Placental changes associated with fetal outcome in the Plasmodium coatneyi/rhesus monkey model of malaria in pregnancy.

Davison, Billie B.; Cogswell, Frank B.; Baskin, Gary B.; Falkenstein, Kathrine P.; Henson, Elizabeth W.; Krogstad, Donald J.

doi:10.4269/ajtmh.2000.63.158

Cited by 41 publications

(39 citation statements)

References 58 publications

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“…Abortions associated with malaria have also been reported in Plasmodium coatneyi-infected rhesus monkeys (8) and in late gestational P. berghei murine infection (31). Although an immunological basis has been attributed to malarial pathogenesis, few studies have been done to explore this possibility in severe pregnancy outcomes such as abortion and stillbirth, particularly during early gestation.…”

Section: Discussionmentioning

confidence: 99%

Association of Malaria-Induced Murine Pregnancy Failure with Robust Peripheral and Placental Cytokine Responses

Poovassery

Moore

2009

Infect Immun

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Malarial infection in nonimmune pregnant women is a major risk factor for pregnancy failure. The biological mechanisms that underlie malaria-associated fetal loss, however, are poorly understood. Plasmodium chabaudi AS infection during early pregnancy results in midgestational embryonic loss in naive C57BL/6 mice. To define the immunopathogenesis of this malaria-induced pregnancy compromise, cytokine production in plasma, spleen, and placenta cell culture supernatants during the first 11 days of infection and gestation was studied. In infected pregnant mice, systemic interleukin-1␤ and both systemic and splenic gamma interferon levels were elevated relative to those in uninfected pregnant mice, and gamma interferon was also robustly produced within the placenta 1 to 2 days before malaria-induced fetal loss. Although circulating tumor necrosis factor production was not affected by pregnancy or infection, circulating soluble tumor necrosis factor receptor II was highest in infected pregnant mice, particularly those undergoing abortion, but decreased at the placental level preceding abortion. Systemic levels of interleukin-10 were also high in infected mice at this time point, but this cytokine was not detected at the placental level. Histological examination revealed that trophoblast giant cells of aborting mice phagocytosed infected red blood cells and hemozoin. Furthermore, in vitro-cultured trophoblast cells isolated from embryos on day 7 of gestation phagocytosed P. chabaudi AS-infected red blood cells and secreted tumor necrosis factor. These results suggest that systemic and placenta-level proinflammatory antimalarial immune responses, in the absence of adequate and sustained counterregulatory mechanisms, contribute to pregnancy loss in this model.

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Section: Discussionmentioning

confidence: 99%

Association of Malaria-Induced Murine Pregnancy Failure with Robust Peripheral and Placental Cytokine Responses

Poovassery

Moore

2009

Infect Immun

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“…Some progress toward this end has been made using nonimmune, pregnant rhesus monkeys infected with Plasmodium coatneyi (16). In this model, infected monkeys experienced increased rates of abortion and intrauterine growth retardation associated with placental pathology (15,16). Also, the leukocyte profiles were altered in infected pregnant monkeys, with lower CD4 ϩ and CD8 ϩ T-cell and B-cell counts that were suggestive of pregnancy-associated immunomodulation (17).…”

Section: Discussionmentioning

confidence: 99%

Murine Malaria Infection Induces Fetal Loss Associated with Accumulation ofPlasmodium chabaudiAS-Infected Erythrocytes in the Placenta

2006

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Malarial infection in nonimmune women is a risk factor for pregnancy loss, but the role that maternal antimalarial immune responses play in fetal compromise is not clear. We conducted longitudinal and serial sacrifice studies to examine the pathogenesis of malaria during pregnancy using the Plasmodium chabaudi AS/C57BL/6 mouse model. Peak parasitemia following inoculation with 1,000 parasite-infected murine erythrocytes and survival were similar in infected pregnant and nonpregnant mice, although development of parasitemia and anemia was slightly accelerated in pregnant mice. Importantly, pregnant mice failed to maintain viable pregnancies, most aborting before day 12 of gestation. At abortion, maternal placental blood parasitemia was statistically significantly higher than peripheral parasitemia. Infected mice had similar increases in spleen size and cellularity which were statistically significantly higher than in uninfected mice. In contrast, splenocyte proliferation in response to mitogenic stimulation around peak parasitemia was statistically significantly reduced in both groups of infected mice compared to uninfected, nonpregnant mice, suggesting that lymphoproliferation is not a good indicator of the antimalarial immune responses in pregnant or nonpregnant animals. This study suggests that while pregnant and nonpregnant C57BL/6 mice are equally capable of mounting an effective immune response to and surviving P. chabaudi AS infection, pregnant mice cannot produce viable pups. Fetal loss appears to be associated with placental accumulation of infected erythrocytes. Further study is required to determine to what extent maternal antimalarial immune responses, anemia, and placental accumulation of parasites contribute to compromised pregnancy in this model.Malaria continues to be a major public health problem in the developing world, causing an estimated 300 to 500 million cases each year and 1 to 2 million deaths (3). In regions where malaria is endemic, the related morbidity and mortality are primarily borne by children and pregnant women. Although women living in areas of high endemicity acquire protective immunity against severe malaria, this protection is markedly compromised in the first and second pregnancies (5, 44) and is characterized by maternal anemia (33,41,56) and low birth weight babies (20,60,66) who are at increased risk to die early in life (60). In contrast, in areas with low or unstable transmission of malaria, exposure is not constant enough to result in effective immunity in the population. In these settings, pregnancy outcome is severely compromised, and pregnant women of all parities are at greater risk of developing severe disease than nonpregnant women. Pregnant women living in areas of low endemicity experience high rates of abortion, stillbirth, and low birth weight babies (47,55,57,58,79).Most of our understanding of the biological basis for the increased susceptibility of pregnant women to malarial infection is from studies conducted with pregnant women living in high-transmissio...

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“…60,78 It is significant that while increases in inducible liver enzymes are a common feature of severe malaria in adult humans, there are only rare reports of centrilobular hepatic necrosis. 20,24 Kidney. Kidneys from P. coatneyi-infected rhesus macaques in one study had varying degrees of acute tubular necrosis, accompanied by hyaline droplet degeneration characterized by expansion of the cytoplasm of the tubular epithelium with eosinophilic globules that are interpreted as possible protein resorption (Fig.…”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

“…Furthermore, there was typically infarction of the basal plate with small numbers of neutrophils admixed with pigment-laden macrophages. 20 Other Systems. Although other organ systems, such as the respiratory and hematopoietic systems, are involved in the pathophysiology of severe malaria in humans, the histopathologic examination of P. coatneyi infection in any species of NHP is significantly lacking.…”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

A Review of Plasmodium coatneyi–Macaque Models of Severe Malaria

et al. 2015

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Malaria remains one of the most significant public health concerns in the world today. Approximately half the human population is at risk for infection, with children and pregnant women being most vulnerable. More than 90% of the total human malaria burden, which numbers in excess of 200 million annually, is due to Plasmodium falciparum. Lack of an effective vaccine and a dwindling stockpile of antimalarial drugs due to increased plasmodial resistance underscore the critical need for valid animal models. Plasmodium coatneyi was described in Southeast Asia 50 years ago. This plasmodium of nonhuman primates has been used sporadically as a model for severe malaria, as it mimics many of the pathophysiologic features of human disease. This review covers the reported macroscopic, microscopic, ultrastructural, and molecular pathology of P. coatneyi infection in macaques, specifically focusing on the rhesus macaque, as well as describing the critical needs still outstanding in the validation of this crucial model of human disease.

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Placental changes associated with fetal outcome in the Plasmodium coatneyi/rhesus monkey model of malaria in pregnancy.

Cited by 41 publications

References 58 publications

Association of Malaria-Induced Murine Pregnancy Failure with Robust Peripheral and Placental Cytokine Responses

Association of Malaria-Induced Murine Pregnancy Failure with Robust Peripheral and Placental Cytokine Responses

Murine Malaria Infection Induces Fetal Loss Associated with Accumulation ofPlasmodium chabaudiAS-Infected Erythrocytes in the Placenta

A Review of Plasmodium coatneyi–Macaque Models of Severe Malaria

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