Plasmodium vivax Latent Liver Stage Infection and Relapse: Biological Insights and New Experimental Tools

Author:

Schäfer Carola1,Zanghi Gigliola1,Vaughan Ashley M.12,Kappe Stefan H.I.123

Affiliation:

1. Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington 98109, USA;, , ,

2. Department of Pediatrics, University of Washington, Seattle, Washington 98105, USA

3. Department of Global Health, University of Washington, Seattle, Washington 98195, USA

Abstract

Plasmodium vivax is the most widespread human malaria parasite, in part because it can form latent liver stages known as hypnozoites after transmission by female anopheline mosquitoes to human hosts. These persistent stages can activate weeks, months, or even years after the primary clinical infection; replicate; and initiate relapses of blood stage infection, which causes disease and recurring transmission. Eliminating hypnozoites is a substantial obstacle for malaria treatment and eradication since the hypnozoite reservoir is undetectable and unaffected by most antimalarial drugs. Importantly, in some parts of the globe where P. vivax malaria is endemic, as many as 90% of P. vivax blood stage infections are thought to be relapses rather than primary infections, rendering the hypnozoite a major driver of P. vivax epidemiology. Here, we review the biology of the hypnozoite and recent discoveries concerning this enigmatic parasite stage. We discuss treatment and prevention challenges, novel animal models to study hypnozoites and relapse, and hypotheses related to hypnozoite formation and activation.

Publisher

Annual Reviews

Subject

Microbiology

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