Clinical Studies of Atovaquone, Alone or in Combination with other Antimalarial Drugs, for Treatment of Acute Uncomplicated Malaria in Thailand

Sornchai Looareesuwan Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Department of Immunology and Parasitology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Department of Infectious Diseases, Wellcome Research Laboratories, Pharmaceutical Systems Inc., Bangkok, Thailand

Search for other papers by Sornchai Looareesuwan in
Current site
Google Scholar
PubMed
Close
,
Chaisin Viravan Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Department of Immunology and Parasitology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Department of Infectious Diseases, Wellcome Research Laboratories, Pharmaceutical Systems Inc., Bangkok, Thailand

Search for other papers by Chaisin Viravan in
Current site
Google Scholar
PubMed
Close
,
H. Kyle Webster Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Department of Immunology and Parasitology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Department of Infectious Diseases, Wellcome Research Laboratories, Pharmaceutical Systems Inc., Bangkok, Thailand

Search for other papers by H. Kyle Webster in
Current site
Google Scholar
PubMed
Close
,
Dennis E. Kyle Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Department of Immunology and Parasitology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Department of Infectious Diseases, Wellcome Research Laboratories, Pharmaceutical Systems Inc., Bangkok, Thailand

Search for other papers by Dennis E. Kyle in
Current site
Google Scholar
PubMed
Close
,
David B. Hutchinson Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Department of Immunology and Parasitology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Department of Infectious Diseases, Wellcome Research Laboratories, Pharmaceutical Systems Inc., Bangkok, Thailand

Search for other papers by David B. Hutchinson in
Current site
Google Scholar
PubMed
Close
, and
Craig J. Canfield Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Department of Immunology and Parasitology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Department of Infectious Diseases, Wellcome Research Laboratories, Pharmaceutical Systems Inc., Bangkok, Thailand

Search for other papers by Craig J. Canfield in
Current site
Google Scholar
PubMed
Close
Restricted access

The therapy of Plasmodium falciparum malaria continues to be a problem in many parts of Southeast Asia because of multidrug resistance to nearly all existing antimalarial drugs. Atovaquone is a novel hydroxynaphthoquinone with broad spectrum anti-protozoal activity. We recently evaluated the antimalarial activity of atovaquone in a series of dose-ranging studies in 317 patients with malaria at the Bangkok Hospital for Tropical Diseases. Originally, the drug was administered alone. Using atovaquone alone resulted in satisfactory, initial clinical responses in all patients; the mean parasite and fever clearance times were 62 and 53 hr, respectively. However, irrespective of the duration of therapy, overall cure rates were approximately 67%. In vitro sensitivity studies on parasites taken from patients prior to treatment and at the time of recrudescence showed a marked decrease in susceptibility to atovaquone in the recrudescent parasites. To improve cure rates, atovaquone was administered in combination with other drugs with antimalarial activity. Proguanil and tetracycline were chosen due to laboratory evidence of potentiation; doxycycline was selected because it has a longer half-life than tetracycline. Although pyrimethamine did not show laboratory evidence of potentiation with atovaquone, it was chosen as an alternative inhibitor of dihydrofolic acid reductase with a longer half-life than proguanil. The clinical studies with these drug combinations confirmed the laboratory results with marked improvement in cure rates for proguanil, tetracycline, and doxycycline; pyrimethamine showed only minimal improvement. Proguanil was subsequently selected as the preferred drug partner because of its long record of safety and the ability to use the drug in pregnant women and children. Of the 104 patients with falciparum malaria treated with atovaquone plus proguanil for 3–7 days, 101 were cured and had virtually no adverse side effects. The combination of atovaquone and proguanil also was effective in eliminating erythrocytic forms of P. vivax, but parasitemia recurred in most patients.

Author Notes

Past two years Past Year Past 30 Days
Abstract Views 5556 4246 422
Full Text Views 134 44 1
PDF Downloads 154 20 0
 

 

 

 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save