A Randomized Trial to Compare the Safety, Tolerability, and Effectiveness of 3 Antimalarial Regimens for the Prevention of Malaria in Nigerian Patients With Sickle Cell Disease

Rasaq Olaosebikan, Kolade Ernest, Kalifa Bojang, Olugbenga Mokuolu, Andrea M Rehman, Muna Affara, Davis Nwakanma, Jean-René Kiechel, Taofik Ogunkunle, Tope Olagunju, Rukayat Murtala, Peter Omefe, Tosin Lambe, Surajudeen Bello, Olayinka Ibrahim, Benedict Olorunsola, Ayotade Ojuawo, Brian Greenwood, Paul Milligan, Rasaq Olaosebikan, Kolade Ernest, Kalifa Bojang, Olugbenga Mokuolu, Andrea M Rehman, Muna Affara, Davis Nwakanma, Jean-René Kiechel, Taofik Ogunkunle, Tope Olagunju, Rukayat Murtala, Peter Omefe, Tosin Lambe, Surajudeen Bello, Olayinka Ibrahim, Benedict Olorunsola, Ayotade Ojuawo, Brian Greenwood, Paul Milligan

Abstract

Background: Malaria prophylaxis is recommended for persons with sickle cell disease (SCD), but the value of this has been questioned. The aim of this study was to find out whether intermittent preventive treatment (IPT) with a fixed-dose combination of mefloquine-artesunate (MQAS) or sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) was more effective than daily proguanil for malaria prevention in subjects with SCD.

Methods: Patients with SCD were randomized to receive daily treatment with proguanil or IPT with either MQAS or SPAQ once every 2 months at routine clinic visits. Patients were followed up for 14 months.

Findings: A total of 270 patients with SCD were studied, with 90 in each group. Adherence to the IPT regimens was excellent, but 57% of patients took <75% of their daily doses of proguanil. IPT was well tolerated; the most common side effects were vomiting and abdominal pain. Protective efficacy against malaria, compared with daily proguanil, was 61% (95% confidence interval, 3%-84%) for MQAS and 36% (40%-70%) for SPAQ. There were fewer outpatient illness episodes in children who received IPT than those who received proguanil.

Conclusions: IPT with MQAS administered to patients with SCD during routine clinic visits was well tolerated and more effective in preventing malaria than daily prophylaxis with proguanil.

Clinical trials registration: NCT01319448 and ISRCTN46158146.

Keywords: chemoprevention; intermittent preventive treatment; malaria; mefloquine-artesunate; proguanil; prophylaxis; sickle cell disease.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Trial profile. Each visit represents a bimonthly visit to the sickle cell clinic. Abbreviations: MQAS, mefloquine-artesunate; SP, sulfadoxine-pyrimethamine; SPAQ, sulfadoxine-pyrimethamine plus amodiaquine.

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Source: PubMed

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