Enhanced Gametocyte Formation in Young Erythrocytes by <i>Plasmodium falciparum</i> In Vitro

Trager, William; Gill, Gokal S.

doi:10.1111/j.1550-7408.1992.tb01476.x

Cited by 82 publications

(60 citation statements)

References 16 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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“…Nutrients present within the infected erythrocyte would be exhausted by the developing parasite over this prolonged time period (33,36) and may be a factor in the difficulty of inducing gametocyte formation in vitro. Immature erythrocytes (reticulocytes) supported better gametocyte formation than did mature erythrocytes (84). Other factors affecting gametocyte formation may include variations in nutrients present in serum supplements of growth medium, absence of essential activating factors in RPMI 1640, and selection of non-gametocyte-forming populations under in vitro conditions.…”

Section: Gametocytogenesismentioning

confidence: 99%

Cultivation of Plasmodium spp

Schuster

2002

Clin Microbiol Rev

102

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Cultivation of both human and non-human species of Plasmodium spp., the causal agent of malaria, has been a major research success, leading to a greater understanding of the parasite. Efforts at cultivating the organisms in vitro are complicated by the parasites' alternating between a human host and an arthropod vector, each having its own set of physiological, metabolic, and nutritional parameters. Life cycle stages of the four species that infect humans have been established in vitro. Of these four, P. falciparum remains the only species for which all stages have been cultured in vitro; different degrees of success have been achieved with the other human Plasmodium spp. The life cycle includes the exoerythrocytic stage (within liver cells), the erythrocytic stage (within erythrocytes or precursor reticulocytes), and the sporogonic stage (within the vector). Culture media generally consist of a basic tissue culture medium (e.g., minimal essential medium or RPMI 1640) to which serum and erythrocytes are added. Most of the efforts have been directed toward the stage found in the erythrocyte. This stage has been cultivated in petri plates or other growth vessels in a candle jar to generate elevated CO2 levels or in a more controlled CO2 atmosphere. Later developments have employed continuous-flow systems to reduce the labor-intensive nature of medium changing. The exoerythrocytic and sporogonic life cycle stages have also been cultivated in vitro. A number of avian, rodent, and simian malarial parasites have also been established in vitro. Although cultivation is of great help in understanding the biology of Plasmodium, it does not lend itself to use for diagnostic purposes

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“…The initiation of gametocytogenesis and modulation of gametocyte production in a natural infection is influenced by host environmental factors, including stress induced by host immunity , antimalarial drug treatment (Dunyo et al 2006), or anemia (Nacher et al 2002), as well as host genetic factors such as human hemoglobin variants ( Fig. 1, see inset, top) (Trager and Gill 1992;Gouagna et al 2010). Similarly, under in vitro conditions, increased gametocyte production was seen at higher parasite densities (Bruce et al 1990), in the presence of parasite-conditioned medium (Williams 1999;Dyer and Day 2003), and, on addition of human serum , erythroid progenitor cells (Peatey et al 2013) or antimalarial drugs (Buckling et al 1999).…”

Section: Mechanisms Of Sexual Commitment and Gametocyte Sequestrationmentioning

confidence: 99%

Biology of Malaria Transmission

Meibalan

Marti

2016

Cold Spring Harb Perspect Med

138

137

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Understanding transmission biology at an individual level is a key component of intervention strategies that target the spread of malaria parasites from human to mosquito. Gametocytes are specialized sexual stages of the malaria parasite life cycle developed during evolution to achieve crucial steps in transmission. As sexual differentiation and transmission are tightly linked, a deeper understanding of molecular and cellular events defining this relationship is essential to combat malaria. Recent advances in the field are gradually revealing mechanisms underlying sexual commitment, gametocyte sequestration, and dynamics of transmissible stages; however, key questions on fundamental gametocyte biology still remain. Moreover, species-specific variation between Plasmodium falciparum and Plasmodium vivax transmission dynamics pose another significant challenge for worldwide malaria elimination efforts. Here, we review the biology of transmission stages, highlighting numerous factors influencing development and dynamics of gametocytes within the host and determinants of human infectiousness. C urrent measures for malaria elimination have been inspired by the Global Malaria Eradication Program (GMEP), which operated under the World Health Organization (WHO) between 1955 and 1969. The strategy of GMEP was largely based on dichlorodiphenyltrichloroethane (DDT)-based indoor residual spraying (DDT-IRS) complemented with mass drug administration (Pampana 1969). Although GMEP was able to eliminate malaria from many regions of the world, it was eventually abandoned because of technical challenges, increasing spread of both insecticide resistance and drug-resistant parasite strains, and lack of continuous political support (Najera et al. 2011 ual parasites and early transmission stages, whereas mature infectious transmission stages are unaffected. To block transmission, ACT is often combined with the only transmissionblocking drug on the market, Primaquine. However, recent emergence of artemisinin resistance in Southeast Asia asks for urgent evaluation of alternative treatment strategies (Noedl et al. 2008;Dondorp et al. 2009;Mbengue et al. 2015;Straimer et al. 2015).Of the five Plasmodium species known to cause malaria in humans, Plasmodium falciparum is lethal and responsible for severe disease pathology and the majority of deaths due to malaria, especially in sub-Saharan Africa. Plasmodium vivax typically causes milder infections than P. falciparum but has a much greater geographical distribution (Gething et al. 2012). The clinical symptoms of malaria are largely a result of the replication of asexual stages in human blood, but transmission to mosquitoes is only achieved through the development of sexual stages, termed gametocytes. To abrogate transmission of P. falciparum, we must be able to clear asexual and sexual stages from the human host, eventually rendering an individual noninfectious to mosquitoes. However, in the case of P. vivax, elimination is highly challenging because of the relapse of dormant liver-stage h...

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Enhanced Gametocyte Formation in Young Erythrocytes by Plasmodium falciparum In Vitro

Cited by 82 publications

References 16 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

Cultivation of Plasmodium spp

Biology of Malaria Transmission

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