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Background  Malaria and schistosomiasis often overlap in tropical and subtropical countries and impose tremendous disease burdens; however, the extent to which schistosomiasis modifies the risk of febrile malaria remains unclear.    Methods  We evaluated the effect of baseline  S. haematobium  mono-infection, baseline  P. falciparum  mono-infection, and co-infection with both parasites on the risk of febrile malaria in a prospective cohort study of 616 children and adults living in Kalifabougou, Mali. Individuals with  S. haematobium  were treated with praziquantel within 6 weeks of enrollment. Malaria episodes were detected by weekly physical examination and self-referral for 7 months. The primary outcome was time to first or only malaria episode defined as fever (≥37.5°C) and parasitemia (≥2500 asexual parasites/µl). Secondary definitions of malaria using different parasite densities were also explored.    Results  After adjusting for age, anemia status, sickle cell trait, distance from home to river, residence within a cluster of high  S. haematobium  transmission, and housing type, baseline  P. falciparum  mono-infection (n = 254) and co-infection (n = 39) were significantly associated with protection from febrile malaria by Cox regression (hazard ratios 0.71 and 0.44;  P  = 0.01 and 0.02; reference group: uninfected at baseline). Baseline  S. haematobium  mono-infection (n = 23) did not associate with malaria protection in the adjusted analysis, but this may be due to lack of statistical power. Anemia significantly interacted with co-infection ( P  = 0.009), and the malaria-protective effect of co-infection was strongest in non-anemic individuals. Co-infection was an independent negative predictor of lower parasite density at the first febrile malaria episode.    Conclusions  Co-infection with  S. haematobium  and  P. falciparum  is significantly associated with reduced risk of febrile malaria in long-term asymptomatic carriers of  P. falciparum . Future studies are needed to determine whether co-infection induces immunomodulatory mechanisms that protect against febrile malaria or whether genetic, behavioral, or environmental factors not accounted for here explain these findings.

plos neglected tropical diseases

Co-infection of Long-Term Carriers of Plasmodium falciparum with Schistosoma haematobium Enhances Protection from Febrile Malaria: A Prospective Cohort Study in Mali