Malaria pharmacovigilance in Africa: lessons from a pilot project in Mpumalanga Province, South Africa.

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-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.