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Reduced Risk of Uncomplicated Malaria Episodes in Children with Alpha⁺-Thalassemia in Northeastern Tanzania

The prevalence of human red blood cell (RBC) polymorphisms is high in areas of intense Plasmodium falciparum transmission, and individuals carrying these genetic traits are believed to be partially protected against severe malaria. However, it remains uncertain how RBC polymorphisms affect the susceptibility to uncomplicated malaria. We compared the risk of suffering from febrile, uncomplicated malaria between individuals carrying three common RBC polymorphisms (sickle cell trait, alpha⁺-thalassemia, and glucose-6-phosphate-dehydrogenase deficiency) and controls. The study was performed in an area of intense malaria transmission where 202 individuals 0–19 years of age were monitored clinically for a period of 6 months. RBC polymorphisms were assessed with molecular methods, and plasma antibodies to P. falciparum variant surface antigens (anti-VSA IgG) and glutamate-rich protein (anti-GLURP IgG) were measured with flow cytometry and ELISA assays, respectively. Regression analyses showed that alpha⁺-thalassemia was associated with a reduced risk of uncomplicated malaria episodes and that this advantageous effect seemed to be more predominant in children older than 5 years of age, but was independent of levels of antibodies to VSA and GLURP.

Received August 15, 2007. Accepted for publication January 11, 2008.

Acknowledgments: The authors thank all study participants including their parents/guardians, as well as village helpers and health management teams in Tanga region for participation. We highly appreciate the technical assistance of Maiken Visti, Juma Akida, and Hatibu Athumani. The study was conducted under the auspices of the Joint Malaria Programme, a collaborative research initiative between Centre for Medical Parasitology at the University of Copenhagen, Kilimanjaro Christian Medical College, London School of Hygiene and Tropical Medicine and the Tanzania National Institute for Medical Research.

Financial support: The field study was funded by ENRECA Programme Grant 104.Dan.8.L.312. AE was supported by DANIDA Grant 91203.

^* Address correspondence to Anders Enevold, Centre for Medical Parasitology, Institute for International Health, Immunology and Microbiology, Øster Farimagsgade 5, Building 22+23, PO Box 2099, 1014 Copenhagen K, Denmark. E-mail: enevold{at}cmp.dk

Authors’ addresses: Anders Enevold, Michael Alifrangis, Ib C. Bygbjerg, and Thor G. Theander, Centre for Medical Parasitology, Institute for International Health, Immunology and Microbiology, CSS, Øster Farimagsgade 5, Building 22+23, PO Box 2099, 1014 Copenhagen K, Denmark, Tel: 45-3532-7680, Fax: 45-3532-7851, E-mails: enevold{at}cmp.dk, alifrangis{at}cmp.dk,I.Bygbjerg{at}pubhealth.ku.dk, and theander{at}cmp.dk. John P. Lusingu, Bruno Mmbando, and Martha M. Lemnge, National Institute for Medical Research, Tanga Medical Research Centre, PO Box 5004, Tanga, Tanzania, Tel: 255-2726-46084, Fax: 255-2726-43869, E-mails: jlusingu{at}tanga.mimcom.net, brmm{at}pubhealth.ku.dk, and mlemnge{at}tanga.mimcom.net. Lasse S. Vestergaard, Department of Epidemiology, Building 37/219, Statens Serum Institute, Copenhagen, Denmark, Tel: 45-32683-695, E-mail: lav{at}ssi.dk.