Anti-MSP-10 IgG indicates recent exposure to Plasmodium vivax infection in the Peruvian Amazon

Abstract

BACKGROUNDSerological tools for the accurate detection of recent malaria exposure are needed to guide and monitor malaria control efforts. IgG responses against Plasmodium vivax and P. falciparum merozoite surface protein-10 (MSP10) were measured as a potential way to identify recent malaria exposure in the Peruvian Amazon.METHODSA field-based study included 470 participants in a longitudinal cohort who completed a comprehensive evaluation: light microscopy and PCR on enrollment, at least 1 monthly follow-up by light microscopy, a second PCR, and serum and dried blood spots for serological analysis at the end of the follow-up. IgG titers against novel mammalian cell-produced recombinant PvMSP10 and PfMSP10 were determined by ELISA.RESULTSDuring the follow-up period, 205 participants were infected, including 171 with P. vivax, 26 with P. falciparum, 6 with infections by both species but at different times, and 2 with mixed infections. Exposure to P. vivax was more accurately identified when serological responses to PvMSP10 were obtained from serum (sensitivity, 58.1%; specificity, 81.8%; AUC: 0.76) than from dried blood spots (sensitivity, 35.2; specificity, 83.5%; AUC: 0.64) (PAUC < 0.001). Sensitivity was highest (serum, 82.9%; dried blood spot, 45.7%) with confirmed P. vivax infections occurring 7-30 days before sample collection; sensitivity decreased significantly in relation to time since last documented infection. PvMSP10 serological data did not show evidence of interspecies cross-reactivity. Anti-PfMSP10 responses poorly discriminated between P. falciparum-exposed and nonexposed individuals (AUC = 0.59; P > 0.05).CONCLUSIONAnti-PvMSP10 IgG indicates recent exposure to P. vivax at the population level in the Amazon region. Serum, not dried blood spots, should be used for such serological tests.FUNDINGCooperative agreement U19AI089681 from the United States Public Health Service, NIH/National Institute of Allergy and Infectious Diseases, as the Amazonian International Center of Excellence in Malaria Research.

Keywords: Diagnostics; Epidemiology; Immunology; Infectious disease; Malaria.

Figure 1. Study area.

CAH, Cahuide; LUP, Lupuna.

Figure 2. Flow diagram of study participants and characteristics of malaria infections detected during their follow-up.

*Only last infections were considered in individuals with recurrent infections during the follow-up.

Figure 3. ROC curves and AUCs of serological responses for detecting malaria exposure.

(A) using PvMSP10 antigen, (B) using PfMSP10 antigen.

Figure 4. ROC curves and AUCs of serological responses for detecting P.

vivaxmalaria exposure. (A) Discrimination assessment in individuals aged less than 15 years and in those aged at least 15 years. (B) Discrimination between individuals with asymptomatic infections and those without infections and between individuals with symptomatic infections and those without infections.

Figure 5. Serological responses against PvMSP10 with the time since last P.

vivaxinfection. (A and B) Box plots (25th–75th percentiles) of corrected OD values on, respectively, serum and DBS samples. Horizontal bars inside the boxes represent the median of OD values in each group. (C and D) Dot plots of the sensitivity of dichotomized serological results in detecting malaria exposure using respectively serum and DBS samples, showing mean and 95% confidence limits in each group estimated by the Wilson score method.

Figure 6. P. vivax age-seroprevalence curves according to sample type (serum or dried blood spot) for study participants.

(A) Serum and (B) DBS samples. Dots represent observed prevalence, while lines represent fitted curves derived from catalytic models. SCRs (λ) and seroreversion rates (SRRs, ρ) estimated by catalytic models and corresponding 95% CIs estimated by Bootstrap methods are shown on the top right of each plot.