Abstract
BackgroundAntibodies are important in the control of blood stage Plasmodium falciparum infection. It is unclear which antibody responses are responsible for, or even associated with protection, partly due to confounding by heterogeneous exposure. Assessment of response to partially effective antimalarial therapy, which requires the host to assist in clearing parasites, offers an opportunity to measure protection independent of exposure.MethodsA cohort of children aged 1–10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for uncomplicated malaria. Serum samples from the time of malaria diagnosis and 14 days later were analyzed for total IgG to 8 P. falciparum antigens using a quantitative indirect ELISA. Associations between antibody levels and risk of treatment failure were estimated using Cox proportional hazard regression.ResultsHigher levels of antibodies to apical membrane antigen 1 (AMA-1), but to none of the other 7 antigens were significantly associated with protection against treatment failure (HR 0.57 per 10-fold increase in antibody level, CI 0.41–0.79, p = 0.001). Protection increased consistently across the entire range of antibody levels.ConclusionsMeasurement of antibody levels to AMA-1 at the time of malaria may offer a quantitative biomarker of blood stage immunity to P. falciparum, a tool which is currently lacking.
Highlights
Malaria remains one of the leading causes of morbidity and mortality in children living in sub-Saharan Africa [1]
We have previously described an association between clinical surrogates of host immunity and protection from failure after treatment with amodiaquine plus sulfadoxine-pyrimethamine (AQ+SP) in a cohort of children in Kampala, Uganda [12]
29 of the 244 treatments resulted in treatment failure, giving a 63-day risk of treatment failure of 13%; there was a median of 2 treatments per subject; the mean age at enrollment was 6.0 years; 45.9% of the participants lived within 50 meters of a swamp that bordered the study site; and asymptomatic parasitemia was detected within 180 days prior to malaria diagnosis for 29.0% of the treatments
Summary
Malaria remains one of the leading causes of morbidity and mortality in children living in sub-Saharan Africa [1]. The development of acquired immunity to Plasmodium falciparum prevents much of this morbidity in older children and adults, but it is slow to develop and requires repeated episodes of malaria. It is difficult in such studies to distinguish decreased risk due to immunologic protection from decreased malaria incidence due to a lack of parasite exposure [7,8,9], making it challenging to identify associations between antibody responses and the incidence of malaria. Antibodies are important in the control of blood stage Plasmodium falciparum infection. It is unclear which antibody responses are responsible for, or even associated with protection, partly due to confounding by heterogeneous exposure. Assessment of response to partially effective antimalarial therapy, which requires the host to assist in clearing parasites, offers an opportunity to measure protection independent of exposure
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