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Several studies have focused their attention on the relationship between host genetic factors and susceptibility/resistance to severe malaria. However, there is a paucity of information concerning the role of host genetic factors in asymptomatic malaria, a form of low-grade Plasmodium falciparum infection without clinical symptoms. We investigated in this study the potential relationship between the host (human) genetic polymorphisms (glucose-6-phosphate dehydrogenase [G6PD], mannose binding lectin [MBL], tumor necrosis factor 
[TNF ]-308 and -238, and nitric oxide synthase 2 [NOS2]-954) and the prevalence and profile of asymptomatic P. falciparum infection in 158 Gabonese schoolchildren. We found that G6PD A- heterozygous females (18 of 74) have a low prevalence of asymptomatic malaria (38.9% versus 67.3%; P = 0.03, by chi-square test). Children heterozygous for TNF -238 (25 of 156) carry high number of diverse infecting parasite genotypes (2.5 versus 1.99; variance F = 3.05). No statistically significant association was found between MBL, TNF -308, or NOS2 polymorphisms and asymptomatic malaria. Upon combining our data on asymptomatic forms with those from the literature for others forms, we conclude that G6PD A- heterozygous females are protected against all forms of P. falciparum malaria, and that the TNF -238A allele confers protection against clinical malaria.
Received March 7, 2002. Accepted for publication May 28, 2002.
Acknowledgments: We thank L. Sica, P. Millet, F. Lekoulou, P. Tshipamba, R. Nabias, A. Luty, H. Tiga, D. Lewobo, and J. Lansoud-Soukate for field assistance. We are indebted to the villagers, especially the children, for their participation in this study.
Financial support: This study was funded by the Centre International de Recherches Médicales (CIRMF-Gabon), which is supported by the Government of Gabon, ELF-Gabon, and the Ministère Français des Affaires Etrangères.
Disclaimer: The opinions or assertions contained in this manuscript are the private ones of the authors and are not to be construed as the official or reflecting views of the Department of Defense or the United States Army Medical Research Institute of Infectious Diseases.
Authors’ addresses: Landry-Erik Mombo and Rajagopal Krishnamoorthy, Institut National de la Santé et de la Recherche Médicale, Unité 458, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France. Francine Ntoumi, Cyrille Bisseye, Simon Ossari, and Chang Yong Lu, Centre International de Recherches Médicales de Franceville, BP 769, Franceville, Gabon. Ronald L. Nagel, Division of Hematology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461.
Reprint requests: Landry-Erik Mombo, Institut National de la Santé et de la Recherche Médicale, Unité 458, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France, Telephone: 33-1-40-03-19-01, Fax: 33-1-40-03-19-03, E-mail: lemombo{at}yahoo.com
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