Hospital-based norovirus surveillance in children <5 years of age from 2017 to 2019 in India.

After the introduction of the rotavirus vaccine into the Universal Immunization Program in India in 2016, relatively few studies have assessed the prevalence and epidemiological patterns of acute gastroenteritis (AGE) among hospitalized children ≤5 years of age. We used a uniform protocol to recruit children with AGE as well as standardized testing and typing protocols. Stool specimens from children with AGE younger than 5 years of age admitted to six hospitals in three cities in India were collected from January 2017 through December 2019. Norovirus was detected by real-time reverse transcription-polymerase chain reaction (RT-qPCR) followed by typing positive specimens by conventional RT-PCR and Sanger sequencing. Norovirus was detected in 322 (14.8%) of 2182 specimens with the highest rate in 2018 (17.6%, 146/829), followed by 2019 (14.4%, 122/849) and 2017 (10.7%, 54/504). Rotavirus vaccine status was known for 91.6% of the children of which 70.4% were vaccinated and 29.6% not. Norovirus positivity in rotavirus-vaccinated children was 16.3% and 12% in unvaccinated children. GII.4 Sydney[P16] (39.3%), GII.4 Sydney[P31] (18.7%), GII.2[P16] (10%), GI.3[P13] (6.8%), GII.3[P16] (5.9%), and GII.13[P16] (5%) accounted for 85.8% (188/219) of the typed strains. Our data highlight the importance of norovirus in Indian children hospitalized with AGE.

Etiology of diarrheal hospitalizations following rotavirus vaccine implementation and association of enteric pathogens with malnutrition among under-five children in India.

Malnourished children are at higher risk of mortality and morbidity following diarrheal illness and certain enteropathogens have been associated with malnutrition in children. Very few studies have comprehensively looked at the etiology of diarrhea in malnourished children and most have used conventional diagnostic methods with suboptimal sensitivity. We used a highly sensitive molecular approach against a broad range of pathogens causing diarrhea and examined their association with malnutrition. In addition, we looked at the pathogen diversity of pediatric diarrhea, three years after the nationwide rotavirus vaccine introduction to understand the evolving landscape of pathogens, which is crucial for planning strategies to further reduce the diarrhea burden. Clinical details and diarrheal stool samples were collected from hospitalized children aged < 5 years from three sentinel sites in India for a period of one year. The samples were tested by qPCR for 16 established causes of diarrhea using TaqMan Array Cards. A total of 772 children were enrolled, from whom 482 (62.4%) stool specimens were tested. No specific pathogen was associated with diarrhea among children with acute or chronic malnutrition compared to those with better nutritional status. Overall, adenovirus was the leading pathogen (attributable fraction (AF) 16.9%; 95% CI 14.1 to 19.2) followed by rotavirus (AF 12.6%; 95% CI 11.8 to 13.1) and Shigella (AF 10.9%; 95% CI 8.4 to 16.4). The majority of diarrhea requiring hospitalization in children aged < 2 years could be attributed to viruses, while Shigella was the most common pathogen among children aged > 2 years. These data on the prevalence and epidemiology of enteropathogens identified potential pathogens for public health interventions.

Whole-genome characterization of common rotavirus strains circulating in Vellore, India from 2002 to 2017: emergence of non-classical genomic constellations.

Rotaviruses (RVs) are the most common etiological agent of acute gastroenteritis among young children, even after vaccine introduction in low-income countries. A whole-genome classification representing the 11 RV genes, was introduced for surveillance and characterization of RVs. This study characterized the common circulating strains in Vellore, India from 2002 to 2017 to understand rotavirus strain diversity and evolution using Whole genome sequencing (WGS) carried out on Illumina MiSeq. The 89% (92% of Wa-like, 86% of DS-1-like) of strains had classical constellations, while reassortant constellations were seen in 11% (8% of Wa-like, 14% of DS-1-like) of the strains. The rare E6-NSP4 in combination with DS-1 like G1P[8] and the emergence of the OP-354 subtype of P[8] were identified. Phylogenetics of RV strains revealed multiple subtypes circulating in the past 15 years, with strong evidence of animal to human gene transmission among several strains.

Understanding Rotavirus Vaccine Efficacy and Effectiveness in Countries with High Child Mortality.

Rotavirus claims thousands of lives of children globally every year with a disproportionately high burden in low- and lower-middle income countries where access to health care is limited. Oral, live-attenuated rotavirus vaccines have been evaluated in multiple settings in both low- and high-income populations and have been shown to be safe and efficacious. However, the vaccine efficacy observed in low-income settings with high rotavirus and diarrheal mortality was significantly lower than that seen in high-income populations where rotavirus mortality is less common. Rotavirus vaccines have been introduced and rolled out in more than 112 countries, providing the opportunity to assess effectiveness of the vaccines in these different settings. We provide an overview of the efficacy, effectiveness, and impact of rotavirus vaccines, focusing on high-mortality settings and identify the knowledge gaps for future research. Despite lower efficacy, rotavirus vaccines substantially reduce diarrheal disease and mortality and are cost-effective in countries with high burden. Continued evaluation of the effectiveness, impact, and cost-benefit of rotavirus vaccines, especially the new candidates that have been recently approved for global use, is a key factor for new vaccine introductions in countries, or for a switch of vaccine product in countries with limited resources.

Rotavirus Strain Distribution before and after Introducing Rotavirus Vaccine in India.

In April 2016, an indigenous monovalent rotavirus vaccine (Rotavac) was introduced to the National Immunization Program in India. Hospital-based surveillance for acute gastroenteritis was conducted in five sentinel sites from 2012 to 2020 to monitor the vaccine impact on various genotypes and the reduction in rotavirus positivity at each site. Stool samples collected from children under 5 years of age hospitalized with diarrhea were tested for group A rotavirus using a commercial enzyme immunoassay, and rotavirus strains were characterized by RT-PCR. The proportion of diarrhea hospitalizations attributable to rotavirus at the five sites declined from a range of 56-29.4% in pre-vaccine years to 34-12% in post-vaccine years. G1P[8] was the predominant strain in the pre-vaccination period, and G3P[8] was the most common in the post-vaccination period. Circulating patterns varied throughout the study period, and increased proportions of mixed genotypes were detected in the post-vaccination phase. Continuous long-term surveillance is essential to understand the diversity and immuno-epidemiological effects of rotavirus vaccination.