Associations between Antibodies to a Panel of Plasmodium falciparum Specific Antigens and Response to Sub-Optimal Antimalarial Therapy in Kampala, Uganda

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.

Acquired Antibodies to Merozoite Antigens in Children from Uganda with Uncomplicated or Severe Plasmodium falciparum Malaria

“…For example, presence of antibodies against Rh2 and AMA1 in ELISAs correlated to invasion for both tested clinical isolates, and antibodies against AMA1 in ELISAs also correlated to affinity SPR results, indicating that this protein might be targeted by functionally important, high-affinity antibodies that could contribute to protection from severe malaria. Our findings are consistent with recent studies from Uganda (76,77) that showed a strong association between antibodies against AMA1 and protection against malaria. Other antigens, such as MSP1, showed no difference in antibody levels between uncomplicated and severe malaria and did not show any correlations with invasion.…”

Analysis of antibody profiles in symptomatic malaria in three sentinel sites of Ivory Coast by using multiplex, fluorescent, magnetic, bead-based serological assay (MAGPIX™)

“…2 , was significant for 50 % of the biomarkers. These results are in agreement with several studies involving sulfadoxine–pyrimethamine or amodiaquine treatment, showing a significant association of higher levels of antibodies to GLURP [ 47 ], AMA1 [ 48 ] and MSP1 [ 49 ] antigens with a lower risk of treatment failure. Another study showed the contribution of antibodies to the Ring Erythrocyte Surface antigen to the therapeutic response in Thai patients treated with artesunate [ 50 ].…”

Immunity as a predictor of anti-malarial treatment failure: a systematic review

“…A further two studies investigated the association between P. falciparum antibody responses and chloroquine treatment failure (CQ) [ 22 , 26 ] (Table 2 ). The included studies reported total IgG responses to antigens P. falciparum merozoite antigens (MSP1 [ 23 , 27 ], MSP1-19 [ 22 , 24 – 26 ], MSP1 Block 2 proteins [ 23 ], MSP2 [ 24 , 28 ], MSP3 [ 22 , 24 ], EBA-175 [ 27 ], AMA-1 [ 24 , 26 – 28 ]) and antigens expressed on the surface of Pf -IE (VSAs [ 27 , 28 ], RESA [ 29 ],), as well as schizont extract [ 27 ]. Two studies reported IgG responses to the glutamate rich protein (GLURP) [ 22 , 24 ], which is expressed in multiple parasite life stages but was analysed with merozoite specific responses (Table 2 ).…”