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J Infect Dis. 2015 Jun 15;211(12):1987-96. doi: 10.1093/infdis/jiu814. Epub 2014 Dec 17.

IFNγ Responses to Pre-erythrocytic and Blood-stage Malaria Antigens Exhibit Differential Associations With Past Exposure and Subsequent Protection.

Author information

1
Department of Medicine, San Francisco General Hospital, University of California.
2
Infectious Diseases Research Collaboration.
3
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
4
Department of Medicine, San Francisco General Hospital, University of California Department of Pediatrics, University of California, San Francisco.

Abstract

BACKGROUND:

The malaria-specific T-cell response is believed to be important for protective immunity. Antimalarial chemoprevention may affect this response by altering exposure to malaria antigens.

METHODS:

We performed interferon γ (IFNγ) ELISpot assays to assess the cellular immune response to blood-stage and pre-erythrocytic antigens longitudinally from 1 to 3 years of age in 196 children enrolled in a randomized trial of antimalarial chemoprevention in Tororo, Uganda, an area of high transmission intensity.

RESULTS:

IFNγ responses to blood-stage antigens, particularly MSP1, were frequently detected, strongly associated with recent malaria exposure, and lower in those adherent to chemoprevention compared to nonadherent children and those randomized to no chemoprevention. IFNγ responses to pre-erythrocytic antigens were infrequent and similar between children randomized to chemoprevention or no chemoprevention. Responses to blood-stage antigens were not associated with subsequent protection from malaria (aHR 0.96, P = .83), but responses to pre-erythrocytic antigens were associated with protection after adjusting for prior malaria exposure (aHR 0.52, P = .009).

CONCLUSIONS:

In this high transmission setting, IFNγ responses to blood-stage antigens were common and associated with recent exposure to malaria but not protection from subsequent malaria. Responses to pre-erythrocytic antigens were uncommon, not associated with exposure but were associated with protection from subsequent malaria.

KEYWORDS:

IFNγ; T cell; antimalarial chemoprevention; falciparum; immunity; malaria

PMID:
25520427
PMCID:
PMC4836719
DOI:
10.1093/infdis/jiu814
[Indexed for MEDLINE]
Free PMC Article

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