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Background  The importance of  Cryptosporidium  as a pediatric enteropathogen in developing countries is recognized.    Methods  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.    Findings   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.    Conclusions  The enormous African/Asian  Cryptosporidium  disease burden warrants investments to develop vaccines, diagnostics and therapies.

plos neglected tropical diseases

The Burden of Cryptosporidium Diarrheal Disease among Children &lt; 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)