Limits...
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.

Show MeSH

Related in: MedlinePlus

Relationship between anti-apical membrane antigen 1 (AMA-1) antibody levels and risk of treatment failure.A consistent relationship was seen across the range of values observed. Anti-AMA-1 levels (log-transformed) were divided into five equal intervals, each representing a 10-fold increase in level.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3526588&req=5

pone-0052571-g003: Relationship between anti-apical membrane antigen 1 (AMA-1) antibody levels and risk of treatment failure.A consistent relationship was seen across the range of values observed. Anti-AMA-1 levels (log-transformed) were divided into five equal intervals, each representing a 10-fold increase in level.

Mentions: To further examine the dose-response relationship between anti-AMA-1 levels on Day 0 and treatment failure, antibody levels were divided into 5 equal intervals, each representing a 10-fold increase. There was a consistent, fairly linear relationship between anti-AMA-1 levels and protection against treatment failure over the entire range of measured responses (Figure 3). All malaria treatments in children with responses in the top 36% of the range were associated with successful clearance of parasites.


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)

Relationship between anti-apical membrane antigen 1 (AMA-1) antibody levels and risk of treatment failure.A consistent relationship was seen across the range of values observed. Anti-AMA-1 levels (log-transformed) were divided into five equal intervals, each representing a 10-fold increase in level.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0052571-g003: Relationship between anti-apical membrane antigen 1 (AMA-1) antibody levels and risk of treatment failure.A consistent relationship was seen across the range of values observed. Anti-AMA-1 levels (log-transformed) were divided into five equal intervals, each representing a 10-fold increase in level.
Mentions: To further examine the dose-response relationship between anti-AMA-1 levels on Day 0 and treatment failure, antibody levels were divided into 5 equal intervals, each representing a 10-fold increase. There was a consistent, fairly linear relationship between anti-AMA-1 levels and protection against treatment failure over the entire range of measured responses (Figure 3). All malaria treatments in children with responses in the top 36% of the range were associated with successful clearance of parasites.

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