SAMJ Vol 106, No 10 (2016) by HMPG

OCTOBER 2016

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GUEST EDITORIAL Antibiotic stewardship – partnering with nurses and pharmacists CME Intimate partner violence IN PRACTICE Causes of childhood deaths – too many unknowns Oesophageal button batteries – a surgical emergency CASE REPORT Angio-oedema associated with colistin RESEARCH Cardiovascular disease risk in teachers – a substantial future burden Inappropriate medicine prescribing among the elderly

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OCTOBER 2016

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GUEST EDITORIALS

Passing the baton to pharmacists and nurses: New models of antibiotic stewardship for South Africa? A J Brink, D van den Bergh, M Mendelson, G A Richards

The future cost of cancer in South Africa: An interdisciplinary cost management strategy K Sartorius, B Sartorius, P S Govender, V Sharma, A Sheriff

EDITOR’S CHOICE

CORRESPONDENCE

Cancer research in South African academic and research institutions R P Abratt

South Africa’s adoption of the World Health Organization’s ‘test and treat’ guidelines: Are we too ambitious? K Govender

Biomedical research and capacity building: Bilateral collaboration between research institutes in South Africa and Cameroon G B Jacobs, G M Ikomey

TECHNICAL EDITORS Emma Buchanan Paula van der Bijl

Alpha-thalassaemia trait as a cause of unexplained microcytosis in a South African population A R Bird

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

Private practice-driven research S Mashaphu, B Chiliza

Effects of oestrogen on prepubescent children F Daubenton

IZINDABA

22 25 26

Election politics ride roughshod over clinicians, patients Living their passion for upliftment – RuDASA award winners An uphill battle – getting rehab into mainstream rural medicine

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 CEO AND PUBLISHER Hannah Kikaya | Email: hannahk@hmpg.co.za MANAGING EDITORS Ingrid Nye Claudia Naidu

PRODUCTION MANAGER Emma Jane Couzens DTP AND DESIGN Carl Sampson CHIEF OPERATING OFFICER Diane Smith | Tel. 012 481 2069 Email: dianes@hmpg.co.za

CME 27

GUEST EDITORIAL How can we manage intimate partner violence better? K Joyner

ARTICLES Intimate partner violence is everyone’s problem, but how should we approach it in a clinical setting? C Gordon

Intimate partner violence: A helpful guide to legal and psychosocial support services C Lopes

Mental health, intimate partner violence and HIV N Woollett, A M Hatcher

ONLINE SUPPORT Gertrude Fani FINANCE Tshepiso Mokoena HMPG BOARD OF DIRECTORS Prof. M Lukhele (Chair), Dr M R Abbas, Dr M J Grootboom, Mrs H Kikaya, Prof. E L Mazwai, Dr M Mbokota, Dr G Wolvaardt ISSN 0256-9574 SAMA website: www.samedical.org Journal website: www.samj.org.za

IN PRACTICE CLINICAL UPDATE 39 ‘Esprit de corps’: Towards collaborative integration of pharmacists and nurses into antimicrobial stewardship programmes in South Africa N Schellack, R Pretorius, A P Messina 41

Molecular detection of carbapenemase-producing genes in referral Enterobacteriaceae in South Africa: A short report O Perovic, E Britz, V Chetty, A Singh-Moodley

CLINICAL ALERT Button batteries in the oesophagus: A surgical emergency K Milford, A Numanoglu, A Brooks, S Cox

JOURNAL ADVERTISING Charles William Duke Reneé Hinze Ladine van Heerden Azad Yusuf Charmalin Simpson Ismail Davids

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Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer R P Abratt

MEDICINE AND THE LAW Sudden and unexpected childhood deaths investigated at the Pretoria Medico-Legal Laboratory, South Africa, 2007 - 2011 B S van Deventer, S H Rossouw, L du Toit-Prinsloo

CLINICAL PRACTICE The microbiome in chronic inflammatory airway disease: A threatened species R J Green, A van Niekerk, A C Jeevarathnum, C Feldman, G A Richards, on behalf of the South African Allergic Rhinitis Working Group

CASE REPORTS HIV/AIDS-associated Kaposi’s sarcoma of the gastrointestinal tract: A pictorial spectrum N Patel, P Naidoo, P Mosiane, C Jann-Kruger

Diagnostic challenges with acellular bacterial meningitis Y Moolla, L Naidoo

Angio-oedema associated with colistin A A Abulfathi, T Greyling, M Makiwane, M Esser, E Decloedt

RESEARCH South African congenital disorders data, 2006 - 2014* V Lebese, C Aldous, H L Malherbe

Risk of cardiovascular disease among teachers in Cape Town: Findings of the South African PaCT pilot study* E C Laurence, J Volmink, T M Esterhuizen, S Dalal, M D Holmes

Outcomes of treatment of drug-susceptible tuberculosis at public sector primary healthcare clinics in Johannesburg, South Africa: A retrospective cohort study* E P Budgell, D Evans, K Schnippel, P Ive, L Long, S Rosen

Inappropriate medicine prescribing in older South Africans: A cross-sectional analysis of medicine claims data* J A van Heerden, J R Burger, J J Gerber

Comparison of the prevalence and characteristics of inpatient adverse events using medical records review and incident reporting* W M Macharia, C M Muteshi, S Z Wanyonyi, A M Mukaindo, A Ismail, H Ekea, A Abdallah, J M Tole, A K Ngugi

Strengthening rural health placements for medical students: Lessons for South Africa from international experience* J E Doherty, I Couper

*Full article available online only.

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OCTOBER 2016

Background photo: Pharmacist dispensing ARVs | REUTERS/Thomas Mukoya Hexagon photos: Elderly woman taking prescription drugs | Jeffrey B. Banke; Button battery in the oesophagus | Milford et al.; Intimate partner violence | Sinisha Karich

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OCTOBER 2016

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GUEST EDITORIAL

Passing the baton to pharmacists and nurses: New models of antibiotic stewardship for South Africa? The decrease in effectiveness of antibiotics due to their overuse and misuse, resulting in increasing bacterial resistance, is a public health crisis of international concern, threatening modern medicine, animal health and food security.[1,2] The recent identification of two new plasmid-mediated genes (mcr-1 and mcr-2)[3,4] that confer resistance to colistin, an antibiotic of last resort in the treatment of multidrugresistant Gram-negative bacteria, underscores a crisis that it is estimated will cause 10 million deaths per annum by 2050, result in huge morbidity, and wipe out in excess of USD100 trillion from the world’s economy. An international One Health response is required, co-ordinated at the highest level.[5] South Africa (SA) is not exempt from this crisis,[6-8] and has reacted by developing a national antimicrobial resistance strategy framework[9] and an implementation plan,[10] interwoven with the government’s annual performance plan. The One Health national response focuses on increasing public awareness, improving infection prevention, heightening surveillance of antibiotic consumption and resistance, and antibiotic stewardship (AS), the optimisation of appropriate antibiotic use. A practical guide to AS for SA is being developed to tackle the virtual absence of stewardship in hospitals and the community for antibiotics used in human and animal health.[11,12] Such a guide will need to take into account what the best model for AS in SA would be. Human health AS programmes (ASPs) reported from resource-rich countries have shown that interventions to reduce excessive antibiotic prescribing can reduce resistance and improve microbiological and clinical outcomes,[13] but do ASP models from high-income countries translate to SA? Historically, notable barriers to implementation of ASPs in SA have been a lack of healthcare professionals with the expertise to lead programmes, a problem compounded by geographical disparity, and a lack of understanding of the contextual and behavioural determinants that influence local prescribing practices. The first ASPs introduced in SA followed the model of AS teams led by infection specialists at public sector, central academic hospitals and their outreach sites, which focused on AS ward rounds to change prescribing practice.[14] The attractiveness of this model is its ability to reduce overall antibiotic use, prevent patients who do not require antibiotics from receiving them in the first place, and transfer AS skills to junior and senior doctors, microbiologists, pharmacists, nurses, infection control practitioners, medical students and other allied health professionals who attend the stewardship ward rounds. Two national training centres have now been funded to rapidly train prescriber-pharmacist-hospital manager teams from provincial hospitals throughout SA to promote the initiation of ASPs in their hospitals and in turn train local practitioners in stewardship. More recently, a model focused on non-specialist pharmacists, which demonstrated a sustainable reduction in antibiotic use across 47 Netcare hospitals, has highlighted the opportunity to widen the net of interventionists.[15] The Netcare model promoted collaborative action utilising existing resources and the concept of ‘low-hanging fruit’ across a diverse group of urban and rural SA private hospitals. The 5-year study, involving stepwise change management and quality improvement principles including behaviour change techniques, utilised non-specialised pharmacists to co-ordinate a prospective audit and feedback strategy targeting antibiotics used for >7 days, concurrent use of more than four antibiotics, redundant or double

antibiotic coverage and increased use of microbiological cultures. Notably, the process measures were introduced following extensive consultation with all stakeholders, emphasising the need for change and establishing clinician collaboration in so doing. The results were impressive: 116 662 patients received antibiotics during 104 weeks of standardised audit, measurement and feedback, with 7 934 interventions by pharmacists recorded for the targeted measures, indicating that almost one in 15 inpatient prescriptions required intervention. In a previous survey in SA intensive care units,[11] antibiotic duration was found to be inappropriate in 53.2% and 81.7% of public and private sector patients, respectively. It was therefore not surprising that excessive duration represented the majority (39.2%) of the pharmacist interventions. This simple protocol led to a reduction in mean antibiotic use, recorded as daily doses per 100 patient days, from 101.38 (95% confidence interval (CI) 93.5 - 109.72) in the pre-implementation phase to 83.04 (95% CI 74.87 - 91.22) in the post-implementation phase (p<0.0001), a decline of 18.1% (95% CI 15.71 - 20.4). This study attests to the fact that AS can be introduced successfully into hospitals across the country that have never practised stewardship before, utilising non-infection specialists, which is especially relevant to low- and middle-income countries with limited human resources. An important question is whether the same intervention would work in the SA public sector, where the majority of the population receives healthcare. Pharmacists would need to be trained in monitoring antibiotic use, ASP project managers would need to be appointed to co-ordinate implementation and monitoring, and ‘protected’ stewardship time would have to be agreed upon, i.e. pharmacists (one or more) would be allowed time, according to the size of the hospital, to conduct antibiotic audit rounds. If successful, ‘higher-level fruit’ could be targeted, either by pharmacists alone or by pharmacists in partnership with other healthcare professionals. Like pharmacists, nurses are a potential cadre of healthcare professionals with a proven track record in antimicrobial prescribing in SA. Primary care nurses safely initiate and re-prescribe anti retroviral therapy without detrimental effect.[16] Furthermore, primary care nurses are at the frontline of antibiotic prescribing in the Practical Approach to Care Kit (PACK) adult intervention, a symptom-based set of guidelines for management of common conditions in primary care.[17] Appropriate antibiotic use is written into this practical kit for nurses to direct antibiotic management. In many neighbouring countries, antibiotic stewardship has been woven into programmes such as the integrated management of childhood illness and its adolescent/adult equivalent, where once again nurses, and indeed community health workers, play a leading stewardship role.[18] In hospitals, intensive care unit nurses would be an ideal group to take on a greater stewardship role. Will doctors, the actual prescribers, and a group notoriously keen on safeguarding clinician prescribing autonomy, embrace pharmacists and nurses as equals in the drive towards optimising antibiotic use? The potential for pharmacist- and nurse-led models of AS to complement that of clinicians affords an exciting opportunity for SA to offer an integrated range of ASP models to serve the whole population. It will require commitment from government, hospital, clinician, pharmacist and nurse leadership to acknowledge and support their central role. It is time that we as doctors welcome other

October 2016, Print edition

GUEST EDITORIAL

cadres of healthcare professionals as antibiotic stewards in their own right, able to intervene to ensure appropriate use of antibiotics and in so doing joining the fight to sustain this vital, global resource. Acknlowledgement. We thank Angeliki P Messina, Charles Feldman, Piet J Becker, Debra A Goff, Karri A Bauer and Dilip Nathwani, co-authors of the Lancet Infectious Diseases article[15] on which this editorial is based.

Adrian J Brink Ampath National Laboratory Services, Milpark Hospital, Johannesburg, South Africa; and Division of Infectious Diseases and HIV Medicine, Department of Medicine, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa brinka@ampath.co.za Dena van den Bergh Department of Quality Leadership, Netcare Hospitals, Johannesburg, South Africa Marc Mendelson Division of Infectious Diseases and HIV Medicine, Department of Medicine, Faculty of Health Sciences, Groote Schuur Hospital, University of Cape Town, South Africa Guy A Richards Department of Critical Care, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

1. Gelband H, Miller-Petrie M, Pant S, et al. The state of the world’s antibiotics, 2015. http://cddep.org/ publications/state_worlds_antibiotics_2015 (accessed 21 November 2015). 2. Review on Antimicrobial Resistance. Tackling drug resistant infections globally. Final report and recommendations. http://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover. pdf (accessed on 14 July 2016). 3. Liu YY, Wang Y, Walsh TR, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR1 in animals and human beings in China: A microbiological and molecular biological study. Lancet Infect Dis 2016;16(2):161-168. DOI:10.1016/S1473-3099(15)00424-7 4. Xavier BB, Lammens C, Ruhal R, Kumar-Singh S, Butaye P, Goossens H, Malhotra-Kumar S. Identification of a novel plasmid-mediated colistin-resistance gene, MCR-2, in Escherichia coli, Belgium, June 2016. Euro Surveill 2016;21(27):pii=30280. DOI:10.2807/1560-7917.ES.2016.21.27.30280 5. Laxminaryan R, Amábile-Cuevas C, Cars O, et al. UN high-level meeting on antimicrobials – what do we need? Lancet 2016; 388 (10041):218-220. DOI:10.1016/S0140-6736(16)31079-0 6. Brink A, Feldman C, Richards G, Moolman J, Senekal M. Emergence of extensive drug resistance (XDR) among Gram-negative bacilli in South Africa looms nearer. S Afr Med J 2008;98(8):586-590. 7. Mendelson M, Whitelaw A, Nicol M, Brink A. Wake up, South Africa! The antibiotic ‘horse’ has bolted. S Afr Med J 2012;102(7):607-608. 8. Coetzee J, Corcoran C, Prentice E, et al. Emergence of plasmid-mediated colistin resistance (MCR1) among Escherichia coli isolated from South African patients. S Afr Med J 2016;106(5):449-450. DOI:10.7196/SAMJ.2016.v106i5.10710 9. National Department of Health, South Africa. Antimicrobial Resistance National Strategy Framework 2014-2024. http://www.health.gov.za/index.php/antimicrobial-resistance (accessed 14 July 2016). 10. National Department of Health, South Africa. Implementation Plan for Antimicrobial Resistance National Strategy Framework 2014-2019. http://www.health.gov.za/index.php/antimicrobial-resistance (accessed on 14 July 2016). 11. Paruk F, Richards GA, Scribante J, Bhagwanjee S, Mer M, Perrie H. Antibiotic prescription practices and their relationship to outcome in South African intensive care units. S Afr Med J 2012;102(7):613616. 12. Altiner A, Knauf A, Moebes J, Sielk M, Wilm S. Acute cough: A qualitative analysis of how GPs manage the consultation when patients explicitly or implicitly expect antibiotic prescriptions. Fam Pract 2004;21(5):500-506. DOI:10.1093/fampra/cmh505 13. Davey P, Brown E, Charani E, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2013 Apr 30;4:CD003543. DOI:10.1002/14651858. CD003543.pub3 14. Boyles, Whitelaw A, Bamford C, et al. Antibiotic stewardship ward rounds and a dedicated prescription chart reduce antibiotic consumption and pharmacy costs without affecting inpatient mortality or readmission rates. PLoS One 2013;8(12):e79747. DOI:10.1371/journal.pone.0079747 15. Brink AJ, Messina AP, Feldman C, et al. on behalf of the Netcare Antimicrobial Stewardship Study Alliance. Antimicrobial stewardship across 47 South African hospitals: An implementation study. Lancet Infect Dis 2016;16(9):1017-1025. DOI:10.1016/S1473-3099(16)30012-3 16. Fairall L, Bachmann MO, Lomard C, et al. Task shifting of antiretroviral treatment from doctors to primary-care nurses in South Africa (STRETCH): A pragmatic parallel cluster-randomised trial. Lancet 2012;380(9845):889-898. DOI:10.1016/S0140-6736(12)60730-2 17. Knowledge Translation Unit PACK Western Cape, South Africa. http://knowledgetranslation.co.za/ programmes/pack-adult-wc-sa/ (accessed 14 July 2016). 18. World Health Organization. Integrated Management of Childhood Illness. http://www.who.int/ maternal_child_adolescent/topics/child/imci/en/ (accessed 14 July 2016).

S Afr Med J 2016;106(10):947-948. DOI:10.7196/SAMJ.2016.v106i10.11448

October 2016, Print edition

Oxytocin/Ergometrine

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

GUEST EDITORIAL

The future cost of cancer in South Africa: An interdisciplinary cost management strategy The exponential rise in cancer costs in South Africa (SA) was illustrated in a recent Sunday Times article entitled ‘The cost of cancer can be a debt sentence’.[1] Our minister of health talks of a ‘war’ against the high costs of cancer drugs, and epidemiologists project a sharply rising incidence. Eminent international medical journals, such as The Lancet, underline the fact that cancer cost is a growing international problem that confronts even the richest countries. Indeed, the question may be posed: if richer countries in the world are battling to cover the costs of cancer, what is the prognosis for SA?

The future incidence of cancer

Epidemiologists predict a major increase in cancer in the developing world, with 60% of all new cases coming from Africa, Asia and South/ Central America.[2] In SA the projected increase is even greater, and a recent article in The Lancet[3] projected a 78% increase by 2030. Rapidly changing lifestyles, uncontrolled urbanisation, pollution, population ageing, endemic viral infection (HBV/HIV/HPV) and an epidemic of obesity provide a lethal cocktail of infectious and lifestyle cancer risk factors in SA.[4,5]

International trends in cancer cost

The cost of healthcare is a growing international problem. In the USA ~62% of all personal bankruptcies (2007) were caused by healthcare costs.[2] The cost of cancer management has ‘skyrocketed’, as illustrated in the European Union, which recorded a cost (in SA terms) of more than ZAR2 500 billion in 2009 that included direct healthcare costs, lost productivity and loss of family savings.[6] It appears that the doctrine of justum pretium (‘a fair price’) has been ignored by the pharmaceutical sector. Of the 12 drugs approved by the Food and Drug Administration in the USA for various cancer indications in 2012, 11 were priced above ZAR1.5 million per patient per year.[7] At the 2015 American Society of Clinical Oncology annual meeting, Dr Leonard Saltz wryly commented that ipilumumab (immune checkpoint inhibitor) was almost ‘4 000 times the cost of gold’.

SA cancer cost squeeze

Cancer management programmes in SA are threatened by a cost squeeze caused by a constrained gross domestic product in the face of a simultaneous increase in incidence and cost. Just recently, the Sandton Oncology Centre complained that, although the cost of cancer drugs was high, they often only make up a fraction of the total cost. Costs such as surgery, inpatient care, consultations and repetitive diagnostic and staging investigations have ratcheted up expenses exponentially. Because of these costs, medical aid limits are increasingly unable to cover even older-generation therapies, let alone more targeted interventions. The provision of new-generation immunotherapy drugs such as ipilumumab has a price tag of ZAR1 million, and trastuzumab costs ZAR25 000 per treatment. A mastectomy plus trastuzumab costs ZAR500 000, and immunotherapy for metastatic melanoma ~ZAR1 million.

SA private cancer healthcare

Providing healthcare cover for cancer is a high-risk business. A PricewaterhouseCoopers survey of the industry indicated escalating hospital and specialist costs, an ageing risk profile and an increase in unhealthy members. General agreement in this sector is that

innovative thinking is needed to embrace new technology combined with a preventive approach, as well as lower the cost of drugs. Without these changes, a typical medical aid cover of ZAR200 000 400 000 will be increasingly inadequate to cover conservative cancer management programmes, let alone newer-generation therapies.

SA public healthcare and cancer cost

The projected cost squeeze could preclude the public healthcare sector from providing even the most cost-effective treatment programmes. An example is radiotherapy, which is routinely provided to ~50% of all patients diagnosed with cancer.[8] Currently, the public sector has <1 linear accelerator (0.4) per million people compared with the recommended minimum of at least 1 per million as per International Atomic Energy Agency (IAEA) and World Health Organization (WHO) guidelines and 3 per million as per the Econex report. [9] Significant shortfalls are even more pronounced in the poorer provin ces, explaining the current delays for patients accessing radiotherapy. In addition, 25% of the country’s oncologists are required to service more than 75% of the population, contributing to a general shortage of oncology healthcare staff in the public healthcare sector, including medical physicists, radiotherapists, oncologists and trained nurses. A combination of long treatment delays, limited resources, differentially skilled personnel, high patient volumes and advanced disease stage on presentation makes for a challenging environment to deliver optimal cancer care outcomes.[10,11] What will happen if the incidence of cancer increases by 78%?

A strategic rethink

Interdisciplinary planning is necessary to commercialise new diagnostic, surgical, radiotherapy and pharmaceutical technologies that can diagnose and treat cancer at an early stage. At the same time, efficient and cost-effective treatment can leverage the maximum out of the current resources. Public-private partnerships must also be explored to take advantage of better infrastructural capacity in the private sector, and a national strategic cancer control plan should be developed by all stakeholders to ensure the development of legislative (e.g. alcohol, sugar, smoking), educational (e.g. smoking, diet, exercise) and prophylactic (e.g. HBV/HPV vaccination) programmes. The development of better databases, and training of and incentives for oncology personnel, should be a national priority from primary to specialist level.[8] The retention of oncologists in the public sector institutions could also be prioritised and include compulsory service for newly qualified specialists, tagged with incentives to stay in the public sector. In addition, oncology exposure at undergraduate level needs to be improved so that primary care physicians are better equipped to make an early diagnosis of cancer. The cost benefit of national screening programmes for common malignancies can also be explored beyond cervical cancer and a standardised treatment plan for pre-malignant lesions developed. A public sector capital investment in radiotherapy infrastructure such as simulators, linear accelerators and brachytherapy units in accordance with WHO and IAEA guidelines, together with necessary maintenance contracts, will obviate delays in patients accessing radiotherapy in the curative and palliative context. Palliative care facilities and trained personnel also need to be urgently developed to manage terminally ill cancer patients.

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GUEST EDITORIAL

Interdisciplinary research funding in SA needs to be encouraged in order to better understand the demographic and molecular aetiology of cancer in the country. Emerging opportunities supported by the National Research Foundation and the Medical Research Council are increasingly encouraging collaborative research in the BRICS countries (Brazil, Russia, India, China and South Africa) or developed/developing country research partnerships. The cost of cancer drugs is multi-tiered. At present, they are more expensive in developed countries such as the USA and differentially discounted in developing countries. Nevertheless, the discounted price of new-generation cancer drugs is still unaffordable in developing countries and especially in sub-Saharan Africa.[12] The reduction of these costs is an international issue that must precipitate government and NGO lobbies in international forums to allow SA to adopt a patent bypass approach (as in India), or alternatively to reduce differential pricing even further. In parallel, there is a need to keep looking at making more efficient use of budget allocations for drugs, with many oncologists continuing to prescribe two to three lines of chemotherapy in very advanced stages, and requesting repeated costly investigations because of the fear of litigation. K Sartorius Faculty of Commerce, University of the Witwatersrand, Johannesburg, South Africa; Public Health Medicine, School of Nursing and Public Health, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZuluNatal, Durban; and Medical Research Council/University of KwaZulu-Natal Gastrointestinal Cancer Research Centre, Durban, South Africa kurt.sartorius@wits.ac.za B Sartorius Public Health Medicine, School of Nursing and Public Health, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban; and Medical Research Council/ University of KwaZulu-Natal Gastrointestinal Cancer Research Centre, Durban, South Africa

P S Govender Medical Research Council/University of KwaZulu-Natal Gastrointestinal Cancer Research Centre, Durban; Inkosi Albert Luthuli Central Hospital, Durban; and Acting Head of Oncology, School of Clinical Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa V Sharma Head of Oncology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa A Sheriff Acting Head of Oncology, Universitas Hospital and Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa; and President of the College of Radiation Oncologists, South Africa 1. Laganparsad M. The cost of cancer can be a debt sentence. http://www.timeslive.co.za/ sundaytimes/stnews/2016/02/21/Cost-of-cancer-can-be-a-debt-sentence (accessed 3 September 2016). 2. Hoen ET, Law L-M. Access to Cancer Treatment. Oxford, UK: Oxfam GB, 2015. 3. Stefan DC, Elzawawy AM, Khaled HM, et al. Developing cancer control plans in Africa: Examples from five countries. Lancet Oncol 2013;14(4):e189-e195. DOI:10.1016/S1470-2045(13)70100-1 4. Stewart B, Wild CP, eds. World Cancer Report 2014. International Agency for Research on Cancer, World Health Organization, 2014. http://www.thehealthwell.info/node/725845 (accessed 2 Septem ber 2016). 5. Gopal S, Achenbach CJ, Yanik EL, Dittmer DP, Eron JJ, Engels EA. Moving forward in HIV-associated cancer. J Clin Oncol 2014;32(9):876-880. DOI:10.1200/JCO.2013.53.1376 6. Luengo-Fernandez R, Leal J, Gray A, Sullivan R. Economic burden of cancer across the European Union: A population-based cost analysis. Lancet Oncol 2013;14(12):1165-1174. DOI:10.1016/S14702045(13)70442-X 7. Experts in Chronic Myeloid Leukemia. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: From the perspective of a large group of CML experts. Blood 2013;121(22):4439-4442. DOI:10.1182/blood-2013-03-490003 8. Morhason-Bello IO, Odedina F, Rebbeck TR, et al. Challenges and opportunities in cancer control in Africa: A perspective from the African Organisation for Research and Training in Cancer. Lancet Oncol 2013;14(4):e142-e151. DOI:10.1016/S1470-2045(12)70482-5 9. Econex. The human resource supply constraint: The case of doctors. Health Reform Note 8. November 2010. http://econex.co.za/publication/health-reform-note-8/ (accessed 12 September 2016). 10. Grover S, Balogun OD, Yamoah K, et al. Training global oncologists: Addressing the global cancer control problem. Front Oncol 2015;5:80. DOI:10.3389/fonc.2015.00080 11. Sharma V, Gaye PM, Wahab SA, et al. Patterns of practice of palliative radiotherapy in Africa, Part 1: Bone and brain metastases. Int J Radiat Oncol Biol Physics 2008;70(4):1195-1201. DOI:10.1016/j. ijrobp.2007.07.2381 12. Kingham TP, Alatise OI, Vanderpuye V, et al. Treatment of cancer in sub-Saharan Africa. Lancet Oncol 2013;14(4):e158-e167. DOI:10.1016/S1470-2045(12)70472-2

S Afr Med J 2016;106(10):949-950. DOI:10.7196/SAMJ.2016.v106i10.11375

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EDITOR’S CHOICE

CME: Intimate partner violence

On 27 May 2016, the 69th World Health Assembly endorsed the global plan of action to strengthen the role of health systems within a national multisectoral response to address interpersonal violence, especially against women and children. This landmark plan was adopted with a resolution (EB 138.R3) co-sponsored by 44 member states. It will promote the achievement of the Sustainable Development Goals, including historic Goal 5 (achieve gender equality and empower all women and girls), Goal 16 (promote peace, justice and inclusive societies) and Goal 3 (ensure healthy lives and promote wellbeing for all at all ages). These initiatives coalesce with, and will add to, attaining the objectives of the new Global Strategy for Women’s, Children’s, and Adolescents’ Health. The era of making excuses for not addressing sexual, domestic and child abuse effectively in clinical practice is over. This issue points to the evidence base and provides clinicians with current, contextual approaches to providing care for intimate partner violence (IPV). It also offers insight into key dynamics within IPV, and the vital interface between IPV, HIV and mental health.

Integrating pharmacists and nurses into antimicrobial stewardship programmes in South Africa

The worldwide spread of antimicrobial resistance (AMR) has been labelled a global health crisis, and it is estimated that by 2050, 10 million lives a year will be at risk as a consequence of antibioticresistant infections, predominantly bacterial. In South Africa (SA), except for tuberculosis, HIV and colistin use in animals, the impact of AMR in the respective sectors is unknown, and a national strategy of utilising all resources to cover more territory to fight AMR is mandatory. The need for wider engagement of healthcare professionals in antimicrobial stewardship programmes (ASPs) is therefore pivotal. To highlight the indispensable role of pharmacists in recruiting multidisciplinary teams and in co-ordination of interdisciplinary clinician and nurse engagement in antimicrobial stewardship (AS) interventions, Brink et al.[1] recently presented a prospective audit and feedback model for AS in infectious disease-constrained, non-academic settings. This SA study was performed in 47 Netcare hospitals, focusing on basic interventions implemented by pharmacists in consultation with prescribers, and demonstrated a significant reduction in overall antibiotic consumption of 18.1% in 116 662 patients. The Netcare model also confirmed that quality improvement science skills are critical in implementing and maintaining an ASP and that stewardship, dependent on local context and resources, can become embedded in existing systems, which is the key to sustainability. A proposed study of process and outcome measures for the management of communityacquired pneumonia is planned nationally, to promote collaboration and team involvement between private and public sector pharmacists on how to co-ordinate, implement and monitor ASPs. As for pharmacists, inclusion in ASPs of the broad-based, multidisciplinary registered nurses (RNs) could have a substantial impact.[2] RNs play an essential role in monitoring compliance with institutional guidelines and best practice, monitoring for drug allergies and side-effects, obtaining and reporting of therapeutic levels, management and administration of medicines with mixed dosages, e.g. insulin, and ensuring timely and correct administration of antimicrobials.[3] A study conducted in 33 Netcare hospitals found that pharmacists and nurses can collectively improve the timeous administration of antibiotics.[4] As Brink et al.[5] and Schellack et al.[6] stress in their guest editorial and ‘In Practice’ article in this issue of SAMJ, recognition and acknowledgment of the potential role of healthcare workers other than doctors are critical to ensure sustainable antimicrobial preservation.

Sudden and unexpected childhood deaths – too many unknowns

Sudden and unexpected death is well known to occur in infants, and although sudden deaths are less frequent after the first birthday, they still account for a significant proportion of childhood deaths. In 2009, 1.9% of the total deaths in the USA were childhood deaths. In SA this proportion was much higher at 11.85%. According to the law, sudden and unexpected deaths are generally investigated as unnatural deaths. Establishing an exact underlying anatomical cause of death will depend on available resources and can be difficult in a substantial proportion of cases. A retrospective case audit from the Pretoria Medico-Legal Lab oratory[5] looked at sudden and unexpected deaths of children aged 1 - 18 years. Most of the deaths were of children aged 1 - 5 years. In 28.6% of cases the medicolegal investigation, including the autopsy, could not establish the cause of death. The fact that the cause of the largest proportion of deaths could not be ascertained emphasises the need for consideration of additional investigative techniques, such as molecular/genetic screening, which have provided an underlying cause of death in a significant number of cases in other countries. There is a lack of published research on the causes and incidence of sudden unexpected deaths in children in SA, and further research in this area is needed.

Cardiovascular disease among Cape Town’s teachers – a substantial future burden

Long-term cohort studies are needed in Africa, with the accelerating epidemic of cardiovascular and other non-communicable diseases across the continent. Hence the establishment of the Partnership for Cohort Research and Training (PaCT), which has set up pilot studies in SA, Uganda, Tanzania, and Nigeria. The SA site additionally studied the prevalence of cardiovascular disease risk factors, and categorised participants’ 10-year predicted risk of a cardiovascular event.[6] Teachers from 111 public schools in the Metro South Edu cation District in Cape Town were enrolled between January 2011 and May 2012. Most (70.3%) of participants were female, and the mean age was 46.3 years. The prevalence of CVD risk factors was high: 48.5% for hypertension, 20.5% for hypercholesterolaemia, 18.0% for smoking, 10.1% for diabetes, 10.4% for chronic kidney disease, and 84.7% for overweight or obesity; 18.7% of participants were at high risk of a heart attack or stroke within 10 years. It is clear that cardiovascular disease will soon impose a substantial burden on Cape Town’s education system. BF 1. Brink AJ, Messina AP, Feldman C, et al. on behalf of the Netcare Antimicrobial Stewardship Study Alliance. Antimicrobial stewardship across 47 South African hospitals: An implementation study. Lancet Infect Dis 2016;16(9):1017-1025. DOI:10.1016/S1473-3099(16)30012-3 2. Olans RN, Olans RD, DeMaria A. The critical role of the staff nurse in antimicrobial stewardship – unrecognized, but already there. Clin Infect Dis 2016;62(1):84-89. DOI:10.1093/cid/civ697 3. Edwards, R, Drumright, LN, Kiernan, M, Holmes, A. Covering more territory to fight resistance: Considering nurses’ role in antimicrobial stewardship. J Infect Prev 2011;12(1):6-10. DOI:10.1177/1757177410389627 4. Messina AP, van den Bergh D, Goff DA. Antimicrobial stewardship with pharmacist intervention improves timeliness of antimicrobials across thirty-three hospitals in South Africa. Infect Dis Ther 2015;4(Suppl 1):5-14. DOI:10.1007/s40121-015-0082-x 5. Brink AJ, van den Bergh D, Mendelson M, Richards GA. Passing the baton to pharmacists and nurses: New models of antibiotic stewardship for South Africa? S Afr Med J 2016;106(10):947-948. DOI:10.7196/SAMJ.2016.v106i10.11448 6. Schellack N, Pretorius R, Messina AP. ‘Esprit de corps’: Towards collaborative integration of pharmacists and nurses into antimicrobial stewardship programmes in South Africa. S Afr Med J 2016;106(10):973974. DOI:10.7196/SAMJ.2016.v106i10.11468 7. Van Deventer BS, Rossouw SH, du Toit-Prinsloo L. Sudden and unexpected childhood deaths investigated at the Pretoria Medico-Legal Laboratory, South Africa, 2007 - 2011. S Afr Med J 2016;106(10):983-985. DOI:10.7196/SAMJ.2016.v106i10.11170 8. Laurence EC, Volmink J, Esterhuizen TM, Dalal S, Holmes MD. Risk of cardiovascular disease among teachers in Cape Town: Findings of the South African PaCT pilot study. S Afr Med J 2016;106(10):9961001. DOI:10.7196/SAMJ.2016.v106i10.10869

October 2016, Print edition

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

CORRESPONDENCE

Cancer research in South African academic and research institutions

To the Editor: A valuable overview of cancer research in South African (SA) academic and research institutions during 2013 - 2014 has recently been published.[1] The titles of 556 research projects were reviewed and divided into basic science, clinical and public health domains. These domains contained 46%, 54% and 13% of the projects, respectively. The projects could fit into more than one domain, resulting in a total of 113%. The authors rightly note the relative dearth of projects on public health – only 13% of all projects. These studies are important for cancer prevention, early diagnosis and cost-effective management. However, these findings also suggest that there is a need for an increase in joint projects by researchers in all the domains. Only 13% of all projects were in more than one domain. Both basic scientists and clinical researchers may contribute to translational research, which is key to understanding the scientific basis of cancer control programmes. SA has a proud and productive history of collaboration between researchers. Examples are the linking of asbestos exposure to mesothelioma and the initial development of computed tomography. [2] The research community will promote joint projects by having regular meetings of basic science, clinical and public health representatives, which aim to bring together fellow researchers with common interests but different backgrounds. We can complement face-to-face meetings with virtual meetings at a low cost. These could take place within universities, within regions or nationally. The latter would be particularly valuable in SA, with its varied regions and mix of established and new universities. Research to improve healthcare thrives on synergy as well as scientific rigour. R P Abratt

Head of Clinical Governance, Independent Clinical Oncology Network, South Africa; and Emeritus Professor of Radiation Oncology, Faculty of Health Sciences, University of Cape Town, South Africa raymond.abratt@cancernet.co.za 1. Moodley J, Stefan DC, Sewram V, Ruff P, Freeman M, Asante-Shongwe K. An overview of cancer research in South African academic and research institutions, 2013-2014. S Afr Med J 2016;(6):607610. DOI:10.7196/SAMJ.2016.v106i6.10314 2. Abratt RP. Value of participating in clinical research (Editorial). S Afr Med J 2001;91(7):575.

S Afr Med J 2016;106(10):951. DOI:10.7196/SAMJ.2016.v106i10.11220

South Africa’s adoption of the World Health Organization’s ‘test and treat’ guidelines: Are we too ambitious?

To the Editor: Health minister Dr Aaron Motsoaledi has announced that South Africa will adopt the World Health Organization (WHO)’s new ‘test and treat’ guidelines from September 2016, enabling all patients living with HIV to be eligible for antiretroviral therapy (ART). This radical policy change is evidenced by the Strategic Timing Anti-Retroviral Treatment (START) study,[1] a 2011 trial conducted in 35 countries with 4 685 participants, half of whom initiated ART immediately when diagnosed with HIV and the other half as soon as their CD4 count dropped <350 cells/µL. The study indicated a beneficial effect of immediate ART for both AIDS-related and nonAIDS-related events, and also reported no increased rates of adverse effects associated with this strategy. This evidence was so compelling

that the trial was stopped prematurely, as it was unethical to delay ART to those not on treatment. It has been suggested that the ‘test and treat’ guidelines hold the potential to eliminate the epidemic by breaking the cycle of HIV transmission and reducing ART costs in the long term; however, numerous modelling studies have found contradictory evidence to the WHO model, which under-estimated the survival time on ART and ignored the threat of resistance developing after widespread ART use.[2,3] Furthermore, it is not clear how the already overstrained healthcare system will deal with a high influx of patients on treatment, who would require baseline CD4 count testing as well as virological monitoring. A drastic increase in patient turnover could result in resources being further strained, especially with regard to clinical and laboratory capacity. This may result in the patients most at risk of death with comorbidities and low CD4 counts being missed by the healthcare system. It is suggested that before implementing a ‘test and treat’ strategy, which may not be sustainable, achieving universal access to treatment with gradual increments in CD4 criteria later on may be more effective in eliminating the epidemic. However, the policy wheels were already in motion from September, and it is now more important than ever that clinicians maintain vigilance to diagnose HIV-infected patients at a high risk of poor outcomes in the midst of an influx of generally healthier HIV-infected patients. Kumeren Govender

5th-year MB ChB student, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa kumereng@gmail.com 1. Lundgren JD, Babiker AG, Gordin F, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 2015;373(9):795-807. DOI:10.1056/NEJMoa1506816 2. Dodd PJ, Garnett GP, Hallett TB. Examining the promise of HIV elimination by ‘test and treat’ in hyper-endemic settings. AIDS 2010;24(5):729-735. DOI:10.1097/QAD.0b013e32833433fe 3. Wagner BG, Blower S. Universal access to HIV treatment versus universal ‘test and treat’: Transmission, drug resistance & treatment costs. PLoS One 2012;7(9):e41212. DOI:10.1371/journal.pone.0041212

S Afr Med J 2016;106(10):952. DOI:10.7196/SAMJ.2016.v106i10.11308

Biomedical research and capacity building: Bilateral collaboration between research institutes in South Africa and Cameroon

To the Editor: Collaboration is important in standardising research practice. We established a successful partnership between the Virology/Immunology Unit at the Centre for the Study and Control of Communicable Diseases, University of Yaoundé I, Cameroon, and the Division of Medical Virology, Stellenbosch University, South Africa (SA). Our research is focused on HIV, hepatitis, HPV and tuberculosis and on capacity building. We briefly highlight the challenges we have faced. The majority of African countries are classified as low- or middleincome countries.[1] Many African countries do not have the capacity to perform much-needed basic health research. Factors that hamper progress include lack of resources, limited knowledge and the absence of financial incentives,[2] and have resulted in gaps in basic scientific knowledge. There is a strong need to strengthen African research and development.[3] Health research on the continent has focused on HIV/AIDS, malaria and tuberculosis, as these are the communicable diseases with the highest health burden.[4] There are many areas of neglected research that could be strengthened, given the necessary resources.[5] The most substantial research for the continent has come

October 2016, Print edition

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CORRESPONDENCE

from SA, Nigeria and Kenya, contributing more than 50% of health publications.[4] Collaboration has the potential to strengthen research capacity.[6] African research institutions, however, do not collaborate with each other, but seek partnerships with the USA or Europe, in order to secure funding and insure high-quality outputs. Our study involves an African-African collaboration (middle to low income).

Research and funding

Successful research relies on sustainable funding for laboratory reagents, equipment, salaries, students and capacity development. Most of the funding for African research comes from outside Africa, such as from the National Institutes of Health, Wellcome Trust and the European Union-Africa partnerships.[7,8] The African Union has previously committed 1% of its GDP to research, while local governments only spend a fraction of that on health research.[9] We ourselves have secured funding from the HIV Trust (UK) and SA’s National Research Foundation (NRF). Student and staff mobility is generously supported by our institutional travel grants, which provide incentives to promote African collaboration. The NRF has a mandate to promote research focus areas in the country and within Africa.[10] We continue to seek for country-specific and international grants.

Capacity building

There is no doubt that human expertise is extremely valuable. There is a general lack of researcher professionals in Africa.[2] We have engaged in research projects that facilitate capacity building. We jointly supervise postgraduate and medical students. Mobility grants have allowed a small group of students to receive training at our partner institutions, training that they would not otherwise have received. Many qualified students leave their research environment after their studies for greener pastures.[11] We have also seen that many postgraduates often do not publish their work, other than their formal thesis, as doing this holds no benefits for their immediate careers in Africa. A huge amount of completed research is therefore lost to the scientific community. If we are going to build research capacity, we need to maintain qualified researchers and create an atmosphere conducive to research.

Cultural differences

Africa is highly diverse in its cultures. We need to consider the social, political and economic environment of each country. SA, with 11 official languages and many racial and ethnic groups, has a background of segregation and is still dealing with many sensitive issues surrounding the topic. SA has seen a huge influx of African migrants seeking better opportunities. This includes the research sector, with many African students doing their formal training at SA institutions but not returning home after their studies.[12] Cameroon is mainly English and French speaking, and has approximately 250 ethnicities, each with its own cultural background. However, research should not be done in isolation. We can achieve much more together. Partners should agree beforehand on their joint focus areas, respecting cultural traditions while creating platforms for collaborative projects. Working with different international groups should be seen as expanding the research niche, while giving the opportunity to expand our knowledge of world cultures.

Conclusion

We believe that an intercontinental partnership has the potential to enhance research outputs for Africa. We, as African scientists,

need to prioritise and focus on key research areas.[4] There has been significant progress, with many programmes in place to promote research within Africa. These include the World Health Organization Regional Office for Africa, African Society for Laboratory Medicine, and Strengthening Laboratory Management Toward Accreditation programmes. [13] We have had several postgraduate students working on our research projects, some of whom who have already obtained their degrees. Various students also had the opportunity to visit their partner laboratories. We believe that this facilitates capacity development. Sustainable funding sources remain the biggest challenge. With the combined strength of our student, staff and research capabilities we are aiming to enhance the quality and quantity of our outputs, and we have the ability to produce significant research data that can positively influence health policies in Africa. We strongly recommend that African countries focus on building and maintaining research capacity on the continent. Authorship. GBJ and GMI contributed equally to this letter. They are principal investigators at their respective institutions.

G B Jacobs

Centre for the Study and Control of Communicable Diseases, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa graeme@sun.ac.za

G M Ikomey

Centre for the Study and Control of Communicable Diseases, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Cameroon 1. World Bank data. http://data.worldbank.org/about/country-and-lending-groups (accessed 1 Septem ber 2016). 2. Nachega JB, Uthman OA, Ho YS, et al. Current status and future prospects of epidemiology and public health training and research in the WHO African region. Int J Epidemiol 2012;41(6):1829-1846. DOI:10.1093/ije/dys189 3. Nwaka S, Ilunga TB, da Silva JS, et al. Developing ANDI: A novel approach to health product R&D in Africa. PLoS Med 2010;7(6):e1000293. DOI:10.1371/journal.pmed.1000293 4. Uthman OA, Wiysonge CS, Ota MO, et al. Increasing the value of health research in the WHO African Region beyond 2015 – reflecting on the past, celebrating the present and building the future: A bibliometric analysis. BMJ Open 2015;5(3):e006340. DOI:10.1136/bmjopen-2014-006340 5. Hopkins AD. Neglected tropical diseases in Africa: A new paradigm. Int Health 2016;8(Suppl 1):i28-i33. DOI:10.1093/inthealth/ihv077 6. Volmink J, Dare L. Addressing inequalities in research capacity in Africa. BMJ 2005;331(7519):705706. DOI:10.1136/bmj.331.7519.705 7. H3Africa consortium. Research capacity: Enabling the genomic revolution in Africa. Science 2014;344(6190):1346-1348. DOI:10.1126/science.1251546 8. Collins FS, Farrar J. Opinion: On ‘Funding research in Africa’. 28 November 2014. The Scientist: Exploring Life, Inspiring Innovation. http://www.the-scientist.com/?articles.view/articleNo/41549/ title/Opinion--On--Funding-Research-in-Africa-/ (accessed 7 September 2016). 9. Khan MJ. Africa’s plan of action for science and technology and indicators: South African experience. African Statistical Journal, Human Sciences Research Council 2008;163-176. http://www.hsrc.ac.za/en/ research-data/view/3863 (accessed 7 September 2016). 10. South African National Research Foundation. www.nrf.ac.za (accessed 1 September 2016). 11. Adedokun BO, Olopade CO, Olopade OI. Building local capacity for genomics research in Africa: Recommendations from analysis of publications in Sub-Saharan Africa from 2004 to 2013. Glob Health Action 2016;9:31026. DOI:10.3402/gha.v9.31026 12. Statistics South Africa. Mid-year population estimates 2015. 31 July 2015. https://www.statssa.gov.za/ publications/P0302/P03022015.pdf (accessedf 1 June 2016). 13. Alemnji GA, Zeh C, Yao K, Fonjungo PN. Strengthening national health laboratories in sub-Saharan Africa: A decade of remarkable progress. Trop Med Int Health 2014;19(4):450-458. DOI:10.1111/ tmi.12269

S Afr Med J 2016;106(10):953. DOI:10.7196/SAMJ.2016.v106i10.11365

Alpha-thalassaemia trait as a cause of unexplained microcytosis in a South African population

To the Editor: I read the article by Loonat et al.[1] with interest. In the early 1980s a study was undertaken at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa (SA), to assess the frequency with which a low red cell mean corpuscular volume

October 2016, Print edition

CORRESPONDENCE

(MCV) was associated with the presence of thalassaemia or an abnormal haemoglobin.[2] Between January 1979 and December 1980, 730 patients with an MCV of ≤60 fl were investigated. Forty-six (6.4%) were found to carry a β-thalassaemia gene and 20 (2.7%) had an abnormal haemoglobin, most commonly Hb E. The prevalence of thalassaemia was highest in individuals of mixed ethnic origin, and abnormal haemoglobins were found exclusively in this population, although the numbers of white and black patients were much smaller in comparison. Alpha-thalassaemia was not tested for, as the technology was unavailable at the time owing to cost constraints. Nevertheless the findings confirmed that patients with persistent unexplained microcytosis/hypochromia should be screened for thalassaemia and haemoglobin variants. A further survey of blood donors of mixed racial origin was undertaken to determine the prevalence of inherited haemoglobin disorders in this population more accurately.[3] Globin synthesis studies and DNA analyses were performed in donors with microcytosis or hypochromia or both associated with normal ferritin, Hb A2 and Hb F levels. DNA was analysed by Southern blotting and hybridisation with an α-globin complementary DNA probe and a γ-globin genomic probe. In 989 donors screened, Hb S and E were the commonest structural variants detected, each with a prevalence of 1%. Hb C was detected in just 1 donor. Seven donors had β-thalassaemia trait (0.8%) and 2 had hereditary persistence of fetal haemoglobin. A total of 45 donors had DNA analyses. Thirtythree were documented as having α-thalassaemia, the majority (n=24) of whom were heterozygous for the α+ (–α/) haplotype, with an observed frequency of 0.023. I am not clear whether other haemoglobin variants, in particular Hb E, were screened for in the study by Loonat et al.[1] Hb E was first described in Thailand and is common in South-East Asia. Many South-East Asians who were brought to the Cape in the early years of settlement were from Indonesian islands, and presumably this accounts for the presence of Hb E in the mixed-race population of the Western Cape. The heterozygous and homozygous states for Hb E are benign conditions clinically, but individuals often have red cell microcytosis and/or hypochromia.[4] The βE gene results in inefficient synthesis, as borne out by studies that show decreased βE globin chain synthesis,[5] and there is also evidence that the βE messenger RNA is relatively unstable.[6] It therefore appears that the βE gene leads to a mild form of β-thalassaemia. The double heterozygous condition of Hb E/β-thalassaemia is, however, a major public health hazard in the Far East, India, Pakistan and Bangladesh, with a clinical picture akin to that of thalassaemia major. Milder forms of Hb E/βthalassaemia have also been described and are perhaps the result of Hb E interaction with β+-thalassaemia. With regard to α-thalassaemia, other studies in southern Africa include those of Ramsay and Jenkins,[7] Mathew et al.[8] and Rousseau and Mathew. [9] The former studied a group of San in the Kalahari region of Namibia and found the –α/ determinant to occur at a frequency of 0.06. They postulated that the –α/ haplotype has a significant protective effect against malaria. Rousseau and Mathew[9] performed follow-up DNA analyses on neonates with Hb Bart’s detected in cord blood samples. The –α/ determinant was the most frequent haplotype and the observed frequency was very similar to that in the donor study. Krause et al.[10] summarised their 30-year experience in testing for haemoglobinopathies in Johannesburg: five common α-globin deletions were identified with 10 genotypes. The most common deletion identified was –α3.7 in individuals of different ethnicities.

Red cell microcytosis/hypochromia is most commonly caused by iron deficiency and chronic inflammatory or infectious disorders. However, in patients with persistent unexplained microcytosis and/ or hyopchromia following a thorough haematological assessment, a full investigation for the presence of a haemoglobinopathy is warranted. Haemoglobinopathies are not the most common monogenic disorders in SA, but from the data summarised above it is clear that they do occur at significant frequencies in high-risk minority groups, and when detected appropriate genetic counselling can be offered. It is also important that these patients are identified, since they may receive inappropriate chronic therapy such as iron medication. A R Bird

Western Province Blood Transfusion Service, Cape Town, South Africa arbird27@gmail.com 1. Loonat SB, Naran NH, Thein SL, Alli NA. Alpha-thalassaemia trait as a cause of unexplained microcytosis in a South African population. S Afr Med J 2016;106(3):276-279. DOI:10.7196/ SAMJ.2016.v106i3.1063 2. Bird AR, Karabus CD, Hartley PS. Microcytic anaemia and haemoglobinopathy in Cape Town children. S Afr Med J 1982;62(13):429-430. 3. Bird AR, Ellis P, Wood K, et al. Inherited haemoglobin variants in a South African population. J Med Genet 1987;24(4):215-219. DOI.10.1136/JMG.24.4.215 4. Fairbanks VF, Gilchrist GS, Brimhall JJ, et al. Haemoglobin E trait re-examined: A cause of microcytosis and erythrocytosis. Blood 1979;53(1):109-115. 5. Bird AR, Wood K, Leisegang F, et al. Haemoglobin E variants: A clinical, haematological and biosynthetic study of 4 South African families. Acta Haematol (Basel) 1984;72(2):135-137. DOI.1159/000206374 6. Traeger J, Wood WG, Clegg JB, et al. Defective synthesis of Hb E is due to reduced levels of βE mRNA. Nature 1980:288(5790):497-499. DOI.10.1038/288497ao 7. Ramsay M, Jenkins T. α-thalassaemia trait in Africa: The oldest malaria protective trait? Lancet 1984;324(8399):410. DOI.10.1016/S0140-6736(84)90581-6 8. Mathew CGP, Rousseau J, Rees J, Harley EH. The molecular basis of alpha thalassaemia in a South African population. Br J Haematol 1983;55(1):103-111. DOI.10.1111/j.1365-2141.1983.tb01228.x 9. Rousseau J, Mathew CGP. The incidence of Hb Barts and alpha thalassaemia genotypes in a South African population. Acta Haematol (Basel) 1985;73(3):159-162. DOI.10.1159/000206310 10. Krause A, Wainstein T, Essop FB, Goodyear Q. Testing for haemoglobinopathies in Johannesburg, South Africa: A 30-year review. S Afr Med J 2013;103(12 Suppl 1):989-993. DOI.10.7196/SAMJ.7255

S Afr Med J 2016;106(10):954. DOI:10.7196/SAMJ.2016.v106i10.11134

Private practice-driven research

To the Editor: When working in private practice, we all come across questions we are curious to explore, but clinical research has long been viewed as the domain of tertiary medical institutions, or so-called ivory towers. Research does not need to be relegated to academics alone, as integrating clinical research within private practice can be intellectually stimulating and rewarding on many levels. As research funding and grants become increasingly scarce, there will be an increasing need for private practitioners to participate in clinical research,[1] both in cohort studies and in the further testing and development of new therapies. The purpose of this letter is to encourage colleagues in the private sector to participate in clinical research, which can transform the way they practise; however, the demands of doing research should not be underestimated. Those of us who work in the private sector see our main priority as the care and treatment of our patients, so we have significant time constraints with regard to conducting research. The simplest way to get started in clinical research is to look at your own practice and think of a difficult or interesting clinical conundrum that you would like to answer. This could be as simple as analysing data on your patients’ outcomes or their pathways to care. The outcomes range from simple yet important events such as relapse or hospitalisations to more complex phenomena such as quality of life. In fact, you may already be collecting these data on your patients during routine clinical practice in order to improve the quality of your service.

October 2016, Print edition

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CORRESPONDENCE

Challenges

Private practice settings have unique features that make it challenging to conduct research. Most colleagues worry when they enter private practice that they will not have time to engage in clinical research or other educational activities that drew them to specialise in the first place. Colleagues are busy with high patient loads, managing their business and personnel, and time-consuming administrative duties. In addition, most of us are not affiliated to an academic or training institution, where most research is traditionally carried out, and therefore feel that we do not have access to supervision and mentorship from our senior colleagues in academia. Some important ethical issues also need to be explored. For example, conducting research on your own patients may require careful consideration of patient autonomy and informed consent. [2] Concerns have been raised regarding the practice of recruiting one’s own patients into clinical trials and clinical research, but to exclude such subjects would result in the effective exclusion of private practice as a viable environment in which to conduct such research. Following proper ethical guidelines when one is involved in clinical trials or clinical research in the private setting will be of paramount importance. The general requirement is to obtain ethical clearance from the hospital review board. If the hospital does not have an ethics review board, one would have to seek a central ethics committee. However, we can all strive to be scientist-practitioners, and to both consume and contribute to research literature.

Benefits

The patient population, treatment needs and availability of resources differ substantially between private and public healthcare patients, but in both sectors there is new knowledge to be learned and shared with the medical community. There are many private practitioners who have presented very interesting cases at continuing medical education meetings. Many of these cases deserve to be written up and shared more widely with other colleagues. Intellectual stimulation and adding variety to the daily task of seeing patients can be rewarding. The opportunity to travel to academic meetings and conferences to present one’s work is very gratifying. Making contributions to the understanding of disease processes and development of new therapies helps fulfil our own intellectual curiosity, as well as leading to improved patient outcomes and assisting colleagues who may have challenges with similar cases. Clinical trials can also build up your practice in two ways: bringing new patients to your practice and increasing community awareness of your practice. Industry-sponsored trials relieve you of the task of having to create a study design or clinical protocol. They also provide training and some remuneration for the time spent participating in the trial. The training can be particularly helpful in building up the confidence one needs to pursue one’s own research. Clinical research conducted in the private setting can potentially strengthen the clinical skills of any clinician. The patient pool available to clinicians in private practice is considerably smaller than that in state institutions. As waiting periods are often shorter in private practice, clinicians may see a different patient population (e.g. at an earlier stage of the illness). Including these patients in research will add valuable information that may ultimately improve delivery of care to patients. Recently, research conducted by colleagues in academic settings has been criticised as detached from the common issues faced by ordinary clinicians.

Lastly, we need data to support some of our unique clinical practices. It is clear that a large number of our psychiatric patients need more than one psychotropic agent in order for them to do well, yet we were taught simple pharmacological practices of monotherapy that did not take complex comorbidities into account.[3] Data from private practices could help us argue for increased funding from medical insurance companies, ultimately leading to better patient care.

Conclusion

The practice of medicine today is driven by evidence. Although clinicians based in public health services have access to a wider population base, private practice-based research will be extremely useful as it will supply data that can increase the speed of implementation of new evidence-based practices into direct patient care. Private practice is a viable environment for conducting research, and clinical research should no longer be relegated to the halls of academia. Sibongile Mashaphu

Department of Psychiatry, School of Clinical Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa mashaphus@hotmail.com

Bonginkosi Chiliza

Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa

1. Gevers W. Clinical research in South Africa: A core asset under pressure. Lancet 2009;374(9692):760762. DOI:10.1016/S0140-6736(09)61119-3 2. Kass NE, Sugarman J, Faden R, Schoch-Spana M. Trust, the fragile foundation of contemporary biomedical research. Hastings Cent Rep 1996;26(5):25-29 DOI: 10.2307/3528467 3. Correll CU, Gallego JA. Antipsychotic polypharmacy: A comprehensive evaluation of relevant correlates of a long-standing clinical practice. Psychiatr Clin North Am 2012;35(3):661-681. DOI:10.1016/j.psc.2012.06.007

S Afr Med J 2016;106(10):955. DOI:10.7196/SAMJ.2016.v106i10.11254

Effects of oestrogen on prepubescent children

To the Editor: It has been brought to my attention by a troubled patient I am treating that oestrogen cream (combined oestriol and oestradiol) is being prescribed and sold without adequate warnings about its dangerously detrimental effects on the bones of developing children. After very easily acquiring oestrogen cream from an anti-ageing clinic, and seeing the compounding pharmacy’s website on which the cream is simply described in glowing terms as a health-enhancing supplement, my patient unfortunately used some on her two prepubescent children. The cream has had a profound effect on their growth and development, resulting in stunting, and has also had a negative effect on their weight and body shape. My patient’s confidence in using oestrogen cream was reinforced by its having previously being prescribed to one of her daughters by a GP. The girl had recurrent urethral sensitivity, and my patient was told that oestriol cream (Femigel) would ‘thicken the skin’. The package insert, which she read, mentioned only breast enlargement in males and a few other minor side-effects. There was no mention of any bone-altering or negative developmental effects. The oestrogen cream my patient acquired for herself had no warnings or side-effect information at all. This cream is currently being sold with a small sticker, warning that a few hours should elapse after application

October 2016, Print edition

CORRESPONDENCE

before handling pets and children. No reason is given for this caution. This cream should be supplied with an insert making it absolutely clear that oestrogen exposure results in epiphyseal fusion and growth plate senescence resulting from the death of proliferating chondrocytes in developing bones. If this information had come with the cream, for example in the form of a prominent ‘WARNING’ stating that ‘A few applications will lead to stunted growth of the long bones in children’, it is highly unlikely that my patient would have used it and this tragedy would not have occurred. It appears that a miniscule amount of cream will result in developmental effects, and it is dangerous if left lying in a drawer accessible to playing children, or even if the jar is emptied and used for another purpose.

There needs to be far more caution in the handling of these natural hormones, and doctors should ensure that they prescribe these creams only where absolutely necessary. I would value the thoughts and comments of colleagues who have more experience of these products. Are the current regulations governing the use of natural products sufficient to protect the public? François Daubenton

Psychiatrist in private practice, Cape Town, South Africa dauby@iafrica.com S Afr Med J 2016;106(9):843. DOI:10.7196/SAMJ.2016.v106i9.10456

Conﬁdence Through Clinical and Real World Experience1-3 #1 NOAC prescribed by Cardiologists* Millions of Patients Treated Across Multiple Indications4 References: 1. Patel M.R., Mahaffey K.W., Garg J. et al. Rivaroxaban versus warfarin in non-valvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91. 2. Tamayo S., Peacock W.F., Patel M.R., et al. Characterizing major bleeding in patients with nonvalvular atrial fibrillation: A pharmacovigilance study of 27 467 patients taking rivaroxaban. Clin Cardiol. 2015;38(2):63–8. 3. Camm A.J., Amarenco P., Haas S. et al. XANTUS: A Real-World, Prospective, Observational Study. 4. Calculation based on IMS Health MIDAS, Database: Monthly Sales December 2015. For full prescribing information, refer to the package insert approved by the Medicines Regulatory Authority (MCC). S4 XARELTO ® 10 (Film-coated tablets). Reg. No.: 42/8.2/1046. Each film-coated tablet contains rivaroxaban 10 mg. PHARMACOLOGICAL CLASSIFICATION: A.8.2 Anticoagulants. INDICATION: Prevention of venous thromboembolism (VTE) in patients undergoing major orthopaedic surgery of the lower limbs. S4 XARELTO ® 15 and XARELTO ® 20 (Film-coated tablets). Reg. No.: XARELTO ® 15: 46/8.2/0111; XARELTO ® 20: 46/8.2/0112. Each film-coated tablet contains rivaroxaban 15 mg (XARELTO ® 15) or 20 mg (XARELTO ® 20). PHARMACOLOGICAL CLASSIFICATION: A.8.2 Anticoagulants. INDICATIONS: (1) Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (SPAF); (2) Treatment of deep vein thrombosis (DVT) and for the prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE); (3) Treatment of pulmonary embolism (PE) and for the prevention of recurrent pulmonary embolism (PE) and deep vein thrombosis (DVT). HCR: Bayer (Pty) Ltd, Reg. No.: 1968/011192/07, 27 Wrench Road, Isando, 1609. Tel: 011 921 5044 Fax: 011 921 5041. L.ZA.MKT.GM.01.2016.1265 *Impact RX Data Oct - Dec 2015 NOAC: Non Vitamin K Oral Anticoagulant

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

IZINDABA

Election politics ride roughshod over clinicians, patients ‘In individuals, insanity is rare; but in groups, parties, nations and epochs, it is the rule.’ (Friedrich Nietzsche) Strange things happen at election time. Patient care and doctor support can come a very poor second to tub-thumping and vote-collecting – that’s if the stories of two hospital CEOs with impeccable and impressive track records, highly respected among their rural peers, can be believed. Weird as it may seem, this year’s Rural Doctors of South Africa (RuDASA) Lifetime Achiever Award recipient Dr Victor Fredlund, age 60, CEO of Mseleni Hospital, spent nearly 4 months at home on officially enforced leave (until this July). Aspirant local political candidates and unions led a charge against his withdrawal of job offers from two cleaners and his firing of a third. Head office bureaucrats insisted that the removal of the veteran stalwart from the far northern KwaZuluNatal (KZN) hospital was ‘for his own safety’, bickering, fudging and stalling way after any perceived threat to him had evaporated. Then, seemingly at a loss over how to justify his lengthy absence, they charged him in August – for doing exactly what they’d advised him to do. It got every bit as bizarre for Dr Roger Walsh, CEO at Fort England Psychiatric Hospital in Grahamstown, and his senior clinical staff, culminating in Walsh being ordered by Eastern Cape Health Department superintendent-general Dr Thobile Mben gashe to repair to the provincial headquarters during a wildcat strike in mid-July – also for his own ‘safety’. Walsh refused, citing a Bisho-ordered independent legal probe that had wholly cleared him and his management of 36 fatuous union charges involving alleged wrongdoing, mismanagement, negligence and corruption. The probe, which found local shop stewards ignorant of the terms and conditions of employment and ‘in need of training’, was ignored by Bisho head office, which also reneged on an earlier promise to secure a court interdict against the illegal mid-July wildcat strike. Members of the three unions had barged into wards, blowing whistles and beating sticks on tables and countertops, ordering workers out, allegedly threatening to burn their homes and at one stage allegedly assaulting Walsh. On 18 July, the strikers reportedly stole keys to

the kitchen and for the food delivery van. Thinly spread senior clinicians comforted and tended to upset patients, administered medicines, cooked food and ordered sandwiches. Fort England houses 300 patients with mental health disorders, some of them ‘extremely disturbed and needing constant supervision’, plus 26 prisoners and some of the ‘most difficult and dangerous’ state patients in the country. Walsh’s team warned Bisho that ‘without proper supervision there is a danger of violence, escapes and relapsing of psychosis going unnoticed’. Back in KZN, Mseleni Hospital’s Fredlund said of his union saga: ‘It’s just bizarre. The province’s charge is that I wilfully and deliberately abused my power in dismissing a guy who failed to declare a previous assault conviction in his job application and that I withdrew the job applications of two others who allegedly falsified their addresses. That’s precisely what head office advised me to do.’ He was speaking just hours after his disciplinary hearing ended on 10 August. Nearly a month later, he received an email clearing him of all charges. By then he had unilaterally instructed 20 head officesuspended general orderlies and his five pivotal managers to return to work, but received instructions that he must charge his chief matron, the human resources manager and the systems manager – for allegedly illegally hiring some orderlies.

One of two local political ward aspirants allegedly called for the hospital to be torched at a rowdy public meeting where Fredland and his management were publicly accused of taking back-handers and being corrupt in making appointments. As at Fort England, where his clinical colleague Walsh was hand-picked by the ‘union-proof ’ (and thus short-lived) former superintendent-general, Dr Siva Pillay, to sort out and improve services at the strife-torn hospital complex, local political conditions were ripe for the picking. The 20 Mseleni District Hospital general orderly positions came up for grabs earlier this

October 2016, Print edition

Rachel and Victor Fredlund.

year. There were 2 720 applicants. Poverty and joblessness are endemic in the coastal bushland district, 60 km from Mozambique and close to the sprawling Lake Sibayi. Locals catch fish and grow crops to survive and, unsurprisingly, believe that any local jobs should be for local folk, a belief reinforced by politicians at local rallies. When it emerged that two of the Mseleni Hospital job applicants were not locals and had allegedly falsified their addresses, it was quick and easy to breathe the tinder into conflagration. One of two local political ward aspirants allegedly called for the hospital to be torched at a rowdy public meeting where Fredlund and his management were publicly accused of taking back-handers and being corrupt in making appointments. The meeting was held in a community hall Fredlund had built. A long list of historical grievances was produced. Two political candidates (initially both ANC) vied to outdo each other and demanded the heads of Fredlund, the hospital matron, the human resources officer and the systems manager (all were put on enforced leave by head office).

Keeping a stiff (and hairy) upper lip

Fredlund and his colleagues made medical history by describing what is now known as Mseleni hip disease, a uniquely localised condition for which they regularly conduct surgery. No such operation happened for 4 months this year as Fredlund – a devout

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IZINDABA

Mseleni Hospital’s Dr Kobus Viljoen accepts the RuDASA Lifetime Achievement Award on colleague Dr Victor Fredlund’s behalf.

Christian, who displays no noticeable rancour – champed at the bit at home. His medical manager, Dr Kobus Viljoen, who stood in as CEO, has the required expertise, but was tied up running the hospital and unavailable to do surgery. Viljoen wore his sentiments about the treatment of his senior colleague on his face in the form of a full beard – he stopped shaving in protest on 3 March, the day he took over as acting CEO, removing it when Fredlund was cleared. Among the many anomalies in the saga: the provincial labour relations handbook stipulates a maximum 60-day period of suspension without charge. Fredlund was kept at home for nearly twice this long without charge. Anaesthetic machines used to gauge the hospital’s oxygen supply system stood unserviced for months, putting patients in potential danger and at one stage almost forcing the transferral of 40 maternity ward patients to another hospital. A provincial special investigations unit’s lengthy probe into Fredlund (encouraged by him) was kept under wraps, in spite of repeated demands that it to be made public. The provincial health department was represented by a lawyer at Fredlund’s hearing in alleged contravention of its own disciplinary code.

Resignations

Even Fredlund’s long-suffering, seemingly phlegmatic response had its limits. He was ready to appeal to the labour court if necessary. ‘My real frustration is that this is distracting from the battle of fighting disease and poverty. If you’re looking for a battle, there are plenty of things out there to fight, not

each other,’ he observed wryly. He declines to even try to quantify any real patient harm caused by his and his senior clinical and administrative colleagues’ lengthy enforced absences. However, Izindaba learnt that at least 19 staff members resigned, including his entire HR department, with none of their functions restored. Adds Fredlund: ‘I run quite a [proficient] clinical team, and I’m not indispensable. There just wasn’t that much senior cover in my absence. I cannot say how many patients died or not because I wasn’t there, but one friend of mine, a local pastor (and patient), died while I was away. My medical staff did a fantastic job in my absence under extreme pressure and abuse. Obviously our system was working very well, so it had degrees of buffering. A lot of people stood in and did a great job. But instead of rising to the occasion, they were trying to save a sinking ship. We were on the rise.’ Mseleni Hospital won the national Batho Pele service delivery award (across all government departments) last November. The year before that it won the KZN Premier’s service excellence award and the year before that the MEC (for KZN Health) service excellence award. ‘Then the [provincial] DoH takes our management apart and plants an atom bomb,’ Fredland observes. The veteran hospital chief refuses to see the dark side. A friend and confidant to local chiefs and community leaders, he says some good has come of the madness. ‘I’ve been seen to be vulnerable by the community – so many have come to express love and concern. Young and old stop me on the roadside and ask if they can come to my house and pray.’ The local chief intervened very effectively at one stage to berate rowdy agitators, threatening to banish them from the district if they continued to ‘act like children’. Last month the chief invited Fredlund and his wife over for supper, where they prayed for them. Fredlund’s wife, Rachel, had facilitated the building of a direly needed orphanage near the hospital, tragically burnt down (due to an electrical fault) in June last year, with one child fatality. The 55 orphans were farmed out to other institutions across the country, but plans for rebuilding have stalled as the Department of Social Development struggles to come to terms with new building regulations and to approve a new plan. Meanwhile, Rachel Fredlund has already raised ZAR2 million of the 3 million needed for its reconstruction. The similar political deconstruction of a much-improved provincial healthcare facility was still playing out at Fort England at the time of writing. Walsh and his physician

October 2016, Print edition

wife Michelle were known and loved in the Barkley East District, where they selflessly ran the local district hospital for many years before his October 2012 appointment. The change saw him encounter some initial tension over nurses’ scope of practice and a 1-day strike, to which he responded with the ‘no-work, no-pay’ rule. Under orders to reduce costs, he further raised the ire of the unions when he swapped seven cleaners from better-paid Sunday shifts to Monday ones where only two were on shift. He also made cleaners work a 5-day instead of a 4-day week. The measures immediately improved his hospital’s national core standards cleanliness scorecard. However, there was a price. His shop stewards refused to re-engage until he was removed as CEO. Mindful of the union-linked fates of Dr Kobus Coetzer, the CEO removed from Livingstone Hospital in Port Elizabeth (under similar circumstances) and Dr Nthombi Qangule, Dora Nginza Hospital’s CEO in East London, banished to health department headquarters in Bisho,[1] Walsh resolved to stay put, resisting repeated senior officials ‘suggestions’ that he be redeployed to Bisho.

Fredlund observes wryly: ‘My real frustration is that this is distracting from the battle of fighting disease and poverty. If you’re looking for a battle, there are plenty of things out there to fight, not each other.’ Walsh’s courage saw his entire senior clini cal staff close ranks behind him – and led to the three unions (the National Educa tion, Health and Allied Workers’ Union (NEHAWU), the Democratic Nursing Organi sation of South Africa (DENOSA) and the National Union of Public Service and Allied Workers (NUPSAW)) upping the ante. Finally, an advocate was hired to do a probe, taking 90 days to produce a report which was sent to head office on 15 July this year. No fault was found with Walsh or his management. The unions, unhappy with its contents, threatened to ‘bring the hospital to a standstill’ and wrote that they would ‘forcefully remove’ Walsh and his ‘poor’ management team. The hospital leadership met with head office officials, urging them not to give in to ‘intimidation, threats and hooliganism’. Walsh’s appeal to health MEC Phumzile Dyanti to secure a court interdict against the disruptive unions led to her questioning his physical

IZINDABA

safety before purportedly agreeing to the interdict. Instead of the interdict, however, the province’s senior manager for tertiary hospitals arrived at his house on the evening of 18 July, saying Mbengashe had ‘conceded to the unions’ and that Walsh ‘must move to Bisho’. (Mbengashe’s predecessor, Dr Siva Pillay, considered a maverick by Bisho’s political elite, had by then long been worked out.[2]) Walsh took legal advice and was told that the ‘move to Bisho’ instruction was both unreasonable and unlawful. He asked for written instruction, which Mbengashe duly supplied on 25 July, alleging that Walsh’s removal was in the best interest of patients, continued service delivery and his own safety. In the letter, Mbengashe ordered Walsh not to report at Fort England until 5 August. Says Walsh: ‘When I went back to work the unions wanted to know what I was still doing there.’ He took the most pragmatic option – a holiday with his wife in Namibia until 26 August. Upon his return Mbengashe reinstituted the probe, which included fresh allegations against him. Walsh underwent a 4-hour grilling, with Mbengashe again ordering him to stay away from the hospital because ‘I cannot afford any industrial action at this time.’

Doctor bodies, provinces respond

Dr Desmond Kegakilwe, Chairperson of RuDASA, said that Walsh and Fredlund were clearly dedicated, vocation-driven doctors who helped develop healthcare delivery systems independently of political dispensations or changes. ‘These are not the first such cases. No matter how good and dedicated you are, you will always end up the victim if corruption comes in and you are the obstacle to whatever agenda these corrupt individuals have. Political power is used to give out this and do that and nepotism comes in. As an organisation we will fight tooth and nail against this. We must optimise service delivery – you can’t sacrifice it on the altar of individual agendas, however powerful the people are. Our objective is quality rural healthcare. We’re going to be watching these and similar cases very carefully in future.’ A spokesman for the KZN Department of Health, Sam Mkhwanazi, e-mailed a detailed list of questions, responded: ‘There are ongoing disciplinary matters involving a number of officials from Mseleni Hospital. However, it is not the practice of the department to ventilate in the public [sic] internal and confidential matters which are employer employee-related.’

The chairperson of the South African Medical Association (SAMA), Dr Mzukisi Grootboom, said ‘It boggles the mind that somebody [referring to Fredlund] would get such accolades from the very department which, when he most needed them, decided to turn a blind eye for political expediency.’ SAMA was ‘extremely perturbed’ at the treatment meted out to doctors who had dedicated most of their lives to servicing needy outlying communities, especially in the context of a country with a dire shortage of rural doctors and basic healthcare services. Demanding that they be fully reinstated until transparent probes were completed, Grootboom said SAMA would not rest until proper processes were followed. The Eastern Cape health department failed to respond to SMSs, voice messages or e-mails. Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(10):956-958. DOI:10.7196/SAMJ.2016.v106i10.11435 1. Bateman C. PE hospital turmoil: CEO leaves, nurses snore in patient beds. S Afr Med J 2016;106(4):320. DOI:10.7196/ SAMJ.2016.v106i4.10763 2. Bateman C. E-Cape’s corruption busting chief finally ousted. S Afr Med J 2013;103(4):215-217. DOI:10.7196/SAMJ.2013. v103i4.11435. DOI:10.7196/6862

Living their passion for upliftment – RuDASA award winners From celebrating the work of a rare rural audiologist to lauding the selfless lifetime achievements of a veteran community change-agent, the Rural Doctors’ Asso ciation of South Africa (RuDASA) awards at its 20th annual conference in Grahamstown on 8 August showcased vocation-driven talent. A near-gold-standard audiology service set up over the past 3 years at the remote but historically award-winning Eastern Cape Zithulele Hospital won the Rural Rehabilitation Worker of the Year for University of KwaZulu-Natal audiology graduate Lineo Lecheko. Enhancing Zithu lele’s multidisciplinary approach, Lecheko’s screening of multidrug-resistant tuberculosis patients has led to vastly improved local hearing outcomes. Patients newly fitted with hearing aids (rare in rural areas) regularly travel long distances just to bring homegrown gifts to thank her for helping transform their worlds. Her initial impact drew the attention

of the provincial treasury, which boosted her work with more than ZAR1 million of audiology equipment and facilitated the placement of an audiology community service assistant.

Epitomising knowledgeto-practice

RuDASA’s Rural Doctor of the Year for 2016 was Dr Nomlindo Makubalo, who started out by winning a bursary to add an MB ChB degree to her medical technology diploma before qualifying and gaining experience in paediatrics, genetics and advanced health management. As the Eastern Cape’s Dis trict Clinical Specialist Team leader, she co-ordinates child healthcare and colle gial training. The citation lauds her major contribution to Child Programme Improve ment Plans (PIP), the procurement of critical hospital equipment and high-care beds, new neonatal units in district hospitals, HIVpositive patient tracing, and establishing

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Award-winning audiologist Lineo Lecheko, with Maryke Bezuidenhout, Rural Rehab South Africa chair.

vital protocols such as the Helping Babies Breathe, Management of Small and Sick Neonates and Emergency Triage Assessment and Treatment. Her training of doctors and nurses in early identification of children with genetic conditions has boosted outcomes in the province, while emergency medical

IZINDABA

service waiting times have improved mark edly under her leadership in the Nelson Mandela Bay and Sarah Baartman districts.

Together with his equally tireless wife Rachel, he continually hosts destitute and homeless local children in the wooden home they built, and has sponsored the living expenses and school/ university fees of countless others over the years. The prestigious RuDASA Lifetime Achieve ment Award for 2016 went to the sprightly 35-year missionary veteran CEO of Mseleni Hospital in KwaZulu-Natal, Dr Victor Fredlund, age 60, whose leadership and compassion have impacted on virtually every sphere of life in the district. From building toilets to teaching basic sanitation, pumping water from nearby Lake

Sibayi to reticulate through the hospital and surroun ding community, Fredlund has also helped buy community tractors for ploughing, set up market and subsistence gardens, built classrooms, a 1 000-seater community hall, a computer centre and sports facilities, facilitated a local market and launched several youth employment projects. His upliftment includes the Lulisanda Kumtwana project, which at one stage had 3 000 registered orphans under its care, many of them AIDS orphans. He pioneered the concept of academic scholarships for rural children, the local teaching of maths and science and the bursary-linked return of healthcare workers to their own communities. Together with his equally tireless wife Rachel, he continually hosts destitute and homeless local children in the wooden home they built, and has sponsored the living expenses and school/university fees of countless others over the years. Accepting the award on his behalf, Mseleni senior medical officer Dr Kobus Viljoen said the Fredlund household overnight was a mix of foreign students, volunteers and

children – often with Fredlund entertaining them on his trusty guitar. A fearless surgeon with a penchant for cardiology, he had conducted ‘every ectomy and otomy in the book’, and regularly did hernia repairs, hysterectomies and total hip replacements, while his clinical brag list included three fullterm extrauterine deliveries (incidence 1 in 30 000). He summed up Fredlund by quoting former US president, Harry Truman: ‘It’s amazing what you can accomplish if you don’t mind who gets the credit.’ The Rural Nurse of the Year award went to Sister Charlotte Stemmet, whose versatile mobile clinic design went into production in the Western Cape recently, while Prince Maletje Maleka won the Clinical Associate of the Year award for his ‘Street Medicine’ project in Tshwane. Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(10):959. DOI:10.7196/SAMJ.2016.v106i10.11436

An uphill battle – getting rehab into mainstream rural medicine Rehabilitation healthcare professionals starting out in a rural hospital need to socialise with and educate clinicians, develop community networks and support groups and build referral systems, if they want to be effective and get to grips with a resource-scarce environment. That’s the advice Maryke Bezuidenhout, a physiotherapist of 14 years’ experience at Manguzi Hospital in far northern KwaZuluNatal and chairperson of the Rural Rehab South Africa (RuReSa), had for colleagues at the Rural Doctors Association of South Africa (RuDASA) annual conference in Grahams town this August. Bezuidenhout believes that a crucial adjunct to clinical knowledge is the ability to socialise and befriend your medical colleagues. ‘You can draw up a formal system and it might work in the private sector, but with the staff turnover in public, you ride on personality and connecting. People are less likely to be shitty to you if they know you personally.’ She and her rehab colleagues at Manguzi use a WhatsApp group. Instead of making it ‘super-clinical, we have regular chats with our doctors. When we talk about stroke, we talk about the lived experience of

stroke survivors,’ she explains. Bezuidenhout said it was a mistake to assume doctors were up to date with rehabilitation medicine. She gave the example of how crucial bowel and bladder control was to spinal patients and how quickly patients could develop chronic kidney disease. ‘Unattended, a patient can die a long, slow death – you have to tailor a programme suited to the specific individual and get all the consumables to them at home – it takes a lot of co-ordination.’ She also urged doctors to ‘look for all things an able-bodied person would have’, citing patients with mental disorders who research had shown died 15 - 20 years earlier than the general population. ‘It’s not the mental health: it’s that doctors don’t treat them as a normal person with normal problems. The response is usually “go and see the psychiatrist”.’

Networking across rutted rural roads

Speaking in the midst of an obstacle course set up to give RuDASA delegates a mild feel of what it might be like to negotiate a rocky river bed or mountainside path in a wheelchair, she stressed the utility of mid- level and community healthcare workers. With so few rehabilitation profess ionals

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available, nurturing both of these cadres and holding education and training workshops so that they could assess and follow up patients in their homes was ‘vital’ to successful outcomes. Linking community healthcare workers to any disabled peoples’ organisations (or creating them) further strengthened rehabilitative care. Bezuidenhout urged newly posted rehab workers to begin their own electronic monitoring system for rehabilitative devices, which very often went missing when patients no longer needed them or died. Also, if there was no rehab referral system at the hospital, ‘don’t reinvent the wheel – find out from a functioning hospital – and don’t wait for people to refer to you. A functioning referral system takes years to build. Giving doctors pamphlets won’t work, but quarterly talks to your nurses and doctors, and sharing outcomes do. Go and pick patients out of the outpatients’ queue, screen the benches,’ she urged. Chris Bateman chrisb@hmpg.co.za S Afr Med J 2016;106(10):960. DOI:10.7196/SAMJ.2016.v106i10.11437

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GUEST EDITORIAL

How can we manage intimate partner violence better? On 27 May 2016, the 69th World Health Assembly endorsed the global plan of action to strengthen the role of health systems within a national multisectoral response to address interpersonal violence, especially against women and children.[1] This landmark plan was adopted with a resolution (EB 138.R3) co-sponsored by 44 mem ber states. It will promote the achievement of the Sustainable Development Goals, including historic Goal 5 (achieve gender equa lity and empower all women and girls), Goal 16 (promote peace, justice and inclusive societies) and Goal 3 (ensure healthy lives and promote wellbeing for all at all ages).[1] These initiatives coalesce with, and will add to, attaining the objectives of the new Global Strategy for Women’s, Children’s, and Adolescents’ Health.[1] The era of making excuses for not addressing sexual, domestic and child abuse effectively in clinical practice is over. These issues point to an evidence base and provide clinicians with current contextual approaches to providing care for intimate partner violence (IPV). They also offer insight into key dynamics within IPV, and the vital interface between IPV, HIV and mental health. Gordon[2] discusses practical steps for identifying and managing IPV against women. This is enhanced by her sensitive, insightful discussion of why women tend neither to report nor to leave their abusive partners and the multiple masked ways in which such patients present. Her extensive clinical experience guides the reader through dealing with IPV. This is complemented by Lopes’s[3] in-depth guide to legal and support services. With a psychology background, and years of experience of non-governmental organisations, Lopes offers a vital understanding of the dynamics of IPV and provides a detailed account of how to secure a protection order within the vagaries of our current court system. Lopes also supplies helpful information regarding referral to shelters, complete with an updated contact list for shelters nationwide. An established working relationship with a social worker is critical, but when they are overloaded, it is important to utilise alternative referral resources. Furthermore, there appears to be little emphasis on, or resources provided for, prevention and early intervention programmes. It became clear from work in the Witzenberg area, Cape Winelands, South Africa, that children are routinely removed in cases where domestic violence is reported, thereby further traumatising both mother and children.[4] Woollett and Hatcher[5] explore key intersections between mental health, IPV and HIV and recommend that HIV care is recognised as an optimal entry point for identifying patients who are living with mental disorders and/or IPV. They introduce the concept of ‘continuous trauma’, which marks a vital evolution in our understanding of trauma beyond post-traumatic stress disorder, where the traumatic stress is no longer current or real. Continuous trauma offers a far more appropriate understanding of the ongoing psychological effect

of living with IPV, where threat and danger are ever present. Woollett and Hatcher[5] also highlight recent national evidence that increased depressive symptoms among women were linked to a perceived frequency of neighbourhood domestic violence, thereby revealing the community level mental health effects of neighbourhood violence. They discuss clinical concepts and interventions for mental health and IPV, noting that recent studies suggest that mental health treatment may reduce IPV, symptoms of mental disorder and risk of future violent victimisation, even if the partners remain together. The ‘separation assumption’ refers to the commonly held belief that partners experiencing IPV should end the relationship, and that it is our duty to encourage them to do so. A woman in a physically violent relationship is more at risk of being murdered when she leaves her partner, and for 2 years thereafter.[6] Is it not therefore highly unethical to urge her to leave? Only when she requests this, can we encourage and support her, including referral to a safe place. In this instance she is advised not to inform her partner, and to take her children with her. Statistics indicating that 1 in 3 or 4 women has experienced IPV in their lifetime can be misleading, as it appears to be an isolated event. Typically, IPV escalates in severity over time, involving multiple violations. Similarly, while the term ‘victim’ is used by authors to align with national initiatives around victim empowerment, in my view the victims comprise our notorious intimate femicide statistics, while those who are still alive, are survivors. Kate Joyner Division of Nursing, Department of Interdisciplinary Health Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa katejoyner.kj@gmail.com 1. World Health Organization. Global Strategy for Women’s, Children’s, and Adolescents’ Health 2016 - 2030. Geneva: WHO, 2016. http://who.int/reproductivehealth/topics/violence/action-plan-endorsement/en/ (accessed 21 August 2016). 2. Gordon C. Intimate partner violence is everyone’s problem, but how should we approach it in a clinical setting? S Afr Med J 2016;106(10):962-965. DOI:10.7196/SAMJ.2016.v106i10.11408 3. Lopes C. Intimate partner violence: A helpful guide to legal and psychosocial support services. S Afr Med J 2016;106(10):966-968. DOI:10.7196/SAMJ.2016.v106i10.11409 4. Rees K, Zweigenthal Z, Joyner K. Implementing intimate partner violence care in a rural sub-district of South Africa: A qualitative evaluation. Global Health Action 2014;7:24588. DOI:10.3402/gha. v7.24588 5. Woollett N, Hatcher AM. Mental health, intimate partner violence and HIV. S Afr Med J 2016;106(10):969-972. DOI:10.7196/SAMJ.2016.v106i10.11410 6. Sharps PW, Koziol-McLain J, Campbell J, McFarlane J, Sachs C, Xu X. Missed opportunities for prevention of femicide by health care providers. Prev Med 2001;33(5):373-380.

S Afr Med J 2016;106(10):961. DOI:10.7196/SAMJ.2016.v106i10.11460

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Intimate partner violence is everyone’s problem, but how should we approach it in a clinical setting? C Gordon, MB ChB, DMH (SA), Dip HIV Man (SA), MPhil (Health Professions Education) Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Cape Town, South Africa Corresponding author: C Gordon (c.gordon@uct.ac.za)

Intimate partner violence (IPV) is a silent public health epidemic in South Africa (SA). Interpersonal violence in SA is the second highest burden of disease after HIV/AIDS, and for women 62% of the former is ascribed to IPV. SA, therefore, has the highest reported intimate femicide rate in the world. IPV has far-reaching consequences, stretching across generations. The cost to the economy and burden on health services are considerable. IPV presents in many ways, cutting across all medical disciplines. Therefore, all medical professionals should be conversant with this issue. This article provides essential, practical steps required for identifying and managing IPV, applicable to any setting. These steps are summarised as six Rs: Realise that abuse is happening (be aware of cues); Recognise and acknowledge the patient’s concerns; Relevant clinical assessment; Risk assessment; cRisis plan; and Refer as needed for medical, social, psychological and/or legal assistance. S Afr Med J 2016;106(10):962-965. DOI:10.7196/SAMJ.2016.v106i10.11408

Intimate partner violence (IPV) is a silent public health epidemic in South Africa (SA), despite progressive reforms in the constitution, legal system, and the implementation of a Victim Empowerment Programme.[1,2] It is also a substantial cause of morbidity and mortality. Despite the human rights ethos of our constitution, far from being a national priority, identifying and managing IPV remain largely unaddressed. When victims seek help, most do so through the healthcare system,[3] yet undergraduate medical curricula persistently produce healthcare professionals unprepared for IPV. As IPV cuts across all medical disciplines, all practitioners should be conversant and competent with this issue.

The Domestic Violence Act

The definition of the SA Domestic Violence Act No. 116 of 1998[4] extends beyond physical and sexual abuse to include ‘verbal and psychological abuse; economic abuse; intimidation; harassment; stalking; damage to property; entry into the complainant’s residence without consent, where the parties do not share the same residence; or any other controlling or abusive behaviour towards a complainant’. Central to this definition is the perpetrator’s desire to subjugate or control the victim, including sexual entitlement, coupled with the belief that this is their right.[4] Domestic violence can occur in any current or previous relationship – even with a rejected suitor. Although IPV also affects men, this article focuses on IPV against women, as it is widespread.

Potential consequences of IPV

Consequences of IPV are profound and far reaching. SA’s female homicide rate is six times higher than global estimates and the highest reported intimate femicide rate internationally.[5,6] IPV harms sexual and reproductive health, causing higher risks of contracting HIV and other sexually transmitted infections (STIs). [1,7] Significantly, victims are less likely to be tested for HIV or to seek medical care, fearing either violence or abandonment if their partner learns that they are HIV-positive.[7] Abused women have higher rates of unintended pregnancies, abortions, miscarriages, preterm deliveries and stillbirths.[8] Furthermore, mental health issues

such as depression, suicidality, anxiety and substance abuse are common.[9] IPV impacts on health-seeking behaviour, resulting in poorer control of chronic diseases. Everyday functioning at work or home can also be affected, including parenting behaviour.[10] No discussion about IPV is complete without considering the children in an abusive household. In the case of perpetrators of IPV, there are high rates of family violence, i.e. abuse of partner and children. Children who witness abuse, or who are themselves abused, can exhibit impaired functioning in a number of different spheres. Child maltreatment is also a well-described risk factor for both experiencing and perpetrating IPV and sexual violence in the future.[10] Impaired health-seeking behaviour extends to child health, as children of abused mothers have a higher under-5 mortality rate.[10] IPV can have a staggering impact on the economy. One study in the UK estimated largely hidden costs of IPV to be almost GBP23 billion per annum.[11] Medical costs to patients and with regard to the economy arise not only from specific interventions such as mental healthcare or surgery, but also from repeated visits for various nonspecific ailments when the diagnosis of IPV is missed. Workplace-related issues such as poorer overall functioning, absenteeism or abuse of resources (such as repeated phoning of victims by perpetrators) further deepen the economic impact of IPV. Importantly, all these effects may persist long after a woman has escaped the abusive relationship. Providers of care may assume that asking about IPV is intrusive or offensive. Nevertheless, women appreciate being asked about IPV sensitively, even if they are not being abused.[12] Lack of time is another highly relevant issue in SA, where state services suffer chronic staffing shortages and are overburdened owing to large numbers of patients. Even in private practice, consultation time is limited. Practically, it is difficult to screen every patient, but certain cues and red flags should prompt further exploration.

Why don’t women report, and why don’t they leave their partner?

Multiple reasons prevent women from reporting abuse. A lack of human rights awareness about IPV, which is consonant with the

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normalisation of abuse in SA, means that women tend not to frame their experiences as abuse. Access to sensitive care is a further barrier – either as physical access to medical or legal facilities (distance, cost of travel) or a lack of access due to abuse being missed (or ignored) by providers. Poor knowledge about, or faith in, the legal system also contributes to this situation. Furthermore, abusers often intimidate women into not reporting and/or withdrawing cases (perpetrators may threaten harm to children, taking children away, or abandonment).[10] Reasons for not leaving an abusive situation echo reasons for non-reporting.[13] Many SA women remain profoundly economically disempowered, as they rely on their partners for financial support, which makes escape arduous. However, even well-educated and/or economically independent women have difficulty leaving an abusive relationship. IPV engenders a complex psychological cycle where victims are made to believe that they deserve the abuse. Victims’ self-esteem can erode to the degree that they feel fortunate to have a partner, that they would never cope without their partner or are unworthy of finding other partners. Love of the partner and hope of change also contribute to these factors. To complicate matters, women become alienated from health professionals, who label them as irresponsible or unco-operative for not leaving.[11]

How do victims of IPV present?

Patients experiencing IPV commonly present with seemingly unrelated problems, or with multiple ‘soft’ nonspecific somatic or emotional complaints. Chronic headaches and other pain syndromes, depression, anxiety, post-traumatic stress disorder and substance abuse are cues for possible IPV.[3] Body language is critical – often the only signs being the patient’s demeanour or style of interaction. Examples are failure to make eye contact, defensive posture, appearing fearful or anxious, vague and non-committal answers, or declining to answer questions. Entry points into the healthcare system can be obvious (e.g. emergency rooms), or more subtle, such as repeated visits to primary care centres, mental health services, general practice or other disciplines, where IPV is unlikely to be identified.[1] Further examples of how IPV can present are set out below.

Red flags that could prompt suspicion of IPV[3,9]

General • Chronic pain syndromes (including headaches, backache and pelvic pain) • Vague, nonspecific somatic complaints, often ongoing • Poorly controlled chronic conditions • Poor day-to-day functioning • An accompanying partner who dominates the conversation, answers on behalf of the patient and/or refuses to leave the room • Anxious, defensive, submissive, or reluctant engagement with the health professional; poor eye contact; conversely, frankly aggressive behaviour. Psychiatric • Depression • Sleeping problems (unable to fall asleep, waking up in the middle of the night and/or ‘thinking too much’) • Anxiety, panic attacks • Post-traumatic stress disorder • Substance abuse.

Gynaecological/obstetric • STIs (acute or chronic), including pelvic inflammatory disease, HIV, syphilis • Sexual dysfunction • Unplanned or unwanted pregnancy; miscarriage; termination of pregnancy • Antepartum haemorrhage • Injuries • Repeated injuries, casualty visits or injuries that do not match the description of the cause. Children • Any suspicion of child abuse should prompt consideration of IPV in the home.

How to ask the question

Health professionals are often uncertain how to enter into a discussion with patients regarding IPV. The need to open this line of enquiry may happen at any point in the health professional-patient relationship. Firstly, confidentiality should be assured, implying a private setting for the consultation. The clinician’s communication skills and body language are important factors in inspiring trust. The following opening questions may be used as needed, keeping in mind that these may also be applicable to past relationships:[3,9] • Are you in a relationship? Are you unhappy in your relationship? • Is everything all right at home? • Often when I see patients with this kind of problem (referring to any of the red flag presentations), it may be caused by other problems, e.g. stress. Are you experiencing or have you experienced any kind of difficulties with your partner? • Has your partner ever threatened you or forced you to do some thing you didn’t want to do? • Have you ever felt afraid of your partner? • Does your partner try to control you (such as who you see, how you dress) or refuse to give you money? The patient’s right to refuse to answer, despite being given an ade quate opportunity to disclose any abuse, should be respected. Table 1 gives further do’s and don’ts in a consultation. Table 1. Do’s and don’ts in a consultation Do

Don’t

• Establish trust • Assure the patient that you believe her (this alone may prove to be enormously therapeutic) • Do a relevant clinical assessment • Inform the patient that abuse is unacceptable • Do a risk assessment • Create a crisis plan • Document in detail • Provide information (posters, pamphlets, websites, telephone numbers of NGOs) • Refer for appropriate medical, psychological, social and legal assistance

• Impose your own judgements on the patient (the frame of reference is what is stated in the Domestic Violence Act of 1998) • Ignore or invalidate the patient’s complaints • Instruct the patient to leave her partner (if a victim is unprepared, she is at great risk of serious harm)

NGO = non-governmental organisation.

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My patient is being abused – now what?

Table 2. Contact details of NGOs

An approach to IPV, using the author’s mnemonic, is summarised below:

NGO

Contact details

National crisis helpline (Lifeline)

0861 322 322

Email: counselling

Managing IPV in a nutshell: The six Rs Realise that abuse is happening (be aware of cues and red flags) Recognise and acknowledge the patient’s concerns Relevant clinical assessment Risk assessment CRisis plan Refer as needed for medical, social, psychological or legal assistance

Should a patient disclose abuse, further action must be taken in accordance with their wishes. Management should encompass empowerment, entailing a thorough health assessment and the provision of information, including options for further care that match the patient’s individual needs. Importantly, ensure that any symptoms (especially vague and nonspecific ones) are not attributable to organic causes. A thorough history and examination should be conducted to exclude these, and further investigation arranged if necessary. Clinical assessment should be guided by the patient’s presenting complaint so that appropriate interventions can be made in the correct sequence (e.g. to address STIs, rape, and depression). A critical facet of managing IPV is to conduct a risk assessment, which necessitates the following questions: • Does the woman fear for her life or safety? • Is she being threatened with serious harm? • Are there children involved in the abuse? • Is the abuse escalating? • Is a weapon involved? (Note: this need not be a weapon in the traditional sense; it could be any object that is being used to harm the woman or child) • Does the partner abuse substances? Should the woman be at immediate risk of serious harm, she (and her children) should be urgently referred to a shelter or be kept in a facility until the former can be arranged, if she so chooses. The importance of documentation cannot be overstated,[9] whether these are patient notes, a formal legal document such as the J88 form, or a sexual assault kit form (which a patient would only have if she has opened a case). Specifics of the nature of abuse should be documented. Exact examples should be given, e.g. verbatim quotes from the patient, and/or outlining what has been said or done by the partner. The name of the abuser and nature of the relationship should be stated. A risk assessment should be done and recorded. Physical injuries should be described, measured and illustrated with diagrams, even if this is not done on the specific legal form. Photographs are very useful (e.g. of injuries, damage to property – taken by patients). The patient should keep evidence of harassment, e.g. text messages or emails. Documentation could mean the difference between: • procuring a protection order or not • opening a successful case or not • clinician being subpoenaed for testimony or not (most probably if the documentation is incomplete) • success or failure of conviction of the perpetrator. Key to managing IPV is identification and referral to systems that can offer comprehensive care.[3] Referral could include information

lifelinecounselling@gmail.com

Stop Gender-Based Violence Helpline

0800 150 150

People Opposed to Women Abuse

011 642 4345

National Network on Violence Against Women

012 321 4959

Sanja Bornman, attorney in the Lawyers for Human Rights Gender Equality Programme Website

021 424 8561

www.lhr.org.za

posters or pamphlets. Patients should be given a referral letter to the mental health nurse at their clinic and contact details of local, relevant non-governmental organisations (NGOs). Some of these are listed in Table 2. Patients may need several follow-up visits at the clinic or practice to attend to all their needs – as with any complex chronic disorder. It is essential that facility/practice managers have updated lists and contact details of local NGOs, shelters and safehouses (Table 2); doctors should insist on this. A crisis plan should be made if the patient wishes to leave a partner and/or the residence that they share, as outlined below:[14] Crisis plan • Leave when your partner is not around, and take your children with you. • Identify places where you can use a telephone quickly. • Always carry a list of emergency numbers. • Put money away safely for transport in an emergency. • Have extra keys for the house and/or car. • Pack clothes for yourself (and children) in a bag, and keep in a safe place (e.g. neighbour’s house). • Ensure that you have essential documents, such as identification documents, birth and marriage certificates, medical aid card, children’s road-to-health cards, and savings/credit cards. • Ensure that someone trustworthy has certified copies of your protection orders, warrants for arrest and other legal documents.

Legal information

Offer legal information if the patient so desires. (A detailed explana tion of the practicalities for securing a protection order is provided in the article by Lopes.[15]) • Protection order (preferable option): • obtain from magistrate’s court (not police station); therefore not a criminal case unless perpetrator violates the order • specifically designed as a behaviour modification mechanism to protect against IPV • available after hours in an emergency • does not expire. • A charge (secondary option due to limitations in scope and issues with regard to police attitudes towards IPV): • laid at police station, opens criminal case • IPV cannot be reported as a crime, but other charges can be laid; e.g. physical or sexual assault

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• in the case of physical violence, a J88 form will be issued, which must be completed by the doctor who first sees the patient. In the case of sexual violence, a rape kit is issued.

What if the patient refuses help?

This is a mentally competent adult’s prerogative. Health professionals are only obliged by law to act in cases of child abuse. Our responsibility is to accurately inform the patient to enable her to make informed decisions. Offer follow-up visits at an appropriate facility to assess her situation and state of mind over time and make an effort to provide continuity of care.

Summary

IPV is a chronic and complex medical condition warranting the same degree of care as other serious, potentially life-threatening conditions. It is every health professional’s responsibility to detect and manage it. Health professionals have enormous power and influence to either re-empower or further disempower women. A single consultation can affect the person’s life profoundly, even if all that is needed is to confidentially talk about the situation. An initial consultation may (or may not) be time consuming, but if done correctly the first time, subsequent visits and management should be much simpler.

1. Martin LJ, Jacobs T. Screening for Domestic Violence: A Policy and Management Framework for the Health Sector. Cape Town: Institute of Criminology, University of Cape Town, 2003. 2. National Department of Health. National Implementation Plan for the Service Charter for Victims of Crime. Pretoria: NDoH, 2007. http://www.justice.gov.za/vc/docs/2007VCIMPL/2007%20Impl%20Plan%2015%20 Nov_CHP_10.pdf (accessed 18 March 2014). 3. Joyner K, Mash R. Recognizing intimate partner violence in primary care: Western Cape, South Africa. PLoS ONE 2012;7(1):e29540. DOI:10.1371/journal.pone.0029540 4. Republic of South Africa. Domestic Violence Act 116, 1998 (Act No. 116 of 1998). Government Gazette No. 19537:2. 1998. 5. Seedat M, van Niekerk A, Jewkes R, et al. Violence and injuries in South Africa: Prioritising an agenda for prevention. Lancet 2009;374(9694):1011-1022. DOI:10.1016/s0140-6736(09)60948-x 6. Abrahams N, Jewkes R, Martin L, et al. Mortality of women from intimate partner violence in South Africa: A national epidemiological study. Violence Victims 2009;24(4):546-556. DOI:10.1891/08866708.24.4.546 7. Fox AM, Jackson SS, Hansen NB, et al. In their own voices: A qualitative study of women’s risk for intimate partner violence and HIV in South Africa. Violence against Women 2007;13(6):583-602. DOI:10.1177/1077801207299209 8. Shamu S, Abrahams N, Temmerman M, et al. ‘That pregnancy can bring noise into the family’: Exploring intimate partner sexual violence during pregnancy in the context of HIV in Zimbabwe. PLoS ONE 2012;7(8):e43148. DOI:10.1371/journal.pone.0043148 9. Martin LJ, Artz L. The health care practitioner’s role in the management of violence against women in South Africa. CME 2006;24(2):72-76. 10. World Health Organization. Understanding and Addressing Violence against Women. Geneva: WHO, 2012. 11. World Health Organization/London School of Hygiene and Tropical Medicine. Preventing Intimate Partner and Sexual Violence against Women: Taking Action and Generating Evidence. Geneva: WHO, 2010. 12. Richardson J, Coid J, Petruckevitch A, Wai S, Moorey S, Feder G. Identifying domestic violence: A cross sectional study in primary care. BMJ 2002;324(7332):274-277. DOI:10.1136/bmj.324.7332.274 13. Rhodes NR, Baranoff-McKenzie E. Why do battered women stay? Three decades of research. Aggress Violent Behav 1998;3(4):391-406. DOI:10.1016/s1359-1789(97)00025-6 14. South African Police Service. Domestic Violence. http://www.saps.gov.za/resource_centre/women_ children/domestic_violence.php (accessed 3 August 2015). 15. Lopes C. Intimate partner violence: A helpful guide to legal and psychosocial support services. S Afr Med J 2016;106(10):966-968. DOI:10.7196/SAMJ.2016.v106i10.11409

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

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Intimate partner violence: A helpful guide to legal and psychosocial support services C Lopes, BA Hons (Psychology) Heinrich Böll Foundation Southern Africa, Cape Town, South Africa Corresponding author: C Lopes (claudia.lopes@za.boell.org)

Violence against women is a significant problem that profoundly affects the physical and mental wellbeing of those affected. While medico legal interventions in South Africa have been firmly established to respond to sexual offences, no formal protocols on intimate partner violence interventions at primary healthcare level are in place yet. In support of recent policy recommendations for the development of a combined health and social sector system response to intimate partner violence, this article provides health professionals with insight into domestic violence and current legal and psychosocial support services. It focuses on how to support and advise abused women about practicalities of obtaining protection orders and accessing shelter services. S Afr Med J 2016;106(10):966-968. DOI:10.7196/SAMJ.2016.v106i10.11409

Underreporting of sexual and domestic violence (DV) offences and problematic police recording of DV cases in particular are barriers to fully understanding the scale of violence against women. However, the available evidence paints a grim picture: police crime statistics between 2007 and 2013 (2013 being the final year of gender disaggregated data) reveal 1 016 588 cases of contact crimes committed against women.[1] Femicide is a major contributing factor, as 50.3% of female homicides in South Africa (SA) are committed by intimate partners.[2] The impact of intimate partner violence (IPV) is considerable. Yet, provincial studies found that in a sample of 216 women accessing shelters for IPV, only one had been referred by a medical professional.[3,4] Given our excessive rates of IPV, with concomitant multiple adverse health and developmental consequences for women and their children, medical personnel should take IPV more seriously. While IPV occurs in all forms of sexual relationships, and involves any gender, statistically men are the greatest perpetrators of IPV. This article therefore makes overall reference to IPV against women.

Understanding IPV

Commonly, women remain in abusive relationships for many years, suffering a multitude of devastating, life-altering consequences.[5] These women are often harshly judged for ‘choosing’ to stay in or for not reporting an abusive relationship. This secondary victimisation reveals a lack of insight into IPV and how it effects the psyche of an abused woman. IPV entails different patterns of behaviour with the intention to exert power and control over an intimate partner. Most easily recognised are injuries sustained from being physically assaulted. However, some perpetrators inflict injuries that are not visible. Victims may also mask such injuries by wearing less revealing clothes or by denying or excusing injuries sustained. Downplaying or justifying the occurrence of abuse is closely associated with experiencing emotional and psychological abuse. Perpetrators commonly accuse victims of provoking the abuse, constantly reinforcing why the abuse is ‘justified’, which leads victims to believe they deserve the punishment. This psychologically abusive strategy is compounded by negative comments, swearing, insults, criticism and humiliation in public, all of which further erode the victim’s sense of self-worth. This reinforces her insecurity and subservience to the perpetrator’s greater power. Another technique abusers commonly employ to control and manipulate their partner is to isolate her from family, friends and

other support networks. Combined with limiting her access to resources by withholding her wages or preventing her from obtaining a job (economic abuse), this isolation traps her further. Forced sexual intimacy is a pervasive form of IPV, yet usually overlooked (ignored) owing to cultural beliefs of male marital ownership. Indeed, girls nationwide are socialised by their mothers to expect marriage to entail such difficulties. An additional, rather confusing factor is that she may still love the abuser. The deterioration of an abusive relationship is often gradual, characterised by cyclical periods of ‘normalcy’ (‘honeymoon phase’), tension building and bouts of violence that escalate in severity over time.[5] During the honeymoon phase, the perpetrator is loving and apologetic, promising that the violence will never happen again. This is seldom the case. Soon tension starts to build as the perpetrator finds fault to justify further violence. Similarly, a victim may fluctuate between loving and hating her partner. The presence of children is often a decisive factor for not leaving an abusive partner. The abuser may emotionally blackmail the victim by threatening that should she leave, her children will be removed from her care. She may also believe that it is in her children’s best interest to live with both parents (a false, but frequently socially reinforced perception). Reasons for remaining in abusive relationships equally affect disclosure of abuse. This is often associated with guilt regarding disloyalty to the abuser and/or feeling ashamed and humiliated by the abuse. Many women are too frightened to leave or report the abuse in case of further victimisation, i.e. losing her children, becoming destitute, or that she may not be believed or supported.

Effective responses to IPV: Support and advice

Effective health system responses include acknowledging IPV and that it is unacceptable.[6] This is particularly imperative in SA, where multiple forms of violence are seen as normative. Understanding the complexity of IPV is key to establishing a caring, empathetic and non-judgemental response. If you suspect abuse, the following are some suggested approaches: • Ensure that it is safe to talk to the victim, with minimal interruptions. She should preferably be on her own. • Starting the conversation may be difficult, but you may gently explore what it is that you have noticed that causes you concern.

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• Importantly, she should know that the conversation will be confi dential and therefore not shared with her partner or anyone close to her. Inform her, however, that you will record the information in her medical record, as she may need evidence of abuse in future. • Gently explain that your intention is to help her. Be open to the possibility that she may deny abuse or not want to confide in you. If so, assure her that she can return to you should she feel differently. If the victim is open to discussing the situation: • Acknowledge that she is not alone as other women have been/are in similar circumstances. • Acknowledge possible feelings of fear, embarrassment, guilt and/or shame. • Do not ask her what she did to have caused the abuse. Nothing done or said can justify abusers’ behaviour. • Only make promises that you can keep. • Encourage and support her to make her own decisions. Do not tell her to leave the relationship. It is her choice. • Do not do anything that will make her uncomfortable or that she is not ready for, and certainly do not put either of you in harm’s way by offering to talk to the abuser. Lastly, assist by exploring available options with her. If she, for example, prefers to remain in the relationship but wants the abuse to stop, advise how she can apply for a protection order. If she wishes to leave the relationship, enquire about how she will support herself and/or whether she can stay with family and/or friends who could emotionally support her. If neither of these options is feasible, assist her with accessing a shelter for abused women. The next section dis cusses both these interventions.

Legal recourses available to victims: Applying for a protection order

The Domestic Violence Act (DVA) No. 116 of 1998[7] provides protection to those directly affected by DV. While this article focuses on DV within intimate relationships (past, present or perceived), it also occurs in other domestic relationships such as members of a family or people sharing a living space. The DVA enables victims (complainants) to apply for a protection order against perpetrators of abuse (respondents). Family members are also eligible for protection if they are directly affected by the abuse. In addition to the types of abuse referred to above, the DVA lists intimidation, harassment, stalking, damage to property, and entry into a victim’s residence. To apply for a protection order, complainants present at the magistrate court nearest to their home or work during court hours. In an emergency outside court hours, the complainant must present at their closest police station and explain how she will suffer undue harm if not urgently assisted. A third party may apply on behalf of a complainant if same has given written consent to do so. Written consent is not required if the complainant is <18 years of age, mentally disabled, or in situations where the court is satisfied that the complainant was unable to provide consent. At court, the application process is as follows: • The complainant completes Form 2, which is available from the court clerk. • This clerk has a duty to inform applicants about the DVA and to assist with the completion of application forms. In some courts, non-profit organisations are available to assist complainants with completing the form.[8] • The form requests information such as the complainant’s and respondent’s contact details; abuse suffered; use of weapons; reasons why the application should be granted; and types of protection required.

• Supporting documents, such as photographs of damage to person and/or property, police reports, a health professional’s letter, Form J88 and/or affidavits by witnesses, will strengthen the application. • Once completed, the clerk submits the form to the magistrate, who decides whether to grant an interim protection order. • If an interim order is granted, it only comes into force once served on the respondent (generally by police). It is issued with a notice for the respondent to appear on a date set by the court (return date). • On the return date, the respondent can argue his/her case at a hearing presided over by the magistrate. Based on the evidence presented, the magistrate decides whether to grant a final protection order. • A warrant of arrest is attached to any order (interim or final) granted. This enables the police to arrest the perpetrator if s/he fails to adhere to the terms set out in the order. In granting an order the court can (among any other action it deems fit): • prohibit the respondent from committing or enlisting other’s help to commit any act of IPV • prohibit the respondent from entering the complainant’s home or shared residence (or part thereof), or prohibit the respondent from preventing the complainant entry into a shared residence • prohibit the respondent from harassing the complainant at work • seize any firearm or dangerous weapon in possession of the respondent • order that the respondent pay rent and/or other forms of monetary relief • refuse or allow only conditional contact with a child if the court deems it to be in the child’s best interest. Unfortunately, even though the DVA is progressive in nature, problems have been experienced with its implementation. Although it provides for an applicant to apply for an order during court operating hours, in practice it depends on the court’s capacity (e.g. at Wynberg Magistrate’s Court in Cape Town, applications are normally only accepted until mid-morning). While anyone who is affected by DV can apply for a protection order, foreign nationals have reported difficulties in doing so. In response to the latter example, Sanja Bornman, attorney in the Lawyers for Human Rights Gender Equality Programme, suggests that if anyone is being denied the service, they should challenge the service provider to produce proof that foreign nationals are excluded.[8] Furthermore, police do not always respond as mandated by law. Sometimes, despite the presence of a protection order and a warrant of arrest, police opt to warn the perpetrator instead of arresting him.[9] Elsewhere, officers stated that a protection order could only be applied for if a charge against the perpetrator had been laid. This is untrue. A victim has the right to lay a charge of abuse, but is not required to do so to be granted a protection order.[4] In addition to requiring the police to act in cases of contravention of a protection order, both the DVA and the South African Police Services’ National Instructions place a duty on police to assist victims of DV to obtain medical treatment, to collect personal items from their residence, and to find suitable shelter.

Sheltering services for abused victims

Shelters provide women and their children with respite from IPV – a safe space to gather their thoughts and feelings while planning for their future. The provision of shelter services in SA falls under the Victim Empowerment Programme of the Department of Social Development (DSD). DSD’s Minimum Standards on Shelters specifies that shelters must meet the basic needs of women and their children (such as food, clothing and protection), as well as provide counselling, support and skills development.[10] In practice, with sufficient funding, shelters can

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provide invaluable care and assistance to victims. This includes individual counselling, support groups and extramural activities. Among other psychosocial support provision, shelters help women to access healthcare and may assist with their legal needs, such as applying for protection orders, laying charges of abuse, instituting divorce proceedings, and applying for grants and legal documents such as birth certificates or identity documents. They may also assist women with finding employment. Most shelters provide on-site crèche facilities for young children. Older children may be assisted to relocate to schools closer to the shelter, or shelters may provide financial assistance for travel to and from their current school. To refer a patient, the National Shelter Movement of SA, an umbrella body represent ing 78 shelters across the country, advises that you have the following information at hand: • their name, age, contact details, and contact information of next of kin (if appropriate) • languages spoken (will a translator be needed?) • level of education (can she read and write?) • area(s) in which she (and abuser) currently reside • brief history of abuse and most recent episode • history of any psychiatric and/or substance abuse disorders, disabilities or chronic ill ness(es) • citizenship status (SA or foreign?)[8] • gender and ages of children, including whether she is pregnant. Note that shelters’ admission criteria differ and some: • may not take children above a certain age (particularly boys) • are unable to care for those with untreated psychiatric or substance abuse conditions • may not have facilities to accommodate persons with disabilities • require a referral letter and/or protection order before admittance. While length of stay varies, most shelters offer 3 - 5 months’ accommodation. Although some charge a minimal service fee if a woman is employed, the majority cover the costs of her stay for free. To find a suitable shelter in your province, please contact the relevant provincial shelter representative (Table 1).

Conclusion

Considering the physical and psychological impact of IPV, including its interrelationship with HIV transmission and teenage pregnancies, it is likely that women and girls will access healthcare prior to seeking intervention from the police or courts. Although attempts have been made to introduce IPV

Table 1. Executive and provincial representatives of the National Shelter Movement of South Africa, 2016 Provincial representatives

Province

Telephone number

Email address

Zubeda Dangor: executive head

Gauteng

011 854 5804 083 289 8818

zubeda@nisaa.org.za

Joy Lange: executive member and provincial representative

Western Cape

021 448 6792 071 906 3949

joy@stanneshomes.org.za

Fisani Mahlangu: executive member and provincial representative

Mpumalanga

013 243 2732 079 310 9633

mburgvictimsupport@telkomsa.net mahlangufisani@yahoo.com

Sabera Timol

KwaZulu-Natal

031 207 6483 072 446 3337

krc@telkomsa.net

Sarah Lekale

Free State

057 353 2865 072 144 7171

lekalese@webmail.co.za lekalese@gmail.com

Rina van der Berg

North West

014 574 3476 072 348 6526

gracecentre@mweb.co.za

Nomawethu Kunene

Gauteng

011 412 1940 011 693 1945 071 930 9734

nomawethu.kunene@gmail.com

Marihet Infintino

Gauteng

011 869 5856 082 449 5210

marihetinfo@amcare.org.za

Rosaline Bailey

Northern Cape

053 631 4379 072 444 3095

ectc@telkomsa.net

Mercy Cwayi

Eastern Cape

042 293 3985 072 692 8392

oneagleswings@telkomsa.net

screening guidelines for some health professionals,[11-13] there is no formalised protocol on interventions at a primary healthcare level and training of healthcare providers is scanty.[5] This is particularly problematic in a country notorious for some of the highest rates of violence against women globally. A recent policy brief recommends the development of a concerted holistic health and social development sector strategy to aid the identification and management of IPV cases.[13] The adoption of such an initiative, combined with current legal and psychosocial support services available to victims, will go a long way to supporting abused women and their children and safeguarding their rights to be free from violence. 1. Watson J. The role of the state in addressing sexual violence: Assessing police and health service delivery challenges faced by sexual offences victims. African Policing Civilian Oversight Policy Brief 2015(13). 2. Abrahams N, Mathews S, Jewkes R, Martin LJ, Lombard J. Every eight hours: Intimate femicide in South Africa 10 years later! South African Medical Research Council Research Brief. 2012. http://www.mrc.ac.za/policybriefs/everyeighthours.pdf (accessed 24 August 2016). 3. Bhana K, Vetten L, Makhunga L, Massawe D. Shelters Housing Women who have Experienced Abuse: Policy, Funding and Practice. Johannesburg: Tshwaranang Legal Advocacy Centre, 2012. 4. Bhana K, Lopes C, Massawe D. Shelters Housing Women who have Experienced Abuse: Policy, Funding and Practice. Profiling Three Shelters in the Western Cape. Cape Town: Heinrich Böll

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Foundation and Tshwaranang Legal Advocacy Centre, 2012. 5. Watson J, Lopes C. Women Reach Out: A Reflection on Violence Against Women and Women’s Stories of Hope. Cape Town: Rural Education, Awareness and Community Health, 2012. 6. Rees K, Zweigenthal V, Joyner K. Health sector responses to intimate partner violence: A literature review. Afr J Primary Health Care Fam Med 2014;6(1). DOI:10.4102/phcfm.v6i1.712 7. Republic of South Africa. Domestic Violence Act 116, 1998 (Act No. 116 of 1998). Government Gazette No. 19537:2. 1998. 8. Gordon C. Intimate partner violence is everyone’s problem, but how should we approach it in a clinical setting? S Afr Med J 2016;106(10):962-965. DOI:10.7196/SAMJ.2016.v106i10.11408 9. Lopes C, Massawe D, Mangwiro, M. Criminal Justice Responses: Assessing Implementation of the Domestic Violence Act in Gauteng. Cape Town: Heinrich Böll Foundation and Tshwaranang Legal Advocacy Centre to End Violence Against Women, 2013. 10. National Department of Social Development. Minimum standards on shelters for abused women. 2001. http://www.gov.za/sites/www. gov.za/files/shelter_0.pdf (accessed 24 August 2016). 11. Bateman C. ‘Formulaic’ gender-abuse guidelines seldom followed. S Afr Med J 2012;102(6):343-345. DOI:10.7196/SAMJ.5965 12. Van Heyningen T, Myer L, Tomlinson M, Field S, Honikman S. Preliminary Recommendations for Primary Level Screening of Perinatal Populations for Depression, Anxiety and Suicidal Ideation and Behaviour in South Africa. Perinatal Mental Health Project, University of Cape Town. 2015. http://pmhp.za.org/ wp-content/uploads/Screening_Advisory_PMHP.pdf (accessed 6 September 2016). 13. Joyner K, Rees K, Honikman S. Intimate partner violence in South Africa: How to break the vicious cycle. Alan J Flisher Centre for Public Mental Health, Policy brief, 2015. http://pmhp.za.org/wp-content/uploads/IPV_policybrief.pdf (accessed 24 August 2016).

Additional reading Fredericks J, Sanger C. A Simplified Guide to the Domestic Violence Act. Cape Town: Women’s Legal Centre, 2014. http://www.wlce.co.za/ images/domesticviolenceguide.pdf (accessed 24 August 2016). Women’s Aid. The Survivor’s Handbook. Bristol: Women’s Aid Federation of England, 2009.

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

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Mental health, intimate partner violence and HIV N Woollett,1 MA (Psychology, Art Therapy); A M Hatcher,1,2 MPhil (Sociology) 1 2

Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Corresponding author: N Woollett (woollettn@gmail.com)

Intimate partner violence (IPV) and HIV are intersecting epidemics in South Africa (SA). Despite recognition that IPV and HIV are bidirectionally linked, less attention has been given to mental health – a key health condition that is at the nexus of both violence and HIV/AIDS. While SA healthcare professionals have made great strides in treating HIV, the corresponding conditions of IPV and mental health receive far less clinical care. Treating mental health has the potential to positively effect HIV care and treatment, but is also a powerful gateway to enhanced comprehensive health in patients. Improving skills in managing the mental health of patients will lead to better health for them and quality of life for affected families. It can also assist health systems to deal more effectively with complex cases that so rarely achieve positive health outcomes. S Afr Med J 2016;106(10):969-972. DOI:10.7196/SAMJ.2016.v106i10.11410

The golden thread: A focus on mental health

Mental health is the common element linking HIV and IPV (Fig. 1). Poor mental health is a symptom of both violence and HIV, but it may also serve as a mediator between the two conditions.

Clinic

Gender inequality

Policies

Socioeconomics

Stigma and silence Post-conflict factors

Provide training, skills and attitudes

Protocols

Job aids and tool

Ongoing support

Mental health

Patient

One in three women worldwide reports physical and/or sexual violence from an intimate partner.[1] Intimate partner violence (IPV) poses a significant public health problem in South Africa (SA). Associated with health risk behaviours and increased use of medical services,[2] it is linked to high rates of HIV infection among young girls and women.[3] Mental health is a major underlying condition that exacerbates the comorbidities of IPV and HIV, and may be an important mediator between IPV and HIV outcomes. In the general population, the 12-month prevalence of any Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)/Composite International Diag nostic Interview (CIDI) mental disorder in a national epidemiological study was 16.5%, with 26.2% of respondents classified as severe cases and an additional 31.1% as moderately severe cases, indicating that mental health problems affect a large portion of the population.[4] The most pervasive mental health consequences of IPV and HIV in the SA context tend to be depression, post-traumatic stress disorder (PTSD) and alcohol/substance use disorders.[4-6] It is also likely that all three disorders are comorbid in this population, requiring a nuanced treatment plan that integrates management of all through one feasible intervention.

Community

Intersecting epidemics

IPV

HIV/AIDS

Fig. 1. Conceptual framework linking mental health to HIV and IPV.

There is a bidirectional relationship between HIV and mental health. In SA studies, high rates of depression and PTSD have been reported among individuals with HIV.[7] Complex reasons for this include premorbid mental conditions, effects of the virus on the central nervous system, psychologi-

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cal impact of living with HIV/AIDS and disclosure, side-effects of medication, and consequent social stigma and discrimination.[8] Conversely, research indicates that women with mental health problems, particularly comorbid drinking and substance use problems, are at heightened risk for HIV,

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primarily as a result of high sexual risk-taking behaviour.[9] Common mental disorders compromise quality of life and functional outcomes in HIV-positive individuals.[5] Furthermore, traumatic stress, or exposure to traumatic events/situations, whereby individuals are overwhelmed by an inability to cope with the experience, accelerates disease progression in HIV-infected individuals by suppressing immune functioning.[5] Addressing traumatic stress and its mental health burden through effective and timeous interventions offers an opportunity to make a transformational impact on the HIV epidemic and patients’ lives. Similarly, there is a bidirectional relationship between IPV and mental health. Traumatic stress is the primary mechanism by which IPV might cause subsequent depression, suicide attempts and PTSD.[5,6] These common mental health problems tend to be most significantly related to IPV. Equally, research suggests that women with mental health difficulties are more likely to experience violence victimisation, particularly those with depression and PTSD. Both conditions are highly prevalent common mental health problems in SA.[4,6] Lastly, there is a bidirectional relationship between HIV and IPV. The latter leads to an increased risk of incident HIV infection among women,[10] and male perpetrators of violence are more likely to be HIV positive, thereby further increasing the possibility of transmission.[11] Conversely, HIV leads to violence because it causes relationship conflict – disclosing one’s HIV status to a partner leads to arguments and blaming one person for ‘bringing’ the disease into the relationship.[12] Among women already living with HIV, experiencing IPV halves their odds of treatment adherence.[13] An important evolution of the thinking around trauma has come with the notion of continuous trauma, which attempts to define traumatic stress when there is a psychological impact that is real and ongoing, with current threat and danger.[14] This is a deviation from the more common understanding of PTSD that implicitly manages the effects of trauma in the past, with an acceptance that the threat is no longer current and real. Although some people who have experienced traumatic events in the past may currently reside in an objectively safe environment, this is not the case in contexts of protracted civil conflict, mass displacement, enduring IPV or high levels of community violence. In these circumstances, ongoing threat and danger is an inescapable part of daily life. Such conditions affect millions of people worldwide, particularly in post-conflict settings such as SA. Continuous traumatic stress therefore offers a particularly valuable local clinical dimension, with concomitant treatment recognising the ongoing nature of the traumatic experience.[14] It is important to note that IPV has mental health consequences for both victims and their communities. A recent nationally representative study in SA found that increased depressive symptoms among women are associated with an increase in the perceived frequency of neighbourhood domestic violence, highlighting the communitylevel mental health effects of such violence.[15] In addition, mental health treatment alleviates the suffering of victims, and recent studies suggest that the treatment itself may reduce IPV, mental problem symptoms, and risk of future violent victimisation, even if women do not leave their violent partners.[16]

Recommendations with regard to clinical skills

Both IPV and mental disorders are common, but unfortunately remain largely unrecognised and untreated within the health system.[1] Considering that patients are more likely to seek healthcare for HIV than for mental health or IPV, providers of HIV care are an optimal entry point for identifying these patients. Interventions to manage both

mental health and IPV need to be simple enough to be incorporated into existing standard packages of care in HIV treatment settings. Interventions should be brief, culturally adaptable, and scalable to settings where task-shifting models of care can be employed.

Clinical concepts

Several underlying ideas inform how mental health and IPV care are delivered. Non-judgemental, caring support is essential for stigmatised health challenges such as IPV and mental health. Women who experience violence and mental health problems need health professionals to provide front-line support: kindness, attentive listening, sensitive non-judgemental enquiry about their needs, validation of women’s disclosure without pressure, and help with access to referrals – all in a safe and containing encounter.[1,17] This approach is consistent with ‘psychological first aid’, a first response to individuals undergoing traumatic events.[1] Arguably, this is not a difficult undertaking and falls in line with ethical codes of conduct for health professionals. Unfortunately, however, such skills are scarce owing to provider attitudes, lack of values clarification, gender inequitable norms, personal experience of violence, mental health difficulties, and HIV.[18] Trauma-informed care is central to safe, effective delivery of mental health and IPV treatment. Typically, victims are in a state of shock and sometimes experiencing traumatic stress when health professionals encounter them. The definition of trauma is underscored by the event having caused intense fear, helplessness or horror. Patients have a strong need to feel safe. Clinicians must increase feelings of safety by asking what women need to help them feel safe. Privacy and confidentiality are paramount. Often these comprise a kind demeanour, and especially for children/adolescents it may be having a known ‘safe person’ near them. Simply ask to find out. Patient-centred care is optimal in treating mental problems, IPV and HIV. With this approach the client’s priorities and preferences lead the clinical treatment plan. In cases of IPV, for example, it is not helpful to inform victims that they should leave the perpetrator or escape dangerous situations. IPV victims are aware of this and are the experts of their own relationships. Clinicians should provide information about the client’s options and offer services, not ‘fix the problem’.

Clinical interventions for mental health

A number of interventions can be provided at the clinic for mental health treatment: • In recent years, effective models for feasible and acceptable mental health treatment in low-resource settings have been developed using paraprofessionals and trained community counsellors to deliver established psychotherapies adapted for local settings. Most of these models are group based to improve effect, and tend to be aligned with evidence-based, trauma-focused cognitive behavioural therapy interventions. There is also consistent mentor ship and supervision for those providing care.[15] • Meditation and mindfulness-based practices can be used as a means of managing what is often experienced as uncontrollable anxiety responses. • Psycho-education crucially involves the validation of responses and experiences as context related and, to a large degree, context appropriate. • Anxiety management and some cognitive restructuring elements are recommended for the treatment of continuous traumatic stress.[14] The objective of cognitive restructuring is to assist patients to endure

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Table 1. Basic and comprehensive clinical services for IPV and mental health Level

Task

Basic care

Comprehensive services

Create referral list

List names and phone numbers for basic local referrals (shelter, police, counselling, medicolegal)

Set meetings with local referrals (shelter, police, counselling, medicolegal, legal assistance, social grants, migrants, child abuse, alcohol abuse)

Create master list of active referrals: those that readily accept new clients

Build referral network

Set regular meetings with referrals to identify better ways to cross refer and manage cases

Sensitise staff

Host 2-hour workshop introducing clinic staff to the topics of IPV and mental health

Host half-day workshops introducing clinic staff to the topics of gender, IPV, mental health, and importance of HIV care

Train providers

Train dedicated providers (at least two per clinic) on identifying IPV/mental health, addressing these topics in the health sector, onwards referral (~10 hours)

Train dedicated providers (at least two per clinic) on basic topics and mental health/IPV/HIV intersections, impact on retention and adherence, trauma-informed care, empathetic and therapeutic skills, prevention of motherto-child transmission considerations (~40 hours)

Ongoing mentorship and debriefing

Lead biweekly meetings with select providers to discuss cases and debrief challenges

Lead weekly meetings with all staff to discuss difficult cases, record treatment approaches, debrief challenges, and share professional impact of the work

Supervision

Provide dedicated providers with biweekly professional supervision with a psychologist or social worker to prevent vicarious trauma and ensure casework is managed at professional and emotional levels

Ask about IPV

Ask for a basic IPV screening for any client that seems to need additional help (targetted screening)

Ask validated IPV tool for all clients (universal screening)

Ask about immediate safety

Make sure client feels safe returning home

Ask about suicidality, child danger, and patient safety returning home. Any positive response triggers a safety protocol (immediate, active referral to psychiatry, shelter, or police)

Assess mental health

Ask two screening questions to assess common mental health disorders

Treat common mental health disorders

If psychotropic medication is indicated, utilise primary healthcare resources

Implement an evidenced-based lay healthworker mental health programme

Empathetic listening

Use kind, non-judgemental approaches in assisting patients

Use kind, non-judgemental approach, employ therapeutic techniques around discussing IPV or mental health challenges, create client-centred safety plans, actively contain strong emotions

Onward referrals

Give patients a referral slip containing phone numbers for additional services

Discuss options with patients for onwards referral. Offer to write a referral letter or phone on behalf of client. Record referral in patient file

Patient

Clinical services

Provider

Building blocks

Community

Description

living in such contexts without becoming totally hopeless, apathetic and disengaged or antisocial and highly aggressive. • Social support, in the form of carefully facilitated support groups or therapeutic sessions, is a critical factor in ameliorating the effect of trauma. Health professionals are well positioned to offer support to victims who come into their care.

Clinical interventions for IPV

While IPV interventions are in their infancy, the following promising practices are being tested worldwide: • Post-exposure prophylaxis (PEP) for HIV after rape or sexual assault must be provided by healthcare professionals as part of post-rape care for victims who are HIV negative (see PEP Guidelines[19]).

• IPV screening at the clinic coupled with empowerment counselling and referrals may reduce further experience of violence.[20,21] Our team is currently testing an intervention, i.e. Safe & Sound in antenatal care (trial registered at ISRCTN: 35969343). Based on lessons from Safe & Sound, Table 1 provides a summary of the clinical services required for basic and comprehensive care for IPV and mental health. It simultaneously illustrates how to create a basic package of IPV services within a clinic setting or how to offer comprehensive IPV care. • Health worker home visits around the time of pregnancy can reduce the experience of violence for up to 2 years post partum.[22] The Domestic Violence Enhanced (DOVE) home visitation programme consists of six brochure-driven sessions, each lasting 15 - 25 minutes.[22] Home visits are led by a combination of lay and professional healthcare workers.

October 2016, Print edition

CME

Male perpetrators of IPV have a high prevalence of HIV and mental disorders, particularly alcohol use disorders, depression and PTSD.[23] While the search for effective mental healthcare strategies to reduce recidivism among perpetrators is ongoing, treatment of alcohol use disorders is emerging as a method of reducing male perpetration.[15]

Non-clinical interventions for IPV

At a population level, interventions that address the underpinning societal gender norms that perpetuate IPV against women and girls are essential.

Supporting staff to tackle mental health and IPV

Often, clinic staff are limited in their abilities to help patients effectively if they are working in chaotic, stressful and unsupportive environments. The mental health of staff is hugely important, as they often confront sensitive and difficult issues that may precipitate emotional distress, defensiveness or self-disclosure. Management of these factors can take a heavy toll on their own wellbeing. Curbing potential vicarious trauma in health professionals through regular debriefing, targeted training in mental healthcare, diversity in case loads and recognition of the difficulty of the work by management is recommended. Also facilitating a supportive, efficient and utilised employee assistance programme for healthcare providers through the National Department of Health is recommended.

Conclusion

Healthcare professionals, especially those engaged with HIV-positive patients, are uniquely placed to identify mental health problems and IPV and to promote early intervention and appropriate intersectoral referral. This will possibly also improve retention in care and adherence to treatment – all fundamental health system goals. Implementing this approach is a powerful opportunity to improve job satisfaction among health professionals. Addressing mental health problems in patients will have positive effects on other areas of health, such as HIV and IPV, leading to relief of suffering in patients and engaging the powerful positive potential of the healthcare system. Interventions to reduce IPV at the neighbourhood level could positively have an impact on other dimensions of population and economic health, including healthcare costs, economic productivity, and broader gender equity.

1. Garcia-Moreno C, Hegarty K, Lucas d’Oliveira AF, et al. The health-systems response to violence against women. Lancet 2014;385(9977):1567-1579. DOI:10.1016/s0140-6736(14)61837-7 2. Gass JD, Stein DJ, Williams DR, et al. Intimate partner violence, health behaviours, and chronic physical illness among South African women. S Afr Med J 2010;100(9):582-585. 3. Jewkes RK, Dunkle K, Nduna M, Shai N. Intimate partner violence, relationship power inequity, and incidence of HIV infection in young women in South Africa: A cohort study. Lancet 2010;376(9734):41-48. DOI:10.1016/s0140-6736(10)60548-x 4. Williams DR, Herman A, Stein DJ, et al. Twelve-month mental disorders in South Africa: Prevalence, service use and demographic correlates in the population-based South African Stress and Health Study. Psychol Med 2008;38(2):211-220. DOI:10.1017/s0033291707001420 5. Seedat S. Interventions to improve psychological functioning and health outcomes of HIV-infected individuals with a history of trauma or PTSD. Curr HIV/AIDS Rep 2012;9(4):344-350. DOI:10.1007/s11904-012-0139-3 6. Devries KM, Mak JY, Bacchus LJ, et al. Intimate partner violence and incident depressive symptoms and suicide attempts: A systematic review of longitudinal studies. PLoS Med 2013;10(5):1-11. DOI:10.1371/journal.pmed.1001439 7. Myer L, Smit J, Roux LL, et al. Common mental disorders among HIV-infected individuals in South Africa: Prevalence, predictors and validation of brief psychiatric rating scales. AIDS Patient Care STDs 2008;22(2):147-158. DOI:10.1089/apc.2007.0102 8. Freeman M, Nkomo N, Kafaar Z, et al. Factors associated with prevalence of mental disorders in people living with HIV/AIDS in South Africa. AIDS Care 2007;19(10):1201-1209. DOI:10.1080/09540120701426482 9. Pitpitan EV, Kalichman SC, Eaton LA, et al. Gender-based violence and HIV sexual risk behavior: Alcohol use and mental health problems as mediators among women in drinking venues, Cape Town. Soc Sci Med 2012;75(8):1417-1425. DOI:10.1016/j.socscimed.2012.06.020 10. Li Y, Marshall CM, Rees HC, et al. Intimate partner violence and HIV infection among women: A systematic review and meta-analysis. J Int AIDS Soc 2015;17(1):1-12. DOI:10.7448/ias.17.1.18845 11. Dunkle KL, Decker MR. Gender-based violence and HIV: Reviewing the evidence for links and causal pathways in the general population and high-risk groups. Am J Repro Immunol 2012;69:1-7. DOI:10.1111/aji.12039 12. Colombini M, James C, Ndwiga C, et al.The risks of partner violence following HIV status disclosure, and health service responses: Narratives of women attending reproductive health services in Kenya. J Int AIDS Soc 2016;19(1):1-7. DOI:10.7448/ias.19.1.20766 13. Hatcher AM, Smout EM, Turan JM, Christofides N, Stoeckl H. Intimate partner violence and engagement in HIV care and treatment among women: A systematic review and meta-analysis. AIDS 2015;29(16):2183-2194. DOI:10.1097/qad.0000000000000842 14. Kaminer D, Eagle G, Crawford-Browne S. Continuous traumatic stress as a mental and physical health challenge: Case studies from South Africa. J Health Psych 2016;21(1):1-12. DOI:10.1177/1359105316642831 15. Meffert SM, McCulloch CE, Neylan TC, et al. Increase of perceived frequency of neighborhood domestic violence is associated with increase of women’s depression symptoms in a nationally representative longitudinal study in South Africa. Soc Sci Med 2015;131:89-97. DOI:10.1016/j.socscimed.2015.03.008 16. Iverson KM, Gradus JL, Resick PA, et al. Cognitive-behavioral therapy for PTSD and depression symptoms reduces risk for future intimate partner violence among interpersonal trauma survivors. J Consult Clin Psychol 2011;79(2):193-202. DOI:10.1037/a0022512 17. Joyner K, Theunissen L, de Villiers L, et al. Emergency care provision for, and psychological distress in, survivors of domestic violence. S Afr Fam Pract 2007;49(3):15-15d. DOI:10.1080/20786204.2007.10873523 18. Jina R, Jewkes R, Christofides N, et al. Knowledge and confidence of South African health care providers regarding post-rape care: A cross-sectional study. BMC Health Ser Res 2013;13(257):1-12. DOI:10.1186/1472-6963-13-257 19. Moorhouse M, Bekker LG, Black V, et al. Guideline on the management of occupational and nonoccupational exposure to the human immunodeficiency virus and recommendations for post-exposure prophylaxis: 2015 Update. S Afr J HIV Med 2015;16(1):1-14. DOI:10.4102/sajhivmed.v16i1.399 20. Kiely M, El-Mohandes AA, El-Khorazaty MN, Blake SM, Gantz MG. An integrated intervention to reduce intimate partner violence in pregnancy: A randomized controlled trial. Obstet Gynecol 2010;115(2):273-283. DOI:10.1097/aog.0b013e3181cbd482 21. Tiwari A, Leung WC, Leung TW, Humphreys J, Parker B, Ho PC. A randomised controlled trial of empowerment training for Chinese abused pregnant women in Hong Kong. Br J Obstet Gynaecol 2005;112(9):1249-1256. DOI:10.1111/j.1471-0528.2005.00709.x 22. Sharps PW, Bullock LF, Campbell JC, et al. Domestic violence enhanced perinatal home visits: The DOVE randomized clinical trial. J Women’s Health (Larchmt) 2016, May 20. [Epub ahead of print] DOI:10.1089/jwh.2015.5547 23. Machisa MT, Christofides N, Jewkes R. Structural pathways between child abuse, poor mental health outcomes and male-perpetrated intimate partner violence (IPV). PLoS ONE 2016;11(3):e0150986. DOI:0.1371/journal.pone.0150986

October 2016, Print edition

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IN PRACTICE

CLINICAL UPDATE

‘Esprit de corps’: Towards collaborative integration of pharmacists and nurses into antimicrobial stewardship programmes in South Africa N Schellack,1 BCur, BPharm, PhD; R Pretorius,2 BCur, MCur, PhD; A P Messina,3 BPharm epartment of Pharmacy, School of Health Care Sciences, Sefako Makgatho Health Sciences University, Pretoria, South Africa D Africa Unit for Transdisciplinary Health Research, Faculty of Health Sciences, North-West University (Potchefstroom Campus), South Africa 3 Department of Quality Leadership, Netcare Hospitals, Johannesburg, South Africa 1 2

Corresponding author: N Schellack (natalie.schellack@smu.ac.za)

With the global threat of antimicrobial resistance now more emergent than ever, there should be wider collaboration between members of the multidisciplinary healthcare team. This article proposes possible ways of engagement between the pharmacist, nurse and doctor. The pharmacist and nurse are placed in an ideal position through united efforts (camaraderie) to redirect healthcare towards improved patient outcomes while also reducing antimicrobial resistance. S Afr Med J 2016;106(10):973-974. DOI:10.7196/SAMJ.2016.v106i10.11468

The current situation

Except for academic centres, in many developing countries it is difficult to replicate resource-abundant stewardship models that are mostly driven by medical microbiology teams and infectious disease (ID) specialists.[2,3] In this regard, effective ASPs depend largely on monitoring practices, teamwork in developing and implementing interventions, and organisational infrastructure.[2] It is therefore critical in the SA context to utilise the existing resources of pharmacists and registered nurses (RNs), who are well placed to co-ordinate anti-infective management and improve patient outcomes. To date, initiatives in SA to promote optimal antimicrobial prescribing have primarily targeted the practices of hospital-based doctors. In addition, until recently very little consideration has been afforded to the contribution nurses can make in anti-infective management and in the development and maintenance of ASPs. This raises the question of how we can broaden involvement of other healthcare professionals in ASPs, build the necessary skills and adapt organisational structures to facilitate effective deployment and integration in the SA national antimicrobial resistance strategy framework[4] and implementation plan.[5]

The role of pharmacists and nurses

Internationally, pharmacists are accepted as equal antimicrobial stewardship (AS) partners. Their focus is to ensure optimal use of antimicrobials and participation or even a leading role in multidisciplinary working groups and committees. Depending on the level of training, the range of antimicrobial management interventions is potentially vast. These include monitoring therapy for appropriateness, providing pharmacokinetic and pharmacodynamic consultation services,

in-service training of young doctors, collaborative research into new methods of persuasive interventions, and measuring consumption. To highlight the indispensable role of pharmacists in recruiting multidisciplinary teams and in co-ordination of interdisciplinary clinician and nurse engagement in AS interventions, Brink et al.[6] recently presen ted a prospective audit and feedback model for AS in ID-constrained, non-academic settings. This SA study was performed in 47 Netcare hospitals, focusing on basic interventions implemented by pharmacists in consultation with prescribers, and demonstrated a significant reduction in overall antibiotic consumption of 18.1% in 116 662 patients.[6] The Netcare model also confirmed that quality improvement science skills are critical in implementing and maintaining an ASP and that stewardship, dependent on local context and resources, can become embedded in existing systems, which is the key to sustainability. A proposed study of process and outcome measures for the management of communityacquired pneumonia is planned nationally, to promote collaboration and team involvement between both private and public sector pharmacists on how to co-ordinate, implement and monitor ASPs. As for pharmacists, inclusion in ASPs of the broad-based, multi disciplinary RNs could have a substantial impact.[3] RNs play an essential role in monitoring compliance with institutional guidelines and best practice, monitoring for drug allergies and side-effects, obtain ing and reporting of therapeutic levels, management and administration of medicines with mixed dosages, e.g. insulin, and ensuring timely and correct administration of antimicrobials.[7] A study conducted in 33 Netcare hospitals found that pharmacists and nurses can collectively improve the timeous administration of antibiotics.[8] Among other things, the study involved institutional system changes and the creation of awareness of administration priority, changing perceptions on waiting times for fixed dosing schedules, and adding commonly prescribed antibiotics to ward stock to prevent delays in administration. The improvement in hang-time compliance (anti biotic administration within 1 hour) in 32 985 patients following implementation of a process improvement protocol was significant.[8] The decisive role of RNs is exemplified by Brink et al.[9] in a study evaluating improved compliance with four perioperative antibiotic process measures (antibiotic choice, dose, duration and timing) in 34 private SA hospitals. Theatre, anaesthetic and surgical ward RNs assisted

October 2016, Print edition

IN PRACTICE

Table 1. Potential collaborative interventions of pharmacists and registered nurses Intervention

Integrative role of registered nurses and pharmacists

Antifungal stewardship

Monitoring the duration and necessity of antifungal therapy following review of β-D-glucan assays and risk scores (100% negative predictivity if both negative)[10]

Emergency department stewardship

Actively participate in creating empirical guidelines based on syndromic antibiograms for common communityacquired infections, ensuring that appropriate cultures are taken, and follow-up of appropriate antimicrobial therapy after discharge, subsequent to culture sensitivity results[11]

Hand hygiene campaigns

Assisting with independent audit of hand hygiene compliance monitoring as part of hospital strategies for process improvement and increased awareness of their collective role and responsibility in infection prevention practices[12]

Indwelling device management

Monitoring appropriate device days, changing devices when needed, and excluding indwelling devices as the source of infection to prevent the irrational use of antimicrobials

Therapeutic drug monitoring

Therapeutic drug monitoring to facilitate effective antimicrobial therapy and timeously identify drug administration problems, including those involving intravenous administration

Vaccination campaigns

Monitoring adherence to vaccination directives and immunisation schedules to reduce mortality and morbidity in preventable infections[13]

the AS teams in significantly improving compliance with the timely administration of antibiotics prior to surgical incision; a 19.7% reduction in the surgical site infection rate in 24 206 surgical cases from a mean group rate of 2.46 (95% confidence interval (CI) 2.18 - 2.73) before intervention to 1.97 after intervention (95% CI 1.79 - 2.15) (p=0.0029) was demonstrated. Collectively these local studies illustrate that integrating nurses in ASPs may contribute to a shared sense of responsibility in the care of the patient, increased professional autonomy, and negating the idea that AS is outside the scope of nursing responsibility and expertise. Whereas behavioural changes associated with successful implementation of ASPs among doctors have been studied elsewhere, globally no or very few data for nurses exist. Other potential collaborative interventions in conjunction with AS teams are outlined in Table 1.

Importance of education and training

The current content and effectiveness of antimicrobial stewardship education of healthcare professionals (HCPs) other than doctors in SA are suboptimal. Furthermore, undergraduate education is variable; a recent study of final-year pharmacy students across SA universities documented significant differences between the eight universities with regard to undergraduate AS education.[14] Furthermore, specialisation in pharmacy at a postgraduate level is not yet formally recognised by the South African Pharmacy Council and not widely available. With regard to nursing, the curriculum currently involves modules on microbiology and pharmacology. However, these are mostly presented as pure rather than applied science, and a new committee to drive change in collaboration with the South African Nursing Council, training institutions and the healthcare industry should be considered. In addition, information on local nurse practitioners’ attitudes, perceptions, and knowledge with regard to antimicrobial use and resistance is mandatory.[15] Local literature on the knowledge and perceptions of nursing practitioners will enable targeted campaigns and short courses focusing on the role of the RN in AS, such as obtaining appropriate specimens for culture, assessing patient response to antimicrobial therapy, and decreasing hospital-acquired infections through the implementation of care bundles, thus increasing awareness and vigilance among RNs during the administration of antimicrobials. RNs also need to contribute to research in the field by investigating strategies that involve and define nurse involvement and ascertain the impact they could have on antimicrobial utilisation and infection prevention beyond hand hygiene. This would be of particular relevance to community RNs and retail pharmacists from an outpatient or primary care viewpoint; to date, few stewardship interventions have targeted general practitioners and non-hospital-based HCPs in SA.

Towards the future of integrated teams

Pharmacists and RNs are well positioned to actively collaborate in AS teams and substantially contribute to optimal antimicrobial management in acute, ward and outpatient settings. However, given the absence of institutional ID resources in most SA hospitals, recruitment and active participation of more prescribers such as surgeons, intensive care physicians, paediatricians and others in such teams are necessary. For such initiatives to positively and sustainably impact on outcomes, it is therefore necessary to gain a contextual understanding of the barriers and facilitators to pharmacists and nurses contributing to AS, and how this role may be developed in the future. ‘Esprit de corps’, a French term referring to a shared spirit of comradeship, enthusiasm and devotion to a cause among the members of a group, reflects such a united front to tackle antimicrobial resistance in SA. Recognition and acknowledgment of the potential role of HCPs other than doctors are critical to ensure sustainable antimicrobial preservation. 1. O Neill J. The Review on Antimicrobial Resistance. Final report. http://amr-review.org/Publications (accessed 18 August 2016). 2. Charani E, Edwards R, Sevdalis N, et al. Behaviour change strategies to influence antimicrobial prescribing in acute care: A systematic review. Clin Infect Dis 2011;53(7):651-662. DOI:10.1093/cid/cit212 3. Olans RN, Olans RD, DeMaria A. The critical role of the staff nurse in antimicrobial stewardship – unrecognized, but already there. Clin Infect Dis 2016;62(1):84-89. DOI:10.1093/cid/civ697 4. National Department of Health, South Africa. Antimicrobial Resistance National Strategy Framework 2014-2024. http://www.health.gov.za/index.php/antimicrobial-resistance (accessed 14 August 2016). 5. National Department of Health, South Africa. Implementation Plan for Antimicrobial Resistance National Strategy Framework 2014-2019. http://www.health.gov.za/index.php/antimicrobial-resistance (accessed 20 July 2016). 6. Brink AJ, Messina AP, Feldman C, et al., on behalf of the Netcare Antimicrobial Stewardship Study Alliance. Antimicrobial stewardship across 47 South African hospitals: An implementation study. Lancet Infect Dis 2016;16(9):1017-1025. DOI:10.1016/S1473-3099(16)30012-3 7. Edwards R, Drumright LN, Kiernan M, Holmes A. Covering more territory to fight resistance: Considering nurses’ role in antimicrobial stewardship. J Infect Prev 2011;12(1):6-10. DOI:10.1177/1757177410389627 8. Messina AP, van den Bergh D, Goff DA. Antimicrobial stewardship with pharmacist intervention improves timeliness of antimicrobials across thirty-three hospitals in South Africa. Infect Dis Ther 2015;4(Suppl 1):5-14. DOI:10.1007/s40121-015-0082-x 9. Brink AJ, Messina AP, Feldman C, et al. From guidelines to practice: A pharmacist-driven prospective audit and feedback improvement model for peri-operative antibiotic prophylaxis in 34 South African hospitals. J Antimicrob Chemother 2016 (in press). 10. Posteraro B, Tumbarello M, de Pascale G, et al. (1,3)-β-D-glucan-based antifungal treatment in critically ill adults at high risk of candidaemia: An observational study. J Antimicrob Chemother 2016;71(8):2262-2269. DOI:10.1093/jac/dkw112 11. Pulcini C. Antimicrobial stewardship in emergency departments: A neglected topic. Emerg Med J 2015;32:506. DOI:10.1136/emermed-2014-204220 12. Mendelson M, Matsotso MP. A global call for action to combat antimicrobial resistance: Can we get it right this time? S Afr Med J 2014;104(7):478-479. DOI:10.7196/SAMJ.8534 13. Fong DJ. Immunizations: Demonstrating the value of the community pharmacist and enabling HIT progress. 2016. http://www.wolterskluwercdi.com/blog/immunizations-demonstrating-valuecommunity-pharmacist-and-enabling-hit-progress/ (accessed 27 July 2016). 14. Burger M, Fourie J, Loots D, et al. Knowledge and perceptions of antimicrobial stewardship concepts among final year pharmacy students in pharmacy schools across South Africa. South Afr J Infect Dis 2016;1(1):1-7. DOI:10.1080/23120053.2016.1192808 15. Abbo L, Smith L, Pereyra M, et al. Nurse practitioners’ attitudes, perceptions, and knowledge about antimicrobial stewardship. J Nurse Pract 2012;8(5):370-376. DOI:10.1016/j.nurpra.2012.01.023

Accepted 5 September 2016.

October 2016, Print edition

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IN PRACTICE

CLINICAL UPDATE

Molecular detection of carbapenemase-producing genes in referral Enterobacteriaceae in South Africa: A short report O Perovic,1,2 MD, DTM&H, FCPath (SA) (Micro), MMed (Micro); E Britz,1 MB ChB, MPH; V Chetty,1 MPH; A Singh-Moodley,1 BSc, BMedSc Hons, MMedSc, PhD 1 2

entre for Opportunistic, Tropical and Hospital Infections, National Institute for Communicable Diseases, Johannesburg, South Africa C Department of Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Corresponding author: O Perovic (olgap@nicd.ac.za)

Molecular confirmation of carbapenemase-producing Enterobacteriaceae (CPE) was introduced in South Africa (SA) at the end of 2011. We report on the detection of these resistance genes based on referral isolates. Enterobacteriaceae with non-susceptibility to any of the carbapenems according to defined criteria for antimicrobial susceptibility testing results were sent to a reference laboratory. A proportion of isolates had limited demographic, epidemiological and clinical data available. Organism identification was reconfirmed using reference laboratory methods, and the presence of carbapenemases was confirmed with a real-time polymerase chain reaction. We analysed 1 503 significant isolates received for confirmation from the National Health Laboratory Service and some private laboratories during 2012 - 2015 and confirmed one or more carbapenemase-producing genes in 68% of isolates, the most common organism being Klebsiella pneumoniae (60%). The most common carbapenemase genes were blaNDM, followed by blaOXA-48 and its variants. BlaOXA-48 and its variants demonstrated non-susceptibility to ertapenem in 89% of the isolates when analysed by the phenotypic method, and to ceftazidime in 34%. Overall, the detection rate for carbapenemases in K. pneumoniae blood isolates in the public sector was 1.9% during the 4-year period. This report indicates the presence of CPE in SA, and it is important for all healthcare workers to be aware of this major public health threat so that infection prevention and control measures can be implemented to prevent the spread of CPE in healthcare facilities. S Afr Med J 2016;106(10):975-977. DOI:10.7196/SAMJ.2016.v106i10.11300

Enterobacteriaceae are a large group of Gram-negative, rod-shaped bacteria. They are the bacteria most frequently isolated from clinical specimens and may account for up to 80% of all clinically significant isolates from Gram-negative bacilli and up to 50% of all clinically significant bacteria.[1] Enterobacteriaceae cause both nosocomial and community-acquired infections and are increasingly becoming multidrug resistant (MDR) to antimicrobial agents. The past few decades have seen the rapid emergence and spread of antimicrobial resistance, with clinicians having to rely on the carbapenem class of antibiotics to treat these resistant organisms. [2] However, increasing rates of carbapenem resistance are being reported.[3] The mechanism of resistance to carbapenems among Enterobacteriaceae is complex and mediated by several different mechanisms, such as the over-production of ampC enzymes, extended-spectrum betalactamases (ESBLs), carbapenemases that inactivate the β-lactam antibiotics, including the carbapenems, efflux pumps and deletion of porins.[3-5] There are several classes of carbapenemase-produ cing Enterobacteriaceae (CPE), which include non-metalloenzymes (Klebsiella pneumoniae carbapenemases (KPC), Guiana extendedspectrum β-lactamases (GES), oxacillinase-type carbapenemases (OXA-48) and their derivatives) and metallo-β-lactamases (MBL) (imipenemases (IMP), Verona integron-encoded MBL (VIM) and New Delhi metallo-β-lactamase (NDM-1/2)). CPE are associated with increased morbidity and mortality as a result of limited treatment options rather than the expression of specific virulence characteristics.[6,7] CPE also have the potential for widespread transmission of carbapenem resistance owing to easily transmissible resistance genes on plasmids and chromosomes.[6,7] The focus given to

carbapenemase detection despite all other mechanisms of resistance was due to the availability of molecular test methods. Among all CPE, the most common enzyme was NDM-1.[3] NDM-1 was first described in 2008 in a Swedish patient returning from New Delhi, India,[8] in both Escherichia coli and K. pneumoniae isolates, which carried the novel MBL gene (blaNDM-1).[9] NDM-1 has subsequently been reported worldwide, with most early cases of NDM-1 diagnosed in the UK having epidemiological links with the Indian subcontinent.[8]

Objective

To demonstrate the presence of carbapenemases in Enterobacteri aceae over a 4-year period, based on a referral system for confirmation of CPE genes.

Methods

Carbapenem non-susceptible, clinically significant isolates from the Enterobacteriaceae family were submitted to the Antimicrobial Resistance Laboratory (AMRL) at the National Institute for Communicable Diseases (NICD), Johannesburg, South Africa (SA), for confirmation of carbapenemase-producing genes from 2012 through 2015. Referral of isolates by public and private microbiology laboratories was based on non-susceptibility to carbapenems by disc diffusion (Kirby-Bauer method, using Oxoid Antimicrobial Susceptibility Test Discs (Oxoid, UK)) or minimal inhibitory concentration (MIC) testing methods interpreted by the Clinical and Laboratory Standards Institute guideline.[10] Submission practice from public laboratories was based on a guideline from the reference

October 2016, Print edition

laboratory at the NICD and from private laboratories on a voluntary basis. Organism identification was reconfirmed using automated systems (VITEK 2 (bio Mèrieux, France) and/or Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-ToF, Bruker Daltonik GmbH, Germany), and anti microbial susceptibility testing (AST) was done using the MicroScan Walkaway system (Siemens, USA) at the AMRL. For molecular methods, DNA was extracted from purity plates using a crude boiling method at 95oC for 25 minutes. The supernatant was harvested and screened for blaNDM, blaKPC, blaOXA-48 and its variants, blaGES, blaIMP and blaVIM, using a real-time polymerase chain reaction (LightCycler 480 II, Roche Applied Science, Germany), the LightCycler 480 Probes Master kit (Roche Diagnostics, USA) and individual LightMix Modular kits (Roche Diagnostics, USA). Kit-positive controls as well as in-house controls were used in all assays (blaNDM, ATCC BAA21246; blaKPC, ATCC BAA1705; blaOXA-48 and its variants, NCTC13442; blaGES, clinical isolate; blaIMP, NCTC 13476; and blaVIM, clinical isolate). Sterile water was used as a negative control.

Statistical analysis

Where appropriate, we calculated frequencies and percentages and used the χ2 test/Fisher’s exact test to compare categorical variables. Statistical analyses were performed using STATA 14 (StataCorp, USA).

Ethical considerations

Laboratory-based antimicrobial resistance surveillance for nosocomial bacteria was approved by the Human Research Ethics Committee (Medical) at the University of the Witwatersrand, Johannesburg (clearance certificate no. M10464).

Results

We analysed 1 503 clinically significant Entero bacteriaceae isolates received for carbapenemase-producing gene confir mation. The age distribution of patients with carbapenem-resistant Enterobacteriaceae (CRE) infections showed two significant peaks, in children aged 0 - 5 years and in adults aged 30 - 40 years (p=0.05). Blood was the most common specimen type (25%), followed by urine (22%). We confirmed ESBL in 93% of isolates by the automated MIC method. Furthermore, carbapenemase-producing genes were con firmed molecularly in 68% of isolates (1 021/1 503). Of all Enterobacteriaceae, the most common was K. pneumoniae (60%),

Carbapenemase-producing genes

IN PRACTICE

blaNDM

59%

blaOXA-48

29%

blaVIM

blaIMP

blaGES

blaKPC

1% 0

100

Confirmed genes, % Fig. 1. Carbapenemase-producing genes detected in 1 021 Enterobacteriaceae isolates referred to the AMRL at the NICD, 2012 - 2015.

followed by Enterobacter cloacae (14%) and Serratia marcescens (6%). The most common carbapenemase-pro ducing genes were blaNDM, followed by blaOXA-48 (Fig. 1). Carbapenemases were con firmed in 672 K. pneumoniae isolates (68%), and blaNDM was the most common gene identified (58%). Of the blaNDM-positive isolates, 0.8% and 0.6% showed susceptibility to ertapenem and ceftazidime, respectively. BlaOXA-48 and its derivatives demonstrated susceptibility to ertapenem in 11% of isolates and to ceftazidime in 66%. The detection rate of carbapenemases among all K. pneumoniae blood isolates from public laboratories during the 4-year period was 1.9%. Based on voluntary referral practice, we could not estimate the preva lence of carbapenemases for all Enterobacteriaceae isolates and specimen types in SA.

Discussion

This short report describes emerging resistance to carbapenems in Enterobacteri acae over a 4-year period in SA. We detected the presence of major carbapenemases, i.e. NDM, OXA-48 and VIM. In a previous laboratory-based anti microbial resistance surveillance study conducted in 2010 - 2012, no isolates containing blaNDM or blaKPC were found, and blaGES and blaVIM were confirmed in <0.1%.[11] The present report suggests rapid dissemination of these genes once they are introduced into the environment, and we describe its longitudinal nature, which is in line with the global dissemination.[12] The vast majority of the referral isolates produced ESBL, which is to be expected owing to the MDR patterns of these

October 2016, Print edition

organ isms and compares with a previous surveillance report.[11] Enterobacteriaceae extensively exhibit MDR patterns, which enable them to persist and spread rapidly in healthcare settings.[13] Our results indicate that blaOXA-48-positive isolates could be missed in 11% of isolates owing to susceptibility to ertapenem, yet 43% were sensitive to imipenem and 57% to meropenem, which demonstrated that AST methods cannot be used for screening of these enzymes. This differs from an Indian study that showed 75% sensitivity to ertapenem and 84% sensitivity to imipenem and meropenem.[14] Poirel et al.[15] pointed out menace behaviour of these enzymes and the difficulties this poses for phenotypic detection. As we report here, some of these enzymes will be overlooked, particularly if carbapenems are used as indicators for AST resistance screening. There are various approaches to the control of MDR organisms. Carmeli et al.[16] indicated that the objective for control should be eradication, while others such as Thurlow et al.[17] considered that a wider approach is needed once endemicity is established. Thurlow et al.[17] also suggested that reducing the burden of CPE on patients’ skin should be explored further as a way of reducing cross-transmission at long-term healthcare hospitals, where endemicity is most likely. Clinicians and infection control practitioners should be aware of the presence of carbapenemases in Enterobacteriaceae and its implications for infection prevention and control in the SA setting.

Study limitations

This report has a number of limitations. Owing to lack of policies and voluntary

IN PRACTICE

practice in sending isolates for confirmation to the reference laboratory, we were unable to determine the national prevalence of CPE or to establish whether there has been an increase in CPE in SA. Changes in submission practices and/or increased awareness of CPE infections undoubtedly influenced the number of isolates referred to the reference laboratory. However, this analysis reports a minimum estimate of the presence of CPE organisms and carbapenemase-producing genes in the country. Missing demographic, epidemiological and clinical data reduced our ability to analyse laboratory data in more meaningful ways. Surveillance for CPE through the Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA) surveillance platform was introduced at 12 sentinel sites in four SA provinces in 2015. Future analysis of surveillance data for CPE should provide a more representative estimate of their prevalence and distribution in SA.

Conclusions

This report indicates the presence of CPE in SA. It is essential for all clinicians to be aware of this major public threat and be prepared to act if CPE occurs in patients. At all healthcare facilities, the importance of enforcing infection prevention and control measures to prevent the spread of CPE should be emphasised. Importantly, antimicrobial stewardship programmes should be implemented at facility level to prevent selection pressure on bacterial organisms to develop resistance. Acknowledgements. We thank all members of the AMRL at the NICD, and particularly Rubeina Badat, Naseema Bulbulia and Ruth Mohlabeng for their technical support. We also thank Penny Crowther for database design.

1. Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH. Enterobacteriaceae: Introduction and identification. In: Farmer JJ III, ed. Manual of Clinical Microbiology. Philadelphia: Elsevier, 2003:647. 2. Jacob JT, Klein E, Laxminarayan R, et al. Vital signs: Carbapenem-resistant Enterobacteriaceae. MMWR Morb Mortal Wkly Rep 2013;62(9):165-170. 3. Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2011;17(10):1791-1798. DOI:10.3201/eid1710.110655 4. Spellberg B, Blaser M, Guidos RJ, et al. Combating antimicrobial resistance: Policy recommendations to save lives. Clin Infect Dis 2011;52(Suppl 5):S397-S428. DOI:10.1093/cid/cir153 5. Nordmann P, Poirel L, Dortet L. Rapid detection of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2012;18(9):1503-1507. DOI:10.3201/eid1809.120355 6. Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 2008;29(12):1099-1106. DOI:10.1086/592412 7. Yigit H, Queenan AM, Anderson GJ, et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001;45(4):11511161. DOI:10.1128/AAC.45.4.1151-1161.2001 8. Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009;53(12):50465054. DOI:10.1128/AAC.00774-09 9. Brink AJ, Coetzee J, Clay CG, et al. Emergence of New Delhi metallo-beta-lactamase (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC-2) in South Africa. J Clin Microbiol 2012;50(2):525-527. DOI:10.1128/JCM.02234-12 10. Patel JB, Cockerill FR, Eliopoulos GM, et al. Performance Standards for Antimicrobial Susceptibility Testing. 26th ed. Wayne, Penn., USA: Clinical and Laboratory Standards Institute, 2016. 11. Perovic O, Singh-Moodley A, Duse AG, et al. National sentinel site surveillance for antimicrobial resistance in Klebsiella pneumoniae isolates in South Africa, 2010 - 2012. S Afr Med J 2014;104(8):563568. DOI:10.7196/SAMJ.7617 12. Tangden T, Giske CG. Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: Clinical perspectives on detection, treatment and infection control. J Intern Med 2015;277(5):501-512. DOI:10.1111/joim.12342 13. Tzouvelekis LS, Markogiannakis A, Psichogiou M, Tassios PT, Daikos GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: An evolving crisis of global dimensions. Clin Microbiol Rev 2012;25(4):682-707. DOI:10.1128/CMR.05035-11 14. Sugumar M, Kumar KM, Manoharan A, Anbarasu A, Ramaiah S. Detection of OXA-1 beta-lactamase gene of Klebsiella pneumoniae from blood stream infections (BSI) by conventional PCR and in-silico analysis to understand the mechanism of OXA mediated resistance. PLoS One 2014;9(3):e91800. DOI:10.1371/journal.pone.0091800 15. Poirel L, Bonnin RA, Nordmann P. Genetic support and diversity of acquired extended-spectrum betalactamases in Gram-negative rods. Infect Genet Evol 2012;12(5):883-893. DOI:10.1016/j.meegid.2012.02.008 16. Carmeli Y, Akova M, Cornaglia G, et al. Controlling the spread of carbapenemase-producing Gramnegatives: Therapeutic approach and infection control. Clin Microbiol Infect 2010;16(2):102-111. DOI:10.1111/j.1469-0691.2009.03115.x 17. Thurlow CJ, Prabaker K, Lin MY, Lolans K, Weinstein RA, Hayden MK. Anatomic sites of patient colonization and environmental contamination with Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae at long-term acute care hospitals. Infect Control Hosp Epidemiol 2013;34(1):56-61. DOI:10.1086/668783

Accepted 26 July 2016.

CLINICAL ALERT This open access article is distributed under CC-BY-NC 4.0.

Button batteries in the oesophagus: A surgical emergency

K Milford,1 MB ChB; A Numanoglu,1 MB ChB, FCS; A Brooks,2 FC Cardio (SA); S Cox,1 MB ChB, FCS, Cert Paed Surg ivision of Paediatric Surgery, Red Cross War Memorial Childrenâ&#x20AC;&#x2122;s Hospital and Faculty of Health Sciences, University of Cape Town, D South Africa 2 Christiaan Barnard Division of Cardiothoracic Surgery, Red Cross War Memorial Childrenâ&#x20AC;&#x2122;s Hospital and Faculty of Health Sciences, University of Cape Town, South Africa 1

Corresponding author: K Milford (karenmilford@gmail.com)

We describe two cases of missed battery ingestion that led to extensive morbidity, requiring surgical management that would not have been necessary had the batteries been removed timeously. S Afr Med J 2016;106(10):978-980. DOI:10.7196/SAMJ.2016.v106i10.11172

Small children frequently ingest foreign bodies.[1] The true incidence of this is unknown, and most foreign bodies will pass through the gastrointestinal tract unnoticed and without causing any harm.[2] Large or unusually shaped objects, however, may become lodged in the oesophagus and require endoscopic removal or advancement into the stomach. Button batteries

need to be dealt with particularly urgently as they cause complications that can lead to extensive morbidity and even mortality. We describe two cases of missed battery ingestion seen in Cape Town, South Africa, that led to extensive morbidity, requiring surgical management that would not have been necessary had the batteries been removed timeously.

October 2016, Print edition

IN PRACTICE

Case 1

A previously well 11-month-old boy was brought to a local facility with symptoms of a lower respiratory tract infection (tachypnoea, coughing and fever). A chest radiograph demonstrated a circular foreign body at the level of the cricopharyngeus muscle. Endoscopy was performed and a button battery was removed. Sloughing and necrosis of the oesophageal mucosa was noted at the time of endoscopy. Four days later, when the patient’s symptoms had not settled, he underwent a computed tomography (CT) scan of the chest, which demonstrated a tracheo-oesophageal fistula (Fig. 1). At this point he was referred to Red Cross War Memorial Children’s Hospital (RCWMCH), Cape Town. At RCWMCH, he initially underwent defunctioning oesophagostomy, Nissen fundoplication and placement of a gastrostomy tube. Three weeks later he was taken for rightsided thoracotomy and underwent repair of the fistula; the oesophageal defect was sutured and an intercostal flap placed over the tracheal defect. Six weeks after this his oesophagostomy was reversed. He required dilatations of the oesophagostomy site for ~7 months (Fig. 2). He is now symptom free and growing well.

Case 2

A 6-year-old girl was taken to a general practitioner after swallowing a watch battery. The family was told that as long as she was passing stool normally, the battery would pass and that they need not worry about it. A year later she presented again with dysphagia and symptoms of aspiration (coughing after feeds and recurrent respiratory tract infections). A chest radiograph revealed a foreign body in the oesophagus (Fig. 3). The oesophagus proximal to this was dilated and had an air/fluid level, and the lung fields showed features suggestive of aspiration pneumonia. A CT scan revealed a foreign body lodged posterior to the oesophagus and medial to the arch of the aorta (Figs 4 and 5). The patient was taken to theatre, where oesophagoscopy revealed a tight oesophageal stricture but no visible foreign body. She then underwent thoracotomy and an inflammatory oesophageal stricture was identified, containing an alkali button battery. The stricture was

resected and a primary oesophageal ana stomosis was performed (Fig. 6). The patient is now eating well and gaining weight.

Fig. 5. 3D reconstruction of CT images demon strating relationship of button battery to aortic arch (arrow) in patient 2.

Fig. 1. CT cross-section through chest of patient 1, demonstrating tracheo-oesophageal fistula (arrow). Fig. 3. Chest radiograph demonstrating button battery in the oesophagus of patient 2. Note the dilated proximal oesophagus containing an air/ fluid level, and the ‘halo’ sign indicating that this object is probably a battery, not a coin.

Fig. 2. Contrast swallow demonstrating stricture at level of previous defunctioning oesophagostomy (arrow), requiring dilatation.

Fig. 4. CT cross-section through chest of patient 2, demonstrating a foreign body posterior to the oesophagus and medial to the aortic arch (arrow).

October 2016, Print edition

Fig. 6. Postoperative contrast swallow showing oesophagus after resection of stricture and primary oesophageal anastomosis in patient 2.

IN PRACTICE

Pathology

Button batteries are small, disc-shaped batteries, commonly used to power small electronic devices such as wrist watches, clocks, calculators, kitchen scales and some toys. They are typically 5 - 25 mm in diameter and 1 - 6 mm high. A button battery is a single-cell unit, with one half-cell being the cathode, or positive electrode, and the other half being the anode, or negative electrode. Anodes are commonly composed of metals such as zinc or lithium, and cathodes are commonly composed of substances such as manganese dioxide, silver oxide, carbon monofluoride, cupric oxide or oxygen. The anode and cathode are separated by an electrolyte, which allows the flow of electric charge between the two. [3] In alkaline batteries, this electrolyte is potassium hydroxide. Typically, batteries that become lodged in the oesophagus are 20 mm or more in diameter.[4-6] Once the battery is in the restricted space of the oesophagus and in contact with its endothelium, which creates a circuit, it rapidly starts heating up, causing thermal cell damage. In addition, the casing erodes and leaks metals and hydroxide anions. This causes an increase in pH with resulting liquefactive necrosis, as well as cytotoxic damage. All these changes can occur within 2 hours of ingestion.[7] The complications of this damage to the oesophageal wall are serious. Oesophageal perforation can occur,[8] and the battery can then go on to erode into surrounding structures. The literature describes a wide range of complications, including aorto-oesophageal fistula,[9,10] which commonly presents as a herald bleed followed by a fatal upper gastrointestinal bleed, bilateral vocal cord paralysis,[9] tracheo-oesophageal fistula,[11] commonly presenting as aspiration pneumonia, oesophageal necrosis[6] and oesophageal stenosis.[5,6]

Diagnosis and investigation

All children who present with a history of possible button battery ingestion should be investigated. The ingestion may be self-reported or witnessed by a caregiver. A plain anteroposterior chest radiograph will either confirm the presence of a button battery lodged in the oesophagus, or reassure the clinician and family that the battery has passed beyond the oesophagus and into the gastrointestinal tract. When a foreign body is confirmed to be lodged in the vicinity of the mediastinum, a lateral chest radiograph is useful in that it will help to determine the position in the mediastinum[12] and also provide more information as to the nature of the object.[13] In many cases, button battery ingestion may occur unnoticed, and children may be investigated after presenting with the symptoms of complications. These include abdominal pain,[6,9,14] respiratory symptoms such as distress and tachypnoea,[6] coughing,[9] wheezing or stridor,[10,13] and symptoms of oesophageal obstruction such as dysphagia, drooling[5,9] and vomiting.[2] Particularly ominous is history of haematemesis.[10] In the case of oesophageal impaction, a chest radiograph will reveal a smooth, round object, most commonly lodged in the cricopharyngeal area, in the middle third of the oesophagus where the left main bronchus crosses the oesophagus (as this is anatomically the most narrow part of the oesophagus) or at the lower oesophageal sphincter. [2] The most commonly ingested foreign body is a coin,[1,2,13,14] and if the ingestion went unwitnessed the battery may be mistaken for a coin on a plain radiograph.[12,13] Clues that one may be dealing with a button battery rather than a coin may be found on the lateral film, where one side of the battery is perfectly flat while the other is convex,[13] and one may see the ‘step-off ’ sign, which refers to the ‘step’ between the battery

and its casing.[11] In addition, on a well-exposed film there is a rim of lucency on the inside edge of the battery,[13] also known as the ‘halo’ sign (Fig. 3).[11] The chest radiograph may also reveal features of complications of ingestion, such as pneumothorax and pneumomediastinum,[4,8,13] lung field infiltrates[9] and proximal oesophageal dilatation, as described in case 2 above. If there is evidence of complications, there may be value in doing further studies such as a contrast swallow examination[8] or a CT scan.

Management

Because oesophageal button batteries cause local damage so rapidly, they must be removed as a matter of urgency. The practice at RCWMCH is to take children with an acute history and no radiographic features of complications to theatre urgently, and to remove the battery endoscopically under general anaesthesia. This approach is supported by the literature.[6,9,10,14] At the time of endoscopy, the oesophagus is assessed for evidence of injury (mucosal burns, necrosis or perforation), and further management is based on these findings. In the case of children who present with radiographic evidence of complications or who are severely ill, the child is stabilised from a respiratory and haemodynamic point of view, and then further imaging is undertaken before formulating a surgical plan. This usually requires a right thoracotomy, with repair of the injured structures. Button batteries that have passed beyond the oesophagus can be monitored, as they usually pass through the gastrointestinal tract spontaneously.[2] If they remain in the stomach for >48 hours, endoscopy should be performed to remove them.[2,15]

Conclusion

Button battery ingestion is common, and is associated with serious morbidity and possible mortality. Any child with a history of button battery ingestion should be investigated with a chest radiograph, and any patient with a foreign body impacted in the oesophagus should be referred to an appropriate centre for urgent endoscopic retrieval. 1. Van As AB, Du Toit N, Wallis L, Stool D, Chen X, Rode H. The South African experience with ingestion injury in children. Int J Pediatr Otorhinolaryngol 2003;67(Suppl. 1):175-178. DOI:10.1016/j.ijporl.2003.08.021 2. Uyemura MC. Foreign body ingestion in children. Am Fam Physician 2005;72(2):287-291. DOI:10.1016/j.arcped.2011.05.007 3. MIT School of Engineering. How does a battery work? http://engineering.mit.edu/ask/how-doesbattery-work (accessed 27 May 2016). 4. Marom T, Goldfarb A, Russo E, Roth Y. Battery ingestion in children. Int J Pediatr Otorhinolaryngol 2010;74(8):849-854. DOI:10.1016/j.ijporl.2010.05.019 5. Litovitz T, Schmitz BF. Ingestion of cylindrical and button batteries: An analysis of 2 382 cases. Pediatrics 1992;89(4 Pt 2):747-757. 6. Yardeni D, Yardeni H, Coran AG, Golladay ES. Severe esophageal damage due to button battery ingestion: Can it be prevented? Pediatr Surg Int 2004;20(7):496-501. DOI:10.1007/s00383-004-1223-6 7. Chevin JC, Attik G, Dika H, et al. Button battery induced cell damage: A pathophysiological study. Electrochem Commun 2008;10(11):1756-1760. DOI:10.1016/j.elecom.2008.09.002 8. Samad L, Ali M, Ramzi H. Button battery ingestion: Hazards of esophageal impaction. J Pediatr Surg 1999;34(10):1527-1531. DOI:10.1016/S0022-3468(99)90119-7 9. Hamilton JM, Schraff SA, Notrica DM. Severe injuries from coin cell battery ingestions: 2 case reports. J Pediatr Surg 2009;44(3):644-647. DOI:10.1016/j.jpedsurg.2008.10.110 10. Mortensen A, Hansen NF, Schiødt OM. Fatal aortoesophageal fistula caused by button battery ingestion in a 1-year-old child. Am J Emerg Med 2010;28(8):984.e5-984.e6. DOI:10.1016/j.ajem.2010.01.007 11. Grisel JJ, Richter GT, Casper KA, Thompson DM. Acquired tracheoesophageal fistula following disc-battery ingestion: Can we watch and wait? Int J Pediatr Otorhinolaryngol 2008;72(5):699-706. DOI:10.1016/j.ijporl.2008.01.015 12. George AP, Alaani A, Carlin WV. The difficulty identifying unknown swallowed foreign bodies on plain X-ray. Int J Pediatr Otorhinolaryngol Extra 2008;3(1):1-2. DOI:10.1016/j.pedex.2007.06.004 13. Lee SC, Ebert CS, Fordham L, Rose AS. Plain films in the evaluation of batteries as esophageal foreign bodies. Int J Pediatr Otorhinolaryngol 2008;72(10):1487-1491. DOI:10.1016/j.ijporl.2008.06.013 14. Timmers M, Snoek KG, Gregori D, Felix JF, van Dijk M, van As SA. Foreign bodies in a pediatric emergency department in South Africa. Pediatr Emerg Care 2012;28(12):1348-1352. DOI:10.1097/PEC.0b013e318276c20e 15. Lee JH, Lee JH, Shim JO, Lee JH, Eun BL, Yoo KH. Foreign body ingestion in children: Should button batteries in the stomach be urgently removed? Pediatr Gastroenterol Hepatol Nutr 2016;19(1):20-28. DOI:10.5223/pghn.2016.19.1.20

Accepted 20 June 2016.

October 2016, Print edition

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

IN PRACTICE

CLINICAL ALERT

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer R P Abratt, FC Rad Onc (SA), MMed (RadT) Head of Clinical Governance, Independent Clinical Oncology Network, South Africa; and Emeritus Professor of Radiation Oncology, Faculty of Health Sciences, University of Cape Town, South Africa Corresponding author: R P Abratt (raymond.abratt@cancernet.co.za)

The drug cost of adjuvant trastuzumab to benefit one patient with localised human epidermal growth factor receptor 2 (HER2)-positive breast cancer depends on the baseline survival rate (BLSR) of the prognostic group of the patient. This varies from ZAR13 752 900 (BLSR 90%) to ZAR4 006 100 (BLSR 60%). All treated patients are exposed to potential toxicity. The value and affordability of treatments need to be considered, as there are finite resources available in our healthcare system. All patients must have access to cost-effective treatments. However, patient selection for expensive treatments is important, as expenditure on patients where the gains are relatively small will result in resources not being available for other patients. The state, healthcare institutions and the pharmaceutical industry need to work together to optimise the benefits of treatment to patients. S Afr Med J 2016;106(10):981-982. DOI:10.7196/SAMJ.2016.v106i10.11141

The rapid increase in costs in medicine has highlighted the affordability and value of medical treatments.[1] Affordability is the cost relative to the amount that the purchaser is able to pay. Value is the ratio of patient benefit to cost. A topical issue is the affordability and value of adjuvant trastuzumab for 1 year after surgery for localised human epidermal growth factor receptor 2 (HER2)-positive breast cancer, particularly in low- and middle-income countries. Affordability and value differ in patient groups with different baseline prognoses. This is illustrated below using the hazard ratio (HR) of survival rates obtained from a Cochrane review[2] and personal communication with Roche. The HR is the ratio of the relative survival of two patient groups, with and without the test therapy. This ratio will not vary much over time. Patients can be divided into prognostic groups with different outcomes, depending on tumour stage and nodal status. For an assessment of affordability, a specific time point needs to be determined for the calculation of baseline survival. Expected baseline survival rates (BLSRs) for periods up to 15 years can be determined with breast cancer outcome calculators, which are available on the internet (e.g. https://www.adjuvantonline.com/ and http://www. lifemath.net/cancer/breastcancer/therapy).

Number needed to treat (NNT) to benefit one patient at any selected endpoint

For clinical purposes, this may be approximated from the BLSR and the HR. The HR for overall survival in the calculation below was 0.69 (95% confidence interval (CI) 0.58 - 0.81). • The number of patients who will benefit when 100 patients are treated = (100 – BLSR) × (1 – HR). • Therefore, for a BLSR survival rate of 90%, the number who will benefit = 10 × 0.31 = 3. The survival rate therefore increases from 90% to 93%. • The NNT to benefit one patient = 100/3 = 33. More accurate numbers can be determined using more sophisticated formulae.[3]

Toxicity

The relative risk (RR) for increased toxicity for congestive heart failure = 5.11 (90% CI 3.00 - 8.72), and for decrease in left ventricular ejection fraction = 1.83 (90% CI 1.36 - 2.47). Toxicity risk occurs in all treated patients, which means that the higher the BLSR, the higher is the proportion of patients who are free of disease who are exposed to potential toxicity. The toxicity also has cost implications, as all patients need to have their left ventricular function evaluated objectively with an echocardiogram or multigated acquisition (MUGA) scan every 3 months while on treatment.

The drug costs for 1 year on adjuvant trastuzumab

This analysis will restrict itself to a review of immediate drug costs alone, which are the largest cost factor. It excludes costs related to the facility fee, professional fees or associated investigations. A full economic analysis will include these costs as well as downstream costs for possible toxicity and savings from benefit. The drug cost of 17 cycles of trastuzumab, allowing for vial sharing, for 1 year is ZAR413 000. There are proponents for the use of adjuvant trastuzumab in all scenarios. The NNT to benefit one patient at a selected endpoint and the related drug cost to benefit one patient are shown in Table 1. The table indicates that the drug cost to benefit one patient ranges from ZAR13 752 900 (BLSR 90%) to ZAR4 006 100 (BLSR 60%).

Clinical ethics

It is a principle of clinical ethics that the clinician should provide the best treatment possible with available resources, provided there is evidence of benefit and the clinician is prepared to undertake the treatment. In the Cochrane analysis,[2] the comment is made that the data indicate that the same efficacy is achieved with <6 months of treatment compared with 12 months of treatment and that there is less cardiac toxicity, but that this is not statistically significant with the numbers in the relevant studies. These studies are underpowered and there is relatively little incentive to undertake them. Although this is

October 2016, Print edition

IN PRACTICE

Table 1. NNT to benefit one patient and the related drug costs with adjuvant trastuzumab in patients with breast cancer[3] Patient baseline survival rate, %

Survival rate with trastuzumab, %

NNT to benefit one patient

Drug cost (ZAR) to benefit one patient

33.4

13 794 200

17.5

7 227 500

12.2

5 038 600

9.7

4 006 100

a lower level of evidence compared with that found with higher numbers, it is not an absence of evidence. Where funders are not able to provide 12 months of trastuzumab, as

happens at present in state institutions and the lower-level medical schemes, <6 months of trastuzumab should be considered as a treatment option to benefit patients.

Clinicians rightly wish to extend the benefits from advances in cancer treatment to all suitable patients. This requires an appreciation of the costs involved and an ongoing engagement of state and healthcare institutions and the pharmaceutical industry. 1. Abratt RP. Modelling cost-effective therapies. S Afr Med J 2015;105(11):884. DOI:10.7196/SAMJ.2015.v105i11.9880 2. Moja L, Tagliabue L, Balduzzi S, et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev 2012, Issue 4. Art. No.: CD006243. DOI:10.1002/14651858.CD006243 3. Altman DG, Andersen PK. Calculating the number needed to treat for trials where the outcome is time to an event. BMJ 1999;319(7223):1492-1495. DOI:http://dx.doi.org/10.1136/bmj. 319.7223.1492

Accepted 14 June 2016.

MEDICINE AND THE LAW

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

Sudden and unexpected childhood deaths investigated at the Pretoria Medico-Legal Laboratory, South Africa, 2007 - 2011

B S van Deventer, BSc, BSc Hons (Medical Criminalistics); S H Rossouw, MB ChB, MMed (Med Forens), MA; L du Toit-Prinsloo, MB ChB, Dip For Med (SA) Path, FC For Path (SA), MMed (Path) (Forens) Department of Forensic Medicine, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa Corresponding author: L du Toit-Prinsloo (lorraine.dutoit@up.ac.za)

Background. Sudden and unexpected death is well known to occur in infants, and although sudden deaths are less frequent after the first birthday, they still account for a significant proportion of childhood deaths. In 2009, 1.9% of the total deaths in the USA were childhood deaths. In South Africa (SA) this proportion was much higher at 11.85%. According to the law, sudden and unexpected deaths are generally investigated as unnatural deaths. Establishing an exact underlying anatomical cause of death will depend on available resources and can be difficult in a substantial proportion of cases. Methods. A retrospective descriptive case audit was conducted at the Pretoria Medico-Legal Laboratory (PMLL), SA, from 1 January 2007 through to 31 December 2011. All children aged 1 - 18 years who died suddenly and unexpectedly were included. Results. Ninety-eight cases were identified, which constituted nearly 1% of total admissions to the PMLL. The majority of the deaths were of children aged 1 - 5 years, and the male/female ratio was 1.04:1. In the largest proportion of cases (n=28, 28.6%), the medicolegal investigation, including autopsy and ancillary investigations, did not establish an underlying anatomical cause of death. In the cases where a cause of death was established, pneumonia was the most common diagnosis (n=22, 22.4%). Conclusions. The fact that the cause of the largest proportion of deaths could not be ascertained emphasises the need for consideration of additional investigative techniques, such as molecular/genetic screening, which have provided an underlying cause of death in a significant number of cases in other countries. There is a lack of published research on the causes and incidence of sudden unexpected deaths in children in SA, and further research in this area is needed. S Afr Med J 2016;106(10):983-985. DOI:10.7196/SAMJ.2016.v106i10.11028

The sudden and unexpected death of a child is defined as ‘the death of a child which was not anticipated as a significant possibility, 24 hours before the death, or where there was a similarly unexpected collapse leading to, or preceding the events which led to the death’. [1] Such deaths are well known to occur in the first year of life, after the neonatal period, and become less frequent after the first birthday. According to South African (SA) legislation, sudden deaths are classified as unnatural deaths in terms of the Regulations Regarding the Rendering

of Forensic Pathology Service R636 and are referred for medicolegal investigation in accordance with the provisions of the Inquests Act 58 of 1959. In a significant proportion of these cases the cause will remain unascertained, so it is of the utmost importance to carry out every possible investigation.[2-4] In 2009, 48 033 (1.9%) of 2 437 163 deaths in the USA were of children aged 0 - 18 years.[5] In the same year in SA, 69 878 children died (11.85% of total deaths).[6,7]

October 2016, Print edition

IN PRACTICE

16 12

Cases, n

12 8

4 2

er No ve m be r De ce m be r

to b

t us

pt em

Au g

ne Ju

ay M

il Ap r

ar ch M

ar ru

Fe b

Fig. 1. Distribution of cases according to month (N=98).

80 70 60 50 40 30 20 10 0

Histology

Toxicology

Virology

Microbiology

Fig. 2. Ancillary examinations performed (N=98). 30

Cases, n

22 19

20 15 9

9 6

5 0

i rta

Results

During the 5-year study period, 11 416 cases were admitted to the PMLL, 98 of which

Methods

A retrospective case audit was done of all sudden and unexpected deaths of children aged 1 - 18 years investigated at the Pretoria Medico-Legal Laboratory (PMLL), SA, from 1 January 2007 through to 31 December 2011. Data recorded in each case included the month of death, demographic details, autopsy findings (including ancillary investigations) and primary medical cause of death. Histological slides were reviewed by two independent pathologists. Approval was obtained from the Faculty of Health Sciences Research Ethics Committee, University of Pretoria (Ref. no. 75/2013). Infants were excluded from the study. Sudden deaths in infancy are not uncommon, and in the USA 70% of these are determined to be due to sudden infant death syndrome (SIDS).[14]

were noted, typically at the change of seasons in March and November (Fig. 1). A complete autopsy with evisceration of all organ blocks was conducted on all cases. Fig. 2 illustrates the number of anci llary investigations performed in these cases. Histological investigations were done in 73/98 cases (74.5%), toxicological investi gations in 33/98 cases (33.7%) and virological and microbiological investi gations in 1 case (1.0%) each. Review of the histological examinations showed that between 2 and 20 microscopy slides were

were children aged 1 - 18 years who had died suddenly and unexpectedly (the study popu lation). These sudden and unexpected deaths equate to ~1% of all admissions to the PMLL. The gender distribution was relatively equal, with a male/female ratio of 1.04:1. The majority of the deaths were of children aged 1 - 5 years (n=50, 51.0%) followed by 23 deaths in the 16 - 18-year age group (23.5%), 15 deaths of 11 - 15-year-olds (15.3%) and 10 deaths in the 6 - 10-year age group (10.2%). The largest number of deaths occurred in August. Some seasonal peaks

Cases, %

The vast majority of sudden unexpected deaths of adults are due to coronary artery disease, but in children the causes are more diverse and include sudden cardiac death (SCD), central nervous system abnormalities (especially in children with epilepsy), and infectious disease (mainly in developing countries).[8-11] SCD is reported to be the most prevalent cause of death, especially in the young (people aged <40 years). Structural abnormalities of the heart are detected at autopsy in most cases of SCD, but morphological abnormalities are absent in a significant proportion.[3,9-10,12] It has been suggested that some of the latter cases may be explained by cardiac channelopathies such as long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia.[3,9-10,12] Many sudden unexpected deaths in children remain a mystery, without a possible explanation for the cause. The proportion of sudden deaths with no morphological abnormalities can range from 3% to 53%. The absence of morphological findings at autopsy emphasises the importance of thorough investigations, additional examin ations, and research into these deaths to obtain a better understanding of the underlying pathophysiology and to implement possible preventive measures.[3,9,13] There is a paucity of published data on the causes and incidence of sudden unexpected deaths of children in SA. The objective of this study was to review these cases in order to document possible risk factors and trends, and identify potential strategies to prevent sudden unexpected death in children. We also envision that this study will lead to further research in this field.

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Fig. 3. Causes of death (N=98).

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tis

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IN PRACTICE

reviewed on each case (total 493 slides, average number per case 7). The organ most often sampled was the lungs, followed by the brain and heart. In 40/73 cases (54.8%) the histological examination did not contribute to ascertaining the cause of death, in 18/73 cases (24.7%) the histological findings confirmed the macroscopic diagnosis, and in 15/73 cases (20.5%) the cause of death was determined by means of the histological examination alone. Independent review of the microscopy slides revealed no discrepancy with the diagnosis in the majority of cases (42/73, 57.5%), minor discrepancies in 14/73 cases (19.2%) and major discrepancies in 17/73 cases (23.3%). In 28/98 cases (28.6%), no anatomical cause of death was identified after completion of the autopsy (including ancillary investigations). Pneumonia was diagnosed in 22 of the cases in which a cause of death was ascertained, 9 cases were deemed to be due to unspecified ‘natural causes’, and in 9 cases the investigations had not been completed pending the availability of toxicology results. Meningitis was diagnosed in 6 cases and myocarditis in 5. The remaining 19 cases included gastroenteritis, aspiration and malignancy (Fig. 3). Analysis of the ages of the children and the causes of death revealed that 15 of the 28 deaths with unascertained causes (53.6%) and 15 of the 22 deaths from pneumonia (68.2%) occurred in children aged between 1 and 5 years.

Discussion

Sudden and unexpected deaths in children in the USA accounted for 3% of all sudden deaths in 2009.[14] Krous et al.[15] reported an incidence of 1.5 deaths per 100 000 live births for sudden unexplained death in childhood (SUDC) in the USA (sudden death in infants was excluded). In northern Spain (1990 - 1997) the reported mortality rate for sudden unexpected non-violent death in children between the ages of 1 and 19 years was 1.7 per 100 000 persons per year, with 9% of all non-violent deaths in this age category being sudden and unexpected.[8] In our study, these deaths accounted for approximately 1% of the total caseload at the PMLL. Our results showed an equal distribution of deaths between boys and girls. Typically, the male/female ratio of cases admitted to the PMLL is 3:1. Most deaths (51.0%) occurred in children aged 1 5 years. In Ireland (1994 - 2008), 5% of all deaths in children under the age of 5 were sudden and unexpected.[16] The SUDC Foundation in the USA documented the rate of sudden unexpected childhood deaths in children aged 1 - 4 years as 1.3 per 100 000 children in 2014.[17] In our study, pneumonia was determined to be the cause of death in 22.4% of the total number of cases, with the majority of these deaths occurring in children aged 1 - 5 years. It can be postulated that younger children are at an increased risk of death from pneumonia. The importance of ancillary investigations in these cases, especially histological examination of tissue slides, could prove essential in making or confirming the diagnosis. The cause of death was ascertained on the basis of the histological findings alone in only 20.5% of our cases. This is lower than the 54% reported by Weber et al.[18] Deaths for which no cause can be ascertained at autopsy (as in the largest proportion of our cases) are referred to as autopsy-negative sudden unexpected deaths (ANSUDs). As ANSUDs represent a significant proportion of total cases in our study, it would be useful

to attempt to identify the underlying mechanisms that contributed to these sudden deaths.[3,9,13,19] Advances in postmortem genetic testing (so-called ‘molecular autopsy’) have made it possible to identify an underlying genetic cause for some sudden unexpected deaths, indicating a cardiac-related cause of death in 35% of these deaths in children and in 10 - 15% of cases of SIDS.[2,9]

Conclusions

In SA, no genetic or molecular testing is currently being done in the forensic setting owing to the high costs involved. Nevertheless, the way forward in this country is to consider a thorough molecular autopsy in each case of unexplained death to determine the cause, including cardiological and genetic evaluation of the first- and second-degree relatives of the deceased. From an ethical perspective, the question that arises is how much longer we can continue to tell family members that we do not know why their seemingly healthy beloved child died suddenly and unexpectedly. It is of utmost importance that these tests be implemented in SA in order to establish the prevalence of mutations that can result in sudden death, give answers to parents who have lost a child, and provide preventive strategies for the next of kin. Continued research in this area and studies of such cases are an absolute necessity. 1. Sidebotham P, Fleming PJ. Unexpected Death in Childhood: A Handbook for Practitioners. Chichester, UK: John Wiley & Sons, 2007:xiii. 2. Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C. Prevalence of long QT sydrome gene variants in sudden infant death syndrome. Circulation 2007;115(3):361-367. DOI:10.1161/ CIRCULATIONAHA.106.658021 3. Byard RW, ed. Sudden pediatric death: An overview. In: Sudden Death in the Young. 3rd ed. New York: Cambridge University Press, 2010:1-2. 4. Côté A. Investigating sudden unexpected death in infancy and early childhood. Pediatr Respir Rev 2010;11(4):219-225. DOI:10.1016/j.prrv.2009.12.002 5. Centers for Disease Control and Prevention. National vital statistics reports. Deaths final data for 2009. http://www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_03.pdf (accessed 10 June 2016). 6. Population Reference Bureau. 2009 world population data sheet. Updated 2014. http://www.prb.org/ Publications/Datasheets/2009/2009wpds.aspx (accessed 2 October 2013). 7. Statistics South Africa. Statistical Release P0309.3: Mortality and causes of death in South Africa, 2009: Findings from death notification. www.statssa.gov.za/publications/P03093/P030932009.pdf (accessed 10 June 2016). 8. Morentin B, Aguilera B, Garamendi PM, Suarez-Mier MP. Sudden unexpected non-violent death between 1 and 19 years in North Spain. Arch Dis Child 2000;82(6):456-461. DOI:10.1136/adc.82.6.456 9. Doolan A, Langlois N, Chiu C, Ingles J, Lind JM, Semsarian C. Postmortem molecular analysis of KCNQ1 and SCN5A genes in sudden unexplained death in young Australians. Int J Cardiol 2008;127(1):138-141. DOI:10.1016/j.ijcard.2007.05.001 10. Basso C, Calabrese F, Corrado D, Thiene G. Postmortem diagnosis in sudden cardiac death victims: Macroscopic, microscopic and molecular findings. Cardiovasc Res 2001;50(2):290-300. DOI:10.1016/ S0008-6363(01)00261-9 11. Donner EJ. Explaining the unexplained; expecting the unexpected: Where are we with sudden unexpected death in epilepsy? Epilepsy Curr 2011;11(2):45-49. DOI:10.5698/1535-7511-11.2.45 12. Tester DJ, Spoon DB, Valdivia HH, Makielski JC, Ackerman MJ. Targeted mutational analysis of the RyR2-encoded cardiac ryanodine receptor in sudden unexplained death: A molecular autopsy of 49 medical examiner/coroner’s cases. Mayo Clin Proc 2004;79(11):1380-1384. DOI:10.4065/79.11.1380 13. Tester DJ, Ackerman MJ. The molecular autopsy: Should the evaluation continue after the funeral? Pediatr Cardiol 2012;33(3):461-470. DOI:10.1007/s00246-012-0160-8 14. Chugh SS, Reinier K, Balaji S, et al. Population-based analysis of sudden death in children: The Oregon Sudden Unexpected Death Study. Heart Rhythm 2009;6(11):1618-1622. DOI:10.1016/j. hrthm.2009.07.046 15. Krous HF, Chadwick AE, Crandall L, Nadeau-Manning JM. Sudden unexpected death in childhood: A report of 50 cases. Pediatr Dev Pathol 2005;8(3):307-319. DOI:10.1007/s10024-005-1155-8 16. McGarvey CM, O’Regan M, Cryan J, et al. Sudden unexplained death in childhood (1-4 years) in Ireland: An epidemiological profile and comparison with SIDS. Arch Dis Child 2012;97(8):692-697. DOI:10.1136/archdischild-2011-301393 17. The Sudden Unexplained Death in Childhood Foundation. SUDC statistics. http://sudc.org/MedicalForensic/SUDC-Statistics (accessed 10 June 2016). 18. Weber MA, Pryce JW, Ashworth MT, Malone M, Sebire NJ. Histological examination in sudden unexpected death in infancy: Evidence base for histological sampling. J Clin Pathol 2012;65(1):58-63. DOI:10.1136/jclinpath-2011-200224 19. Semsarian C, Hamilton RM. Key role of the molecular autopsy in sudden unexpected death. Heart Rhythm 2012;9(1):145-150. DOI:10.1016/j.hrthm.2011.07.034

Accepted 27 June 2016.

October 2016, Print edition

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

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CLINICAL PRACTICE

The microbiome in chronic inflammatory airway disease: A threatened species R J Green,1 PhD, DSc; A van Niekerk,2 MB ChB, MMed; A C Jeevarathnum,1 MB BCh, FCPaed (SA), MMed, Cert Pulmonology (SA) Paed; C Feldman,3 PhD, DSc; G A Richards,3 MB ChB, FCP (SA), PhD; on behalf of the South African Allergic Rhinitis Working Group epartment of Paediatrics and Child Health, Faculty of Health Sciences, University of Pretoria, South Africa D Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Pretoria; and Nectare Clinton Clinic, Johannesburg, South Africa 3 Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 1 2

Corresponding author: R J Green (robin.green@up.ac.za)

The human body is exposed to a multitude of microbes and infectious organisms throughout life. Many of these organisms colonise the skin, gastrointestinal tract (GIT) and airway. We now recognise that this colonisation includes the lower airway, previously thought to be sterile. These colonising organisms play an important role in disease prevention, including an array of chronic inflammatory conditions that are unrelated to infectious diseases. However, new evidence of immune dysregulation suggests that early colonisation, especially of the GIT and airway, by pathogenic micro-organisms, has deleterious effects that may contribute to the potential to induce chronic inflammation in young children, which may only express itself in adult life. S Afr Med J 2016;106(8):779-781. DOI:10.7196/SAMJ.2016.v106i8.11159

Every organ system of the human body is alive with micro-organisms, i.e. the microbiome. This constitutes a group of microbial organisms that inhabit every system of the body and consists of microbial species and their associated genomes living on, and in, humans. Although there are multiple distinct microbiomes found at distinct sites and there is individual variation, the composition at any site is broadly similar in health. The microbiome interacts extensively with the host and outnumbers human gene content 100-fold. Among its functions are to afford mucosal protection to allergens and infecting organisms,[1] which also contribute to metabolic capacity and drive immune development. Disturbances in the microbiome are associated with many inflammatory and autoimmune diseases. The human body is exposed to a multitude of microbes and infectious organisms throughout life. Many of these organisms colonise the skin, gastrointestinal tract (GIT) and airway. We now recognise that this colonisation includes the lower airway, previously thought to be sterile. These colonising organisms play an important role in disease prevention, including an array of chronic inflammatory conditions that are unrelated to infectious diseases. However, new evidence of immune dysregulation suggests that early colonisation, especially of the GIT and airway, by pathogenic micro-organisms, has deleterious effects that may contribute to the potential to induce chronic inflammation in young children, which may only express itself in adult life. Atopic individuals, who have an underlying allergic condition, have frequent disease exacerbations, mostly produced by infectious organisms, viruses and bacteria, depending on the specific condition. A new concept is emerging in the aetiology and therefore the prevention of many chronic diseases (including allergy, metabolic syndrome and other chronic inflammatory conditions) through a new understanding of the importance of the interaction of the body with the human microbiome early in life. In the aetiology of allergic conditions it is now well known that allergic predisposition is conveyed on a genetically at-risk young child by the interaction of perturbation of the child’s gastrointestinal microbiome, lack of allergen exposure early in life (and especially foods in the young

gut) and absence of immune-modulatory support.[2] This model is well developed in the context of food allergy and atopic dermatitis, but there is a paucity of data on these associations with airway allergic diseases.[3] Therefore, although it seems likely that an allergic diathesis develop ing in a young child will ultimately lead to allergic rhinitis and atopic asthma through the concept of the allergic march, there must be other or additional mechanisms to explain the onset of these airway inflammatory diseases.[3] The local airway microbiome is important in this regard and changes here may well spell the onset of disease. Since the description of the hygiene hypothesis by Strachan[4] in 1989, there has been significant work in this domain. While the original hypothesis derived from his study showed that a child’s risk of developing allergic rhinitis (hay fever) was inversely related to the number of older siblings in the family, and the suggestion that microbial exposure early in life protects against allergic rhinitis, eczema and asthma, the term has evolved. More appropriate terms may be the microbial hypothesis (avoiding an overemphasis on cleanliness), old-friends hypothesis (implying that microbes that were beneficial for immune system development have been eliminated or replaced) and probably most correctly the biodiversity hypothesis or biome depletion.[5] The real problem is that many chronic inflammatory diseases, including allergy, are associated with both a replacement and a depletion of the normal microbiome (Fig. 1). The normal microbiome (both diversity and content) is important in its interaction with pattern recognition receptors on epithelial cells, which, in turn, regulate the relationship between pro- and antiinflammatory cytokines, chemokines and mediators.[6] Finally, once a chronic inflammatory airway disease has developed, there is an ongoing and important relationship with the local micro biome in disease exacerbations. Organisms are more numerous in the upper-respiratory than the lowerrespiratory tract. Healthy subjects demonstrate a diverse microbiome, which often includes potential pathogens such as Pseudomonas aerugi nosa, Staphylococcus aureus and various streptococcal species. When infection ensues, the microbiome is disrupted, causing community collapse with loss of diversity and overgrowth of pathogenic species.[1]

October 2016, Print edition

IN PRACTICE

Despite the seemingly unrelated association between the early gut and the respiratory tract, there is a certain cross-talk between the microbiome in the GIT and the airway through a gut-respiratory tract axis so that changes in the GIT microbiome create physiological changes in the airway (Fig. 2).[7]

Chronic airway disease and bacterial colonisation of the respiratory tract

There is now clear evidence that colonisation of the nasopharynx in the first month of life by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis is positively associated with recurrent wheeze, followed by asthma by 5 years of age.[8] It may be true that the origin of allergic rhinitis has a similar link.

The bacterial microbiome in chronic rhinosinusitis

Once a chronic allergic and inflammatory diathesis is established in the upper-respira

tory tract, both the nose and sinuses become inflamed and symptoms ensue. These sites also harbour a microbiome that is intimately involved in the allergic disease process, both chronically and during disease exacerbations. It is difficult to call this the normal microbiome, as the airway is already ill. It is a resident microbiome. Conventional culture of airway secretions may reveal the usual bacterial species, including S. aureus (and coagulase-negative staphylococci), streptococci spp., H. influenzae and anaerobes (Prevotella and Peptostreptococcus). How ever, there is significant variability between studies.[6] New techinques employing the 16S rRNA gene wide sequencing have uncovered a population of bacteria that are not found on conventional culture. However, different studies reveal different organisms. Stephenson et al.[9] identified anaerobic bacteria (Diaphorobacter, Peptoniphilus) in 78% and 72% of chronic rhinosinusitis cases, respectively, but not in controls, and S. aureus was found in half of the chronic rhinosinusitis cases, while it was detected in all controls.[9]

Host

Allergy, structural abnormalities

Dysbiosis Resident microbiome

Inflammation

Fig. 1. The microbiome-inflammation interaction – microbiome depletion in the upper-respiratory tract and disease. Lactobacilli bifidobacter

Bugs

Swallowed

Lung

Microbiota (including soluble) gut immune system

Immune regulation

Fig. 2.The gut-respiratory tract axis of allergy development.

The fungal and viral microbiome in chronic rhinosinusitis

Just as there is a resident bacterial microbiome in chronic rhino sinusitis, there is also a fungal microbiome. Species, including Candida, Aspergillus and Mucor, differ in studies and may even be found in asymptomatic control subjects.[12] Employing multiplex polymerase chain reaction for respiratory viruses, viral nucleic acid sequences have been found in 64% of sinus scrapings and 50% of nasal lavage samples in a chronic rhinosinusitis group of patients.[13] These were significantly higher than in controls (30% and 14% in scraping and lavage, respectively) and rhinovirus was the most frequently detected virus.[13]

Biofilm

Pathogens, e.g. Staphylococcus aureus Potentially Pneumococcus and (+ superantigen IgE) Haemophilus influenzae

Pulmonary immune response

Another study, however, revealed Pseudo monas, Citrobacter, Haemophilus propioni bacterium, Staphylococcus and Streptococcus as the resident microbiomes.[10] There are a number of confounders in these studies, however, which may in part explain different organism identification. These confounders include antibiotic use, steroid use, sampling method, exacerbations, variability in constitutive epithelial host-defense molecule secretion based on the region of the nose and sinuses sampled, and lastly the associated comorbidities.[11] It seems that an explanation for these study differences lies therein that the microbiome is individual specific, which may be one of the explanations for difficulty in therapeutic attempts.

October 2016, Print edition

Many of the early microbiological studies of bacteria, including their discovery and characterisation, were performed with planktonic bacteria, which are characterised as individual free-living (free-swimming) bacteria.[14] Even currently, standard laboratory culture techniques use planktonic bacteria that grow rapidly in nutrient-rich media. However, with the use of modern molecular techniques, it has become apparent that there are large populations of organisms in the human host that cannot be cultured by these standard techniques, as these organisms have adapted to a different type of growth.[14] Most bacteria exist in complex, tightknit colonies or communities often strongly adherent to surfaces; it has been reported that <1% of bacteria exist in planktonic form and that ≥99% of bacteria live in these types of biofilms.[14-16] Biofilms comprise highly structured communities of bacteria that exist within an extracellular matrix that consists of polysaccharides, nucleic acids and proteins, the so-called extracellular polymeric substances.[15,16]

IN PRACTICE

The formation of mature biofilms occurs in stages, proceeding through a number of well-characterised steps that are regulated by the bacterial quorum sensing system.[15-17] The latter involves communication between the bacterial cells through the release of small protein pheromones that control bacterial gene expression and therefore co-ordinate their behaviour.[18] Many bacteria, particularly those associated with chronic infection, including S. pneumoniae, P. aeruginosa, H. influenzae, S. aureus and Escherichia coli, are known to produce biofilm.[17-19] The characteristics of the micro-organisms in biofilm differ greatly from those of planktonic bacteria.[14] Bacteria within biofilms undergo changes in their expression of virulence factors and/or surface mole cules, their utilisation of nutrients, and their cell turnover rates.[19] Also, very importantly, there is an increase in antibiotic resistance in bacterial biofilms. Bacterial biofilms may be up to 1 000 times more resistant to antibiotics than planktonic bacteria, which are geneti cally identical.[15] The mechanism of antibiotic resistance appears to be multifactorial, including factors such as impeded penetration of antibiotics into the biofilm.[19] However, one important mechanism relates to a slow metabolic rate and turnover of bacteria deep within the nutrient-depleted zone of the biofilm so that these micro-organisms are less susceptible to antibiotics that target cell wall synthesis, which are much more active against bacteria that turn over rapidly.[15,19] Biofilm bacteria are also more resistant to host defences, which frequently results in both persistence of the biofilms and ongoing surrounding inflammation.[15] We are beginning to understand the important role of bacterial biofilms in a number of infections, including chronic lower-airway infections, such as cystic fibrosis, bronchiectasis and chronic obstructive pulmonary disease; device-related infections; and various otolaryngology conditions, including chronic rhinosinusitis, among many others, which are extremely difficult to treat.[14-16,19]

Current status of probiotic use in chronic airway disease management

It is theoretically possible that restoration of the microbiome could increase resistance to infection and decrease allergic responses. In this regard, numerous studies have been performed, most relying on the link between the gut and the respiratory tract, the so-called gutrespiratory tract axis. Unfortunately, these studies have generally been small, have used multiple different probiotics in different doses, and have utilised different administration schedules. A recent systematic review of the literature showed seven randomised, placebo-controlled trials involving the use of different probiotics. Two studies (N=170) specifically evaluated quality of life (QOL), frequency of symptoms, and level of bother, and found a statistically significant improvement. Although there was a decrease in episodes of rhinitis per year, there was no change in blood or immunological parameters and no effect on time free from rhinitis episodes or mean duration of episodes.[20] Similarly, a more recent systematic review and meta-analysis involving MEDLINE, Embase and Cochrane Library databases, found 21 double-blind randomised controlled trials and two randomised crossover studies (N=1 919) involving multiple probiotics, populations and outcomes.[21] Seventeen of these showed significant clinical benefit in one or more outcome measures; however, six showed no benefit. Among the trials eligible for meta-analysis, the rhinitis QOL score improved significantly, but there was no effect on total symptom score or IgE. Their conclusion was ‘that probiotics may be beneficial in improving symptoms and QOL in patients with allergic rhinitis; however, current evidence remains limited due to study heterogeneity and variable outcome measures. Additional high-quality studies are needed to establish appropriate recommendations.’[21] Some unanswered questions therefore arise from these studies and this replacement concept. These include what mixture of probiotics is

best, what the timing of administration should be, and where best the probiotics should be sited (the gut or directly into the nose or sinuses). As there is good evidence for efficacy (microbial burden change and inflammatory response modification) in mouse models for topical application of probiotics, this model needs urgent human studies.

Conclusion

The microbiome in the upper-respiratory tract is a dynamic organ. Dysbio sis is easy to produce in many disease states, and with the use of many drug therapies, including antibiotics and nasal steroids, the upper-respiratory tract is susceptible to significant pertubations and exacerbations. As studies demonstrating that restoring the microbiome in the nose and sinuses are currently not effective, it seems prudent to try to protect the resident or normal microbiome at all costs. Both the microbiome of the young gut and that of the upperrespiratory tract early in life are vital to disease prevention, as when dysbiosis and depletion occur, chronic inflammatory disease ensues. As a society, and as a scientific community, we need to look carefully at the many strategies we currently allow that interfere with the health of this important human asset, the normal microbiome. Once gone, it is almost certainly too late to retrieve it. Conflict of interest. The South African Allergic Rhinitis Working Group is an independent organisation. An annual meeting is supported by an unrestricted educational grant from Aspen Pharma. The South African Allergic Rhinitis Working Group: M Hockman (chair), R Friedman (deputy chair), H Lewis, M Davis, C Els, S Motakef, S Bouwer, P Crossland, A McCulloch, P Pio, M Gill, J Coetzee, K Kalideen, C Lodder. 1. Cope EK, Lynch SV. Novel microbiome-based therapeutics for chronic rhinosinusitis. Curr Allergy Asthma Rep 2015;15(3):504. DOI:10.1007/s11882-014-0504-y 2. Von Mutius E. Allergies, infections and the hygiene hypothesis: The epidemiological evidence. Immunobiology 2007;212(6):433-439. 3. Holt PG, Strickland DH, Hales BJ, Sly PD. Defective respiratory tract immune surveillance in asthma: A primary casual factor in disease onset and progression. Chest 2014;145(2):370-378. DOI:10.1378/ chest.13-1341 4. Strachan DP. Hay fever, hygiene and household size. BMJ 1989;299(6710):1259-1260. DOI:10.1136/ bmj.299.6710.1259 5. Green RJ. The interaction of respiratory allergies and ‘infection’. Curr Allergy Clin Immunol 2015;28:84-87. 6. Mahdavinia M, Keshavarzian A, Tobin MC, Landay AL, Schleimer RP. A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS). Clin Exp Allergy 2016;46(1):21-41. DOI:10.1111/cea.12666 7. Bassis CM, Erb-Downward JR, Dickson RP, et al. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. MBio 2015;6(2):e00037. DOI:10.1128/mBio.00037-15 8. Bisgaard H, Hermansen MN, Buchvald F, et al. Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med 2007;357(15):1487-1495. DOI:10.1056/NEJMoa052632 9. Stephenson MF, Mfuna L, Dowd SE, et al. Molecular characterization of the polymicrobial flora in chronic rhinosinusitis. J Otolaryngol Head Neck Surg 2010;39(2):182-187. 10. Stressmann FA, Rogers GB, Chan SW, et al. Characterization of bacterial community diversity in chronic rhinosinusitis infections using novel culture-independent techniques. Am J Rhinol Allergy 2011;25(4):e133-e140. DOI:10.2500/ajra.2011.25.3628 11. Ramakrishnan VR, Hauser LJ, Feazel LM, Ir D, Robertson CE, Frank DN. Sinus microbiota varies among chronic rhinosinusitis phenotypes and predicts surgical outcome. J Allergy Clin Immunol 2015;136(2):334-342. DOI:10.1016/j.jaci.2015.02.008 12. Cleland EJ, Bassiouni A, Boase S, Dowd S, Vreugde S, Wormald PJ. The fungal microbiome in chronic rhinosinusitis: Richness, diversity, postoperative changes and patient outcomes. Int Forum Allergy Rhinol 2014;4(4):259-265. DOI:10.1002/alr.21297 13. Cho GS, Moon BJ, Lee BJ, et al. High rates of detection of respiratory viruses in the nasal washes and mucosae of patients with chronic rhinosinusitis. Clin Microbiol 2013;51(3):979-984. DOI: 10.1128/JCM.02806-12 14. Pragman AA, Berger JP, Williams BJ. Understanding persistent bacterial lung infections: Clinical implications informed by the biology of the microbiota and biofilms. Clin Pulm Med 2016;23(2):57-66. DOI:10.1097/cpm.0000000000000108 15. Post JC, Hiller NL, Nistico L, et al. The role of biofilms in otolaryngologic infections: Update 2007. Curr Opin Otolaryngol Head Neck Surg 2007;15(5):347-351. 16. Al-Mutairi D, Kilty SJ. Bacterial biofilms and the pathophysiology of chronic rhinosinusitis. Curr Opin Allergy Clin Immunol 2011;11(1):18-23. DOI:10.1097/ACI.0b013e3283423376 17. Suntharalingam P, Cvitkovitch DG. Quorum sensing in streptococcal biofilm formation. Trends Microbiol 2005;13(1):3-6. DOI:10.1016/j.tim.2004.11.009 18. Moscoso M, García E, López R. Pneumococcal biofilms. Int Microbiol 2009;12:77-85. 19. Hall-Stoodley L, Stoodley P. Evolving concepts in biofilm infections. Cell Microbiol 2009;11(7):1034-1043. DOI:10.1111/j.1462-5822.2009.01323.x 20. Das RR, Singh M, Shafiq N. Probiotics in treatment of allergic rhinitis. World Allergy Organ J 2010;3(9):239-244. DOI:10.1097/WOX.0b013e3181f234d4 21. Zajac AE, Adams AS, Turner JH. A systematic review and meta-analysis of probiotics for the treatment of allergic rhinitis. Int Forum Allergy Rhinol 2015;5(6):524-532. DOI:10.1002/alr.21492

Accepted 14 June 2016.

October 2016, Print edition

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

IN PRACTICE

CASE REPORT

HIV/AIDS-associated Kaposi’s sarcoma of the gastrointestinal tract: A pictorial spectrum N Patel,1 BA Hons, MA, MB BCh; P Naidoo,2 BPharm, MMedSc (Pharmacol), MB BCh; P Mosiane,3 MB ChB, FCPath (SA); C Jann-Kruger,4 FCS (SA) epartment of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa D Medical Affairs, AstraZeneca South African Region, Johannesburg, South Africa 3 Department of Anatomical Pathology, National Health Laboratory Service, University of the Witwatersrand, Johannesburg, South Africa 4 Department of Surgery, Edenvale General Hospital, Johannesburg, South Africa 1 2

Corresponding author: N Patel (niravpatel44@gmail.com)

We briefly report two cases of HIV/AIDS-associated Kaposi’s sarcoma affecting the gastrointestinal tract. Both patients were seen at Edenvale General Hospital, Johannesburg, South Africa. S Afr Med J 2016;106(10):986-987. DOI:10.7196/SAMJ.2016.v106i10.11277

Case reports

A 71-year-old man presented with a 2-month history of malaise, weakness, dizziness, loss of weight and diarrhoea. He had no significant past medical, surgical or social history. His retroviral disease status was unknown. On examination he was cachexic and pale with no other significant clinical findings. He was subsequently admitted for investigation. Blood results on admission were as follows: haemoglobin 5.5 g/dL and HIV-positive, with an absolute CD4 count of 116 cells/µL. There were no significant findings on abdominal ultrasound. The second case was a 49-year-old woman who presented with diarrhoea, vomiting and weakness of 3 months’ duration. In addition she reported a ‘rash’ that had preceded these symptoms. She was HIV-positive with a CD4 count of 89 cells/µL and had been on highly active antiretroviral therapy (HAART) for 1 month. In addition she was being treated for pulmonary tuberculosis, and was in the intensive phase of therapy. On examination she appeared wasted and pale and had violaceous skin lesions, with similar lesions in her mouth. Her haemoglobin concentration was 4.8 g/dL. As part of the workup for symptomatic anaemia, both patients underwent endoscopy. Oesophagogastroduodenoscopy demonstrated multiple broad-based umbilicated violaceous nodules in the oesophagus, stomach and duodenum. Colonoscopy demonstrated broadbased violaceous nodules throughout the large intestine, some of which were circumferential and partially occluded the lumen of the large intestine. Selected images obtained during endoscopy are presented in Figs 1 (A and B) and 2 (A).

Fig. 1. A and B. Stomach lesions of female patient.

Fig. 2. Male patient. A: Lesions in the colon. B: Strong nuclear staining for human herpesvirus B, 400× magnification.

A biopsy of lesions identified during endo scopy confirmed Kaposi’s sarcoma (KS) (Fig. 2, B). The first patient was started on HAART and referred to the medical oncology department at Charlotte Maxeke Johannesburg Academic Hospital for further management. The patient defaulted and was lost to followup. The file for the second patient was lost. All attempts to contact both patients were unsuccessful.

October 2016, Print edition

Ethical clearance was received from the University of the Witwatersrand Human Research Ethics Committee (Ref. no. M140152).

Conclusion

Given the nonspecific nature of presenting symptoms and signs and the fact that KS is the most common gastrointestinal malignancy in patients with AIDS, a high index of suspicion in at-risk patients may

IN PRACTICE

aid in the early diagnosis and management of this life-threatening disease.[1] Endoscopy is an effective means of early diagnosis and may allow for earlier initiation of HAART in asymptomatic patients.

1. Weber JN, Carmichael DJ, Boylston A, Munro A, Whitear WP, Pinching AJ. Kaposi’s sarcoma of the bowel – presenting as apparent ulcerative colitis. Gut 1985;26(3):295-300.

Accepted 19 July 2016.

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

Diagnostic challenges with acellular bacterial meningitis

Y Moolla, MB ChB, FCP (SA), MMed; L Naidoo, MB BCh Department of Internal Medicine, Addington Hospital, Durban, South Africa Corresponding author: Y Moolla (moollayusuf@hotmail.com)

An immunocompetent adult presenting with acellular pneumococcal meningitis is a rare occurrence and may pose a diagnostic challenge. S Afr Med J 2016;106(10):988-989. DOI:10.7196/SAMJ.2016.v106i10.10670

Acute bacterial meningitis is a medical emergency and requires prompt diagnosis because it is associated with significant morbidity and mortality.[1,2] The incidence ranges from 5 per 100 000 persons in southern Africa to 12 per 100 000 in Africa.[3,4] Up to 50% of survivors may suffer from long-term neurological sequelae.[5-7] Better outcomes have resulted from early initiation of appropriate therapy; however, this has to be balanced with prompt confirmation of diagnosis, as inappropriate empirical therapy carries the risk of side-effects, cost burden and increased nosocomial infection.[8-11]

Case report

A 60-year-old woman with no comorbidities had complained of head ache, fever, general malaise and photophobia. She had no symp toms of an upper respiratory tract infection and had not travelled recently. She had no surgical history of splenectomy and did not consume alcohol. This was her first presentation for medical care. On examination she was haemodynamically stable with a temperature of 38°C. No rashes were present. She was alert and orientated. Signs of meningism were present, which included Kernig’s and Brudzinsksi’s signs. There were no cranial nerve palsies, and neither motor nor sensory abnormalities were elicited. Other systems were clinically unremarkable. The laboratory investigations revealed a haemoglobin concen tration of 9.5 g/dL, a normal platelet count (352 × 109/L) and leuco cytosis (white cell count 14.98 × 109/L). Her C-reactive protein (CRP) was markedly raised at 381 nmol/L and the plasma glucose level was 7.1 mmol/L. As no clinical signs of raised intracranial pressure were present, a lumbar puncture was performed. The findings of the cerebrospinal fluid (CSF) examination are shown in Table 1. Other tests performed included a non-reactive HIV ELISA and syphilis serology. The patient was started empirically on high-dose intravenous ceftriaxone in view of the clinical suspicion of meningitis. Her symptoms resolved 2 days later, and she had an uncomplicated inpatient stay with no neurological sequelae.

Discussion

We were fortunate that our patient presented with the classic signs and symptoms of meningitis. It is integral to note that the symptoms of meningitis, which may include headache, nausea and vomiting, have poor sensitivity and specificity for the diagnosis of meningitis, as demonstrated in a meta-analysis of 845 patients.[12] The classic clinical signs of Kernig and Brudzinski have value in ruling in the diagnosis of meningitis; however, these traditional signs have poor sensitivity and their absence cannot be used to rule out the disease. [8,13,14] The performance of a lumbar puncture is fundamental, as CSF examination is needed to establish the diagnosis.[15] Consistent CSF findings with acute bacterial meningitis include a polymorphonuclear pleocytosis, hypoglycorrhachia and a raised CSF protein level.[2,8,16] Despite our patient’s reduced CSF glucose and raised protein, the inconsistent polymorph cell count was striking. Based on clinical suspicion, CSF and laboratory determinants, she was treated for acute

Table 1. Findings on CSF examination CSF characteristics Appearance

Clear

Opening pressure (cm H2O)

Glucose (mmol/L)

Protein (g/L)

3.14

Polymorphs

Lymphocytes

Erythrocytes

Ratio CSF glucose/serum glucose

Very low

Gram stain

Positive

Culture

Streptococcus pneumoniae sensitive to penicillin G/ceftriaxone

Cryptococcal antigen test

Negative

October 2016, Print edition

IN PRACTICE

bacterial meningitis. CSF Gram stains and culture results confirming Streptococcus pneumoniae were only available after 48 hours. While CSF Gram stain testing has a high specificity for bacterial meningitis, it lacks sensitivity and was proven to be helpful in only 30 - 40% of patients.[17,18] There have been documented cases of bacterial meningitis in the absence of pleocytosis, with a particular occurrence in chil dren.[19,20] Normal CSF meningitis may occur when underlying immunosuppressive states are present; however, this acellular pheno [15,21] menon is exceptionally rare in an immunocompetent adult. We have noted only eight similar cases of acellular pneumococcal meningitis in the literature.[21-28] Additional markers that may assist in the diagnosis of acute bacterial meningitis exist, but their diagnostic role in the current guidelines is modest. The CSF glucose/blood glucose ratio is a simple marker that is often utilised, but it should be emphasised that it was shown to predict the presence of bacterial meningitis more precisely than routine CSF measurements.[29] CSF lactate has the ability to differentiate bacterial meningitis from aseptic meningitis with robust accuracy; however, this test is often unavailable.[30,31] Serum CRP and procalcitonin are useful markers as well, with the latter carrying a strong diagnostic odds ratio.[32,33] Molecular diagnostic testing, such as nuclear acid amplification tests, has been shown to facilitate the diagnosis in 33% of patients in whom the diagnosis could not be made conventionally.[34] Other future diagnostic aids may include immunochromographic testing, and the use of complement component 3, apolipoprotein A-1 and kinnogen-1.[35] Our experience highlights the rare occurrence of acellular bacterial meningitis in an immunocompetent adult. A heightened index of suspicion based on symptoms and clinical examination should prompt early appropriate antibiotic therapy. Swift, simple, highly sensitive investigations beyond routine tests may assist in supporting the diagnosis of meningitis in these challenging cases.

Learning points

• Acellular bacterial meningitis is rare in an immunocompetent adult. • The CSF glucose/blood glucose ratio and CSF lactate may assist in the diagnosis of bacterial meningitis. • Prompt empirical therapy improves outcomes. 1. Durand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meningitis in adults: A review of 493 episodes. N Engl J Med 1993;328:21-28. DOI:10.1056/NEJM199301073280104 2. Van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004;351:1849-1859. DOI:10.1056/ NEJMoa040845 3. Bill PLA, Bhigjee AI. Bacterial meningitis and viral infections of the nervous system. CME 1994;12:413427. 4. O’Dempsey TJ, McArdle TF, Lloyd-Evans N, et al. Pneumococcal disease among children in a rural area of West Africa. Pediatr Infect Dis J 1996;15(5):431-437. DOI:10.1097/00006454-199605000-00010

5. Weisfelt M, Hoogman M, van de Beek D, de Gans J, Dreschler WA, Schmand BA. Dexamethasone and longterm outcome in adults with bacterial meningitis. Ann Neurol 2006;60(4):456-468. DOI:10.1002/ana.20944 6. De Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549-1556. DOI:10.1056/NEJMoa021334 7. Bohr V, Paulson OB, Rasmussen N. Pneumococcal meningitis. Late neurologic sequelae and features of prognostic impact. Arch Neurol 1984;41(10):1045-1049. 8. Boyles TH, Bramford C, Bateman K, et al. Guidelines for the management of acute meningitis in children and adults in South Africa. South Afr J Epidemiol Infect 2013;28(1):5-15. 9. Miner JR, Heegaard W, Mapes A, Biros M. Presentation, time to antibiotics, and mortality of patients with bacterial meningitis at an urban county medical center. J Emerg Med 2001;21(4):387-392. DOI:10.1016/S0736-4679(01)00407-3 10. Swingler G, Delport S, Hussey G. An audit of the use of antibiotics in presumed viral meningitis in children. Pediatr Infect Dis J 1994;13(12):1107-1110. DOI:10.1097/00006454-199412000-00007 11. Parasuraman TV, Frenia K, Romero J. Enteroviral meningitis: Cost of illness and considerations for the economic evaluation of potential therapies. Pharmacoeconomics 2001;19(1):3-12. DOI:10.2165/00019053-200119010-00001 12. Attia J, Hatala R, Cook DJ, Wong JG. The rational clinical examination. Does this adult patient have acute meningitis? JAMA 1999;282(2):175-181. DOI:10.1001/jama.282.2.175 13. Fitch MT, van de Beek D. Emergency diagnosis and treatment of adult meningitis. Lancet Infect Dis 2007;7(2):191-200. DOI:10.1016/S1473-3099(07)70050-6 14. Waghdhare S, Kalantri A, Joshi R, Kalantri S. Accuracy of physical signs for detecting meningitis: A hospital-based diagnostic accuracy study. Clin Neurol Neurosurg 2010;112(9):752-757. DOI:10.1016/j.clineuro.2010.06.003 15. Brouwer MC, Thwaites GE, Tunkel AR, van de Beek D. Dilemmas in the diagnosis of acute communityacquired bacterial meningitis. Lancet 2012;380(9854):1684-1692. DOI:10.1016/S0140-6736(12)61185-4 16. Van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. Community-acquired bacterial meningitis in adults. N Engl J Med 2006;357:44-53. DOI:10.1056/NEJMra052116 17. Feigin RD, McCracken GH Jr, Klein JO. Diagnosis and management of meningitis. Pediatr Infect Dis J 1992;11(9):785-814. DOI:10.1097/00006454-199209000-00039 18. Spanos A, Harrell FE Jr, Durack DT. Differential diagnosis of acute meningitis: An analysis of the predictive value on initial observations. JAMA 1989;262(19):2700-2707. DOI:10.1001/ jama.1989.03430190084036 19. Coll MT, Uriz MS, Pineda V, et al. Meningococcal meningitis with ‘normal’ cerebrospinal fluid. J Infect 1994;29(3):289-294. DOI:10.1016/S0163-4453(94)91197-5 20. Polk DB, Steele RW. Bacterial meningitis presenting with normal cerebrospinal fluid. Pediatr Infect Dis J 1987;6(11):1040-1042. 21. Fishbein DB, Palmer DL, Porter KM, Reed WP. Bacterial meningitis in the absence of CSF pleocytosis. Arch Intern Med 1981;141(10):1369-1372. 22. Domingo P, Mancebo J, Blanch L, Coll P, Net A, Nolla J. Bacterial meningitis with ‘normal’ cerebrospinal fluid in adults: A report on five cases. Scand J Infect Dis 1990;22(2):115-116. DOI:10.3109/00365549009023130 23. Uchihara T, Ichikawa K, Yoshida S, Tsukagoshi H. Positive culture from normal CSF of Streptococcus pneumoniae meningitis. Eur Neurol 1996;36(4):234. DOI:10.1159/000117256 24. Gutiérrez-Macías A, García-Jiménez N, Sánchez-Muñoz L, Martinez-Ortiz de Zarate M. Pneumo coccal meningitis with normal cerebrospinal fluid in an immunocompetent adult. Am J Emerg Med 1999;17(2):219. DOI:10.1016/S0735-6757(99)90074-8 25. Alvarez EF, Olarte KE, Ramesh MS. Purpura fulminans secondary to Streptococcus pneumoniae meningitis. Case Rep Infect Dis 2012;2012:508503. DOI:10.1155/2012/508503 26. Ris J, Mancebo J, Domingo P, Cadafalch J, Sanchez M. Bacterial meningitis despite ‘normal’ CSF findings. JAMA 1985;254(20):2893-2894. DOI:10.1001/jama.1985.03360200043019 27. Suzuki H, Tokuda Y, Kurihara Y, Suzuki M, Nakamura H. Adult pneumococcal meningitis presenting with normocellular cerebrospinal fluid: Two case reports. J Med Case Rep 2013;7:294. DOI:10.1186/1752-1947-7-294 28. Tamune H, Takeya H, Suzuki W, et al. Cerebrospinal fluid/blood glucose ratio as an indicator for bacterial meningitis. Am J Emerg Med 2014;32(3):263-266. DOI:10.1016/j.ajem.2013.11.030 29. Huy NT, Thao NTH, Diep Doan TN, Kikuchi M, Zamora J, Hirayama K. Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: A systemic review and meta-analysis. Crit Care 2010;14(6):R240. DOI:10.1186/cc9395 30. Sakushima K, Hayashino Y, Kawaguchi T, Jackson JL, Fukuhara S. Diagnostic accuracy of cerebrospinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis: A meta-analysis. J Infect 2011;62(4):255-262. DOI:10.1016/j.jinf.2011.02.010 31. Rajs G, Finzi-Yeheskel Z, Rajs A, Mayer M. C-reactive concentrations in cerebral spinal fluid in Grampositive and Gram-negative bacterial meningitis. Clin Chem 2002;48(3):591-592. 32. Vikse J, Henry BM, Roy J, Ramakrishnan PK, Tomaszewski KA, Walocha AJ. The role of serum procalcitonin in the diagnosis of bacterial meningitis in adults: A systematic review and meta-analysis. Int J Infect Dis 2015;38(1):68-76. DOI:10.1016/j.ijid.2015.07.011 33. Parent du Châtelet I, Traore Y, Gessner BD, et al. Bacterial meningitis in Burkina Faso: Surveillance using field-based polymerase chain reaction testing. Clin Infect Dis 2005;40(1):17-25. DOI:10.1086/426436 34. Cordeiro AP, Pereira RAS, Chapeaurouge A, et al. Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets. BMC Genomics 2015;16(5):1-9. DOI:10.1186/1471-2164-16-S5-S11

Accepted 17 February 2016.

October 2016, Print edition

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

IN PRACTICE

CASE REPORT

Angio-oedema associated with colistin A A Abulfathi,1 MBBS; T Greyling,2 MB ChB, FCP (SA), Cert ID (SA) Phys; M Makiwane,1 MB ChB, Dip HIV Man (SA), PG Dip (Pharm Med); M Esser,3 MB ChB, MMed (Paed), Cert Rheum; E Decloedt,1 MB ChB, BSc Hons (Pharm), FCCP (SA), MMed (Clin Pharm) Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa Division of Infectious Diseases, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa 3 Immunology Unit, Medical Microbiology, National Health Laboratory Service Tygerberg; and Department of Pathology, Stellenbosch University, Tygerberg, Cape Town, South Africa 1 2

Corresponding author: A A Abulfathi (aaabulfathi@sun.ac.za)

A 50-year-old woman known to have type 1 diabetes mellitus presented with a rare case of angio-oedema associated with colistin use. The angio-oedema was temporally associated with the use and discontinuation of colistin with the reasonable exclusion of important differential diagnoses. Pseudoallergy may be a probable underlying mechanism. However, we cannot exclude the possibility of hereditary angio-oedema type 2 or 3, or that her concomitant medications (particularly enalapril) and her renal impairment contributed to the risk and severity of her angio-oedema.

Case report

A 50-year-old woman presented to Tygerberg Hospital, Cape Town, South Africa (SA), with dysuria, and suprapubic and lower abdominal pain. She was known to have had type 1 diabetes mellitus for 24 years and had microvascular complications in the form of retinopathy (with blindness of the right eye), neuropathy and nephropathy. Her estimated glomerular filtration rate had declined from a baseline of 31 mL/min/1.73 m2 2 months earlier to 18 mL/min/1.73 m2 at presentation. She was admitted with sepsis due to a complicated urinary tract infection and her urine cultured Acinetobacter baumannii, sensitive only to colistin. She was initiated on intravenous colistin, dose adjusted for her degree of renal impairment. Five hours after the infusion, she developed urticaria and angio-oedema involving the face, lips and tongue, but with no laryngeal involvement or anaphylaxis. She had no personal or family history of angio-oedema or of any other allergy or atopy. She was not known to have had prior exposure to colistin. At the time of angio-oedema diagnosis, she had received subcutaneous insulin (24 years), enalapril (5 years), amlodipine (5 years), simvastatin (5 years), aspirin (5 years), furosemide (1 year) and colistin (5 hours) (Fig. 1). The patient was successfully managed with prompt discontinuation of the colistin infusion, administration of promethazine, hydro cortisone, oxygen via facemask and

22 March 2015

9 March 2015

We present what is to our knowledge a rare presentation of colistin-induced angiooedema.[1]

19 March 2015

S Afr Med J 2016;106(10):990-991. DOI:10.7196/SAMJ.2016.v106i10.10835

Actraphane Amlodipine Enalapril Furosemide Aspirin Simvastatin Colistin Hydrocortisone Promethazine Tigecycline & rifampicin

Date of admission

Angio-oedema

Resolution

Fig. 1. Causality assessment.

supportive care, with provision for escala tion of care if symptoms worsened. There was no indication for intubation, and the angio-oedema resolved over 72 hours. Her A. baumannii urosepsis was successfully treated with intravenous tigecycline and oral rifampicin. Angiotensin-converting enzyme inhibitor (ACE-I) angio-oedema was considered,[2-5] as

October 2016, Print edition

ACE-I angio-oedema may develop months or even years after commencing therapy.[2,4,6] However, she improved and had complete resolution of symptoms despite continuing with enalapril. While other concomitant medications (insulin, amlodipine, furosemide, simvastatin) could theoretically cause angio-oedema, it is highly unlikely because of their continued use.

IN PRACTICE

Hereditary angio-oedema (HAE) type 1 or 2 is unlikely because of the absence of a family history and the first occurrence in the patient’s 6th decade.[4,7] HAE-1 was excluded with a normal C4 level of 0.23 g/L (normal range 0.20 - 1.00) and a slightly elevated C1 esterase inhibitor (C1-INH) level of 0.49 g/L (0.21 - 0.40). The normal C4 level makes HAE-2 unlikely, but a definite diagnosis requires evaluation of the function of C1-INH, which is not readily available in SA. The elevated C1-INH level observed in our patient may have been due to the underlying sepsis. HAE-3, which is more common in females and at an older age, remains a possibility, but F-12 gene mutation testing is unavailable in SA. Acquired angio-oedema, also known as acquired C1-INH defi ciency, is due to autoantibodies against C1-INH as a result of autoimmune or lymphoproliferative diseases.[3,8] This was considered because our patient had type 1 diabetes mellitus and was therefore at risk of other autoimmune diseases. However, she had a normal C3 level of 1.05 g/L (0.50 - 1.53). The temporal association between the administration of colistin and development of symptoms that resolved with the prompt discontinuation of colistin makes the diagnosis of colistin-induced angio-oedema likely. Rechallenge with colistin would have confirmed our diagnosis but was considered inappropriate. Pseudoallergy may be the most likely mechanism for our patient’s colistin-induced angio-oedema. This is a result of the offending agent binding directly to mast cells and inducing their degranulation with release of inflammatory mediators, particularly histamine,[3] leading to angio-oedema and urticaria.[9] It does not require IgE mediation[3,10] and no prior sensitisation is needed.

Conclusion

We present what is to our knowledge a rare case of colistininduced angio-oedema temporally associated with the use and discontinuation of colistin with the reasonable exclusion of important differential diagnoses. However, we cannot exclude the possibility that her concomitant medication (particularly enalapril) and her renal impairment contributed to the risk and severity of her angiooedema. 1. Medicines & Healthcare Products Regulatory Agency. Public Assessment Report: Decentralised procedure: Colistimethate sodium. http://www.mhra.gov.uk/home/groups/par/documents/ websiteresources/con152847.pdf (accessed 25 August 2016). 2. Lipski SM, Casimir G, Vanlommel M, Jeanmaire M, Dolhen P. Angiotensin-converting enzyme inhibitors-induced angioedema treated by C1 esterase inhibitor concentrate (Berinert®): About one case and review of the therapeutic arsenal. Clin Case Rep 2015;3(2):126-130. DOI:10.1002/ccr3.171 3. Jaiganesh T, Wiese M, Hollingsworth J, et al. Acute angioedema: Recognition and management in the emergency department. Eur J Emerg Med 2013;20(1):10-17. DOI:10.1097/MEJ.0b013e328356f76e 4. Javaud N, Charpentier S, Lapostolle F, et al. Angiotensin-converting enzyme inhibitor-induced angioedema and hereditary angioedema: A comparison study of attack severity. Intern Med 2015;54(20):2583-2588. DOI:10.2169/internalmedicine.54.4181 5. Decloedt E, Freercks R, Maartens G. Cerebral angioedema associated with enalapril. Br J Clin Pharmacol 2009;68(2):271-273. DOI:10.1111/j.1365-2125.2009.03452.x 6. Orr KK, Myers JR. Intermittent visceral edema induced by long-term enalapril administration. Ann Pharmacother 2004;38(5):825-827. DOI:10.1345/aph.1D458 7. Moran E, Isaacs GS, Naidoo B, Pudifin DJ. Hereditary C1 esterase deficiency in a Zulu kindred. S Afr Med J 2009;99(1):40-42. 8. Triggianese P, Chimenti MS, Toubi E, et al. The autoimmune side of hereditary angioedema: Insights on the pathogenesis. Autoimmun Rev 2015;12(8):4-8. DOI:10.1016/j.autrev.2015.03.006 9. Grigoriadou S, Longhurst HJ. Clinical Immunology Review Series: An approach to the patient with angio-oedema. Clin Exp Immunol 2009;155(3):367-377. DOI:10.1111/j.1365-2249.2008.03845.x10 10. Lewis LM. Angioedema: Etiology, pathophysiology, current and emerging therapies. J Emerg Med 2013;45(5):789-796. DOI:10.1016/j.jemermed.2013.03.045

Accepted 29 March 2016.

October 2016, Print edition

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

RESEARCH

South African congenital disorders data, 2006 - 2014 V Lebese, BSc Hons; C Aldous, PhD; H L Malherbe, MSc School of Clinical Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa Corresponding author: H L Malherbe (helen@hmconsult.co.za)

Background. The National Department of Health in South Africa (SA) routinely collects congenital disorder (CD) data for its national CD surveillance system. The current system has been implemented since 2006, but no reports on the data collected, methodology, achievements or challenges have been published to date. Objectives. To ascertain the effectiveness of the current national CD surveillance system and its implementation. Method. A descriptive, retrospective study using an audit of the current database was undertaken to evaluate the number of notifications received, types of CDs reported and the quality of reporting across SA for data received from 2006 to 2014. Results. A total of 14 571 notifications were received, including 13 252 CDs and 1 319 zero notifications, across all nine provinces. Commonly reported CDs included Down syndrome, cleft lip and palate, talipes equinovarus, neural tube defects and albinism. Conclusions. The major challenges identified included erratic compliance by health facilities and a lack of healthcare providers trained in human genetics related to CDs. This has led to misdiagnosed and undiagnosed CDs, collectively resulting in under-reporting of cases by >98% during the review period. Owing to limited human and financial resources, it is recommended that the surveillance system be modified into an electronic format. This should be piloted alongside relevant training in specific sentinel sites, to improve data coverage and quality for further evaluation. S Afr Med J 2016;106(10):992-995. DOI:10.7196/SAMJ.2016.v106i10.11314

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i10.11314

Risk of cardiovascular disease among teachers in Cape Town: Findings of the South African PaCT pilot study E C Laurence,1 MB ChB, MSc (Clin Epidemiol); J Volmink,1,2 BSc, MB ChB, MPH, DPhil; T M Esterhuizen,1 MSc (Epidemiol); S Dalal,3 PhD; M D Holmes,3,4 MD, DrPH entre for Evidence-based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa C South African Cochrane Centre, South African Medical Research Council, Tygerberg, Cape Town, South Africa 3 Department of Epidemiology, Harvard School of Public Health, Boston, USA 4 Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA 1 2

Corresponding author: E C Laurence (carienl@sun.ac.za)

Background. The accelerating epidemic of cardiovascular disease (CVD) and other non-communicable diseases (NCDs) highlights the need to establish long-term cohort studies in Africa. Objective. The Partnership for Cohort Research and Training (PaCT) seeks to study NCDs in South Africa (SA), Uganda, Tanzania and Nigeria on a long-term basis. Pilot studies at each site have tested feasibility. The SA site additionally studied the prevalence of CVD risk factors and categorised participants’ 10-year predicted risk of a cardiovascular event. Methods. We enrolled teachers from 111 public schools in the Metro South Education District in Cape Town, SA, between January 2011 and May 2012. Participants completed a self-administered questionnaire and biological measurements, and chose post or email for 6-month follow-up.

October 2016, Print edition

RESEARCH

Results. The participation of schools was permitted by 53.2% of principals, and 489 of 1 779 teachers agreed to participate. Of teachers willing to participate in the follow-up, 52% were retained, three-quarters by post and a quarter by email. Their mean age was 46.3 years and 70.3% were female. The prevalence of CVD risk factors was high and featured hypertension (48.5%), hypercholesterolaemia (20.5%), smoking (18.0%), diabetes (10.1%) and chronic kidney disease (10.4%), while 84.7% were overweight or obese. Of the participants, 18.7% were at high risk of a heart attack or stroke within 10 years. Conclusion. Establishing a cohort study among teachers has challenges but also opportunities for addressing CVD, which will soon impose a substantial burden on Cape Townâ&#x20AC;&#x2122;s education system. S Afr Med J 2016;106(10):996-1001. DOI:10.7196/SAMJ.2016.v106i10.10869

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i10.10869

Outcomes of treatment of drug-susceptible tuberculosis at public sector primary healthcare clinics in Johannesburg, South Africa: A retrospective cohort study E P Budgell,1 MSc; D Evans,1 PhD; K Schnippel,2,3 MPA; P Ive,3 MB BCh, FCP (SA), DTM&H, Dip HIV Man (SA); L Long,1 MCom; S Rosen,1,4 MPA ealth Economics and Epidemiology Research Office, Department of Internal Medicine, Faculty of Health Sciences, University of the H Witwatersrand, Johannesburg, South Africa 2 Right to Care, Johannesburg, South Africa 3 Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 4 Center for Global Health and Development, Boston University, Boston, USA 1

Corresponding author: S Rosen (sbrosen@bu.edu)

Background. Despite the large number of tuberculosis (TB) patients treated in South Africa (SA), there are few descriptions in the published literature of drug-susceptible TB patient characteristics, mode of diagnosis or treatment outcomes in routine public sector treatment programmes. Objective. To enhance the evidence base for public sector TB treatment service delivery, we reported the characteristics of and outcomes for a retrospective cohort of adult TB patients at public sector clinics in the Johannesburg Metropolitan Municipality (JHB), SA. Methods. We collected medical record data for a retrospective cohort of adult (â&#x2030;Ľ18 years) TB patients registered between 1 April 2011 and 31 March 2012 at three public sector clinics in JHB. Data were abstracted from National TB Programme clinic cards and the TB case registers routinely maintained at study sites. We report patient characteristics, mode of diagnosis, mode of treatment supervision, treatment characteristics, HIV status and treatment outcomes for this cohort. Results. A total of 544 patients were enrolled in the cohort. Most (86%) were new TB cases, 81% had pulmonary TB, 58% were smearpositive at treatment initiation and 71% were HIV co-infected. Among 495 patients with treatment outcomes reported, 80% (n=394) had successful outcomes, 11% (n=55) were lost to follow-up, 8% (n=40) died and 1% (n=6) failed treatment. Conclusions. Primary healthcare clinics in JHB are achieving relatively high rates of success in treating drug-susceptible TB. Missing laboratory results were common, including follow-up smears, cultures and drug susceptibility tests, making it difficult to assess adherence to guidelines and leaving scope for substantial improvements in record-keeping at the clinics involved. S Afr Med J 2016;106(10):1002-1009. DOI:10.7196/SAMJ.2016.v106i10.10745

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i10.10745

October 2016, Print edition

RESEARCH

Inappropriate medicine prescribing in older South Africans: A cross-sectional analysis of medicine claims data J A van Heerden, BPharm; J R Burger, BPharm, MPharm, PhD (Pharm Pract); J J Gerber, BSc (Pharm) Hons, BSc (Ind Pharm), MSc (Ind Pharm) Hons, BSc (Pharmacol), DSc (Pharm) Medicine Usage in South Africa (MUSA), Faculty of Health Sciences, North-West University (Potchefstroom campus), South Africa Corresponding author: J Burger (johanita.burger@nwu.ac.za) Background. Prescribing for older patients is a well-recognised problem, and inappropriate items are prescribed frequently. Several tools and criteria are available to promote rational prescribing in older patients. Objective. To determine the prevalence of potentially inappropriate prescriptions (PIPs) in older South African patients. Methods. A retrospective drug utilisation review was conducted using medicine claims data over a 1-year period. Patients aged ≥65 years with at least one paid claim for any medicine item during this period were included. The prevalence of PIPs was identified by applying the 2012-Beers criteria list. Results. A total of 103 420 patients, mean age 74.0 years (standard deviation 6.7), 57.1% female, were included in the analysis. The number of PIPs identified was 562 852 in 71 206 patients (68.9%). The most common medicines inappropriately prescribed were oestrogen (oral and patch formulations only) (12.4%), meloxicam (7.3%), amitriptyline and combinations thereof (6.5%), diclofenac (6.4%), ibuprofen (6.1%), alprazolam (5.3%), meprobamate and combinations thereof (5.0%), sliding-scale insulin (3.3%), amiodarone (3.1%) and doxazosin (2.6%). Medicines were inappropriately prescribed to women statistically significantly more often than to men (1.9:1; p<0.001), although this difference was not of practical significance (Cramér’s V=0.06). Conclusions. Medicine use in older patients must be appropriate and evaluated regularly. According to explicit criteria, PIPs were found to be common in older patients registered on the database. Monitoring of PIPs may increase the quality of prescribing, but explicit criteria cannot substitute for clinical judgement based on the individual patient. S Afr Med J 2016;106(10):1010-1016. DOI:10.7196/SAMJ.2016.v106i10.10627

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i10.10627

Comparison of the prevalence and characteristics of inpatient adverse events using medical records review and incident reporting W M Macharia,1 MB ChB, MMed (Paeds), MSc; C M Muteshi,2 MB ChB, MMed (O&G); S Z Wanyonyi,2 MB ChB, MMed (O&G); A M Mukaindo,2 MMed (O&G); A Ismail,1 MB ChB, MMed (Paeds); H Ekea,3 MB ChB; A Abdallah,4 MB ChB, MMed (Surg); J M Tole,1 MB ChB, MMed (Paeds); A K Ngugi,5 BSc, MSc, PhD epartment of Paediatrics, Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya D Department of Obstetrics and Gynaecology, Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya 3 Department of Medicine, Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya 4 Department of Surgery, Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya 5 Population Health Sciences, Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya 1 2

Corresponding author: W M Macharia (william.macharia@aku.edu)

Background. Information on adverse events (AEs) in hospitalised patients in developing countries is scanty. Objective. To compare the magnitude and characteristics of inpatient AEs in a tertiary, not-for-profit healthcare facility in Kenya, using medical records review and incident reporting.

October 2016, Print edition

RESEARCH

Methods. Estimation of prevalence was done using incidents reported in 2010 from a random sample of medical records for hospital admissions. Nurse reviewers used 18 screening criteria, followed by physician reviewers to confirm occurrence. An AE was defined as an unexpected clinical event (UE) associated with death, disability or prolonged hospitalisation not explained by the disease condition. The kappa statistic was used to estimate inter-rater agreement, and analysis was done using logistic regression. Results. The study identified 53 UEs from 2 000 randomly selected medical records and 33 reported UEs from 23 026 admissions in the index year. The prevalences of AEs from medical records review and incident reports were 1.4% (95% confidence interval (CI) 0.9 - 2.0) and 0.03% (95% CI 0.012 - 0.063), respectively. Compared with incident reporting, review of medical records identified more disability (13.2% v. 0%; p=0.03) and prolonged hospital stays (43.4% v. 18.2%; p=0.02). Conclusions. Review of medical records is preferable to incident reporting in determining the prevalence of AEs in health facilities with limited inpatient quality improvement experience. Further research is needed to determine whether staff education and a positive culture change through promotion of non-punitive UE reporting or a combination of approaches would improve the comprehensiveness of AE reporting. S Afr Med J 2016;106(10):1021-1036. DOI:10.7196/SAMJ.2016.v106i10.10619

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i10.10619

Strengthening rural health placements for medical students: Lessons for South Africa from international experience J E Doherty, BVSc, MPhil, DHSM; I Couper, BA, MB BCh, MFamMed, FCFP (SA) Centre for Rural Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: J E Doherty (dohertyj@telkomsa.net)

Background. This article derives lessons from international experience of innovative rural health placements for medical students. It provides pointers for strengthening South African undergraduate rural health programmes in support of the governmentâ&#x20AC;&#x2122;s rural health, primary healthcare and National Health Insurance strategies. Methods. The article draws on a review of the literature on 39 training programmes around the world, and the experiential knowledge of 28 local and international experts consulted through a structured workshop. Results. There is a range of models for rural health placements: some offer only limited exposure to rural settings, while others offer immersion experiences to students. Factors facilitating successful rural health placements include faculty champions who drive rural programmes and persuade faculties to embrace a rural mission, preferential selection of students with a rural background, positioning rural placements within a broader rural curriculum, creating rural training centres, the active nurturing of rural service staff, assigning students to mentors, the involvement of communities, and adapting rural programmes to the local context. Common obstacles include difficulties with student selection, negative social attitudes towards rural health, shortages of teaching staff, a sense of isolation experienced by rural students and staff, and difficulties with programme evaluation. Conclusions. Faculties seeking to expand rural placements should locate their vision within new health system developments, start off small and create voluntary rural tracks, apply preferential admission for rural students, set up a rural training centre, find practical ways of working with communities, and evaluate the educational and clinical achievements of rural health placements. S Afr Med J 2016;106(5):524-527. DOI:10.7196/SAMJ.2016.v106i5.10216

Full article available online at http://dx.doi.org/10.7196/SAMJ.2016.v106i5.10216

October 2016, Print edition

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The convenient pocket-sized design enables you to fit it comfortably into your hospital bag or coat pocket, so it The convenient pocket-sized design enables you to fit it comfortably into your hospital bag or coat pocket, so it can always be at hand for ready reference. South African Medicines Formulary (SAMF), a joint initiative of the can always be at hand for ready reference. South African Medicines Formulary (SAMF), a joint initiative of the University of Cape Town’s Division of Clinical Pharmacologyyand the Health and Medical Publishing Group, University of Cape Town’s Division of Clinical Pharmacolog and the Health and Medical Publishing Group, publishers for the South African Medical Association, provides easy access to the latest, scientifically accurate publishers for the South African Medical Association, provides easy access to the latest, scientifically accurate information, including full drug profiles, clinical notes and special prescriber’s points. The thoroughly updated information, including full drug profiles, clinical notes and special prescriber’s points. The thoroughly updated 12th edition of SAMF is your essential reference to the rational, cost-effective and safe use of medicines. 12th edition of SAMF is your essential reference to the rational, cost-effective and safe use of medicines.

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True (A) or false (B): SAMJ Towards collaborative integration of pharmacists and nurses into antimicrobial stewardship programmes in South Africa (SA) 1. By involving nurses in the antibiotic stewardship process, there was a 19.7% reduction in surgical site infection in this study. 2. Postgraduate specialisation in pharmacy at postgraduate level is not yet formally recognised by the South African Pharmacy Council and not widely available. Sudden and unexpected childhood deaths investigated at the Pretoria Medico-Legal Laboratory, South Africa, 2007 - 2011 3. Most sudden and unexpected childhood deaths occurred in children aged 1 - 5 years. Risk of cardiovascular disease (CVD) among teachers in Cape Town: Findings of the South African PaCT pilot study 4. According to the World Health Organization, >1.1Â million deaths in the African region in 2005 were caused by CVD and over half of these were due to ischaemic heart disease and stroke. 5. In this study, 48.5% had hypertension, but less than half reported being on antihypertensive treatment. Outcomes of treatment of drug-susceptible tuberculosis at public sector primary healthcare clinics in Johannesburg, SA: A retrospective cohort study 6. In SA, nearly two-thirds (61%) of all notified tuberculosis cases are HIV-infected. 7. Treatment outcomes for tuberculosis are poorer in HIV-infected patients.

CME Intimate partner violence is everyoneâ&#x20AC;&#x2122;s problem, but how should we approach it in a clinical setting? 11. Intimate partner violence presents predominantly in the form of physical abuse. 12. Women largely appreciate being asked about intimate partner violence. 13. A healthcare worker should always insist that a woman in an abusive situation must leave her partner. 14. Evidence of intimate partner violence can only be recorded on a J88 form. Intimate partner violence: A helpful guide to legal and psychosocial support services 15. To apply for a protection order, the complainant must lay a criminal charge against the perpetrator. 16. A protection order can only be applied for during court hours. 17. It is the role of the police to assist abused women with finding shelter. 18. All shelters for abused women require women to pay. Mental health, intimate partner violence and HIV 19. Mental health, intimate partner violence and HIV are intersecting epidemics. 20. Providers of HIV care could be the optimal entry point for identifying patients suffering from mental health problems and intimate partner violence.

Inappropriate medicine prescribing in older South Africans: A cross-sectional analysis of medicine claims data 8. One of the medicines most commonly prescribed inappropriately was oestrogen (oral and patch formulations only). 9. Elderly women were more likely to have inappropriate prescriptions than elderly men. 10. Altered pharmacokinetics and pharmacodynamics associated with ageing may contribute to drugs being classified as inappropriate for use in older adults.

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October 2016, Print edition

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