TY - JOUR
T1 - Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa
T2 - Multicentre, randomised, double blind, four arm study
AU - Schlagenhauf, Patricia
AU - Tschopp, Alois
AU - Johnson, Richard
AU - Nothdurft, Hans D.
AU - Beck, Bernhard
AU - Schwartz, Eli
AU - Herold, Markus
AU - Krebs, Bjarne
AU - Veit, Olivia
AU - Allwinn, Regina
AU - Steffen, Robert
PY - 2003/11/8
Y1 - 2003/11/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037802243&partnerID=8YFLogxK
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C2 - 14604928
AN - SCOPUS:0037802243
SN - 0959-8146
VL - 327
SP - 1078
EP - 1081
JO - The BMJ
JF - The BMJ
IS - 7423
ER -