Randomized, placebo-controlled trial of atovaquone/proguanil for the prevention of Plasmodium falciparum or Plasmodium vivax malaria among migrants to Papua, Indonesia.
ABSTRACT The increasing prevalence of resistance to antimalarial drugs reduces options for malaria prophylaxis. Atovaquone/proguanil (Malarone; GlaxoSmithKline) has been >95% effective in preventing Plasmodium falciparum malaria in lifelong residents of areas of holoendemicity, but data from persons without clinical immunity or who are at risk for Plasmodium vivax malaria have not been described. We conducted a randomized, double-blinded study involving 297 people from areas of nonendemicity in Indonesia who migrated to Papua (where malaria is endemic) < or =26 months before the study period. Subjects received prophylaxis with 1 Malarone tablet (250 mg of atovaquone and 100 mg of proguanil hydrochloride; n=148) or placebo (n=149) per day for 20 weeks. Hematologic and clinical chemistry values did not change significantly. The protective efficacy of atovaquone/proguanil was 84% (95% confidence interval [CI], 44%-95%) for P. vivax malaria, 96% (95% CI, 72%-99%) for P. falciparum malaria, and 93% (95% CI, 77%-98%) overall. Atovaquone/proguanil was well tolerated, safe, and effective for the prevention of drug-resistant P. vivax and P. falciparum malaria in individuals without prior malaria exposure who migrated to Papua, Indonesia.
Article: Antimalarial Drug Toxicity[Show abstract] [Hide abstract]
ABSTRACT: Malaria, caused mostly by Plasmodium falciparum and P. vivax, remains one of the most important infectious diseases in the world. Antimalarial drug toxicity is one side of the risk-benefit equation and is viewed differently depending upon whether the clinical indication for drug administration is malaria treatment or prophylaxis. Drug toxicity must be acceptable to patients and cause less harm than the disease itself. Research that leads to drug registration tends to omit two important groups who are particularly vulnerable to malaria — very young children and pregnant women. Prescribing in pregnancy is a particular problem for clinicians because the risk-benefit ratio is often very unclear. The number of antimalarial drugs in use is very small. Despite its decreasing efficacy against P. falciparum, chloroquine continues to be used widely because of its low cost and good tolerability. It remains the drug of first choice for treating P. vivax malaria. Pruritus is a common adverse effect in African patients. As prophylaxis, chloroquine is usually combined with proguanil. This combination has good overall tolerability but mouth ulcers and gastrointestinal upset are more common than with other prophylactic regimens. Sulfadoxine/pyrimethamine is well tolerated as treatment and when used as intermittent preventive treatment in pregnant African women. Sulfadoxine/pyrimethamine is no longer used as prophylaxis because it may cause toxic epidermal necrolysis and Stevens Johnson syndrome. Mefloquine remains a valuable drug for prophylaxis and treatment. Tolerability is acceptable to most patients and travellers despite the impression given by the lay press. Dose-related serious neuropsychiatric toxicity can occur; mefloquine is contraindicated in individuals with a history of epilepsy or psychiatric disease. Quinine is the mainstay for treating severe malaria in many countries. Cardiovascular or CNS toxicity is rare, but hypoglycaemia may be problematic and blood glucose levels should be monitored. Halofantrine is unsuitable for widespread use because of its potential for cardiotoxicity. There is renewed interest in two old drugs, primaquine and amodiaquine. Primaquine is being developed as prophylaxis, and amodiaquine, which was withdrawn from prophylactic use because of neutropenia and hepatitis, is a potentially good partner drug for artesunate against falciparum malaria. Atovaquone/proguanil is a new antimalarial combination with good efficacy and tolerability as prophylaxis and treatment. The most important class of drugs that could have a major impact on malaria control is the artemisinin derivatives. They have remarkable efficacy and an excellent safety record. They have no identifiable dose-related adverse effects in humans and only very rarely produce allergic reactions. Combining an artemisinin derivative with another efficacious antimalarial drug is increasingly being viewed as the optimal therapeutic strategy for malaria.Drug Safety 01/2004; 27(1). DOI:10.2165/00002018-200427010-00003 · 2.62 Impact Factor
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ABSTRACT: A randomized, double-blinded, placebo-controlled study was conducted to examine the effect of spatial repellent (SR) in households at risk of malaria in Indonesia. Following presumptive radical cure for malaria in 180 adult men representing sentinels of new infection in four clusters within two villages, all households were given either metofluthrin or placebo mosquito coils. Weekly blood smear screening and human-landing mosquito catches were done throughout the 6 months intervention. Malaria infections occurred in 61 subjects living in placebo households and 31 subjects living in SR coil households, suggesting a 52% protective effect of SR. Likewise, anopheles indoor human landing rates were 32% lower in homes receiving SR coils. Differences in the malaria attack rate between SR- and placebo-treated homes was significant when not accounting for the effects of clustering. When the analysis was adjusted for intra-cluster correlation, the differences between SR- and placebo-treated homes were not statistically significant. The findings provide evidence of SR public health benefit and support a larger trial statistically powered to detect those effects.The American journal of tropical medicine and hygiene 10/2014; 91(6). DOI:10.4269/ajtmh.13-0735 · 2.74 Impact Factor