Heterogeneity in response to serological exposure markers of recent Plasmodium vivax infections in contrasting epidemiological contexts

Abstract

Background Antibody responses as serological markers of Plasmodium vivax infection have been shown to correlate with exposure, but little is known about the other factors that 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. Methodology We validated a panel of 34 SEMs in a Peruvian cohort with up to three years’ longitudinal follow-up using a multiplex 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 previous infection. Receiver Operating Characteristic (ROC) analysis was used to test the performance of SEMs to identify P. vivax infections in the previous 9 months. Principal findings Antibody titers were associated with age, the number of blood-stage infections, and time since previous P. vivax infection in all three study sites. The association between antibody titers and time since previous P. vivax infection was stronger in the low transmission settings of Thailand and Brazil compared to the higher transmission setting in Peru. Of the SEMs tested, antibody responses to RBP2b had the highest performance for 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. Conclusions In low transmission settings, P. vivax SEMs can accurately identify individuals with recent blood-stage infections. In higher transmission settings, the accuracy of this approach diminishes substantially. We recommend using P. vivax SEMs in low transmission settings pursuing malaria elimination, but they are likely to be less effective in high transmission settings focused on malaria control.

Untangling population structure and genetic diversity of reticulocyte binding protein 2b (PvRBP2b) erythrocytic stage vaccine candidate in worldwide Plasmodium vivax isolates

“…According to the antibody response in cohort studies, PvRBP2b (aa: 161–1454 and 1986–2653) showed the highest performance for categorizing new exposure and introduced as the top marker for detection of blood-stage P . vivax infections within the previous nine months in Thailand, Peru, and Brazil regions [ 18 ]. Furthermore, it has been shown that naturally acquired human antibodies against N-terminus of PvRBP2b can inhibit parasite invasion [ 19 ].…”

Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modeling the balance between public health impact and overtreatment

“…A limitation of our analysis is that we do not account for potential variation between geographic regions and across transmission intensities, factors which are known to affect diagnostic accuracy [ 30 ]. Another limitation of this analysis is that we did not account for the effects of targeting diagnostics and treatment strategies at high-risk populations.…”

Malaria transmission structure in the Peruvian Amazon through antibody signatures to Plasmodium vivax

“…vivax than children or newcomers) or ii) labor exposure (i.e., people in adult age increase their chances of exposure by working in forest-related jobs). Our previous work showed that antibody levels increased with the recency of infection, the number of blood-stage infections and age [ 14 ]. However, age is the stronger predictor for antibody levels in communities with high transmission level [ 14 ].…”

“…Our previous work showed that antibody levels increased with the recency of infection, the number of blood-stage infections and age [ 14 ]. However, age is the stronger predictor for antibody levels in communities with high transmission level [ 14 ]. The presence of livestock in the households has been associated with low P .…”

“…vivax have been developed and validated for their use in low transmission settings [ 13 ]. These serological markers of exposure were able to detect recent exposure in participants from longitudinal cohorts of road and riverine communities with moderate-to-high transmission of the Peruvian Amazon, although performance was notably lower than in low endemic settings [ 14 ].…”