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Associations between antibodies to a panel of Plasmodium falciparum specific antigens and response to sub-optimal antimalarial therapy in Kampala, Uganda.

Keh CE, Jha AR, Nzarubara B, Lanar DE, Dutta S, Theisen M, Rosenthal PJ, Dorsey G, Nixon DF, Greenhouse B - PLoS ONE (2012)

Bottom Line: 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.Higher 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, USA.

ABSTRACT

Background: 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.

Methods: A 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.

Results: Higher 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.

Conclusions: Measurement 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.

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Related in: MedlinePlus

Sample inclusion.Malaria treatments with amodiaquine+sulfadoxine-pyrimethamine (AQ+SP) and available samples for inclusion in the study. Further details on children not randomized have been previously described [17].
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pone-0052571-g001: Sample inclusion.Malaria treatments with amodiaquine+sulfadoxine-pyrimethamine (AQ+SP) and available samples for inclusion in the study. Further details on children not randomized have been previously described [17].

Mentions: Over the course of the study, 601 total subjects were enrolled and 329 children were randomized in the clinical trial of combination antimalarial therapy. Children randomized to AQ+SP were followed up to 28 months on this therapy. The prevalence of asymptomatic parasitemia in this cohort was 18.6% at enrollment and fell to 2.3% during the study [17]. 129 children were treated with AQ+SP for a total of 396 treatments. The 63-day risk of recrudescence (treatment failure) in this treatment arm was 11% [12]. Samples from 106 participants meeting inclusion criteria were available for antibody analysis, representing 244 treatments (Day 0) and 184 follow-up samples (Day 14) (Figure 1). In this subset, 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 (range 1–11); the mean age at enrollment was 6.0 years (range 1.2–10.0 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.


Associations between antibodies to a panel of Plasmodium falciparum specific antigens and response to sub-optimal antimalarial therapy in Kampala, Uganda.

Keh CE, Jha AR, Nzarubara B, Lanar DE, Dutta S, Theisen M, Rosenthal PJ, Dorsey G, Nixon DF, Greenhouse B - PLoS ONE (2012)

Sample inclusion.Malaria treatments with amodiaquine+sulfadoxine-pyrimethamine (AQ+SP) and available samples for inclusion in the study. Further details on children not randomized have been previously described [17].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3526588&req=5

pone-0052571-g001: Sample inclusion.Malaria treatments with amodiaquine+sulfadoxine-pyrimethamine (AQ+SP) and available samples for inclusion in the study. Further details on children not randomized have been previously described [17].
Mentions: Over the course of the study, 601 total subjects were enrolled and 329 children were randomized in the clinical trial of combination antimalarial therapy. Children randomized to AQ+SP were followed up to 28 months on this therapy. The prevalence of asymptomatic parasitemia in this cohort was 18.6% at enrollment and fell to 2.3% during the study [17]. 129 children were treated with AQ+SP for a total of 396 treatments. The 63-day risk of recrudescence (treatment failure) in this treatment arm was 11% [12]. Samples from 106 participants meeting inclusion criteria were available for antibody analysis, representing 244 treatments (Day 0) and 184 follow-up samples (Day 14) (Figure 1). In this subset, 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 (range 1–11); the mean age at enrollment was 6.0 years (range 1.2–10.0 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.

Bottom Line: 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.Higher 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, USA.

ABSTRACT

Background: 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.

Methods: A 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.

Results: Higher 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.

Conclusions: Measurement 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.

Show MeSH
Related in: MedlinePlus