Atovaquone-proguanil for recrudescent Plasmodium falciparum in Vietnam
ABSTRACT Malarone, a fixed combination of atovaquone with proguanil (AP), has recently been recognized as a promising treatment against multidrug-resistant Plasmodium falciparum. In Vietnam, the first-line treatment for P. falciparum malaria is currently a combination of mefloquine and an artemisinin derivative, and the use of AP has not been explored. The aim of the present study, based in Vietnam, was to assess the efficacy of AP when used to treat P. falciparum recrudescences that had occurred after primary treatment with mefloquine-artesunate. All but two of the 39 patients investigated completed follow-up. The mean parasite- and fever-clearance times [and 95% confidence intervals (CI)] after AP treatment were 36 (30-42) and 21 (18-24) h, respectively. Most (32) of the 37 infections that were followed adequately appeared to be eradicated by the AP, the other five recrudescing once more. The overall cure 'rate' and (CI) was 86% (76%-98%). All of the patients tolerated the AP well. Atovaquone-proguanil appears to be a safe and promising alternative treatment for P. falciparum infections in South-east Asia, although the combination is relatively expensive and may not clear some infections with multidrug-resistant parasites.
- SourceAvailable from: Tamirat Gebru Woldearegai
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- "In a study from Vietnam, it has been reported that the combination of atovaquone with proguanil (AP) yielded an overall cure rate of 86% to treat recrudescent P. falciparum infections that had occurred after primary treatment with other antimalarials. In their study, the authors recommended AP as a safe and promising alternative treatment for P. falciparum infections in South-East Asia . "
ABSTRACT: Atovaquone is part of the antimalarial drug combination atovaquone-proguanil (Malarone) and inhibits the cytochrome bc1 complex of the electron transport chain in Plasmodium spp. Molecular modelling showed that amino acid mutations are clustered around a putative atovaquone-binding site resulting in a reduced binding affinity of atovaquone for plasmodial cytochrome b, thus resulting in drug resistance. The prevalence of cytochrome b point mutations possibly conferring atovaquone resistance in Plasmodium falciparum isolates in atovaquone treatment-naïve patient cohorts from Lambaréné, Gabon and from South Western Ethiopia was assessed. Four/40 (10%) mutant types (four different single polymorphisms, one leading to an amino acid change from M to I in a single case) in Gabonese isolates, but all 141/141 isolates were wild type in Ethiopia were found. In the absence of drug pressure, spontaneous and possibly resistance-conferring mutations are rare.Malaria Journal 02/2006; 5(1):112. DOI:10.1186/1475-2875-5-112 · 3.49 Impact Factor
Article: Modern Malaria Chemoprophylaxis[Show abstract] [Hide abstract]
ABSTRACT: Currently available medications for malaria chemoprophylaxis are efficacious but the problems of patient compliance, the advance of parasite drug resistance, and real or perceived serious adverse effects mean that new chemical compounds are needed.Primaquine, which has been widely used to treat relapsing malaria since the 1950s, has been shown to prevent malaria when taken daily. Tafenoquine is a new 8-aminoquinoline with a much longer half-life than primaquine. Field trials to date indicate that tafenoquine is efficacious and can be taken weekly or perhaps even less frequently. Both primaquine and tafenoquine require exact knowledge of a person's glucose 6-phosphate dehydrogenase status in order to prevent drug-induced haemolysis. Other potential malaria chemoprophylactic drugs such as third-generation antifol compounds and Mannich bases have reached advanced preclinical testing. Mefloquine has been seen to cause serious neuropsychiatric adverse effects on rare occasions. Recent public controversy regarding reputedly common serious adverse effects has made many Western travellers unwilling to take mefloquine. Special risk groups exposed to malaria, such as long-term travellers, children, pregnant women, aircrew and those requiring unimpeded psychomotor reactions, migrants returning to visit malarious countries of origin and febrile persons who have returned from malaria endemic areas, all require a nuanced approach to the use of drugs to prevent malaria. The carrying of therapeutic courses of antimalarial drugs to be taken only if febrile illness develops is indicated in very few travellers despite its appeal to some who fear adverse effects more than they fear potentially lethal malaria infection. Travellers with a significant exposure to malaria require a comprehensive plan for prevention that includes anti-mosquito measures but which is still primarily be based on the regular use of efficacious antimalarial medications.Drugs 02/2005; 65(15):2091-110. DOI:10.2165/00003495-200565150-00003 · 4.13 Impact Factor