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Am. J. Trop. Med. Hyg., 68(5), 2003, pp. 590-597
Copyright © 2003 by The American Society of Tropical Medicine and Hygiene

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ASSOCIATION OF INTERFERON-{gamma} RESPONSES TO PRE-ERYTHROCYTIC STAGE VACCINE CANDIDATE ANTIGENS OF PLASMODIUM FALCIPARUM IN YOUNG KENYAN CHILDREN WITH IMPROVED HEMOGLOBIN LEVELS: XV. ASEMBO BAY COHORT PROJECT

JOHN M. O. ONG’ECHA, ALTAF A. LAL, DIANNE J. TERLOUW, FEIKO O. TER KUILE, SIMON K. KARIUKI, VENKATCHALAM UDHAYAKUMAR, ALLOYS S. S. ORAGO, ALLEN W. HIGHTOWER, BERNARD L. NAHLEN, AND YA PING SHI
Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Previous studies in animal models have revealed an association between interferon-{gamma} (IFN- {gamma}), produced by CD8+ T cells and irradiated sporozoite-induced sterile immunity. To determine whether IFN-{gamma} can serve as a marker of pre-erythrocytic protective immunity in individuals naturally exposed to malaria, we characterized IFN-{gamma} and lymphocyte proliferative responses to previously defined CD8+ cytotoxic T lymphocyte (CTL) epitopes from six pre-erythrocytic stage antigens in 107 children six months to two years old from a community-based birth cohort in western Kenya. We found that IFN- {gamma} positive responders had higher hemoglobin (Hb) levels and significantly reduced prevalence of severe malarial anemia one month after the test compared with IFN- {gamma} non-responders, suggesting that IFN- {gamma} immune responses to these pre-erythrocytic antigens were associated with protection against malarial anemia. Children who responded by lymphocyte proliferation had a significantly longer time to first documented malaria parasitemia after birth; however, there was no correlation between the presence of lymphocyte proliferative response and higher Hb levels. We propose that IFN- {gamma} production could be used as a potential marker of protective immunity against malaria associated anemia in young children living in malaria holoendemic areas.

Acknowledgments: We thank all the residents of Asembo Bay area who participated in this study. We are grateful to all the CDC-Kenya Medical Research Institute (KEMRI) field station staff for their technical support, and to Davy Koech (Director of KEMRI) for his approval with regard to publication of this manuscript. We also thank Danny Jue and the staff of the Biotechnology Core Facility (National Center for Infectious Diseases, CDC) for the synthesis of the peptides used in this study, Kevin DeCock (Director of the CDC Program in Kenya) for comments, and Mary Bartlett (Division of Parasitic Diseases, National Center for Infectious Diseases, CDC) for editorial assistance. The results of this study were presented in part at the 48th Annual Meeting of the American Society for Tropical Medicine and Hygiene, November 20–December 2, 1999, Washington, DC (Abstract # 384).

Financial support: This work was supported in part by grants from the U.S. Agency for International Development (HRN-6001-A-004010-00) and the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases.

Authors’ addresses: John M. O. Ong’echa and Alloys S.S. Orago, Department of Zoology, Kenyatta University, PO Box 43844, Nairobi, Kenya. Altaf A. Lal, Dianne J. Terlouw, Feiko O. ter Kuile, Venkatachalam Udhayakumar, and Allen W. Hightower, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Mailstop F-12, 4770 Buford Highway, Atlanta, GA 30341. Simon K. Kariuki, Kenya Medical Research Institute, Centre for Vector Biology and Control Research, PO Box 1578, Kisumu, Kenya. Ya Ping Shi, Kenya Medical Research Institute, Center for Vector Biology and Control Research, PO Box 1578, Kisumu, Kenya and Molecular Vaccine Section, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Mailstop F-12, 4770 Buford Highway, Atlanta, GA 30341, Telephone: 770-488-4047, Fax: 770-488-4454, E-mail: Yshi{at}kisian.mimcom.netor yps0{at}cdc.gov. Bernard L. Nahlen, Roll Back Malaria, World Health Organization, 1211 Geneva 27, Switzerland.




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Copyright © 2003 by the American Society of Tropical Medicine and Hygiene.