Known markers of seroincidence were selected based on available evidence from P. Identification and screening of target sequencesįig 1 outlines the experimental strategy used in the identification of the target sequences of interest. These reagents will also serve as an important set of tools to help identify correlates of immunity to P. By assessing relative variable importance within these models, we identify the antigen responses contributing most to model predictions and potential serological tools for use in epidemiological studies. To illustrate how these data can be used to identify seropositive individuals, we utilise data-adaptive statistical methods (boosted regression trees) to classify exposed individuals. The development of such well-validated species-specific tools represent a potentially important serosurveillance tool to help monitor for historical P. knowlesi-specific amino acid sequences, using publicly available in silico tools. In this study, we describe the development and evaluation of a panel of novel recombinant antigens based on P. Key to achieving this goal would be the development of sensitive and accurate tools to help monitor the transmission of infection. knowlesi recommended the urgent development of P. The 2011 WHO consultation panel on the public health importance of P. vivax ( ), potentially making it difficult to distinguish between the two species where infections are co-endemic. For example, PK66 ( PkAMA1) and PkSPATR (secreted protein with altered thrombospondin repeat) share 86% and 85% amino acid identity respectively with P. knowlesi have a high level of sequence homology with orthologues from other Plasmodium species and, as such, are not applicable to identifying species-specific antibody responses. The few recombinant protein reagents that do exist for P. Such information can also help to evaluate the impact of how control measures targeting a single species might affect the transmission and immunological profile of other co-endemic species. It is important to distinguish between human serological responses to different Plasmodium species to improve our understanding of immunity to these infections, as well as define the geographical spread of infection. One key requirement for serological studies is the identification of Plasmodium species-specific biomarkers, particularly in regions where multi-species infections are likely to occur. Such antibodies can be utilised in serological assays, accurately estimating the incidence and exposure to Plasmodium parasites. Studies have shown that antibodies to Plasmodium proteins persist for long periods, even in the context of limited exposure or absence of infection. falciparum with potential delay of appropriate treatment associated with case fatalities. Recent publications have also demonstrated misdiagnosis of P. malariae, historically leading to the misdiagnosis of P. knowlesi is morphologically similar to P. knowlesi has the potential to cause severe disease in endemic regions, and is now the most common cause of clinical malaria in Malaysia. knowlesi infections are a growing public health threat in South East Asia, particularly in Malaysia. Plasmodium knowlesi is a simian parasite which can cause zoonotic malaria in humans. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. RWM is supported by an MRC Career Development Award (MR/M021157/1) jointly funded by the UK Medical Research Council and UK Department for International Development. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: The Wellcome Trust (091924/Z/10/Z) and the Medical Research Council (G1100796 ). Received: DecemAccepted: ApPublished: June 14, 2018Ĭopyright: © 2018 Herman et al. Barry, Walter and Eliza Hall Institute, AUSTRALIA PLoS Negl Trop Dis 12(6):Įditor: Alyssa E. (2018) Identification and validation of a novel panel of Plasmodium knowlesi biomarkers of serological exposure. Citation: Herman LS, Fornace K, Phelan J, Grigg MJ, Anstey NM, William T, et al.
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