AbstractBackgroundAntibody responses to serological markers of Plasmodium vivax infection have been shown to correlate with exposure, but little is known about the other factors which affect antibody responses in naturally infected people from endemic settings. To address this question, we studied IgG responses to novel serological exposure markers (SEMs) of P. vivax in three settings with different transmission intensity.MethodologyWe validated a panel of 34 SEMs in a Peruvian cohort with up to three years’ longitudinal follow-up using the Luminex® platform and compared results to data from cohorts in Thailand and Brazil. Linear regression models were used to characterize the association between antibody responses and age, the number of detected blood-stage infections during follow-up, and time since the last infection. Receiver Operating Characteristic (ROC) analysis was used to test the performance of SEMs to identify P. vivax infections in the last 9 months.Principal findingsAntibody titers were associated with age, the number of blood-stage infections, and time since last P. vivax infection in all three study sites. The association between antibody titers and time since last P. vivax infection was stronger in the low transmission settings of Thailand and Brazil compared to the high transmission setting in Peru. Of the SEMs tested, antibody responses to RBP2b had the highest performance of classifying recent exposure in all sites, with area under the ROC curve (AUC) = 0.83 in Thailand, AUC = 0.79 in Brazil, and AUC = 0.68 in Peru.ConclusionsIn low transmission settings, P. vivax SEMs can accurately identify individuals with recent blood-stage infections. In high transmission settings, the accuracy of this approach diminishes substantially. We recommend the application of P. vivax SEMs for use in low transmission settings pursuing malaria elimination, but they appear less useful in high transmission settings focused on malaria control.Author SummaryPlasmodium vivax still poses a threat in many countries due to its ability to cause recurrent infections. Key to achieving the goal of malaria elimination is the ability to quickly detect and treat carriers of relapsing parasites. Failing to identify this transmission reservoir will hinder progress towards malaria elimination. Recently, novel serological markers of recent exposure to P. vivax (SEM) have been developed and validated in low transmission settings. It is still poorly understood what factors affect the antibody response to these markers when evaluated in contrasting endemic contexts. To determine the factors that influence the antibody response to SEM, we compare the antibody levels in three sites with different transmission intensity: Thailand (low), Brazil (moderate) and Peru (high). In this study, we found that transmission intensity plays a key role in the acquisition of the antibody repertoire to P. vivax. In highly endemic sites, the immunological memory resulting from a constant and sustained exposure will impact the performance of SEMs to detect individuals with recent exposure to P. vivax. In summary, SEMs that perform well in low transmission sites do not perform as well in high transmission regions.
Polymorphisms in B Cell Co-Stimulatory Genes Are Associated with IgG Antibody Responses against Blood–Stage Proteins of Plasmodium vivax
