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    Antibody signatures of asymptomatic Plasmodium falciparum malaria infections measured from dried blood spots

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    Author
    Markwalter, Christine F
    Nyunt, Myat Htut
    Han, Zay Yar
    Henao, Ricardo
    Jain, Aarti
    Taghavian, Omid
    Felgner, Philip L
    Han, Kay Thwe
    Nyunt, Myaing M
    Plowe, Christopher V
    Date
    2021-09-23
    Journal
    Malaria Journal
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1186/s12936-021-03915-8
    Abstract
    Background: Screening malaria-specific antibody responses on protein microarrays can help identify immune factors that mediate protection against malaria infection, disease, and transmission, as well as markers of past exposure to both malaria parasites and mosquito vectors. Most malaria protein microarray work has used serum as the sample matrix, requiring prompt laboratory processing and a continuous cold chain, thus limiting applications in remote locations. Dried blood spots (DBS) pose minimal biohazard, do not require immediate laboratory processing, and are stable at room temperature for transport, making them potentially superior alternatives to serum. The goals of this study were to assess the viability of DBS as a source for antibody profiling and to use DBS to identify serological signatures of low-density Plasmodium falciparum infections in malaria-endemic regions of Myanmar. Methods: Matched DBS and serum samples from a cross-sectional study in Ingapu Township, Myanmar were probed on protein microarrays populated with P. falciparum antigen fragments. Signal and trends in both sample matrices were compared. A case-control study was then performed using banked DBS samples from malaria-endemic regions of Myanmar, and a regularized logistic regression model was used to identify antibody signatures of ultrasensitive PCR-positive P. falciparum infections. Results: Approximately 30% of serum IgG activity was recovered from DBS. Despite this loss of antibody activity, antigen and population trends were well-matched between the two sample matrices. Responses to 18 protein fragments were associated with the odds of asymptomatic P. falciparum infection, albeit with modest diagnostic characteristics (sensitivity 58%, specificity 85%, negative predictive value 88%, and positive predictive value 52%). Conclusions: Malaria-specific antibody responses can be reliably detected, quantified, and analysed from DBS, opening the door to serological studies in populations where serum collection, transport, and storage would otherwise be impossible. While test characteristics of antibody signatures were insufficient for individual diagnosis, serological testing may be useful for identifying exposure to asymptomatic, low-density malaria infections, particularly if sero-surveillance strategies target individuals with low previous exposure as sentinels for population exposure.
    Rights/Terms
    © 2021. The Author(s).
    Keyword
    Antibody responses
    Asymptomatic malaria
    Protein microarrays
    Serology
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/16729
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12936-021-03915-8
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