Plasmodium falciparum: Enhanced Gametocyte Formationin Vitroin Reticulocyte-Rich Blood

Trager, William; Gill, Gokal S.; Lawrence, Christine; Nagel, Ronald L.

doi:10.1006/expr.1998.4347

Cited by 75 publications

(59 citation statements)

References 8 publications

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“…Importantly though, only gametocytes, the sexual stages that are infective to mosquitoes, are important in malaria transmission. The factors triggering gametocyte development are unclear, but young erythrocytes and reticulocytes have been implicated in gametocyte development both experimentally and in field studies (33,41,42). Indeed, in both the P. fragile-infected and SIV-P. fragile-coinfected animals, we observed an increase in the percentage of gametocytes, both absolute and relative to total parasite number, during the initial drop in hematocrit (see Fig.…”

Section: Resultsmentioning

confidence: 71%

Evidence for an Increased Risk of Transmission of Simian Immunodeficiency Virus and Malaria in a Rhesus Macaque Coinfection Model

Trott

Chau

Hudgens

et al. 2011

J Virol

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In sub-Saharan Africa, HIV-1 infection frequently occurs in the context of other coinfecting pathogens, most importantly, Mycobacterium tuberculosis and malaria parasites. The consequences are often devastating, resulting in enhanced morbidity and mortality. Due to the large number of confounding factors influencing pathogenesis in coinfected people, we sought to develop a nonhuman primate model of simian immunodeficiency virus (SIV)-malaria coinfection. In sub-Saharan Africa, Plasmodium falciparum is the most common malaria parasite and is responsible for most malaria-induced deaths. The simian malaria parasite Plasmodium fragile can induce clinical symptoms, including cerebral malaria in rhesus macaques, that resemble those of P. falciparum infection in humans. Thus, based on the well-characterized rhesus macaque model of SIV infection, this study reports the development of a novel rhesus macaque SIV-P. fragile coinfection model to study human HIV-P. falciparum coinfection. Using this model, we show that coinfection is associated with an increased, although transient, risk of both HIV and malaria transmission. Specifically, SIV-P. fragile coinfected macaques experienced an increase in SIV viremia that was temporarily associated with an increase in potential SIV target cells and systemic immune activation during acute parasitemia. Conversely, primary parasitemia in SIV-P. fragile coinfected animals resulted in higher gametocytemia that subsequently translated into higher oocyst development in mosquitoes. To our knowledge, this is the first animal model able to recapitulate the increased transmission risk of both HIV and malaria in coinfected humans. Therefore, this model could serve as an essential tool to elucidate distinct immunological, virological, and/or parasitological parameters underlying disease exacerbation in HIV-malaria coinfected people.

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Section: Resultsmentioning

confidence: 71%

Evidence for an Increased Risk of Transmission of Simian Immunodeficiency Virus and Malaria in a Rhesus Macaque Coinfection Model

Trott

Chau

Hudgens

et al. 2011

J Virol

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“…There are strong indications that the triggering of the gametocyte pathway is affected by the presence of reticulocytes or very young erythrocytes (479,482), which are characterized by a relatively high RNA content, hemoglobin synthesis, and the fact that they are less dense than mature erythrocytes (479). Reticulocytes are the preferred cells for gametocyte development (157), and their formation is increased in erythropoiesis, induced by the production of erythropoietin (EPO) by anemic hosts.…”

Section: What Triggers the Sexual Pathway?mentioning

confidence: 99%

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

2011

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SUMMARY Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.

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“…Other annotated genes, however, encoded molecules, which do not play obvious roles in sexual differentiation, such as three merozoite surface proteins and one erythrocyte and one retyculocyte binding antigens. Although it might be tempting to speculate that presence of the latter is related to the observed increased efficiency of gametocyte production in young red blood cells [36], differential expression of such transcripts are more likely due to parasite clone-specific gene expression or uncontrolled environmental differences between the asexual parasites in the 3D7 and F12 cultures.…”

Section: Analysis Of the Gene Cluster Upregulated In 3d7 Parasitesmentioning

confidence: 99%

Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum

Silvestrini

Bozdech

Lanfrancotti

et al. 2005

Molecular and Biochemical Parasitology

147

148

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A genome-wide expression analysis was undertaken to identify novel genes specifically activated from early stages of gametocytogenesis in Plasmodium falciparum. A comparative analysis was conducted on sexually induced cultures of reference parasite clone 3D7 and its gametocyteless derivative clone F12. Competitive hybridisations on long-oligomer microarrays representing 4488 P. falciparum genes identified a remarkably small number of transcripts differentially produced in the two clones. Upregulation of the mRNAs for the early gametocyte markers Pfs16 and Pfg27 was however readily detected in 3D7, and such genes were used as reference transcripts in a comparative time course analysis of 3D7 and F12 parasites between 30 and 40 h post-invasion in cultures induced to enter gametocytogenesis. One hundred and seventeen genes had expression profiles which correlated to those of pfs16 and pfg27, and Northern blot analysis and published proteomic data identified those whose expression was gametocyte-specific. Immunofluorescence analysis with antibodies against two of these gene products identified two novel parasite membrane associated, sexual stage-specific proteins. One was produced from stage I gametocytes and the second showed peak production in stage II gametocytes. The two proteins were named Pfpeg-3 and Pfpeg-4, for P. falciparum proteins of early gametocytes.

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Plasmodium falciparum: Enhanced Gametocyte Formationin Vitroin Reticulocyte-Rich Blood

Cited by 75 publications

References 8 publications

Evidence for an Increased Risk of Transmission of Simian Immunodeficiency Virus and Malaria in a Rhesus Macaque Coinfection Model

Evidence for an Increased Risk of Transmission of Simian Immunodeficiency Virus and Malaria in a Rhesus Macaque Coinfection Model

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum

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