BMJ  2003;327:1078 (8 November), doi:10.1136/bmj.327.7423.1078

Paper

Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study

¹ Division of Epidemiology and Communicable Diseases, Institute for Social and Preventive Medicine, University of Zurich, Zurich, Switzerland, ² Department of Biostatistics, Institute for Social and Preventive Medicine, University of Zurich, ³ Military Performance Division, US Army Research Institute of Environmental Medicine, ⁴ Department of Infectious Diseases and Tropical Medicine, University of Munich, ⁵ Swiss Tropical Institute, Basel, ⁶ Chaim Sheba Medical Center, Tel Hashomer, University of Tel Aviv, ⁷ Institute for Medical Virology, J W Goethe University, Frankfurt/Main

Objective To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers.

Design Randomised, double blind, study with placebo run-in phase.

Setting Travel clinics in Switzerland, Germany, and Israel.

Main outcome measure Proportion of participants in each treatment arm with subjectively moderate or severe adverse events.

Participants 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil.

Results A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n = 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013).

Conclusions Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.

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