A 72-year-old Japanese woman with rheumatoid arthritis whose activity decreased with previous treatments had recurrent thunderclap headaches during an atovaquone regimen for the treatment of pneumocystis pneumonia. The recurrent headaches disappeared after discontinuation of the drug. Brain magnetic resonance images showed multiple cerebral vasoconstrictions of cerebral arteries with vasogenic ...

Atovaquone is an anti-malarial drug used in combination with proguanil (e.g. Malarone(TM)) for the curative and prophylactic treatment of malaria. Atovaquone, a 2-hydroxynaphthoquinone, is a competitive inhibitor of the quinol oxidation (Q(o)) site of the mitochondrial cytochrome bc(1) complex. Inhibition of this enzyme results in the collapse of the mitochondrial membrane potential, disruption...

Drug resistance compromises control of malaria. Here, we show that resistance to a commonly used antimalarial medication, atovaquone, is apparently unable to spread. Atovaquone pressure selects parasites with mutations in cytochrome b, a respiratory protein with low but essential activity in the mammalian blood phase of the parasite life cycle. Resistance mutations rescue parasites from the dru...

Proguanil in combination with its synergistic partner atovaquone has been used for malaria treatment and prophylaxis decades. However mode of action is not fully understood. Here we yeast to investigate activity. inhibits growth, causes cell death acts synergy atovaquone. It was previously proposed that the drug would target system maintains mitochondrial membrane potential when respiratory cha...

Malaria-related morbidity and mortality are greatest among young children in areas with high malaria transmission intensity. An open-label, randomized study was done to evaluate the efficacy and safety of the combination of atovaquone and proguanil formulated as pediatric-strength tablets (20 and 8 mg/kg of body weight, respectively, administered once daily for 3 days), compared with amodiaquin...

The mitochondrial bc(1) complex is a multisubunit enzyme that catalyzes the transfer of electrons from ubiquinol to cytochrome c coupled to the vectorial translocation of protons across the inner mitochondrial membrane. The complex contains two distinct quinone-binding sites, the quinol oxidation site of the bc(1) complex (Q(o)) and the quinone reduction site (Q(i)), located on opposite sides o...

Clinical failure of Malarone™ chemoprophylaxis is extremely rare. We report a case of Plasmodium falciparum malaria in a returned traveler to Ghana who fully adhered to atovaquone-proguanil (Malarone™) chemoprophylaxis daily dosing, yet took the pills on an empty stomach. Screening of the P. falciparum isolate revealed triple codon mutation of Dhfr at positions 51, 59, and 108. Plasma drug leve...

Atovaquone is a unique naphthoquinone with broad-spectrum antiprotozoal activity. It is effective for the treatment and prevention of Pneumocystis carinii pneumonia (PCP), it is effective in combination with proguanil for the treatment and prevention of malaria, and it is effective in combination with azithromycin for the treatment of babesiosis. There is also limited experience with other prot...

The lung pathogen Pneumocystis spp. is the causative agent of a type of pneumonia that can be fatal in people with defective immune systems, such as AIDS patients. Atovaquone, an analog of ubiquinone (coenzyme Q [CoQ]), inhibits mitochondrial electron transport and is effective in clearing mild to moderate cases of the infection. Purified rat-derived intact Pneumocystis carinii cells synthesize...