The hypnozoite and relapse in primate malaria

Cogswell, Frank B.

doi:10.1128/cmr.5.1.26

Cited by 128 publications

(135 citation statements)

References 62 publications

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“…This raises the hypothesis that parasites might become quiescent when associated with hair follicles and act as a source of infection relapses, as proposed for the hypnozoites of P. vivax in the liver (31).…”

Section: Discussionmentioning

confidence: 99%

Development of the malaria parasite in the skin of the mammalian host

Gueirard

Tavares²,

Thiberge³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

122

109

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The first step of Plasmodium development in vertebrates is the transformation of the sporozoite, the parasite stage injected by the mosquito in the skin, into merozoites, the stage that invades erythrocytes and initiates the disease. The current view is that, in mammals, this stage conversion occurs only inside hepatocytes. Here, we document the transformation of sporozoites of rodentinfecting Plasmodium into merozoites in the skin of mice. After mosquito bite, ∼50% of the parasites remain in the skin, and at 24 h ∼10% are developing in the epidermis and the dermis, as well as in the immunoprivileged hair follicles where they can survive for weeks. The parasite developmental pathway in skin cells, although frequently abortive, leads to the generation of merozoites that are infective to erythrocytes and are released via merosomes, as typically observed in the liver. Therefore, during malaria in rodents, the skin is not just the route to the liver but is also the final destination for many inoculated parasites, where they can differentiate into merozoites and possibly persist.intravital imaging | Plasmodium | schizogony M alarial infection starts with the inoculation of Plasmodium sporozoites by mosquitoes probing the vertebrate skin for blood. The highly motile sporozoites eventually invade host target cells where they differentiate and divide into numerous merozoites, the parasite form that invades erythrocytes and initiates the pathogenic phase of malarial infection. The host cell type in which sporozoites transform into merozoites, however, differs between Plasmodium species. In species that infect birds, sporozoites differentiate inside macrophages primarily in the skin but also in the spleen, liver, and bone marrow (1). In species that infect mammals, sporozoites are known to differentiate only inside hepatocytes in the liver (2-4).The first demonstration that sporozoites of mammal-infecting Plasmodium species develop inside hepatocytes was made in 1948 after i.v. inoculation of sporozoites of P. cynomologi into rhesus monkeys (2). In addition to reporting fully mature parasites inside hepatocytes, the authors also documented the persistence of immature and dormant forms of the parasite in the liver several months after the initial inoculation, which they proposed to be the cause of relapses (5), and were later called hypnozoites (6). Subsequent work indicated that sporozoites of species that infect humans (7) also undergo complete development inside hepatocytes.Since these early studies, P. berghei and the related P. yoelii species, which infect rodents, have been used as practical and safe models for studying the pre-erythrocytic phase of malaria. These parasites were shown to differentiate in the liver of laboratory rodents (8), and the P. berghei/rodent system was used to demonstrate that the majority of sporozoites were inoculated by mosquitoes in the skin rather than directly into the blood circulation (9), as traditionally assumed. More recently, the generation of fluorescent P. berghei parasites, alo...

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Section: Discussionmentioning

confidence: 99%

Development of the malaria parasite in the skin of the mammalian host

Gueirard

Tavares²,

Thiberge³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

122

109

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“…It has long been known that there is significant geographical variation in the rate at which a 'strain' of P. vivax may relapse (Coatney and Cooper, 1948;Winckel, 1955;Garnham et al, 1975). The exact mechanism through which hypnozoite relapses are triggered is unknown (Cogswell, 1992;Prudencio et al, 2006;Baird, 2009;Mueller et al, 2009a). One theory is that the mechanism is an adaptive trait of the parasite to sequester or 'hibernate' during times when climatic conditions would be inhospitable to the Anopheles vector of the disease (Shute et al, 1976;Baird and Rieckmann, 2003;White, 2011).…”

Section: The Global Distribution Of P Vivax Infectionsmentioning

confidence: 99%

The Global Public Health Significance of Plasmodium vivax

Battle

Gething

Elyazar

et al. 2012

Advances in Parasitology

113

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“…2,3 Similarities include a 48-hour asexual cycle, parasitemias within the same range as those of P. vivax, 4 and the capacity to produce relapses. 5 Macaca fascicularis is the natural host for P. knowlesi; thus, the rhesus Macaca mulatta is considered an experimental host. 2 It has a 24-hour cycle of schizogony, which replicates rapidly to produce extremely high parasitemias.…”

Section: Introductionmentioning

confidence: 99%

Cytokine responses during acute simian Plasmodium cynomolgi and Plasmodium knowlesi infections.

Praba-Egge¹,

Montenegro²,

Cogswell³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. Experimental infection of non-human primates with simian malaria parasites offers a controlled system to study malarial immunity. Plasmodium cynomolgi (P. vivax-like) and P. knowlesi (P. falciparum-like) infections in the rhesus monkey were used as a model to test the hypothesis that initial acute infection stimulates type 1/pro-inflammatory cytokine expression followed by a gradual type 2/anti-inflammatory response upon re-infection. This study analyzed cytokine gene expression (interleukin-12, interferon-␥, tumor necrosis factor-␣ ‫ס‬ type 1; interleukin-4, interleukin-10 ‫ס‬ type 2) using a semi-quantitative reverse transcriptase−polymerase chain reaction in monkeys infected with each of the parasites (three per group). Clinicoparasitologic and serologic parameters were also monitored. Monkeys were reinfected to assess whether enhanced immunity could increase parasite clearance. The immune response to P. cynomolgi infection in rhesus monkeys seemed to be mediated by anti-parasite, pro-inflammatory responses during primary infection with a transition to protective type 2 responses after repeat infection. The immune responses to P. knowlesi infection were more varied. Anti-inflammatory responses were more prevalent during primary infection. Repeat infection stimulated a wide variety of responses; most included expression of tumor necrosis factor-␣, a cytokine that has been associated with inflammatory and host-destructive effects (weight loss, fever, anemia). These observations further confirmed that the simian malaria/rhesus monkey model is well suited for studies on the regulation of immunity to acute Plasmodium infection.

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The hypnozoite and relapse in primate malaria

Cited by 128 publications

References 62 publications

Development of the malaria parasite in the skin of the mammalian host

Development of the malaria parasite in the skin of the mammalian host

The Global Public Health Significance of Plasmodium vivax

Cytokine responses during acute simian Plasmodium cynomolgi and Plasmodium knowlesi infections.

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