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Antibodies by Non-Febrile, Smear-Negative Individuals from a Malaria Epidemic-Prone Setting in Ethiopia are Strongly Reactive to Plasmodium falciparum Blood-Stage Vaccine Candidate Antigens

Hassen Mamo, Nnaemeka C Iriemenam, Klavs Berzins and Beyene Petros

Background: Plasmodium falciparum malaria remains a major public health concern globally though there is some decline due to scale-up of control efforts. Evaluation of the anti-malarial immune profile, in populations residing in epidemic-prone areas in the dry season or at the time when vector control largely reduced man-mosquito contact, would help predict malaria burden when future epidemics occur. Methods: A cross-sectional study was designed to investigate antibody responses to four P. falciparum blood stage vaccine candidate antigens in non-febrile individuals from Shewa Robit in north-central Ethiopia where malaria transmission was expected at a minimal level as a result of the sampling season and effective vector control. Blood samples were analyzed microscopically for Plasmodium detection. The enzyme-linked immunosorbent assay (ELISA) was used to measure immunoglobulin (IgG) antibodies to apical membrane antigen 1 (AMA1), glutamaterich protein (GLURP) R2 region and merozoite surface protein 2 (MSP2) allelic variants. Results: Study participants were smear-negative for Plasmodium infection. While 51 (22%) of the participants reported that they had never been exposed to clinical malaria in life, 177 (78%) reported at least one clinical malaria episode with laboratory confirmed P. falciparum infection. The antigens tested were well-recognized by the test sera although significant differences were observed in antibody prevalence and level between the different antigens and there was inter-individual variability. IgG response to the antigens showed age-related pattern but without evidence of relation with status and frequency of reported past exposure to clinical malaria. Conclusion: The data suggests that individuals in an epidemic-prone malaria setting have reactive and stable antibodies that readily recognize P. falciparum blood-stage vaccine candidate antigens in the absence of slidepositivity. Analysis of age-related pattern in antibody level showed positive association with age but unrelated with increasing frequency of reported episode suggesting the role of intrinsic age-related factors in malaria immune maturation.