title: Co-infection of long-term carriers of Plasmodium falciparum with Schistosoma haematobium enhances protection from febrile malaria: a prospective cohort study in Mali.
abstract: 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.
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Safiatou
authors.initials: S
authors.lastname: Doumbo
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Tuan M
authors.initials: TM
authors.lastname: Tran
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Jules
authors.initials: J
authors.lastname: Sangala
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Shanping
authors.initials: S
authors.lastname: Li
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Didier
authors.initials: D
authors.lastname: Doumtabe
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Younoussou
authors.initials: Y
authors.lastname: Kone
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Abdrahamane
authors.initials: A
authors.lastname: Traoré
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Aboudramane
authors.initials: A
authors.lastname: Bathily
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Nafomon
authors.initials: N
authors.lastname: Sogoba
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Michel E
authors.initials: ME
authors.lastname: Coulibaly
authors.affiliation: Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Aissata
authors.initials: A
authors.lastname: Ongoiba
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Kassoum
authors.initials: K
authors.lastname: Kayentao
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Mouctar
authors.initials: M
authors.lastname: Diallo
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Zongo
authors.initials: Z
authors.lastname: Dramane
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Crompton
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Ogobara
authors.initials: O
authors.lastname: Doumbo
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques, and Technology of Bamako, Bamako, Mali.
authors.forename: Boubacar
authors.initials: B
authors.lastname: Traore
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000453:epidemiology / Q000469:parasitology*; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology*; D008297:Male; D008302:Mali / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D011446:Prospective Studies; D012548:Schistosoma haematobium / Q000302:isolation & purification*; D012553:Schistosomiasis haematobia / Q000453:epidemiology / Q000469:parasitology*; D055815:Young Adult