Impact of the indigenous rotavirus vaccine Rotavac in the Universal Immunization Program in India during 2016-2020

Abstract

In 2016, India introduced Rotavac (G9P[11]), an indigenous oral rotavirus vaccine administered at 6, 10 and 14 weeks of age through the Universal Immunization Program. Evaluating its effectiveness under routine programmatic conditions is critical, given the variable performance of rotavirus vaccines in low- and middle-income countries. Here we assessed Rotavac's real-world effectiveness and impact across 31 hospitals in 9 states between 2016 and 2020 using a test-negative case-control design. Overall, 24,624 children were enrolled in surveillance (62% male and 38% female). Of 8,372 children aged 6-59 months eligible for effectiveness analysis (1,790 rotavirus-positive cases and 5,437 rotavirus-negative controls), 6,646 received 3 doses and 581 were unvaccinated. The adjusted vaccine effectiveness of 3 doses against severe rotavirus gastroenteritis was 54% (95% confidence interval (CI) 45% to 62%), with 1,574 vaccinated cases versus 5,072 vaccinated controls. Among children aged 6-23 months (1,486 vaccinated cases and 4,595 vaccinated controls), genotype-specific adjusted vaccine effectiveness was 51% (95% CI 36% to 62%) for G3P[8], 81% (95% CI 73% to 87%) for G1P[8] and 64% (95% CI 21% to 83%) for G1P[6]. Following vaccine introduction, rotavirus positivity among hospitalized children declined from 40% to 20%. These findings confirm that Rotavac provides substantial protection against severe rotavirus disease, including nonvaccine strains, and performs comparably to internationally licensed vaccines in similar settings.

Fig. 1. Data flow of enrolled children and identification of age-eligible children based on the date of introduction of rotavirus vaccine in the UIP.

A flow diagram outlining the data collection process for study surveillance, presenting the layout of participants from initial screening to eligibility assessment and inclusion in final analysis and providing details of exclusion stepwise.

Fig. 2. Impact of rotavirus vaccine after its introduction in the UIP in India shown by comparing the pre- and postvaccination introduction surveillance periods.

A comparison of rotavirus positivity during prevaccination period and postvaccination period from five selected study sites. The bars indicate the number of rotavirus-positive cases (N = 2,530) and rotavirus-negative cases (N = 5,744) among children under 5 years admitted with AGE in the study settings by month and year of surveillance. The blue colored solid line shows the percentage of rotavirus-positives among children enrolled in the surveillance by month and year of surveillance. The blue dotted line shows the percentage of children who had received at least a single dose of rotavirus vaccine at the time of enrollment into the study surveillance. The orange straight line shows the time of rotavirus vaccine introduction into the UIP in India. The data during the prevaccine period from 2012 to 2016 were collected as a part of National Rotavirus Surveillance Network^,. The postvaccine data were collected as a part of present study during the time period 2016–2020.

Fig. 3. Reduction in proportions of rotaviral diarrheal disease among children under 5 years during the rotavirus vaccine postintroduction period in the study sites.

The percentage reduction in rotavirus positivity among children under 5 years after the introduction of rotavirus vaccination. The green bars show the percentage of children under 5 years of age who tested positive for rotavirus gastroenteritis during the prevaccination period stratified by their age groups (N = 4,163). The blue bars show the percentage of children under 5 years of age who tested positive for rotavirus gastroenteritis during the postvaccination period stratified by their age groups (N = 4,336). The dotted line shows the coverage of rotavirus vaccine during the study period of 2016–2020 for each age group. The data during the prevaccine period were collected as a part of National Rotavirus Surveillance Network (2012–2016) using similar protocol^,. Postvaccine data were collected as a part of present study (2016–2020). The details are further elaborated in Extended Data Table 6.

Extended Data Fig. 1. Map of India showing the phased introduction by states of Rotavac^TM vaccine in the Universal Immunization Program in India from 2016 to 2018.

This map was generated using licensed version of ArcGIS® software to demonstrate the states in India that were part of the surveillance and introduction times of rotavirus vaccine in each of the participating states. Vaccine effectiveness surveillance data were collected from all nine states from January 2016 to January 2020. Data for assessing the impact of the vaccine were obtained from four states with pre-vaccination data from September 2012 to April 2016, post-vaccination data from May 2016 to June 2020, and from Tamil Nadu from 2018 to January 2020. A uniform protocol was followed throughout the surveillance period.

Extended Data Fig. 2. Study flow diagram.

Shows the protocol followed at all the study sites for enrolment and collection of data. EIA- enzyme immunoassay; MoHFW- Ministry of Health and Family Welfare, Government of India.

Extended Data Fig. 3. Timeliness of rotavirus and pentavalent vaccines among age-eligible children in the Universal Immunization Program in India.

Rotavirus vaccines and pentavalent vaccines are administered to children at 6, 10, and 14 weeks of age in the Universal Immunization Program in India. This figure shows the comparison between cumulative percentages of vaccinated children across timelines during the surveillance. A delay is observed in the completion of the series of both vaccines.