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HOST POLYMORPHISMS AND THE INCIDENCE OF MALARIA IN UGANDAN CHILDREN

Mutations in ß-globin, glucose-6-phosphate dehydrogenase, and promoters for tumor necrosis factor- and inducible nitric oxide synthase (iNOS) were examined for associations with the incidence of symptomatic malaria in a cohort of 307 Ugandan children. After adjustment of incidence rates for age, water source, use of preventative measures, and proximity to mosquito breeding sites, glucose-6-phosphate dehydrogenase A- heterozygous females had a significantly higher incidence of malaria (incidence rate ratio [IRR] = 1.63, P = 0.03) and a trend towards higher parasite densities (37,100 versus 26,200 parasites/µL; P = 0.18) compared with wild-type children. Male hemizygotes had trends in the same direction. Heterozygotes for sickle hemoglobin had trends toward a lower incidence of malaria and lower parasite density at presentation. Heterozygotes for the iNOS promoter G954C polymorphism, but not other promoter polymorphisms, had a significantly lower incidence of malaria compared with wild-type children (IRR = 0.69, P = 0.05). Host polymorphisms appear to impact upon the incidence of uncomplicated malaria in Ugandan children.

Received April 9, 2004. Accepted for publication July 9, 2004.

Acknowledgments: We thank the clinical study team of Adithya Cattamanchi, Moses R. Kamya, Sarah Staedke, Anne Gasasira, Denise Njama, B. M. Karakire, Marx Dongo, Sam Nsobya, Moses Kiggundu, Christopher Bongole, Regina Nakafero, Bridget K. Nzarubara, Pauline Byakika, and Sarah Kibirango; the community leaders from the Kawempe Division of Kampala; and the study participants and their parents/guardians for their contributions to the study.

Financial support: This study was supported by the National Institutes of Health (grants UO1AI52142 and T32AI07641).

Disclosure: The authors have no conflicting interests to declare. Authors’ address: Sunil Parikh, Grant Dorsey, and Philip J. Rosenthal, Division of Infectious Diseases, Department of Medicine, San Francisco General Hospital, University of California, Box 0811, San Francisco, CA 94110, Telephone: 415-206-8687, Fax: 415-648-8425, E-mails: sunil{at}itsa.ucsf.edu, grantd{at}itsa.ucsf.edu, and rosnthl{at}itsa.ucsf.edu

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