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

ABSTRACT

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.