Identification of Molecular Markers of Hypnozoite Carriage in P. vivax-Infected Persons
Abstract
Fiscal Year 2016 Peer Reviewed Medical Research Program Topic Area: Malaria. There are two major human pathogens that cause malaria, Plasmodium falciparum and P. vivax. While P. falciparum is more commonly known, P. vivax is endemic in more areas of the world than P. falciparum. P. vivax is uniquely suited to be refractory to eradication because of its ability to cause a latent form of the parasite in the liver. This persistent parasite forms after the bite of a mosquito injects the parasite into the skin and it travels to the liver. Here the parasite grows for a few days before it releases thousands of parasites into the blood stream, causing signs and symptoms of disease. A subset of the parasite population that infects the liver does not immediately replicate and stays in a single-cell state, the latent hypnozoite. This single-cell hypnozoite can be activated months to years later causing a blood-stage infection. Very little is known about the latent hypnozoite, and our models to study the hypnozoite are limited. After a person is infected with P. vivax, their acute blood stage infection can be symptomatic or asymptomatic. In either case, there is no way for us to know that a person has latent hypnozoites in their liver. This proposal seeks to identify biomarkers present in the blood, serum, urine, or stool that denote liver infection with hypnozoites. We will use human liver-chimeric mouse to model P. vivax infection and sample biofluids for parasite nucleic acid. The identification of RNA differentially expressed in biofluids of mice with latent infection versus those uninfected will suggest candidate RNA to serve as a biomarker. We will also specifically sample single liver infected cells to identify RNA that is present in the infected cell and may be transported to the biofluids. This proposal combines several advances in technologies that will ensure success in the identification of a biomarker. This biomarker can then be used to develop a diagnostic test for latent P. vivax infection, which will have profound implications for the malaria eradication effort.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710213
Entities
People
- Erika L Flannery
Organizations
- Center for Global Infectious Disease Research
- United States Army