The importance of maintaining the fidelity of the mitochondrial genome is underscored by the presence of various repair pathways within this organelle. Presumably, the repair of mitochondrial DNA would be of particular importance in organisms that possess only a single mitochondrion, like the human pathogens Plasmodium falciparum and Toxoplasma gondii. Understanding the machinery that maintains...

Atovaquone is an FDA-approved anti-malarial drug, which first became clinically available in the year 2000. Currently, its main usage is for the treatment of pneumocystis pneumonia (PCP) and/or toxoplasmosis in immune-compromised patients. Atovaquone is a hydroxy-1,4-naphthoquinone analogue of ubiquinone, also known as Co-enzyme Q10 (CoQ10). It is a well-tolerated drug that does not cause myelo...

Understanding the mode of action antimalarials is central to optimizing their use and discovery new therapeutics. Currently used belong a limited series chemical structures mechanisms are coutinuously debated. Whereas involvement reactive species that in turn kill parasites sensitive oxidative stress, accepted for artemisinins, little known about generation such case quinolines or hydroxynaphto...

Cytauxzoon felis, an emerging virulent protozoan parasite that infects domestic cats, is treated with atovaquone and azithromycin (A&A). Atovaquone targets parasite cytochrome b. We characterized the C. felis cytochrome b gene (cytb) in cats with cytauxzoonosis and found a cytb genotype that was associated with survival in A&A-treated cats.

OBJECTIVES A systematic review and meta-analysis of the effectiveness of atovaquone-proguanil (Malarone) as a chemoprophylactic agent against malaria. METHODS The data sources searched for this study included Cochrane systematic reviews (on infectious diseases), MEDLINE and EMBASE, Web of Knowledge and Annals of Tropical Medicine. All unconfounded randomized controlled trials assessing the ch...

BACKGROUND We conducted a randomized, placebo-controlled, double-blind trial to establish the efficacy of atovaquone-proguanil to prevent malaria with the goal of simulating weekly dosing in a human Plasmodium falciparum challenge model. METHODS Thirty volunteers randomly received 1 of the following dose regimens: (1) 250 milligrams of atovaquone and 100 milligrams of proguanil (250/100 milli...

Atovaquone (also called Mepron, or 566C80) is a napthoquinone used for the treatment of infections caused by pathogens such as Plasmodium spp. and Pneumocystis carinii. The mechanism of action against the malarial parasite is the inhibition of dihydroorotate dehydrogenase (DHOD), a consequence of blocking electron transport by the drug. As an analog of ubiquinone (coenzyme Q [CoQ]), atovaquone ...

PURPOSE To evaluate the effects of drug therapy on the clinical course of acute acquired Toxoplasma retinochoroiditis and on the number of Toxoplasma cysts present in the brain and ocular tissues in the hamster animal model. METHODS The Syrian golden hamster animal model of Toxoplasma retinochoroiditis was used. In acute disease, systemically administered atovaquone was compared with conventi...

Over 1 billion people globally are estimated to be infected with Toxoplasma gondii with severe or unknown consequences and no safe and effective therapies are available against congenital or persistent chronic infection. We propose that atovaquone and diclazuril synergistically protect against fetal-maternal toxoplasmosis. METHODS Programmed pregnant mice were treated with atovaquone and dicl...

Atovaquone is a component of Malarone, a widely prescribed antimalarial combination, that targets malaria respiration. Here we show that parasites with high-level resistance to an inhibitor of dihydroorotate dehydrogenase demonstrate unexpected atovaquone tolerance. Fortunately, the tolerance is diminished with proguanil, the second partner in Malarone. It is important to understand such "genet...