Plasmodium coatneyi-infected rhesus monkeys: a primate modelfor human cerebral malaria

Aikawa, Masamichi; Brown, Arthur E.; Smith, Christopher; Tegoshi, Tatsuya; Howard, Russell J.; Hasler, Thomas; Ito, Yoichi; Collins, William E.; Webster, H. K.

doi:10.1590/s0074-02761992000700074

Cited by 9 publications

(11 citation statements)

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“…21,22 Experimental infections of rhesus monkeys with P. coatneyi reproduce several histopathologic findings reported in humans infected with P. falciparum. 17,18,[23][24][25] We describe here the first case of disseminated intravascular coagulation (DIC) and peripheral gangrene in a rhesus macaque experimentally infected with P. coatneyi. Although platelet dysfunction and increased pro-coagulant activity is a common finding in severe malaria, DIC complicated with symmetrical peripheral gangrene is very rare.…”

Section: Introductionmentioning

confidence: 99%

Disseminated Intravascular Coagulation Complicated by Peripheral Gangrene in a Rhesus Macaque (Macaca Mulatta) Experimentally Infected With Plasmodium Coatneyi

Moreno¹,

García²,

Cabrera-Mora³

et al. 2007

The American Journal of Tropical Medicine and Hygiene

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We report the first case of disseminated intravascular coagulation (DIC) complicated by peripheral gangrene induced by Plasmodium coatneyi in rhesus monkeys. Ten days after experimental challenge, numerous petechiae were noted over the trunk and extremities, with polychromasia, severe anemia, thrombocytopenia, and moderate parasitemia. These changes were accompanied by elevated serum activity of blood urea nitrogen, creatinine, transaminases, and creatinine phosphokinase. The animal received intravenous fluid support, artemether, and blood transfusion. Three days after treatment, the platelet counts returned to normal, and parasitemia was abated. However, several areas of skin discoloration with gangrenous tissue in the hands and the tail were observed. Coagulation profile showed elevated D-dimers and elevated levels of fibrinogen/fibrin degradation products with low levels of protein S functional activity. DIC with peripheral gangrene is very rare in Plasmodium-infected individuals. Our results indicate that the experimental model of P. coatneyi infection of rhesus monkeys is important for studies of malarial anemia and coagulopathy.

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Section: Introductionmentioning

confidence: 99%

Disseminated Intravascular Coagulation Complicated by Peripheral Gangrene in a Rhesus Macaque (Macaca Mulatta) Experimentally Infected With Plasmodium Coatneyi

Moreno¹,

García²,

Cabrera-Mora³

et al. 2007

The American Journal of Tropical Medicine and Hygiene

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“…Various investigators have studied P. coatneyi in terms of its morphology, [1][2][3][4][5] physiology, [6][7][8][9][10][11] ultrastructure, 5,12 pathology, [13][14][15][16][17][18][19][20] in vitro culture, [21][22][23][24][25] immunology, [26][27][28][29][30][31][32][33][34][35] sequestration, [36][37][38][39][40][41][42] transmission, [1][2][3]29,[43][44][45][46] chemotherapy, …”

Section: Introductionmentioning

confidence: 99%

Plasmodium coatneyi: observations on periodicity, mosquito infection, and transmission to Macaca mulatta monkeys.

Collins

Warren²,

Sullivan³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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Abstract. Plasmodium coatneyi has adapted well to experimental studies with Macaca mulatta monkeys and Anopheles dirus mosquitoes. Studies were made to determine 1) the course of asexual parasitemia, 2) periods when infective gametocytes were produced, 3) the laboratory-reared mosquitoes susceptible to infection, 4) the mosquito most capable of transmitting the infection to monkeys via bite, 5) the pattern of recrudescence, and 6) the prepatent periods following the bites of infected An. dirus mosquitoes. The period when infective gametocytes are produced is concentrated primarily in the first week when parasitemia exceeds 1,000/l. Mosquitoes were more heavily infected on days when the asexual parasite counts were highest. Gametocyte counts were generally low. Mature forms of the parasite markedly sequestered giving a pattern of high-low periodicity. Anopheles dirus and An. freeborni mosquitoes were nearly equal in terms of their ability to support oocyst development. Other species (An. stephensi, An. maculatus, and An. gambiae,) were less supportive. High sporozoite densities in the salivary glands were frequently produced in An. dirus and sporozoite transmission was obtained via the bites of these mosquitoes after 12-18 days of extrinsic incubation. Prepatent periods ranged from 10 to 15 days. The presence of frequent parasitic recrudescences suggests mechanisms similar to that seen in human infections with P. falciparum. It is proposed that P. coatneyi in M. mulatta monkeys can be a suitable model for studies on cerebral pathology, vaccine efficacy, and the testing of antimalarial drugs.

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“…In contrast, P. fragile infection is more readily controlled (11). Further, P. fragile can be continuously cultured in vitro (9) and, therefore, has been more frequently used for drug and vaccine studies than has P. coatneyi (4,15,21,43). Lastly, P. fragile is not infectious to humans (49), which is an important consideration for biosafety management.…”

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confidence: 99%

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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Plasmodium coatneyi-infected rhesus monkeys: a primate modelfor human cerebral malaria

Cited by 9 publications

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Disseminated Intravascular Coagulation Complicated by Peripheral Gangrene in a Rhesus Macaque (Macaca Mulatta) Experimentally Infected With Plasmodium Coatneyi

Disseminated Intravascular Coagulation Complicated by Peripheral Gangrene in a Rhesus Macaque (Macaca Mulatta) Experimentally Infected With Plasmodium Coatneyi

Plasmodium coatneyi: observations on periodicity, mosquito infection, and transmission to Macaca mulatta monkeys.

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

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