Atovaquone plus proguanil versus halofantrine for the treatment of imported acute uncomplicated Plasmodium falciparum malaria in non-immune adults: a randomized comparative trial.

In endemic zones, the atovaquone-proguanil (AP) combination is well tolerated and effective in treating acute, uncomplicated malaria. Trials involving non-immune patients are lacking, however. We conducted a randomized, multicenter open-label trial to determine the efficacy and tolerability of the AP combination (1,000 mg + 400 mg once daily for 3 days) in comparison with halofantrine (HF) (1,500 mg in 3 doses) in non-immune adults with imported uncomplicated Plasmodium falciparum malaria. Follow-up visits were programmed on Days 7, 14, 21, 28, and 35 after hospital discharge. Out of 48 patients enrolled in the study, 41 were assessable for the cure rate (21 in the AP group and 20 in the HF group). All the patients were cured. The mean parasite clearance time was longer (63+/-23 hours) in the AP group than in the HF group (48+/-15 hours) (P = 0.02). The frequency of gastrointestinal adverse events was higher in the AP group. No noteworthy electrocardiographic changes were observed, particularly in the QTc interval. The AP combination appears to be a valuable alternative treatment in non-immune adults.

[1]  Akhil B. Vaidya,et al.  A Mechanism for the Synergistic Antimalarial Action of Atovaquone and Proguanil , 1999, Antimicrobial Agents and Chemotherapy.

[2]  C. Canfield,et al.  Atovaquone-proguanil compared with chloroquine and chloroquine-sulfadoxine-pyrimethamine for treatment of acute Plasmodium falciparum malaria in the Philippines. , 1999, The Journal of infectious diseases.

[3]  C. Canfield,et al.  Atovaquone and proguanil versus pyrimethamine/sulfadoxine for the treatment of acute falciparum malaria in Zambia. , 1999, Clinical therapeutics.

[4]  S. Looareesuwan,et al.  Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand. , 1999, The American journal of tropical medicine and hygiene.

[5]  R. Snow,et al.  30 years of science and technology: the example of malaria , 1997, The Lancet.

[6]  W. Milhous,et al.  Atovaquone and proguanil for the treatment of malaria in Brazil. , 1997, The Journal of infectious diseases.

[7]  B R Mirdha,et al.  Laboratory diagnosis of malaria. , 1997, Journal of clinical pathology.

[8]  F. Gay,et al.  In vitro response of Plasmodium falciparum to atovaquone and correlation with other antimalarials: comparison between African and Asian strains. , 1997, The American journal of tropical medicine and hygiene.

[9]  C. Katlama,et al.  Atovaquone as long‐term suppressive therapy for toxoplasmic encephalitis in patients with AIDS and multiple drug intolerance , 1996, AIDS.

[10]  D. Warhurst,et al.  ACP Broadsheet no 148. July 1996. Laboratory diagnosis of malaria. , 1996, Journal of clinical pathology.

[11]  P. Kremsner,et al.  Atovaquone and proguanil for Plasmodium falciparum malaria , 1996, The Lancet.

[12]  A. Viguier,et al.  Electrocardiographic changes and halofantrine plasma level during acute falciparum malaria. , 1996, The American journal of tropical medicine and hygiene.

[13]  S. Luby,et al.  Cardiac effects of standard-dose halofantrine therapy. , 1996, The American journal of tropical medicine and hygiene.

[14]  P. Chiodini,et al.  Evaluation of atovaquone in the treatment of patients with uncomplicated Plasmodium falciparum malaria. , 1995, The Journal of antimicrobial chemotherapy.

[15]  D. Neau,et al.  Cardiac complications of halofantrine: a prospective study of 20 patients. , 1995, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[16]  C. Canfield,et al.  Interactions of atovaquone with other antimalarial drugs against Plasmodium falciparum in vitro. , 1995, Experimental parasitology.

[17]  W. Hughes.  The role of atovaquone tablets in treating Pneumocystis carinii pneumonia. , 1995, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[18]  P. Chiodini,et al.  Multiresistant falciparum malaria cured using atovaquone and proguanil. , 1994, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[19]  J. Karbwang,et al.  Clinical Pharmacokinetics of Halofantrine , 1994, Clinical pharmacokinetics.

[20]  J. Falloon,et al.  Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. , 1993, The New England journal of medicine.

[21]  D. Kyle,et al.  Cardiac effects of antimalarial treatment with halofantrine , 1993, The Lancet.

[22]  G. Luzzi,et al.  Adverse Effects of Antimalarials , 1993, Drug safety.

[23]  K. Goa,et al.  Halofantrine , 2012, Drugs.

[24]  P. Phillips-Howard,et al.  Risk of malaria in British residents returning from malarious areas. , 1990, BMJ.

[25]  S. Ahnve,et al.  Correction of the QT interval for heart rate: review of different formulas and the use of Bazett's formula in myocardial infarction. , 1985, American heart journal.

[26]  R. Williams,et al.  Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum anti-protozoal activity , 1985, Parasitology.

[27]  M R Prabha Adhikari,et al.  Severe and complicated malaria. , 2002, Indian journal of medical sciences.

[28]  R. Steffen,et al.  Imported malaria (1985-95): trends and perspectives. , 1999, Bulletin of the World Health Organization.

[29]  H. Webster,et al.  Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. , 1996, The American journal of tropical medicine and hygiene.

[30]  World malaria situation in 1991. , 1993, Canada communicable disease report = Releve des maladies transmissibles au Canada.

[31]  Robert Steffen,et al.  3. Travel medicine—prevention based on epidemiological data , 1991 .

[32]  W. Gutteridge,et al.  566C80: a potent broad spectrum anti-infective agent with activity against malaria and opportunistic infections in AIDS patients. , 1991, Drugs under experimental and clinical research.

[33]  R. Steffen,et al.  Travel medicine--prevention based on epidemiological data. , 1991, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[34]  P. Phillips-Howard,et al.  Malaria incidence and prevention among European and North American travellers to Kenya. , 1990, Bulletin of the World Health Organization.

[35]  S. Parr,et al.  Clinical experience with halofantrine in the treatment of malaria. , 1990, Drugs under experimental and clinical research.

[36]  H. Webster,et al.  Malaria: treatment efficacy of halofantrine (WR 171,669) in initial field trials in Thailand. , 1988, Bulletin of the World Health Organization.