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

Joyner C, Barnwell JW, Galinski MR - Front Microbiol (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Malaria Host-Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University Atlanta, GA, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Shared infection characteristics of human and simian malaria parasites..
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Figure 1: Shared infection characteristics of human and simian malaria parasites..

Mentions: To investigate hypnozoites and relapses, Aotus or Saimiri species can be infected with NHP-adapted P. vivax strains via mosquito inoculation or syringe injection of sporozoites into a blood vessel (Table 1; Galinski and Barnwell, 2012; Galinski et al., 2013). Similar to human infections, relapsing, recrudescing, or chronic infection profiles can be observed in these models provided the animals are splenectomized to interfere with an overly robust removal of infected erythrocytes (Figure 1). In contrast to relapses, recrudescences are the result of untreated or persistent blood-stage infections that become sub-patent, below the level of detection by microscopy, followed by an eventual return to patency; such recurring parasitemias are distinct from relapse parasitemias that are due to the activation of hypnozoites and release of a new brood of merozoites from the liver.


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

Joyner C, Barnwell JW, Galinski MR - Front Microbiol (2015)

Shared infection characteristics of human and simian malaria parasites..
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4374475&req=5

Figure 1: Shared infection characteristics of human and simian malaria parasites..
Mentions: To investigate hypnozoites and relapses, Aotus or Saimiri species can be infected with NHP-adapted P. vivax strains via mosquito inoculation or syringe injection of sporozoites into a blood vessel (Table 1; Galinski and Barnwell, 2012; Galinski et al., 2013). Similar to human infections, relapsing, recrudescing, or chronic infection profiles can be observed in these models provided the animals are splenectomized to interfere with an overly robust removal of infected erythrocytes (Figure 1). In contrast to relapses, recrudescences are the result of untreated or persistent blood-stage infections that become sub-patent, below the level of detection by microscopy, followed by an eventual return to patency; such recurring parasitemias are distinct from relapse parasitemias that are due to the activation of hypnozoites and release of a new brood of merozoites from the liver.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Malaria Host-Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University Atlanta, GA, USA.

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.

No MeSH data available.


Related in: MedlinePlus