Project Details

Early Career

Status: Funded - Closed

Norovirus genetic characterization and clinical severity of diarrhea in a "post-rotavirus" setting

Sarah-Blythe Ballard, M.D., MPH


BACKGROUND: Diarrhea is a leading cause of mortality in children younger than five worldwide.  In settings where vaccines against rotavirus, the number one cause of severe childhood diarrhea, have been implemented, norovirus is rapidly becoming the number one cause of medically-attended diarrhea in this age group.

GAP: Norovirus detection and genetic characterization require molecular techniques, which are often unavailable in the low- and middle-income countries (LMIC) where most diarrhea deaths occur.  However, norovirus vaccines are currently in development, and data from LMIC populations are essential to ensuring that the public health impact of these vaccines to decrease morbidity and mortality is fully realized.

HYPOTHESIS: Norovirus is the predominant diarrhea-associated pathogen in medically attended cases of gastroenteritis in Lima, Peru, where widespread vaccination against rotavirus was implemented in 2009.  Specific norovirus genotypes, as defined by polymerase and capsid region sequencing, are associated with specific symptoms and levels of clinical severity.

METHODS: From October 2013 through April 2015, we enrolled children accessing care at Instituto Nacional de Salud del Niño, a government hospital that treats children with diarrhea from Lima’s lowest socioeconomic strata.  Diarrhea severity was scored, stools tested for enteric pathogens, and norovirus characterized by genotype/variant.  Regression methods were used estimate the relationship between specific norovirus genotypes/variants and gastroenteritis.

RESULTS: During the study period, 1,241 children (709 diarrhea cases and 531 asymptomatic controls) were enrolled in the study.  Ninety percent of enrollees had received two doses of Rotarix, the vaccine against rotavirus that is used in Peru.  Among diarrhea case stool samples, the pathogen prevalence was: 39% norovirus; 19% bacteria; 7% rotavirus; and 5% parasites.  The predominant norovirus variant in children with diarrhea was GII.4 Sydney (91%).  Given the predominance of this pandemic strain, diarrhea severity could not be associated with specific variants.  Among control stool samples from asymptomatic children, the pathogen prevalence was: 20% norovirus; 8% bacteria; 7% parasites; and 3% rotavirus. The predominant norovirus variant in children without diarrhea was GII.4 (48%).  The median annual household income reported by caregivers of children with diarrhea was $306 USD (Interquartile Range [IQR] 252-360).  The perceived cost of each diarrhea episode was $75 (IQR: 54-117).  Among the 33% of caregivers who have jobs outside the house, the median number of workdays lost due to the child’s diarrhea episode was 3 (IQR: 1.5-4.5).  As a result of the time and expense associated with a single diarrhea episode, 53% of caregivers reported being worried about not having enough money to buy food, while 17% reported not having sufficient funds to buy food. 

IMPACT: Norovirus was the predominant diarrhea-associated pathogen in medically-attended children presenting to the children’s hospital in Lima, Peru.  Significant indirect costs were incurred from a single episode of acute diarrhea, and these costs contributed to food insecurity in a segment of the study population.  These results will be useful in guiding candidate norovirus vaccine evaluation and implementation in Peru, and serve as a model for other settings.

Supervising Institution:

Robert Gilman

Project Location:
United States, Peru

Award Amount: