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

BackgroundThe importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized.MethodsData 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.FindingsCryptosporidium 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.ConclusionsThe enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies.

Natural History of Cryptosporidiosis in a Birth Cohort in Southern India

“…The high rates of infection in this study are likely due to intensive surveillance and use of sensitive diagnostic methods and complementation by serology, as reported for other enteric pathogens [5, 22]. A recent report building on the case-control analysis from the Global Enteric Multicenter Study (GEMS) study also demonstrated the importance of cryptosporidial infection, although the focus was on severe disease and mortality [2]. Similar to this study, the GEMS reanalysis showed that cryptosporidial diarrhea was more common in toddlers (Table 2).…”

“…Cryptosporidium species is a major pathogen causing moderate to severe diarrhea in children [1, 2]. In India alone, cryptosporidiosis causes 3.9–7.1 million diarrheal episodes, 66 400–249 000 hospitalizations, and 5800–14 600 deaths in children aged <2 years [3].…”

Genome-wide association study of cryptosporidiosis in infants implicatesPRKCA

“…Cryptosporidiosis is a leading cause of diarrhea and is estimated to be responsible for greater than 200,000 deaths in young children in South Asia and Sub-Saharan Africa each year. (2) Beyond the immediate infection, cryptosporidiosis is also associated with long term sequelae including malnutrition and neurocognitive developmental deficits. (3–6) The majority of human infections are caused by the C. hominis, C. meleagridis, and C. parvum species, members of the phylum Apicomplexa.…”

Household Transmission Study of Cryptosporidiosis in Bangladesh

“…Globally, cryptosporidiosis is a leading cause of diarrhea in young children, and annually it is estimated there are 2.9 to 4.7 million Cryptosporidium-attributable cases in children younger than two years of age in sub-Saharan Africa and South Asia (1,2). Both diarrheal and subclinical Cryptosporidium infections have been associated with growth faltering and cognitive deficits (3,4).…”