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 ...

BACKGROUND Many conventional treatments for uncomplicated malaria are failing because malaria parasites develop resistance to them. One way to combat this resistance is to treat people with a combination of drugs, such as atovaquone-proguanil. OBJECTIVES To compare atovaquone-proguanil with other antimalarial drugs (alone or in combination) for treating children and adults with uncomplicated ...

Atovaquone, a substituted hydroxynaphthoquinone, is a potent antimalarial drug that acts by inhibiting the parasite's mitochondrial cytochrome bc1 complex (cyt bc1). Mutations in cyt bc1 confer atovaquone resistance. Here we describe the X-ray structure of mitochondrial cyt bc1 from Saccharomyces cerevisiae with atovaquone bound in the catalytic Qo site, at 3.0-Å resolution. A polarized H-bond ...

BACKGROUND Toxoplasma is an important source of foodborne hospitalization with no safe and effective therapy against chronic or congenital Toxopalsmosis. Atovaquone is a drug of choice but not approved for use in congenital Toxoplasmosis. We hypothesized atovaquone to be safe and effective against feto-maternal Toxoplasmosis. MATERIAL/METHODS Programmed pregnant mice were i.p. infected with 5...

Pneumocystis jiroveci (human-derived P. carinii) is an opportunistic pathogenic fungus which causes pneumonia and is life-threatening in immunocompromised individuals. Spontaneously acquired resistance to atovaquone, a hydroxynaphthoquinone that is used to treat P. jiroveci infections, was linked to mutations in the mitochondrially encoded cytochrome b gene. Because P. jiroveci cannot be easily...

We report a novel association between the commonly used antimalarial medication atovaquone/proguanil and drug-induced autoimmune-like hepatitis. The patient developed severe liver disease fulfilling biochemical, immunologic, and histologic criteria for the diagnosis of autoimmune hepatitis after the inadvertent rechallenge with the offending drug, which had caused self-limited hepatitic symptom...

Rapid emergence of resistance to atovaquone, which targets electron transport in the malaria parasite mitochondrion, relegated its use to prophylaxis and even cast a shadow over the development of drugs targeting other parasite mitochondrial pathways. Here we argue for a renewed focus on the mitochondrion as a drug target, focusing particularly on the issues of resistance. We posit a hypothesis...

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 con...

We report a case of a patient returning from Cameroon who developed Plasmodium ovale malaria, despite atovaquone/proguanil (AP, Malarone) prophylaxis, which is widely used for the prevention of chloroquine-resistant malaria. AP is indeed active only on schizont blood forms of P. ovale but not against liver-stage hypnozoites and does not realize effective prophylaxis against delayed onset of P. ...