Last Updated: 30/04/2025
Identification of Molecular Markers of Hypnozoite Carriage in P. vivax-Infected Persons
Objectives
The objectives of this study are:
- To identify circulating host- or parasite-derived RNAs that are differentially present in biofluids of P. vivax-infected mice harboring hypnozoites, compared to uninfected controls.
- To detect host- and parasite-derived RNAs within single, parasite-infected hepatocytes and assess whether these transcripts can be reliably detected in biofluids using a highly sensitive assay.
- To integrate findings from both targeted and untargeted transcriptomic approaches to support the identification of a robust biomarker indicative of P. vivax hepatic latency.
Successful elimination of malaria remains particularly challenging for the relapsing species Plasmodium vivax and P. ovale. Relapse is driven by hypnozoites—dormant liver-stage forms that can reactivate months or even years after the initial infection, leading to renewed clinical disease and potential transmission. Primaquine, the only licensed drug effective against hypnozoites, poses limitations due to its long treatment duration and its toxicity in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating pre-screening before administration. A non-invasive, sensitive diagnostic marker for hypnozoite carriage would significantly aid efforts toward malaria elimination by identifying individuals at risk of relapse.
Recent advances in the immunocompromised human liver-chimeric mouse model have enabled the study of P. vivax liver-stage biology, including long-term persistence of hypnozoites. Hypnozoites have been shown to persist for up to 49 days in this model, growing slowly over time. Although liver-stage host-parasite interactions remain poorly characterized, parallels from blood-stage malaria suggest that parasites can remodel host cells and modulate the host environment in detectable ways. It is hypothesized that these interactions during latency result in the release of host- or parasite-derived RNAs into biofluids, which can be captured using advanced RNA isolation and detection technologies. By leveraging this model system and high-sensitivity transcriptomic techniques, it may be possible to detect circulating RNA signatures associated with hypnozoite infection, thereby offering a potential biomarker for latency.
Jul 2017 — Feb 2020
$323,715
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