Contributors: Malaria : parasites et hôtes - Malaria : parasites and hosts; Institut Pasteur Paris (IP); Epidémiologie et Analyse des Maladies Infectieuses - Infectious Disease Epidemiology and Analytics; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB; Swiss Tropical and Public Health Institute Basel; Université de Bâle = University of Basel = Basel Universität (Unibas); The Walter and Eliza Hall Institute of Medical Research (WEHI); Burnet Institute Melbourne, Victoria; University of Melbourne; London School of Hygiene and Tropical Medicine (LSHTM); This work is supported by the Bill and Melinda Gates Foundation grants (INV009103 & VISPA INV024368) and NHMRC grants (GNT1102297 & GNT1171795) and is part of the International Centers of Excellence for Malaria Research program “Understanding, tracking and eliminating malaria transmission in the Asia–Pacific Region,” funded by the National Institutes of Health, MD, US (grant 1U19AI129392-01). IM is supported by an NHMRC Principal Research Fellowship (GNT1155075). MTW is supported by the Agence Nationale de la Recherche Investissement d’Avenir Programme, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID) and INCEPTION program (ANR-16-CONV-0005). LJR is supported by an NHMRC Career Development Fellowship (GNT1161627).; ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016)
نبذة مختصرة : International audience ; Background Eliminating Plasmodium vivax will require targeting the hidden liver-stage reservoir of hypnozoites. This necessitates new interventions balancing the benefit of reducing vivax transmission against the risk of over-treating some individuals with drugs which may induce haemolysis. By measuring antibodies to a panel of vivax antigens, a strategy of serological-testing-and-treatment ( Pv SeroTAT) can identify individuals with recent blood-stage infections who are likely to carry hypnozoites and target them for radical cure. This provides a potential solution to selectively treat the vivax reservoir with 8-aminoquinolines. Methods Pv SeroTAT can identify likely hypnozoite carriers with ~80% sensitivity and specificity. Diagnostic test sensitivities and specificities ranging 50–100% were incorporated into a mathematical model of vivax transmission to explore how they affect the risks and benefits of different Pv SeroTAT strategies involving hypnozoiticidal regimens. Risk was measured as the rate of overtreatment and benefit as reduction of community-level vivax transmission. Results Across a wide range of combinations of diagnostic sensitivity and specificity, Pv SeroTAT was substantially more effective than bloodstage mass screen and treat strategies and only marginally less effective than mass drug administration. The key test characteristic determining of the benefit of Pv SeroTAT strategies is diagnostic sensitivity, with higher values leading to more hypnozoite carriers effectively treated and greater reductions in vivax transmission. The key determinant of risk is diagnostic specificity: higher specificity ensures that a lower proportion of uninfected individuals are unnecessarily treated with primaquine. These relationships are maintained in both moderate and low transmission settings (qPCR prevalence 10% and 2%). Increased treatment efficacy and adherence can partially compensate for lower test performance. Multiple rounds of Pv SeroTAT with a lower performing test may lead ...
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