Abstract
BackgroundPlasmodium knowlesi is the most common cause of malaria in Malaysian Borneo, with reporting limited to clinical cases presenting to health facilities and scarce data on the true extent of transmission. Serological estimations of transmission have been used with other malaria species to garner information about epidemiological patterns. However, there are a distinct lack of suitable serosurveillance tools for this neglected disease.Methodology/Principal findingsUsing in silico tools, we designed and expressed four novel P. knowlesi protein products to address the distinct lack of suitable serosurveillance tools: PkSERA3 antigens 1 and 2, PkSSP2/TRAP and PkTSERA2 antigen 1. Antibody prevalence to these antigens was determined by ELISA for three time-points post-treatment from a hospital-based clinical treatment trial in Sabah, East Malaysia (n = 97 individuals; 241 total samples for all time points). Higher responses were observed for the PkSERA3 antigen 2 (67%, 65/97) across all time-points (day 0: 36.9% 34/92; day 7: 63.8% 46/72; day 28: 58.4% 45/77) with significant differences between the clinical cases and controls (n = 55, mean plus 3 SD) (day 0 p<0.0001; day 7 p<0.0001; day 28 p<0.0001). Using boosted regression trees, we developed models to classify P. knowlesi exposure (cross-validated AUC 88.9%; IQR 86.1–91.3%) and identified the most predictive antibody responses.Conclusions/SignificanceThe PkSERA3 antigen 2 had the highest relative variable importance in all models. Further validation of these antigens is underway to determine the specificity of these tools in the context of multi-species infections at the population level.
Highlights
Plasmodium knowlesi is a simian parasite which can cause zoonotic malaria in humans [1]
Malaria caused by Plasmodium knowlesi is the most common form of the disease in Malaysia
The parasite is transmitted from monkeys to humans via the bite of an infected mosquito, with the resulting P. knowlesi infection potentially leading to severe symptoms and in some cases, death
Summary
Plasmodium knowlesi is a simian parasite which can cause zoonotic malaria in humans [1]. P. knowlesi has the potential to cause severe disease in endemic regions [3], and is the most common cause of clinical malaria in Malaysia [4]. Studies have shown that antibodies to Plasmodium proteins persist for long periods [11], even in the context of limited exposure or absence of infection. Such antibodies can be utilised in serological assays, accurately estimating the incidence and exposure to Plasmodium parasites [12, 13]. Plasmodium knowlesi is the most common cause of malaria in Malaysian Borneo, with reporting limited to clinical cases presenting to health facilities and scarce data on the true extent of transmission. There are a distinct lack of suitable serosurveillance tools for this neglected disease
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