SAMJ Vol 106, No 4 (2016) by HMPG

APRIL 2016

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EDITORIALS Where are the males? Unpacking the new proposed regulations for South African traditional health practitioners CME Acute viral bronchiolitis (part 1) IN PRACTICE Fetal assessment and negligent misdiagnosis A multifaceted hospital-wide intervention to increase hand hygiene compliance Biofilms associated with bowel necrosis Case report: Autoimmune dermatitis triggered by medical abortion RESEARCH Where do children die and what are the causes? The S’Khokho ‘bushcan’ initiative HIV and diabetes mellitus – a deadly combination Socioeconomic factors associated with asthma prevalence and severity Additional content available in the full online issue, SAMJ Vol. 106 No. 4

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APRIL 2016

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FROM THE EDITOR

Where are we now? B Farham

FROM THE CEO

A new vision for the SAMJ – and a call for papers H Kikaya

EDITOR’S CHOICE

CORRESPONDENCE

The simple bread tag – a menace to society? More warnings in our digital era A B van As, R J England, A Numanoglu

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

IZINDABA

12 16 18 19

Vaccines: SA’s immunisation programme debunked PE hospital turmoil: CEO leaves, nurses snore in patient beds Budget squeeze: Cutting clinicians hurts patients ‘My advice was evidence based’ – Noakes

MANAGING EDITORS Ingrid Nye Claudia Naidu

EDITORIALS Where are the males? Diversity, proportionality and Health Sciences admissions D Benatar

NEWS EDITOR Chris Bateman | Email: chrisb@hmpg.co.za

Unpacking the new proposed regulations for South African traditional health practitioners R A Street

DTP AND DESIGN Carl Sampson

CME

GUEST EDITORIAL Acute viral bronchiolitis in South Africa: Diagnosis and current management R J Green, H J Zar

HEAD OF SALES AND MARKETING Diane Smith | Tel. 012 481 2069 Email: dianes@hmpg.co.za

ARTICLES Acute viral bronchiolitis in South Africa: Diagnostic flow D A White, H J Zar, S A Madhi, P Jeena, B Morrow, R Masekela, S Risenga, R J Green

Acute viral bronchiolitis in South Africa: Strategies for management and prevention H J Zar, S A Madhi, D A White, R Masekela, S Risenga, H Lewis, C Feldman, B Morrow, P Jeena

ACTING 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, N Khumalo, R C Pattinson, A Rothberg, A A Stulting, J Surka, B Taylor, M Blockman HMPG

IN PRACTICE

TECHNICAL EDITORS Emma Buchanan Paula van der Bijl

PRODUCTION MANAGER Emma Jane Couzens

JOURNAL ADVERTISING Charles William Duke Benru de Jager Reneé van der Ryst Ladine van Heerden Azad Yusuf ONLINE SUPPORT Gertrude Fani FINANCE Tshepiso Mokoena

HEALTHCARE DELIVERY 30 A call to action: Addressing the reproductive health needs of women with drug-resistant tuberculosis K Schnippel, N Ndjeka, F Conradie, R Berhanu, Z Claasen, S Banoo, C Firnhaber

HMPG BOARD OF DIRECTORS Prof. M Lukhele (Chair), Dr M R Abbas, Dr M J Grootboom, Mrs H Kikaya, Prof. E L Mazwai, Dr M Mbokota, Dr G Wolvaardt

A multifaceted hospital-wide intervention increases hand hygiene compliance B Patel, H Engelbrecht, H McDonald, V Morris, W Smythe

ISSN 0256-9574

CLINICAL ALERT Intracranial complications of Serratia marcescens infection in neonates A Madide, J Smith

Biofilms associated with bowel necrosis: A newly recognised phenomenon in infants G Brisighelli, S Cox, A Theron, K Pillay, H Rode

MEDICINE AND THE LAW A child’s potential claim for negligent misdiagnosis: The case of H v. Fetal Assessment Centre P Mahery

ISSUES IN PUBLIC HEALTH The impact of the Medicines Control Council backlog and fast-track review system on access to innovative and new generic and biosimilar medicines of public health importance in South Africa H M J Leng, A M Pollock, D Sanders

April 2016, Print edition

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ONLINE CONTENTS LISTED IN Index Medicus (Medline) Excerpta Medica (EMBASE) Biological Abstracts (BIOSIS) Science Citation Index (SciSearch) Current Contents/Clinical Medicine

CASE REPORTS Orbital apex syndrome caused by aspergilloma in an immunocompromised patient with cutaneous lymphoma: A case report of a rare entity A Cheko, S Jung, S Teuber-Hanselmann, A W Oseni, A Tsogas, M Scholz, A K Petridis

Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion L Mbonile

RESEARCH

SAMJ SUBSCRIPTION RATES Local subscriptions ZAR 1 368.00 p.a. Foreign subscriptions ZAR 3 108.00 p.a. Single copies ZAR114.00 local, ZAR 259.00 foreign

Where do children die and what are the causes? Under-5 deaths in the Metro West geographical service area of the Western Cape, South Africa, 2011* A E Reid, M K Hendricks, P Groenewald, D Bradshaw

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

Antiretroviral therapy programme outcomes in Tshwane district, South Africa: A 5-year retrospective study* N Mlangeni, F Senkubuge

Clinician compliance with laboratory monitoring and prescribing guidelines in HIV-1-infected patients receiving tenofovir* R de Waal, K Cohen, M P Fox, K Stinson, G Maartens, A Boulle, M-A Davies

The S’Khokho ‘bushcan’ initiative: Kick a bush and condoms fall out* J Pienaar

Piloting a national laboratory electronic programme status reporting system in Ekurhuleni health district, South Africa* N Cassim, L M Coetzee, D K Glencross

A deadly combination – HIV and diabetes mellitus: Where are we now?* S Pillay, C Aldous, F Mahomed

The other side of surveillance: Monitoring, application, and integration of tuberculosis data to guide and evaluate programme activities in South Africa* L J Podewils, L Bronner Murrison, C Bristow, N Bantubani, L D Mametja

A randomised controlled trial comparing oxytocin and oxytocin + ergometrine for prevention of postpartum haemorrhage at caesarean section* S Koen, L C Snyman, R C Pattinson, J A Makin

Evaluating current knowledge of legislation and practice of obstetricians and gynaecologists in the management of fetal remains in South Africa* L du Toit-Prinsloo, C Pickles, H Lombaard

Socioeconomic factors associated with asthma prevalence and severity among children living in low-income South African communities* A R Yakubovich, L Cluver, R Gie

*Full article available online only.

CAREERS & CLASSIFIEDS

CPD QUESTIONS

Subscriptions: Tel. 012 481 2071 Email: members@samedical.org The SAMJ is published monthly by the Health and Medical Publishing Group (Pty) Ltd, Co. registration 2004/0220 32/07, a subsidiary of SAMA. HEAD OFFICE Health and Medical Publishing Group (Pty) Ltd Block F, Castle Walk Corporate Park, Nossob Street, Erasmuskloof Ext. 3, Pretoria, 0181 Tel. 012 481 2069 Email: dianes@hmpg.co.za EDITORIAL OFFICE Suites 9 & 10, Lonsdale Building, Gardener Way, Pinelands, 7405 Tel. 021 532 1281 | Cell. 072 635 9825 Email: publishing@hmpg.co.za Please submit all letters and articles for publication online at www.samj.org.za © Copyright: Health and Medical Publishing Group (Pty) Ltd, a subsidiary of the South African Medical Association Use of editorial material is subject to the Creative Commons Attribution – Non-commercial Works Licence. http://creativecommons.org/licenses/by-nc/3.0 Printed by TANDYM PRINT

APRIL 2016

Additional content available in the full online issue, SAMJ Vol. 106 No. 4

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April 2016, Print edition

RESEARCH Where do children die and what are the causes? The S’Khokho ‘bushcan’ initiative HIV and diabetes mellitus – a deadly combination Socioeconomic factors associated with asthma prevalence and severity Additional content available in the full online issue, SAMJ Vol. 106 No. 4

FROM THE EDITOR

Where are we now? As the new year started, this caught my eye in my daily trawl of online news: ‘Potato-rich diet “may increase pregnancy diabetes risk”’. This BBC news item, based on an article[1] in the British Medical Journal, suggests that women who eat potatoes in any form most days of the week have an increased risk of diabetes during pregnancy. The risk is probably triggered by the massive rise in blood sugar levels that all starchy carbohydrates cause. But the interesting thing about the news item was not so much the potentially increased risk of gestational diabetes caused by eating potatoes daily, but the comment of ‘British experts’ who said the ‘proof was lacking’ and that people need to eat lots of starchy foods for fibre, as well as fresh fruit (known to be high in sugars) and vegetables. The UK advice is that people should get about one-third of their daily intake from starchy foods such as potatoes, and there is no limit to how much carbohydrate people should eat. Another major issue in the news overseas is the idea of taxing sugary drinks, since these are now thought to be a major cause of obesity in the UK and the USA – although there is little actual evidence of direct causality. Mexico has apparently already put a tax on sugary drinks and the indications are that there may be a decrease in consumption, although it is probably too early to say, and certainly too early to see any public health benefits. A recent Lancet article[2] modelling a reduction in sugar in carbonated drinks and fruit juices over a period of 5 years (without replacing the sugar with artificial sweeteners) suggests that this could significantly reduce levels of obesity and type 2 diabetes. But the assumption again is that it is specifically sugar that is the main culprit in both conditions. So, where are we now? We have a situation where people are slowly starting to become aware of the amount of sugar in carbonated drinks and fruit juices, and possibly also added sugar in other foods generally. ‘Experts’ are telling them this is bad and that people must cut down on the amount of sugar in their diets. But at the same time these same ‘experts’ are telling people that saturated fat is still bad and, on top of this, that people must eat lots of starchy foods because of the fibre content. Both the UK[3] and US[4] dietary guidelines were updated in 2015, but you could be forgiven for thinking that little has changed – this in spite of the great fanfare around cholesterol no longer being demonised when the USA guidelines were released. All these guidelines actually said was that dietary cholesterol was no longer thought to cause increased blood cholesterol, so people could stop worrying about eating eggs. As in the UK guidelines, starchy

foods are still recommended as a major part of the diet, in the main because of their fibre content. And, as in the UK guidelines, saturated fat is still enemy number one. As Nina Teicholz, writing in the BMJ last year,[5] said: ‘The expert report underpinning the next set of US Dietary Guidelines for Americans fails to reflect much relevant scientific literature in its reviews of crucial topics and therefore risks giving a misleading picture ... The omissions seem to suggest a reluctance by the committee behind the report to consider any evidence that contradicts the last 35 years of nutritional advice.’ Much the same could be said of the many commentators on the various news items that the lay press cull from the academic journals. Whenever a study suggests that starchy foods are a problem or that saturated and other fats are a necessary and desirable part of the diet, conventional wisdom comes to the fore and the advice of the past 35 years is once again uncritically trundled out. It has struck me in my foraging through both lay and academic literature over the past couple of years that the change in the way that our food is produced – largely as a result of the initiation of the guidelines of 35 years ago – has spawned not only major research drives aimed at trying to defeat the surge of obesity and related diseases, but the rise and rise of the pharmaceutical companies that are exploiting the potential for drug treatment of diseases that are diet related. And all we need to do is eat real food. Bridget Farham

Acting Editor ugqirha@iafrica.com 1. Bao W, Tobias DK, Hu FB, Chavarro JE, Zhang C. Pre-pregnancy potato consumption and risk of gestational diabetes mellitus: Prospective cohort study. BMJ 2016;352:h6898. DOI:10.1136/bmj.h6898 2. Ma Y, He FJ, Yin Y, Hashem KM, MacGregor GA. Gradual reduction of sugar in soft drinks without substitution as a strategy to reduce overweight, obesity, and type 2 diabetes: A modelling study. Lancet Diabetes Endocrinol 2016;4(2):105-114. DOI:10.1016/S2213-8587(15)00477-5 3. Scientific Advisory Committee on Nutrition. Carbohydrates and Health. London: The Stationery Office, 2015. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/445503/ SACN_Carbohydrates_and_Health.pdf (accessed 10 March 2016). 4. Dietary Guidelines Advisory Committee. Scientific report. 2015. http://health.gov/ dietaryguidelines/2015-scientific-report/ (accessed 10 March 2016). 5. Teicholz N. The scientific report guiding the US dietary guidelines: Is it scientific? BMJ 2015;351:h4962. DOI:10.1136/bmj.h4962

S Afr Med J 2016;106(4):314. DOI:10.7196/SAMJ.2016.v106i4.10764

April 2016, Print edition

FROM THE CEO

A new vision for the SAMJ – and a call for papers Medical journals, unlike their basic science cousins, are the link between medical science and practice.[1] Not only do they seek to disseminate new knowledge, but they also intend to influence outcomes – the application of new knowledge to the treatment of patients. But this laudable goal creates a dilemma: who are medical journals actually for? The scientists or the doctors? Or perhaps the small group of specialists who are both? This question is crucial because it influences every aspect of a journal’s operations. What content to publish; how to present information; the policies and procedures that govern decisionmaking; and, in the internet age, even the choice of publication medium. The SAMJ and, by extension, its publisher the Health and Medical Publishing Group (HMPG), a wholly owned subsidiary of the South African Medical Association (SAMA), has historically addressed this challenge by trying to do it all: to be a scientific journal that targets researchers to publish their work, but with an editorial policy that favours mostly general-interest, non-academic doctors who are members of SAMA.[2] The problem is that these constituencies have distinctly different needs. Doctors generally read medical journals in a similar way to how they might approach a newspaper: to be informed, interested and kept up to date.[1,3] Researchers, however, read the content in a different way. For scientists, a journal is not read as a monthly digest; instead they identify content through online searches to use in their work. This latter approach renders the printed issues into which journals are carefully arranged all but irrelevant. During the past 5 years and more, the calls for the SAMJ to do better at serving both these audiences, with their divergent needs, have grown louder. Recommendations for change were most clearly articulated in a 2009 report[2] published by the Academy of Sciences of South Africa. The report summarised the conclusions of a panel chaired by Prof. Bongani Mayosi, convened to consider the future of South Africa (SA)’s clinical research. Devoting an entire chapter to scholarly journals, the report issued a strong call to action to SAMA to ensure that the SAMJ and its daughter titles better support both medicine and science, including building capacity of the next generation of researchers. Since that call was made, the need for reform has become even more pertinent. SA has moved into a phase where, with the National Health Insurance programme,[4] it is grappling with one of the most ambitious health reforms ever conceived. Decisions that affect the way healthcare is delivered, regulated and funded are being made every day. In the absence of a robust evidence base of contextually relevant, locally conducted research studies, disseminated through a strong local academic publishing industry, the risk is that this reform will roll on without properly incorporating the extensive knowledge and expertise of the professions that will determine its success. As the only general medical journal in the country, there is no more appropriate champion for evidence-based decision-making in health than the SAMJ. This realisation, coupled with the very clear recommendations of academic medical communities,[2] has led to a concrete plan of action – proposed by HMPG and endorsed by SAMA – for implementing change. Henceforth, the SAMJ will respond to researchers’ stated priorities: fast publication; robust and efficient peer review; wide dissemination of published findings; and, crucially, no editorially imposed limit on the numbers or type of papers accepted, as long as quality criteria are met.

The journal will expand its remit, not just actively seeking ‘general’ content, but instead capturing the spectrum of medical and health sciences, grouped by relevance to the country’s burdens of disease. To accommodate the anticipated volume increase, the online version of the journal will be far more extensive than it has been in the past. Accepted papers will be edited and published online as soon as they are ready, without being held up by the print schedule. The print edition will also be changing: its focus, in recognition of the priorities of its mainly practising-physician readership, will be to provide a platform for education and debate, distilling the most crucial practice-relevant findings from the research content published rapidly online, and complementing it with many more commissioned reviews, commentaries and editorials that provide valuable context and highlight learning points. While much of the internal restructuring underpinning this reform is already complete, the most crucial aspect is the recruitment of an expanded Editorial Advisory Board, led by the Editor-in-Chief, to strengthen the relationship between the journal and its audiences. Over the coming weeks, we will be announcing a series of appointments that we hope will provide the expanded SAMJ – and HMPG – with the academic direction and passion it needs. With this new approach, building on the consensus of influential medical academics while staying true to its practice-changing aims, the SAMJ intends to ensure that the ancient medical journal paradox of how to combine science and practice is resolved in favour of building the necessary solid evidence base to support SA though its ambitious health transition – and, by doing so, to become the natural home for SA’s health and medical research that the Academy of Sciences has acknowledged that the country desperately needs.

Call for papers

To accompany the new vision of the SAMJ, the journal is launching its first Call for Papers targeting health and medical research that relates to SA’s quadruple burden of disease. The best of the submissions for each of the four burdens will be published in special themed issues that will also highlight policy-relevant research gaps. Please send your submissions, including a covering letter introducing the work, to submissions@hmpg.co.za by 30 April 2016. Hannah Kikaya CEO and Publisher, Health and Medical Publishing Group, South Africa 1. Smith R. The trouble with medical journals. J R Soc Med 2006;99(3):115-119. DOI:10.1258/ jrsm.99.3.115 2. Mayosi B, Dhai A, Folb P, et al. on behalf of the Academy of Sciences of South Africa. Revitalising Clinical Research in South Africa: A Study on Clinical Research and Related Training in South Africa. Pretoria: Academy of Sciences of South Africa, 2009. http://www.assaf.org.za/files/2009/09/ASSAfClnical-Report-Summary.pdf (accessed 22 March 2016). 3. Van Niekerk JP. Our journals in flux. S Afr Med J 2010;100(4):189. 4. National Department of Health of South Africa. National Health Insurance for South Africa: Towards Universal Health Coverage. Pretoria: National Department of Health, 2015.

S Afr Med J 2016;106(4):315. DOI:10.7196/SAMJ.2016.v106i4.10817

April 2016, Print edition

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CORRESPONDENCE

The simple bread tag – a menace to society? More warnings in our digital era

To the Editor: We read with great interest the article on the public health issue of ‘The simple bread tag – a menace to society?’ in the May 2015 issue of the SAMJ.[1] We are delighted that the authors have directed the medical fraternity to one of the most common public health problems in early childhood, and agree that these bread tags should be removed from use.

Fig. 1. Abdominal radiograph demonstrating SIM card at level of T11 vertebra (arrow).

Ingestion of a foreign body is the fifth most common presentation to paediatric emergency departments. Analysis of figures from our institution previously found that the number of ingestion injuries was comparable with the number of assaults as a cause for trauma unit attendance; although falls, motor vehicle accidents and burns were more frequent. Toddlers and young children are inquisitive and tend to explore objects with their mouths, and are therefore inherently prone to ingestion accidents. Button batteries are a particular concern owing to their ability to cause transmural ulceration; however, the range of potentially ingestible objects is vast. We recently treated an 8-month old female infant who presented with non-bilious vomiting for 2 days. She was mildly dehydrated and had a fever of 37.9°C. No haematemesis or diarrhoea were reported. Two weeks earlier, her mother had witnessed her grasp and swallow a SIM card, but had not noted any further sequelae or sought medical advice. An abdominal radiograph demonstrated a mobile phone SIM card at the level of T11 (Fig. 1). It was decided the SIM card should be removed as it had not passed within 2 weeks and was confounding the clinical picture. Under general anaesthesia, flexible endoscopy visualised the SIM card within the stomach, lodged at the level of the pylorus (Fig. 2). Manipulation was challenging, but eventually the card was removed with the aid of a rigid oesophagoscope and appropriate retrieval forceps. Widespread availability, exchange, smaller size and disposal of SIM cards are resulting in infants being increasingly exposed to them. This situation is becoming more prevalent in developing societies as the mobile phone becomes the primary system of communication, and SIM card purchase is cheap and often unregulated. The shiny microchip surface makes them attractive to young children at a stage when they are developing hand-to-mouth skills. We recommend that all parents of young infants are reminded of these dangers to increase vigilance within the home. Resources and information on child safety topics are nowadays widely available from the internet.[2] A B van As, R J England, A Numanoglu Department of Paediatric Surgery, Red Cross War Memorial Children’s Hospital and Faculty of Health Sciences, University of Cape Town, South Africa sebastian.vanas@uct.ac.za 1. Karro R, Goussard P, Loock J, Gie R. The simple bread tag – a menace to society? S Afr Med J 2015;105(5):342-344. DOI:10.7196/SAMJ.8996 2. Childsafe South Africa. Safety tips. http://www.childsafe.org.za (accessed 4 February 2016).

Fig. 2. Endoscopic view of SIM card in stomach.

S Afr Med J 2016;106(4):316. DOI:10.7196/SAMJ.2016.v106i4.10634

April 2016, Print edition

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IZINDABA

Vaccines: SA’s immunisation programme debunked South Africa (SA)’s high-priority, underfunded Expanded Programme on Immuni sation (EPI) is understaffed and close to rudderless, with inaccurate data collection on vaccine coverage continuing apace while actual management of the programme deteriorates by the month. The top national Department of Health (NDoH) EPI managers resigned in August and December last year, taking with them large chunks of institutional memory and invaluable expertise. SA remains in the top five underperforming EPI African countries (according to World Health Organization (WHO) standards), for the third year running. According to Johann van den Heever, the recently resigned (in December) national EPI manager, a ‘lack of leadership vision’ and a ZAR1.4 billion national budget provides exclusively for vaccine purchase, hugely under-prioritising human resources, social mobilisation and surveillance, supervision, and monitoring and evaluation. The ongoing frustrations of inaccurate and unscientific data collection, severe understaffing and lack of a pragmatic operational budget led to his resignation. A former Gauteng EPI and communicable diseases specialist (8 years), he has spent the past 11 years as national EPI manager. His national senior specialist, Dr Ntombenhle Ngcobo, resigned last August, followed by their EPI data manager. None of this leadership had been replaced by early March this year. According to Van den Heever, only six of the original 13 national EPI posts (created in 1994) remain, all with

Johann van den Heever, recently resigned national EPI manager.

relatively junior incumbents, making basic data quality audits and accurate evaluations for immunisation even more difficult. The NDoH’s national vaccination coverage figure stands at 90% – a full 20% higher than the WHO/UNICEF estimate (a sore point with both parties). Calling into question the NDoH and WHO estimates, Van den Heever says that SA has little idea of its infant population, upon which any vaccine coverage estimate must be based. It was ‘absolutely imperative’ for any national health immunisation programme to have an electronic register of its target population (starting with infants), supported by a national EPI coverage survey to provide a performance measurement baseline. By having an immunisation register linked to the procurement of vaccines, the country would save millions of rands. There never seemed to be any money for operational costs. ‘If you don’t have money for proper support, monitoring and evaluation in the provinces, don’t hold quarterly EPI provincial manager meetings to strengthen all aspects of the programme, including surveillance, or fail to interrogate the data and progress, or have an opportunity to do training, supervision and motivation of staff – and you replace all this with maybe one teleconference per province per year – you could end up with a huge problem,’ he said. Late, incomplete data were being used, with

some of the country’s 52 health districts at times not entering any data for up to 3 months, while others had ‘very poor’ immunisation coverage. District Health Information System (DHIS) staff were supposed to send the data to the provincial health departments and then to the national District Health Information Unit, which then forwarded the data to the (now non-existent) national EPI manager. Routine data (denominators) collected through the DHIS did not include all doses of all antigens administered. There are just no proxies for antigens administered. If some vaccines at, say, 6 weeks of (infant) age were out of stock, one could not ‘assume’ that all the 6-week doses were administered if only one of those doses (assumed to be proxy) was collected in the DHIS. This provided a false sense of the true coverage of all the 6-week doses administered. ‘How they can then claim SA is doing a good job of immunisation is beyond my comprehen sion,’ he said. An electronic register of births, which with the support of the Department of Home Affairs could strengthen the Stats SA annual birth cohort denominators to the NDoH, with reliable figures up to subdistrict or health facility level, would already be a significant contribution towards more accurate calcu lation of immunisation coverage. The WHO recommended that countries conduct a national EPI coverage survey every 5 years, with the provinces completing one

A poster illustrating how the vaccine vial monitor shows when vaccines should be discarded.

April 2016, Print edition

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IZINDABA

every 3 years, yet this was not done. Home Affairs and Stats SA were unable to provide government with a denominator with which to calculate vaccination coverage. The possibility of a WHO-acceptable national EPI coverage survey was explored with UNICEF and the WHO in November 2013 (and costed at ZAR20 million), but never got off the ground. ‘If we ever have a true polio case we wouldn’t be able to detect it in time before many others were infected, because we are not meeting the WHO-required EPI priority disease surveillence standards,’ he added.

National cold-chain manager, Mr Sim Langa admitted that he was understaffed. He said he adapted by identifying and supporting poorly performing districts, and ‘depending on resources’ checked up on between 5% and 10% of all vaccination facilities. Van den Heever said it was therefore ‘impossible to say’ how much of the ZAR1.4 billion worth of vaccines was actu ally going into children, what percentage was expiring as a result of inaccurate stock control, and how much was being thrown away because of cold-chain mismanagement or non-WHO-compliant refrigerators. Prof. Shabir Madhi, Executive Director of the National Institute of Communicable Dis eases and Deputy Chairperson of the National Advisory Group on Immunisation, told Izindaba that without a national audit of vaccine storage and reliable, accurate figures of children vaccinated and meeting vaccine-preventable disease surveillance standards, at all facilities, it was impossible to estimate coverage or vaccine-related mortality and morbidity. He said that the Office for Healthcare Standards Compliance was due to present an audit of all facilities to government ‘within weeks’. However, this would be far broader than vaccines. He confirmed that all facilities were meant to use WHO-approved vaccine-only fridges. Mahdi is internationally recognised for his research on the safety, immunogenicity and efficacy of vaccines for child populations.

understaffed. He said he adapted by identi fying and supporting poorly performing districts and ‘depending on resources’ checked up on between 5% and 10% of all vaccination facilities (of which there are 3 000 - 4 000). ‘If I had a magic wand I’d want a system that enables me to inspect temperature ranges nationally. The cold chain management is not perfect,’ he added. Van den Heever said that provincial inventories of cold-chain equipment down to facility level were simply not kept. If the cold chain broke, senior clinical staff often took vaccines home to store in their own (inappropriate) fridges. Every WHO-approved fridge is supposed to have an internal contin uous monitoring device with a temperature chart on the outside on which readings are manually recorded twice a day to ensure that vaccines remain at between 2oC and 8oC. However, in practice fridges had been found with insulin and HIV medication (incorrectly) stored with the vaccines. This leads to constant opening and closing of the fridge door and inevitable breaks in the required vaccine temperature range. All vaccine vials carry a temperature and time-sensitive vaccine vial monitor tag of a light square within a dark circle. If the square turns the same colour as the circle or becomes darker, or the date on the vial is beyond its expiry date, the vial must be discarded. Van den Heever said that when vaccines lost efficacy/potency it was usually due to overstocking of vaccines or temperature control dysfunction. ‘And if they run out, they borrow from the clinic next door and don’t record it. One simply doesn’t know how effective vaccine management is at facility level,’ he said. Prof. Gregory Hussey, Dean of the Fac ulty of Health Sciences at the University of Cape Town and Chairperson of the National Advisory Group on Immunisation, said his committee was meeting national Minister of

National cold-chain manager: ‘we inspect 5 - 10% of facilities’

Van den Heever said the national cold-chain manager responsible for vaccine supply and quality control, Mr Sim Langa, was ‘hugely overworked’. Langa admitted that he was

Health Dr Aaron Motsoaledi and senior vaccine programme directors at the end of March and would emphasise the importance of a better operational EPI budget. He said the challenge had been to underpin the introduction of vaccines with sound managerial expertise which was devolved via individual provinces to their district health services. If there had been serious cold-chain failures, there would have been major outbreaks of vaccine-preventable diseases (like the KwaZulu-Natal diphtheria outbreak last year). He admitted that, at EPI national level, ‘there are issues and we need to take them seriously’.

Senior EPI specialist identifies shortcomings

Ngcobo confirmed that data from the DHIS were poor, and said the WHO and UNICEF simply ignored them. The true vaccination percentage probably lay somewhere between the overinflated DHIS figures and the more conservative WHO/UNICEF estimates. She agreed with Van den Heever that not conducting a national EPI coverage survey and failing to assessing stock availability countrywide were major problems. She singled out the widespread practice of allocating the pharmacy assistant job to nursing assistants at clinics, saying that the latter resented the job and put in no effort, resulting in poor stock management. A study of 31 Tshwane (Pretoria) clinics she conducted in April last year showed that most had stock-outs for 2 weeks to a month, especially of the pneumococcal conjugate vaccine, rotavirus and the pentavalent vaccine. The causes were poor stock management, unreliable deliveries, lack of pharmacy assistants and limited fridge capacity. Their emergency ordering system was also dysfunctional. Ngcobo recommended that the entire Tshwane supply chain be restructured and overhauled, using modern technology. ‘You can just imagine what happens to rural Transkei and Zululand,’ she added. The NDoH recently piloted an electronic medicines surveillance system at 39 (of over 500) public sector hospitals to ‘strengthen demand planning and governance’, and in August 2014 instituted the cellphone SMS (text message) MomConnect programme, which now has 42 000 pregnant women subscribers who receive term-tailored health messages. Both initiatives, although in their infancy, hold long-term promise in helping to address EPI problems. Chris Bateman chrisb@hmpg.co.za

A vial of polio vaccine, with its vaccine vial monitor indicating that it has expired.

April 2016, Print edition

S Afr Med J 2016;106(4):318-319. DOI:10.7196/SAMJ.2016.v106i4.10765

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IZINDABA

PE hospital turmoil: CEO leaves, nurses snore in patient beds Longstanding critical staff shortages in the maternity unit at Port Elizabeth’s Dora Nginza Hospital came to a head in midFebruary with a 3-day nurses’ strike, the enforced departure of the CEO, and nearly burnt-out doctors being prevented from doing ward rounds by strikers. Official documents in the possession of Izindaba reveal doctor allegations of leadership autocracy, major staff shortages, non-appointment of consultants to available posts, outstanding overtime payments, lack of academic support and burn-out. Combined, the doctors claim, these conditions have led to patient care being compromised, which was aggravated by the nurses’ strike from 10 to 12 February. At least one pregnant woman died during the strike, although Izindaba could not establish whether or not this was due to strike-compromised care. Eight doctors per shift were covering a 60-bed antenatal ward, a 70-bed postnatal ward, a 43-bed gynaecological ward, an 18-bed high-care unit, a 9-bed labour ward, a 4-bed observation ward and a teeming outpatient clinic – around the clock. The unresolved issues led to major differences between the maternity unit chief Dr Mfundo Mabenge, a member of the National Committee for the Confidential Enquiries into Maternal Deaths (the ‘Saving Mothers, Saving Babies’ committee), and his CEO, Dr Nthombi Quangule. These came to a head, said Izindaba sources in both Bisho (the provincial health department head office) and at the hospital, when Quangule sent an ambulance to fetch Mabenge from his home after he took a few days off to relieve burn-out.

Surprise visit catches nurses asleep in ward beds

Then, just days before the strike, Quangule, in an unannounced late-night medical ward inspection, surprised eight nurses – the entire complement for the ward – asleep in unoccupied patient beds. A disciplinary hearing was pending at the time of going to print, Bisho confirmed. The Eastern Cape health department also began a probe into Quangule’s ‘autocratic’ behaviour and her alleged lack of response to doctor complaints, temporarily relieving her of

her post. The probe findings, which would lead either to her return to her post or the continuation of her temporary replacement, Dr Bawinile Ndlovu, were due at the end of February. All the worker unions involved (the National Education, Health and Allied Workers’ Union (NEHAWU), the Health & Other Services Personnel Trade Union of South Africa (HOSPERSA) and the Democratic Nursing Organisation of South Africa (DENOSA)) called for Quangule’s sacking after a high-level Bisho delegation and a local parliamentary portfolio committee visited the hospital, promising to rectify matters with a detailed plan of action. Quangule was then advised to stay away for her own safety.

Factors contributing to the hospital crisis included the inefficient use of staff and a recent major growth in services. The latter was prompted by a new system decanting patients from other districts to Dora Nginza Hospital before a new staffing plan could be implemented. Izindaba doctor sources said the stalled appointment of senior doctors in the obstet rics and gynaecology unit was leading to senior doctors being overburdened because they had to perform all the caesarean sections (junior doctors may not operate independently). On average, 800 babies are born at the hospital each month. The doctors said that plans for training, and better equipment at clinic level, were abandoned owing to budget constraints. Izindaba is in possession of a letter, dated 4 January 2015, from Dr Lungile Pepeta, paediatrics chief at Dora Nginza Hospital, and addressed to the entire provincial health leadership. In it he said that the Port Elizabeth Hospital Complex was being prevented from replacing medical staff who had left the department during the previous 3 months. ‘The department has issued circulars stating that the appointment of staff will be centralised and that there will

April 2016, Print edition

no replacement of Medical officer posts that have been vacated in order for them to take up funded registrar posts – this has placed unbearable strain in the system.’ Pepeta went on to cite post-community service officers who wanted to remain in the hospital complex not being absorbed.

Hospital accreditation in danger, chief warns

Pepeta warned that with a Health Prof essions Council of South Africa train ing accreditation inspection due in Feb ruary, several departments, including cardio thoracic surgery, obstetrics and gynaecology and psychiatry, stood to lose their training status. He expressed shock at the ‘ongoing notion by the provincial leadership’ that specialist numbers were sufficient, when in fact they were worse than the doctorpopulation ratios of several low-income African countries. One estimate puts the Eastern Cape doctor/patient ratio at one doctor per 10 000 people (ten times less than the World Bank prescription of 1/1 000 people). Speaking to Izindaba, a spokesman for the provincial health department, Siyanda Manana, denied that any moratorium on filling posts existed, saying the procedure was to identify a critical post and then write a motivation to the Cost Containment Committee, which sat weekly. He stressed that the post needed already to have had funding allocated to it. The CEO, Quangule, could not be blamed for this, he added. Factors contributing to the hospital crisis included the inefficient use of staff and a recent major growth in services. The latter was prompted by a new system decanting patients from other districts to Dora Nginza Hospital before a new staffing plan could be implemented. Everything possible would be done to retain longstanding and highly valued staff, he added. Union spokespersons declined to comment until the probe and disciplinary hearing were completed. Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(4):320. DOI:10.7196/SAMJ.2016.v106i4.10763

IZINDABA

Budget squeeze: Cutting clinicians hurts patients The ranks of senior public healthcare administrators swelled by 12% over the past 3 years v. a 3.5% growth among all physicians, pharmacists and pathologists over the same period. This previously unpublicised skewed progression has further bolstered appeals by healthcare professional groups to stop the wide-scale, debilitating freezing of clinical posts. Izindaba’s extraction and review of national public healthcare staff data brings some factual context to ongoing political rhetoric over whether or not clinical posts are being frozen in the current severely constrained economic climate. The South African Medical Association (SAMA) and the Rural Health Advocacy Project (RHAP) claim that health minister Dr Aaron Motsoaledi is playing political semantics by denying that his provincial healthcare counterparts are ‘freezing’ posts, asking him and finance minister Pravin Gordhan to address the ‘real issue’ of funding and protecting critical healthcare posts. The Izindaba review lends credence to longstanding speculation that hard-pressed provincial chief financial managers are panicking at their shrinking budgets, particularly after unions (mainly the National Education and Health Workers’ Union, NEHAWU) won a 10% wage increase totalling ZAR69 billion over the 2015/16 financial year (part of a 3-year settlement). The implications for healthcare delivery – without alternative extra sources of revenue and with the pending expensive implementation of actual National Health Insurance funding – are dire. The widespread blocking or closing down of critical clinical service delivery posts from December last year through January (when most doctors and nurses were seeking them) is, according to SAMA, ‘dangerously short-sighted’. SAMA Chairperson Dr Mzukisi Grootboom says that not only will it hurt the most vulnerable patient populations and increase existing billion-rand litigation claims, but it will aggravate work pressures as clinical staff are stretched to breaking point after colleagues leave, creating a ‘domino effect’ and leading to the potential collapse of untenably staffed district hospitals and community health centres. In spite of the overall national increase from 18 701 clinical staff in September 2012 to 19 352 (35%) by

September 2015, this clinical staff component suddenly plummeted by 327 members (–1.7%) from March to September last year – exactly when financial austerity measures were introduced. Nursing numbers virtually flatlined from 134 153 in September 2012 to 134 453 in September 2013 and 134 811 in September 2014 before suddenly increasing by 1.2% to 136 439 in September last year.

Budget-breakers remain stubbornly in place

Says Daygan Eagar, programme manager for the RHAP and veteran provincial healthcare financial watchdog: ‘While bringing in community service doctors made a huge difference to delivery, and although it increased costs, the glaring primary cost factors have always been higher-than-inflation salary increases and a rapidly growing administrative cadre.’ This happened regardless of how the economy was performing, with the current strain on the national fiscus hugely constricting current provincial budget allocations. Both Eagar and Izindaba Treasury sources agreed that government negotiators ‘tend to give in’ at wage negotiations with the powerful NEHAWU. Grootboom said that although mention was made of a process whereby critical posts could be unfrozen and advertised, the reality was that this was a long bureaucratic procedure that sometimes required approval from the premier’s office. Izindaba’s 11% administrative expansion figure depicts health directors level up to directors-general. Provinces that have

April 2016, Print edition

frozen clinical healthcare staff posts are North West, the Eastern Cape, KwaZuluNatal, Mpumalanga and the Free State. Eagar said that in his experience, even when ‘exceptional circumstances’ were proven and budgets could be freed up, it took between 6 months and a year to fill an unfrozen post. Over the past 3 years the total public sector healthcare staff complement (clinical and nonclinical) has dropped from 314 859 people to 309 367 (–1.8%) – this after continual growth up to 2012, although Izindaba sources stressed that this figure, while illustrating a marked trend, might not be entirely accurate owing to ‘data collection issues’.

Who will care for the growing AIDS population?

With an estimated 3% staff turnover, the state should be able to replace 9 000 posts without increasing expenditure. Significant savings could be achieved by only filling say 7 000 posts, yet unless a pragmatic process for quickly refilling critical posts is in place, the net result could be near-chaos, given the 400 000 annual increase in AIDS patients alone. National health department staff figures show that as of September last year there were 511 senior managers (directors up to directorsgeneral) – up from 457 in September 2012 (a 12% increase), with a gradual upward creep every year in between. In the category of ‘core administration’ (low-level admin posts such as financial clerks, credit controllers, materialrecording and transport clerks, human resource clerks, managers and cashiers), numbers increased by 4 005 between 2013 and 2015 (also up 12%). In September 2012 there were 34 284 core admin staff, dropping slightly to 33 331 in September 2013 and then inexorably increasing to 36 136 in September 2014 and up again to 37 336 in September last year. Izindaba sources said that some ‘shrewd innovative thinking’ would be necessary to correct the current skewed human resource healthcare delivery model. Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(4):321. DOI:10.7196/SAMJ.2016.v106i4.10762

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‘My advice was evidence based’ – Noakes The Health Professions Council of South Africa (HPCSA) this February closed its case against University of Cape Town emeritus professor Tim Noakes on a charge of unprofessional conduct and will resume with cross-examination of the controversial A-rated scientist on 17 October. Noakes was allegedly unprofessional in giving unconventional, non-evidence-based advice to a breastfeeding mother on a social network. The charge followed two tweets Noakes made to breastfeeding mother Pippa Leenstra on 4 February 2014, saying that good first foods for infant weaning are low carbohydrate, high fat. Johannesburg dietitian Claire Julsing Strydom, then president of the Association for Dietetics in South Africa, responded to Leenstra on Twitter, lodging a complaint with the HPCSA on 5 February. The HPCSA formally charged Noakes in September 2014.

The HPCSA’s last expert witness at the February hearing was Stellenbosch Uni versity psychiatry professor Willie Pienaar, a part-time bioethics lecturer. At the earlier (November 2015) session, the HPCSA called Julsing Strydom as a factual witness and heard testimony by retired NorthWest University nutrition professor Este Vorster, North-West University nutrition professor Salome Kruger, Medical Research Council unit head and paediatrics professor Muhammed Ali Dhansay, and HPCSA legal officer Nkagiseng Madube. Vorster, Kruger, Dhansay and Pienaar suggested that Noakes was in a doctor/patient relationship with Leenstra and that the advice he gave was unconventional because it was not evidence based. Madube contended that the HPCSA had followed due process in charging him, which Noakes’ legal team strongly contested. Noakes himself began testifying to the HPCSA Professional Conduct Committee,

April 2016, Print edition

chaired by Pretoria advocate Joan Adams, on 10 February. He denied that he was in a doctor-patient relationship with Leenstra, saying he had not practised medicine for more than 10 years. As a scientist, his main concern was to give people evidence-based information from which they could make up their own minds. His testimony lasted nearly 40 hours and was supplemented by 4 000 pages and 900 slides with study references to suggest that his advice was evidence based. Noakes stressed that his advice was only ‘unconventional’ to anyone who failed to study the evidence. The case is being heard in Newlands, Cape Town. Marika Sboros BizNews.com, Johannesburg and London sborosm@gmail.com S Afr Med J 2016;106(4):322. DOI:10.7196/SAMJ.2016.v106i4.10764

EDITORIAL

Where are the males? Diversity, proportionality and Health Sciences admissions The demographic profile of students at South African (SA) medical schools has under gone significant changes in recent decades; there are now many more ‘black’ and female students than there were 2 decades ago. The altered racial profile is obviously partly attributable to the end of formal discrimination, but more proximately, is largely the result of affirmative action policies that have favoured applicants from previously disadvantaged ‘race’ groups. Applicants from these groups may be admitted with lower entrance scores. The increase in the number of female students over the same 2-decade period is not attributable to an end of formal discrimination, which ended much earlier than discrimination against blacks, or to the introduction of affirmative action. For entirely different reasons, the balance of male and female students in MB ChB programmes has gradually shifted, with female students now the majority (Table 1). In this way, MB ChB programmes are no longer dissimilar from enrolments in allied health programmes, where females have long predominated. The predominantly female enrolment – although not the product of affirmative action – sheds important light on rationales that are regularly provided for racial preference in admissions policies, not only in the country’s medical schools but also throughout SA universities. It is therefore worth considering those rationales and the way they are illuminated by the asymmetrical proportion of male and female Health Sciences students.

Racial preference

One argument for racial preference is redress, in which the favouring of black students on the grounds of their race is justified as a measure to redress past injustices. Blacks, it is argued, are suffering the legacy of past discrimination. They are economically worse off and suffer consequent educational disadvantage at primary and secondary level. In other words, the metaphorical playing fields are not level and therefore some racial preference is necessary in order to redress this injustice. An important challenge to this argument is that it cannot justify favouring those black applicants who are not suffering the legacy of past discrimination. Middle-class and wealthy black applicants, who have attended

superior schools, may share a skin colour with those who are suffering the protracted effects of past discrimination; however, they are not themselves suffering those effects, and thus favouring them – as SA universities do – cannot be justified by the redress argu ment. It is at this point that the diversity argument is invoked. According to this argument, it is important to have a diverse student body for any one of a number of possible reasons. However, the diversity argument is, in fact, not actually a diversity argument. The term diversity is imported from the USA where blacks are a minority of the population and where (far more modest) programmes of racial preference have been instituted in order to secure some minimal representation of African Americans in the student body. In SA, where the majority of the popu lation is black, diversity in this sense can be obtained even without the extreme forms of racial preference that constitute current policy. Thus when SA advocates of affirmative action employ the term diversity they actually mean proportionality. The goal is to have the racial demographics of the student population reflect the racial demographics of the country.

Proportions of males

Is proportionality a genuine commitment or is it rather a rationalisation of a pre conceived idea about the justifiability of racial preference? The gender profile of Health Sciences students in SA provides a helpful test case. If there were a genuine commitment to proportionality, one would think that something would have been done

about the dearth of males in SA medical schools. At the University of Cape Town (UCT), for example, only 36% of MB ChB students and only 35% of all students in the Faculty of Health Sciences are male. Those figures are far from reflective of the demographics of the country. The figures for MB ChB (and some related programmes) are particularly important because there is a stronger case to be made for gender proportionality in medicine than in other areas of study. This is because many people have a reasonable preference for doctors of the same sex as themselves. Just as some women prefer to consult female doctors and physiotherapists and to be attended to by female nurses, so some men may prefer to consult and be cared for by male practitioners. Such preferences have a rational basis.[1] The same cannot be said for preferences to have a lawyer, architect, engineer or quantity surveyor of a particular race or sex – or a doctor of a particular race. (To have a doctor who speaks one’s language is a reasonable preference, but if that were the rationale for affirmative action then preference should be given not on the basis of race but rather on the basis of competence or fluency in a language underrepresented among medical practitioners.)

Possible responses

How might those who defend racial prefer ence in admissions but who are unconcerned about the disproportionately few males in medical schools respond? They might argue that there are not as disproportionately few males as there are blacks and therefore there is currently a

Table 1. Percentage of female students in Health Science faculties*

University

MB ChB, %

All undergraduate, %

Postgraduate, %

Health Sciences total, %

UCT

Wits

UFS

UCT= University of Cape Town; Wits = University of the Witwatersrand; SU = Stellenbosch University; UFS = University of the Free State; UP = University of Pretoria. *All the data are for 2014 and were obtained from each of the named universities. (Thanks to Lara Davison for obtaining the information.) Percentages are rounded up or down. Data from some universities has been omitted because it was incomplete, contradictory or otherwise unreliable. The percentage of female MB ChB students at the University of the Free State is much smaller than at other medical schools. I have some reason for thinking that this is on account of a (now-revised) policy of admitting equal numbers of male and female students, but repeated requests to UFS for clarification have been unanswered.

April 2016, Print edition

EDITORIAL

much stronger proportionality-based case for racial preference than there is for favouring males in admissions to medical schools. However, there clearly are some programmes in which males are a very tiny fraction of all students. For example, only 4.5% of BSc Speech-Language Pathology students at UCT are male, even though approximately 50% of all South Africans are males. If extremely disproportionate percentages were the basis for racial preference then the argument would also apply to those programmes in which males constitute an extremely small proportion of students. Another possible argument is that males (qua males), unlike blacks, are not the victims of past discrimination and it is for this reason that racial preference is required. However, the proportionality argument is different from the redress argument. We have already seen that the redress argument does not apply to all blacks, which is exactly why defenders of racial preference in admissions retreat to the proportionality argument. Thus, the proportionality defence of racial preference cannot be rescued by appealing to a redress argument. This is because the redress argument does not apply to all those whom it favours, namely those blacks who suffer no disadvantage that needs to be redressed. In response to this, it might be suggested that while economically and privileged blacks are not disadvantaged in those ways, they nonetheless are the victims of subtle forms of prejudice or discrimination that partially explain their underrepresentation in the absence of racial preference. However, if one wishes to advance that argument, then one may have to consider the possibility that (different) subtle forms of prejudice and discrimination explain part of the sex imbalance among Health Sciences students. When females are underrepresented in the senior professoriate and in disciplines such as engineering, there is much handwringing and the assumption is that discrimination of some kind explains the problem. However, it is highly implausible to think that prejudice and discrimination are always to blame when women are underrepresented in desirable areas but that prejudice and subtle discrimination play absolutely no role when men are underrepresented.[2] For example, gender roles and the designation of some professions as â&#x20AC;&#x2DC;femaleâ&#x20AC;&#x2122; may militate against males entering them. Consider, for example, the prejudices against male nurses. The fact that these arguments fail suggests an inconsistent acceptance of the proportionality argument among those who invoke

it in defence of racial preference and yet are happy to let the chips fall where they do when it comes to the disproportionately few males in medical schools.

What ought to be done?

The full argument advanced to defend current affirmative action admissions policies would suggest that the correct response to the disproportionately few males in various Health Sciences programmes would be a policy of sex-based preference for males. However, I have argued elsewhere against race-based preferences[3,4] and I similarly think that sex-based preference is problematic, whether the beneficiaries are male or female.[5] This does not mean that nothing can be done about the uneven enrolments of males and females. There are forms of affirmative action that do not involve any noxious preferences. For example, one might, in the first instance, try to understand why more males with competitive matriculation marks are not applying for Health Sciences programmes (as they once did in the case of the MB ChB), preferring now instead to apply for other courses of study.[6] Therefore, some research needs to be done. With the results in hand, one would be better placed to determine whether careers in medicine and other healthcare professions could be made more attractive to males, thereby increasing the number of male applicants who could be admitted using the same criteria and standards as are used for female applicants. D Benatar Department of Philosophy, Faculty of Humanities, University of Cape Town, South Africa Corresponding author: D Benatar (philosophy@uct.ac.za) 1. Benatar D. The Second Sexism: Discrimination Against Men and Boys. Malden: Wiley-Blackwell, 2012:149-150. 2. Benatar D. The Second Sexism: Discrimination Against Men and Boys. Malden MA: Wiley-Blackwell, 2012. 3. Benatar D. Justice, Diversity and Racial Preference: A Critique of Affirmative Action, S Afr Law J 2008;125(2):274-306. 4. Benatar, D. Just admissions: South African universities and the question of racial preference. S Afr J High Educ 2010;24(2):258-267. 5. Benatar D. The Second Sexism: Discrimination Against Men and Boys. Malden: Wiley-Blackwell, 2012:212-238. 6. Ncayiyana DJ. Feminisation of the South African medical profession â&#x20AC;&#x201C; not yet nirvana for gender equity S Afr Med J 2011;101(1):5.

S Afr Med J 2016;106(4):323-324. DOI:10.7196/SAMJ.2016.v106i4.10569

April 2016, Print edition

EDITORIAL

Unpacking the new proposed regulations for South African traditional health practitioners Traditional health practitioners (THPs) are an integral part of the history and culture of South Africa (SA). Many traditional healers and users of traditional medicine agree that there is a need to regulate the system. To this end, over the years, healers have initiated over 100 different traditional healer associations countrywide.[1,2] More recently, however, steps have been taken to regulate the estimated 200 000 THPs[3] under one professional statutory body.[4]

The Traditional Health Practitioners Act

The Traditional Health Practitioners Act 22 of 2007[4] aims to: (i) create an Interim Traditional Health Practitioners Council; (ii) provide a regulatory framework to ensure the efficacy, safety and quality of traditional healthcare services; and (iii) provide for the management and control over the registration, training and conduct of practitioners, students and specified categories in the THP profession. The Act defines four categories of THPs, namely diviners (sangoma), herbalists (inyanga), traditional birth attendants (ababelethisi) and traditional surgeons (ingcibi).

The establishment of a new Council

Under the Act,[4] the Interim Traditional Health Practitioners Council, appointed by the Mini ster of Health, should comprise one THP per province as well as a representative of each of the four THP categories. Over and above this, the Council must also include a legal expert, a member of the Health Professions Council of SA (a medical practitioner), a member of the SA pharmacy council (a pharmacist), community representatives and representatives of the Department of Health. In early 2013, the Council was inaugurated,[5] and the sections of the Act that allowed the Council to become functional came into effect on 1 May 2014.[6] The mandate of the Council is drawn from the Bill of Rights in the SA Constitution, the National Health Act 61 of 2003 as well as the THP Act 22 of 2007.[5] The interim Council now has extensive powers to oversee the registration and regulation of the practice of THPs by setting practice standards.

The proposed regulations

On 3 November 2015, after consultation with the interim Council, the Minister of Health published the much-anticipated

THP Regulations to elicit comments from interested persons.[7] However, the lack of substantive detail in the proposed regulations leaves a lot of room for interpretation and speculation. In four brief pages, a regulatory framework for traditional healers, students (abatwasa) and trainers is proposed. This is followed by three separate pro forma registration documents for THPs, students and/or trainers. It is not clear whether all registrations will commence simultaneously or in a step-wise manner. The latter seems more plausible, as a knock-on effect is anticipated for certain registration categories.

Mandatory registration for all SA THPs

In terms of section 21 of the Act, ‘no person may practise as a traditional health practitioner within the Republic unless he or she is registered in terms of this Act’. Section 21 of the Act also clearly states that an application must be accompanied by proof that the applicant is an SA citizen. The fact that only SA citizens may apply for registration will have financial consequences for foreigners currently offering traditional healing services. Apart from an SA identity document, further required documentation listed in the pro forma document includes ‘proof of qualification as

THP (if any)’ and ‘highest standard passed (attach certified copy, if any)’. It is not clear if registration will continue even if those documents do not exist. The next schedule of the Regulations states that all THPs ‘must undergo education or training at any accredited training insti tution or educational authority or with any traditional tutor’. The relationship between the schedules relating to registration and training is unclear. Will registration be delayed or conditional until a THP has undergone specified training? Even more elusive are the minimum standards and levels of training.

Minimum training standards for student THPs

Unlike for current practising THPs, mini mum requirements for prospective student THPs are clearly outlined and nobody is allowed to start traineeship unless he or she is registered as a student. Once again, the proposed regulations stress an SA identify document as a necessary supporting document. Minimum education, length of training and minimum age are the three items specified for student THPs (Table 1). All student THPs need to provide proof

Table 1. Minimum standards for student training[7] Student category

Minimum period of training

Minimum competencies

Minimum age for THP registration (years)*

Diviner

12 months

Diagnosis, preparation of herbs and traditional consultation

Herbalist

12 months

Identification and preparation of herbs, sustainable collection of herbs, dispensing of herbs and consultation

Traditional birth attendant

12 months

Handling issues of conception, pregnancy, delivery of baby and pre- and postnatal care

Traditional surgeon (circumcision)

5 years (which includes observation in 3 initiation schools and supervised practice for 2 years)

Not specified

*‘to qualify for registration for a certificate entitling the holder thereof to registration in terms of the Act’

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EDITORIAL

of adult basic education and training (ABET) level 1 or equivalent. The longest training period is for a traditional surgeon, whereby the trainee must conduct observation in three initiation schools and do supervised practice for 2 years, bringing the full training to a minimum of 5 years. The minimum age for registration as a traditional surgeon and traditional birth attendant are the same – 25 years of age. It is not clear why a potential traditional birth attendant should wait until he or she is at least 25 years of age considering that the training programme need only be 12 months long and that no prerequisite education is required other than ABET level 1. For all categories, after training, the registered student will need to submit a logbook to the Council that details the observations and procedures undertaken.

Accreditation system for trainers and training institutions

Under the Act,[4] an ‘accredited institution’ means ‘an institution, approved by the Council, which certifies that a person or body has the required capacity to perform the functions within the sphere of the National Quality Framework (NQF) contemplated in the SA Qualifications Authority Act 58 of 1995’. The NQF has been specifically designed to integrate education and training into a single framework, and combine separate education and training systems into a single, national system.[8] The proposed Regulations do not prescribe specific content or a curriculum for training, but the section under minimum standards for student training (Table 1) provides a very general outline of what is expected. In the list of supporting documents for trainers is the request for copies of teaching/learning materials. However, the actual process for vetting the submitted curricula is not provided. It is also not clear how the submission of training materials by individual THPs may culminate into a national training programme under the NQF. The submission of teaching/learning materials to the Registrar and/or Council is noteworthy and part of a larger discourse regarding intellectual property rights. Intellectual property rights are at the epicentre of numerous contemporary policy debates, both locally and abroad[9] and the proposed Regulations are timely with the recently published draft Protection, Promotion, Development and Management of Indigenous Knowledge Systems Bill by the SA Department of Science and Technology.[10]

Conclusions

SA has legislation that regulates almost all of its healthcare systems. [2] The THP Act finally provides legitimisation of an overwhelmingly popular indigenous healthcare system. However, as a consequence of the legal acknowledgement of THPs, traditional medicine products must now also be brought under regulatory measures. If traditional medicines are to be prescribed, marketed and sold as part of a healthcare system recognised under SA law, they must meet the same stringent standards.[3] Acknowledgement. The content is solely the responsibility of the author and does not necessarily represent the official views of the South African Medical Research Council or the University of KwaZulu-Natal.

R A Street Environment and Health Research Unit, South African Medical Research Council, Durban, South Africa, and Discipline of Occupational and Environmental Health, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa Corresponding author: R A Street (renee.street@mrc.ac.za) 1. Pretorius E. Traditional healers. S Afr Health Rev 1999:249-256. 2. Gqaleni N, Moodley I, Kruger H, Ntuli A, McLeodiv H. Traditional and complementary medicine: Healthcare delivery. S Afr Health Rev 2007:175-188. 3. Hassim A, Heywood M, Berger J. Health and Democracy: A Guide to Human Rights, Health Law and Policy in Post-apartheid South Africa. Cape Town: Siber Ink, 2007. 4. South African Department of Health. Traditional Health Practitioners Act 22 of 2007. Pretoria; Department of Health, 2007. 5. South African Department of Health. Interim Traditional Health Council Inaugurated. 2013. http:// www.sabinetlaw.co.za/health/articles/interim-traditional-health-council-inaugurated (accessed 9 January 2016). 6. President of the Republic of South Africa. Commencement of certain sections of the Traditional Health Practitioners Act Proclamation, 2007 (22 of 2007). Proclamation Notice No. 29 of 2014. In: Government Gazette No. 37600. Pretoria: Government Printing Works, 2014. 7. South African Department of Health. Notice 1052: Traditional Health Practitioners Regulations 2015. In: Government Gazette No. 39358. Pretoria: Government Printing Works, 2015. 8. The South African Qualifications Authority (SAQA). The South African National Qualifications Framework. http://www.saqa.org.za/list.php?e=NQF (accessed 11 January 2016). 9. Teljeur E. Intellectual Property Rights in South Africa: An Economic Review of Policy and Impact. Johannesburg: The Edge Institute, 2003. 10. South African Department of Science and Technology. Notice 243 of 2015. Protection, Promotion, Development and Management of Indigenous Knowledge Systems Bill, 2014. Pretoria: Government Printing Works, 2015.

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GUEST EDITORIAL

Acute viral bronchiolitis in South Africa: Diagnosis and current management This issue of CME profiles acute viral bronchiolitis – a common condition that is often not serious. Nonetheless, each year a number of infants, particularly those with an underlying susceptibility to severe disease, are admitted to hospital or even to paediatric intensive care units. This series of articles highlights the diagnostic principles involved, and emphasises the principles of management and prevention. Acute viral bronchiolitis occurs primarily in infants <1 year of age. It is frequently the first episode of a wheezing illness in a child. This episode should never be labelled asthma, although it may lead to subsequent wheezing and even asthma later in life, which has implications for management and certainly for prevention. Children develop a common cold and then the viruses involved may produce inflammation in the lower respiratory tract airways. Lower respiratory tract infection, in cases of bronchiolitis, usually has a viral aetiology and does not require antibiotic management. It is distinguished from pneumonia in that, although producing fast breathing, it causes hyperinflation of the chest, which suggests airway involvement – not air-space disease. Any infant presenting to a doctor with cough and age-specific fast breathing, must be assessed for hypoxia. Peripheral oxygen saturation is the only test routinely required in such children. If hypoxic, the infant must receive oxygen via nasal prongs or face mask and be admitted to hospital. As bacterial co-infection is rare, testing for bacterial involvement is unnecessary and unreliable in all but the sickest of children. It also implies that therapy should not include the routine use of antibiotics, which is unnecessary and potentially dangerous, as the emergence of resistant pathogens is an important concern with over-use and abuse of these drugs. Most routine therapies for asthma are ineffective for bronchiolitis and should not be used, including bronchodilators (oral and nebulised), steroids (oral, systemic or nebulised), montelukast and all the over-the-counter cough and cold medicines. A number of studies have shown that physiotherapy, which is so popular in South Africa (SA), worsens hypoxia, and should therefore be discontinued in such cases. While hypertonic saline nebulisation was suggested as an effective therapy for bronchiolitis, reducing the need for and duration of hospitalisation, recent large studies have shown that it is ineffective. It should therefore not be recommended. There are important preventive modalities for bronchiolitis, including isolation of children with colds (i.e. sick children should not go to crèches for a few days), and teaching children (and adults looking after infants) to practise sneeze and cough hygiene. Prevention does not include the use of prophylactic antibiotics for children with upper respiratory tract infections; their use is strongly discouraged. Prevention of respiratory syncytial virus (RSV) disease in young children may be the most effective strategy to reduce the burden of disease, especially in children at high risk of developing severe disease.[1] The monoclonal antibody, palivizumab, administered monthly throughout the RSV season to infants and children at high risk of severe RSV disease, has been shown to be effective for prevention. Furthermore, palivizumab has also been proven to reduce RSV disease, wheezing and recurrent wheezing episodes in the first year of life when administered to late preterm infants.[2]

However, its use is limited by its high cost and the need for monthly intramuscular injections during the RSV season. More recently, increased attention has been given to the development of an effective RSV vaccine, particularly targeted at pregnant women, as a strategy for prevention of RSV disease in their offspring in the first months of life.[3] This is an attractive strategy for which the results of clinical trials are awaited. The two CME articles in this edition of SAMJ are a concise reflection of the evidence with regard to acute viral bronchiolitis. The guideline committee has reviewed the available literature in making these recommendations. Each section has been fully referenced. The first article[4] gives a step-wise approach to the diagnosis of acute viral bronchiolitis, suggesting that ‘less is more’ by way of tests in patients with this condition; that many tests are inappropriate; and that important tests such as peripheral oxygen saturation must be appropriately performed. The second article[5] is a summary of what should be used with regard to treatment and prevention. A number of guidelines for the management and prevention of acute viral bronchiolitis are published worldwide annually. These have been consulted in our recommendations. However, none perfectly fits the disease entity, organism seasonality, duration and specific considerations for SA. Hence the need for local guidelines on this topic. It is hoped that these will guide local healthcare practitioners, funders and policy makers in ensuring the best care of children in SA. R J Green Guest editor Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Pretoria, and Steve Biko Academic Hospital, Pretoria, South Africa robin.green@up.ac.za H J Zar Guest editor Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, and MRC Unit on Child and Adolescent Health, Faculty of Health Sciences, University of Cape Town, South Africa heather.zar@uct.ac.za 1. Shi T, Balsells E, Wastnedge E, et al. Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta-analysis. J Glob Health 2015;5(2):020416. DOI:10.7189/jogh.05.020416 2. Blanken MO, Rovers MM, Molenaar JM, et al. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med 2013;368(19):1791-1799. DOI:10.1056/NEJMoa1211917 3. Mazur NI, Martinón-Torres F, Baraldi E, et al. Lower respiratory tract infection caused by respiratory syncytial virus: Current management and new therapeutics. Lancet Respir Med 2015;3(11):888-900. DOI:10.1016/S2213-2600(15)00255-6 4. White DA, Zar HJ, Madhi SA, et al. Acute viral bronchiolitis in South Africa: Diagnostic flow. S Afr Med J 2016;106(4):328-329. DOI:10.7196/SAMJ.2016.v106i4.10441 5. Zar HJ, Madhi SA, White DA, et al. Acute viral bronchiolitis in South Africa: Strategies for management and prevention. S Afr Med J 2016;106(4):330-332. DOI:10.7196/SAMJ.2016.v106i4.10437

S Afr Med J 2016;106(4):327. DOI:10.7196/SAMJ.2016.v106i4.10704

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CME

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

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

Bronchiolitis may be diagnosed on the basis of clinical signs and symptoms. In a young child, the diagnosis can be made on the clinical pattern of wheezing and hyperinflation. Clinical symptoms and signs typically start with an upper respiratory prodrome, including rhinorrhoea, low-grade fever, cough and poor feeding, followed 1 - 2 days later by tachypnoea, hyperinflation and wheeze as a consequence of airway inflammation and air trapping. The illness is generally self limiting, but may become more severe and include signs such as grunting, nasal flaring, subcostal chest wall retractions and hypoxaemia. The most reliable clinical feature of bronchiolitis is hyperinflation of the chest, evident by loss of cardiac dullness on percussion, an upper border of the liver pushed down to below the 6th intercostal space, and the presence of a Hoover sign (subcostal recession, which occurs when a flattened diaphragm pulls laterally against the lower chest wall). Measurement of peripheral arterial oxygen saturation is useful to indicate the need for supplemental oxygen. A saturation of <92% at sea level and 90% inland indicates that the child has to be admitted to hospital for supplemental oxygen. Chest radiographs are generally unhelpful and not required in children with a clear clinical diagnosis of bronchiolitis. Blood tests are not needed routinely. Complete blood count tests have not been shown to be useful in diagnosing bronchiolitis or guiding its therapy. Routine measurement of C-reactive protein does not aid in management and nasopharyngeal aspirates are not usually done. Viral testing adds little to routine management. Risk factors in patients with severe bronchiolitis that require hospitalisation and may even cause death, include prematurity, congenital heart disease and congenital lung malformations. S Afr Med J 2016;106(4):328-329. DOI:10.7196/SAMJ.2016.v106i4.10441

Clinical manifestations

Bronchiolitis is a viral‐induced lower respiratory tract infection that occurs predominantly in children <2 years of age, particularly infants. Many viruses have been proven or attributed to cause bronchiolitis, including and most commonly the respiratory syncytial virus (RSV) and rhinovirus. Bronchiolitis may be diagnosed on the basis of clinical signs and symptoms. In a young child, the diagnosis can be made on the clinical pattern of wheezing and hyperinflation. Clinical symptoms and signs typically start with an upper respiratory prodrome, including rhinorrhoea, low-grade fever, cough and poor feeding, followed 1 - 2 days later by tachypnoea, hyperinflation and wheeze as a consequence of airway inflammation and air trapping.[1] The illness is generally self limiting, but may progressively become more severe and include signs such as grunting, nasal flaring, subcostal chest wall retractions and hypoxaemia.[2] The most reliable clinical feature of bronchiolitis is hyperinflation of the chest, evident by loss of cardiac dullness on percussion, an upper border of the liver pushed down to below the 6th intercostal space, and the presence of a Hoover sign (subcostal recession, which occurs when a flattened diaphragm pulls laterally against the lower chest wall).

Measurement of peripheral arterial oxygen saturation is useful to indicate the need for supplemental oxygen. A saturation of <92% at sea level and 90% inland indicates that the child requires hospital admission for supplemental oxygen.

Investigations Chest radiographs

Chest radiographs (CXRs) are generally unhelpful and not required in children with a clear clinical diagnosis of bronchiolitis. Risk of airspace disease appears to be particularly low in children with saturation >92% and with mild to moderate distress.[3] A temperature ≥38°C has been shown to be a clinical predictor of radiographic abnormalities.[4] CXRs in bronchiolitis show signs of hyperinflation, peribronchial thickening or patchy areas of consolidation and collapse, which may be confused with signs of pneumonia. A CXR should only be done in the following instances:[2,4,5] • if complications are suspected, e.g. pleural effusion or pneumo thorax • severe cases • temperature ≥38°C

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CME

• uncertain diagnosis • if the child fails to improve or if their condition deteriorates.

Haematology

Blood tests are not needed routinely. Com plete blood count tests have not been shown to be useful in diagnosing bronchiolitis or guiding its therapy.[2] Routine measurement of C-reactive protein does not aid in manage ment.[6] If the infant appears severely ill, consider alternative diagnoses (bacterial co-infection and other causes of airway obstruction). Clinical signs of concern include pallor, lethargy, severe tachycardia, high tempera ture, hypotonia or seizures. In cases of serious sepsis investigations may include a CXR, blood culture, and urinary and cere brospinal fluid analysis.[5]

Nasopharyngeal aspirates

Nasopharyngeal aspirates (NPAs) are not usually taken and viral testing adds little to routine management,[7] but NPAs are needed to inform surveillance, measuring burden of disease and also in the following cases:[5,7] • neonates (<1 month) • history of apnoea with illness • bed management to allow cohorting of patients. NPAs should be immersed in viral transport medium at 4 - 8°C and transported to an appropriate laboratory within 72 hours of collection. Specimens should be tested by multiplex real-time reverse-transcription poly merase chain reaction (rRT-PCR) assay for respiratory viruses. Comparative studies have shown that rRT-PCR assays are substantially more sensitive than conventional methods, such as viral culture and immunofluorescence assays, for detecting respiratory viruses.[8] Furthermore, multiplex rRT-PCR has a significant advantage, as it permits simul taneous amplification of several viruses in a single reaction, facilitating a cost-effective diagnosis.[8]

Risk factors for severe disease

In infants and young children respiratory virus es have the propensity to produce more serious lower respiratory tract illnesses, bronchiolitis

and pneumonia. Infants <1 year of age are at greatest risk of bronchiolitis, and the disease is more severe when risk factors are present (Table 1).[9-15] Debate about the importance of respiratory syncytial virus infection as a cause of hospitalisation in late preterm infants has raged because of the cost of prophylactic therapy. Recent reports have suggested that these infants are at equal risk and require prophylaxis.[16,17] South African studies have revealed that the mean duration of symptoms following bronchiolitis was 12 days (95% confidence interval 11 - 14 days). After 21 and 28 days, 18% and 9%, respectively, were still ill. Thirty-four percent of these children were seen by a physician during an unscheduled visit.[18] Finally, the respiratory viruses, especially RSV, may predispose to recurrent episodes of wheezing and possibly asthma.[19,20] Table 1. Risk factors for severe bronchiolitis, requiring hospitalisation or causing mortality Premature infants Congenital heart disease Congenital lung malformations Chronic lung disease Neuromuscular disease Age <6 months Male sex Siblings living in the household Daycare attendance Exposure to tobacco smoke Immune compromise (malignancy, primary immunodeficiency, HIV*) *Risk greatest for pneumonia.

Table 2. Differential diagnosis of bronchiolitis Acute symptoms Bronchopneumonia Pertussis Foreign body Myocarditis Recurrent wheeze Cystic fibrosis Cardiac disease HIV/tuberculosis

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Differential diagnosis

The differential diagnosis of respiratory symptoms is wide, but where hyperinflation and wheeze occur the conditions listed in Table 2 should be considered. References 1. Wohl MEB. Bronchiolitis. In: Chernick V, Boat TF, Wilmot RW, Bush A, eds. Kendig’s Disorders of the Respiratory Tract in Children. Philadelphia: Saunders, 2006:423-432. DOI:10.1016/ B978-0-7216-3695-5.50029-8 2. American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics 2006;118(4):1774-1793. DOI:10.1542/ peds.2006-2223 3. Schuh S, Lalani A, Allen U, et al. Evaluation of the utility of radiography in acute bronchiolitis. J Pediatr 2007;150:429-433. DOI:10.1016/j.jpeds.2007.01.005 4. Ecochard-Dugelay E, Beliah M, Perreaux F, et al. Clinical predictors of radiographic abnormalities among infants with bronchiolitis in a pediatric emergency department. BMC Pediatrics 2014;14:143. DOI:10.1186/1471-2431-14-143 5. Gavin R, Sheperd M. Starship Clinical Guideline. http:// www.adhb.govt.nz/starshipclinicalguidelines/_Documents/ Bronchiolitis.pdf (accessed 15 May 2015). 6. Moodley T, Masekela R, Kitchin O, Risenga S, Green RJ. Acute viral bronchiolitis. Aetiology and treatment implications in a population that may be HIV co-infected. S Afr J Epidemiol Infect 2010;25(2):6-8. 7. Zorc JJ, Hall CB. Bronchiolitis: Recent evidence on diagnosis and management. Pediatrics 2010;125:342-349. DOI:10.1542/ peds.2009-2092 8. Pretorius MA, Madhi SA, Cohen C, et al. Respiratory viral coinfections identified by a 10-plex real-time reverse-tran scription polymerase chain reaction assay in patients hospitalized with severe acute respiratory illness – South Africa, 2009 - 2010. J Infect Dis 2012;206(S1):S159-S165. DOI: 10.1093/infdis/jis538 9. Stein RT, Sherill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 1999;354:541-545. DOI:10.1016/S0140-6736(98)10321-5 10. Dominquez-Pinilla N, Belda Hofheinz S, Vivanco Martinez JL, et al. Respiratory syncytial virus in immunocompromised patients in a pediatric hospital: 5 years experience. An Pediatr (Barc) 2015;82(1):35-40. DOI:10.1016/j.anpedi.2014.04.016 11. Cohen C, Walaza S, Moyes J, et al. Epidemiology of viral-associated acute lower respiratory tract infection among children <5 years of age in a high HIV prevalence setting, South Africa, 2009 - 2012. Pediatr Infect Dis J 2015;34:66-72. DOI: 10.1097/INF.0000000000000478 12. Schuster JE, Williams JV. Human metapneumovirus. Pediatr Rev 2013;34:558-565. DOI:10.1542/pir.34-12-558 13. Asner S, Stephens D, Pedulla P, Richardson SE, Robinson J, Allen U. Risk factors and outcomes for respiratory syncytial virusrelated infections in immunocompromised children. Pediatr Infect Dis J 2013;32:1073-1076. DOI:10.1097/INF.0b013e31829dff4d 14. Moyes J, Cohen C, Pretorius M, et al. Epidemiology of respira tory syncytial virus-associated acute lower respiratory tract infection hospitalizations among HIV-infected and HIVuninfected South African children, 2010-2011. J Infect Dis 2013;208(Suppl 3):S217-S226. DOI:10.1093/infdis/jit479 15. Tempia S, Walaza S, Viboud C, et al. Mortality associated with seasonal and pandemic influenza and respiratory syncytial virus among children <5 years of age in a high HIV prevalence setting – South Africa, 1998 2009. Clin Infect Dis 2014;58:1241-1249. DOI:10.1093/cid/ciu095 16. Resch B, Paes B. Are late preterm infants as susceptible to RSV infection as full term infants? Early Hum Dev 2011;87(Suppl 1):S47-S49. DOI:10.1016/j.earlhumdev.2011.01.010 17. Madhi SA, Venter M, Alexandra R, et al. Respiratory syncytial virus associated illness in high‐risk children and national characterisation of the circulating virus genotype in South Africa. J Clin Virol 2003;27:180‐189. 18. Swingler GH, Hussey GD, Zwarenstein M. Duration of illness in ambulatory children diagnosed with bronchiolitis. Arch Pediatr Adolesc Med 2000;154:997-1000. DOI:10.1001/ archpedi.154.10.997 19. Sigurs N, Gustafsson PM, Bjarnason R, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy by age 13 years. Am J Respir Crit Care Med 2005;171:137-141. DOI:10.1164/rccm.200406-730OC 20. Lotz MT, Moore ML, Peebles RS Jr. Respiratory syncytial virus and reactive airway disease. Curr Top Microbiol Immunol 2013;372:105-118. DOI:10.1007/978-3-642-38919-1_5

CME

Acute viral bronchiolitis in South Africa: Strategies for management and prevention H J Zar,1 MB BCh, FC Paed (SA), PhD; S A Madhi,2 MB BCh, MMed (Paed), FC Paed (SA), PhD; D A White,3 MB BCh, FC Paed (SA), MMed (Paed), Dip Allerg (SA), Cert Pulmonology (SA) Paed; R Masekela,4 MB BCh, MMed (Paed), Cert Pulmonology (SA) Paed, Dip Allerg (SA), FCCP, PhD; S Risenga,5 MB ChB, FC Paed (SA), Dip Allerg (SA), Cert Pulmonology (SA) Paed; H Lewis,6 MB ChB, MMed; C Feldman,7 MB BCh, FCP (SA), FRCP, PhD, DSc; B Morrow,8 BSc (Physio), PG Dipl (Health Research Ethics), PhD; P Jeena,4 MB ChB, FC Paed (SA), Cert Pulmonology (SA) Paed epartment of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, and MRC Unit on Child and Adolescent Health, D Faculty of Health Sciences, University of Cape Town, South Africa 2 Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa 3 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 4 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of KwaZulu-Natal, Durban, South Africa 5 Department of Pulmonology, Faculty of Health Sciences, University of Limpopo, Polokwane, and Pietersburg Hospital, South Africa 6 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Pretoria, South Africa 7 Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 8 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, South Africa 1

Corresponding author: H Zar (heather.zar@uct.ac.za) Management of acute viral bronchiolitis is largely supportive. There is currently no proven effective therapy other than oxygen for hypoxic children. The evidence indicates that there is no routine benefit from inhaled, rapid short-acting bronchodilators, adrenaline or ipratropium bromide for children with acute viral bronchiolitis. Likewise, there is no demonstrated benefit from routine use of inhaled or oral corticosteroids, inhaled hypertonic saline nebulisation, montelukast or antibiotics. The last should be reserved for children with severe disease, when bacterial co-infection is suspected. Prevention of respiratory syncytial virus (RSV) disease remains a challenge. A specific RSV monoclonal antibody, palivizumab, administered as an intramuscular injection, is available for children at risk of severe bronchiolitis, including premature infants, young children with chronic lung disease, immunodeficiency, or haemodynamically significant congenital heart disease. Prophylaxis should be commenced at the start of the RSV season and given monthly during the season. The development of an RSV vaccine may offer a more effective alternative to prevent disease, for which the results of clinical trials are awaited. Education of parents or caregivers and healthcare workers about diagnostic and management strategies should include the following: bronchiolitis is caused by a virus; it is seasonal; it may start as an upper respiratory tract infection with low-grade fever; symptoms are cough and wheeze, often with fast breathing; antibiotics are generally not needed; and the condition is usually self limiting, although symptoms may occur for up to 4 weeks in some children. S Afr Med J 2016;106(4):330-332. DOI:10.7196/SAMJ.2016.v106i4.10437

Management of bronchiolitis

Management of acute bronchiolitis is largely supportive.[1] There is currently no proven effective therapy other than oxygen for hypoxic children (Table 1).[2,3] The following supportive treatments have been used for the management of bronchiolitis: • humidified oxygen • inhaled short-acting bronchodilator therapy • nebulised hypertonic saline (3% or 5%) • corticosteroids: oral or nebulised • inhospital use of antiviral treatments, e.g. ribavirin in ventilated children • montelukast • antibiotics. Humidified low-flow oxygen (0.5 - 3.0 L/min) applied by nasal prongs is effective for hypoxic

children. Nasal prongs give a maximum inspired oxygen of 28 - 35% except in small infants, when higher oxygen concentrations may be obtained. Headbox oxygen is an alternative and is well tolerated by young Table 1. Therapies that may be beneficial in the management of bronchiolitis and those that are currently not routinely indicated Beneficial therapies Humidified oxygen Therapies not routinely indicated Bronchodilators Adrenaline Steroids (oral, systemic or nebulised) Montelukast Physiotherapy Mucolytics and decongestants

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infants. It requires no humidification, but high flow and a mixing device are needed to ensure that the correct oxygen concentration is delivered. However, there is wastage of oxygen and the delivered oxygen concentration (FiO2) is unpredictable. Facemask oxygen delivers between 28% and 65% oxygen at a flow rate of 6 - 10 L/min. In severely hypoxic infants who are not ventilated, oxygen should be administered using a polymask, which enables FiO2 concentrations of 60 - 80% being achieved. Oxygen should be weaned when the child improves clinically and as hypoxia resolves. Rapid, short-acting inhaled bronchodilator therapy such as albuterol or salbutamol has not shown any important clinical benefits in the treatment of bronchiolitis.[1,4] A Cochrane review (30 trials, 1 992 infants, including inpatient and emergency settings) reported no effects

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in oxygen saturation, reduction in hospital admission after outpatient treatment, duration of hospitalisation or time to resolution of illness at home.[4] Given the potential for adverse side-effects and the cost of these treatments, bronchodilators should not be recommended for the routine management of bronchiolitis. For studies of adrenaline compared with placebo, a Cochrane review (19 studies, 2 256 children) suggested a short-term benefit from adrenaline, especially in the first 24 hours of the illness.[5] No differences were found for length of hospital stay, but there was some evidence that adrenaline was effective for reducing the number of hospital admissions.[5] One large, high-quality trial suggested that combined treatment with dexamethasone and adrenaline may significantly reduce the number of admissions.[5] However, there is currently insufficient evidence to support the use of adrenaline for the treatment of bronchiolitis among children admitted to hospital. Inhaled ipratropium bromide is an ineffective treatment.[6] Conflicting data have been reported for the efficacy of hypertonic saline nebulisation administered as nebulised 3% or 5% saline for acute bronchiolitis. A 2013 Cochrane review (11 trials, 1 090 child ren) reported a reduction in duration of hospital stay and improve ment in clinical scores in children who were inpatients, but no short-term effects in children in four trials done in an emergency unit setting.[7] However, recently the largest reported randomised controlled study of nebulised hypertonic saline in acute bronchiolitis: randomised controlled trial and economic evaluation (SABRE) in hypoxic children, found no difference in outcomes between children who received hypertonic saline compared with those who received standard care.[8] Other recently published randomised trials have also added to the evidence against the use of hypertonic saline in bronchiolitis, showing no difference in length of hospital stay, clinical scores or improvement in oxygenation compared with children receiving normal saline nebulisation or salbutamol.[9-12] The current evidence does not demonstrate consistent benefit with the use of hypertonic saline; currently, this strategy should therefore not be recommended. Systemic or inhaled corticosteroids have been shown not to be effective in reducing hospital admission or improving clinical scores in ambulatory patients.[1,13] However, among inpatients, corticosteroids improved clinical scores within the first 12 hours, but did not have any effect on length of stay. Therefore, corticosteroids should not be routinely recommended.[13] Five randomised controlled trials have shown no evidence of benefit for inhaled corticosteroids started in the acute phase of bronchiolitis for prevention of post-bronchiolitic wheezing.[14] Routine use of systemic or inhaled steroids in the management of bronchiolitis is therefore not indicated. Montelukast has no effect on the clinical course or outcome of bronchiolitis. A study of montelukast (4 mg daily until discharge) found that it demonstrated no improvement in the clinical course of the disease.[15] In a study of post-bronchiolitis wheeze, montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children.[16] Similarly, aerosolised ribavirin has been reported not to have any significant consistent beneficial effect in the management of bron chiolitis.[1,17] The use of chest physiotherapy has been shown not to change the course of bronchiolitis or its outcome. Chest physiotherapy using vibration and percussion techniques does not reduce the length of hospital stay or oxygen requirements or improve the severity clinical scores in infants with acute bronchiolitis.[18] Finally, a Cochrane review of antibiotics compared with placebo for bronchiolitis, including two studies of azithromycin compared with placebo, found no difference in length of hospital stay, duration

of oxygen administration or readmission rates.[19] Antibiotics should therefore not be used routinely in bronchiolitis, except in children with severe disease in whom bacterial lower respiratory tract infection is suspected.

Prevention of RSV disease in high-risk children

The specific RSV monoclonal antibody, palivizumab, is available for children at risk of severe bronchiolitis. With regard to RSV-associated morbidity, the risk of hospitalisation is 5.2/1 000 (4.8 - 5.7) cases.[20] However, this risk rapidly increases with decreasing gestational age, being 19.3/1 000 in premature infants <29 weeks of gestational age and with congenital heart defects. RSV hospitalisation rates are highest at 120.8/1 000 in the first 6 months after delivery, declining to 63.2/1 000 at 6 - 12 months of age and to 18.2/1 000 in the >12-month age group.[20] Similarly, the risk of hospitalisation in children with chronic lung disease of prematurity is 562.5/1 000 in the <6-month age group, 214.3/1 000 in the 6 - 12-month age group, and 73.4/1 000 in those >12 months of age.[20] Palivizumab has been demonstrated to be effective in reducing RSV-related hospi talisation and the need for intensive care unit (ICU) admission among all premature infants and those with bronchopulmonary dysplasia by 55%, with an adjusted risk reduction of 3 - 9% in a Level 1 study.[21] Meta-analysis has confirmed this across all populations of preterm infants.[22] This monoclonal antibody has also been shown to reduce duration of hospitalisation stay and need for oxygen in young children with congenital heart defects.[23] Given the current burden of RSV disease, it is estimated that the number needed to treat to prevent one hospitalisation from RSV disease in premature infants and children with chronic lung disease or congenital heart defects is between 16 and 23, which increases sixfold for the prevention of ICU admission or death. At the current cost of palivizumab, it is extremely expensive to recommend its widespread use; it is therefore restricted to high-risk groups.[24] For the prevention of RSV-associated bronchiolitis, the South African (SA) guideline for the use of palivizumab recommends that it should be restricted for use in the first 6 months of life in highrisk children, defined as premature infants.[21,22] Furthermore, infants with chronic lung disease of prematurity or those with congenital heart defects with signi ficant haemodynamic instability (complex lesions with pulmonary hypertension) and the premature neonate who is a graduate of an ICU and has ongoing respiratory or cardiac compromise (diuretic, oxygen or corticosteroid dependent), should be covered during the first 24 months of life and during the RSV season. RSV prophylaxis may be considered in children with profound immunocompromise or pulmonary neuro muscular disease. The value of palivizumab is uncertain in children with Down syndrome, cystic fibrosis, recurrent wheeze and in nosocomial outbreaks. It would be appropriate to use palivizumab between January and May in high-risk infants (<6 months old), as the RSV season in SA is between February and June.[25] The standard dose of 15 mg/kg given monthly for 5 months is advocated. All risk groups who are resident in hospital and for whom palivizumab is indicated, should be initiated on palivizumab in hospital as per guidelines, and not only after they are discharged.

Indications for palivizumab

Indications for palivizumab are the following: • Premature infants of gestational age of <36 weeks at birth and <6 months of age at the start of the RSV season (February). Prophylaxis should be continued until the end of the RSV season (last dose in May).

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• Children of any gestation and <24 months of age at the start of the RSV season, with any of the following: chronic lung disease of prematurity, chronic lung disease, primary immunodeficiency, haemodynamically sig nificant congenital heart disease. • High-risk premature infants should com mence their prophylaxis while still in hospital.

RSV vaccine

While RSV vaccine development was stalled for many years owing to the adverse effects associated with a formalin-inactivated vac cine, substantial progress has recently been made in the development of a possible vaccine.[26] There are several candidate vac cines undergoing Phase 1 trials and two undergoing Phase 2 studies (a live atten uated vaccine for immunisation of infants and an F-protein vaccine for immunisation of pregnant women as a strategy to protect infants). A Phase 3 study, using a novel strategy of immunisation of pregnant women in their last trimester of pregnancy, has begun. This strategy will potentially be effective to prevent disease in young infants by transplacental antibody transfer and prevention of infection in mothers. Such a strategy may have to be coupled with vaccination of infants to enable more protection of young children for the first two years of life.

Parent and caregiver education

Management of children with bronchiolitis requires that parents or caregivers be edu cated about the condition. This is critical when children are not admitted to hospital, but also after discharge. The key elements of an educational message are listed in Table 2.

Table 2. Key elements of an educational message for parents of children with bronchiolitis The condition may start as an upper respiratory tract infection with low-grade fever Symptoms are cough and wheeze and often fast breathing Bronchiolitis is caused by a virus; antibiotics are not needed Bronchiolitis is usually self limiting, although symptoms may occur for up to 4 weeks in some children References 1. Castro-Rodriguez JA, Rodriguez-Martinez CE, SossaBriceño MP. Principal findings of systematic reviews for the management of acute bronchiolitis in children. Paediatr Respir Rev 2015;15:S1526-1542. 2. Rojas-Reyes MX, Granados Rugeles C, Charry-Anzola LP. Oxygen therapy for lower respiratory tract infections in children between 3 months and 15 years of age. Cochrane Database Syst Rev 2014;12:CD005975. DOI:10.1002/14651858.CD005975.pub3 3. Beggs S, Wong ZH, Kaul S, Ogden KJ, Walters JA. High-flow nasal cannula therapy for infants with bronchiolitis. Cochrane Database Syst Rev 2014;1:CD009609. DOI:10.1002/14651858. CD009609.pub2 4. Gadomski AM, Scribani MB. Bronchodilators for bronchio litis. Cochrane Database Syst Rev 2014;6:CD001266. DOI: 10.1002/14651858.CD001266.pub4.CD001266 5. Hartling L, Bialy LM, Vandermeer B, et al. Epinephrine for bronchiolitis. Cochrane Database Syst Rev 2011;6:CD003123. DOI:10.1002/14651858.CD003123.pub3 6. Henry RL, Milner AD, Stokes GM. Ineffectiveness of ipratropium bromide in acute bronchiolitis. Arch Dis Child 1983;58:925-926. DOI:10.1136/adc.58.11.925 7. Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulised hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev 2013;7:CD006458. DOI: 10.1002/14651858.CD006458.pub3 8. Everard ML, Hind D, Ugonna K, et al. SABRE: A multicentre randomised control trial of nebulised hypertonic saline in infants hospitalised with acute bronchiolitis. Thorax 2014;69:1105-1112. DOI:10.1136/thoraxjnl-2014-205953 9. Sharma BS, Gupta MK, Rafik SP. Hypertonic (3%) saline vs 0.93% saline nebulization for acute viral bronchiolitis: A randomized controlled trial. Indian J Pediatr 2013;50:743-477. DOI:10.1007/s13312-013-0216-8 10. Teunissen J, Hochs AH, Vaessen-Verberne A, et al. The effect of 3% and 6% hypertonic saline in viral bronchiolitis: A rando mised controlled trial. Eur Respir J 2014;44:913-921. DOI: 10.1183/09031936.00159613 11. Wu S, Baker C, Lang ME, et al. Nebulized hypertonic saline for bronchiolitis: A randomized clinical trial. JAMA Pediatr 2014;168:657-663. DOI:10.1001/jamapediatrics.2014.301

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12. Jacobs JD, Foster M, Wan J, et al. 7% hypertonic saline in acute bronchiolitis: A randomized controlled trial. Pediatrics 2014;133:e8-e13. DOI:10.1542/peds.2013-1646 13. Fernandes RM, Bialy LM, Vandermeer B, et al. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev 2013;6:CD004878. DOI: 10.1002/14651858.CD004878.pub4 14. Blom D, Ermers M, Bont L, van Aalderen WM, van Woensel JB. Inhaled corticosteroids during acute bronchiolitis in the prevention of post-bronchiolitic wheezing. Cochrane Database Syst Rev 2007;1:CD004881. DOI:10.1002/14651858. CD004881.pub3 15. Amirav I, Luder AS, Kruger N, et al. A double-blind, placebocontrolled, randomized trial of montelukast for acute bronchiolitis. Pediatrics 2008;122:1249-1255. DOI:10.1542/peds.2008-1744 16. Peng WS, Chen X, Yang XY, Liu EM. Systematic review of montelukast’s efficacy for preventing post-bronchiolitis wheezing. Pediatr Allergy Immunol 2014;25(2):143-150. DOI: 10.1111/pai.12124 17. Ventre K, Randolph A. Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children. Cochrane Database Syst Rev 2007;1:CD000181. DOI: 10.1002/14651858 18. Roqué i Figuls M, Giné-Garriga M, Granados Rugeles C, Perrotta C. Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old. Cochrane Database Syst Rev 2012;2:CD004873. DOI: 10.1002/14651858.CD004873.pub4 19. Farley R, Spurling GK, Eriksson L, Del Mar CB. Antibiotics for bronchiolitis in children under two years of age. Cochrane Database Syst Rev 2014;10:CD005189. DOI:10.1002/14651858. cd005189.pub4 20. American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014;134(2):415-420. DOI:10.1542/ peds.2014-1665 21. The Impact-RSV study Group. Palivizumab, a humanized respiratory syncyctial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high risk infants. Pediatrics 1998;102:531-537. DOI:10.1542/ peds.102.3.531 22. Wegzyn C, Toh LK, Notario G, et al. Safety and effectiveness of palivizumab in children at high risk of serious disease due to respiratory syncytial virus infection: A systematic review. Infect Dis Ther 2014;3:133-158. 23. Feltes TF, Cabalka AK, Meissner HC, et al., Cardiac Synagis study group. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with haemodynamically significant congenital heart disease. J Pediatr 2003;143:532-540. DOI:10.1067/S0022-3476(03)00454-2 24. Wang D, Bayliss S, Meads C. Palivizumab for immuno prophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high risk infants and young children: A systematic review and additional economical modelling of subgroup analyses. Health Technol Assess 2011;15:9971018. DOI:10.3310/hta15050 25. Pretorius MA, Madhi SA, Cohen C, et al. Respiratory viral coinfections identified by a 10-plex real-time reverse-transcription polymerase chain reaction assay in patients hospitalized with severe acute respiratory illness – South Africa, 2009 - 2010. J Infect Dis 2012;206(S1):S159-S65. DOI:10.1093/infdis/jis538 26. Resch B. Respiratory syncytial virus infection in high-risk infants – an update on palivizumab prophylaxis. Open Microbiol J 2014;8:71-77. DOI:10.2174/1874285801408010071

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HEALTHCARE DELIVERY

A call to action: Addressing the reproductive health needs of women with drug-resistant tuberculosis K Schnippel, N Ndjeka, F Conradie, R Berhanu, Z Claasen, S Banoo, C Firnhaber Kathryn Schnippel is Senior Epidemiologist at Right to Care, Johannesburg, South Africa, and is also Senior Researcher at the Clinical HIV Research Unit, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg. Norbert Ndjeka is Director: Drug-Resistant TB, TB & HIV at the National TB Control & Management Cluster, National Department of Health, South Africa. Francesca Conradie is MDR-TB Technical Advisor at Right to Care and Clinical Research Advisor, Clinical HIV Research Unit. Rebecca Berhanu is Infectious Disease Fellow at the Department of Medicine, Division of Infectious Diseases, University of North Carolina, USA. Zerilda Claasen is Technical Advisor, Drug-Resistant TB, TB & HIV, National TB Control & Management Cluster. Shabir Banoo is Head: Pharmaceutical Policy at the Research and Services Support Unit, Right to Care. Cynthia Firnhaber is Associate Professor in Internal Medicine, Clinical HIV Research Unit, and the Head of Research at Right to Care. Corresponding author: K Schnippel (kschnipp@gmail.com)

Although there is substantial risk to maternal and neonatal health in the situation of pregnancy during treatment for rifampicin-resistant tuberculosis (RR-TB), there is little evidence to guide clinicians as to how to manage this complexity. Of the 49 680 patients initiated on RR-TB treatment from 2009 to 2014 in South Africa, 47% were women and 80% of them were in their reproductive years (15 - 44). There is an urgent need for increased evidence of the safety of RR-TB treatment during pregnancy, increased access to contraception during RR-TB treatment, and inclusion of reproductive health in research on the prevention and treatment of TB. S Afr Med J 2016;106(4):333-334. DOI:10.7196/SAMJ.2016v106i4.10205

An analysis of the global burden of tuberculosis (TB) during pregnancy estimated that each year, more than 8 400 pregnant women in South Africa (SA) have active TB.[1] To put this burden into context, across sub-Saharan Africa, the combination of TB and HIV in pregnancy is a leading cause of maternal mortality[2] and in SA an estimated 65% of TB patients are HIV-positive. SA also ranks among the top countries in the world in terms of the number of TB patients with rifampicinresistant TB (RR-TB),[3] including multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB. RR-TB requires 18 - 24 months of complex treatment with a high frequency of adverse drug reactions and poor treatment outcomes. Globally less than 50% of the 2011 cohort of MDR-TB patients were treated successfully.[3] Globally, there is scant evidence on the safety of second-line TB medications during pregnancy. Clinicians rely on data extrapolated from decades-old clinical trials[4] or from limited case series.[5] Clinicians must weigh the scant safety data against evidence that delayed RR-TB treatment may increase the risk of obstetric and neonatal complications from TB disease,[6] ongoing transmission, and that suboptimal RR-TB treatment can lead to failure and the amplification of resistance.

bedaquiline. SA has universal testing for rifampicin resistance with public sector coverage of Xpert MTB/RIF since the end of 2013.

Estimating the burden of pregnancy during RR-TB treatment in SA

The University of the Witwatersrand Human Research Ethics Committee approved this retrospective, de-identified, secondary analysis in April 2015.

In order to quantify the risk of pregnancy and RR-TB treatment, we analysed the drug-resistant TB case registry in SA to assess the number of women receiving RR-TB during their reproductive years.

Setting and treatment guidelines

SA RR-TB patients receive a standardised regimen: 6 months of an injectable drug (kanamycin or amikacin) and 18 - 24 months of moxifloxacin, ethionamide, terizidone and pyrazinamide. Patients with second-line drug resistance, toxicity, or contraindications to the standardised regimen can access individualised regimens including capreomycin, para-aminosalicylic acid, clofazimine, linezolid and

Data extraction and analysis

The Electronic DR-TB Register (EDRweb) is the RR-TB national case register and, since 2012, has been used for reporting to the World Health Organization (WHO). A census of patients registered in the EDRweb from January 2009 to December 2014 was exported (N=53 623). Registrations missing sex, report of rifampicin resistance or date of treatment initiation details were excluded. Pregnancy and pregnancy outcomes are not routinely reported in the EDRweb. Descriptive counts and proportions for gender, age category (0 - 14, 15 - 29, 30 - 44, 45 - 59, 60+), HIV status (negative, positive or unknown), history of prior TB treatment with any outcomes, and category of drug resistance (RR-TB and MDR-TB or secondline drug resistance as indicated by XDR-TB case registration) are presented. Differences of proportions were estimated using Pearson’s χ2 and p-values are presented. All analyses were conducted in Stata SE version 13 (College Station, USA).

Ethical approval

Results

From 2009 to 2014, 49 680 patients with RR-TB were registered and initiated on second-line TB treatment in the EDRweb. Nearly half (47.2%, n=23 428) were female. Males had a median age of 37 (interquartile range (IQR) 30 - 45) years and females a median age of 32 (IQR 26 - 40) years. Eighty percent (n=18 750) of the women treated for RR-TB were aged 15 - 44 years. At initiation of RR-TB treatment (Table 1), women were younger (40.0% v. 24.9% aged <30), more likely to be HIV-infected (68.0% v.

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IN PRACTICE

57.2%), less likely to have a history of TB treatment prior to their RR-TB diagnosis (60.8% v. 65.7%), and more likely to have XDR-TB (6.9% v. 6.2%) than men. Women aged 15 - 44 years were more likely to be HIVpositive than women <15 years or >44 years (70.8% v. 53.9%, p<0.000).

An urgent call to action

From 2009 to 2014, 23 428 women initiated RR-TB treatment in SA. Of these women on second-line TB treatment, 80% were of reproductive age. In contrast, a 2012 review of TB treatment in pregnant and postpartum women found only eight published case reports to guide second-line TB treatment during pregnancy, describing outcomes for 73 women.[5] Most (68.0%) of the women treated for RR-TB in SA are also HIV-positive, yet the case reports describe outcomes for just six HIV-positive women.[5] These numbers should serve as an urgent call to action: 1. Collect more evidence of the safety of second-line TB treatment during pregnancy Mothers with RR-TB and their clinicians are faced with a difficult decision. Should they treat the mother’s RR-TB and expose the fetus to potentially toxic drugs, or delay or stop treatment and face the risk of maternal or fetal mortality or the amplification of drug resistance? The principal concern is ototoxicity related to the injectable drugs, among the mainstays of second-line TB treatment. More evidence of the safety of second-line TB treatment during pregnancy is urgently needed to inform these decisions. This is a broader call than adverse drug event monitoring given the importance of also reporting the outcomes of TB and pregnancy even in the absence of adverse drug events. Monitoring RR-TB and pregnancy outcomes requires co-ordination across different facilities and health directorates, as women need to be identified during antenatal care and followed through delivery and postpartum. The drugs-exposure pregnancy register led by the WHO can serve as a model of a feasible system for resourcelimited contexts.[7] 2. Ensure access to effective contraception during second-line TB treatment Currently, contraception services in SA are offered at primary healthcare level while RR-TB services are more centralised, often still at hospital level. Offering effective contraception to women on second-line TB treatment could reduce the number of pregnancies during active TB. Integration of

Table 1. Differences in baseline characteristics of RR-TB patients registered in the EDRweb, 2009 - 2014, by sex All RR-TB

Female, n (%)

Male, n (%)

Total, n (%)

23 428 (47.2)

26 242 (52.8)

49 680 (100)

768 (3.3)

584 (2.2)

1 352 (2.7)

Age (years)

p-value <0.000*

0 - 14 15 - 29

8 597 (36.7)

5 994 (22.7)

14 541 (29.3)

30 - 44

10 153 (43.3)

12 575 (47.9)

22 728 (45.7)

45 - 59

3 233 (13.8)

6 107 (23.3)

9 340 (18.8)

≥60

687 (2.9)

1 032 (3.9)

1 719 (3.5)

5 288 (22.6)

8 389 (32.0)

13 677 (27.5)

HIV infection

<0.000

HIV-negative HIV-positive

15 936 (68.0)

15 011 (57.2)

30 947 (62.3)

HIV unknown

2 214 (9.4)

2 842 (10.8)

5 056 (10.2)

No prior TB

9 158 (39.2)

8 966 (34.3)

18 124 (36.6)

History of TB

14 191 (60.8)

17 187 (65.7)

31 378 (63.4)

RR- or MDR-TB 21 816 (93.1)

24 614 (93.8)

46 430 (93.5)

XDR-TB

1 628 (6.2)

3 250 (6.5)

Previous TB

<0.000

Drug resistance

<0.001 1 622 (6.9)

*p-values estimated using χ2 difference of proportions.

family planning services within the RR-TB units is therefore urgently needed. 3. Ensure women’s health is included in research on prevention and treatment of TB Effective TB research is the third pillar of the WHO strategy to end TB. This research must address women’s health, especially reproductive health. More information and evidence on effective TB prophylaxis for women and infants, pharmacokinetics of TB drugs in pregnancy and pharmacokinetics of contraceptives and antiretrovirals during TB treatment is needed urgently.[8]

Conclusion

In SA, where the burden of RR-TB and TB/ HIV co-infection is high, there is an urgent need for increased evidence of the safety of RR-TB treatment during pregnancy. Increased access to contraception during RR-TB treatment and inclusion of reproductive health in research on the prevention and treatment of TB need to be addressed. Acknowledgements. The analysis presented here is based on data collected by the SA Department of Health and extracted with the support of S’celo Dlamini and Nontobeko Msthali. Funding. N Ndjeka is responsible for the DRTB programme within the SA National TB Programme. K Schnippel, F Conradie, R Berhanu,

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S Banoo and C Firnhaber were supported through USAID cooperative agreement #674-A-12-00020 to Right to Care. Z Claasen is supported by the Lilly Foundation grant to FHI360. The content of the article is the responsibility of the authors and does not necessarily reflect the views of the SA government, USAID or the US government. The funders had no role in the study design, collection, analysis and interpretation of the data, in manuscript preparation or in the decision to publish. 1. Sugarman J, Colvin C, Moran AC, Oxlade O. Tuberculosis in pregnancy: An estimate of the global burden of disease. Lancet Glob Health 2014;2(12):e710-716. DOI:10.1016/S2214109X(14)70330-4 2. Grange J, Adhikari M, Ahmed Y, et al. Tuberculosis in association with HIV/AIDS emerges as a major nonobstetric cause of maternal mortality in Sub-Saharan Africa. Int J Gynaecol Obstet 2010;108(3):181-183. DOI:10.1016/j.ijgo.2009.12.005 3. World Health Organization (WHO). Global Tuberculosis Report 2014. Geneva: WHO, 2014. http://www.who.int/tb/ publications/global_report/en/ (accessed 15 November 2015) 4. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. 9th ed. Philadelphia: Lippincott Williams & Wilkins, 2011:1703. 5. Mathad JS, Gupta A. Tuberculosis in pregnant and postpartum women: Epidemiology, management, and research gaps. Clin Infect Dis 2012;55(11):1532-1549. DOI:10.1093/cid/cis732 6. Figueroa-Damian R, Arredondo-Garcia JL. Pregnancy and tuberculosis: Influence of treatment on perinatal outcome. Am J Perinatol 1998;15(5):303-306. DOI:10.1055/s-2007-993948 7. Mehta U, Clerk C, Allen E, et al. Protocol for a drugs exposure pregnancy registry for implementation in resourcelimited settings. BMC Pregnancy Childbirth 2012;12(1):89. DOI:10.1186/1471-2393-12-89 8. McIlleron H, Abdel-Rahman S, Dave JA, Blockman M, Owen A. Special populations and pharmacogenetic issues in tuberculosis drug development and clinical research. J Infect Dis 2015;211(Suppl 3):S115-S125. DOI:10.1093/infdis/jiu600

Accepted 23 October 2015.

IN PRACTICE

HEALTHCARE DELIVERY

A multifaceted hospital-wide intervention increases hand hygiene compliance B Patel, H Engelbrecht, H McDonald, V Morris, W Smythe Dr Bhavna Patel is the Chief Executive Officer at Groote Schuur Hospital, Cape Town, South Africa. Srs Heather Engelbrecht, Vida Morris and Heidi McDonald are all registered nurses, responsible for the management of infection prevention and control at Groote Schuur Hospital. Mr Wynand Smythe is registered as a PhD candidate in the Department of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town, and works as a research pharmacist in the Clinical Research Centre at UCT. Corresponding author: B Patel (bhavna.patel@westerncape.gov.za)

Background. Hand hygiene is an important and basic practice that should be used by all healthcare staff to protect both themselves and their patients against infection. Unfortunately hand hygiene compliance remains poor. Objective. To show an improvement in hand hygiene compliance using a multifaceted approach. Methods. This was a quasiexperimental pre-post intervention study design with a number of standardised interventions to promote hand hygiene. The World Health Organization hand hygiene multimodal (five-step) intervention approach was used. The study ran from June 2015 to August 2015 in 11 selected wards of a 975-bed tertiary and quaternary care public hospital (Groote Schuur Hospital, Cape Town, South Africa). The outcome was to assess improvement in hand hygiene compliance monthly over the 3 months, compared with non-intervention wards and compared with the wards’ own performance measured in 2014. The study included both descriptive and analytical components. Results. Post intervention, hand hygiene compliance showed a statistically significant improvement for before patient contact from 34% in 2014 to 76% in 2015 (p<0.05) and for after patient contact from 47% in 2014 to 82% in 2015 (p<0.05). Conclusion. The intervention improved hand hygiene compliance and can easily be replicated in other wards, resulting in sustaining a culture of hand hygiene improvement and behavioural change throughout the hospital. S Afr Med J 2016;106(4):335-341. DOI:10.7196/SAMJ.2016.v106i4.10671

Hospital-acquired infections remain a global concern, with prevalence rates in the USA ranging from 3.5% to 9.9%,[1] almost one-third of infections being preventable. In South Africa (SA), about one in seven patients entering health facilities may be at risk of developing a hospitalacquired infection. This results in significant morbidity and mortality, pressures on the need for intensive care beds, and the direct and indirect costs of these infections.[2] Factors contributing to this risk include indiscriminate use of antibiotics over the years, resulting in drugresistant organisms and more recently multidrug-resistant organisms. Patients may be discharged by the time the infection presents and it can then also spread in the community, making it difficult to distinguish between community-acquired and hospital-acquired infections. As there is no monitoring of these infections the prevalence cannot be measured, but it is estimated that approximately 10 - 25% of patients admitted to SA hospitals may acquire an infection.[3] Hand washing with soap and water is considered to be hygienic. However, the use of antiseptic agents for cleansing hands emerged when a French pharmacist demonstrated their benefits when managing corpses, and in 1825 suggested their use to doctors attending to patients with contagious diseases. Semmelweis first showed that the cleansing of hands with an antiseptic agent may reduce healthcare-associated transmission of contagious diseases.[4] Organisms that cause hospital-acquired infections are usually transmitted through contact with the patient by doctors, nurses, physiotherapists and other hospital personnel. This can be through skin-to-skin contact, direct spread for droplets >5 microns in size and airborne spread for droplets <5 microns in size.[2] Besides general safety precautions, hand hygiene has been recommended as the single most important measure in preventing hospital-acquired infections. The Centers for Disease Control (CDC) guidelines suggest hand

washing with antimicrobial soap between every patient contact and before and after performing invasive procedures.[4] Despite these guidelines, hand hygiene compliance is frequently poor. Healthcare workers in intensive care units (ICUs) have been reported as failing to wash their hands more than half of the recommended times, and even when performed, the procedure was inadequate.[5] Less than 50% compliance has been found when comparing different hospital wards among different professional categories of healthcare workers.[6] Compliance also decreased depending on the patient demand and intensity of care. Reasons for failure to comply noted by healthcare workers included skin irritation, inaccessible supplies, interference with work, forgetfulness, emergency care, understaffing and high workload. [6] A 2009 multicentre study found that baseline com pliance in an ICU was 26%, with 36% for non-ICU settings.[7] A systematic review of 96 studies published before 2009 reflected an average compliance of 40%.[8] The agents used for washing or disinfecting hands should be able to eliminate transient flora, but micro-organisms can only be killed using antiseptic agents. Alcohol-based preparations have the more rapid action of all antiseptics, and are more convenient than others because of their rapid evaporation and spreading quality.[6] Increasing compliance in the use of these agents for hand washing remains a problem. Educational programmes, communication campaigns, visual reminders, audits and constant supervision and monitoring must be employed to improve compliance. Such interventions have changed cultural behaviours, and institutions have been successful in sustaining these improvements.[6,9,10] Materials used to implement such improvements include the CDC[4] and World Health Organization (WHO) guidelines.[11]

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IN PRACTICE

Infrastructural requirements such as the availability and accessibility of hand sanitisers, alcohol-based rub solutions and dispensers must also be in place. An increase in hand hygiene compliance from 23% to 48% was demonstrated following the introduction of an easily accessible alcohol-based waterless sanitiser dispenser.[12] Others have also looked at factors that affect ease of access and result in improved hand hygiene performance, e.g. the placement, proximity, cost, staff acceptance, durability, maintenance and environmental customisation of the device.[7] Groote Schuur Hospital (GSH), Cape Town, SA, is a 975-bed speci alist and subspecialist hospital. Antimicrobial resistance has increased over the past 2 - 3 years, particularly resistance to the carbapenems. Globally, the dissemination of New Delhi metallo-beta-lactamase1-containing Gram-negative bacteria and carbepenem-resistant Klebsiella pneumoniae increases fears of an international meltdown in treating infections. For some organisms the last-line antimicrobial agents are also starting to show some resistance, which could spark an era of morbidity and mortality that modern medicine and technology will not be able to control. One of the best preventive measures would be to decrease the spread of infection through practising basic precautionary measures such as hand washing. A baseline audit in 2014 on hand hygiene at GSH reflected an average performance of 34% for the hospital. This study was a multifaceted, hospital-wide hand hygiene intervention using the WHO approach and developing a model to sustain a change in culture in our institution.

Objective

To measure whether there was an improvement in hand hygiene compliance before and after contact with the patient over the period June - August 2015 in 11 selected wards at GSH, while implementing hospital-specific standardised interventions including the appointment of a ward hand hygiene champion, an educational programme, posters, presentations and regular audits and feedback. Compliance was measured monthly over the 3 months and compared with non-intervention control wards and the wards’ own performance during the previous year.

Methods Approval

The study was approved by the Human Research Ethics Committee, Faculty of Health Sciences, University of Cape Town, South Africa (HREC/REF:077/2015). Institutional ethics approval was granted by the hospital research ethics committee. Each participant was asked to give written informed consent at the start of the educational programme.

Study design

This was a quasiexperimental pre-post interventional design con ducted over the 3 months June - August 2015 to statistically compare the practice of hand hygiene in 11 selected educational intervention wards over the study period with similar control wards that did not receive the intervention and with the wards’ own performance during the previous year. Descriptive and analytical components were included.

Study population and sampling

All staff working in the selected wards across all disciplines, irres pective of their professional category or rank, were included. A sample size of 146 for the intervention group was calculated using a 95% confidence interval, 80% power and an estimated compliance improvement rate of 50%.

Information, consent and procedures

Each ward selected a hand hygiene champion who facilitated the activities of the intervention. Using the WHO hand hygiene multi modal (five-step) intervention approach, the study procedure included the following: 1. A prestudy needs-assessment questionnaire ensured that all infrastructural and consumable requirement needs were met. 2. A hospital-specific standardised training presentation was prepared and the champions were trained on how to conduct the presentation at least once per week to ensure that all ward staff received the training. Participants were given an information sheet and consent form at the start of the educational session. 3. Posters were placed above the basins in the ward and the champions were asked to provide ad hoc in service training (Appendix 1, available in the online version of this article) based on the WHO ‘five moments of hand hygiene’ intervention approach. 4. Standardised hand hygiene audit tools and observation methods were used to assess the performance of the staff for adherence to the five moments of hand hygiene, while working with the patients. This was done once per month over the 3-month period by the independent infection control team. These tools provided the data from which compliance was measured. The same tool was used in the previous year, from which the baseline measure of compliance was determined. 5. Monthly feedback was provided to the hand hygiene champions, and performance graphs were circulated for use in the educational sessions. Furthermore, there was leadership and commitment from hospital management to ensure that these measures would assist in creating a continuous culture of improvement and behaviour change among the staff.

Statistical analysis

The primary outcome was hand hygiene compliance, which was calculated by dividing the number of hand hygiene episodes by the number of potential opportunities. This measure was calculated before and after contact with patients over both years. Using the statistical package Statistica (version 12), factorial repeated measures analysis of variance (ANOVA) was applied to consider the effect of intervention and contact occasion, intervention ward and contact occasion, intervention and year on hand hygiene compliance.

Results

Over the period June 2015 - August 2015, the hand hygiene cham pions in the 11 wards trained 557 staff using the hospital-specific standardised educational presentation provided. Of these, 497 (89.2%) gave written consent for participation. They comprised 110 medical doctors (22.1%), 273 nursing staff (54.9%) and 114 other staff (22.9%), including cleaners, porters and allied health staff. During the audits 497 observations were recorded over the 3-month period. All the intervention wards showed an improvement in hand hygiene compliance from the 1st month to the 3rd month, from a combined average improvement from 55% to 73% for before patient contact and from 56% to 79% for after patient contact (Fig. 1). While all wards progressively improved over the 3 months, one of the two surgical wards, a gynaecological ward and theatre areas dipped in performance during the second month and also showed the smallest percentage improvement (<10%) from the first to the third month. The greatest improvement (50%) was seen in the ICU and the second surgical ward. For these same intervention wards, the difference in hand hygiene compliance between the intervention and control wards was

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100.0 80.0 60.0 40.0 20.0 0

y y l re U re gy ty tal ry ry ca og og o at IC rge rge ent rni na col col edi he iol e c t u u o T d y a S S e n e M a c a M N n O R n ge Gy er m E 1st intervention

2nd intervention

Compliance before patient contact, %

IN PRACTICE

100.0 80.0 60.0 40.0 20.0 0

l y y gy gy cal gy tre ity tre ta er er rg urg cen tern ona colo colo edi hea iolo u T d a S S y e M On M Ne na Ra nc ge Gy er Em

1st intervention

3rd intervention

2nd intervention

3rd intervention

Fig. 1. Hand hygiene compliance before and after patient contact from June to August 2015.

Hand hygiene compliance, %

100.0

Before contact After contact

80.0

60.0

40.0

20.0

0.0

Control

1st intervention

Last intervention

100.0 80.0 60.0 40.0 20.0 0.0

l y l l re U y ty ty al IC log rni rni dic dica log gica gica ent co ate ate Me Me dio ur Sur y c e S Ra nc na M M ge Gy er Em

Hand hygiene compliance, %

Fig. 2. Hand hygiene compliance between the intervention and control wards. Applying a factorial repeated measures ANOVA to consider the effect of intervention and contact occasion, intervention ward and contact occasion, intervention and year on hand hygiene compliance found a significant effect on hand hygiene compliance (ANOVA, F=2.74465, p=0.037588). Bars sharing a common symbol (*) are significantly different (t=3.04641, p=0.005006).

120.0 100.0 80.0 60.0 40.0 20.0 0.0

Discussion

l y l l re U y ty ty al IC log rni rni dic dica log gica gica ent co ate ate Me Me dio ur Sur y c e S Ra nc na M M ge Gy er Em

Compliance before patient contact, 2014

Compliance after patient contact, 2014

Compliance before patient contact, 2015

Compliance after patient contact, 2015

Fig. 3. Overall improvement in hand hygiene compliance in 2015 compared with 2014.

significant (p<0.05) (Fig. 2). The greatest improvement was seen in the maternity, surgical and trauma wards. The intervention wards also improved in com pliance from their 2014 baseline performance to the 2015 post-intervention assessment by a combined average of 34% to 76% (range 3.5 - 80.5) and 47% to 82% (range 4.5 - 87.5) for before and after patient contact, respectively (Fig. 3).

All the wards reflected an improvement in compliance before and after patient contact, with five of the 11 wards increasing compliance by more than 50%. The poor performance in the medical ward was related to repeated change of the hand hygiene champion. Applying a factorial repeated measures ANOVA, year and contact occasion were found to have a significant effect on hand hygiene compliance (F=10.0717, p=0.001303) (Fig. 4).

The nursing staff showed better compliance than the other healthcare categories and were more willing to be the ward champions. Doctors performed better when the hand hygiene champion was also a doctor. Difficulties encountered by the hand hygiene champions included: • Staff rotations and turnover as a result of doctor and nurse rotations and dependence on agency staff in some wards. • Lack of support from the managers to release staff for training, mainly due to staff shortages to cover the clinical work, but to lack of commitment from managers in some instances. • Keeping staff motivated. This problem was approached by changing the presentation to include stimulation in the form of additional learning. • Time constraints for the champions to cover their normal daily duties and be the ward hand hygiene champion.

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Notable findings included the role of the hand hygiene champion in the ward, and the significant improvement in hand hygiene compliance over the 3-month period compared with similar control wards and the wards’ own performance in 2014. While poor performance may be due to a lack of knowledge, the improvement can be attributed to the educational training and visual reminders, but mostly to the role that the champions played in motivating and constantly observing the hand hygiene practices. The results achieved by improving knowledge together with visual reminders, audits and regular feedback show that use of a multimodal approach should be promoted. Nurses were more compliant than doctors, but with a doctor as the hand hygiene champion, the training, supervision and

Hand hygiene compliance, %

IN PRACTICE

100.0 Before contact After contact

80.0 60.0

# *

40.0 20.0 0.0

2014

2015 Year

Fig. 4. Overall hand hygiene compliance in 2014 and 2015. Bars sharing a common symbol are significantly different (t=3.04641, p=0.005006). Differences before patient contact (*) t=–3.66521, p=0.001771; differences after contact (#) t=–4.58698, p=0.000229.

compliance of other doctors were easier and better than when a nurse was appointed as the champion. This mind-set culture of assuming that the doctor is always right should be used to the advantage of such a programme and can be of value if combined with education on hospital-acquired infection rates and antibiotic stewardship, creating a comprehensive approach to patient management. A multidisciplinary team approach in the ward, together with such a comprehensive management system, could enhance the quality of patient care. Standardising the educational material assisted the champions in presenting the same message in all areas and in every session, but they noted that staff who attended more than one session needed additional stimulation. Additional presentations should therefore be prepared for ongoing education and to retain staff motivation. The challenge of sustaining the improved hand hygiene compliance and improving performance further was taken forward by the ward champions, who also served as role models for other wards where the same programme could be started. Unfortunately, owing to the lack of adequate data on specific ward infection rates, this improvement cannot be matched to clinical outcomes.

Study limitations

Despite the success of the programme, the study has limitations. The main limitation was the quasiexperimental design, where there may have been selection bias in the choice of the intervention wards, although an attempt was made to ensure that one ward was selected from every department at the hospital. Similarly, the control wards were selected to match the intervention wards in size, staff numbers and patient type. The sample size was also not the same for the pre- and post-intervention phases, because staff moved between wards. Randomisation of the wards and ensuring a stable sample was not feasible because the study was performed in one hospital in the hope of showing improved hand hygiene compliance using a programme that could be replicated in other wards. The intervention group received educational training from the selected champion for the area, which may have introduced bias. Although standardised educational material was provided for training, the champions could have interpreted the material differently and in-house supervision could also have been different in the different wards, depending on the respective champion.

Inter-observer bias was present because three different investigators performed the audits, but this small number and standardised audit tool reduced variability. However, it introduced a Hawthorne effect because staff were aware of being observed by the investigators’ audits. Other confounding factors that could not be measured include the role of leadership and commitment from the hospital senior managers. This is evidenced by the number of hand hygiene promotional activities held at the hospital and the participation in a hand hygiene relay event on International Hand Hygiene Day. Such awareness could also introduce bias in compliance with hand hygiene and hence the outcome of the study. Control for this was beyond the scope of this study, and we had to rely on the experience of the staff concerned. Other studies[5,6,8-10] have also shown an improvement in hand hygiene compliance, with some using the WHO multimodal approach, but this study is different in that it achieved similar results over a short period of time, using ward staff working under severe resource constraints. While it can be argued that the results could be considered more scientifically sound if the study had been done over a longer period, the ability to replicate the results of intervention using this simple method has been valuable in helping to improve hand hygiene compliance and thereby reduce hospital-acquired infections.

Conclusion

This study shows that hand hygiene compliance can be improved by using the WHO five-step multimodal approach and appointing champions for an area. This could reduce hospital-acquired infections and decrease antibiotic resistance, which would greatly improve patient care and reduce the future cost of healthcare. The role of the ward champion can be extended to an infection prevention and control link programme, since such improvements must be sustained through behaviour and a culture change management process, which could also provide a model for further research. 1. Kampf G, Kramer A. Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs. Clin Microbiol Rev 2004;17(4):863-893. DOI: 10.1128/CMR.17.4.863893.2004 2. Brink A, Feldman C, Duse A, et al. Guidelines for the management of nosocomial infections in South Africa. S Afr J Epidemiol Infect 2006;21(4):152-160. 3. Whitelaw A. Hospital acquired infections: A review. Health 24, 2014. http://www.health24.com/ Medical/Diseases/Hospital-Acquired-Infections-20120721 (accessed 5 January 2015). 4. Boyce JM, Pittet D. Guideline for hand hygiene in health-care settings. Recommendations of the healthcare infection control practices advisory committee and the HICPAC/ SHEA/ APIC/IDSA Hand Hygiene task force. MMWR Morb Mortal Wkly Rep 2002;51(RR-16):1- 45. 5. Lam BCC, Lee J, Lau YL. Hand hygiene practices in a neonatal intensive care unit: A multimodal intervention and impact on nosocomial infection. Pediatrics 2004;114(5):565-571. DOI:10.1542/ peds.2004-1107 6. Pittet D. Improving adherence to hand hygiene practice: A multidisciplinary approach. Emerg Infect Dis 2001;7(2):234-240. DOI:10.3201/eid0702.700234 7. Babiarz LS, Savoie B, McGuire M, McConnell L, Nagy P. Hand sanitizer-dispensing door handles increase hand hygiene compliance: A pilot study. Am J Infect Control 2014;42(4):443-445. DOI:10.1016/j.ajic.2013.11.009 8. Erasmus V, Daha TJ, Brug H, et al. Systematic review of studies on compliance with hand hygiene guidelines in hospital care. Infect Control Hosp Epidemiol 2010;31(3):283-294. DOI:10.1086/650451 9. Mestre G, Berbel C, Tortajada P, et al. ‘The 3/3 strategy’: A successful multifaceted hospital wide hand hygiene intervention based on WHO and continuous improvement methodology. PLoS One 2012;7(10):1-12. DOI:10.1371/journal.pone.0047200 10. Al-Tawfiq JA, Abed MS, Al-Yami N, Birrer RB. Promoting and sustaining a hospital-wide, multifaceted hand hygiene program resulted in significant reduction in health care-associated infections. Am J Infect Control 2013;41(6):482-486. DOI:10.1016/j.ajic.2012.08.009 11. World Health Organization. The WHO guidelines on hand hygiene in health care. 2009. http://apps. who.int/iris/bitstream/10665/44102/1/9789241597906_eng.pdf (accessed 7 March 2015). 12. Bischoff WE, Reynolds TM, Sessler CN, Edmond MB, Wentzel RP. Handwashing compliance by health care workers: The impact of introducing an accessible, alcohol-based hand antiseptic. Arch Intern Med 2000;160(7):1017-1021. DOI: 10.1001/archinte.160.7.1017

Accepted 14 February 2016.

Appendix 1 is available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.10671

April 2016, Print edition

IN PRACTICE

CLINICAL ALERT

Intracranial complications of Serratia marcescens infection in neonates A Madide, J Smith Ayanda Madide was employed as a paediatrician/neonatologist in the Division of Neonatology, Department of Paediatrics and Child Health, Tygerberg Children’s Hospital, Stellenbosch University, Cape Town, South Africa. She relocated to the UK in 2015. Dr Madide’s main interests include the provision of ‘hands‐on’ clinical care and perinatal morbidity and mortality. Prof. Johan Smith is the clinical head of the neonatal intensive care unit and level III neonatal service of the Department of Paediatrics and Child Health at Tygerberg Children’s Hospital. His main interests are neonatal pulmonology and surfactant development. Corresponding author: J Smith (js7@sun.ac.za)

Even though Serratia marcescens is not one of the most common causes of infection in neonates, it is associated with grave morbidity and mortality. We describe the evolution of brain parenchymal affectation observed in association with S. marcescens infection in neonates. This retrospective case series details brain ultrasound findings of five neonates with hospital-acquired S. marcescens infection. Neonatal S. marcescens infection with or without associated meningitis can be complicated by brain parenchymal affectation, leading to cerebral abscess formation. It is recommended that all neonates with this infection should undergo neuro-imaging more than once before discharge from hospital; this can be achieved using bedside ultrasonography. S Afr Med J 2016;106(4):342-344. DOI:10.7196/SAMJ.2016.v106i4.10206

Serratia marcescens infection has occurred sporadically from 2010 to 2014 in our 126-bed neonatal unit, with a tendency towards cluster infections. In each instance, staff at the Unit for Infection Prevention and Control, Tygerberg Hospital, Cape Town, South Africa employed their expertise to investigate, identify and man age appropriately the root cause of the cluster infection. On two separate occasions, colonised respiratory support equipment and suction points were identified as sources of infection; this situation was rectified. We recently noted a pattern of brain ultrasound findings consistently associated with the identification of S. marcescens septicaemia in neonates. These findings have not been noted in septicaemia secondary to other micro-organisms. The majority of neonates with such ultrasound findings died, despite intensive care and appropriate antimicrobial treatment having been instituted. We describe a case series of five neonates with S. marcescens nosocomial infection in whom the abovementioned pattern was evident. In patient 1, autopsy characterisation of these findings was done. Ethical approval for the case series and a waiver of individual informed consent were granted by the Human Health Research Ethics Committee of Stellenbosch University, protocol number N15/08/068.

Case 1

Patient 1 was delivered by caesarean section because of maternal pre-eclamptic toxaemia and fetal affectation at an estimated 30 weeks

of gestation (birth weight 1 460 g). Apart from antiretroviral, antihyper tensive and antenatal corticosteroids medication, his mother had received no other treatment and had had a healthy pregnancy. He progressed well and was admitted to the neonatal high-care ward for further care because of a very low birth weight. He had a normal baseline full blood count and was treated with intravenous aminophylline and oral nevirapine for apnoea and HIV prophylaxis, respectively. He was commenced on formula feeds on his second day of life and required no respiratory support. On day 6, he developed respiratory distress and progressed to hypoxic respiratory failure accompanied by convulsions, for which he had to be intubated and transferred to the neonatal intensive care unit (NICU) for venti latory support. At this time, an infection screen was performed and he was commenced on meropenem and vancomycin anti microbial therapy. A cranial ultrasound scan done on admission to the NICU showed a premature brain compatible with an estimated gestation al age of 32 weeks, minimal vessel pulsation and predominant findings in the bilateral parieto-occipital area. The latter had welldefined hyperechogenicities with areas of cystic breakdown, predominantly on the left side. These findings were thought to represent ischaemic parenchymal injury and areas of white matter infarcts. The patient had a persistent low-voltage pattern on amplitudeintegrated electro-encephalography, remained

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in intractable hypotension and metabolic aci dosis and succumbed to his illness within a day of admission to the NICU. His parents granted permission for an autopsy, and soon after he died, telephonic notification of Gramnegative bacilli on blood culture was received from the microbiology laboratory. This was later confirmed to be extended-spectrum betalactamase (ESBL)-producing S. marcescens. Fig. 1 shows the predominant cranial ultra sound results of right parieto-occipital wedgeshaped hyperechogenicity in this patient; mode rate lenticulostriate vasculopathy can also be

Fig. 1. Right parasagittal image.

Fig. 2. Right parasagittal image approximately 12 hours later.

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seen. Cranial ultrasonography was perform ed through the anterior fontanelle with an 8 MHz curvilinear probe using a Vivid S5 General Elec tric Healthcare ultrasound machine (USA). Fig. 2 shows progressive change to cystic breakdown of the same area approximately 12 hours later. In Fig. 3, the beginning of cystic break down within a hyperechogenic area is noted in the left posterior parietal region. Autopsy findings included extensive white matter necrosis of the temporal lobes, haem orrhagic infarction of temporal and occipital lobes, leptomeningitis in sections of the parietal cortex, and haemorrhagic necrosis of the cerebellum. The brainstem was also noted to be disintegrated.

Cases 2 - 5

Details of four other patients with similar clinical and microbiological findings are given in Table 1, and the associated cranial ultrasound findings can be seen in Fig. 4. The images of patient 2 were obtained with an 8 MHz sector probe using a Vivid S5 General Electric Healthcare ultrasound

Fig. 3. Left parasagittal image.

machine. The images of patients 3, 4 and 5 were obtained using a 10 MHz sector probe (Antares Sonoline Siemens Medical Solutions, USA).

Discussion

S. marcescens is an Enterobacteriaceae micro-organism that is widespread in the environment, but not a common component of the human faecal flora. Most infections are acquired exogenously and spread in and among hospitals.[1] Hand-held transmission appears to be the primary mechanism of nosocomial spread. Environmental sources in hospitals have been found to include suction taps, colonised disinfectants or soap, and inadequately sterilised breast pumps and respirators. Disease in humans has been associated with infection of the urinary tract, respiratory tract, local wounds and central vein catheters. Colonisation in neonatal units has been associated with up to a tenfold increase in the rate of S. marcescens bacteraemia and meningitis.[2] Significant brain injury caused by ventriculitis, brain abscesses or porencephalic cysts is described in the majority of infants with meningitis. In our neonatal unit, we have noted intracranial complications in the presence or absence of meningitis. NICUs in developed countries have reported serial infection outbreaks with this micro-organism over the past decade, although not all of these focused primarily on associated neurological morbidity. In a recently published report from Italy,[3] sepsis and pneumonia were the most severe clinical features described, with a mortality

rate of 7%. Only 1 of 18 affected neonates was found to have meningitis and a brain abscess. This neonate survived.[3,4] Published reports on neonatal S. marcescens infection in developing countries are limited with regard to availability and content. A global report on causes of neonatal sepsis in developing countries cited Serratia species as the fifth most common cause, accounting for 0.5% and 0.3% of early and late neonatal sepsis, respectively.[5] In their report on bloodstream infections in neonates in a developing country over a 12-month period, Ballot et al.[6] do not mention S. marcescens as one of the causative organisms. Unpublished data from our institution detailing infection patterns in very-low-birth-weight infants over an 18-month period, found that ESBLproducing S. marcescens accounted for 12% of late-onset neonatal sepsis. S. marcescens and ESBL-producing S. marcescens account ed for 5% and 8%, respectively, of infectionrelated mortality over a 24-month period in our unit. Published case reports describe diagnosis of brain abscesses after an initial diagnosis of S. marcescens septicaemia and menin gitis.[7,8] In our unit, three babies on whom cerebrospinal fluid (CSF) analysis had not been done died within 24 hours of onset of illness. Of the two survivors we describe, one had abnormal CSF analysis results of high protein, pleiocytosis and no organisms on culture, while the other had normal CSF results on two separate occasions. In both instances, the lumbar puncture and CSF analysis were done only after the diagnosis of septicaemia and commencement of

Table 1. Summary of details of patients with Serratia marcescens Patient details

Age at Serratia diagnosis

Cranial ultrasound findings

Outcome

Case 2 GA 29 wks BW 1 608 g Positive

6 days CUS on day 6

Minimal cerebrovascular pulsation. Right-side moderate lenticulostriate vasculopathy. Bilateral extensive frontoparietal well-circumscribed hyperechogenicity with areas of echolucent breakdown

Died on day 6

Case 3 GA 31 wks BW 1 370 g Negative

7 days CUS on day 7

Bilateral frontoparietal parenchymal hyperechogenicity with areas of echolucent cystic breakdown. Bilateral basal ganglia/thalamic hyperechogenicity

Died on day 7

Case 4 GA 33 wks BW 1 550 g Positive

9 days CUS on days 9, 11 and 16

Initial bilateral anterior and posterior irregular hyperechogenicity. Progressed to echolucent cystic breakdown 48 hours later and to well-circumscribed thickwalled lesions with central echolucency 7 days later – suggestive of abscess formation

Alive on discharge

Case 5 GA 26 wks BW 840 g Negative

6 days CUS on days 33 and 47

Bilateral frontoparietal and parieto-occipital well-circumscribed thick-walled echolucent cystic lesions suggestive of abscess formation

Alive on discharge

GA = gestational age; BW = birth weight; CUS = cranial ultrasound findings; positive/negative relates to maternal HIV serology.

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IN PRACTICE

Patient

Image 1

sizes of these thick-walled cysts tend to remain the same on serial imaging. We postulate that the initial changes represent areas of ischaemic injury, which progress to infarction and liquefaction, and that the cysts represent abscess formation within the brain parenchyma. We conclude that in a neonate who suddenly and unexpectedly becomes ill, cranial ultrasonography should be an urgent additional investigation. If changes such as inhomogeneous hyperechogenicities are noted, brain affectation by a serious bacterial infection such as S. marcescens should be considered and appropriate anti足 biotic cover instituted without delay. Follow-up imaging within 24 - 48 hours and again within 7 and 14 days in survivors will aid in identifying progression of injury and planning for neurosurgical intervention and rehabilitation. We suggest that cranial ultrasonography should be performed more than once before discharge from hospital in all neonates diagnosed with Serratia septicaemia, regardless of the presence or absence of neurological symptoms or an abnormal CSF analysis. This is based on our subsequent observations of intracranial complications, including abscess formation in neurologically asymptomatic neonates with normal CSF findings, as in the case of patient 5. We also propose that good-quality bedside neuro-imaging can be undertaken with ultrasonography as often as clinically required in these critically ill neonates, without the need to move them from the NICU.

Image 2

Case 2: right and left parasagittal views

Case 3: coronal and right parasagittal views

Case 4: left and right parasagittal views

Case 4: 7 days later, left and right parasagittal views

Case 5: coronal views

Case 5: parasagittal left view

Fig. 4. Patient cranial ultrasound images.

antibiotic therapy. With the exception of only one patient, we describe changes in the brain before the diagnosis of Serratia infection had been made in the babies with acute onset of illness. We also describe the progression and changing pattern

of these lesions. The progression seems to be that of ill-defined parenchymal hyperechogenicities, leading to cystic breakdown of these areas within 24 hours and culminating in areas of well-defined thick-walled cysts containing debris. The

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1. Donnenberg MS. Enterobateriaceae. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, vol 2. 7th ed. Philadelphia, USA: Churchill Livingstone Elsevier, 2010. 2. Gruber WC, Fisher RG. Serratia. In: Feigin RD, Cherry JD, eds. Feigin and Cherry Textbook of Paediatric Infectious Diseases, vol. 1. 4th ed. Philadelphia, USA: Saunders, 1998. 3. Casolari C, Pecorari M, Della Casa E, et al. Serratia marcescens in a neonatal intensive care unit: Two long-term multiclone outbreaks in a 10-year observational study. New Microbiol 2013;36:373-383. 4. Samuelsson A, Isaksson B, Hanberger H, Olhager E. Late-onset neonatal sepsis, risk factors and interventions: An analysis of recurrent outbreaks of Serratia marcescens, 2006 - 2011. J Hosp Infect 2014;86:57-63. DOI:10.1016/j.jhin.2013.09.017 5. Zaidi AKM, Thaver D, Ali SA, Khan TA. Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr Infect Dis J 2009;28:S10-S18. 6. Ballot DE, Nana T, Sriruttan C, Cooper PA. Bacterial blood足 stream infections in neonates in a developing country. ISRN Pediatrics 2012;2012:508512. DOI:10.5402/2012/508512 7. Hirooka MT, de Vasconcellos Fontes RB, Diniz EM, Pinto FC, Matushita H. Cerebral abscess caused by Serratia marcescens in a premature neonate. Arq Neuropsiquiatr 2007;65(4-A):1018-1021. 8. Messerschmidt A, Prayer D, Olischar M, Pollak A, Birnbacher R. Brain abscesses after Serratia marcescens infection on a neonatal intensive care unit: Differences on serial imaging. Neuroradiology 2004;46(2):148-152.

Accepted 23 October 2015.

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CLINICAL ALERT

Biofilms associated with bowel necrosis: A newly recognised phenomenon in infants G Brisighelli, S Cox, A Theron, K Pillay, H Rode Dr Giulia Brisighelli is a registrar in paediatric surgery at the UOC Chirurgia Pediatrica, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy. She worked as supernumerary registrar in paediatric surgery at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa. Dr Sharon Cox is the Head of the Clinical Unit in the Department of Paediatric Surgery at Red Cross War Memorial Children’s Hospital and is affiliated to the Faculty of Health Sciences at the University of Cape Town. Dr André Theron is a senior paediatric surgical registrar working at Red Cross War Memorial Children’s Hospital. He has a keen interest in neonatal surgery. Associate Professor Komala Pillay is a paediatric pathologist at the National Health Laboratory Service and University of Cape Town, based at Red Cross War Memorial Children’s Hospital. Prof. Heinz Rode is Emeritus Professor of Paediatric Surgery, based at Red Cross War Memorial Children’s Hospital and affiliated to the Faculty of Health Sciences at the University of Cape Town. Corresponding author: S Cox (sharon.cox@uct.ac.za)

Background. A biofilm is defined as a collection of organisms attached to a surface and surrounded by a matrix. Objective. To present three cases in which bowel necrosis coexisted with biofilm. Methods. The medical records, bacteriological findings and tissue biopsies from three infants with bowel necrosis who subsequently died from sepsis were analysed. Tissue sent for histological evaluation was prepared for light microscopy. Haematoxylin and eosin (H&E), Sandiford and Alcian blue/periodic acid Schiff (ABPAS) stains were performed. Tissue samples were ex-waxed for electron microscopy in one case. Results. The three patients described all had necrotic bowel at laparotomy, all cultured Klebsiella pneumoniae from peritoneal pus swabs, and all died despite appropriate antibiotics. All specimens showed varying degrees of bowel necrosis and an organising acute peritoneal reaction. In addition, all showed colonies of Gram-negative bacteria within a mucopolysaccharide matrix. Conclusions. The identification of biofilms in necrotic bowel has raised questions regarding their clinical implications. Further studies are needed to evaluate all resected necrotic bowel for biofilms and the clinical implications of this finding. S Afr Med J 2016;106(4):345-347. DOI:10.7196/SAMJ.2016.v106i4.10425

The term biofilm has been used to describe a well-organised microbial community enmeshed in a polymeric, carbohydrate-rich extracellular matrix and adhering to an inanimate or living surface.[1] The organisms within it become highly resistant to antibiotic therapy and to the immune system.[2] The reasons for this are complex and are related to the inability of antibiotics to diffuse through the biofilm, to changes in the organisms resulting from the increasing hypoxia within the biofilm, and to the development of persistent resistant cells thought to be a mechanism of survival by the micro-organisms. [3] Although biofilms have been detected in several mucosal locations, their ability to trigger human disease is still a matter of active investigation.[4] The pathogenic role of biofilms has been established for oral infections, chronic wounds, indwelling medical and surgical devices, and implants.[1,3,5] Currently, the link between gastrointestinal infections and biofilms in infants is less clear.[6] We encountered three infants with necrotic small bowel in whom special staining techniques on histological specimens of their resected bowel revealed an abundance of Klebsiella-associated intramural biofilm formations. This phenomenon has not been described before in necrotic bowel in infants and may be of significance in the pathogenesis of bowel necrosis and the medical and surgical management thereof, and have implications in the understanding of the disease process. The objective of this article is to present three cases in which bowel necrosis coexisted with biofilm.

Methods

The medical records, bacteriological findings and tissue biopsies from three infants who underwent laparotomy for volvulus, necrotising enterocolitis (NEC) and spontaneous intestinal perforation, and who

subsequently died from sepsis, from March 2014 to March 2015 at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa, were analysed. Tissue sent for histological evaluation was prepared for light microscopy to assess its architecture, and haematoxylin and eosin (H&E), Sandiford and Alcian blue/periodic acid Schiff (ABPAS) stains were performed. The cases were assessed for extent of necrosis, inflammation, organisation and viral inclusions. On the Sandiford stain Gram-positive organisms are blue-black and Gramnegative organisms are red. The ABPAS stains neutral mucins and fungal walls bright red or magenta, and acid mucopolysaccharides blue. Tissue samples from one patient were also ex-waxed for electron microscopy analysis.

Results Case 1

A male infant born at 34 weeks’ gestation, birth weight 1 800 g, underwent laparotomy and subsequent relook for midgut volvulus with extensive small-bowel necrosis on day 25 of life. Postoperatively he remained hypotensive and septic, and died the following day. Blood cultures remained negative, but a pus swab from the peri toneum was positive for extended-spectrum beta-lactamaseproducing K. pneumoniae. Histological examination of the resected bowel showed extensive, acute, full-thickness haemorrhagic coagulative necrosis with no significant inflammation or organisation. A prominent serosal biofilm (Fig. 1) comprising Gram-negative bacterial bacilli was highlighted on the Sandiford special stain within an acidic mucopolysaccharide

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matrix (ABPAS) (Fig. 2, A, B and C). The bacterial organisms were also present in the subserosal vessels, and similar scattered colonies were noted on the mucosal surface and intramurally. No viral inclusions, ova, parasites or fungal organisms were identified. Transmission electron microscopy demon strated the bacilli within a matrix consistent with mucopolysaccharide (Fig. 3). Fig. 1. Low-power view of the ABPAS stain, showing a blue biofilm along the serosal surface.

C Fig. 2. (A) Medium-power view of the H&E stain, showing the mucoid colonies. (B) Highpower view of the Sandiford stain, showing the Gram-negative bacilli. (C) High-power view of the ABPAS stain, showing the bacilli surrounded by mucopolysaccharide (stains blue on the ABPAS stain).

Fig. 3. Transmission electron microscopy showing bacterial bacilli surrounded by a matrix.

Case 2

A male infant born at 28 weeks’ gestation, birth weight 1 180 g, had a difficult neonatal course including respiratory distress due to hyaline membrane disease and NEC and was readmitted with sepsis, pneumonia, anaemia and oedema. He underwent laparotomy for abdominal distension due to a colonic stricture, and subsequent relook laparotomy showed extensive adhesions, exudative fibrin and multiple large pockets of pus. Necrotic bowel was resected. He remained unstable on inotropic and ventilator support and died 24 hours later with sepsis and multiorgan failure. Blood culture always remained negative, but a pus swab from the peritoneum revealed abundant growth of multidrug-resistant K. pneumoniae. Histological examination of the resected bowel, during the second procedure, showed transmural necrosis with an acute inflammatory response. There was adjacent organisation and regenerative epithelium. In addition, numerous colonies of Gramnegative bacilli within a mucoid matrix were present transmurally, highlighted on the Sandiford and ABPAS stains. Focal colonies within the submucosa appeared to be within vessels. No viral inclusions, ova, parasites or fungal organisms (ABPAS) were identified.

Case 3

A 3-day-old female infant born at 31 weeks’ gestation, birth weight 1 180 g, under went laparotomy and a subsequent relook for a focal mid-jejunal perforation. Postoperatively she remained septic with coagulopathy, thrombocytopenia, hyper glycaemia and acute kidney failure, and died on day 12. Blood culture and pus swab from the wound were positive for extended-spectrum beta-lactamase-producing Klebsiella. Histological examination of the resec ted bowel, during the first procedure, showed areas of mucosal ulceration and perforation, with transmural necrosis and an organising acute peritoneal reaction. Focally, on the mucosal aspect, colonies of Gram-negative bacteria were noted within

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a mucopolysaccharide matrix. The viable mucosa showed superficial ischaemia and interstitial haemorrhage. In addition, abundant Gram-positive cocci were present (Sandiford stain). Despite numerous blood cultures taken pre- and postoperatively, Klebsiella was identi fied on blood culture only once in case 3. In all cases, bacteriological cultures from pus swabs taken from the peritoneal cavity showed an abundant growth of a very resistant, extended-spectrum beta-lactamase K. pneumoniae species.

Discussion

The presence of biofilm formation in necro t ic bowel has not been identified previously in infants, although it is well documented in septic patients with implan ted medical and surgical devices, central venous and urinary catheters, and dental and chronic wound infections.[1,3,4] Although the function of biofilms is unknown, their presence in necrotic bowel must have implications for the pathogenesis of bowel necrosis and for its medical and surgical management. In our study, after conventional staining of a bowel specimen, excessive protein matrix was identified. The specimen was therefore subjected to biofilm specific staining. This led to further biofilm identification on subsequent specimens of necrotic bowel. The exact process by which biofilmassociated micro-organisms can cause disease is speculative at present.[7] Parsek and Singh,[6] in 2003, suggested four criteria to define infections caused by biofilms: • The infecting bacteria are adherent to some substratum or are surface associated. • Direct examination of infected tissue shows bacteria living in cell clusters, or microcolonies, encased in an extracellular matrix. The matrix may often be composed of bacterial and host components. • The infection is generally confined to a particular location. Although dissemination may occur, it is a secondary phenomenon. • The infection is difficult or impossible to eradicate with antibiotics despite the fact that the responsible organisms are susceptible to killing in the planktonic state. The encapsulated aggregations of organ isms, which can form within hours, are highly resistant to antibiotic therapy and to systemic and local defence mechanisms.[8,9] Biofilm infections are rarely resolved, and tissue adjacent to the biofilm may undergo

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collateral damage by immune complexes and invading neutrophils. [8] The reasons for this are multifactorial, with changes in the microorganism, the development of resistant endotoxin formation and inability of antibiotics to diffuse through the biofilm’s polysacchariderich matrix.[3,7] Although K. pneumoniae is present as a saprophyte in the gastro intestinal tract, the identification of intramural Klebsiella biofilms has not been published in the English paediatric literature.[5,10] The question of whether Klebsiella-associated biofilms were direct aetiological factors in causing bowel necrosis and the death of the patients reported on cannot be proven, but their presence satisfies all four of the Parsek and Singh postulates.[6] We postulate that this sole offending organism shielded from environmental defence mechanisms could have played a part in the unfolding pathogenesis, either as a direct pathogen or promoter thereof. The identification of Klebsiella biofilm in necrotic bowel has created a therapeutic dilemma. In K. pneumoniae, many studies have been performed in order to better highlight the mechanisms underlying this resistance, and have demonstrated that limitation of the penetration of antibiotic molecules through the biofilm matrix is not the main reason for the increasing resistance; rather it is the slow growth rate of Klebsiella spp. in the centre of the biofilm. In any case, other mechanisms are involved, and further studies are required to elaborate on new concepts in the preventive measures against nosocomial K. pneumoniae infections in the future.[11] In chronic surface wounds with biofilms, the latter can be eradicated with topical bioflammacide therapy; this would not be an option for gastrointestinal disease.[12]

Conclusion

The identification of Klebsiella-associated biofilms in necrotic bowel of three infants in our institution has raised questions regarding the clinical implications of these biofilms. In future, all resected necrotic bowel should be investigated for presence of biofilms, and the clinical implications of a finding evaluated. If the presence of biofilm is confirmed in the majority of patients with bowel necrosis who died, this may represent a major therapeutic challenge. 1. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: A common cause of persistent infections. Science 1999;284(5418):1318-1322. DOI:10.1126/science.284.5418.1318 2. Wilson M. Bacterial biofilms and human disease. Sci Prog 2001;84(Pt 3):235-254. DOI:10.3184/003685001783238998 3. Kennedy P, Brammah S, Wills E. Burns, biofilm and a new appraisal of burn wound sepsis. Burns 2010;36(1):49-56. DOI:10.1016/j.burns.2009.02.017 4. Dongari-Bagtzoglou A. Pathogenesis of mucosal biofilm infections: Challenges and progress. Expert Rev Anti Infect Ther 2008;6(2):201-208. DOI:10.1586/14787210.6.2.201 5. Von Rosenvinge EC, O’May GA, Macfarlane S, Macfarlane GT, Shirtliff ME. Microbial biofilms and gastrointestinal diseases. Pathog Dis 2013;67(1):25-38. DOI:10.1111/2049-632X.12020 6. Parsek MR, Singh PK. Bacterial biofilms: An emerging link to disease pathogenesis. Annu Rev Microbiol 2003;57(1):677-701. DOI:10.1146/annurev.micro.57.030502.090720 7. Donlan RM, Costerton JW. Biofilms: Survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 2002;15(2):167-193. DOI:10.1128/cmr.15.2.167-193.2002 8. Stewart PS, Costerton JW. Antibiotic resistance of bacteria in biofilms. Lancet 2001;358(9276):135-138. DOI:10.1016/s0140-6736(01)05321-1 9. Hammond AA, Miller KG, Kruczek CJ, et al. An in vitro biofilm model to examine the effect of antibiotic ointments on biofilms produced by burn wound bacterial isolates. Burns 2011:37(2):312321. DOI:10.1016/j.burns.2010.09.017 10. Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: Epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 1998;11(4):589-603. 11. Vuotto C, Longo F, Balice MP, Donelli G, Varaldo PE. Antibiotic resistance related to biofilm formation in Klebsiella pneumoniae. Pathogens 2014;3(3):743-758. DOI:10.3390/pathogens3030743 12. Phillips P, Wolcott R, Fletcher J, Schultz G. Biofilms made easy. Wounds international 2010. http:// www.woundsinternational.com/made-easys/view/biofilms-made-easy (accessed 12 January 2016).

Accepted 12 December 2015.

MEDICINE AND THE LAW

A child’s potential claim for negligent misdiagnosis: The case of H v. Fetal Assesment Centre P Mahery Prinslean Mahery is a lecturer in family law at the Oliver Schreiner School of Law, University of the Witwatersrand, Johannesburg, South Africa. Corresponding author: P Mahery (prinslean.mahery@wits.ac.za)

South African law recognises a financial claim against a health provider for negligently failing to advise an expectant mother that she might give birth to a child suffering from a severe health condition or congenital disability. In December 2014, the Constitutional Court handed down a judgment that could lead to financial claims by the child, who was subsequently born with a severe health condition or disability. This judgment thus creates a framework to legally recognise a claim by a child whose current health condition was negligently misdiagnosed before birth. The contents and effects of the judgment are discussed in this article. S Afr Med J 2016;106(4):348-349. DOI:10.7196/SAMJ.2016v106i4.9724

Case report

A health provider who fails to advise a pregnant woman that her child could be born with a severe health condition or congenital disability could face financial liability in terms of South African (SA) law.[1,2] In the case of H v Fetal Assesment Centre,[3] a mother gave birth to a boy suffering from Down syndrome. She initiated a financial claim on behalf of the child against the Fetal Assesment Centre (FAC) in the High Court (HC) for failing to advise her of the risk that the child she was carrying

could be born with this disorder. This is the so-called ‘wrongful life’ claim. The Supreme Court of Appeal (SCA) has defined a ‘wrongful life’ claim as ‘an action brought by a deformed child, who was born as a result of negligent diagnosis or other act by a doctor’ (in para 1).[4] The HC (in the FAC case) rejected the claim off-hand on the grounds that SA law does not recognise it. In terms of our current law, parents can claim for their financial loss suffered in these cases as a result of the additional costs of now caring for a child who has serious health challenges or

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disability. SA law thus limits the claim for monetary relief to the parent and does not extend the claim to the child once born. This legal position was confirmed and ultimately dead-ended by the SCA in the Stewart[5] case. The High Court in the FAC case was therefore bound by the SCA decision, which is why it rejected the child’s claim. The matter was appealed to the Constitutional Court (CC).

Findings and outcome

The CC found that the current approach to these cases was too narrow and paid little attention to constitutional values (para 23). It found that the issue in this type of case was ‘whether our constitutional values and rights should allow the child, in the circumstances of this case, to claim compensation for a life with disability’ (para 24). The court accepted that it was possible that upon further judicial investigation, such a claim might not be allowed in terms of our law but felt that the possibility of recognising the claim could not simply be regarded as a closed issue (para 24). It was further accepted that should the child’s claim be recognised, it would only come into existence once the child is born alive (para 50), similar to the approach for a claim in a case of prenatal physical injury.[6] The child claimant would also still have to show negligence on the part of the health provider (para 75). The CC considered how other countries responded to a child’s claim in such cases and looked at whether or not our law could accommodate the claim. It found that the child’s claim could exist in our law. The CC did not consider questions on the extent of expenses the child could claim for (para 77). The HC now has to reconsider the child’s potential claim following the CC’s decision (para 66). The CC found that all decisions in relation to this type of claim by a child will have to be done in accordance with constitutional principles and having regard to children’s rights, particularly the right to have their best interests considered as of paramount importance in these cases (paras 42, 49 and 69). The appeal was therefore successful to the extent that the CC decision gives the child a window of opportunity to raise a claim.

Discussion

Several times in the judgment, the CC made it clear that if the child’s claim was allowed it could be limited to the extent that the health provider was liable against either the parent or the child and not to both (para 70). The loss or harm suffered by the child relates to the fact that currently the child has no recognised claim if the parents for some reason failed to claim against the health provider. The child’s loss is rooted in the fact that in the absence of a claim by the parents, the health provider could avoid liability for medical misdiagnosis. What could be problematic with this approach is that that the child’s claim depends on the parents. The child is thus not viewed as an independent being. This appears contrary to what the CC held in S v. M,[7] where it said that: ‘Every child has his or her own dignity. If a child is to be constitutionally imagined as an individual with a distinctive personality, and not merely as a miniature adult waiting to reach full size, he or she cannot be treated as a mere extension of his or her parents, umbilical destined to sink or swim with them.’ (para 18) The CC’s approach in the FAC case appears to be narrow. What would happen if the parents did claim but the claim was unsuccessful on technical grounds? Would it mean that the child would have to suffer under that loss and have no ability to reapproach the court to consider the substance of the claim against the health provider? The decision by the CC reopens the door to consider claims by a child in cases of prenatal misdiagnosis, which was basically a

closed matter after the Stewart case. However, the CC could not make the final decision regarding the development of our common law to allow for the child’s claim owing to a lack of evidence and therefore sent the case back to the HC (para 48). Despite this, the CC judgment gives guidance on how future courts should approach this matter. The CC judgment emphasised that courts faced with this issue must make their findings based on constitutional principles such as the best interests of the child. If we compare our constitutional principles and national laws against some of the countries noted in the CC judgment that recognise such claims (such as The Netherlands) (paras 44 and 45), it is clear that our legal system is more aligned with countries that do recognise the child’s claim given that our Constitution protects the rights of the child explicitly in section 28. It is therefore perhaps more likely than not that the ultimate decision in these cases will be to recognise the existence of the child’s separate claim in cases of medical misdiagnosis. The extent of the claim, the requirements for a successful claim and the potential remedies associated with the claim are matters that the courts will determine on a case-by-case basis. Any judicial inconsistencies arising from such cases could then again end before the CC for legal certainty on those issues.

Conclusion

Although the CC’s consideration of the viability of a child’s claim was mostly theoretical in nature, it could come to the same conclusions should the issue find its way back to the CC in the future and the necessary evidence be produced. Therefore, courts such as the HC cannot simply ignore the CC’s analysis. These courts will find particular assistance from the CC’s judgment on how to limit the child’s claim if recognised. The child’s potential separate claim will ensure that health providers who negligently failed to advise parents of the possibility of giving birth to a child with serious health challenges or disability will not escape liability if parents failed to pursue a claim against the health provider. However, given the narrow approach of the CC to merge the child’s claim with that of the parent, the deterring effect of recognising the child’s claim might not be that significant because the health provider would still only be liable against a single claim. This is not very different to the current law. The significance of this judgment for health providers is thus twofold. In the first instance, currently the child’s claim is not recognised in our law so the health provider could escape liability if parents do not claim. This CC judgment does open the door to potential claims by a child in the event of a parent being unable to claim. Secondly, even if following the CC judgment the child’s claim is recognised, it might not be recognised as a separate claim from that of parents, and the health provider would be likely to be held liable for a single claim in the case of medical misdiagnosis. This case could thus spell the start of new developments in recognising a child’s claim in wrongful life cases. Health providers will have to wait and see how the law on this matter develops over time. 1. Friedman v. Glicksman 1996 (1) SA 1134 (W). 2. McQuid-Mason D, Dada M. The A - Z of Medical Law. 1st ed. Cape Town: Juta & Company Ltd., 2011:282; 339-340. 3. H v Fetal Assessment Centre (CCT 74/14) [2014] ZACC 34; 2015 (2) BCLR 127 (CC); 2015 (2) SA 193 (CC) (11 December 2014). 4. Mukheiber v. Raath and Others (262/97) [1999] ZASCA 39; [1999] 3 All SA 490 (A) (28 May 1999). 5. Stewart and Another v. Botha and Another (340/07) [2008] ZASCA 84; 2008 (6) SA 310 (SCA); [2009] 4 All SA 487 (SCA) (3 June 2008). 6. Road Accident Fund v. Mtati (332/2004) [2005] ZASCA 65; [2005] 3 All SA 340 (SCA) (1 June 2005). 7. S v. M (CCT 53/06) [2007] ZACC 18; 2008 (3) SA 232 (CC) (26 September 2007).

Accepted 2 December 2015.

April 2016, Print edition

IN PRACTICE

ISSUES IN PUBLIC HEALTH

The impact of the Medicines Control Council backlog and fast-track review system on access to innovative and new generic and biosimilar medicines of public health importance in South Africa H M J Leng, A M Pollock, D Sanders Dr Henry Leng is a senior researcher in the School of Public Health at the University of the Western Cape. Prof. Allyson Pollock is Professor of Public Health Research and Policy at Queen Mary University, London, UK. Prof. David Sanders is Emeritus Professor in the School of Public Health at the University of the Western Cape, Cape Town. Corresponding author: H M J Leng (hmjleng@gmail.com)

The fast-track registration policy of the South African (SA) National Department of Health (DoH) allows for rapid registration of new medicines of public health importance and of all medicines on the Essential Medicines List, most of which are generics. No limit is placed on the number of generic brands of a medicine that can be submitted for fast-track registration. This, together with resource constraints at the regulator, may delay access to important new medicines, new fixed-dose combinations of critical medicines or affordable versions of biological medicines (biosimilars). One reason for not limiting the number of fast-track generic applications was to promote price competition among generic brands. We found this not to be valid, since market share correlated poorly with price. Generic brands with high market share were, mostly, those that were registered first. We propose that the number of generic brands accepted for fast-tracking be limited to not more than seven per medicine. S Afr Med J 2016;106(4):350-353. DOI:10.7196/SAMJ.2016.v106i4.10237

In a recently published article, we tested the widely held belief, particularly among those in the pharmaceutical industry, that the backlog in medicine registration applications at the Medicines Control Council (MCC) was a barrier to access to affordable generic medicines.[1] In the study, we investigated the availability of generic products of eight tracer medicines (amlodipine, ciprofloxacin, fluoxetine, lamivudine, metformin, oxytocin, rifampicin and simvastatin) that are commonly used in the treatment of the most prevalent diseases in SA.[2] Availability was assessed based on the number of generic products for each tracer medicine that had been registered at the time of the study in 2012, as well as the number of generics that were being marketed. We found that for most of the tracer medicines, more generics had been registered than were being sold in the market. When data were aggregated, they showed that only 54% of all registered generic brands for the eight medicines were marketed, which suggests that the backlog was not a hindrance to access to these medicines. In 2003, the DoH implemented a fast-track registration policy, not only for new chemical entities (NCEs) considered essential for national health and which may not be on the Essential Medicines List (EML), but also for all medicines on the EML, the majority of which are generics.[3,4] We found that for the period between 2007 and 2012, more generic medicines were registered through expedited review (fast track) than NCEs.[1] Since no limit is placed on the number of generics of a particular medicine that can be fast-tracked, it is likely that several generic applications may be in the fast-track system when many generic products for such medicines have already been registered. It is, therefore, not surprising that the fast-track review process, which should lead to a registration decision timeline of not more than 9 months after first submission,[3] is now also taking

considerably longer. A backlog is therefore likely to be present, even in the expedited registration pathway. This, coupled with current shortcomings, such as insufficient skilled manpower and poor infrastructure at the MCC,[5] could prevent innovative as well as cost-effective and new fixed-dose combination (FDC) therapies from reaching patients timeously. According to the minutes of the Industry Task Group meeting held in March 2015,[6] the MCC has been allocating applications for review received from January until March 2012. This implies that the applications that make up the backlog are all those received up to December 2011 and which have not yet been reviewed. These applications will therefore only be evaluated once the MCC has acquired substantial additional capacity to start reviewing backlog applications. A class of important and potentially cost-effective medicines that may be part of the backlog is biosimilar medicines. These are products that are similar, i.e. not identical, to innovator biopharmaceuticals of erythropoietin, filgrastim, growth hormone, infliximab, etc. that are produced by modern biotechnological methods and are already off patent.[7] While many countries in the European Union, as well as Canada, Australia, Korea and even the USA, have registered such products, SA has yet to register its first biosimilar. Biosimilars are significantly cheaper than their innovator counterparts[8] and, consequently, more patients would have access to these medicines once they are registered. In Europe, biosimilars of somatropin, erythropoietin and filgrastim have been available since before 2010.â&#x20AC;&#x201A;[9] Considerable experience has therefore already been gained with the use of these products, so that doubts about their safety and efficacy should no longer exist. The MCC should, therefore, alter its strategy for the allocation of applications for evaluation from using

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Table 1. Date of registration, single exit price per dosage unit and market share of selected tracer medicines as at December 2012 (names of registration holders for each product are included) Active pharmaceutical ingredient (strength/dosage unit)

Brand name

Date of registration (YYYY/MM/DD)

Holder of registration certificate

Price/unit (ZAR)

Market share by volume (%)

Alendronate (70 mg/tablet)

Osteobon

2005/07/29

Cipla Medpro (Pty) Ltd

45.60

44.4

Fosamax*

2002/03/26

MSD (Pty) Ltd

93.84

6.3

Osteonate

2010/11/26

Pharma Dynamics (Pty) Ltd

38.29

1.7

Fosagen

2006/02/17

Mylan (Pty) Ltd

52.54

0.9

Sandoz Alendronate

2006/12/01

Sandoz SA (Pty) Ltd

56.48

0.3

Amloc

2004/09/17

Pharma Dynamics (Pty) Ltd

3.61

37.8

Ciplavasc

2005/02/11

Cipla Medpro (Pty) Ltd

3.50

19.3

Lomanor

2005/09/23

Pfizer Laboratories (Pty) Ltd

3.08

10.0

Norvasc*

1991/11/26

Pfizer Laboratories (Pty) Ltd

6.71

4.6

Amlate

2006/08/11

Dr Reddy’s Laboratories (Pty) Ltd

3.46

3.1

Cifloc

2001/10/08

Dr Reddy’s Laboratories (Pty) Ltd

1.31

21.6

Ciploxx

2003/01/24

Cipla Life Sciences (Pty) Ltd

1.25

17.3

Ciprobay*

1990/06/12

Bayer (Pty) Ltd

10.09

10.6

Austell Ciprofloxacin

2004/07/02

Austell Laboratories (Pty) Ltd

1.07

10.2

Ciprol

2004/07/23

Arrow Pharma South Africa (Pty) Ltd

1.19

6.4

Ciprogen

2003/09/05

Xixia Pharmaceuticals (Pty) Ltd

1.39

5.8

Bio-Ciprofloxacin

2005/10/09

Biotech Laboratories (Pty) Ltd

0.97

4.5

Orpic

2002/09/20

Pharmacare Limited

1.26

2.9

Nuzak

1998/05/25

Cipla Medpro (Pty) Ltd

1.22

45.7

Lorien

1996/03/27

Pharmacare Limited

1.18

24.0

Lilly-Fluoxetine

1995/10/25

Eli Lilly (SA) (Pty) Ltd

3.88

11.7

Rezak

2003/03/07

Ranbaxy (SA) (Pty) Ltd

0.74

4.5

Ranflocs

2003/04/25

Dr Reddy’s Laboratories (Pty) Ltd

0.70

4.3

A-Lennon Fluoxetine

2001/09/21

Zydus Healthcare SA (Pty) Ltd

0.76

2.3

Zydus-Fluoxetine

2005/06/03

Pharmacare Limited

0.74

2.2

Prohexal

2000/12/13

Sandoz SA (Pty) Ltd

1.23

1.9

Prozac*

1986/12/31

Eli Lilly (SA) (Pty) Ltd

14.24

1.2

Actor Fluoxetine

2003/03/07

Cipla Medpro (Pty) Ltd

1.14

1.0

Glucophage*

1975/04/25

Merck (Pty) Ltd

0.49

49.1

Mylan Metformin

2000/12/13

Sandoz SA (Pty) Ltd

0.34

14.4

Sandoz Metformin

1984/03/26

Mylan (Pty) Ltd

0.35

11.5

Arrow Metformin

2005/09/23

Arrow Pharma South Africa (Pty) Ltd

0.36

4.4

Metforal

2002/09/20

Adcock Ingram Limited

0.35

3.4

Metored

2008/08/15

Pharmaplan (Pty) Ltd

0.34

3.1

Accord Metformin

2009/12/04

Accord Healthcare (Pty) Ltd

0.32

2.6

Gluconorm

2007/10/05

Be-Tabs Pharmaceuticals (Pty) Ltd

0.34

2.3

Austell Metformin

2005/09/23

Austell Laboratories (Pty) Ltd

0.36

1.8

Amlodipine (10 mg/ tablet)

Ciprofloxacin (250 mg/ tablet)

Fluoxetine (20 mg/ capsule)

Metformin (500 mg/ tablet)

Continued ...

a specific date of submission such as January 2012 (as it currently does) to selecting product classes or types for which there is a public need, irrespective of when the applications of such products were submitted.

The lack of restrictions on the use of the fast-track review system, such as placing a limit on the number of generics of a specific medicine that can be reviewed and registered via this process, can result in delays in the registration and availability of medicines of

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IN PRACTICE

Table 1. (continued) Date of registration, single exit price per dosage unit and market share of selected tracer medicines as at December 2012 (names of registration holders for each product are included) Active pharmaceutical ingredient (strength/dosage unit) Simvastatin (20 mg/tablet)

Brand name

Date of registration (YYYY/MM/DD)

Holder of registration certificate

Price/unit (ZAR)

Market share by volume (%)

Adco-Simvastatin

2002/09/20

Adcock Ingram Limited

1.02

58.3

Simvacor

2002/11/15

MC Pharma (Pty) Ltd

1.02

7.0

Cipla-Simvastatin

2006/10/06

Cipla Life Sciences (Pty) Ltd

0.97

6.9

Simvotin

2004/05/28

Ranbaxy (SA) (Pty) Ltd

1.10

5.8

Aspen Simvastatin

2005/07/29

Pharmacare Limited

1.10

5.4

Michol

2007/10/05

Ingelheim Pharmaceuticals (Pty) Ltd

1.54

4.4

Zocor*

1990/04/02

MSD (Pty) Ltd

2.45

3.1

Arrow Simvastatin

2006/04/07

Arrow Pharma South Africa (Pty) Ltd

1.07

2.2

Choleste

2007/10/05

Be-Tabs Pharmaceuticals (Pty) Ltd

1.07

1.4

Biovac Simvastatin

2006/12/01

Arrow Pharma South Africa (Pty) Ltd

1.07

0.9

* Innovator product.

public health importance. In our previous study, we found that changes in the treatment guidelines for tuberculosis (TB) may have made some FDC products containing rifampicin obsolete, causing them not to be marketed. New FDC formulations, and even new drugs for the prevention and treatment of multidrugresistant TB, even if fast-tracked, could take significantly longer than the specified 9 months expedited review and registration decision timeline. An example is an application for the registration of a generic version of linezolid that was submitted for fast-track review in May 2013 for the treatment of drug-resistant TB (DRTB). When a final decision on the product was still outstanding more than 16 months after its submission, activists handed over a letter addressed to the Registrar of Medicines, signed by clinicians, civil society organisations and patients with DR-TB, demanding its immediate registration.[10] The product was eventually registered in November 2014 and a second one in March 2015. At least six other generic linezolid tablet formulations (600 mg/tablet), all submitted as fast-track applications, are currently under review. This raises an important issue that needs to be considered if the fast-track review process is to be amended to improve its effectiveness: what should be the number of generics of a specific medicine that are allowed to be fast-tracked, to ensure not only timeous availability but also affordability through robust competition? Should the additional six applications also have been allowed in the fast-track system, which, with the current limited number of evaluators, will take preference over other fast-track applications for medicines for which there may potentially be no alternatives, or if alternatives exist, may not be as effective as the new medicine? Table 1 gives the single exit price per dosage unit (i.e. tablet or capsule) for several brands of each of six tracer medicines, their percentage market share by volume and their date of registration. Whereas the price difference between the generic products and their corresponding innovator is substantial in almost all cases, the variation in price among generics of a specific medicine is often not as large. Exceptions include where the patent holder of the innovator markets a generic version of its own product (a clone or autogeneric) as is the case with the fluoxetine generic Lilly-Fluoxetine which, although priced at only 27% of the cost of the innovator product, Prozac, was three times more expensive than the market leader (Nuzak).

Another observation is that the market leader for a specific medicine is not necessarily the cheapest brand. In the case of the alendronate generics, for example, the cheapest product was Osteonate, which cost 16% less than the market leader, Osteobon. Yet, it only had a market share of 1.5%, whereas Osteobon had a market share of 44.6%. The higher market share was most likely due to earlier entry, since Osteobon was registered before Osteonate. In fact, for most of the other medicines in the sample, the market leader or its follower was registered first. An interesting observation was that one innovator product retained its dominant market position after generics entered. The metformin originator product, Glucophage, was still the market leader (at 49.1% market share) even though it was priced 35% higher than the cheapest generic (Accord Metformin, with a market share of 2.6%) and 31% higher than the generic with the next highest market share (Mylan Metformin, with a market share of 14.4%). This price difference is similar to that found between the highest and lowest priced generics of some of the other tracer medicines. For example, for ciprofloxacin and alendronate, the difference in price between the most and least expensive generics was 40% and 48%, respectively. The price difference between the innovator and generic market leader for the other medicines ranged from 86% for amlodipine to 1067% for fluoxetine. Glucophage was therefore priced at the same level as generics, which ensured its dominant market position. Competition theory predicts that as more competitors enter a market, prices of products will fall. Hence, registering a large number of generics should lower the cost of medicines, increasing their accessibility. Our data show, however, that increasing availability through registration of more generics does not necessarily lead to greater access, as measured by percentage market share, even if these newly registered generics are priced lower than those already in the market. Regression analysis further confirmed the weak relationship (R2<0.05) between price and market share (data not shown). This suggests that at the prevailing price level of generics, other factors are more important determinants of market share. One such factor is market entry, since among our sample of six medicines, the brands with the highest market share were those that had been among the first to obtain registration. The data above, although based on a small sample of medicines, suggest that the contention of promoting competition by registering several generic brands of a medicine to ensure low prices and, hence, affordability to the patient, may not be valid. Affordability appears

April 2016, Print edition

IN PRACTICE

to be a function more of the price difference between the innovator and generics as a group, which can be substantial (>80%), as this has been shown to erode the market share of the innovator. Differences in prices among generic brands do not correlate with market share. What is far more important is market entry. Therefore, in the allocation of fast-track status to generic applications for a medicine that has gone off patent, the promotion of competition should not be a prime consideration, particularly in view of the capacity constraints at the MCC, i.e. the limited number of evaluators currently available. The fasttrack system should at all times be responsive and, consequently, must be reserved for new medicines, a novel formulation or combination of existing medicines based on new treatment guidelines, the first generic of an off-patent medicine, or for unique biologicals such as vaccines and biotechnology products, including biosimilars. Finally, medicines with small local markets for which there are few registered products and suppliers are vulnerable to stock-outs when suppliers decide to discontinue their products. Oxytocin is one such product, with only three registered brands, and which had a market value of ZAR24.9 million in 2012. This is considered small relative to that of other products such as amoxicillin (ZAR441.4 million), tenofovir (ZAR467.5 million), ibuprofen (ZAR498.4 million) and paracetamol (ZAR1.697 billion). The product is only used in the hospital setting and requires cold-chain storage. These factors probably discourage local companies from including oxytocin formulations in their product portfolio. A more recent case involves intravenous rifampicin, which was under threat of being discontinued by the only supplier for this product. [11,12]

It is important, therefore, to ensure that the fast-track system is immediately accessible when applications for such marketvulnerable products are received by the MCC. 1. Leng HMJ, Sanders D, Pollock AP. Pro-generics policies and the backlog in medicines registration in South Africa: Implications for access to essential and affordable medicines. GaBI J 2015;4(2):58-63. DOI:10.5639/gabij.2015.0402.014 2. Coovadia H, Jewkes R, Barron P, Sanders D, McIntyre D. The health and health system of South Africa: Historical roots of current public health challenges. Lancet 2009;374(9692):817-834. DOI:10.1016/S0140-6736(09)60951-X 3. Medicines Control Council. General information guideline, 2008. www.mccza.com (accessed 27 March 2013 and 19 October 2015). 4. National Department of Health of South Africa. National Essential Medicines List. http://www.health. gov.za/index.php/component/phocadownload/category/196 (accessed 9 March 2016). 5. Report of the Ministerial Task Team on the restructuring of the Medicines Regulatory Affairs and Medicines Control Council and recommendations for the new Regulatory Authority for Health Products of South Africa, 2008. http://www.gov.za/sites/www.gov.za/files/Report%20of%20Ministerial%20Task%20 Team%20on%20Restructuring%20of%20Medicines%20Regulatory%20Affairs%20and%20Medicines%20 Control%20Council%20and%20recommendations%20for%20New%20Regulatory%20Authority%20 for%20Health%20Products.pdf (accessed 9 March 2016). 6. Summary of the Industry Task Group meeting held at 09:00 on 17 March 2015 at the Civitas Building. http:// www.mccza.com/documents/97911b47itg_meeting_minutes_march2015.pdf (accessed 20 October 2015). 7. Leng HMJ, Mutoti K, Mbelle N. Regulatory requirements for the development and registration of biosimilars in South Africa. GaBI J 2015;4(3) http://gabi-journal.net/regulatory-requirements-forthe-development-and-registration-of-biosimilars-in-south-africa-2.html (accessed 19 October 2015). 8. Derbyshire M. Reducing the European healthcare budget with generics and biosimilars. GaBI J 2014;3(4):200-201. DOI:10.5639/gabij.2014.0304.046 9. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe. Mol, Belgium: Pro Pharma Communications International, 2011. www.gabionline.net/Biosimilars/General/Biosimilarsapproved-in-Europe (accessed 20 October 2015). 10. Médecins Sans Frontières. DR-TB patients, activists demand registering generic linezolid. 30 October 2014. https://www.msf.org.za/msf-publications/dr-tb-patients-activists-demand-registering-genericlinezolid (accessed 20 October 2015). 11. GroundUp Staff. Life-saving drug stopped by sole supplier. 2015. http://groundup.org.za/article/lifesaving-drug-stopped-sole-supplier_3359 (accessed 16 October 2015). 12. Allafrica.com. South Africa: Essential TB Medicine – Is it Back in Stock? http://allafrica.com/ stories/201511022739.html (accessed 9 March 2016).

Accepted 9 November 2015.

CASE REPORT

Orbital apex syndrome caused by aspergilloma in an immunocompromised patient with cutaneous lymphoma: A case report of a rare entity A Cheko,1 MDS; S Jung,1 MD; S Teuber-Hanselmann,2 MD; A W Oseni,3 MD, MSc; A Tsogkas,1 MD; M Scholz,1 MD; A K Petridis,1 MD Department of Neurosurgery, Sana Hospitals Duisburg, Duisburg, Germany Institute of Neuropathology, University of Duisburg-Essen, Essen, Germany 3 Neurosurgical Division, Department of Surgery, Lagos University Teaching Hospital, Lagos, Nigeria 1 2

Corresponding author: A W Oseni (oseniabidemi@yahoo.com)

A 57-year-old man with a history of chemotherapy because of cutaneous lymphoma presented with an orbital apex syndrome. The cranial computed tomography scan revealed a tumour in the orbital apex, extending intradurally. With a suspected diagnosis of a neoplastic lesion, the patient underwent orbital surgery with optic nerve decompression. Histology revealed an aspergilloma. No other foci were seen and treatment with antifungals was started. In immunocompromised patients with intracranial tumours, infection is always a major consideration in the differential diagnosis, even if the reason for immunosuppression (in this case chemotherapy) dates back several months. Misdiagnosing an orbital apex lesion as a cancer and treating patients primarily with corticosteroids can be life threatening. Removal or biopsy of such lesions is essential in further treatment since antifungals have to be administered as fast as possible. S Afr Med J 2016;106(4):354-355. DOI:10.7196/SAMJ.2016v106i4.9936

Aspergillosis of the brain is very rare, and usually seen in immuno compromised or immunosuppressed patients.[1] Cases where aspergill omas affect the orbital apex are more rare and a literature search

offers only 13 search results. Orbital aspergillomas are associated with infections of the paranasal sinuses. The spores are commonly airborne and inhaled by the host, causing infection of the respiratory system.[2,3]

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IN PRACTICE

Fig. 2. Connective tissue with dense mononuclear infiltrate predominantly composed of neutrophil granulocytes and adjacent cellular detritus (haematoxylin eosin staining, 20-fold image magnification).

Fig. 1. Cranial CT showing a tumourous mass in the left orbital apex (white arrow).

Aspergillus flavus may gain access to the cen tral nervous system (CNS) via haematogenous spread or direct spread from the paranasal sinuses.[2] The ethmoidal and sphenoidal sinuses are usually the loci of the infection, which in immunocompromised individuals, runs a fulminant course unlike the insidious onset in healthy patients.[4] Invasive aspergillosis is a disease of concern, as it is a leading cause of death in patients with haematological malignancies, immunocompromised patients and transplant recipients.[5] Diagnosis requires a high index of suspicion and needs special treatment with mandatory biopsy or the surgical removal of lesions close to the orbit, especially in immunocompromised patients. Antifungal therapy should start as soon as possible after diagnosis. We present a case of a patient treated with chemotherapy for a cutaneous lymphoma who developed an orbital apex syndrome 6 months after his last chemotherapy cycle.

Case report

A 57-year-old patient with features suggestive of an orbital apex syndrome for approximately 5 weeks presented to our department. The main complaints were double vision, opthalmoplegia and visual disturbance. Two days prior to admission he lost vision in the left eye. A cranial computed tomography (CT) scan was performed and a mass around the left orbital apex invading the superior orbital fissure and the optic canal with intradural growth could be seen (Fig. 1). A diagnosis of metastasis was entertained in view of the patient’s background history of cutaneous B-cell lymphoma. No signs of paranasal sinus infection were seen. Corticosteroid therapy had been initiated and the patient was scheduled for tumour removal and optical nerve decompression. The mass was completely excised, and the immediate

postoperative period was uneventful. However, histology of the excised mass revealed it to be an aspergilloma. Corticosteroids were ceased and intravenous antifungal therapy was imme diately initiated. The patient recovered rapidly, particularly his visual problems. Further investigations did not reveal other lesions. Paranasal sinuses, lungs and abdomen were free of any suspicious findings.

Discussion

Aspergillomas of the orbit were reported more often in the 1960s and 1970s and less in the 1980s and 1990s. There was an increase in reports in the first decade of the 20th cen tury. With more efficient antimycotic agents, the incidence of mycotic orbital infections decreased between 1980 and 2000. There was an increase in incidence from 2000 to 2010 since aggressive chemotherapeutic regimens and HIV led to seriously immunocomprom ised patients. [6] However, diagnostic imaging became much more efficient and the lesions could be more easily seen. Since we now have the diagnostic tools to identify such lesions and an increased report rate, the way to avoid fatal misdiagnosis and incorrect treatment strategies is to consider these entities during our differential diagnostic algorithm. In a number of cases, infections began in one of the near sinuses and they could be granulomatous or non-granulomatous.[7] The granulomatous entities can cause a proptosis as well as other clinical signs, whereas the nongranulomatous may be asymptomatic. [3,8] More importantly, even histologically the fungus granuloma of the orbit could be misdiagnosed as a pseudotumour when not specially stained.[3] The granulomatous appearance on haematoxylin eosin staining is that of connective tissue with dense mononuclear infiltrate (Fig. 2). Treating such a patient for a tumour could allow the fungus to grow and prove fatal. In a very honest case report from 1970, the authors reported a case of a 40-year-old female patient with a proptosis who was diagnosed as having

April 2016, Print edition

Fig. 3. Grocott staining reveals septated fungal hyphae, partially showing branching with an angle of 45° as it is seen in Aspergillus spp. (20fold image magnification).

a pseudotumour. [7] Steroid and antimicrobial therapy did not improve the patient’s condition. The authors proceeded with an orbitotomy and suspected a tuberculoma. However, after the treatment with antituberculotics failed to have any effect, they reviewed and scrutinised the histological specimen; on Gridley’s stain they diagnosed an aspergilloma. They could not treat the patient with antimycotics, however, because she was lost to follow-up.[7] The authors had only X-ray imaging in their armamentarium and did not give up on questioning their own diagnosis since in close follow-up, no effects of their treatment could be seen. What led to the right diagnosis was persistent follow-up, doubting their diagnosis and correcting it and the permanent suspicion of another agent than the usual ones. In addition they were brave enough to share their mistakes and publish. We should feel obliged to share our experiences with such rare diseases, to avoid mistreatment, and to make the right diagnosis with specific staining patterns (Fig. 3), and to choose the right therapies. High index of suspicion of possibility of fungal infection in immunocompromised patients, avoidance of steriods coupled with early surgical decompression and commencement of antifungal treatment leads to an improved outcome. 1. Chowdhury FH, Haque MR, Khan SK, Alam SM. Cerebral aspergilloma in a SLE patient: A case report with short literature review. Asia J Neurosurg 2014;9(2):58-61. DOI:10.4103/1793-5482.136710 2. Rudwan MA, Sheikh HA. Aspergilloma of paranasal sinus – a common cause of unilateral proptosis in Sudan. Clin Radiol 1976;27(4):497-502. DOI:10.1016/S0009-9260(76)80116-X 3. Barr A, Nolan M, Grant W, Costello C, Petrou MA. Rhinoorbital and pulmonary zygomycosis post pulmonary aspergilloma in a patient with chronic lymphocytic leukemia. Acta Biomed 2006;77(Suppl 4):13-18. 4. Naik MN, Vemuganti GK, Honavar SG. Primary orbital aspergilloma of the exenterated orbit in an immunocompromized patient. Indian J Med Microbiol 2006;24(3):233-234. 5. Segal BH. Aspergillosis. N Engl J Med 2009;360(18):1870-1884. DOI:10.1056/NEJMra0808853 6. Busch M, Weiler H, Frühmorgen P, Rühl U, Roos W. Paranasal sinus mycetoma with orbital involvement in a patient with AIDS. Bildgebung 1995;62(3):199-201. 7. Chandra P, Ahluwalia BK, Chugh TD. Primary orbital aspergilloma. Br J Ophthalmol 1970;54:693-696. 8. Goel A, Nadkarni T, Desai AP. Aspergilloma in the paracavenous region – two case reports. Neurol Med Chir (Tokyo) 1996;36(10):733-736. DOI:10.2176/nmc.36.7330

Accepted 3 October 2015.

IN PRACTICE

CASE REPORT

Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion L Mbonile, MB ChB, MPH, Pg Dipl (HIV/AIDS Management) Anatomy and Histopathology, Medical Biosciences Department, University of the Western Cape, Cape Town, and Mbeya Referral Hospital, Ministry of Health and Social Welfare, Mbeya, Tanzania Corresponding author: L Mbonile (lmbonile@uwc.ac.za)

Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion. S Afr Med J 2016;106(4):356-358.DOI:10.7196/SAMJ.2016.v106i4.9896

Autoimmune progesterone dermatitis (APD) is a rare condition, characterised by recurrent premenstrual cyclic eruptions.[1] It may present with a variety of cutaneous and mucosal manifestations but urticaria, erythema multiforme, eczematous, and vesicular or papulovesicular eruptions are the most common. APD is considered to be a hypersensitivity reaction to an increased level of endogenous progesterone during the luteal phase of the menstrual cycle. Exposure to exogenous progesterone plays a big role in the pathogenesis of APD. APD was first reported by Gerber[1] in 1921.[2,3]

Clinical examination revealed urticaria, pete chiae and palpable pinpoint purpura lesions, distributed over the legs, forearms, neck and buttocks (Fig. 1, A - D). The pre sumptive diagnosis of autoimmune proges terone dermatitis was made. An intradermal skin test using 0.1 cc of progesterone was performed. The patient immediately deve A

loped a wheal, confirming the diagnosis of APD. She was reluctant to have a skin biopsy. No abnormal values were found in the routine blood chemistry and hormonal examinations. A continuous regimen of an oral contra ceptive pill with 30 mg ethinyl oestradiol and 0.15 mg of levonorgestrel was started on the C

Case report

A 30-year-old black, uniparous woman with no significant past dermatological history and no prior exogenous hormone presented at the clinic complaining of persistent cyclic skin eruptions and urticaria of over 2 months. She reported that symptoms started immediately before getting her normal menstrual cycle after medical abortion. She noted that the pruritic skin lesions were exacerbated 4 - 5 days before the onset of her menses, lasted for ~5 days, and partially improved within 1 - 2 days after the end of the menses. There was no complete clearance of the lesions between menstrual cycles. When she first reported the symptoms to her GP, the initial diagnosis was allergic contact dermatitis and topical steroids were prescribed but only slight improvement was shown.

B D

Fig. 1. Autoimmune progesterone dermatitis. Pruritic, erythematous, and urticarial papules on (A) left forearm; (B) right forearm; (C) left leg; and (D) left side of the neck and face.

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IN PRACTICE

patient. The skin eruptions have not returned since the initiation of this therapy. The medical report request was sent to her first GP and he confirmed that the medical abortion was induced using mifepristone 600 mg with tabs misoprostol (400 mg start then 200 mg three times a day for 4 days). Routine serum β hCG tests, antibiotics and anti-pain medications were also prescribed. APD manifests via the occurrence of cyclic skin eruptions. Women with the disorder commonly present with dermatological lesions in the luteal phase of the menstrual cycle.[4,5] Diagnosis of APD is confirmed by performing a skin allergen test using progesterone.[5] Due to its rarity, APD should be considered a diagnosis of exclusion.[6-9] In this case, we believe symptoms occurred as a result of increased hypersensitivity to endogenous progesterone, triggered immediately after medical abortion.

Discussion

Hormones of the anterior pituitary gland are relatively inactive prior to puberty. They are usually released 2 - 3 years prior to puberty after the initial release of gonadotropin-releasing hormone (GnRH) by the hypothalamus.[10] It is still uncertain what triggers this sudden increase in GnRH a few years after puberty. GnRH is released in a rhythmic, pulsatile manner resulting in the pulsatile release of luteinising hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary gland.[10-12] The primary function of FSH is to stimulate the granulosa cells of the ovary to synthesise oestrogen.[12] For transformation of the oestrogen-secreting stromal cells of the ovary to progestogen-secreting cells, LH is needed. Apart from the stimulation of progesterone production, LH is essential for final oocyte maturation and the trigger of ovulation.[10] Progesterone is secreted by the ovary mainly from the corpus luteum during the second half of the menstrual cycle.[11] Secretion actually begins just before ovulation from the follicle that is destined to release an ovum. Progesterone, like all other steroid hormones, is synthesised from pregnenolone, which in turn is derived from cholesterol. It occurs in the ovary, testes, adrenal cortex [10,11] and placenta. The stimulatory effect of LH on progesterone synthesis and secretion by the corpus luteum is mediated by a membrane-bound receptor linked to a G-protein-coupled signal transduction pathway that increases the synthesis of cyclic adenosine monophosphate (AMP) by the stimulation of adenylyl cyclase. [13] If the ovum is fertilised, implantation takes place about 7 days later, and almost at once the developing trophoblast begins secreting human chorionic gonadotropin (hCG) into the maternal circulation, thereby sustaining the functional life of the corpus luteum. During the second or third month of pregnancy, the developing placenta begins to secrete oestrogen and progesterone in collaboration with fetal adrenal glands, and thereafter the corpus luteum is not essential to continued gestation. Oestrogen and progesterone continue to be secreted in large amounts by the placenta up to the time of delivery. The rate of progesterone increases from a few mg per day secreted during the follicular phase of the cycle, to 10 - 20 mg during the luteal phase and to several hundred mg during the latter part of pregnancy.[6,10-12] APD is a rare disorder characterised by cyclic eruption of varying morphology and distribution.[9,14-16] The eruption is induced by hypersensitivity to endogenous progesterone, and typically occurs during the luteal phase of the menstrual cycle as serum levels of this hormone increase. Partial to complete resolution occurs within days of menstruation, with recurrence during the next menstrual cycle. The eruption may be localised or generalised. Sensitisation with exogenous oestrogen in oral contraceptives may be an inciting factor in some cases.[8,9,17] Pregnancy may either worsen or improve the condition.[6,9] APD symptoms range from minor to severe skin

Table 1. Treatment options used in APD Treatment

Advantage(s)

Pharmacological OCPs

Usually tried as initial therapy

Antihistamines

Fewer side-effects than most other therapies Well tolerated, few side-effects

Conjugated oestrogens

Avoids progesterone component of OCPs

Glucocorticoids

Able to suppress multiple components of the immune system Can be combined with other therapies

GnRH agonists

Often used if OCPs and glucocorticoids are not effective

Alkylated steroids

Can be combined with low-dose steroids

Tamoxifen

Interferes with gonadal hormone receptors Has been used successfully in patients unresponsive to conjugated oestrogen

Surgical Bilateral oophorectomy

Definitive treatment, used if medical options unsuccessful

OCPs = oral contraceptives.

presentations to severe systemic complications such as symptoms of asthma or anaphylaxis.[6,18-20] Dermatological manifestations of APD include: urticaria, angio-oedema, eczema, erythema multiforme, stomatitis, folliculitis, papulopustular/papulovesicular lesions, Stephens-Johnson syndrome, vesiculobullous reactions, dermatitis herpetiformis-like rash and mucosal lesions. The pathogenesis of APD is unknown. It is believed both endo- and exogenous progesterones at some stage stimulate immunoglobulin E (IgE) synthesis. This mechanism has still not been clearly investigated, especially on endogenous progesterone.[21-24] Some authors have suggested that hydrocortisone or 17-α-hydroxyprogesterone have cross-sensitivity with progesterone and may cause initial sensitisation, but this has not been observed in all studies.[6,9] Some researchers have linked APD with specific antibodies, this having been established by using immunofluorescent techniques and basophil degranulation tests. Skin test results with progesterone have shown immediate reactions (within 30 minutes), delayed reactions (24 - 48 hours later) and reactions with both immediate and delayed features.[4,6,18,25] This presumably indicates both type I and type IV hypersensitivity reactions. Progesterone has also been reported to have a direct histamine-releasing effect on mast cells and in one study found an in vitro increase of an interferon-γ release assay, likely from TH1-type cytokines. Other researchers have correlated the presence of APD skin conditions with increased eosinophils levels.[4,6,18,25] In this case the first clinicians failed to link the appearance of current symptoms with APD. This is very common to many patients with APD. The peculiarity of this case is on the timing, as the symptoms started immediately after the induction of medical abortion with mifepristone. Mifepristone (RU 486) is a derivative of the 19-norprogestin norethindrone containing a dimethyl-aminophenyl substituent at the 11β-position.[13,26] It is a potent competitive antagonist of both progesterone and glucocorticoid, binding to their respective receptors. When administered in the early stages of pregnancy,

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mifepristone causes decidual breakdown by blocking the uterine progesterone receptors. This leads to the detachment of the blastocyst, which decreases HCG production. This in turn causes a decrease in progesterone secretion from the corpus luteum, which further accentuates decidual breakdown. Decreased endogenous progesterone coupled with the blockage of progesterone receptors in the uterus increases uterine prostaglandin levels and sensitises the myometrium to the contractile actions of prostaglandins.[26] Mifepristone also affects ovulation. If given accurately in the mid- to late-follicular phase, it delays follicle maturation and the LH surge, and ovulation occurs later than normal.[13,26] Blockage of progesterone receptors by the mifepristone triggers the decrease of progesterone levels in the body. One month after the abortion, the patient expected normal menstrual flow, but this did not happen. This might explain the further drop in oestrogen and progesterone levels or the decrease in sensitivity of the receptors after mifepristone blockage. This might have been taken as normal menstrual flow irregularity, but it explains the decrease from normal levels as a result of medical abortion. Most of the receptors in the body have a common characteristic of increasing or accelerating the action of the hormone or chemical immediately after the blockage or when the hormone levels increase above the normal level. [11,12] Increased receptor sensitivity after blockage is very common. Sensitivity increase from endogenous progesterone after mifepristone blockage can also be due to a negative feedback mechanism as a result of the production of progesterone. With the decrease in the level of progesterone immediately after medical abortion, the hormonal control mechanism of the progesterone might have shifted and caused an abrupt increase in the production of the hormone at the corpus luteum and adrenal cortex, causing APD. This can be explained by the increase of sensitivity to progesterone confirmed by the skin allergen test. As explained above, the pathogenesis of APD is not clearly known, but in this case the increase in progesterone levels 1 month after medical abortion might have stimulated the IgE synthesis, hence causing both type I and type IV hypersensitivity reactions. APD is usually resistant to conventional therapy such as anti histamines.[6] The use of systemic glucocorticoids, usually in high doses, has been reported to control the cutaneous lesions of APD in some cases.[4,6,18,25] This patient was also treated with topical steroids prior to our confirmed diagnosis. Several treatment modalities have been used in the treatment of APD. The most used are the ones that attempt to inhibit the secretion of endogenous progesterone by the suppression of ovulation.[2,6] Table 1 lists some of the pharmacological and surgical strategies used in APD management. OCPs are often tried as initial therapy, but have had limited success, possibly due to the fact that virtually all OCPs have a progesterone component.[6] In this case, OCPs worked very well and there was no need to change the regimen. Some clinicians also reported using conjugated oestrogens. However, due to the increased risk of endometrial carcinoma with unopposed conjugated oestrogens, this treatment is not commonly used.[2,6,27] GnRH agonists, such as buserelin and triptorelin, have been used to induce remission of symptoms by causing ovarian suppression.[6,28-30] However, side-effects include symptoms of oestrogen deficiency (hot flushes, vaginal dryness and decreased bone mineral density) and oestrogen supplementation may be needed.[6,25] Alkylated steroids such as stanozol have been used to successfully suppress ovulation, sometimes in combination with chronic low doses of corticosteroids. Side-effects of alkylated steroids include abnormal facial or body hair growth, hepatic dysfunction and mood disorders.[6] Thorough evaluations should be made if these are given to a patient.

In many cases, anti-oestrogens have been used, most commonly tamoxifen, which can also suppress ovulation.[8,31] Though reported to be used by many clinicians, tamoxifen has shown to be associated with symptoms of oestrogen deficiency and increased risk of venous thrombosis and cataract formation. Extra monitoring is important if it is given to patients with high risk.[6,8,31] Surgery has been used in some severe cases of APD. This line of management is usually taken after medical options have failed. Bilateral oophorectomy is normally used to control severe forms of APD symptoms.[6,8,31]

Conclusion

This was a case of APD which was triggered by increased sensitivity of endogenous progesterone caused by medical abortion. A positive intradermal test with progesterone confirmed the diagnosis, and the response to oral contraceptives was prompt and dramatic. This is one of the rare cases of APD that was induced immediately after a successful medical abortion. 1. Gerber J. Desensitization in the treatment of menstrual intoxication and other allergic symptoms. Br J Dermatol 1930;51(6):265-268. 2. George R, Badawy SZ. Autoimmune progesterone dermatitis: A case report. Case Rep Obstet Gynecol 2012;2012:757854. DOI:10.1155/2012/757854 3. Halevy S, Cohen AD, Lunenfeld E, Grossman N. Autoimmune progesterone dermatitis manifested as erythema annulare centrifugum: Confirmation of progesterone sensitivity by in vitro interferongamma release. J Am Acad Dermatol 2002;47(2):311-313. DOI:10.1186/1476-7961-2-10 4. Kakarla N, Zurawin RK. A case of autoimmune progesterone dermatitis in an adolescent female. J Pediatr Adolesc Gynecol 2006;19(2):125-129. DOI:10.1016/j.jpag.2006.01.050 5. Rasi A, Khatami A. Autoimmune progesterone dermatitis. Int J Dermatol 2004;43(8):588-590. DOI:10.1111/j.1365-4632.2004.02155.x 6. Baptist AP, Baldwin JL. Autoimmune progesterone dermatitis in a patient with endometriosis: Case report and review of the literature. Clin Mol Allergy 2004;2(1):10. DOI:10.1186/1476-7961-2-10 7. Bernstein IL, Bernstein DI, Lummus ZL, Bernstein JA. A case of progesterone-induced anaphylaxis, cyclic urticaria/angioedema, and autoimmune dermatitis. J Womens Health (Larchmt) 2011;20(4):643648. DOI:10.1089/jwh.2010.2468 8. Poffet F, Abraham S, Taramarcaz P, Fontao L, Borradori L. Autoimmune progesterone dermatitis: Potential role of cutaneous angiogenin expression? Dermatology 2011;223(1):32-35. DOI:10.1159/000329427 9. Walling HW, Scupham RK. Autoimmune progesterone dermatitis. Case report with histologic overlap of erythema multiforme and urticaria. Int J Dermatol 2008;47(4):380-382. DOI:10.1111/j.1365-4632.2008.03395.x 10. Odendaal H. Physiology. In: Odendaal H, Schaetzing A, Kruger T, eds. Clinical Gynaecology. 2nd ed. Cape Town: Juta Academic, 2008:71-80. 11. Ganong WF, Barrett KE. Review of medical physiology. New York: McGraw-Hill Medical, 2005:415-457. 12. Hall JE. Guyton and Hall Textbook of Medical Physiology. 12th ed. Philadelphia: Saunders Elsevier, 2011:1003-1015. 13. Williams C, Stan G. Estrogens and progestins. In: Joel Hardman LK, Perry Molinoff, Raymond Ruddon, Alfred Gilman, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 9th ed. New York: McGraw-Hill, 1996:1411-1437. 14. Prieto-Garcia A, Sloane DE, Gargiulo AR, Feldweg AM, Castells M. Autoimmune progesterone dermatitis: Clinical presentation and management with progesterone desensitization for successful in vitro fertilization. Fertil Steril 2011;95(3):9-13. DOI:10.1016/j.fertnstert.2010.10.038 15. Shelley WB, Shelley ED, Talanin NY, Santoso-Pham J. Estrogen dermatitis. J Am Acad Dermatol 1995;32(1):25-31. DOI:10.1016/0190-9622(95)90179-5 16. Stephens CJ. Perimenstrual eruptions. Clin Dermatol 1997;15(1):31-34. DOI:10.1016/S0738081X(96)00107-1 17. Pereira A, Coker A. Hypersensitivity to Mirena – a rare complication. J Obstet Gynaecol 2003;23(1):81. 18. Jenkins J, Geng A, Robinson-Bostom L. Autoimmune progesterone dermatitis associated with infertility treatment. J Am Acad Dermatol 2008;58(2):353-355. DOI:10.1016/j.jaad.2007.10.646 19. Le K, Wood G. A case of autoimmune progesterone dermatitis diagnosed by progesterone pessary. Australas J Dermatol 2011;52(2):139-141. DOI:10.1111/j.1440-0960.2011.00753.x 20. McCalmont TH. Fact or fiction? J Cutan Pathol 2010;37(11):1130-1131. DOI:10.1111/j.16000560.2010.01616.x 21. Anderson RH. Autoimmune progesterone dermatitis. Cutis 1984;33(5):490-491. 22. Chawla SV, Quirk C, Sondheimer SJ, James WD. Autoimmune progesterone dermatitis. Arch Dermatol 2009;145(3):341-342. DOI: 10.1001/archdermatol.2008.605 23. Nasabzadeh TJ, Stefanato CM, Doole JE, Radfar A, Bhawan J, Venna S. Recurrent erythema multiforme triggered by progesterone sensitivity. J Cutan Pathol 2010;37(11):1164-1167. DOI:10.1111/j.16000560.2010.01607.x 24. Németh H1, Kovács E, Gödény S, Simics E, Pfliegler G. Autoimmune progesterone dermatitis diagnosed by intravaginal progesterone provocation in a hysterectomised woman. Gynecol Endocrinol 2009;25(6):410-412. DOI:10.1080/09513590902770164 25. Wintzen M, Goor-van Egmond MB, Noz KC. Autoimmune progesterone dermatitis presenting with purpura and petechiae. Clin Exp Dermatol 2004;29(3):316. DOI:10.1111/j.1365-2230.2004.01516.x 26. Ebadi MS. Desk Reference of Clinical Pharmacology. Florida: CRC Press, 2008. 27. Sasseville D, Wilkinson RD, Schnader JY. Dermatoses of pregnancy. Int J Dermatol 1981;20(4):223241. DOI:10.1111/j.1365-4362.1981.tb04327.x 28. Cocuroccia B, Gisondi P, Gubinelli E, Girolomoni G. Autoimmune progesterone dermatitis. Gynecol Endocrinol 2006;22(1):54-56. DOI:10.1080/09513590500216735 29. Dedecker F, Graesslin O, Quereux C, Gabriel R, Salmon-Ehr V. Autoimmune progesterone dermatitis: A rare pathology. Eur J Obstet Gynecol Reprod Biol 2005;123(1):120-121. DOI:http://dx.doi. org/10.1016/j.ejogrb.2005.03.007 30. Hill JL, Carr TF. Iatrogenic autoimmune progesterone dermatitis treated with a novel intramuscular progesterone desensitization protocol. J Allergy Clin Immunol Pract 2013;1(5):537-538. DOI:10.1016/j. jaip.2013.06.005 31. Teelucksingh S, Edwards CR. Autoimmune progesterone dermatitis. J Intern Med 1990;227(2):143144. DOI:10.1111/j.1365-2796.1990.tb00133.x

Accepted 2 December 2015.

April 2016, Print edition

RESEARCH

Where do children die and what are the causes? Under-5 deaths in the Metro West geographical service area of the Western Cape, South Africa, 2011 A E Reid,1 MB ChB, FCPaed (SA), MMed (Paed), DCH (SA); M K Hendricks,1 MB ChB, MMed (Paed), MTropPaed (LSTM, UK), DCH (SA); P Groenewald,2 MB ChB, MPH; D Bradshaw,2 D Phil (Oxon) 1 2

epartment of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, South Africa D Medical Research Council Burden of Disease Research Unit, Cape Town, South Africa

Corresponding author: A E Reid (reid_dr@yahoo.ie) Background. Accurate child mortality data are essential to plan health interventions to reduce child deaths. Objectives. To review the deaths of children aged <5 years during 2011 in the Metro West geographical service area (GSA) of the Western Cape Province (WC), South Africa, from routine data sources. Methods. A retrospective study of under-5 deaths in the Metro West GSA was done using the WC Local Mortality Surveillance System (LMSS), the Child Healthcare Problem Identification Programme (Child PIP) and the Perinatal Problem Identification Programme (PPIP), and linking where possible. Results. The LMSS reported 700 under-5 deaths, Child PIP 99 and PPIP 252, with an under-5 mortality rate of 18 deaths per 1 000 live births. The leading causes of death were pneumonia (25%), gastroenteritis (10%), prematurity (9%) and injuries (9%). There were 316 in-hospital deaths (45%) and 384 out-of-hospital deaths (55%). Among children aged <1 year, there were significantly more pneumonia deaths out of hospital than in hospital (144 (49%) v. 16 (6%); p<0.001). Among children aged 1 - 4 years there were significantly more injury-related deaths out of hospital than in hospital (43 (47%) v. 4 (9%); p<0.001). In 56 (15%) of the cases of outof-hospital death the child had visited a public healthcare facility within 1 week of death. Thirty-six (64%) of these children had died of pneumonia or gastroenteritis. Conclusions. Health interventions targeted at reducing under-5 deaths from pneumonia, gastroenteritis, prematurity and injuries need to be implemented across the service delivery platform in the Metro West GSA. It is important to consider all routine data sources in the evaluation of child mortality. S Afr Med J 2016;106(4):359-364. DOI:10.7196/SAMJ.2016.v106i4.10521

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.10521

Antiretroviral therapy programme outcomes in Tshwane district, South Africa: A 5-year retrospective study N Mlangeni, MPH, BCur; F Senkubuge, MB ChB, MMed (Public Health), FCPHM (SA) School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, South Africa Corresponding author: N Mlangeni (milo.mlangeni@yahoo.com)

Background. Scaling up of antiretroviral therapy (ART) in South Africa (SA) has resulted in an increase in the number of patients on the national ART programme and an increased workload for ART service providers nationwide. Objectives. To ascertain patient retention on ART after 5 years on treatment in one district of Gauteng Province, SA, establish the number of patients who remained alive on ART after 5 years of treatment, and identify patient-related factors that contributed towards the outcome of each indicator. Methods. A retrospective cohort study of patients initiated on highly active antiretroviral therapy (HAART) between January and March 2007 was carried out. A sample of 381 patients was randomly selected from 1 004 records, and their records were reviewed for visits over the previous 60 months. Summary statistics, Pearsonâ&#x20AC;&#x2122;s Ď&#x2021;2 test and linear regression tests were performed. Results. Of 381 patients, 156 (40.9%) remained alive and active on HAART at their initial sites. The overall mortality rate was 5.0% and the rate of long-term retention in care was 57.4%, excluding those transferred to another site. After 6 months on HAART the mean rise in

April 2016, Print edition

RESEARCH

CD4 count was 113 cells/µL, and after 60 months it was 288 cells/µL. Viral load suppression to <400 copies/mL was achieved in 74.0% of patients at 6 months and 91.0% at 60 months. Conclusions. Immunological and virological outcomes after 5 years on treatment were good. Both these positive outcomes showed that the ART programme was a success. Improved data quality and patient follow-up will further strengthen programme outcomes. S Afr Med J 2016;106(4):365-368. DOI:10.7196/SAMJ.2016.v106i4.9375

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.9375

Clinician compliance with laboratory monitoring and prescribing guidelines in HIV 1-infected patients receiving tenofovir R de Waal,1 MB ChB; K Cohen,2 MB ChB, MSc, MMed, FCFP (SA); M P Fox,3,4 PhD; K Stinson,1,5 PhD; G Maartens,2 MB ChB, MMed, FCP (SA); A Boulle,1 MB ChB, PhD; M-A Davies,1 MB ChB, PhD entre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Faculty of Health Sciences, C University of Cape Town, South Africa 2 Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 3 Boston University Center for Global Health and Development, Boston, USA 4 Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 5 Médecins Sans Frontières, Khayelitsha, Cape Town, South Africa 1

Corresponding author: M-A Davies (mary-ann.davies@uct.ac.za)

Background. Tenofovir is part of the preferred first-line regimen for HIV-infected patients in South Africa (SA), but is associated with kidney toxicity. SA antiretroviral therapy (ART) guidelines recommend creatinine monitoring at baseline (ART start) and at 3, 6 and 12 months, and substituting tenofovir with zidovudine, stavudine or abacavir should creatinine clearance (CrCl) decrease to <50 mL/min. Objective. To assess clinician compliance with tenofovir monitoring and prescribing guidelines. Methods. We described the proportion of adult patients on tenofovir-based first-line ART who were screened for baseline renal impairment, were monitored according to the SA antiretroviral treatment guidelines, and were switched from tenofovir if renal function declined. Results. We included 13 168 patients who started ART from 2010 to 2012. Creatinine concentrations were recorded in 11 712 (88.9%) patients on tenofovir at baseline, 9 135/11 657 (78.4%) at 3 months, 5 426/10 554 (51.4%) at 6 months, and 5 949/ 8 421 (70.6%) at 12 months. At baseline, 227 (1.9%) started tenofovir despite a CrCl <50 mL/min. While on tenofovir, 525 patients had at least one CrCl of <50 mL/min. Of 382 patients with ≥3 months’ follow-up after a CrCl <50 mL/min, 114 (29.8%) stopped tenofovir within 3 months. Clinicians were more likely to stop tenofovir in patients with lower CrCl and CD4 count. Of 226 patients who continued to receive tenofovir and had further CrCls available, 156 (69.0%) had a CrCl ≥50 mL/min at their next visit. Conclusions. Creatinine monitoring is feasible where access to laboratory services is good. Kidney function recovered in most patients who continued to receive tenofovir despite a CrCl <50 mL/min. Further research is needed to determine how best to monitor renal function with tenofovir in resource-limited settings. S Afr Med J 2016;106(4):369-371. DOI:10.7196/SAMJ.2016.v106i4.10153

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.10153

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RESEARCH

The S’Khokho ‘bushcan’ initiative: Kick a bush and condoms fall out J Pienaar, MSc S’Khokho Community Health, KwaZulu-Natal, South Africa Corresponding author: J Pienaar (jpienaar@skhokho.org)

Background. People living in rural areas have limited access to condoms owing to distance, cost and time involved in travelling to public health facilities, around which most condom distribution efforts are centralised. Objective. In an effort to increase access to condoms in these areas, we explored the feasibility and efficacy of condom distribution by placing ‘condocans’ on trees along informal footpaths used by residents. Methods. From October 2012, steel condocans, typically seen in clinic settings, were erected on trees along pathways in bushy areas with high levels of foot traffic at several rural locations in the uMgungundlovu district of KwaZulu-Natal Province, South Africa (SA). Because of their location, the condocans were referred to as ‘bushcans’. Condom uptake was closely monitored, and the bushcans were restocked when necessary. Results. Following the introduction of the bushcans, male condom distribution increased by 237% from October 2012 to December 2012. Condom distribution in these areas increased on average by 187% from October 2012 to October 2015, with more than 408 000 condoms distributed over the 3-year period using the bushcans alone. Discussions with residents revealed that they were pleased about the increased access to condoms via the bushcans, and they recommended other areas for potential implementation of this initiative. Conclusions. The bushcan initiative highlighted the fact that condoms are not as easily accessible to all South Africans as is often thought. By providing access to condoms in a discreet and convenient manner, the bushcans have the potential to increase access to condoms in other rural and periurban areas in SA where communities face similar barriers to access. S Afr Med J 2016;106(4):372-373. DOI:10.7196/SAMJ.2016.v106i4.10146

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.10146

Piloting a national laboratory electronic programme status reporting system in Ekurhuleni health district, South Africa N Cassim, MPH; L M Coetzee, PhD; D K Glencross, MB BCh, MMed (Haematology) National Health Laboratory Service, National Priority Programme, Johannesburg, South Africa, and Department of Haematology and Molecular Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg Corresponding author: N Cassim (naseem.cassim@nhls.ac.za)

Background. The National Health Laboratory Service (NHLS) performs ~4 million CD4 tests per annum for the public health sector at 61 CD4 testing laboratories across South Africa. Currently, CD4 laboratory data captured do not differentiate between antiretroviral treatment (ART) and pre-ART care. Methods. A cross-sectional study was undertaken to evaluate a redesigned Comprehensive Care, Management and Treatment of HIV and AIDS (CCMT) request form, incorporating a two-tick collection procedure linking the CD4 test request to patient CCMT programme status. Field testing was undertaken at three health facilities, where healthcare personnel were required to capture whether the CD4 count requested was a ‘first-ever CD4’, ‘CD4 taken previously, not yet in ART care’ or ‘in ART care’. All data were extracted from the NHLS Corporate Data Warehouse and analysed using Microsoft Excel and Stata-12. Results. A substantial increase in the number of request forms with a CCMT programme status (28.1% v. 84.4%) was reported pre- and post-implementation. Post-implementation data (N=1 004) revealed that 30.8% patients were ART naive (‘first-ever CD4’), with 7.4% ‘not yet on ART’ (median CD4 counts of 150 and 328 cells/µL, respectively). Patients on ART comprised 61.9% of the study group

April 2016, Print edition

RESEARCH

(median CD4 count ~346 cells/µL). Sixty percent of patients were aged between 30 and 44 years, and females predominated (male/ female ratio 0.7:1). Conclusions. A simple modification to the CCMT request form can successfully facilitate collection of programme status. For national implementation, it would be advantageous to have a unique patient identifier to further enhance laboratory-based programmatic monitoring and evaluation. S Afr Med J 2016;106(4):374-377. DOI:10.7196/SAMJ.2016.v106i4.10066

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.10066

A deadly combination – HIV and diabetes mellitus: Where are we now? S Pillay,1 MB ChB, FCP (SA), MMed; C Aldous,2 PhD; F Mahomed,1 MB ChB, FCP (SA), FRCP, Cert Endocrinology 1 2

Department of Internal Medicine, Edendale Hospital, Pietermaritzburg, South Africa School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa

Corresponding author: S Pillay (drspillay@iafrica.com)

Background. The combination of HIV infection and diabetes mellitus (DM) represents a collision of two chronic conditions. Both HIV and DM increase the risk of developing tuberculosis (TB). Health resources in developing countries are already under strain as a result of the TB epidemic and poor diabetic control would further worsen this epidemic. Optimal diabetic control provides one avenue of curbing the TB epidemic in developing countries. Objectives. To establish if there is a difference in blood pressure, lipid and glycaemic control and complications between HIV-infected and uninfected diabetic patients; and to compare characteristics among HIV-infected diabetic patients between those with optimal and suboptimal glycaemic control. Methods. This was a retrospective chart review of all patients who visited the Edendale Hospital diabetic clinic, Pietermaritzburg, from 1 October 2012 to 30 September 2013. Results. There were statistically significant differences noted in the following parameters between HIV-infected and uninfected diabetic patients: (i) mean HbA1c% (11.08% v. 10.14%, respectively); (ii) nephropathy defined by proteinuria (25.66% v. 15.43%); (iii) neuropathy (48.68% v. 42.10%); and (iv) Kidney Disease Outcomes Quality Initiative (KDOQI) stage ≥2 chronic kidney disease (30.87% v. 41.67%). There were no significant differences noted in the percentage of patients achieving the following target parameters between the two cohorts: (i) blood pressure (42.11% v. 35.62%); (ii) total cholesterol (36.84% v. 34.67%); and (iii) triglycerides (42.76% v. 40.19%). Within the HIV-infected diabetic cohort 85.23% displayed suboptimal glycaemic control. A significant percentage of HIV-infected diabetic patients on antiretroviral (ARV) therapy (89.36%) had suboptimal glycaemic control. HIV-infected female diabetic patients showed a significant increased waist circumference when compared with their HIV-uninfected counterparts. Conclusion. HIV-infected diabetic patients had significantly poorer blood sugar control and a higher incidence of neuropathy and nephropathy (when defined by overt proteinuria). There was a non-significant difference noted between the HIV-infected and uninfected diabetic patients with regard to blood pressure and lipid control. The majority of HIV-infected patients on ARVs failed to achieve target glycaemic control. Obesity remains a global challenge, as noted in both the HIV-infected and uninfected diabetic patients. S Afr Med J 2016;106(4):378-383. DOI:10.7196/SAMJ.2016.v106i4.9950

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.9950

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RESEARCH

The other side of surveillance: Monitoring, application, and integration of tuberculosis data to guide and evaluate programme activities in South Africa L J Podewils,1 MS, PhD; L Bronner Murrison,1,2 MPH, PhD; C Bristow,2,3 MSc, MPH, PhD; N Bantubani,2,3 MPH; L D Mametja,4 MPH ivision of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA D Global AIDS Program, Centers for Disease Control and Prevention, Pretoria, South Africa 3 Tuberculosis Research Unit, South African Medical Research Council, Durban, South Africa 4 Department of Tuberculosis Control, National Department of Health, Pretoria, South Africa 1 2

Corresponding author: L J Podewils (lpp8@cdc.gov)

Background. The importance of using surveillance data to monitor and evaluate programme activities has been emphasised in international policies for tuberculosis (TB) control. Objectives. A survey was conducted to assess the use of TB surveillance data to monitor and guide TB programme activities in South Africa (SA). Methods. As part of an evaluation of the SA national TB surveillance system, semi-structured interviews were conducted among TB staff at health facilities and offices in three provinces. At each site, all persons involved with TB care, management and surveillance were invited to participate. Results. At least one person (range 1 - 4) was interviewed at 47/54 health facilities (87.0%), 11/13 subdistrict and district TB offices (84.6%), 2/3 provincial TB offices (66.7%), and at the national level (1/1, 100.0%).Â Of 119 TB staff, 64.7% recognised the purpose of TB surveillance as guiding programme planning, implementation and evaluation. However, only 16.0% reported using data to measure disease burden, 8.4% to monitor trends, and 9.2% to inform resource allocation. The majority reported using TB management tools provided by the national programme, but 44.5% also described using additional tools. Personnel mentioned the need for dedicated surveillance staff, training on recording and reporting, improved computer access, and methods to apply information from surveillance data to the programme. Conclusions. The majority of TB staff understood the purpose of surveillance but did not routinely use data to guide programme planning, implementation and evaluation. Training and supporting TB staff to utilise surveillance data will help improve the TB surveillance system. S Afr Med J 2016;106(4):394-398. DOI:10.7196/SAMJ.2016.v106i4.10207

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.10207

A randomised controlled trial comparing oxytocin and oxytocin + ergometrine for prevention of postpartum haemorrhage at caesarean section S Koen, BSc, MB BCh; L C Snyman, BMedSci, MB ChB, MMed (O&G), FCOG (SA), MPraxMed; R C Pattinson, BSc, MB BCh, FRCOG, MD, FCOG (SA), MMed (O&G), MRCOG; J A Makin, MB BCh, MSc (Clinical Epidemiology) Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, South Africa Corresponding author: S Koen (sandy.koen811@gmail.com)

Background. Globally 166 000 women die annually as a result of obstetric haemorrhage. More than 50% of these deaths occur in subSaharan Africa. Uterine atony is the commonest cause of severe postpartum haemorrhage (PPH). Bleeding at or after caesarean section (CS) is responsible for >30% of maternal deaths due to obstetric haemorrhage in South Africa (SA).

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Objective. To compare oxytocin alone with oxytocin + ergometrine in terms of primary prophylaxis for PPH at the time of CS. Methods. This was a double-blind randomised controlled interventional study comparing oxytocin with oxytocin + ergometrine admini stered during CS. Patients were randomised to receive oxytocin alone intravenously as a bolus or oxytocin + ergometrine intramuscularly, with the placebo being an injection of sterile water. The study population consisted of women undergoing CS at Kalafong Provincial Tertiary Hospital in Atteridgeville, Gauteng, SA. Results. Five hundred and forty women were randomised and data for 416 women, of whom 214 received oxytocin and 202 oxytocin + ergometrine, were available for analysis. In the oxytocin group 19 women (8.9%) required blood transfusion, compared with seven (3.5%) in the oxytocin + ergometrine group (p=0.01; relative risk = 2.78; 95% confidence interval 1.21 - 6.4). There were no statistically significant differences in the mean estimated visual and mean calculated blood loss. Conclusions. The overall need for blood transfusion was significantly reduced by about two-thirds in women receiving the oxytocin + ergometrine combination. Consideration should be given to using oxytocin + ergometrine for prophylaxis of PPH at CS. S Afr Med J 2016;106(4):399-402. DOI:10.7196/SAMJ.2016.v106i4.10133

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.10133

Evaluating current knowledge of legislation and practice of obstetricians and gynaecologists in the management of fetal remains in South Africa L du Toit-Prinsloo,1 MB ChB, DipForMed (SA) Path, FCForPath (SA), MMed (Path) (Forens); C Pickles,2 LLB, LLM, LLD; H Lombaard,3 MB ChB, MMed (OetG), FCOG (SA) epartment of Forensic Medicine, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa D South African Institute for Advanced Constitutional, Public, Human Rights and International Law, University of Johannesburg, South Africa 3 Department of Obstetrics and Gynaecology, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa 1 2

Corresponding author: L du Toit-Prinsloo (lorraine.dutoit@up.ac.za)

Background. In the clinical setting, the main legislative provisions governing the management and ‘disposal’ of fetal remains in South Africa are the Choice on Termination of Pregnancy Act 92 of 1996 and the Births and Deaths Registration Act 51 of 1992. Objectives. To determine obstetricians’ and gynaecologists’ current knowledge of this legislation. Current practice with regard to certification of death and methods of disposal of fetal material was also reviewed. Methods. A questionnaire-based study was conducted. The data collected included demographic details, qualifications, years of experience, working environment (public/private practice), responses to general questions reviewing knowledge of current legislation, and practical experience. Results. Seventy-six questionnaires were returned, with practitioners from the private and public sectors nearly equally represented. It was found that there is a concerning gap in obstetricians’ and gynaecologists’ knowledge of the law, and that some practitioners are acting outside the scope of the law. The study further revealed that patients’ needs are not properly accommodated under the current legislative provisions, because the law prevents certain remains from being respectfully managed. Conclusions. The study findings suggest that improved training of practitioners, together with possible law reform, are required to better serve the needs of patients. S Afr Med J 2016;106(4):403-406. DOI:10.7196/SAMJ.2016.v106i4.10214

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.10214

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Socioeconomic factors associated with asthma prevalence and severity among children living in low-income South African communities A R Yakubovich,1 MSc; L Cluver,2 PhD; R Gie,3 FCP (Paeds) hD student, Department of Social Policy and Intervention, University of Oxford, UK P Department of Social Policy and Intervention, University of Oxford, UK 3 Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa 1 2

Corresponding author: A R Yakubovich (alexa.yakubovich@spi.ox.ac.uk)

Background. Rates of asthma, poverty and social deprivation are high among young people in South Africa (SA), yet asthma interventions largely remain focused on biomedical factors. Objective. To investigate associations between socioeconomic factors and childhood asthma. Methods. We recruited 6 002 children aged 10 - 17 years from six low-income urban and rural sites in three SA provinces. Self-report questionnaires measured health status, sociodemographics and socioeconomic factors. Logistic regression and mediation analyses were used to test models of risk factors for asthma prevalence and severity (frequency of attacks). Results. Child anxiety (odds ratio (OR) 1.08; 95% confidence interval (CI) 1.04 - 1.12) and community violence (OR 1.14; 95% CI 1.00 1.30) were associated with increased odds of having asthma. Children doing more outdoor housework (OR 0.83; 95% CI 0.71 - 0.98) and living in greater poverty (OR 0.93; 95% CI 0.88 - 0.99) had lower odds of having asthma. Severe asthma was predicted by child depression (OR 1.14; 95% CI 1.03 - 1.26) and greater household poverty (OR 1.14; 95% CI 1.01 - 1.28). Most socioeconomic factors operated in â&#x20AC;&#x2DC;risk pathwaysâ&#x20AC;&#x2122;, wherein structural factors (e.g. urban living) were associated with individual factors (e.g. fewer outdoor tasks), which predicted greater odds of having asthma or severe exacerbations. Conclusions. This study suggests the need to consider the context of childhood asthma in SA for improved prevention and treatment. A multidisciplinary approach may be more effective than a biomedical model, given the plausible effects of psychosocial stress and poverty on asthma outcomes. S Afr Med J 2016;106(4):407-412. DOI:10.7196/SAMJ.2016.v106i4.10168

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i4.10168

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True (A) or false (B): SAMJ A multifaceted hospital-wide intervention increases hand hygiene compliance 1. In South Africa (SA), about one in seven patients entering health facilities may be at risk of developing a hospital-acquired infection. 2. An estimated 10 - 25% of patients admitted to hospitals in SA may acquire an infection. Where do children die and what are the causes? Under-5 deaths in the Metro West geographical service area of the Western Cape, SA, 2011 3. There are ample data on causes of death in children specific to districts and subdistricts available in SA. 4. About four times more child deaths are investigated at forensic mortuaries in the Western Cape than elsewhere in the country. Antiretroviral therapy programme outcomes in Tshwane district, SA: A 5-year retrospective study 5. It has been reported that non-retention of patients on antiretroviral therapy in the clinics of SA and the sub-Saharan region ranges from 30% to 40%. The burden of diabetes mellitus in KwaZulu-Natalâ&#x20AC;&#x2122;s public sector: A 5-year perspective (online only) 6. In SA, diabetes mellitus accounts for 58 deaths daily and is the fifth-highest cause of natural deaths. The other side of surveillance: Monitoring, application, and integration of tuberculosis (TB) data to guide and evaluate programme activities in SA 7. In this study 64.7% of staff recognised the purpose of TB surveillance as guiding programme planning, implementation and evaluation. 8. Information on patients confirmed to have TB disease based on a positive sputum smear for the presence of acid-fast bacilli is recorded on a paper TB Register.

A randomised controlled trial comparing oxytocin and oxytocin + ergometrine for prevention of postpartum haemorrhage at caesarean section 9. The overall need for blood transfusion was significantly reduced by about two-thirds in women receiving the oxytocin + ergometrine combination. Socioeconomic factors associated with asthma prevalence and severity among children living in low-income SA communities 10. Severe asthma was predicted by child depression and greater household poverty. CME Acute viral bronchiolitis in SA: Diagnostic flow 11. The clinical pattern of wheezing and hyperinflation in a young child is diagnostic of bronchiolitis. 12. Measurement of peripheral arterial oxygen saturation is useful to indicate the need for supplemental oxygen. 13. CXR is mandatory in a child admitted with bronchiolitis. 14. Complete blood counts have not been shown to be useful in either diagnosing bronchiolitis or guiding its therapy. 15. Infants under 1 year of age are at greatest risk of bronchiolitis. Acute viral bronchiolitis in SA: Strategies for management and prevention 16. There is currently no proven effective therapy for bronchiolitis other than oxygen for hypoxic children. 17. Inhaled ipratropium bromide is ineffective in the treatment of bronchiolitis. 18. The use of chest physiotherapy has not been shown to change the course of bronchiolitis or its outcome. 19. Antibiotics should not routinely be used in bronchiolitis except in children with severe disease in whom bacterial lower respiratory tract infection is suspected. 20. An important educational message to parents of children is that bronchiolitis is caused by a virus; antibiotics are not needed.

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