Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study.
OBJECTIVE
To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers.


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


METHODS
Travel clinics in Switzerland, Germany, and Israel.


METHODS
Proportion of participants in each treatment arm with subjectively moderate or severe adverse events.


METHODS
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.
Schlagenhauf
Patricia
P
Division of Epidemiology and Communicable Diseases, Institute for Social and Preventive Medicine, University of Zurich, Zurich, Switzerland. pat@ifspm.unizh.ch
Tschopp
Alois
A
Johnson
Richard
R
Nothdurft
Hans D
HD
Beck
Bernhard
B
Schwartz
Eli
E
Herold
Markus
M
Krebs
Bjarne
B
Veit
Olivia
O
Allwinn
Regina
R
Steffen
Robert
R
D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara; D000368:Aged; D000962:Antimalarials / Q000009:adverse effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany; D006801:Humans; D007557:Israel; D008288:Malaria / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D013557:Switzerland; D014195:Travel
D000962:Antimalarials