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Eight-Protein Blood Test Can ID Those at Risk of Carrying Hidden Malaria Parasites (Hypnozoites) within Nine Months of Active Infection with Plasmodium vivax; Test Offers Possibility of Reducing P. vivax Prevalence by As Much As 69%; 2 Billion Now at Risk

Plasmodium vivax is the most widespread malaria parasite worldwide, with up to 2,000,000,000 people at risk of infection. As well as causing illness and death in its “active” stage of infection, the parasite can hide as hypnozoites, a dormant stage, in the liver, and is a significant cause of “relapsing” malaria. These hypnozoites, undetectable with current diagnostics, can be responsible for >80% of all blood-stage infections. Identifying and targeting individuals with hypnozoites is thus essential for accelerating and achieving malaria elimination. A major gap in the P. vivax elimination toolkit is the identification of individuals carrying clinically silent and undetectable hypnozoites. The current study developed a panel of serological exposure markers capable of classifying individuals with P. vivax infections within the previous nine months who have a high likelihood of harboring hypnozoites. Using the Perkin-Elmer AlphaScreen system (https://www.perkinelmer.com/Content/RelatedMaterials/Brochures/BRO_Alpha...), the researchers measured IgG antibody responses to 342 P. vivax proteins expressed by a wheat germ cell-free system, invented at Ehime University in Japan, in longitudinal clinical cohorts conducted in Thailand and Brazil, and identified 60 candidate serological markers of exposure. Candidate markers were then validated using samples from year-long observational cohorts conducted in Thailand, Brazil, and the Solomon Islands and antibody responses to eight P. vivax proteins classified P. vivax infections in the previous 9 months with 80% sensitivity and specificity. Mathematical models demonstrate that a serological testing and treatment strategy based on testing for responses to these eight P. vivax proteins could reduce P. vivax prevalence by 59–69%. These eight antibody responses can serve as a biomarker, identifying individuals who should be targeted with anti-hypnozoite therapy. The test offers new opportunities for improving malaria control and elimination strategies.

The results of this study were published online on May 11, 2020 in Nature Medicine. The article is titled “Development and Validation of Serological Markers for Detecting Recent Plasmodium vivax infection.”

The two lead authors of the article are Rhea J. Longley, PhD, Walter and Eliza Hall Institute of Medical Research; and Michael T. White, PhD, Institut Pasteur. The senior author is Ivo Mueller, PhD, Walter and Eliza Hall Institute of Medical Research.

[Press release] [Nature Medicine abstract]

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(A) How to detect dormant hypnozoite of P. vivax? Antibodies can predict recent infections if they have the correct kinetic profile (green line, serological marker of hypnozoite). Antigens selected based on the kinetic profiles in nine months following clearance of infection are candidates for detecting hypnozoites. (B) Hypnozoite biomarkers. Eight antibody responses classified P. vivax infections in the previous 9 months with 80% sensitivity & specificity. (Credit: ©Ehime University).