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Malaria Pharmacovigilance in Africa

Lessons from a Pilot Project in Mpumalanga Province,South Africa

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Abstract

p ]Background and objectives: Prior to the introduction of artemisinin-based combination antimalarial therapy in Mpumalanga province, South Africa, a pharmacovigilance strategy was developed to pilot locally relevant surveillance methods for detecting serious adverse drug reactions (ADRs) and signals related to artesunate plus sulfadoxine/pyrimethamine.

Study design: From 1 March 2002 to 30 June 2004, five methods for detecting ADRs in patients receiving antimalarials were piloted in the rural communities of Mpumalanga province in South Africa: (i) home follow-up of patients by malaria control staff; (ii) enhanced spontaneous reporting of suspected ADRs by health professionals at clinics and hospitals; (iii) active hospital surveillance for malaria-related admissions and patients recently treated for malaria; (iv) a confidential enquiry into malaria-related deaths; and (v) adverse events monitoring during two therapeutic efficacy studies conducted in 2002 and 2004.

Results: During the study period, the malaria control programme was notified of 4778 cases of malaria while sulfadoxine/pyrimethamine monotherapy was the recommended treatment and 7692 cases after the introduction of artesunate plus sulfadoxine/pyrimethamine in January 2003. Of 2393 home follow-up visits of reported cases of malaria, three fatal adverse events were identified where recent use of artesunate plus sulfadoxine/pyrimethamine treatment was reported. Two cases were attributed to poor response to treatment, while one case was considered possibly related to artesunate plus sulfadoxine/pyrimethamine treatment. Clinic and hospital surveillance reported six ADRs in association with sulfadoxine/pyrimethamine treatment, five being treatment failures and one being a non-serious rash. During active hospital surveillance, 38 inpatients exposed to sulfadoxine/pyrimethamine were identified, including one child who experienced pancytopenia following treatment with sulfadoxine/pyrimethamine 11 days before admission; this adverse effect was considered to be possibly due to sulfadoxine/pyrimethamine treatment. The confidential enquiry into malaria- 900 related deaths identified three adverse events, including a death where the contribution of treatment could not be excluded. A therapeutic efficacy study of 95 patients followed over 42 days identified one case of repeated vomiting possibly associated with artesunate plus sulfadoxine/pyrimethamine.

Conclusion: Multifaceted monitoring throughout the malaria patient journey is necessary in developing countries implementing new treatments to safeguard against missing serious complications associated with malaria treatment.

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Acknowledgements

This initiative was the result of collaboration between the Department of Health and Social Services of Mpumalanga province and the University of Cape Town’s Division of Clinical Pharmacology. The South East African Combination Antimalarial Therapy evaluation, within which this study was nested, received core financial support from the United Nations Development Programme/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. The funders had no role in data collection or analysis, decision to publish or preparation of the manuscript. The authors have no conflicts of interest that are directly relevant to the content of this study.

We thank the Mpumalanga Provincial Department of Health and Social Services for appreciating the value of this study and authorising healthcare facility records to be made available. The authors gratefully acknowledge the malaria control programme case investigators who collected all the healthcare facility records and conducted interviews with contacts. The cooperation of the healthcare facility staff and close contacts in providing the necessary data is appreciated. We acknowledge members of the expert review panel for their valuable contributions to ensuring the validity of this enquiry particularly: Dr Armando Sanchez Canal (Tshilidzini Hospital, Limpopo Province), Dr Steven Donohue (University of Limpopo), Dr Norma Cecilia Garcia (Department of Health, Limpopo Province), Dr Frank Hansford (Malaria Control Programme, Limpopo Province), Dr Bernice Harris (National Institute of Communicable Diseases), Dr Jakobus Hugo (Mpumalanga Department of Health and Social Services), Dr Etienne Immelman (Manguzi Hospital, KwaZulu Natal Province), Dr Melanie-Ann John (University of Witwatersrand, South Africa), Dr Bonnie Maloba (National Department of Health, South Africa), Ms Ida Makwetla (Mpumalanga Department of Health and Social Services), Dr Isabela Ribiero (United Nations Development Programme/World Bank/WHO Special Programme for Research and Training in Tropical Diseases) and Dr Gerhard Swart (Mpumalanga Department of Health and Social Services). Special thanks to Mrs Tracey Fourie for organising expert panel review meetings.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory, Cape Town, 7925, South Africa

    Ushma Mehta, Elizabeth Allen & Karen I. Barnes

  2. School of Public Health and Tropical Medicine, James Cook University, Townsville, Queensland, Australia

    Ushma Mehta & David Durrheim

  3. Hunter New England Population Health, Wallsend, New South Wales, Australia

    David Durrheim

  4. Malaria Control Programme, Department of Health and Social Services, Mpumalanga Province, Nelspruit, South Africa

    Aaron Mabuza

  5. Epidemiology Unit, National Institute of Communicable Diseases, Germiston, South Africa

    Lucille Blumberg

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  1. Ushma Mehta
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Correspondence to Ushma Mehta.

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Mehta, U., Durrheim, D., Mabuza, A. et al. Malaria Pharmacovigilance in Africa. Drug-Safety 30, 899–910 (2007). https://doi.org/10.2165/00002018-200730100-00008

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