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J Infect Dis. 2016 Oct 1;214(7):1072-80. doi: 10.1093/infdis/jiw301. Epub 2016 Aug 1.

Quantifying Heterogeneous Malaria Exposure and Clinical Protection in a Cohort of Ugandan Children.

Author information

1
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
2
Infectious Diseases Research Collaboration.
3
Department of Medicine, San Francisco General Hospital, University of California-San Francisco.
4
Department of Medicine, San Francisco General Hospital, University of California-San Francisco Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
5
Division of Global Health Protection, Centers for Disease Control and Prevention, Atlanta, Georgia.
6
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
7
London School of Hygiene and Tropical Medicine, United Kingdom.

Abstract

BACKGROUND:

Plasmodium falciparum malaria remains a leading cause of childhood morbidity and mortality. There are important gaps in our understanding of the factors driving the development of antimalaria immunity as a function of age and exposure.

METHODS:

We used data from a cohort of 93 children participating in a clinical trial in Tororo, Uganda, an area of very high exposure to P. falciparum We jointly quantified individual heterogeneity in the risk of infection and the development of immunity against infection and clinical disease.

RESULTS:

Results showed significant heterogeneity in the hazard of infection and independent effects of age and cumulative number of infections on the risk of infection and disease. The risk of developing clinical malaria upon infection decreased on average by 6% (95% confidence interval [CI], 0%-12%) for each additional year of age and by 2% (95% CI, 1%-3%) for each additional prior infection. Children randomly assigned to receive dihydroartemisinin-piperaquine for treatment appeared to develop immunity more slowly than those receiving artemether-lumefantrine.

CONCLUSIONS:

Heterogeneity in P. falciparum exposure and immunity can be independently evaluated using detailed longitudinal studies. Improved understanding of the factors driving immunity will provide key information to anticipate the impact of malaria-control interventions and to understand the mechanisms of clinical immunity.

KEYWORDS:

epidemiology; heterogeneity in transmission; immunity; malaria

PMID:
27481862
PMCID:
PMC5021229
DOI:
10.1093/infdis/jiw301
[Indexed for MEDLINE]
Free PMC Article

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