Diversity of rotavirus genotypes circulating in children < 5 years of age hospitalized for acute gastroenteritis in India from 2005 to 2016: analysis of temporal and regional genotype variation

Abstract

Background From 2016, the Government of India introduced the oral rotavirus vaccine into the national immunization schedule. Currently, two indigenously developed vaccines (ROTAVAC, Bharat Biotech; ROTASIIL, Serum Institute of India) are included in the Indian immunization program. We report the rotavirus disease burden and the diversity of rotavirus genotypes from 2005 to 2016 in a multi-centric surveillance study before the introduction of vaccines. Methods A total of 29,561 stool samples collected from 2005 to 2016 (7 sites during 2005–2009, 3 sites from 2009 to 2012, and 28 sites during 2012–2016) were included in the analysis. Stools were tested for rotavirus antigen using enzyme immunoassay (EIA). Genotyping was performed on 65.8% of the EIA positive samples using reverse transcription- polymerase chain reaction (RT-PCR) to identify the G (VP7) and P (VP4) types. Multinomial logistic regression was used to quantify the odds of detecting genotypes across the surveillance period and in particular age groups. Results Of the 29,561 samples tested, 10,959 (37.1%) were positive for rotavirus. There was a peak in rotavirus positivity during December to February across all sites. Of the 7215 genotyped samples, G1P[8] (38.7%) was the most common, followed by G2P[4] (12.3%), G9P[4] (5.8%), G12P[6] (4.2%), G9P[8] (4%), and G12P[8] (2.4%). Globally, G9P[4] and G12P[6] are less common genotypes, although these genotypes have been reported from India and few other countries. There was a variation in the geographic and temporal distribution of genotypes, and the emergence or re-emergence of new genotypes such as G3P[8] was seen. Over the surveillance period, there was a decline in the proportion of G2P[4], and an increase in the proportion of G9P[4]. A higher proportion of mixed and partially typed/untyped samples was also seen more in the age group 0–11 months. Conclusions This 11 years surveillance highlights the high burden of severe rotavirus gastroenteritis in Indian children &lt; 5 years of age before inclusion of rotavirus vaccines in the national programme. Regional variations in rotavirus epidemiology were seen, including the emergence of G3P[8] in the latter part of the surveillance. Having pre-introduction data is important to track changing epidemiology of rotaviruses, particularly following vaccine introduction.

Rotavirus Strain Distribution before and after Introducing Rotavirus Vaccine in India

“…There was marked temporal fluctuation, with G9P[8] detected at a high frequency in 2013/2014, only to disappear by 2019/2020, while G12P[6] was high in 2014/2015. Our findings are consistent with surveillance data from India and neighboring countries that also saw the emergence of G12 strains [ 16 ]. We also noted a geographic variation, with G12P[6] and G9P[8] seen more in the southern sites in 2012-2016 and G1P[6] observed more in the northern sites.…”

Prevalence and genetic diversity of gastroenteritis viruses in hospitalized children < 5 years of age in Maharashtra state, Western India, 2017–2019

“…The present study was conducted in collaboration with three tertiary level health‐care centers located in Pune city (Maharashtra state), India, which provides both general and specialized medical care. The enrollment criteria, demographic, and clinical details of the patients were recorded as described earlier 8 . The study was approved by the institutional human ethics committee of the Indian Council of Medical Research, the National Institute of Virology (ICMR‐NIV) Pune, and also from three collaborative hospitals.…”

Phylogenetic analysis of VP7 and VP4 genes of the most predominant human group A rotavirus G12 identified in children with acute gastroenteritis in Himachal Pradesh, India during 2013–2016

“…G12 rotaviruses have been reported at significant prevalence rates from different geographical regions of India since its first detection in 2001; and observed in combination with various P-types mainly with P [6] and P [8] and rarely with P [4] and P [11]. [10][11][12]19,[23][24][25][26] Literature reviewed from 2001 to 2016 showed the proportion of rotavirus infections attributed to G12 strains ranged from 0.5% to 33% in the F I G U R E 4 (A) Alignment of antigenic residues in VP7 between the strains contained in Rotavac® and Rotarix® and G12 strains circulating in Himachal Pradesh. Antigenic residues are divided in three epitopes (7-1a, 7-1b, and 7-2).…”

“…G12 rotaviruses have been reported at significant prevalence rates from different geographical regions of India since its first detection in 2001; and observed in combination with various P‐types mainly with P[6] and P[8] and rarely with P[4] and P[11] 10–12,19,23–26 . Literature reviewed from 2001 to 2016 showed the proportion of rotavirus infections attributed to G12 strains ranged from 0.5% to 33% in the Northern region, 2.4%–18.2% in the Western region, 0.8%–5.6% in the Southern region, and 0.4%–25% in the Eastern region of India 19,26–32 . Earlier, we documented the rotavirus disease burden in children aged <5 years, taking into account rotavirus positivity and strain diversity in HP (North India), where G12 was detected as the most predominant genotype mainly associated with P[6].…”