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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 (<jats:named-content content-type=\"genus-species\">Papio anubis<\/jats:named-content>) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (<jats:italic>n<\/jats:italic>= 8 each) and a schistosomiasis control group (<jats:italic>n<\/jats:italic>= 3) were infected with 500<jats:named-content content-type=\"genus-species\">Schistosoma mansoni<\/jats:named-content>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 (<jats:italic>n<\/jats:italic>= 8) were intravenously inoculated with 10<jats:sup>5<\/jats:sup><jats:named-content content-type=\"genus-species\">Plasmodium knowlesi<\/jats:named-content>parasites and monitored daily for development of severe malaria. A total of 81% of baboons exposed to chronic<jats:named-content content-type=\"genus-species\">S. mansoni<\/jats:named-content>infection with or without praziquantel treatment survived malaria, compared to only 25% of animals infected with<jats:named-content content-type=\"genus-species\">P. knowlesi<\/jats:named-content>only (<jats:italic>P<\/jats:italic>= 0.01). Schistosome-infected animals also had significantly lower parasite burdens (<jats:italic>P<\/jats:italic>= 0.004) than the baboons in the<jats:named-content content-type=\"genus-species\">P. knowlesi<\/jats:named-content>-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<jats:named-content content-type=\"genus-species\">P. knowlesi<\/jats:named-content>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<jats:named-content content-type=\"genus-species\">S. mansoni<\/jats:named-content>attenuates the severity of<jats:named-content content-type=\"genus-species\">P. knowlesi<\/jats:named-content>coinfection in baboons by mechanisms that may enhance innate immunity to malaria.<\/jats:p>","DOI":"10.1128\/iai.00490-15","type":"journal-article","created":{"date-parts":[[2016,2,17]],"date-time":"2016-02-17T03:58:22Z","timestamp":1455681502000},"page":"1320-1330","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi"],"prefix":"10.1128","volume":"84","author":[{"given":"Ruth K.","family":"Nyakundi","sequence":"first","affiliation":[{"name":"Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya"},{"name":"University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onkoba","family":"Nyamongo","sequence":"additional","affiliation":[{"name":"Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeneby","family":"Maamun","sequence":"additional","affiliation":[{"name":"Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercy","family":"Akinyi","sequence":"additional","affiliation":[{"name":"Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Mulei","sequence":"additional","affiliation":[{"name":"Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idle O.","family":"Farah","sequence":"additional","affiliation":[{"name":"Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D'Arbra","family":"Blankenship","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Grimberg","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jann","family":"Hau","sequence":"additional","affiliation":[{"name":"University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indu","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hastings","family":"Ozwara","sequence":"additional","affiliation":[{"name":"Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"King","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Kariuki","sequence":"additional","affiliation":[{"name":"Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.5.2598-2604.2004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/173.1.269"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-5-274"},{"key":"e_1_3_3_5_2","volume-title":"World malaria report\u20132013","author":"World Health Organization","year":"2013","unstructured":"World Health Organization. 2013. 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