Pregnant women with malaria due to infection with Plasmodium falciparum suffer more adverse consequences than P. falciparum-infected nonpregnant women. The more common and serious sequelae include anemia and severe malaria with central nervous system complications. Their infants suffer intrauterine growth retardation (IUGR), low birth weight (LBW), congenital infection and high infant mortality. Although much information has been gleaned from human trials, the conditions, and moral and ethical limitations of human studies of pregnancy preclude manipulation of the system and important data are often uninterpretable due to confounding variables. Due to its close similarity to the human in its clinical and immunological responses to Plasmodium, the nonhuman primate has been widely used as a model to study malaria. Nonhuman primates are also the only animals with a villous, hemochorial placenta like that of man and are, therefore, the animal model of choice in studies of pregnancy. We have established a model of malaria during pregnancy by intravenously inoculating 10 rhesus monkeys (Macaca mulatta) during the first trimester with Plasmodium coatneyi, a """"""""falciparum-type parasite"""""""". All 10 monkeys became parasitemic 7-14 days post-inoculation (PI). Three aborted 7-10 days PI, coincident with high peak parasitemias (41,088-374,325 parasites per mm3), while 7 monkeys carried their infants to term. These 7 infants weighed significantly less at birth than did infants born to normal mothers (p=.0038). Placental weights in the Plasmodium-infected dams were lower than those of controls (p=.0455). Symmetrical IUGR was detected by ultrasound in 1 fetus with a birth weight of 334 grams. Another LBW infant (300 gms) had ultrasound measurments within the normal range. However, this infant's condition at birth was indicative of asymmetrical growth retardation, which is usually associated with uteroplacental insufficiency. The infant with symmetric IUGR died at 5 days of age while the other is alive but congenitally infected. The cord blood smear in the congenitally-infected infant was negative and parasitemia did not manifest itself until 80 days of age. Failure to recover from anemia during the later half of pregnancy was associated with early infant mortality in 4 infants. Histologically, placental lesions resembled those seen in human placentas infected with P. falciparum. The 6 placentas from P. coatneyi-infected dams had more significant pathologic changes than did the placentas from 5 control animals. Lesions indicative of malaria chronicity were related to IUGR and LBW. No correlation could be made between degree of placental damage and fetal mortality, birth weight, or congenital infection.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-36S1
Application #
2795489
Study Section
Project Start
Project End
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
36
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Tulane University
Department
Type
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Mahalingam, Ravi; Kaufer, Benedikt B; Ouwendijk, Werner J D et al. (2018) Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques. J Virol 92:
Kumar, Vinay; Mansfield, Joshua; Fan, Rong et al. (2018) miR-130a and miR-212 Disrupt the Intestinal Epithelial Barrier through Modulation of PPAR? and Occludin Expression in Chronic Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Immunol 200:2677-2689
Parthasarathy, Geetha; Philipp, Mario T (2018) Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. Neurosci Lett 671:38-42
McNamara, Ryan P; Costantini, Lindsey M; Myers, T Alix et al. (2018) Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses. MBio 9:
Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick et al. (2017) MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa. J Acquir Immune Defic Syndr 74:e67-e74
Datta, Dibyadyuti; Bansal, Geetha P; Grasperge, Brooke et al. (2017) Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques. Vaccine 35:7049-7056
Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Parthasarathy, Geetha; Philipp, Mario T (2017) Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi. J Neuroinflammation 14:110

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