title: The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS).
abstract: The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized.
  
  
  
  Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated.
  
  
  
  Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27-4.67) and 3.18 (95% CI, 1.85-4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73-2.08) and 1.36 (95% CI, 0.66-2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33-5.01) and 4.88 (95% CI, 0.82-8.92) in infants and 4.04 (95% CI, 0.56-7.51) and 4.71 (95% CI, 0.24-9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative.
  
  
  
  The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies.
authors.affiliation: Centre pour le Développement des Vaccins, Bamako, Mali.
authors.forename: Samba O
authors.initials: SO
authors.lastname: Sow
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Khitam
authors.initials: K
authors.lastname: Muhsen
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.|Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
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authors.initials: D
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authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.|Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
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authors.initials: WC
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authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.|Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.|Emergent Biosolutions, Gaithersburg, Maryland, United States of America.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.|Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
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authors.initials: TH
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authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
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authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Dipika
authors.initials: D
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authors.affiliation: Department of Paediatrics and Child Health, the Aga Khan University, Karachi, Pakistan.
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authors.initials: AK
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authors.affiliation: International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka, Bangladesh.
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authors.initials: AS
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authors.affiliation: Medical Research Council (United Kingdom) Unit, Fajara, Gambia.|GSK Vaccines, Wavre, Belgium.
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authors.affiliation: Medical Research Council (United Kingdom) Unit, Fajara, Gambia.|GSK Vaccines, Wavre, Belgium.
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authors.affiliation: Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique.|Instituto Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique.|ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
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authors.initials: PL
authors.lastname: Alonso
authors.affiliation: Global Disease Detection Division, Kenya Office of the US Centers for Disease Control and Prevention, Nairobi, Kenya.
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authors.lastname: Breiman
authors.affiliation: Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique.|ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
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authors.affiliation: Centre pour le Développement des Vaccins, Bamako, Mali.
authors.forename: Boubou
authors.initials: B
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authors.affiliation: Centre pour le Développement des Vaccins, Bamako, Mali.
authors.forename: Doh
authors.initials: D
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authors.affiliation: Centre pour le Développement des Vaccins, Bamako, Mali.
authors.forename: Uma
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authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Byomkesh
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authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
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authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
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authors.affiliation: International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka, Bangladesh.
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authors.affiliation: Department of Paediatrics and Child Health, the Aga Khan University, Karachi, Pakistan.
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authors.affiliation: Department of Paediatrics and Child Health, the Aga Khan University, Karachi, Pakistan.
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authors.initials: F
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authors.affiliation: International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka, Bangladesh.
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authors.affiliation: International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka, Bangladesh.
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authors.affiliation: Medical Research Council (United Kingdom) Unit, Fajara, Gambia.
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authors.affiliation: Medical Research Council (United Kingdom) Unit, Fajara, Gambia.
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authors.initials: MJ
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authors.affiliation: Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique.|Instituto Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique.
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authors.initials: I
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authors.affiliation: Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique.|Instituto Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique.
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authors.affiliation: Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique.|Instituto Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique.
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authors.initials: S
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authors.affiliation: Kenya Medical Research Institute/Centers for Disease Control and Prevention, Kisumu, Kenya.
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authors.initials: JO
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authors.affiliation: Kenya Medical Research Institute/Centers for Disease Control and Prevention, Kisumu, Kenya.
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authors.affiliation: Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
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authors.initials: ED
authors.lastname: Mintz
authors.affiliation: Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
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authors.initials: CE
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authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.|Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
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authors.initials: LY
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authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.|Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Sofie
authors.initials: S
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authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.|Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
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authors.initials: SM
authors.lastname: Tennant
authors.affiliation: Centre of Intervention Science in Maternal and Child Health, Centre for International Health, University of Bergen, Bergen, and Department of International Public Health, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Halvor
authors.initials: H
authors.lastname: Sommerfelt
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
authors.affiliation: Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Tomer
authors.initials: T
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authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
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authors.initials: RM
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authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
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authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
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authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
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authors.initials: ER
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authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.|Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
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authors.initials: KL
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mesh_terms: D000346:Afghanistan / Q000453:epidemiology; D017954:Africa South of the Sahara / Q000453:epidemiology; D001208:Asia / Q000453:epidemiology; D016022:Case-Control Studies; D002675:Child, Preschool; D017281:Cost of Illness; D003457:Cryptosporidiosis / Q000453:epidemiology* / Q000401:mortality* / Q000469:parasitology; D003458:Cryptosporidium / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D057225:Data Mining / Q000379:methods; D003906:Developing Countries / Q000191:economics / Q000706:statistics & numerical data; D003967:Diarrhea / Q000453:epidemiology / Q000401:mortality* / Q000469:parasitology; D005243:Feces / Q000469:parasitology*; D005260:Female; D005767:Gastrointestinal Diseases / Q000453:epidemiology* / Q000401:mortality / Q000469:parasitology; D006801:Humans; D007118:Immunoassay; D015994:Incidence; D007194:India / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016133:Polymerase Chain Reaction