Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study. Malarone International Study Team.
BACKGROUND
Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers.


METHODS
In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory.


RESULTS
7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015).


CONCLUSIONS
Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group.
Høgh
B
B
International Travel Vaccination Centre, Copenhagen, Denmark.
Clarke
P D
PD
Camus
D
D
Nothdurft
H D
HD
Overbosch
D
D
Günther
M
M
Joubert
I
I
Kain
K C
KC
Shaw
D
D
Roskell
N S
NS
Chulay
J D
JD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D001007:Anxiety / Q000139:chemically induced; D053626:Atovaquone; D002738:Chloroquine / Q000009:adverse effects / Q000627:therapeutic use; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009285:Naphthoquinones / Q000009:adverse effects / Q000627:therapeutic use; D002727:Proguanil / Q000009:adverse effects / Q000627:therapeutic use; D014195:Travel; D016896:Treatment Outcome
D000962:Antimalarials; D004338:Drug Combinations; D009285:Naphthoquinones; D002738:Chloroquine; D002727:Proguanil; D053626:Atovaquone