Parasite accumulation in placenta of non-immune baboons during Plasmodium knowlesi infection

Abstract

BackgroundPlacental malaria (PM) causes adverse pregnancy outcomes in the mother and her foetus. It is difficult to study PM directly in humans due to ethical challenges. This study set out to bridge this gap by determining the outcome of PM in non-immune baboons in order to develop a non-human primate model for the disease.MethodsTen pregnant baboons were acquired late in their third trimester (day 150) and randomly grouped as seven infected and three non-infected. Another group of four nulligravidae (non-pregnant) infected was also included in the analysis of clinical outcome. Malaria infection was intravenously initiated by Plasmodium knowlesi blood-stage parasites through the femoral vein on 160th day of gestation (for pregnant baboons). Peripheral smear, placental smear, haematological samples, and histological samples were collected during the study period. Median values of clinical and haematological changes were analysed using Kruskal-Wallis and Dunn’s Multiple Comparison Test. Parasitaemia profiles were analysed using Mann Whitney U test. A Spearman’s rank correlation was run to determine the relationship between the different variables of severity scores. Probability values of P <0.05 were considered significant.ResultsLevels of white blood cells increased significantly in pregnant infected (34%) than in nulligravidae infected baboons (8%). Placental parasitaemia levels was on average 19-fold higher than peripheral parasitaemia in the same animal. Infiltration of parasitized erythrocytes and inflammatory cells were also observed in baboon placenta. Malaria parasite score increased with increase in total placental damage score (rs = 0.7650, P <0.05) and inflammatory score (rs = 0.8590, P <0.05). Although the sample size was small, absence of parasitized erythrocytes in cord blood and foetal placental region suggested lack of congenital malaria in non-immune baboons.ConclusionThis study has demonstrated accumulation of parasitized red blood cells and infiltration of inflammatory cells in the placental intravillous space (IVS) of baboons that are non-immune to malaria. This is a key feature of placental falciparum malaria in humans. This presents the baboon as a new model for the characterization of malaria during pregnancy.

Plasmodium knowlesi:a superbin vivononhuman primate model of antigenic variation in malaria

“…Miller et al . described extensive P. knowlesi schizogony in several tissues in rhesus monkeys (Miller et al 1971 ), and more recent studies showed P. knowlesi iRBC distribution in baboon tissues (Ozwara et al 2003 ; Onditi et al 2015 ). Additionally, unlike P. falciparum and P. coatneyi , the P. knowlesi variant antigens are not concentrated at parasite-induced protrusions at the RBC surface (reviewed in Galinski and Corredor, 2004 ).…”

Syncytiotrophoblast Functions and Fetal Growth Restriction during Placental Malaria: Updates and Implication for Future Interventions

“…However, the mTOR inhibitor failed to impede inflammation. Further research on the role of mTOR is necessary in placental malaria animal model, such as the baboon, where Plasmodium knowlesi have been shown to sequester to the placenta [ 83 ]. On the other hand, in vitro studies using the BeWo cell line exposed to malaria-associated cytokines plus chemokines (secreted by human monocytic cell line (THP1) cells that were incubated with P. falciparum infected red blood cells) induced dysregulation of mTOR pathway [ 61 ], suggesting that mTOR pathway in ST might be interfered by placental malaria-inflammatory-cytokines.…”

Infection by Brucella melitensis or Brucella papionis modifies essential physiological functions of human trophoblasts

“…Because Papio sp. are widely used as an animal model to study human reproduction (including placental infection-related pathologies;Onditi et al, 2015) because of their high similarities in placental structure and fetal development(Bauer, 2015), infection with B. papionis in these primatesmight constitute a relevant in vivo model to study Brucella-induced placental disorders. Interestingly, B. papionis replicates actively within human CTB or SYN but only survives in EVT.…”