No more monkeying around: primate malaria model systems are key to understanding Plasmodium vivax liver-stage biology, hypnozoites, and relapses.

Chester Joyner,John W Barnwell,Mary R Galinski

doi:10.3389/fmicb.2015.00145

Abstract

Plasmodium vivax is a human malaria parasite responsible for significant morbidity worldwide and potentially death. This parasite possesses formidable liver-stage biology that involves the formation of dormant parasites known as hypnozoites. Hypnozoites are capable of activating weeks, months, or years after a primary blood-stage infection causing relapsing bouts of illness. Elimination of this dormant parasitic reservoir will be critical for global malaria eradication. Although hypnozoites were first discovered in 1982, few advancements have been made to understand their composition and biology. Until recently, in vitro models did not exist to study these forms and studying them from human ex vivo samples was virtually impossible. Today, non-human primate (NHP) models and modern systems biology approaches are poised as tools to enable the in-depth study of P. vivax liver-stage biology, including hypnozoites and relapses. NHP liver-stage model systems for P. vivax and the related simian malaria species P. cynomolgi are discussed along with perspectives regarding metabolite biomarker discovery, putative roles of extracellular vesicles, and relapse immunobiology.

Highlights

Malaria is responsible for significant morbidity, mortality, and socioeconomic hardships in about 100 countries (World Health Organization, 2014)
Preventing relapse infections is especially important in light of research demonstrating that the majority of Plasmodium vivax malaria episodes are due to relapses, which result from the activation of dormant forms in the liver, and not from new, mosquito-borne infections (Betuela et al, 2012; White et al, 2014)
We have developed P. cynomolgi parasites with integrated transgenes, including a red fluorescent protein gene (Akinyi et al, 2012; unpublished data)

Summary

Introduction

Malaria is responsible for significant morbidity, mortality, and socioeconomic hardships in about 100 countries (World Health Organization, 2014). NHP-MALARIA MODELS OVERVIEW Non-human primate model systems have been instrumental in malaria research for decades whether for furthering basic understanding of Plasmodium biology, malaria pathogenesis, or preclinical investigations pertinent to developing new interventions (Coatney et al, 1971; Collins, 1974; Galinski and Barnwell, 2012; Beignon et al, 2014).

Results

Conclusion