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Antibodies to Plasmodium falciparum Erythrocyte-binding Antigen-175 are Associated With Protection From Clinical Malaria

McCarra, Matthew B. BS*; Ayodo, George PhD; Sumba, Peter O. PhD; Kazura, James W. MD; Moormann, Ann M. MPH, PhD§; Narum, David L. PhD; John, Chandy C. MD, MS*

Pediatric Infectious Disease Journal: December 2011 - Volume 30 - Issue 12 - p 1037–1042
doi: 10.1097/INF.0b013e31822d1451
Original Studies

Background: Antibodies to blood-stage Plasmodium falciparum antigens have been associated with protection against clinical malaria in some studies but not others. Many of these studies have not assessed whether high-titer antibodies are associated with protection and have not adjusted for differences in malaria exposure.

Methods: The presence of high-titer antibodies to apical membrane antigen-1, erythrocyte-binding antigen-175 (EBA-175), and merozoite surface protein-119 (MSP-119) was assessed in 87 children living in a malaria holoendemic area of Kenya. The children were prospectively assessed during 1 year for clinical malaria.

Results: In unadjusted analyses, high-titer antibodies to MSP-119, but not EBA-175 or apical membrane antigen-1, were associated with protection from clinical malaria. However, after adjustment for exposure, only high-titer antibodies to EBA-175 were associated with protection from clinical malaria (hazard ratio, 0.48; 95% confidence interval [CI], 0.24, 0.95; P = 0.03), and with reduced episodes of clinical malaria (incidence rate ratio, 0.50; 95% CI, 0.31, 0.81; P = 0.005). A trend toward increased protection from clinical malaria in children was seen with antibodies to both EBA-175 and MSP-119 (hazard ratio, 0.26; 95% CI, 0.03, 1.94; P = 0.18).

Conclusions: High-titer antibodies to EBA-175 are associated with protection from clinical malaria in children in a malaria holoendemic area of Kenya. Accurate estimates of antibody-associated protection from clinical malaria require adjustment for malaria exposure.

From the *Division of Global Pediatrics, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN; †Centre for Global Health Research, Kenya Medical Research Institute, Kisian, Kenya; ‡Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH; §Department of Pediatrics, University of Massachusetts, Worscester, MA; and ¶Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, Bethesda, MD.

Accepted for publication July 10, 2011.

This study was published with the permission of the Director, Kenya Medical Research Institute.

Supported in part by the Intramural Research Program of the NIH, Malaria Vaccine Development Branch, National Institute for Allergy and Infectious Diseases. Supported in part by grants U01 AI056270 to (C.C.J.) and R01AI043906 to (J.W.K.).

The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Chandy C. John, MD, MS, Division of Global Pediatrics, Department of Pediatrics, University of Minnesota Medical School, 717 Delaware St SE, Rm 366, Minneapolis, MN 55414. E-mail: ccj@umn.edu.

© 2011 Lippincott Williams & Wilkins, Inc.