Asymptomatic P. vivax Malaria Burden and Naturally-Acquired Humoral Response to PvMSP1-19 in a Low Endemic Malaria Area in the Peruvian Amazon Basin
Vidal, Elisa Maria
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Objective: P. vivax (Pv) malaria is the most widely distributed human malaria species in the world, affecting millions of people annually, and the most prevalent species in the Americas. One of the main challenges for the control and elimination of malaria in the region is the presence of Pv malaria and its ability to relapse, as well as the presence of asymptomatic individuals who go undiagnosed, facilitating the persistence of disease. This study sought to improve our understanding of the naturally-acquired humoral response and epidemiology of Pv malaria in a low-endemicity area in the Peruvian Amazon Basin through the analysis of antibodies (Ab) against PvMSP119 recombinant protein, a leading vaccine candidate antigen. Methods: A large dataset of eight community-wide cross-sectional microscopy surveys conducted from 2004-2011 and 294 repository plasma samples of Pv-infected individuals were analyzed using statistical and immunological methods to describe the changing malaria burden in the area, as well as to study naturally-acquired anti-PvMSP119 humoral response in a low-endemic setting. Specifically, we studied the Ab response before, during and after a documented microscopy-positive infection, assessing differences in circulating mean IgG levels and changes in serostatus between symptomatic and asymptomatic subjects both prior and during patent infection, as well as Ab maintenance in symptomatic individuals, assessing the absolute change in IgG levels and serostatus eight to 21 months after infection. Risk factors associated with asymptomatic infection and maintenance of Ab levels were assessed using GLM logistic regression. Results: In the retrospective surveillance study, we observed a significant decline in malaria prevalence in the first years of the survey, followed by sustained low-prevalence, with asymptomatic cases being most common after the sharp decline, and with male individuals, individuals aged 15-44 years, and farmers and laborers at increased risk of infection. Serological analysis revealed that mean pre-infection anti-PvMSP119 IgG was indistinguishable between clinical groups while mean IgG elicited during infection was significantly higher in symptomatic individuals, with pre-infection Ab associated with asymptomatic infection while Ab elicited during infection with symptomatic malaria. The Ab maintenance study found that 43% of seropositive individuals maintained their serostatus eight to 15 months after patent infection, with an estimated half-life of 2.3 years. Increasing age was associated with reduced Ab decline and with increased risk of remaining seropositive over time. Conclusions: The cross-sectional microscopy surveillance confirms that asymptomatic malaria is prevalent in low endemic areas in the Peruvian Amazon Basin, posing a challenge to malaria control efforts in the area. Although Ab can be both a marker of exposure and infection, circulating Ab months prior and during patent Pv infection reflect different risks associated with clinical presentation. Despite low malaria transmission, seropositive anti-PvMSP119 IgG can be maintained eight to 15 months after natural infection, with over 2 years of estimated half-life. The present study supports the hypothesis that malaria infection in areas with reduced transmission can effectively stimulate an Ab response, eliciting naturally-acquired humoral responses capable of controlling clinical disease even under infrequent boosting circumstances. Conducting immuno-epidemiological studies on asymptomatic malaria, with a special focus on Pv, will be crucial for better understanding malaria epidemiology both in Peru and the Americas, and contribute to the successful control and possible elimination of malaria in the region.