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

Patricia Schlagenhauf*, Alois Tschopp, Richard Johnson, Hans D. Nothdurft, Bernhard Beck, Eli Schwartz, Markus Herold, Bjarne Krebs, Olivia Veit, Regina Allwinn, Robert Steffen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 (11 = 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 (11 = 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.

Original languageEnglish
Pages (from-to)1078-1081
Number of pages4
JournalThe BMJ
Volume327
Issue number7423
StatePublished - 8 Nov 2003

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