News Release 

Clinically silent relapsing malaria may still pose a threat

PLOS

Nonhuman primates with clinically undetectable Plasmodium relapse infections still harbor parasitic gametocytes that may be infectious to mosquitoes, according to a study published September 19 in the open-access journal PLOS Pathogens by F. Eun-Hyung Lee and Mary R. Galinski of Emory University, Tracey J. Lamb of the University of Utah, and colleagues. The study has important epidemiological implications relevant to malaria elimination strategies.

The protozoal parasite Plasmodium vivax is a major cause of malaria - a life-threatening mosquito-borne disease responsible for hundreds of thousands of deaths globally each year. P. vivax remains a major obstacle for malaria elimination due to its ability to form dormant stages in the liver. These forms can become activated to cause relapsing blood-stage infections. Relapses remain poorly understood because it is difficult to verify whether P. vivax blood-stage infections in patients are due to new infections or relapses. To address this gap in knowledge, researchers used a nonhuman primate model of malaria, combined with state-of-the-art immunological and molecular techniques, to assess pathogenesis, host responses, and circulating gametocyte levels during relapses.

They found that relapses were clinically silent compared to initial infections, and they were associated with a robust memory B cell response. This response resulted in the production of antibodies that were able to mediate clearance of relapsing, asexual parasites. Despite this rapid immune protection, the sexual-stage gametocytes, which may be infectious to mosquitoes, continued to circulate. According to the authors, the number of clinically silent relapse infections, and their infectiousness to mosquitoes, remains largely unknown and should be evaluated carefully in the future. As a next step on the path to eliminating P. vivax and other relapsing malaria parasites, studies should identify the factors that influence relapse pathogenesis, immunity, and infectiousness to mosquitoes.

"This study shows the explicit benefit of using a nonhuman primate model system to study the immune response and relate the findings to human clinical cases and transmission," states Dr. Galinski. "It is important to know that asymptomatic individuals may carry infectious gametocytes."

Dr. Lamb adds, "This study reveals the role of B cells in the control of relapsing malaria."

Finally Dr. Lee adds, "The nonhuman primate model is ideal to study the true memory B cell responses during relapsing malaria because this question is difficult to answer in human studies."

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Research Article

Funding: This project was funded in part by Federal funds from the US National Institute of Allergy and Infectious Diseases (https://www.niaid.nih.gov), National Institutes of Health, Department of Health and Human Services under contract # HHSN272201200031C (PI: Mary R. Galinski), which established the Malaria Host-Pathogen Interaction Center (MaHPIC), as well as the Office of Research Infrastructure Programs/OD P51OD011132. The Yerkes NHP Genomics Core is supported in part by ORIP/OD P51OD011132. Additional support was provided by 1R01AI121252, 1P01AI125180, P01A1078907, U19AI109962, and 1R01AI123425. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Joyner CJ, Brito CFA, Saney CL, Joice Cordy R, Smith ML, Lapp SA, et al. (2019) Humoral immunity prevents clinical malaria during Plasmodium relapses without eliminating gametocytes. PLoS Pathog 15(9): e1007974. https://doi.org/10.1371/journal.ppat.1007974

Author Affiliations:
Malaria Host-Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States of America
Division of Pulmonary, Allergy, Critical Care, & Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, United States of America
Laboratory of Malaria, Centro de Pesquisas René Rachou-Fiocruz, Belo Horizonte, MG, Brazil
Department of Biology, Wake Forest University, Winston-Salem, North Carolina, United States of America
School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, United States of America
Department of Genetics, University of Georgia, Athens, GA, United States of America
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, United States of America
Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT, United States of America

In your coverage please use this URL to provide access to the freely available paper: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007974

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