Multiple norovirus infections in a birth cohort in a Peruvian Periurban community

Abstract

Background: Human noroviruses are among the most common enteropathogens globally, and are a leading cause of infant diarrhea in developing countries. However, data measuring the impact of norovirus at the community level are sparse.

Methods: We followed a birth cohort of children to estimate norovirus infection and diarrhea incidence in a Peruvian community. Stool samples from diarrheal episodes and randomly selected nondiarrheal samples were tested by polymerase chain reaction for norovirus genogroup and genotype. Excretion duration and rotavirus coinfection were evaluated in a subset of episodes.

Results: Two hundred twenty and 189 children were followed to 1 and 2 years of age, respectively. By 1 year, 80% (95% confidence interval [CI], 75%-85%) experienced at least 1 norovirus infection and by 2 years, 71% (95% CI, 65%-77%) had at least 1 episode of norovirus-associated diarrhea. Genogroup II (GII) infections were 3 times more frequent than genogroup 1 (GI) infections. Eighteen genotypes were found; GII genotype 4 accounted for 41%. Median excretion duration was 34.5 days for GII vs 8.5 days for GI infection (P = .0006). Repeat infections by the same genogroup were common, but repeat infections by the same genotype were rare. Mean length-for-age z score at 12 months was lower among children with prior norovirus infection compared to uninfected children (coefficient: -0.33 [95% CI, -.65 to -.01]; P = .04); the effect persisted at 24 months.

Conclusions: Norovirus infection occurs early in life and children experience serial infections with multiple genotypes, suggesting genotype-specific immunity. An effective vaccine would have a substantial impact on morbidity, but may need to target multiple genotypes.

Keywords: birth cohort; gastroenteritis; infant diarrhea; natural infection; norovirus.

Figure 1.

Cumulative incidence of first and subsequent norovirus-associated infection and diarrhea in a birth cohort of 291 children. A, Survival curves show cumulative incidence of the first through fourth norovirus infections during the first year of life. B, Curves show the cumulative incidence of the first through fourth episodes of norovirus diarrhea for children aged 0–2 years. Percentages show the cumulative incidence, and 95% confidence intervals (shown in brackets) are based on Kaplan-Meier survival analysis.

Figure 2.

Prevalence of norovirus in diarrheal and nondiarrheal stool samples by age. Prevalences are based on cross-sectional analysis of norovirus polymerase chain reaction in 1495 specimens collected during diarrheal episodes and 3690 randomly selected nondiarrheal specimens; 789 specimens collected within 7 days of diarrhea were excluded.

Figure 3.

Duration of norovirus shedding by real-time reverse transcription polymerase chain reaction in 46 randomly selected infection episodes. The boxes represent 25th percentile, median, and 75th percentile, and the whiskers show the minimum and maximum duration of shedding in days. Abbreviations: GI, genogroup I; GII, genogroup II.