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Am. J. Trop. Med. Hyg., 76(2), 2007, pp. 224-231
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

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MEFLOQUINE TREATMENT FOR UNCOMPLICATED FALCIPARUM MALARIA IN YOUNG CHILDREN 6–24 MONTHS OF AGE IN NORTHERN GHANA

DAVID J. FRYAUFF*, SETH OWUSU-AGYEI, GREGORY UTZ, J. KEVIN BAIRD, KWADWO A. KORAM, FRED BINKA, FRANCIS NKRUMAH, AND STEPHEN L. HOFFMAN
US Naval Medical Research Unit No. 3, Cairo, Egypt; Navrongo Health Research Center, Navrongo, Upper East Region, Ghana; Naval Medical Research Center, Silver Spring, Maryland; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana; Department of Public Health and Epidemiology, School of Public Health, University of Ghana, Legon, Ghana

Mefloquine (MQ) single dose 20 mg/kg treatment of falciparum malaria was evaluated in 186 children of 6–24 months of age in northern Ghana. There were 15 RII/RIII-type parasitologic failures, all with Day 2 MQ blood levels significantly lower than children whose parasitemias cleared before Day 7 and remained clear through 28 days. Predictors of RII/RIII parasitologic response were vomiting after MQ dosing, Day 2 MQ levels < 500 ng/mL, and undetectable Day 2 levels of the carboxymefloquine metabolite. There were 50 cases of delayed RI parasitologic failure, but 71% of these cases had undetectable Day 28 blood levels of MQ and drug levels in the remaining 29% ranged below the 620 ng/mL level that suppresses MQ sensitive strains of P. falciparum. Drug levels among infants that tolerated MQ well were not associated with age, weight, hemoglobin, parasitemia, and pre-existing symptoms of vomiting or diarrhea. An observed recurrent parasitemia of 34,400 trophozoites/µL against a MQ blood concentration of 550 ng/mL was taken as indication of tolerance to suppressive levels of the drug at this location.

Received July 26, 2005. Accepted for publication July 6, 2006.

Acknowledgments: The authors thank the parents and children who participated in this study and health workers and the support personnel of the Navrongo Health Research Center. The authors thank Charles Attiogbe of the Noguchi Memorial Institute of Medical Research for work as the study microscopist and Cletus Tindana, Salifu Abdul Rahman, and Paulina Tindana for field supervision. Special thanks are also extended to the study physicians, Drs. Kweku Enos and Mensah-Afful, and to Dr. Alex Nazzar for essential support and advice. This research was approved by scientific and ethical review boards of the Ghanaian Ministry of Health and the US Navy and was conducted in accordance with regulations governing the protection of human subjects in medical research.

Financial support: This study was supported by independent research Grant WU 34 3C30.001.3601 and the US Department of Defense Global Emerging Infections Surveillance and Response System (GEIS). The views of the authors expressed herein do not purport to reflect those of the Ghanaian Ministry of Health, the US Navy, or the US Department of Defense.

* Address correspondence to David J. Fryauff, US Naval Medical Research Unit No. 3, PSC 452 Box 52, FPO AE 09835-0007. E-mail: fryauffd{at}nmrc.navy.mil

Authors’ addresses: David J. Fryauff and Greg Utz, US Naval Medical Research Unit No. 3, PSC 452 Box 52, FPO AE 09835-0007, Telephone: 20-2-342-0576, Fax: 20-2-342-7121, E-mail: FryauffD{at}nmrc.navy.mil and gcutz{at}nmcsd.med.navy.mil. Seth Owusu-Agyei, Navrongo Health Research Center, Navrongo, Upper East Region, Ghana, Telephone: 233-742-22380, Fax: 233-742-22310, E-mail: seth.owusu-agyei{at}ghana-khrc.org. J. Kevin Baird, ALERTAsia Foundation, Jakarta, Indonesia, E-mail: jkevinbaird{at}yahoo.com. Kwadwo A. Koram and Francis Nkrumah, Noguchi Memorial Institute of Medical Research, University of Ghana, Legon, Ghana, Telephone: 233-21-501178, Fax: 233-21-502182, E-mail: KKoram{at}noguchi.mimcom.net and FNkrumah{at}noguchi.mimcom.net. Fred Binka, School of Public Health, University of Ghana, Legon, Ghana, Telephone: 233-21-500799, E-mail: FBinka{at}indepth-nework.org. Stephen L. Hoffman, Sanaria Inc., 12511 Parklawn Drive, Suite L, Rockvile, MD 20852, Telephone: 301-770-3222, Fax: 301-770-5554, E-mail: slhoffman{at}sanaria.com.

Reprint requests: Research Publications Branch, US Naval Medical Research Unit No. 3, PSC 452 Box 5000, FPO AE 09835-0007. E-mail: KaramE{at}namru3.med.navy.mil.






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