Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi

Abstract

c Malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n ‫؍‬ 8 each) and a schistosomiasis control group (n ‫؍‬ 3) were infected with 500 Schistosoma mansoni cercariae. At 14 and 15 weeks postinfection, one group was given praziquantel to treat schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n ‫؍‬ 8) were intravenously inoculated with 10 5 Plasmodium knowlesi parasites and monitored daily for development of severe malaria. A total of 81% of baboons exposed to chronic S. mansoni infection with or without praziquantel treatment survived malaria, compared to only 25% of animals infected with P. knowlesi only (P ‫؍‬ 0.01). Schistosome-infected animals also had significantly lower parasite burdens (P ‫؍‬ 0.004) than the baboons in the P. knowlesi-only group and were protected from severe anemia. Coinfection was associated with increased spontaneous production of interleukin-6 (IL-6), suggesting an enhanced innate immune response, whereas animals infected with P. knowlesi alone failed to develop mitogen-driven tumor necrosis factor alpha and IL-10, indicating the inability to generate adequate protective and balancing immunoregulatory responses. These results indicate that chronic S. mansoni attenuates the severity of P. knowlesi coinfection in baboons by mechanisms that may enhance innate immunity to malaria. P olyparasitism is common in low-resource countries, especially in sub-Saharan Africa. Coinfections may alter disease outcomes and affect both drug and vaccine efficacies (1, 2). The majority of studies on coinfections have focused on interactions between malaria and chronic helminth infections. Interest in studying malaria and schistosomiasis, in particular, comes from the major overlap of the two diseases in areas where they are endemic and the fact that these infections account for a large proportion of global morbidity and mortality (3, 4). Because of the chronicity of schistosome infection, most studies have focused on its impact on susceptibility to clinical malaria.Studies on malaria and schistosomiasis coinfections in human and animal models have generated contradicting results. Although some animal studies have shown that chronic schistosomiasis protects against severe malaria (5), others have reported that a concurrent schistosome infection enhances the severity of malaria (6-10). Many factors may account for these differences, including mouse strain, duration and intensity of the helminth infection, Plasmodium strain or species, inoculum size, or route of malaria infection (skin or blood stage) (11). An important limitat...

An investigation into the role of chronic Schistosoma mansoni infection on Human Papillomavirus (HPV) vaccine induced protective responses

“…This study involved a total of ten Olive baboons (Papio anubis) which were housed at the Institute of Primate Research (IPR [www.primateresearch.org]), Karen, Nairobi, Kenya. This was according to institutional standards and guidelines for primate welfare and housing based on the International Guiding principles for Biomedical [30].…”

“…Both grouped and individual cages were designed to allow natural light and dark cycles and they had ad libitum access to water. They were fed daily with monkey cubes (Unga Farm Care, Ltd, Nairobi, Kenya) and supplemented with fruits and vegetables [30].…”

“…The buffy coat containing the Peripherial blood mononuclear cells was collected and washed twice with 1X PBS at 1500rpm for 10 minutes at 4˚C. The isolated PBMCs were cultures to determine antigen specific T cell reactivity and cytokine production as previously described [30]. Under sterile conditions, PBMCs (1 X 10 6 cells) were plated in 48-well culture plates in 1 ml of complete culture media (RPMI-1640; Sigma-Aldrich, St. Louis, MO, 10%FBS; Gibco, Canada, 1%HEPES; Sigma-Aldrich, Dorset, UK, 1% Gentamycin; Sigma-Aldrich, Dorset, UK, 1% L-glutamin; Fisher Biotech, Wembley, Australia).…”

“…Antigen-specific IL-4 and IFN-γ were detected from culture supernatants at 48 and 72 hours respectively using Human IL-4 ELISA (Mabtech, Sweden) and Monkey IFN-γ ELISA (Ucytech, Netherlands) kits, as indicated by the manufactures instructions and as previously described [30]. Briefly, the supernatants were thawed and diluted with Dilution buffer (PBS 0.5% (w/v) BSA 0.05% (w/v) Tween-20) at a ratio of 1:1.…”

Schistosoma mansoni infection suppresses the growth of Plasmodium yoelii parasites in the liver and reduces gametocyte infectivity to mosquitoes

“…Most laboratory-based animal studies have shown an exacerbation of malaria parasitaemia in Schistosoma infected mice [ 10 – 13 ] whilst others have revealed a protective effect of Schistosoma infection against experimental cerebral malaria and associated mortality [ 14 – 17 ]. In experimental S .…”