Natural History of Cryptosporidiosis in a Birth Cohort in Southern India

Kattula, Deepthi; Jeyavelu, Nithya; Prabhakaran, Ashok D.; Premkumar, Prasanna Samuel; Velusamy, Vasanthakumar; Venugopal, Srinivasan; Geetha, Jayanthi C.; Lazarus, Robin P.; Das, P.B.; Nithyanandhan, Karthick; Chandrabose, Gunasekaran; Muliyil, Jayaprakash; Sarkar, Rajiv; Wanke, Christine; Ajjampur, Sitara Swarna Rao; Babji, Sudhir; Naumova, Elena N.; Ward, Honorine; Kang, Gagandeep

doi:10.1093/cid/ciw730

Cited by 33 publications

(33 citation statements)

References 37 publications

(39 reference statements)

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“…Intensive, active surveillance revealed a high burden of cryptosporidiosis with 64% and 44% of children at the urban and rural site, respectively, experiencing at least 1 Cryptosporidium infection by age 2 years. Consistent with similar prior active surveillance cohort studies in diverse geographic locations, most Cryptosporidium infections occurred in the absence of diarrhea, which we term subclinical [ 2 , 3 , 7 , 9 , 19 ]. The predominance of subclinical infection was particularly striking in rural Mirzapur where only 2% of cryptosporidiosis episodes were diarrheal.…”

Section: Discussionsupporting

confidence: 85%

Species of Cryptosporidia Causing Subclinical Infection Associated With Growth Faltering in Rural and Urban Bangladesh: A Birth Cohort Study

Steiner

Ahmed

Gilchrist

et al. 2018

Clinical Infectious Diseases

107

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Section: Discussionsupporting

confidence: 85%

Species of Cryptosporidia Causing Subclinical Infection Associated With Growth Faltering in Rural and Urban Bangladesh: A Birth Cohort Study

Steiner

Ahmed

Gilchrist

et al. 2018

Clinical Infectious Diseases

107

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“…In LMIC, there is growing evidence that Giardia lamblia [ 3 , 4 ] and Cryptosporidium spp. [ 6 , 33 ] are etiologic agents of enteric infections in infants without overt diarrhea [ 2 , 34 ]. Several factors may explain the excretion of enteric pathogens in the absence of diarrhea, related either to the pathogen (strain virulence, prolonged excretion of cysts), to the host (immune response, nutritional status, microbiota), and/or to the environment [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Subclinical Enteric Parasitic Infections and Growth Faltering in Infants in São Tomé, Africa: A Birth Cohort Study

Garzón

Pereira‐da‐Silva

Seixas

et al. 2018

IJERPH

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The associations between enteric pathogenic parasites and growth in infants in São Tomé were explored using a refined anthropometric approach to recognize early growth faltering. A birth cohort study was conducted with follow-up to 24 months of age. Microscopic examination for protozoa and soil-transmitted helminths was performed. Anthropometric assessments included: z-scores for weight-for-length (WLZ), length-for-age (LAZ), weight (WAVZ) and length velocities (LAVZ), length-for-age difference (LAD), and wasting and stunting risk (≤−1 SD). Generalized additive mixed effects regression models were used to explore the associations between anthropometric parameters and enteric parasitic infections and cofactors. A total of 475 infants were enrolled, and 282 completed the study. The great majority of infants were asymptomatic. Giardia lamblia was detected in 35.1% of infants in at least one stool sample, helminths in 30.4%, and Cryptosporidium spp. in 14.7%. Giardia lamblia and helminth infections were significantly associated with mean decreases of 0.10 in LAZ and 0.32 in LAD, and of 0.16 in LAZ and 0.48 in LAD, respectively. Cryptosporidium spp. infection was significantly associated with a mean decrease of 0.43 in WAVZ and 0.55 in LAVZ. The underestimated association between subclinical parasitic enteric infections and mild growth faltering in infants should be addressed in public health policies.

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“…In regions of endemicity, cryptosporidiosis mostly impacts young children, and risk factors for infection include poverty and overcrowding (4,(8)(9)(10). Livestock serve as an environmental reservoir for C. parvum, and transmission after contact with infected animals or with drinking water contaminated by human or animal waste has been reported previously (11).…”

mentioning

confidence: 82%

Genome-Wide Association Study of Cryptosporidiosis in Infants Implicates PRKCA

Wojcik

Korpe

Marie

et al. 2020

mBio

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Diarrhea is a major cause of both morbidity and mortality worldwide, especially among young children. Cryptosporidiosis is a leading cause of diarrhea in children, particularly in South Asia and sub-Saharan Africa, where it is responsible for over 200,000 deaths per year. Beyond the initial clinical presentation of diarrhea, it is associated with long-term sequelae such as malnutrition and neurocognitive developmental deficits. Risk factors include poverty and overcrowding, and yet not all children with these risk factors and exposure are infected, nor do all infected children develop symptomatic disease. One potential risk factor to explain these differences is their human genome. To identify genetic variants associated with symptomatic cryptosporidiosis, we conducted a genome-wide association study (GWAS) examining 6.5 million single nucleotide polymorphisms (SNPs) in 873 children from three independent cohorts in Dhaka, Bangladesh, namely, the Dhaka Birth Cohort (DBC), the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries (PROVIDE) study, and the Cryptosporidiosis Birth Cohort (CBC). Associations were estimated separately for each cohort under an additive model, adjusting for length-for-age Z-score at 12 months of age, the first two principal components to account for population substructure, and genotyping batch. The strongest meta-analytic association was with rs58296998 (P = 3.73 × 10−8), an intronic SNP and expression quantitative trait locus (eQTL) of protein kinase C alpha (PRKCA). Each additional risk allele conferred 2.4 times the odds of Cryptosporidium-associated diarrhea in the first year of life. This genetic association suggests a role for protein kinase C alpha in pediatric cryptosporidiosis and warrants further investigation. IMPORTANCE Globally, diarrhea remains one of the major causes of pediatric morbidity and mortality. The initial symptoms of diarrhea can often lead to long-term consequences for the health of young children, such as malnutrition and neurocognitive developmental deficits. Despite many children having similar exposures to infectious causes of diarrhea, not all develop symptomatic disease, indicating a possible role for human genetic variation. Here, we conducted a genetic study of susceptibility to symptomatic disease associated with Cryptosporidium infection (a leading cause of diarrhea) in three independent cohorts of infants from Dhaka, Bangladesh. We identified a genetic variant within protein kinase C alpha (PRKCA) associated with higher risk of cryptosporidiosis in the first year of life. These results indicate a role for human genetics in susceptibility to cryptosporidiosis and warrant further research to elucidate the mechanism.

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Natural History of Cryptosporidiosis in a Birth Cohort in Southern India

Cited by 33 publications

References 37 publications

Species of Cryptosporidia Causing Subclinical Infection Associated With Growth Faltering in Rural and Urban Bangladesh: A Birth Cohort Study

Species of Cryptosporidia Causing Subclinical Infection Associated With Growth Faltering in Rural and Urban Bangladesh: A Birth Cohort Study

Subclinical Enteric Parasitic Infections and Growth Faltering in Infants in São Tomé, Africa: A Birth Cohort Study

Genome-Wide Association Study of Cryptosporidiosis in Infants Implicates PRKCA

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