The Epidemiology of Sapovirus in the Etiology, Risk Factors, and Interactions of Enteric Infection and Malnutrition and the Consequences for Child Health and Development Study: Evidence of Protection Following Natural Infection.

BACKGROUND: Sapovirus is one of the principal agents of acute viral enteritis in children. Because it has not been routinely included in diagnostic evaluations, the epidemiology and natural history remain poorly described. METHODS: A birth cohort of 1715 children from 8 countries contributed surveillance samples (n = 35 620) and diarrheal specimens (n = 6868) from 0 to 24 months of age. Sapovirus was detected by quantitative polymerase chain reaction concurrently to other enteropathogens using multiarray cards. Logistic regression was used to identify risk factors, and longitudinal models were employed to estimate incidence rates and evaluate evidence of protective immunity. RESULTS: Sapovirus was detected in 24.7% (n = 1665) of diarrheal stools and 12.8% (n = 4429) of monthly surveillance samples. More than 90% of children were infected and 60% experienced sapovirus diarrhea in the first 2 years of life. Breastfeeding and higher socioeconomic status were associated with reduced incidence of infection and illness. Specimens with sapovirus detected had an increased odds of coinfection with rotavirus (odds ratio [OR], 1.6 [95% confidence interval {CI}, 1.3-2.0]), astrovirus (OR, 1.5 [95% CI, 1.3-1.7]), adenovirus (OR, 1.3 [95% CI, 1.1-1.5]), and Shigella (OR, 1.4 [95% CI, 1.3-1.6]). Prior infection with sapovirus conferred a risk reduction of 22% for subsequent infection (hazard ratio [HR], 0.78 [95% CI, .74-.85]) and 24% for subsequent diarrhea (95% CI, 11.0%-35.0%; HR, 0.76). CONCLUSIONS: Sapovirus is a common cause of early childhood diarrhea. Further research on coinfections is warranted. Evidence of acquired immunity was observed even in the absence of genotype-specific analysis for this pathogen of known genetic diversity.

Astrovirus Infection and Diarrhea in 8 Countries.

BACKGROUND AND OBJECTIVES: Astroviruses are important drivers of viral gastroenteritis but remain understudied in community settings and low- and middle-income countries. We present data from 8 countries with high prevalence of diarrhea and undernutrition to describe astrovirus epidemiology and assess evidence for protective immunity among children 0 to 2 years of age. METHODS: We used 25 898 surveillance stools and 7077 diarrheal stools contributed by 2082 children for enteropathogen testing, and longitudinal statistical analysis to describe incidence, risk factors, and protective immunity. RESULTS: Thirty-five percent of children experienced astrovirus infections. Prevalence in diarrheal stools was 5.6%, and severity exceeded all enteropathogens except rotavirus. Incidence of infection and diarrhea were 2.12 and 0.88 episodes per 100 child-months, respectively. Children with astrovirus infection had 2.30 times the odds of experiencing diarrhea after adjustment for covariates (95% confidence interval [CI], 2.01-2.62; P < .001). Undernutrition was a risk factor: odds of infection and diarrhea were reduced by 10% and 13%, respectively, per increase in length-for-age z score (infection: odds ratio, 0.90 [95% CI, 0.85-0.96]; P < .001; diarrhea: odds ratio, 0.87 [95% CI, 0.79-0.96]; P = .006). Some evidence of protective immunity to infection was detected (hazard ratio, 0.84 [95% CI, 0.71-1.00], P = .052), although this was heterogeneous between sites and significant in India and Peru. CONCLUSIONS: Astrovirus is an overlooked cause of diarrhea among vulnerable children worldwide. With the evidence presented here, we highlight the need for future research as well as the potential for astrovirus to be a target for vaccine development.

Norovirus Infection and Acquired Immunity in 8 Countries: Results From the MAL-ED Study.

BACKGROUND: Norovirus is an important cause of childhood diarrhea. We present data from a longitudinal, multicountry study describing norovirus epidemiology during the first 2 years of life. METHODS: A birth cohort of 1457 children across 8 countries contributed 7077 diarrheal stools for norovirus testing. A subset of 199 children contributed additional asymptomatic samples (2307) and diarrheal stools (770), which were used to derive incidence rates and evaluate evidence for acquired immunity. RESULTS: Across sites, 89% of children experienced at least 1 norovirus infection before 24 months, and 22.7% of all diarrheal stools were norovirus positive. Severity of norovirus-positive diarrhea was comparable to other enteropathogens, with the exception of rotavirus. Incidence of genogroup II (GII) infection was higher than genogroup I and peaked at 6-11 months across sites. Undernutrition was a risk factor for symptomatic norovirus infection, with an increase in 1 standard deviation of length-for-age z score associated with a 17% reduction (odds ratio, 0.83 [95% confidence interval, .72-.97]; P = .011) in the odds of experiencing diarrhea when norovirus was present, after accounting for genogroup, rotavirus vaccine, and age. Evidence of acquired immunity was observed among GII infections only: Children with prior GII infection were found to have a 27% reduction in the hazard of subsequent infection (hazard ratio, 0.727; P = .010). CONCLUSIONS: The high prevalence of norovirus across 8 sites in highly variable epidemiologic settings and demonstration of protective immunity for GII infections provide support for investment in vaccine development.