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)
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