-99. https://doi.org/10.1016/j.sste.2015.12.003 15. Cuadros DF, Abu-Raddad LJ. Spatial variability in HIV prevalence declines in several countries in sub-Saharan Africa. Health Place 2014;28:45-49. https://doi.org/10.1016/j. healthplace.2014.03.007 16. Larmarange J, Bendaud V. HIV estimates at second subnational level from national population-based surveys. AIDS 2014;28(Suppl 4):S469-S476. https://doi.org/10.1097/ QAD.0000000000000480 17. Subnational Estimates Working Group of the HIV Modelling Consortium. Evaluation of geospatial methods to generate subnational HIV prevalence estimates for local level planning. AIDS 2016;30(9):1467-1474. https://doi.org/10.1097/QAD. 0000000000001075 18. Wand H, Ramjee G. Spatial clustering of ‘measured’ and ‘unmeasured’ risk factors for HIV infections in hyper-endemic communities in KwaZulu-Natal, South Africa: Results from geoadditive models. AIDS Care 2015;27(11):1375-1381. https:// doi.org/10.1080/09540121.2015.1096896

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19. Cooke GS, Tanser FC, Barnighausen TW, Newell ML. Population uptake of antiretroviral treatment through primary care in rural South Africa. BMC Public Health 2010;10:585. https://doi. org/10.1186/1471-2458-10-585 20. Chamla DD, Olu O, Wanyana J, et al. Geographical information system and access to HIV testing, treatment and prevention of mother-to-child transmission in conflict affected Northern Uganda. Confl Health 2007;1:12. https://doi.org/10.1186/1752-1505-1-12 21. Eberhart MG, Yehia BR, Hillier A, et al. Behind the cascade: Analyzing spatial patterns along the HIV care continuum. J Acquir Immune Defic Syndr 2013;64(Suppl 1):S42-S51. https://doi.org/10.1097/ QAI.0b013e3182a90112 22. Goswami ND, Schmitz MM, Sanchez T, et al. Understanding local spatial variation along the care continuum: The potential impact of transportation vulnerability on HIV linkage to care and viral suppression in high-poverty areas, Atlanta, Georgia. J Acquir Immune Defic Syndr 2016;72(1):65-72. https://doi.org/10.1097/QAI.0000000000000914 23. Johnson DC, Feldacker C, Tweya H, Phiri S, Hosseinipour MC. Factors associated with timely initiation of antiretroviral therapy in two HIV clinics in Lilongwe, Malawi. Int J STD AIDS 2013;24(1):42-49. https://doi.org/10.1177/0956462412472312 24. Kloos H, Assefa Y, Adugna A, Mulatu MS, Mariam DH. Utilization of antiretroviral treatment in Ethiopia between February and December 2006: Spatial, temporal, and demographic patterns. Int J Health Geogr 2007;6:45. https://doi.org/10.1186/1476-072X-6-45 25. Yao J, Agadjanian V, Murray AT. Spatial and social inequities in HIV testing utilization in the context of rapid scale-up of HIV/AIDS services in rural Mozambique. Health Place 2014;28:133-141. https:// doi.org/10.1016/j.healthplace.2014.04.007 26. Eberhart MG, Yehia BR, Hillier A, et al. Individual and community factors associated with geographic clusters of poor HIV care retention and poor viral suppression. J Acquir Immune Defic Syndr 2015;69(Suppl 1):S37-S43. https://doi.org/10.1097/QAI.0000000000000587 27. Siedner MJ, Lankowski A, Tsai AC, et al. GPS-measured distance to clinic, but not self-reported transportation factors, are associated with missed HIV clinic visits in rural Uganda. AIDS 2013;27(9):1503-1508. https://doi.org/10.1097/QAD.0b013e32835fd873 28. Zhou YB, Liang S, Wang QX, et al. The geographic distribution patterns of HIV-, HCV- and coinfections among drug users in a national methadone maintenance treatment program in Southwest China. BMC Infect Dis 2014;14:134. https://doi.org/10.1186/1471-2334-14-134 29. Pierce SJ, Miller RL, Morales MM, Forney J. Identifying HIV prevention service needs of African American men who have sex with men: An application of spatial analysis techniques to service planning. J Public Health Manag Pract 2007;Suppl:S72-S79. https://doi.org/10.1097/00124784200701001-00012 30. Martinez AN, Lorvick J, Kral AH. Activity spaces among injection drug users in San Francisco. Int J Drug Policy 2014;25(3):516-524. https://doi.org/10.1016/j.drugpo.2013.11.008 31. Lorway R, Khan S, Chevrier C, et al. Sex work in geographic perspective: A multi-disciplinary approach to mapping and understanding female sex work venues in Southwest China. Glob Public Health 2017;12(5):545-564. https://doi.org/10.1080/17441692.2015.1123748 32. Ferguson AG, Morris CN. Mapping transactional sex on the Northern Corridor highway in Kenya. Health Place 2007;13(2):504-519. https://doi.org/10.1016/j.healthplace.2006.05.009 33. Delaney KP, Kramer MR, Waller LA, Flanders WD, Sullivan PS. Using a geolocation social networking application to calculate the population density of sex-seeking gay men for research and prevention services. J Med Internet Res 2014;16(11):e249. https://doi.org/10.2196/jmir.3523 34. Mahler H, Searle S, Plotkin M, et al. Covering the last kilometer: Using GIS to scale-up voluntary medical male circumcision services in Iringa and Njombe Regions, Tanzania. Glob Health Sci Pract 2015;3(3):503-515. https://doi.org/10.9745/GHSP-D-15-00151 35. Shacham E, Thornton R, Godlonton S, Murphy R, Gilliland J. Geospatial analysis of condom availability and accessibility in urban Malawi. Int J STD AIDS 2016;27(1):44-50. https://doi. org/10.1177/0956462415571373 36. Buehler CP, Blevins M, Ossemane EB, et al. Assessing spatial patterns of HIV knowledge in rural Mozambique using geographic information systems. Trop Med Int Health 2015;20(3):353-364. https:// doi.org/10.1111/tmi.12437 37. Leibowitz AA, Mendes AC, Desmond K. Public funding of HIV/AIDS prevention, treatment, and support in California. J Acquir Immune Defic Syndr 2011;58(1):e11-e16. https://doi.org/10.1097/ QAI.0b013e31822101c8 38. Bwambale FM, Ssali SN, Byaruhanga S, Kalyango JN, Karamagi CA. Voluntary HIV counselling and testing among men in rural western Uganda: Implications for HIV prevention. BMC Public Health 2008;8:263. https://doi.org/10.1186/1471-2458-8-263

39. Lippman SA, Shade SB, El Ayadi AM, et al. Attrition and opportunities along the HIV care continuum: Findings from a population-based sample, North West Province, South Africa. J Acquir Immune Defic Syndr 2016;73(1):91-99. https://doi.org/10.1097/QAI.0000000000001026 40. Ramirez-Avila L, Nixon K, Noubary F, et al. Routine HIV testing in adolescents and young adults presenting to an outpatient clinic in Durban, South Africa. PLoS One 2012;7(9):e45507. https://doi. org/10.1371/journal.pone.0045507 41. Peltzer K, Matseke G. Determinants of HIV testing among young people aged 18 - 24 years in South Africa. Afr Health Sci 2013;13(4):1012-1020. https://doi.org/10.4314/ahs.v13i4.22 42. Johnson LF, Chiu C, Myer L, et al. Prospects for HIV control in South Africa: A model-based analysis. Glob Health Action 2016;9(1):30314. https://doi.org/10.3402/gha.v9.30314 43. Space-Time Research Pty Ltd. Census 2011: Interactive data in SuperCROSS. SuperCROSS 8.0.2.32. Pretoria: Statistics South Africa, 2011. 44. Johnson LF, Dorrington RE, Moolla H. Modelling the impact of HIV in South Africaâ&#x20AC;&#x2122;s provinces: Centre for Infectious Disease Epidemiology and Research working paper. University of Cape Town, 2016. http://www.thembisa.org/content/downloadPage/Provinces2016 (accessed 25 July 2017). 45. National Department of Health, South Africa. NDoH Circular: Implementation of the Universal Test and Treat Strategy for HIV Positive Patients and Differentiated Care for Stable Patients. Pretoria: NDoH, 2016. 46. Govindasamy D, Ford N, Kranzer K. Risk factors, barriers and facilitators for linkage to antiretroviral therapy care: A systematic review. AIDS 2012;26(16):2059-2067. https://doi.org/10.1097/QAD. 0b013e3283578b9b 47. BBC News Services. Medical motorbike couriers battle HIV. 12 November 2014. http://www.bbc.com/ news/science-environment-30005764 (accessed 18 November 2016). 48. Columbia University Mailman School of Public Health. ICAP launches boat to support HIV services for Tanzaniaâ&#x20AC;&#x2122;s Lake Victoria Islands. 20 February 2015. http://icap.columbia.edu/news-events/detail/ icap-launches-boat-to-support-hiv-services-to-tanzanias-lake-victoria-islan (accessed 18 November 2016). 49. Wanyama J, Castelnuovo B, Wandera B, et al. Belief in divine healing can be a barrier to antiretroviral therapy adherence in Uganda. AIDS 2007;21(11):1486-1487. https://doi.org/10.1097/ QAD.0b013e32823ecf7f 50. Groh K, Audet CM, Baptista A, et al. Barriers to antiretroviral therapy adherence in rural Mozambique. BMC Public Health 2011;11:650. https://doi.org/10.1186/1471-2458-11-650 51. Root R, Whiteside A. A qualitative study of community home-based care and antiretroviral adherence in Swaziland. J Int AIDS Soc 2013;16:17978. https://doi.org/10.7448/IAS.16.1.17978 52. Kagee A, Remien RH, Berkman A, Hoffman S, Campos L, Swartz L. Structural barriers to ART adherence in southern Africa: Challenges and potential ways forward. Glob Public Health 2011;6(1):83-97. https://doi.org/10.1080/17441691003796387 53. Tuller DM, Bangsberg DR, Senkungu J, Ware NC, Emenyonu N, Weiser SD. Transportation costs impede sustained adherence and access to HAART in a clinic population in southwestern Uganda: A qualitative study. AIDS Behav 2010;14(4):778-784. https://doi.org/10.1007/s10461-009-9533-2 54. Vanmeulebrouk B, Rivett U, Ricketts A, Loudon M. Open source GIS for HIV/AIDS management. Int J Health Geogr 2008;7:53. https://doi.org/10.1186/1476-072X-7-53 55. Kamadjeu R, Tolentino H. Web-based public health geographic information systems for resourcesconstrained environment using scalable vector graphics technology: A proof of concept applied to the expanded program on immunization data. Int J Health Geogr 2006;5:24. https://doi.org/10.1186/1476072X-5-24 56. Tanser FC, le Sueur D. The application of geographical information systems to important public health problems in Africa. Int J Health Geogr 2002;1(1):4. https://doi.org/10.1186/1476-072X-1-4 57. Tanser FC. The application of GIS technology to equitably distribute fieldworker workload in a large, rural South African health survey. Trop Med Int Health 2002;7(1):80-90. https://doi.org/10.1046/ j.1365-3156.2002.00825.x 58. Busgeeth K, Rivett U. The use of a spatial information system in the management of HIV/AIDS in South Africa. Int J Health Geogr 2004;3(1):13. https://doi.org/10.1186/1476-072X-3-13

Accepted 14 August 2017.

December 2017, Print edition

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

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MEDICINE AND THE LAW

Disclosing details about the medical treatment of a deceased public figure in a book: Who should have consented to the disclosures in Mandela’s Last Days? D J McQuoid-Mason, BComm, LLB, LLM, PhD Centre for Socio-Legal Studies, University of KwaZulu-Natal, Durban, South Africa Corresponding author: D J McQuoid-Mason (mcquoidm@ukzn.ac.za)

A recently published book by the head of Nelson Mandela’s medical team made personal disclosures about his treatment of the late president in his final years up until his death. The author claimed that he had written the book at the request of family members. This was contested by some family members and the executors of Mandela’s estate, and the book was subsequently withdrawn by the publishers. The Mandela book case raises ethical and legal questions about who should consent to publication of medical information about public figures after their death. The ethical rules of conduct of the Health Professions Council of South Africa (HPCSA) state that confidential information about a deceased person should only be divulged ‘with the written consent of his or her next of kin or the executor of his or her estate’. ‘Next of kin’ is not defined, however, and problems arise when family members and the executors are divided about giving such written consent. It is recommended that in such cases the specific order of priority for consent by relatives in the National Health Act be followed. However, conduct that is unethical under the rules of the HPCSA may not necessarily be actionable under the law. For instance, the law does not protect the confidentiality of deceased persons, and generally when people die their constitutional and common-law personality rights – including their right to privacy and confidentiality – die with them. This means that the next of kin or executors of the estates of deceased persons may not bring actions for damages on behalf of such persons for breaches of confidentiality arising after their deaths. The next of kin may, however, sue in their personal capacity if they can show that the disclosures were an unlawful invasion of their own privacy. Conversely, if the privacy of interests of the next of kin are not harmed where there has been publication without their consent, they will not be able to sue for damages. S Afr Med J 2017;107(12):1072-1074. DOI:10.7196/SAMJ.2017.v107i12.12764

The recently published book titled Mandela’s Last Days by the head of the late former President Mandela’s medical team[1] made personal disclosures about the medical treatment received by Mandela during the final years leading up to his death. It also mentioned how the family and Mandela’s colleagues reacted to the unfolding drama surrounding his death. The author claimed that he was requested by the family to write the book.[2] He also claimed that a family member had read the contents of the book, and that the family had approved its publication.[3] It was reported in the press that the publication of the book was criticised by Mandela’s widow Graca Machel, the executors of his estate, the Nelson Mandela Foundation and his grandson, Mandla Mandela.[2] As a result, the book was withdrawn from bookshops by its publishers out of respect for the family.[2] Graca Machel and the executors of Mandela’s estate had threatened to take legal action and stated that they intended laying a complaint with the Health Professions Council of South Africa (HPCSA) and the author’s previous employers, the South African National Defence Force. The latter had already distanced itself from the publication.[3] The controversy surrounding which family members consented to the publication of the Mandela book raises questions about publication of medical information about a deceased public figure. These include: (i) when is it ethical to publish such information; (ii) which family members or next of kin must consent to publication of such information; (iii) when is it legal to publish such information; (iv) whether it makes a difference if the deceased is a public figure; and (v) whether family members have

legal standing to prevent or claim damages for such publication on behalf of the deceased.

When is it ethical to publish information about a deceased patient’s medical treatment?

Rule 13(2)(c) of the Ethical Rules of Conduct of the HPCSA[4] state that confidential information about a deceased patient should only be divulged ‘with the written consent of his or her next of kin or the executor of his or her estate’ – except where such information ought to be disclosed in terms of a statute or court order, or the disclosure is justified in the public interest.[5] Where a doctor has made disclosures about a deceased person’s medical treatment in breach of rule 13(2)(c), the deceased person’s next of kin or the executor of his or her estate may file a complaint with the HPCSA, and disciplinary action can be taken against the medical practitioner concerned for unethical conduct.[6] This is the route that Mandela’s widow and executors were threatening to take. [3] Problems arise, however, if some family members give written consent and others do not, and actively oppose the publication. Rule 13(2)(c), however, does not provide a definition of ‘next of kin’. The dictionary (I consulted the Oxford Advanced Learner’s Dictionary of Current English[7]) does not take the matter much further, as it simply defines a person’s ‘next of kin’ as his or her ‘nearest relatives’. This does not answer the question of which next-of-kin relatives take precedence over the others or whether they must all agree.

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Meaning of ‘next of kin’

Where there is a disagreement between family members regarding the granting of written consent for the publication of a deceased patient’s records, the question arises as to whose wishes should prevail as next of kin. Should it be the surviving spouse or partner, or the children of the deceased? As mentioned, there is no definition of the term ‘next of kin’ in the ethical rules of the HPCSA, and the dictionary definition is vague,[7] so it is necessary to look elsewhere. The National Health Act[8] describes the order of persons who can give consent on behalf of incompetent live patients (section 7(1)(b)). It is submitted that this could be used as a guide for determining which next-of-kin relatives should have the right to give written consent for the publication of personal medical information on a deceased person. This is because people who are authorised to give consent to treatment may also decide who has access to information about such treatment. The Act states that a ‘user’ must consent to disclosures in writing (section 14(2)(a)), while the definition of ‘user’ in the Act includes the order of listed persons who make decisions on behalf of mentally incompetent patients (section 1). In terms of the Act, the specific order of precedence is ‘a spouse or partner, a parent, a grandparent, an adult child or a brother or sister of the person’ (section 7(1)(b)). If the National Health Act[8] list of precedence regarding relatives who can give consent to medical treatment were to be followed in the Mandela book case, his widow, Graca Machel, would be the person who would legally have the authority to grant the necessary written consent. His widow would take precedence over his adult children and his ex-wife Winnie Madikizela-Mandela. While the latter is the mother of some of Mandela’s children, she would no longer be regarded as a next of kin because she is divorced from him. The other categories, apart from his children, are not relevant to a person of Mandela’s age at his death. The executors, the Nelson Mandela Foundation, and Mandela’s grandson Mandla Mandela, head of the Mandela clan, were all reported to support the request of Graca Machel that the book be withdrawn.[2]

When is it legal to publish information about a deceased patient’s medical treatment?

Everyone has a constitutional[9] and common-law right to privacy[10] concerning their health status. The right is not unlimited, however, and may be infringed where the person concerned consents, where there is a statutory duty to make disclosure (e.g. in the case of child abuse),[11] where it is reasonable for the media to make the disclosure,[12] where the disclosure is true and in the public interest,[13] or where the disclosure is privileged.[12] The defences to an action for invasion of privacy are similar to those for defamation.[6] The defences of truth and public interest[13] are particularly relevant to disclosures concerning the health status of public figures.

Who is a public figure?

Public figures are people who have by their personality, status or conduct exposed themselves and their families to such a degree of publicity as to justify public disclosures of certain aspects of their private lives.[13] Such persons include politicians, actors, entertainers, sportsmen and sportswomen, war heroes, and others who are regarded as having a limited right to privacy. This is because, as they have sought or consented to publicity, their personalities and affairs have already become public knowledge. In such instances the media has a duty to inform the public about them if their private life and that of their family interfere with their ability to carry out their public or professional duties properly or if they make statements

that are false and blatantly contradict their actions in their personal life.[13] President Mandela was a world-famous public figure, and as such was at the centre of much publicity. However, he was entitled to have his private life respected should he wish it – unless his private life contradicted what he stood for as a statesman. The same applies to his immediate family. His and his family’s wishes for privacy concerning his medical condition during his last years, after he had retired from political life, should have been respected. It is difficult to think of exceptions that would have been in the public interest and could have justified disclosures about Mandela’s medical condition as it impacted on him and his family. An unlikely scenario would have been if he had died immediately before the last general election, and the family had conspired with the ruling party to give the impression that he was still alive in order to use his name to garner support. In such circumstances the disclosures about his medical treatment and the role of the family in a cover up would have been justified. However, such an event did not happen. Disclosures about public figures and their families will be lawful it they are true and in the public interest.[13]

Truth and the public interest

Generally a disclosure about a person’s health status may not be unlawful if the statement is true and in the public interest.[13] Truth does not mean that the disclosure has to be true in all respects, provided it is substantially true in the sense that the material facts are true.[14] Truth alone will not be a defence to a public disclosure concerning a person’s health status or how it impacted on his or her family – it must be linked to public benefit or interest for the defence to succeed.[14] While all the medical information in the Mandela book and the role of his family in his final years may be true, they therefore should not have been published unless it was also in the public interest. Public interest refers to ‘material in which the public has an interest’ – not ‘what the public finds interesting’.[12] It is a difficult concept to define. In the words of one judge: ‘Public interest is a mysterious concept. Like a battered piece of string charged with elasticity, impossible to measure or weigh.’[13] Public interest may include information about the private lives of public figures and their families, but only if such information is relevant to how they or their families conduct themselves in public.[13] For instance, if a politician were to say that all members of parliament should send their children to state rather than private schools, when he himself sends his child to a private school, it would be justifiable to expose such hypocritical behaviour. In the Mandela book case it can be argued that although his last years leading up to his death would be found interesting by the public, it is not necessarily ‘material in which the public has an interest’.

Do the family have standing to sue on behalf of the deceased for invasion of privacy?

Conduct that is unethical under the rules of the HPCSA may not necessarily be actionable under the law. For instance, there is no general protection for the personality rights of deceased persons,[15] although there is some protection in criminal law against interfering with a corpse (e.g. having sexual intercourse with a corpse).[16] Consequently, if a doctor intentionally discloses private information about a deceased patient – outside of a statutory or common-law right to do so – there would be no action for damages in law, because the person is deceased.[15] The next of kin or executor of a deceased person may not sue a doctor who breaches the confidentiality rule regarding medical treatment of the deceased after the latter’s death. [15]

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This is because the right to sue for a breach of confidentiality or invasion of privacy vests in deceased persons during their lifetime, and not in their next of kin or executors after their death.[15] As mentioned above, the deceased person’s next of kin or the executor of his or her estate could, however, file a complaint with the HPCSA in the Mandela case.[3] The next of kin may also sue in their personal capacity for disclosures about a deceased patient’s last years if they can show that the disclosures were an unlawful invasion of their own privacy.[10] An invasion of privacy occurs when a person’s private life is exposed to publicity[17] or when a person’s private life is portrayed in a false light.[18] For instance, if personal information about how certain family members reacted during the period leading up to the death of the patient is disclosed or falsely represented in a publication, the family members might have an action for invasion of privacy. An exception might be where the deceased person is a public figure and the information about the family members is true and in the public interest.[13] The deceased person’s next of kin will also not be able to sue if their privacy interests have not been harmed – even where there has been unethical publication without their consent.

Conclusion

Medical practitioners must be very careful about making disclosures about the medical condition and its impact on the family of their deceased patients – particularly where there is likely to be a dispute between family members. Practitioners should ensure that they obtain written consent from the relevant next of kin. They should attempt to get consensus about the disclosures from the family and executors. However, if they cannot achieve this, they should ensure

that the nearest relatives give consent. In order to determine who the nearest relatives are, they can be guided by the provisions of the National Health Act[8] dealing with the order of persons who can give consent on behalf of incompetent patients (section 7(1)(c)). Acknowledgements. None. Author contributions. Sole author. Funding. None. Conflicts of interest. None. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

Ramlakan V. Mandela’s Last Years. Cape Town: Penguin Random House South Africa, 2017. ANA. Mandela Book pulled off shelves by Penguin. The Mercury 25 July 2017:1. Shaik N. Graca Machel threat to sue over Mandela book. The Mercury 24 July 2017:3. South Africa. Rule 13(2)(c) of the Ethical Rules of Conduct for Practitioners registered under the Health Professions Act, 1974. Government Notice R717 of 4 August 2006, as amended by Government Notice R68 of 2 February 2009. Cf. Khumalo v. Holomisa 2002 (5) SA 401 (CC). South Africa. Rule 2(1) of the Ethical Rules of Conduct for Practitioners registered under the Health Professions Act, 1974. Government Notice R717 of 4 August 2006, as amended by Government Notice R68 of 2 February 2009. Hornby AS. Oxford Advanced Learner’s Dictionary of Current English. 3rd ed. Oxford: Oxford University Press, 1986:466. South Africa. National Health Act, 2003 (Act No. 61 of 2003). South Africa. Section 14 of the Constitution of the Republic of South Africa, 1996. O’Keeffe v Argus Printing and Publishing Co Ltd 1954 (3) SA 254 (C). South Africa. Section 110 of the Children’s Amendment Act, 2007 (Act 41 of 2007). National Media Ltd v Bogoshi 1998 (4) SA 1196 (SCA). Tshabalala-Msimang and Medi-Clinic Ltd v Makhanya 2008 3 BCLR 338 (W). Cf. Johnson v Rand Daily Mail 1928 AD 190. Cf. Spendiff v East London Despatch Ltd 1929 EDL 113. South Africa. Section 14 of the Criminal Law (Sexual Offences and Related Matters) Amendment Act, 2007 (Act No. 32 of 2007). Mhlongo v Bailey 1958 (1) SA 370 (W). Kidson v SA Associated Newspapers Ltd 1957 (3) SA 461 (W).

Accepted 23 August 2017.

CASE REPORT This open-access article is distributed under CC-BY-NC 4.0.

Berg adder (Bitis atropos): An unusual case of acute poisoning

C A Wium, MSc (Pharmacology); C J Marks, MSc (Pharmacology); C E du Plessis, BSc; G J Müller, MB ChB, MMed (Anaes), PhD (Toxicology) Tygerberg Poison Information Centre, Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa Corresponding author: C A Wium (caw@sun.ac.za)

A 5-year-old boy presented to hospital with mild local cytotoxic and severe neurotoxic symptoms. The neurotoxic symptoms included ptosis, fixed dilated pupils and flaccid paralysis with respiratory failure. Mild hyponatraemia was also a clinical feature. After various unsuccessful treatment options were followed, the Tygerberg Poison Information Centre was contacted and a diagnosis of berg adder bite was made. Berg adder bites are uncommon and therefore not usually considered in the differential diagnosis of a patient presenting with an unexplained clinical picture. A timeous poison information helpline consultation is recommended in this situation. S Afr Med J 2017;107(12):1075-1077. DOI:10.7196/SAMJ.2017.v107i12.12763

Case report

At midday, a 5-year-old boy was walking with his grandfather over the sand dunes on a path through the fynbos (natural shrubland or heathland vegetation) in the Betty’s Bay area of the

Western Cape Province, South Africa. He felt a sharp pain on the lateral side of the left foot. The boy and his grandfather thought that he had stepped onto a stick with big thorns, and he limped home. The local injury looked like a scratch mark. Shortly thereafter (within

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1 - 2 hours) he started vomiting and said that he felt tired. These symptoms continued for several hours. He appeared unwell and had difficulty in keeping his eyes open. The family were scheduled to fly from Cape Town to Johannesburg at 17h00 on the same day. Before boarding, the boy had difficulty in walking and had to be carried on board. His eyes remained half closed throughout the flight, and it was reported that he had ‘slept’ during the journey. On arrival in Johannesburg, now 8 - 9 hours after the incident, he was immediately taken to a medical facility. He had difficulty in breathing and was resuscitated, intubated and ventilated. He had prominent fixed dilated pupils and his left foot was red and slightly swollen (Fig. 1). A cranial computed tomography scan of the brain was normal. Standard routine laboratory blood tests (Table 1) as well as serum and urine toxicology screens were done. A high level of benzodiazepines (>200 ng/mL) was detected in the serum and in the urine. The presence of benzodiazepines led medical personnel to consider the possibility of a benzodiazepine overdose. The patient was subsequently transferred to a paediatric intensive care unit where flumazenil, the antidote for benzodiazepine overdose, was administered. Six hours after administration there was no response to the flumazenil. It was then assumed that the high benzodiazepine level was probably due to the midazolam given prior to intubation, and therefore not responsible for the clinical picture. Lumbar puncture was performed, and the results were found to be normal. A full blood count showed the presence of a neutrophil leucocytosis. Liver functions were normal. The pupils were still severely dilated 24 hours after the incident, and an ophthalmologist was therefore consulted. A magnetic resonance imaging scan of the brain and brainstem was normal. A Cape cobra bite was then considered a possible cause of the toxicity, based on a possible snakebite mark on the foot and the accompanying flaccid paralysis. The Cape cobra (Naja nivea) has neurotoxic venom that can cause severe, descending flaccid paralysis due to postsynaptic somatic nerve block.[1] Eight vials (8 × 10 mL) of Polyvalent Snakebite Antiserum (South African Vaccine Producers) were administered. However, the patient did not respond to the antivenom, and the Tygerberg Poison Information Centre (TPIC) was consulted with regard to the unusual clinical presentation. A diagnosis of berg adder bite was made by the TPIC based on the following: • The ‘scratch mark’ and the swelling of the foot, which were considered to be the result of a snakebite[2-4] • Ptosis[2-7] • Marked fixed dilated pupils[2,4,5-7] • Flaccid paralysis with respiratory failure[1,4,9] • Negative response to the Polyvalent Snakebite Antiserum, which is not effective in berg adder envenomation[1]

• The geographical area in which the incident took place. Over a 12-year period, four of the 14 cases of berg adder envenomation dealt with by the TPIC have been from the Betty’s Bay region.[8,9] • The lack of response to flumazenil[10] • The development of hyponatraemia has been described as a complication of berg adder bite, and confirmed the diagnosis.[9] On the recommendation of the TPIC, management was supportive and the hyponatraemia was corrected with normal saline. The patient responded well and was extubated 5 days after the incident. Fig. 2 compares the pupils 3 weeks after the incident with the pupils 6 months after the incident. The dilated pupils were still present 6 months after the incident, and the ophthalmologist prescribed pilocarpine. The senses of taste and smell could not be assessed in this patient during hospitalisation. Loss of sense of taste and smell are usually prominent features of berg adder bite. [1,7,9] However, when specifically asked, the parents reported that after the incident the boy had said on numerous occasions that his favourite food ‘did not taste right’. About a month after the incident, he said that ‘it tastes like it used to’. Fig. 3 shows that the pupils were still dilated after 1 year.

Discussion

The berg adder (Bitis atropos) is a relatively small snake (one of the dwarf/minor adders), with an average adult length of 30 - 40 cm. It is greyish to dark brown with a white dorsolateral line on both sides of the body, with a series of sub-triangular pale-edged markings above the line (Fig. 4).[8] The berg adder is known to be aggressive, and will strike without undue provocation. Its preferred habitat is montane grassland up to a level of 3 000 m, as well as coastal fynbos. [2,8] Berg adder envenomation causes a unique syndrome of cytotoxic and neurotoxic symptoms and signs.[1,2] Local effects include initial pain in the region of the bite mark and swelling.[4,6,7] Systemic effects include paraesthesiae of the tongue and lips, ophthalmoplegia characterised by visual disturbances, ptosis, fixed dilated pupils and loss of eye

Fig. 2. The pupils 3 weeks after the incident (left) compared with the pupils 6 months after the incident (right) (photo: R Grantham).

Fig. 1. The left foot, red and slightly swollen (photo: R Grantham).

Fig. 3. The pupils 1 year after the incident (photo: R Grantham).

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for the presenting symptoms and signs is unknown. This case illustrates that various ineffective and costly treatment modalities could have been avoided with simple symptomatic and supportive care. Berg adder envenomation is uncommon and therefore not usually considered in the differential diagnosis of snakebite or any other unexplained symptoms and signs. Berg adder envenomation may cause life-threatening toxic effects such as respiratory failure and hyponatraemia, and it is therefore recommended that it be considered in the differential diagnosis of patients presenting with both cytotoxic and neurotoxic symptoms. The Poison Information Helpline number is 0861 555 777.

Fig. 4. Berg adder (Bitis atropos) from the Western Cape (photo: J Marais).

movements and accommodation, as well as loss of the sense of smell (anosmia) and taste. The dilated pupils and loss of the sense of smell and taste may take weeks to months to resolve. Late-onset respiratory failure is a complication 6 - 36 hours after the bite, often at a stage when it is not anticipated or expected. [1,4-7] Hyponatraemia, which may lead to convulsions, often develops 2 - 3 days after the bite and should not be interpreted as a syndrome of inappropriate antidiuretic hormone secretion (SIADH). [11] Hyponatraemia is probably the result of a natriuretic peptide in the venom that induces renal sodium loss. It has been shown by Van Zyl et al.[12] that berg adder venom contains at least two phospholipase A2 enzymes, suggesting that the toxic effects are not due to a single component but to the activities of various components. There is no antivenom for berg adder bite.[1,7] Management is symptomatic and supportive, with specific attention given to respiratory function and correction of plasma sodium levels. The sodium level should be recorded at regular intervals and hyponatraemia treated with normal saline. Fluids should not be restricted, and ophthalmological consultation is recommended.[1]

Acknowledgements. We thank Drs D J H Veale and E Decloedt for editing the final manuscript. Author contributions. All the authors contributed to the original discussions regarding the unusual presentation before the diagnosis was made. CAW wrote the article, and CJM, CEduP and GJM critically reviewed it from the beginning of the writing process. Funding. None. Conflicts of interest. None.

1. Muller GJ, Modler H, Wium CA, Veale DJH, Marks CJ. Snake bite in southern Africa: Diagnosis and management. CME 2012;30(10):362-381. http://www.cmej.org.za/index.php/cmej/article/ view/2546/2581 (accessed 5 November 2017). 2. Ellis CG. Special Report: Snakes alive. The berg adder: A unique snake. Practitioner 1979;223(1336):544-547. 3. Paget D, Cock EV. Case history of a berg adder bite. Cent Afr J Med 1979;25(2):30-33. 4. Hurter J. Bitis atropos (berg adder): Envenomation. J Herp Assoc Afr 1986;32(1):33-33. 5. Hurwitz BJ, Hull PR. Berg adder bite. S Afr Med J 1971;45(4 Sept):969-971. 6. Montgomery J. Two cases of ophthalmoplegia due to berg adder bite. Cent Afr J Med 1959:5(4):173-177. 7. Palmer NG. Bitis atropos (berg adder): Envenomation. J Herp Assoc Afr 1986;32(1):31-32. 8. Marais J. Snakes of Southern Africa. 2nd ed. Cape Town: Struik Publishers, 2004:100-101. 9. Muller GJ, van Zyl JM. The unique syndrome of berg adder (Bitis atropos) envenoming. Presented at the World Congress on Animal, Plant & Microbial Toxins, Adelaide, Australia, 14 - 19 September 2003. https://doi.org/10.21236/ada418029 (accessed 14 September 2016). 10. Sivilotti MLA. Flumazenil, naloxone and the ‘coma cocktail’. Br J Clin Pharmacol 2016;81(3):428-436. https://doi.org/10.1111/bcp.12731 11. Cotton MF, Shanhak E, Muller GJ, Heyes L, Lalis NN. The syndrome of inappropriate antidiuretic hormone secretion, an unusual association with presumed snakebite. S Afr Med J 1991;79(12):735-736. 12. Van Zyl JM, Muller GJ, van der Merwe MJ. Purification and properties of two phospholipase A2 enzymes from berg adder (Bitis atropos) venom. S Afr J Sci 2001;97(9-10):437-444.

Conclusion

This case highlights the importance of contacting a poison information helpline timeously, especially in cases where the reason

Accepted 23 August 2017.

December 2017, Print edition

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

RESEARCH

Impact of Xpert MTB/RIF rollout on management of tuberculosis in a South African community B-M Schmidt, MPH; H Geldenhuys, MB ChB; M Tameris, MB ChB; A Luabeya, MB ChB; H Mulenga, MPH; E Bunyasi, MB ChB; T Scriba, PhD; M Hatherill, MD South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa Corresponding author: M Hatherill (mark.hatherill@uct.ac.za) Background. The Xpert MTB/RIF test shortens the time to microbiological confirmation of pulmonary tuberculosis (TB) under research conditions. Objective. To evaluate the field impact of Xpert MTB/RIF rollout on TB diagnostic yield and time to treatment in a South African (SA) community. Methods. We compared TB investigation outcomes for 6-month calendar periods before and after Xpert MTB/RIF rollout in a semi-rural area of SA. The proportion of adult patients who tested positive by sputum smear microscopy, liquid culture or Xpert MTB/RIF and the proportion of positive sputum smear, liquid culture or Xpert MTB/RIF tests were compared. Secondary outcomes included time to laboratory diagnosis and treatment initiation. Data were collected from the National Health Laboratory Service database and from the Western Cape Provincial Department of Health TB register. Results. Regional rollout of Xpert MTB/RIF testing occurred in 2013. Of the 15 629 patients investigated in the post-rollout period, 7.9% tested positive on GeneXpert, compared with 6.4% of the 10 741 investigated in the pre-rollout period who tested positive by sputum smear microscopy (p<0.001). Median laboratory processing time was <1 day for Xpert MTB/RIF (interquartile range (IQR) 0 - 1) compared with 1 day (IQR 0 - 16) for sputum smear microscopy (p=0.001). The median time to TB treatment initiation was 4 days (IQR 2 - 8) after rollout compared with 5 days (IQR 2 - 14) before (p=0.001). Conclusions. Patients investigated for suspected pulmonary TB were more likely to be diagnosed after rollout of Xpert MTB/RIF testing, although the benefit to diagnostic yield was modest, and Xpert MTB/RIF testing was associated with a marginal improvement in time to treatment initiation. S Afr Med J 2017;107(12):1078-1081. DOI:10.7196/SAMJ.2017.v107i12.12502

South Africa (SA) is one of the 22 high tuberculosis (TB) burden countries that account for 83% of cases of TB worldwide.[1] Effective and rapid diagnosis of TB is an important strategy for reducing the burden of TB globally through early treatment initiation. Early initiation of treatment can reduce the opportunity for an infectious person to transmit TB within the community and improve patient treatment outcomes.[2,3] Xpert MTB/RIF is a diagnostic test for TB performed with the GeneXpert device (Cepheid, USA) – an automated, cartridge-based, nucleic amplification assay that detects both the Mycobacterium tuberculosis (MTB) organism and rifampicin resistance directly from sputum.[4] In ideal conditions, sample processing takes 2 hours, with <20 minutes’ hands-on processing time.[5] Sputum testing by the Xpert MTB/RIF test may enable quicker diagnosis and earlier treatment initiation than sputum smear microscopy.[6] Before availability of the Xpert MTB/RIF test, the diagnosis of pulmonary TB in resource-limited settings was based primarily on detection of acid-fast bacilli by sputum smear microscopy. Additional MTB culture might be performed to diagnose suspected smearnegative TB and to detect suspected drug resistance.[7] Sputum smear microscopy is well suited for low-income countries because it is inexpensive and rapid, requires basic laboratory infrastructure and expertise, and is highly specific. However, sputum smear microscopy has relatively low diagnostic sensitivity and cannot detect drug resistance.[7] Sputum MTB culture in liquid or solid medium is more sensitive than smear microscopy and can detect drug resistance, but MTB culture is too slow to have an immediate impact on clinical

management, requiring up to 8 weeks for laboratory processing. Additionally, MTB culture requires expensive equipment, advanced laboratory facilities and highly trained personnel.[4] Since December 2010, the World Health Organization has recommended global rollout of the Xpert MTB/RIF test for diagnosis of pulmonary TB. In SA, Xpert MTB/RIF testing was officially launched in October 2011 and complete implementation was reported by 2013.[8] Per SA national guidelines, TB diagnosis before Xpert MTB/RIF rollout relied on sputum smear microscopy on two different samples from an individual suspected of having pulmonary TB, taken on different days or on the same day at least 1 hour apart. TB diagnosis after Xpert MTB/RIF rollout relies on a single ‘spot’ sputum sample. MTB culture was not routinely performed before Xpert MTB/RIF rollout (and is not routinely performed now), but was requested for investigation of HIV-infected individuals who might have paucibacillary TB disease, or if drug resistance was suspected. All sputum samples were collected by staff at local primary healthcare facilities and processed by a regional National Health Laboratory Service (NHLS) laboratory that generated a paper-based result for the clinic.[9] Under research conditions, the Xpert MTB/RIF test greatly accelerates the time to laboratory diagnosis compared with MTB culture,[3,10] so that time to TB treatment initiation could potentially be reduced significantly – particularly for patients with sputum smear-negative TB disease, who would rely on MTB culture for diagnosis. Additionally, Xpert MTB/RIF has approximately two-fold

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RESEARCH

higher sensitivity than sputum smear microscopy.[10,11] For these reasons it was hoped that Xpert MTB/RIF would be a ‘game-changer’ for TB control.[7] However, the majority of data have been derived from ideal research conditions, and it is unclear what impact Xpert MTB/RIF has had in real-world field settings. Initial reports indicate that the SA Xpert MTB/RIF rollout has not contributed to significant improvement in mortality of patients investigated for pulmonary TB.[12]

Objective

To determine the impact of Xpert MTB/RIF rollout on yield of TB case detection, time to diagnosis and time to treatment initiation in an SA community with a very high incidence of TB.[13,14]

Methods

This before-and-after observational cohort study evaluated the impact of rollout of Xpert MTB/RIF testing on the detection and treatment of new adult pulmonary TB cases in the Cape Winelands East district of the Western Cape Province, SA. The study protocol was approved by the University of Cape Town Human Research Ethics Committee (ref. no. 387/2014). Waiver for individual consent was granted for secondary data analysis of de-identified health systems data. The Cape Winelands East is a semi-rural area with a very high estimated total TB case notification rate of 1 400 per 100 000 population.[14] There are >60 primary healthcare facilities in the district. Data from all adults aged ≥18 years who presented at primary healthcare facilities and were suspected of having pulmonary TB were included for potential analysis. Analyses were conducted for the period May - November in the calendar years 2012 and 2014. These corresponding 6-month periods were selected in order to bracket Xpert MTB/RIF implementation in the Cape Winelands East district, which occurred during 2013, and to adjust for possible seasonal confounders. Data from the two periods were compared for the proportion of patients investigated for TB who tested positive by sputum smear microscopy, liquid culture or Xpert MTB/RIF, and the proportion of sputum smear microscopy, liquid culture or Xpert MRB/RIF tests that were positive. Median time to laboratory diagnosis of pulmonary TB and median time to TB treatment initiation were compared, by test method and by period. Data were collected from the electronic NHLS database that records all microbiological tests for TB in the region, including the type of test (sputum smear microscopy, Xpert MTB/RIF or liquid culture) and the result of each test. Unique individuals tested for pulmonary TB were identified by unique laboratory identifiers. For the analysis of proportion of patients investigated who tested positive, the denominator was the total number of individuals in the study period who were tested, and the numerator was the number of patients with a positive test by a particular method (sputum smear microscopy, Xpert MTB/RIF, liquid culture). For analysis of the proportion of positive tests, the denominator was the total number of tests in the study period, and the numerator the number of positive tests by a particular method. Data for the proportion of tests reported as invalid were collected to evaluate differences between sputum smear microscopy and Xpert MTB/RIF laboratory processes. An invalid result was obtained when a sample was lost or when a test was not completed, for whatever reason. Secondary outcomes evaluated were median time to laboratory diagnosis and median time to TB treatment initiation. Time to laboratory diagnosis was defined as the time in days from when a sputum sample was collected to the time when that test result was reported. Time to TB treatment initiation was defined as the time from when a sputum sample was collected to the time when

TB treatment was recorded as being initiated. The dates of sputum collection and generation of the result report were determined from dates captured on the NHLS electronic database. The dates of treatment initiation for individual patients were retrieved from an electronic TB register maintained by the Western Cape Provincial Department of Health. Statistical tests for comparison of two proportions and Wilcoxon signed rank tests were used, with a threshold for significance of 0.05. Data were analysed using Stata 12 (StataCorp, USA).

Results

A total of 15 629 individuals with suspected TB were screened between May and November 2012 (pre-Xpert MTB/RIF rollout period) and 10 741 between May and November 2014 (post-rollout period). The median age and gender distribution of the patients investigated did not differ between the pre- and post-rollout periods (Table 1). Of the patients tested for TB in the pre-rollout period, 13 279 (85.0%) had sputum smear microscopy and 1 860 (11.9%) had additional liquid culture performed. Post-rollout, as expected, far fewer patients had sputum smear microscopy (n=2 542, 23.7%; p<0.001) or liquid culture (n=832, 7.7%; p<0.001) performed. The proportion of patients with positive sputum smear microscopy results was similar in the two periods (6.4% v. 6.2%; p=0.40), although the proportion of patients with positive liquid cultures was higher in the pre-rollout period than after rollout (1.5% v. 0.9%; p<0.001). In the post-rollout period, 7.9% of patients tested positive on Xpert MTB/ RIF, significantly more than by sputum smear microscopy in the preXpert MTB/RIF period in 2012 (7.9% v. 6.4%; p<0.001). A total of 21 392 samples for TB investigation were processed in the pre-rollout period, compared with 14 858 in the postrollout period. The proportion of sputum smear microscopy-positive samples was similar before and after rollout (5.7% v. 5.0%; p=0.002), the proportion of positive liquid cultures was higher in the prerollout period (3.2% v. 1.8%; p<0.001), and the proportion of positive Xpert MTB/RIF results (5.7%) in the post-rollout period was similar to the proportion of positive sputum smear microscopy results in the pre-rollout period (5.7%; p=0.95). The median time to laboratory diagnosis for sputum smear microscopy in the pre-rollout period was 1 day compared with <1 day for Xpert MTB/RIF in the post-rollout period. The median time to laboratory diagnosis by MTB culture was also slightly longer before than after rollout (39 v. 38 days; p<0.001). The median time to treatment initiation was 5 days before Xpert MTB/RIF rollout, compared with 4 days after rollout (p<0.001) (Table 2).

Discussion

We demonstrated that in a community-based study of the impact of Xpert MTB/RIF rollout in a high-burden primary healthcare setting in SA, patients with pulmonary TB were more likely to be diagnosed in the post-rollout period, when both Xpert and liquid culture were available, than in the pre-rollout period, when only sputum smear microscopy and liquid culture were available. Although the additional benefit to diagnostic yield was modest, it was also associated with a small improvement in time to laboratory diagnosis and time to TB treatment initiation, saving 1 day to start of treatment after Xpert MTB/RIF rollout, compared with the period in which sputum smear microscopy was the primary diagnostic modality. Although minor, this improvement in time to treatment may be clinically important in view of the very high incidence of TB disease in this region (1 400/100 000 population per year).[14] Our findings are consistent with other studies[6,15,16] that have shown that application of Xpert

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RESEARCH

Table 1. Patients investigated for suspected pulmonary TB* Variable Denominator, N Sex, n (%) Male Female Unknown Age (yr), median (IQR) (range) Xpert MTB RIF, n (%) Xpert done Xpert negative Xpert invalid Xpert positive Sputum smear, n (%) Smear done Smear negative Smear invalid Smear positive MTB culture, n (%) Culture done Culture negative Culture invalid Culture positive

Individuals with suspected TB May - November 2012 May - November 2014 15 629 10 741

p-value 0.11

Sputum samples May - November 2012 May - November 2014 21 392 14 858

8 065 (51.6) 7 179 (45.9) 385 (2.5) 37 (28 - 47) (18 - 87)

5 833 (54.3) 4 731 (44.1) 216 (2.0) 36 (28 - 46) (18 - 87)

11 030 (51.6) 9 857 46.1) 505 (2.4) 36 (28 - 47) (18 - 90)

7 949 (53.5) 6 693 (45.1) 216 (1.5) 36 (28 - 46) (18 - 87)

n/a n/a n/a n/a

6 336 (59.0) 5 471 (50.9) 14 (0.1) 851 (7.9

n/a n/a n/a n/a

6 336 (42.6) 5 471 (36.8) 14 (0.1) 851 (5.7)

13 279 (85.0) 11 498 (73.6) 775 (5.0) 1 006 (6.4)

2 542 (23.7) 1 286 (12.0) 592 (5.5) 664 (6.2)

15 620 (73.0) 13 369 (62.5) 1 029 (4.8) 1 222 (5.7)

3 609 (24.3) 1 716 (11.5) 1 155 (7.8) 738 (5.0)

1 860 (11.9) 1 471 (9.2) 152 (1.0) 237 (1.5)

832 (7.7) 664 (6.2) 72 (0.7) 96 (0.9)

4 245 (19.8) 3 187 (14.9) 367 (1.7) 691 (3.2)

2 209 (14.9) 1 748 (11.8) 189 (1.3) 272 (1.8)

0.40 <0.001

<0.001

TB = tuberculosis; IQR = interquartile range; n/a = not applicable. *May - November 2012 represents the pre-rollout period before Xpert MTB/RIF implementation and May - November 2014 the post-rollout period after implementation.

Table 2. Median time to pulmonary TB diagnosis (TTD) and TB treatment initiation (TTI) in patients screened for suspected pulmonary TB* Xpert MTB/RIF TTD (d), median (IQR) Sputum smear TTD (d), median (IQR) Culture TTD (d), median (IQR) TTI (d), median (IQR)

May - November 2012

May - November 2014

n/a

0 (0 - 1)

1 (0 - 16)

2 (1 - 22)

<0.001

39 (37 - 40) 5 (2 - 14)

38 (37 - 40) 4 (2 - 8)

<0.001 <0.001

p-value

MTB/RIF in a primary healthcare programmatic setting can improve the rate of TB case detection and reduce time to TB diagnosis. We also observed a reduction in the number of sputum samples sent for testing (30.5% less) and the number of persons tested for TB (31.3% less) after Xpert MTB/RIF rollout (Table 1), with a consequent reduction in workload for TB clinic staff and laboratory staff in the latter period. However, we could not determine whether this decline reflected a true decline in the community burden of TB disease, and a corresponding reduction in persons presenting to the primary healthcare clinics with suspected TB, or was due to a change in TB screening practices, since pre-rollout sampling required two sputum samples. As expected, fewer sputum samples were sent for smear microscopy in the post-rollout period, but the proportion of positive smear results in both analysis periods was similar, implying that the rate of TB disease among investigated patients did not change, and therefore that the higher proportion of detected TB cases in the post-rollout period was due to more sensitive diagnostic testing using Xpert MTB/RIF. However, although the proportion of individuals screened for TB who had MTB culture performed was

higher before than after Xpert MTB/RIF rollout, the MTB culture positivity rate followed the same trend (1.5% v. 0.9%; p<0.001). This finding might be explained if patients in the later period were slightly more paucibacillary, but not sufficiently so to make an impact on the rate of sputum smear positivity. A consequence of Xpert MTB/RIF rollout was decreased demand for MTB culture testing, which we hypothesise may be due to increased diagnostic confidence in Xpert MTB/RIF and/or the fact that Xpert MTB/RIF tests for rifampicin susceptibility, with less reliance on MTB culture to exclude drugresistant organisms. The rollout of Xpert MTB/RIF testing at primary healthcare level was reportedly completed in this community by 2013, with a corresponding change in the recommended TB testing algorithm from sputum smear microscopy to Xpert MTB/RIF. However, we observed that almost a quarter of individuals with suspected TB who underwent screening in the post-rollout period still underwent sputum smear microscopy and not Xpert MTB/RIF testing. This finding indicates incomplete uptake of the new guidelines,[16] possibly owing to a GeneXpert cartridge shortage in 2013.[15] A forecast

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cartridge price reduction in 2012 caused some countries to delay shipments, with a resultant break in supply and temporary reversion to first-line sputum smear microscopy testing.[15] Creswell et al.[15] also identified lack of or poor infrastructure and interrupted power supply as key barriers to Xpert MTB/RIF implementation. Additional local infrastructure improvements to address issues of uninterrupted electricity supply, climate control, work-space security, ventilation and dust control were required to set up GeneXpert machines. Unlike smear and culture testing, Xpert testing requires an uninterrupted power supply for the duration of the testing cycle.[15]

Study strengths and limitations

The main strengths of our study are that it was pragmatic, based on actual TB programmatic data in a field setting, and represents translation value at primary healthcare level in an endemic community. The benefits, or lack of benefit, of programmatic rollout of Xpert MTB/RIF at community level cannot be assumed from national-level statistics. However, one limitation of our study was that we could not identify the number of tests and the types of tests performed on each individual with suspected TB in this community; rather, we measured the total number of individuals investigated and number of samples processed. While efforts were made to merge databases that captured individual patient-level sputum smear microscopy, Xpert MTB/RIF, and MTB culture results, this was not always technically possible. For example, since all Xpert MTB/ RIF laboratory identifiers were unique, we could not link Xpert MTB/RIF laboratory identifiers to individual patient sputum smear microscopy or MTB culture results. Another limitation of our study was the non-availability of HIV incidence for our study periods, with the latest HIV transmission rate only known for 2016 in the Western Cape (1.4%). It is unclear whether the decline in TB testing with Xpert MTB/RIF may be related to improved control of the HIV epidemic.

Conclusion

In summary, we found that rollout of Xpert MTB/RIF in an SA community with a very high TB burden led to a modest improvement in the rate of detection of pulmonary TB and slightly more rapid treatment initiation among individuals screened at primary healthcare clinics. These benefits were associated with a reduced TB investigation workload for clinic and laboratory staff. These findings support continued use of this diagnostic test in the TB control programme and continued attempts to facilitate universal implementation in SA communities, where marginal

systemic improvements may translate to major individual patient benefit. Acknowledgements. None. Author contributions. B-MS, HG and MH conceptualised the research question; B-MS and HG drafted the protocol and manuscript with oversight from MH; MT, AL, HM and EB contributed intermittently to the various components of both the protocol and the manuscript; and TS contributed to the final drafts of the protocol and the manuscript. Funding. None. Conflicts of interest. None. 1. World Health Organization. Global Tuberculosis Report. 2015. www.who.int/tb/publications/global_ report/gtbr15_main_text.pdf (accessed 15 April 2015). 2. Pinto M, Steffen R, Cobelens F, van den Hof S, Entringer A, Trajman A. Cost-effectiveness of the Xpert® MTB/RIF assay for tuberculosis diagnosis in Brazil. Int J Tuberc Lung Dis 2016;20(5):611-618. https:// doi.org/10.5588/ijtld.15.0455. 3. Boehme CC, Nicol MP, Nabeta P, et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: A multicentre implementation study. Lancet 2011;377(9776):1495-1505. https://doi.org/10.1016/S01406736(11)60438-8 4. Nicol MP. New developments in the laboratory diagnosis of tuberculosis: New and faster ways of diagnosing tuberculosis are needed urgently. CME 2010;28(6):246-250. https://www.ajol.info/index.php/ cme/article/download/71268/60220 (accessed 15 February 2014). 5. Meyer-Rath G, Schnippel K, Long L, et al. The impact and cost of scaling up GeneXpert MTB/RIF in South Africa. PloS One 2012;7(5):e36966. https://doi.org/10.1371/journal.pone 6. Cox HS, Mbhele S, Mohess N, et al. Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: A pragmatic randomised trial. PLoS Med 2014;11(11):e1001760. https://doi.org/10.1371/journal.pmed.1001760 7. Evans CA. GeneXpert – a game-changer for tuberculosis control? PLoS Med 2011;8(7):e1001064. https:// doi.org/10.1371/journal.pmed.1001064 8. National Health Laboratory Service. 2014. www.nhls.ac.za/ (accessed 15 May 2014). 9. National Department of Health, South Africa. South African National Tuberculosis Guidelines. 2014. https://www.idealclinic.org.za/docs/National-Priority-Health-Conditions/National%20TB%20 management%20guidelines%202014.pdf (accessed 15 May 2014). 10. Lawn SD, Mwaba P, Bates M, et al. Advances in tuberculosis diagnostics: The Xpert MTB/RIF assay and future prospects for a point-of-care test. Lancet Infect Dis 2013;13(4):349-361. https://doi.org/10.1016/ S1473-3099(13)70008-2 11. Van Zyl-Smit RN, Binder A, Meldau R, et al. Comparison of quantitative techniques including Xpert MTB/RIF to evaluate mycobacterial burden. PloS One 2011;6(12):e28815. https://doi.org/10.1371/ journal.pone.0028815 12. Churchyard GJ, Stevens WS, Mametja LD, et al. Xpert MTB/RIF versus sputum microscopy as the initial diagnostic test for tuberculosis: A cluster-randomised trial embedded in South African roll-out of Xpert MTB/RIF. Lancet Glob Health 2015;3(8):e450-e457. https://doi.org/10.1016/S2214-109X(15)00100-X 13. Tameris MD, Hatherill M, Landry BS, et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: A randomised, placebo-controlled phase 2b trial. Lancet 2013;381(9871):1021-1028. https://doi.org/10.1016/S0140-6736(13)60177-4 14. Mahomed H, Hawkridge T, Verver S, et al. Predictive factors for latent tuberculosis infection among adolescents in a high-burden area in South Africa. Int J Tuberc Lung Dis 2011;15(3):331-336. https:// www.ncbi.nlm.nih.gov/pubmed/21333099 15. Creswell J, Codlin AJ, Andre E, et al. Results from early programmatic implementation of Xpert MTB/ RIF testing in nine countries. BMC Infect Dis 2014;14:2. https://doi.org/10.1186/1471-2334-14-2 16. Van den Handel T, Hampton KH, Sanne I, Stevens W, Crous R, van Rie A. The impact of Xpert® MTB/RIF in sparsely populated rural settings. Int J Tuberc Lung Dis 2015;19(4):392-398. https://doi.org/10.5588/ ijtld.14.0653

Accepted 17 July 2017.

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Defining the need for surgical intervention following a snakebite still relies heavily on clinical assessment: The experience in Pietermaritzburg, South Africa J P Pattinson,1,2 MB ChB; V Y Kong,1,2 MB ChB, MSc, PhD, MRCS (Ed), FRSPH; J L Bruce,2 FCS (SA); G V Oosthuizen,2 FCS (SA); W Bekker,2 FCS (SA); G L Laing,2 FCS (SA); D Wood,3 MB ChB, PhD; P Brysiewicz,4 PhD; D L Clarke,5,6 FCS (SA), PhD Department of Surgery, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa General Surgery, Pietermaritzburg Hospital Complex, KwaZulu-Natal, South Africa 3 Department of Emergency Medicine, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa 4 School of Nursing and Public Health, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa 5 Department of Surgery, Grey’s Hospital and College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa 6 Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 1 2

Corresponding author: J P Pattinson (paddypattinson@yahoo.com) Background. This audit of snakebites was undertaken to document our experience with snakebite in the western part of KwaZulu-Natal (KZN) Province, South Africa (SA). Objective. To document our experience with snakebite in the western part of KZN, and to interrogate the data on patients who required some form of surgical intervention. Methods. A retrospective study was undertaken at the Pietermaritzburg Metropolitan Trauma Service, Pietermaritzburg, SA. The Hybrid Electronic Medical Registry was reviewed for the 5-year period January 2012 - December 2016. All patients admitted to the service for management of snakebite were included. Results. The offending snake is rarely identified, and the syndromic approach is now the mainstay of management. Most envenomations seen during the study period were cytotoxic, presenting with painful progressive swelling (PPS). We did not see any purely neurotoxic or haemotoxic envenomations. Antivenom is required for a subset of patients. The indications are essentially PPS that increases by >15 cm over an hour, PPS up to the elbow or knee after 4 hours, PPS of the whole limb after 8 hours, threatened airway, shortness of breath, associated clotting abnormalities and compartment syndrome. If no symptoms have manifested within 1 hour of a snakebite, clinically significant envenomation is unlikely to have occurred. Antivenom is associated with a high rate of anaphylaxis and should only be administered when absolutely indicated, preferably in a high-care setting under continuous monitoring. The need for surgery is less well defined. Urgent surgery is indicated for compartment syndrome of the limb, which is a potentially life- and limb-threatening condition. Its diagnosis is usually made clinically, but this is difficult in snakebites. Morbidity and cost increase dramatically once fasciotomy is required, as evidenced by much longer hospital stay. There is frequently a degree of cross-over between cytotoxicity and haemotoxicity in envenomations that require fasciotomy, which means that fasciotomy may result in catastrophic bleeding and should be preceded by the administration of antivenom, especially in patients with a low platelet count or a high international normalised ratio. Physiological and biochemical markers are unhelpful in assessing the need for fasciotomy. Objective methods include measurement of compartment pressures and ultrasound. Conclusion. The syndromic management of snakebite is effective and safe. There is a high incidence of anaphylactic reactions to antivenom, and its administration must be closely supervised. In our area we overwhelmingly see cytotoxic snakebites with PPS. Surgery is often needed, and we need to refine our algorithms in terms of deciding on surgery. S Afr Med J 2017;107(12):1082-1085. DOI:10.7196/SAMJ.2017.v107i12.12628

The management of snakebite injuries remains controversial and a source of endless fascination for surgeons. Treatment can seldom be based on the identity of the snake, as it is very unlikely that the offending reptile can be captured and accurately identified. For this reason, the current approach is a syndromic one, popularised by Blaylock[1] around the turn of the millennium and based on the clinical syndrome seen and the response to treatment. There are essentially three syndromes: painful progressive swelling (PPS), progressive weakness, and bleeding.[1] We have tended to follow this approach to the management of snakebite over the past 10 years at our institution in the western part of KwaZulu-Natal (KZN) Province, South Africa (SA). There is still an area of controversy

surrounding the need for surgical intervention. Most patients will respond to non-operative care, but a subset will require surgery as part of their management. The syndromic approach to management of snakebite recognises the fact that it is usually impossible to adequately identify the type of snake that has bitten the patient. The three recognisable clinical syndromes of PPS, progressive weakness and bleeding[1] correspond to the three venom types, namely cytotoxic, neurotoxic, and haemotoxic. If one of these syndromes has not manifested within 1 hour of a snakebite, clinically significant envenomation is unlikely to have occurred.[2] According to Blaylock,[1] the therapeutic triad of elevation, intravenous fluids and analgesia is the mainstay of managing

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snakebites. Elevation is analgesic and diminishes venous swelling, and intravenous fluids replace the intravascular fluid that has extravasated into the tissues.[1] In addition to these basic supportive interventions, antivenom and surgery are two other interventions that need to be used selectively. Antivenom is needed for a subset of patients. In broad terms the indications include complications of PPS, rapid respiratory deterioration following neurotoxic envenomation, or uncontrolled bleeding.[1] Surgery is indicated mainly for compartment syndrome of the limbs, and debridement following tissue necrosis or secondary sepsis.[3]

Objective

This audit was undertaken to document our experience with snakebite in the western part of KZN, and to interrogate the data on patients who required some form of surgical intervention.

Methods

Clinical setting

This was a retrospective study undertaken at the Pietermaritzburg Metropolitan Trauma Service (PMTS) in Pietermaritzburg, the capital of KZN. The Hybrid Electronic Medical Registry (HEMR) was reviewed for the 5-year period January 2012 - December 2016. The PMTS provides definitive trauma care to the city of Pietermaritzburg. It is one of the largest academic trauma centres in KZN and also serves as the referral centre for 19 rural hospitals in the province, with a total catchment population of over three million.

The study

All patients admitted to our service for management of snakebite were included in this study. Basic demographic data, mechanism of injury and admission physiology were reviewed, as were all operative records. Details of the site of the snakebite, the type of syndrome, the clinical progression of the syndrome, the need for antivenom and need for operative management were recorded. The outcome of each operative intervention was documented. All in-hospital morbidities were reviewed.

The Zululand Scoring System (ZSS)

Wood et al.[4] have proposed a scoring system in snakebites to attempt to predict the likelihood of an active treatment intervention (ATI). ATI includes the administration of antivenom and any surgery (including debridements, amputations or fasciotomies). The scoring system allocates a point for each of age <14 years, admission >7 hours, white cell count >10 × 109/L, international normalised ratio (INR) >1.2, platelet count <92 × 109/L, and haemoglobin concentration <7.4 g/dL. Patients scoring ≥4 are predicted to require an ATI. We set out to use data from the HEMR to see whether the ZSS could be validated.

Ethics approval

Ethics approval for this study and for maintenance of the registry was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (ref. nos BE 207/09 and BCA 221/13).

Results

A total of 222 patients were admitted following a snakebite during the period under review. The male/female ratio was 1.36:1. The average age was 21.4 years. Just under half of the patients (47.8%) were <12 years of age, and just under a third (29.2%) were between 12 and 35 years old. The snakebite was witnessed in 202 cases (91.0%), but the snake was positively identified in only 14 cases (6.3%). The sites of the bites are listed in Table 1. A tourniquet was

Table 1. Sites of the snakebites Area bitten Toes Foot Leg Thigh Fingers Hand Forearm Upper arm Head and neck Trunk

Patients, % 4.1 47.8 19.4 1.4 3.6 13.5 5.4 1.4 2.3 1.4

applied in 8 cases (3.6%). These were applied at the base hospital. The bites were venomous in 200 cases (90.1%) and either nonvenomous or a ‘dry bite’ in the remainder. In 99.1% of cases there was a single bite. Of the bites that were venomous, 187 (93.5%) were cytotoxic and 13 (6.5%) were cytotoxic and haemotoxic. There were no pure haemotoxic or neurotoxic bites. Eighteen patients (8.1%) required intensive care unit (ICU) or high-care admission. In 8 cases (44.4%) this was because of complications of the envenomation, and in 10 cases (55.6%) because of anaphylaxis from antivenom administration.

Antivenom

Antivenom was required in 28 patients (12.6%). Compared with older patients, more patients aged <20 years received antivenom (58.6%). The rate of anaphylaxis was 42.9%. Children (<12 years) were most likely to develop anaphylaxis (58.3%). We did not have any mortality as a result of anaphylaxis, although 13 patients (46.4%) who received antivenom required ICU or high-care admission. Four of these patients required ventilation, 1 as a result of airway compromise after cytotoxic envenomation, and 3 as a consequence of anaphylaxis. Twelve patients (42.9%) who received antivenom required fasciotomy. The average length of stay for a patient who received antivenom was 7.5 days, compared with 2.8 days for those who had simple management.

Surgery

An operation was required in 33 patients (14.9%). Fasciotomy was performed in 14 patients (6.3%). The male/female ratio of patients who required fasciotomy was 1.56:1. A large proportion of patients requiring fasciotomy (50.0%) were between the ages of 13 and 35 years. Fasciotomies were performed equally on the upper and lower limbs, and equally on patients over and under 20 years of age. A total of 6 patients (42.9%) who underwent fasciotomy required highcare or ICU admission postoperatively. Over two-thirds (78.6%) of patients who required fasciotomy needed follow-up surgery for debridement, grafting or closure. The remainder healed by secondary intention, were grafted at base or were lost to follow-up. The average length of hospital stay for patients who received fasciotomy was 13.1 days. This is 10 days longer than the average hospital stay for patients with snakebite who received simple management. Other types of surgery included 16 debridements (7.2%), 12 split-skin grafts (5.4%), and 3 incision and drainages (1.4%). One amputation and one tendon repair were required.

Complications

The following complications were recorded: compartment syndrome 5.9%, acute kidney injury 2.7% and respiratory distress 2.3%. One patient had iatrogenic tendon injury during fasciotomy.

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The Zululand Scoring System

A total of 44 of our patients required an ATI. Of these, 15 had scores of ≥4 points according to Wood et al.’s[4] ZSS (therefore predicting the need for ATI), which gives a positive predictive value of only 34.1%. Of the remaining patients (who did not require an ATI), 78 had sufficient data for a score to be calculated and of these 17 scored ≥4 points, providing a negative predictive value of 78.2%.

Discussion

The management of snakebite depends on the type of envenomation. However, the snake is very seldom identified and clinicians have to manage the bite according to a syndromic approach popularised by Blaylock from Eshowe Hospital in KZN. The most common syndrome has been reported as PPS from cytotoxic venom, most usually due to a bite from a puff adder, rinkhals or Mozambique spitting cobra,[1,5] which is very much in keeping with our findings. We did not manage any purely neurotoxic or haemotoxic bites. This contrasts with reports from our sister institution in Zululand,[5] reflecting the fact that the distribution of the two most notorious neurotoxic snakes, the black and green mambas, is largely in the coastal regions of KZN. The incidence of black mamba bites may in fact be under-reported, as these cases may not reach hospital. The surgical burden in Zululand is lower than in Pietermaritzburg.[5] Purely haemotoxic bites are rare because of the timid nature of the two haemotoxic snakes, the boomslang and vine snake (twig snake). The variation of the distribution of poisonous snakes in KZN is shown in Tables 2 and 3. Antivenom is needed for a subset of patients. There are two major types of antivenom available, namely polyvalent and monovalent, produced by South African Vaccine Producers (SAVP). Polyvalent antivenom is available as an emergency stock item in most hospitals. A list of snakes that polyvalent antivenom is effective against is provided in Table 4. Monovalent antivenom is specific to the boomslang and must be ordered specifically from SAVP. A list of links and contact details is provided in Table 5. According to Blaylock,[1] the indications for antivenom in patients with PPS, our most commonly encountered scenario, include PPS that increases by >15 cm over Table 2. Poisonous snakes most commonly found in Zululand Puff adder (Bitis arietans) Night adder (Causinae rhombeatus) Gaboon viper (Bitis gabonica) Mozambique spitting cobra (Naja mossambica) Rinkhals (Hemachatus haemachatus) Zebra, western barred, or black spitting cobra (Naja nigricincta) Forest or white-lipped cobra (Naja melanoleuca) Snouted or banded Egyptian cobra (Naja annulifera) Black mamba (Dendroaspis polylepis) Green mamba (Dendroaspis angusticeps) Vine or twig snake (Thelotornis species) Boomslang (Dispholidus typus)

Table 3. Poisonous snakes most commonly found in the Pietermaritzburg area Night adder (Causinae rhombeatus) Puff adder (Bitis arietans) Rinkhals (Hemachatus haemachatus) Black mamba (Dendroaspis polylepis)* Boomslang (Dispholidus typus)

an hour, PPS up to the elbow or knee 4 hours after envenomation, PPS of the whole limb after 8 hours, threatened airway, shortness of breath, associated clotting abnormalities and compartment syndrome. The indications for antivenom administration are listed in Table 6. The administration of antivenom is associated with a high rate of anaphylaxis.[5] Our rate of anaphylaxis was 42.9%, which is very much in keeping with reports by other local authors such as Wood et al.,[5] who had a rate of anaphylaxis of 23% (up to 43% in the 10 - 20-year age group). Antivenom must be administered in a highcare setting under continuous monitoring. We follow Wood et al.’s[5] recommendation to administer a dose of intramuscular adrenaline prior to antivenom administration. Although we had no deaths associated with anaphylaxis, just under half of the patients (46.4%) who received antivenom required ICU or high-care admission. More patients aged <20 years than older patients received antivenom. This is in keeping with Wood et al.’s[5] findings. These authors felt that the smaller size of the child in conjunction with equal envenomation from a bite meant that children were more likely to require antivenom than adults.[5] Children (<12 years) were more likely to develop anaphylaxis (58.3%), which is also in keeping with Wood et al.’s[5] findings. The protocol for antivenom administration is set out in Table 7. The need for surgery is less well defined. Urgent surgery is required to manage a compartment syndrome of the limb, which is a potentially life- and limb-threatening condition traditionally diagnosed clinically by a tense and swollen limb with decreased perfusion.[3] This diagnosis is difficult, as a snake envenomation often mimics a compartment syndrome.[3] This is because the majority of cases are exquisitely tender and have ‘pain on passive stretch’ despite the absence of a true compartment syndrome. More reliable signs are a tense compartment with distal loss of sensation. Loss of distal pulse is a late sign. The situation in snakebite is complicated by the fact that the swelling may be confined to the subcutaneous fat and skin, not truly reflecting a compartment syndrome of the deep compartments.[6] Morbidity and cost increase dramatically once Table 4. Envenomations for which polyvalent antivenom is effective Puff adder (Bitis arietans) Gaboon adder (Bitis gabonica) Rinkhals (Haemachatus haemachatus) Green mamba (Dendroaspis angusticeps) Black mamba (Dendroaspis polylepsis) Jameson’s mamba (Dendroaspis jamesoni) Cape cobra (Naja nivea) Forest cobra (Naja melanoleuca) Snouted (Egyptian) cobra (Naja annulifera) Mozambique spitting cobra (Naja mossambica)

Table 5. South African Vaccine Producers contact details Business hours After-hours emergency Fax E-mail Physical address

Postal address

*Less common than in the Zululand area.

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011 386 6063/2 011 386 6000 011 386 6016 megans@savp.co.za cillaf@savp.co.za SAVP, Modderfontein Road, Sandringham, Johannesburg, South Africa PO Box 28999, Sandringham, Johannesburg, 2131

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Table 6. Indications for antivenom administration[1] Cytotoxic (PPS) Swelling extending at 15 cm or more for 1 hour Swelling to the elbow or knee by 3 - 4 hours Swelling of a whole limb within 8 hours Swelling threatening the airway Associated unexplained shortness of breath Associated abnormality of blood clotting (or prior to fasciotomy) Compartment syndrome or compressed major blood vessel

Neurotoxic (progressive weakness) Pins and needles, profuse sweating, and excessive salivation (or metallic taste) after mamba envenomation Shortness of breath due to weakness in the absence of PPS Inability to swallow saliva Generalised weakness in the presence of PPS or generalised muscle pain

Haemotoxic (bleeding) Fang punctures do not stop bleeding and/ or severe headaches, dizziness, fainting or convulsions Active systemic bleeding (not bruising of the bitten limb alone) Non-clotting blood after 20 minutes in an undisturbed, new, dry, clean test tube. Use blood from a healthy person as a control Significant laboratory evidence of a blood clotting abnormality

PPS = painful progressive swelling.

Table 7. Protocol for antivenom administration[5] Discuss with emergency medicine or surgery consultant prior to administration Doctor with airway skills and appropriate drugs and equipment for urgent intubation and ventilation on standby Facemask oxygen and two large-bore intravenous lines Continuous pulse, blood pressure, and oxygen saturation monitoring Resuscitation trolley and defibrillator on standby Intramuscular or subcutaneous adrenaline 0.3 - 0.5 mg (0.01 mg/kg in children) prior to antivenom administration (hydrocortisone and promethazine are no longer given routinely) Polyvalent antivenom 80 mL over 15 minutes (a repeat dose may be given if symptoms continue to progress in 1 - 2 hours)

fasciotomy is required, as evidenced by the much longer hospital stay. This highlights the importance of not performing fasciotomies unnecessarily. While our fasciotomy rate may be appropriate for a referral hospital, it must be kept in mind that some fasciotomies may have been performed unnecessarily and that clinical assessment alone, considering all its limitations in snakebites, may not be sufficient in deciding on the need for fasciotomy. Physiological and biochemical markers are unhelpful in assessing the need for fasciotomy. Objective methods include measuring of compartment pressures and ultrasound.[6] Measuring of compartment pressures is a painful, invasive and cumbersome technique. Wood et al.[4] have advocated the use of ultrasound as a painless and non-invasive technique of diagnosing compartment syndrome in snakebites. In Wood et al.’s[6] study of ultrasound findings in 42 patients with cytotoxic snakebites, it was found that swelling was most commonly confined to the subcutaneous tissues, with the muscle compartment seldom affected. When intramuscular swelling is demonstrated, the diagnosis of compartment syndrome should be considered.[6] Ultrasound may therefore provide the answer. There is frequently a degree of cross-over between cytotoxicity and haemotoxicity in cytotoxic envenomations. This means that fasciotomy may result in catastrophic bleeding and should be preceded by the administration of antivenom, especially in patients with a low platelet count or a high INR.[3] Deranged clotting profiles or low platelets will be resistant to correction until antivenom has been given. Our institution follows a protocol of antivenom administration prior to fasciotomy to reduce intraoperative bleeding. Only patients who underwent fasciotomy did not receive antivenom, and these were delayed presentations (>48 hours after envenomation).

Conclusion

The syndromic management of snakebite is effective and safe. There is a high incidence of anaphylactic reactions to antivenom, and its administration must be closely supervised. In our area we overwhelmingly see cytotoxic snakebites with PPS. Surgery is often needed, and we need to refine our algorithms in terms of deciding on surgery. Acknowledgements. None. Author contributions. All authors: substantial contributions to the conception and design of the work; acquisition, analysis, and interpretation of data for the work; drafting the work and revising it critically for important intellectual content; final approval of the version to be published; agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Funding. None. Conflicts of interest. None. 1. Blaylock RS. The identification and syndromic management of snakebite in South Africa. S Afr Fam Pract 2005;47(9):48-53. https://doi.org/10.1080/20786204.2005.10873288 2. Blaylock RS. Time of onset of clinical envenomation following snakebite in southern Africa. S Afr Med J 1991;80(3):253. 3. Blaylock RS. Femoral vessel entrapment and compartment syndromes following snakebite. S Afr J Surg 2003;41(3):72-73. 4. Wood D, Sartorius B, Hift R. Classifying snakebite in South Africa: Validating a scoring system. S Afr Med J 2016;107(1):46-51. https://doi.org/10.7196/SAMJ.2016.v107.i1.11361 5. Wood D, Webb C, DeMeyer J. Severe snakebites in northern KwaZulu-Natal: Treatment modalities and outcomes. S Afr Med J 2009;99(11):814-818. 6. Wood D, Sartorius B, Hift R. Ultrasound findings in 42 patients with cytotoxic tissue damage following bites by South African snakes. Emerg Med J 2016;33(7). https://doi.org/10.1136/ emermed-2015-205279

Accepted 17 July 2017.

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

RESEARCH

A comparison of private and public sector intensive care unit infrastructure in South Africa S Mahomed, MB ChB, MMed; A W Sturm, MD, PhD; P Moodley, MB ChB, PhD School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZuluNatal, Durban, South Africa Corresponding author: S Mahomed (mahomeds@ukzn.ac.za) Background. Intensive care units (ICUs) are designed to care for patients who are often at increased risk of acquiring healthcareassociated infections. The structure of ICUs should be optimally designed to facilitate the care of these critically ill patients, and minimise their risk of infection. National regulations (R158) were developed to govern the building and registration of private hospitals, and until recently equivalent regulations were not available for public hospitals. Objective. To assess and compare the compliance of ICUs in the private and public sectors with the R158 regulations. Methods. A cross-sectional study design was used to assess the infrastructure of 25 private sector and 6 public sector ICUs in eThekwini Health District, KwaZulu-Natal Province, South Africa. We used the R158 checklist, which was developed by the KwaZulu-Natal Department of Health Private Licensing Unit and Infection Prevention and Control Unit. The aspects covered in the R158 checklist were categorised into the design, general safety and patient services of the ICUs. Results. Most of the ICUs in both sectors met the general safety requirements. There were varying levels of compliance with the design criteria. Only 7 (28.0%) and 1 (16.7%) of the private and public ICUs, respectively, had sufficient space around the beds. Twenty-two private ICUs (88.0%) and 4 public ICUs (66.7%) had isolation rooms, but only some of these isolation rooms (15 private and 2 public) had appropriate mechanical ventilation. None of the ICUs had clinical hand-wash basins in the nurse stations and dirty utility rooms. The majority of the ICUs had the required number of oxygen and electric outlets at the bedside. None of the public ICUs met the light intensity requirement over the bed area. Conclusions. Adequate spacing in ICUs is an issue in many cases. Interventions need to be put in place to ensure that ICUs meet the relevant design standards. There is an urgent need to revise the R158 regulations to reflect current best practices, particularly with regard to infection control. The same standards should be applied to ICUs in the private and public health sectors to maintain quality of care to patients. S Afr Med J 2017;107(12):1086-1090. DOI:10.7196/SAMJ.2017.v107i12.12631

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i12.12631

Mortality trends in the City of Cape Town between 2001 and 2013: Reducing inequities in health P Groenewald,1 MB ChB, MPhil (Public Health); I Neethling,1 MSc; J Evans,2 PhD; V Azevedo,3 MB ChB; T Naledi,2 MB ChB, FCPHM (SA); R Matzopoulos,1 BBusSci, MPhil (Epidemiology), PhD (Public Health); N Nannan,1 MSc (Molecular Biology), MSc (Medical Demography); J Daniels,3 Dip Acupuncture, MPH; D Bradshaw,1 MSc, DPhil (Oxon) Burden of Disease Research Unit, South African Medical Research Council, Cape Town, South Africa Western Cape Government: Health, Cape Town, South Africa 3 City Health, City of Cape Town, South Africa 1 2

Corresponding author: P Groenewald (pamela.groenewald@mrc.ac.za) Background. The City of Cape Town (CoCT), South Africa, has collected cause-of-death data from death certificates for many years to monitor population health. In 2000, the CoCT and collaborators set up a local mortality surveillance system to provide timeous mortality data at subdistrict level. Initial analyses revealed large disparities in health across subdistricts and directed the implementation of public health interventions aimed at reducing these disparatities.

December 2017, Print edition

RESEARCH

Objective. To describe the changes in mortality between 2001 and 2013 in health subdistricts in the CoCT. Methods. Pooled mortality data for the periods 2001 - 2004 and 2010 - 2013, from a local mortality surveillance system in the CoCT, were analysed by age, gender, cause of death and health subdistrict. Age-specific mortality rates for each period were calculated and agestandardised using the world standard population, and then compared across subdistricts. Results. All-cause mortality in the CoCT declined by 8% from 938 to 863 per 100 000 between 2001 - 2004 and 2010 - 2013. Mortality in males declined more than in females owing to a large reduction in male injury mortality, particularly firearm-related homicide. HIV/ AIDS and tuberculosis (TB) mortality dropped by ~10% in both males and females, but there was a marked shift to older ages. Mortality in children aged <5 years dropped markedly, mostly owing to reductions in HIV/AIDS and TB mortality. Health inequities between subdistricts were reduced, with the highest-burden subdistricts achieving the largest reductions in mortality. Conclusions. Local mortality surveillance provides important data for planning, implementing and evaluating targeted health interventions at small-area level. Trends in mortality over the past decade indicate some gains in health and equity, but highlight the need for multisectoral interventions to focus on HIV and TB and homicide and the emerging epidemic of non-communicable diseases. S Afr Med J 2017;107(12):1091-1098. DOI:10.7196/SAMJ.2017.v107i12.12458

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i12.12458

Geographical maldistribution of surgical resources in South Africa: A review of the number of hospitals, hospital beds and surgical beds A J Dell, BSc, MB ChB, PhD; D Kahn, MB ChB, FCS (SA), ChM Department of Surgery, Faculty of Health Sciences, and Groote Schuur Hospital, University of Cape Town, South Africa Corresponding author: A J Dell (angelajdell@gmail.com) Background. The global burden of surgical disease has been studied to a limited extent. Despite the proven benefits of surgery, surgical services remain poorly resourced. Contributing to this global crisis is the critical lack of data regarding available resources. Objective. To analyse the distribution of some resources necessary for the provision of surgical care. The distribution and number of surgical resources (number of surgical beds) relative to the general resources (number of hospitals and total number of beds) in South Africa were analysed. Methods. All hospitals in the country, including those in the public and private sectors, were contacted, and the total number of hospitals, the level of care (district v. regional v. tertiary), the total number of hospital beds, and the number of surgical beds were determined. The data were analysed according to the provincial distribution and the public v. private sector distribution relative to the size of the population. Results. A total of 544 hospitals were included in the study – 327 in the public sector and 217 in the private sector. The public sector hospitals included 257 district-, 49 regional- and 21 tertiary-level hospitals. Nationally, there were 1 hospital, 187 hospital beds and 42 surgical beds per 100 000 population. Gauteng Province (GP), the Eastern Cape, KwaZulu-Natal (KZN) and the Western Cape had the most hospitals and GP had the largest number of private hospitals. GP and KZN had the largest total number of beds (n=29 181 and n=22 889, respectively) and number of surgical beds (n=7 289 and n=4 651, respectively). GP had the largest number of private surgical beds (n=4 837). There was a marked variation in the number of hospitals, total number of beds, and number of surgical beds among provinces. Conclusion. This study provided an estimation of the number of hospitals, total number of beds, and number of surgical beds, and showed a marked variation among provinces and between the public and private sectors. S Afr Med J 2017;107(12):1099-1105. DOI:10.7196/SAMJ.2017.v107i12.12539

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i12.12539

December 2017, Print edition

RESEARCH

Acne in South African black adults: A retrospective study in the private sector T P Zulu, BSc, MB ChB, FC Derm (SA), MMed; A Mosam, MB ChB, FC Derm (SA), MMed, PhD; Y Balakrishna, MSc (Statistics); N C Dlova, MB ChB, FC Derm (SA), PhD Department of Dermatology, School of Clinical Medicine, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Corresponding author: T P Zulu (tpzulu@gmail.com) Background. Acne vulgaris is the most common skin disorder affecting teenagers and young adults, and is becoming increasingly common in middle-aged women. It affects all skin types and ethnic groups, but dark-skinned individuals are burdened by post-inflammatory hyperpigmentation (PIH) as a sequela. PIH causes distress in acne patients even after the inflammatory lesions have resolved. Objective. To describe the characteristics of acne in black South African adults in the private health sector in Durban, KwaZulu-Natal Province. Methods. A retrospective study of records of patients attending two large private dermatology clinics in central Durban, mainly catering for black patients, was performed. Data were collected for the period January - December 2014. Records with acne as a diagnosis were retrieved and analysed with regard to age, demographics, type and severity of acne, therapy, HIV status and outcomes. Results. Of a total of ~3 000 charts available for the 12-month period, 242 had acne as a diagnosis and were retrieved and analysed. Of these patients, 204 (84.3%) were female and the remainder were male. The mean age was 28.5 years (under-18s were excluded from the study). Inflammatory acne was the most frequently encountered form (58.6%). Fifteen patients (6.2%) were on topical treatment only, and 226 (93.4%) were on topical plus systemic treatment. PIH was the most common sequela (81.0% of patients). Conclusions. The majority of the patients were young females with inflammatory acne, and PIH was the most common sequela. Early and vigorous treatment of acne may minimise its complications, including those seen mainly in black patients. S Afr Med J 2017;107(12):1106-1109. DOI:10.7196/SAMJ.2017.v107i12.12419

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i12.12419

Multimorbidity in a large district hospital: A descriptive cross-sectional study S Roche,[1] 4th-year medical student; E de Vries,[2] MB ChB, MFamMed, FCFP (SA) 1 2

Faculty of Health Sciences, University of Cape Town, South Africa School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa; Mitchellâ&#x20AC;&#x2122;s Plain District Hospital, Western Cape Department of Health, Cape Town, South Africa

Corresponding author: E de Vries (elma.devries@westerncape.gov.za) Background. There is substantial research documenting the burden of disease globally and in the South African (SA) primary care context. Few studies address the disease profile and its implications in the SA hospital setting. Objectives. To describe the disease profile in the internal medicine department of a large district hospital, using variables related to comorbidity and patient length of stay. The study included specific exploration into the HIV/tuberculosis (TB) syndemic, the acuity of HIV disease, and lifestyle risk factors. Methods. The sample population consisted of all consecutive admissions to the internal medicine department of a large district hospital in the Cape metropole during May 2015. A retrospective folder review and subsequent data analysis were completed. Results. Hypertension, HIV, type 2 diabetes mellitus, TB and cardiac failure were the five most prevalent diseases. Extensive multimorbidity was observed, with 86.0% of patients suffering from two or more diseases concurrently. The average number of comorbidities per patient was 3.4, although no clear relationship between the number of comorbidities and length of stay was found. Of the various diseases, only TB and HIV were associated with above-average length of stay, particularly among co-infected patients and those who had defaulted from

December 2017, Print edition

RESEARCH

or never received antiretroviral (ARV) treatment. Compared with patients currently receiving ARVs, much higher proportions of patients who had defaulted from or never received ARV treatment had CD4+ counts <200 cells/µL. Of the lifestyle risk factors investigated, a history of excessive alcohol use and/or drug use was associated with an increased length of stay. Most patients were discharged home, with 15.7% being referred to other institutions. Conclusions. Chronic conditions, particularly HIV, TB and non-communicable diseases, represented much of the disease profile in the internal medicine department. Of the comorbidities investigated, the greatest contributor to length of stay was HIV/TB co-infection. Factors such as HIV, TB and substance use that increase length of stay cannot be impacted upon by the district hospital staff in isolation. To improve the health of communities, we require partnerships between doctors, community health providers and patients with their families. Multimorbidity was widespread, suggesting the need to include an understanding of multimorbidity, including the patient perspective, in medical education and health system reform. S Afr Med J 2017;107(12):1110-1115. DOI:10.7196/SAMJ.2017.v107i12.12397

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i12.12397

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 N P Semugoma,1 MD; K Rebe,1,2,3 MB ChB, FCP (SA); M W Sonderup,4 MB ChB, FCP (SA); M Kamkeumah,5 MPH; G de Swardt,2 BA; H Struthers,2,3 PhD; H Eksen,6 BA; J McIntyre,2,5 MB ChB, FRCOG Anova Health Institute, Cape Town, South Africa Anova Health Institute, Johannesburg, South Africa 3 Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 4 Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 5 School of Public Health, Faculty of Health Sciences, University of Cape Town, South Africa 6 Mainline, Amsterdam, the Netherlands 1 2

Corresponding author: K Rebe (rebe@anovahealth.co.za) Background. Hepatitis C virus (HCV) is a chronic infection of increasing importance, especially among people living with HIV/AIDS. Co-infection with HIV can accelerate progression of HCV liver disease to cirrhosis and end-stage liver failure and elevate the risk of hepatocellular carcinoma. Globally, men who have sex with men (MSM) and people who inject drugs are at increased risk of HCV infection compared with the general population. Few studies on HCV in these key populations have been done in South Africa (SA). Objective. To describe the disease burden of HCV in drug-using MSM who attend harm-reduction services at the Anova Health Institute’s Health4Men clinic in Cape Town, SA. Methods. In 2012 - 2014, attendees of an MSM-focused harm-reduction programme were invited to participate in our study. After informed consent, participants completed a brief demographic questionnaire and underwent phlebotomy for anti-HCV antibody, hepatitis B virus (HBV) surface antigen and surface antibody testing. Participants received counselling and education with regard to their results. HIV status was extracted from the case notes of participants who had previously been tested at the study site. Data were analysed using standard statistical techniques. Results. Forty-one MSM were enrolled – 11 (27.0%) tested anti-HCV antibody-positive, indicating prior exposure to HCV or chronic infection; 10/11 (91.0%) were positive for HBV surface antibodies, suggesting previous HBV exposure or vaccination; and 1 (2.0%) screened positive for HBV. Of the HCV-seropositive individuals, HIV status was known in 8/11; 3/8 (37.5%) were HIV-positive. Conclusion. We demonstrated a high burden of HCV exposure or infection among a small urban cohort of MSM who inject drugs. We recommend active screening of MSM (especially those who report drug use) for HCV, and the development of referral networks for access to treatment. S Afr Med J 2017;107(12):1116-1120. DOI:10.7196/SAMJ.2017.v107i12.12623

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i12.12623

December 2017, Print edition

RESEARCH

Auditing stillbirths at Lower Umfolozi War Memorial Regional Hospital: A 12-month review I Govender, MB ChB, MMed, FCPHM, Dip Obst (SA) KwaZulu-Natal Department of Health, Lower Umfolozi War Memorial Regional Hospital, Empangeni, South Africa Corresponding author: I Govender (indira.govender@gmail.com) Background. Although the total number of stillbirths worldwide was estimated at 2.6 million in 2009, there is currently a dearth of literature on stillbirths in developing countries and rural settings, where the majority of such births occur. The ‘Hands Up’ Mortality and Morbidity Extraction Tool (HUMMET), developed at Lower Umfolozi War Memorial Regional Hospital (LUWMRH) in 2010, outlines a systematic approach to summarising individual cases of adverse perinatal outcomes. Objective. To depict the HUMMET form by describing the detailed demographic and obstetric profile of patients who delivered a stillborn infant at LUWMRH, as well as risk factors associated with these stillbirths between 1 April 2014 and 31 March 2015. The findings add to a global initiative advanced by the Lancet series on stillbirths, aimed at raising awareness of stillbirth statistics in low- and middle-income countries. Methods. A total of 310 detailed stillbirth case summaries of 305 patients were collected during the study period, representing 90% of the total number of stillborn infants delivered at LUWMRH. A retrospective audit of the HUMMET forms was conducted and the cases were further summarised in a Microsoft Excel spreadsheet that allowed for a univariate analysis of the variables. Results. The stillbirth rate at LUWMRH is much higher than that at other regional hospitals owing to the number of at-risk referrals and emergency cases from surrounding clinics and district hospitals. Referrals were from local clinics (49%) and district hospitals (45%), 35% of stillbirths were due to abruptio placentae and a large proportion were associated with gestational hypertension, pre-eclampsia and/or eclampsia. Avoidable factors were predominantly a late patient response to reduced fetal movements and delays in transfer to hospital. Twenty percent of stillbirths were associated with inappropriate monitoring or management of the obstetric condition at the district hospital. Conclusion. The HUMMET form provides a systematic approach to analysing cases of perinatal morbidity and mortality in line with the requirements of the Perinatal Problem Identification Programme database, but provides more details on the circumstances and contributing factors. A repeat audit is recommended to determine whether interventions have been effective. S Afr Med J 2017;107(12):1121-1126. DOI:10.7196/SAMJ.2017.v107i12.12491

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i12.12491

Obstetric spinal hypotension: Preoperative risk factors and the development of a preliminary risk score – the PRAM score D G Bishop,1 MB ChB, FCA; C Cairns,1 MB ChB, FCA; M Grobbelaar,1 MB ChB, FCA; R N Rodseth,1,2 MB ChB, FCA, MMed, Cert Crit Care (SA), MSc, PhD Metropolitan Department of Anaesthetics, Critical Care and Pain Management, School of Clinical Medicine, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa 2 Outcomes Research Consortium, Cleveland Clinic, Ohio, USA 1

Corresponding author: D G Bishop (davidgbishop@gmail.com) Background. Obstetric spinal hypotension is a common and important problem during caesarean delivery. Identifying patients at risk for hypotension may guide clinical decision-making and allow timeous referral. Objective. Using preoperative risk factors, to develop a simple scoring system to predict systolic hypotension. Methods. This prospective, single-centre, observational study of patients undergoing elective or urgent caesarean delivery assessed body mass index, baseline heart rate, baseline mean arterial pressure (MAP), maternal age, urgency of surgery (elective v. non-elective) and

December 2017, Print edition

RESEARCH

preoperative haemoglobin concentration as predictors of spinal hypotension (systolic blood pressure <90 mmHg). We used empirical cut-point estimations in a logistic regression model to develop a scoring system for prediction of hypotension. Results. From 504 eligible patients, preoperative heart rate (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.00 - 1.03; p=0.012), preoperative MAP (OR 0.97, 95% CI 0.95 - 0.98; p<0.001) and maternal age (OR 1.05, 95% CI 1.02 - 1.08; p=0.002) were found to be predictors of hypotension. We derived a preliminary scoring system (pulse rate >90 bpm, age >25 years, MAP <90 mmHg â&#x20AC;&#x201C; the PRAM score) for the prediction of systolic hypotension following obstetric spinal anaesthesia. Patients with three factors had a 53% chance of developing hypotension, compared with the overall incidence of 30%. The PRAM score showed good discrimination, with a c-statistic of 0.626 (95% CI 0.576 - 0.676) and good calibration. Conclusions. Preoperative heart rate, preoperative MAP and maternal age were predictive of hypotension in elective and emergency caesarean delivery. The PRAM score shows promise as a simple, practical means to identify these patients preoperatively, but requires prospective validation. S Afr Med J 2017;107(12):1127-1131. DOI:10.7196/SAMJ.2017.v107i12.12390

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i12.12390

Gendered risk factors associated with self-harm mortality among youth in South Africa, 2006 - 2014 N de Wet, PhD Demography and Population Studies, Schools of Social Sciences and Public Health, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: N de Wet (nicole.dewet@wits.ac.za) Background. Despite efforts to reduce self-harm mortality, death rates remain high, with almost 12% of all youth deaths in South Africa (SA) attributed to this cause. There are gendered differences in causes of death among youth, but little is known about the sex-specific risk factors. Objective. To identify the levels and sex-specific determinants of self-harm mortality among youth in SA. Methods. This was a cross-sectional study of SA death notification forms from 2006 to 2014. Descriptive and analytical statistical techniques were used, including cause-specific mortality rates, proportional mortality ratios and logistic regression models. Results. A total of 1 122 youth (15 - 24 years of age) deaths due to self-harm causes were reported over the study period, during which rates of self-harm mortality increased. More deaths of males (n=818) than females (n=304) were reported. Almost 60% of deaths (p<0.05) were of 20 - 24-year-olds, and 46.4% (p<0.05) of those who died had a secondary education. Almost 10% of females (p<0.05) were pregnant at the time of death. Hanging was the most common type of self-harm mortality among males (79.2%) and females (49.3%). While 11.0% (n=90) of self-harm deaths of males were due to poisoning, more females used this method (39.8%, n=121). The probability of self-harm mortality for males increased according to certain provinces of residence. For females the odds were higher for those who were pregnant (odds ratio (OR) 1.3; p<0.05) and non-South African (OR 1.7; p<0.05) and had secondary education (OR 1.4; p<0.05). Conclusions. The study showed gender differentials in the determinants of self-harm mortality among youth in SA. For this reason, uniform approaches to awareness campaigns need to be altered to address the specific needs of youth. While males have higher rates than females, the prevalence of self-harm mortality in pregnant females is of concern and needs to be addressed specifically, as it relates not only to suicidal ideation and behaviour but also to youth sexual and reproductive health programmes in the country. S Afr Med J 2017;107(12):1132-1136. DOI:10.7196/SAMJ.2017.v107i12.12652

Full article available online at https://doi.org/10.7196/SAMJ.2017.v107i12.12652

December 2017, Print edition

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St Marks Group in Auckland, New Zealand seeks a Consultant Breast Radiologist to join our well-established practice and multidisciplinary team of breast specialists. You will have experience in all forms of breast imaging, including digital and analogue mammography, breast ultrasound, as well as ultrasound-guided biopsies, sentinel node injections and preoperative localisations. You should also possess outstanding clinical and interpersonal skills. Full- or part-time (minimum 0.4 FTE) option considered, with assistance offered to obtain further sessions in general radiology. This is an exciting opportunity to deliver a high-quality customer-centred service in both the private St Marks Breast Centre and the public Breastscreen Auckland clinics. You will be part of a progressive and exciting business and a warm and professional team. This is an excellent place to forge your specialist career and contribute to the very best in patient care. We offer an excellent remuneration package, a sign on bonus for a radiologist working a minimum of 0.4 FTE and relocation assistance.

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Our innovative psychiatric services within are recruiting for talented, dynamic and committed consultant psychiatrists across the county of Kent. You will play a key role in helping us deliver an outstanding service through forward thinking, innovation and providing high quality care. Why join us? KMPT can facilitate Skype Interviews and will proactively support you through the recruitment and relocation process, accommodation, bank accounts, including initial relocation payment which will be discussed at interview. Support registration with the GMC/Applications for Highly skilled permits and support with family relocation including Visa documentation etc. We have a highly commended research team and encourage our staff and patients to become involved in research . We have teaching opportunities available with links to UK Universities and an international medical school. We encourage staff development and have an internal leadership and mentoring programme. We offer all newly appointed consultants mentoring to support their development as leaders. “At KMPT we believe that mentoring can help new colleagues ﬁnd their feet and feel conﬁdent and competent more quickly through our Mentoring Service for newly appointed Consultants.” http://staffzone.kmpt.nhs.uk/your-development/ organisational-development/mentoring-service-consultants.htm

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True (A) or false (B): SAMJ Lamivudine monotherapy in children and adolescents: The devil is in the detail 1. About 20% of children on antiretroviral therapy will develop virological failure. 2. One reason for the increased risk of virological failure and drug resistance in children is poor palatability of paediatric drugs. 3. In children with virological failure, associated drug resistance mutations may occur in up to 90% of cases. 4. Any social or financial instability or change has been shown to threaten the sustainability of treatment in children on antiretroviral therapy. 5. Currently, children failing a first-line non-nucleoside reverse transcriptase inhibitor-based regimen are switched to a protease inhibitor-based regimen. Impact of Xpert MTB/RIF rollout on management of tuberculosis in a South African (SA) community 6. In ideal conditions, sample processing with Xpert MTB/RIF takes 2 hours, with <20 minutesâ&#x20AC;&#x2122; hands-on processing time. 7. In the diagnosis of tuberculosis, sputum smear microscopy has relatively low diagnostic sensitivity and cannot detect drug resistance. 8. Sputum culture for Mycobacterium tuberculosis provides immediate results that guide clinical management. 9. Xpert MTB/RIF has approximately two-fold higher sensitivity than sputum smear microscopy. Mortality trends in the City of Cape Town (CoCT) between 2001 and 2013: Reducing inequities in health 10. All-cause mortality in the CoCT declined by 8% from 938 to 863 per 100 000 between 2001 - 2004 and 2010 - 2013.

11. Mortality in males declined more than in females owing to a large reduction in male injury mortality, particularly firearm-related homicide. 12. The sustainable development goals specifically call for reduction of inequity within and among countries. 13. Child mortality has been used as a universal indicator of inequality because it is sensitive to socioeconomic change and therefore extensively used by international agencies to compare health and socioeconomic progress between regions and individual countries. Hepatitis C: An SA 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, SA 14. Hepatitis C was cloned, named, and characterised in 1989. 15. Hepatitis C infection can be cleared spontaneously by effective host immune responses in 18 - 34% of cases. 16. In 20 - 40% of cases of hepatitis C, chronic infection leads to fibrosis, cirrhosis and end-stage liver failure over 20 - 30 years. 17. Hepatitis C infection is curable and the new oral regimens with direct-acting antiviral (DAA) agents have revolutionised management. Obstetric spinal hypotension: Preoperative risk factors and the development of a preliminary risk score â&#x20AC;&#x201C; the PRAM score 18. Spinal hypotension during caesarean delivery occurs commonly and, depending on the definition used, may have an incidence as high as 71%. 19. Hypotension during caesarean delivery is a potentially lifethreatening event and is associated with nausea and vomiting, loss of consciousness, cardiac arrest, death and fetal compromise. 20. Preoperative heart rate, preoperative mean arterial pressure and advancing maternal age are predictive of hypotension.

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December 2017, Print edition

1 Relieves pain

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inflammation

3 Speeds 1 healing

100g available behind the counter

*Nicolas Hall & Company, Benchmarking the World of OTC, DB6,2016. “Voltaren is the world best-selling non-prescription topical pain reliever” Reference: 1. Zacher J et al. 2008. Topical diclofenac and its role in pain and inflammation: an evidence based review. Current Medical Research & Opinion. Vol 24. No 4 (925-950). 20g & 50g

100g Voltaren® Emulgel®. Each 100g contains 1,16g diclofenac diethylammonium corresponding to 1g diclofenac sodium. Reg. no.: U/3.1/77. Botswana:

Reg. no.: B9305535. Namibia:

Reg. no.:04/3.1/0344.

Indicated for use in adults and adolescents older than 12 years. Safety in pregnancy and lactation has not been established. Consult your pharmacist/healthcare professional if needed. Applicant: GlaxoSmithKline Consumer Healthcare SA (Pty) Ltd, Company Reg. No. 2014/173930/07.39 Hawkins Avenue, Epping Industria 1, 7460. Tel. No. 0800 118 274. CHZAF/CHVOLT/0018/17

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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