Rotavirus Vaccine In India Research Articles

Post-introduction evaluation (PIE) of rotavirus vaccine in India

BackgroundIndia became the first country in the WHO South-East Asia Region (SEAR) to introduce the rotavirus vaccine (RVV) in the Universal immunization programme (UIP) in 2016 with nationwide expansion by 2019. It was a landmark move to reduce the diarrheal disease burden in under-five children. To assess the implementation process of introduction of RVV, Post Introduction Evaluation (PIE) was conducted in March 2022. MethodsThe evaluation was conducted across 14 states, 28 districts and 28 health facilities to obtain a nationwide geographical inclusion. Stakeholders involved in program decision-making, planning, training, vaccine delivery, logistics, and communication from all levels (National, state, district, health facility, health worker, caregiver) were interviewed using standardized data collection tool for PIE (adapted from the standard WHO PIE questionnaire) and scripted on a digital tool. ResultsA total of 260 interviews were conducted. Political willingness, well-planned preparedness activities, securing vaccines timely, strong supply chain monitoring, availability of domestic RVV products, quality trainings and intense communication activities were the key factors identified for the successful RVV introduction. Key activities during the introduction included cold chain space assessment, trainings of healthcare workforce, dissemination of job aids, updation of recording & reporting formats and strengthening of AEFI surveillance. Lack of community awareness for immunization in a few areas, fear of AEFI amongst some caregivers and local issues with Alternate Vaccine Delivery (AVD) were some reported challenges in achieving high coverage for RVV. ConclusionsOverall, the nationwide roll-out of RVV was smooth and the vaccine has been well-accepted in the community. The assessment emphasizes on having a well-strategized operational and communication planning, which is very crucial for any new vaccine introduction.

Post-marketing safety surveillance of the rotavirus vaccine in India

BackgroundROTASIIL, an oral live attenuated bovine-human reassortant pentavalent rotavirus vaccine, was approved in 2017. This post-marketing surveillance (PMS) was conducted to collect real-world data on the safety of ROTASIIL in India. MethodsObservational, active PMS was conducted in approximately 10,000 infants aged ≥ 6 weeks. ROTASIIL was administered as a 3-dose regimen, at least 4 weeks apart, beginning at ≥ 6 weeks of age concomitantly with other Expanded Programme on Immunization (EPI) vaccines. Participants were followed for one month after the last dose. The adverse events (AEs) and serious adverse events (SAEs), including intussusception (IS) reported during the follow up period were collected. FindingsA total of 9940 infants were enrolled and were considered for safety analysis. Around 9913 (99.7 %) infants received 2 doses, while 9893 (99.5 %) infants completed all three doses. Total 3693 AEs were reported in 2516 (25.3 %) participants. Most of these AEs were pyrexia (78.01 % of events) and injection-site reactions (19.14 % of events). Nearly all AEs were causally unrelated to orally administered ROTASIIL and could be caused by the concomitant injectable vaccines. Only 4 AEs (2 events of vomiting and 1 event each of discomfort and pyrexia) in 4 (<0.1 %) participants could be related to ROTASIIL. AEs were of mild or moderate severity and all resolved without any sequelae. A total of 2 SAEs (acute otitis media and skull fracture) were reported in 2 (<0.1 %) participants and were not related to ROTASIIL and recovered without sequelae. No case of IS was reported. InterpretationROTASIIL was safe and well tolerated in this study. No safety concerns were reported. FundingThe study was funded by SIIPL which is the manufacturer of the study product.

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.

Estimating the economic impact of pneumococcal conjugate, Haemophilus influenzae type b and rotavirus vaccines in India: National and state-level analyses

Background: To support vaccine decision-making we estimated from the societal perspective the potential health impact and costs averted through immunization with three vaccines – Haemophilus influenzae type b (Hib), pneumococcal conjugate vaccine (PCV) and rotavirus vaccine (RVV). Methods: Based on variability in disease burden, strength of health system and economic status, we selected four states in India: Bihar, New Delhi, Maharashtra and Tamil Nadu. We used secondary data sources to estimate the number of under-5 deaths averted from Hib, pneumococcus and rotavirus in each state and back-calculated the total cases averted. We synthesized available data to estimate the disease burden, treatment cost, caretaker productivity loss and vaccine coverage in each state. A Delphi Survey and roundtable among Indian experts was conducted to reach consensus on model inputs. Results: By scaling up coverage of Hib, PCV and RVV, India could save over US$1 billion (uncertainty range: US$0.9–US$2.4 billion) in economic benefits and avert more than 90,000 needless child deaths each year. An estimated US$1 billion (US$0.9–US$2 billion) or 88% of the total amount of cost savings would be attributable to lost productivity due to premature pneumococcal death. Another US$112.8 million (US$105–297 million), or 10% of the total cost would be accounted by costs related to loss of productivity due to disability as a result of these diseases. Treatment costs of Hib, pneumococcal disease and rotavirus gastroenteritis, would account for US$8.4 million (US$4–12 million) or <1% of the total costs of these diseases. Finally, caretaker productivity loss from seeking care would represent US$1.5 million (US$ 1–4.9 million). Cost savings varied by vaccine, coverage scenarios and states. Conclusions: Hib, PCV and RVV vaccine introduction in India can result in immediate benefits to the government and households in terms of savings.

WITHDRAWN: Estimating the economic impact of pneumococcal conjugate, Haemophilus influenzae type b and rotavirus vaccines in India: National and state-level analyses

WITHDRAWN: Estimating the economic impact of pneumococcal conjugate, Haemophilus influenzae type b and rotavirus vaccines in India: National and state-level analyses

Health impact and cost-effectiveness of a domestically-produced rotavirus vaccine in India: A model based analysis.

BackgroundCurrently, Indian officials are incorporating a domestically manufactured rotavirus vaccine (based on the 116E rotavirus strain) into the country’s universal immunization program; this vaccine will cost significantly less than western rotavirus vaccines. Here, we examine the public health impact, cost, and cost-effectiveness of universal vaccination in India using the 116E vaccine. This work will allow comparison of universal 116E vaccination with other approaches to child mortality reduction, shed light on the future burden of rotavirus disease in India, and help stakeholders understand future resource needs.MethodsUsing information from published literature, we developed a dynamic simulation model of rotavirus transmission, natural history, and related utilization among Indian infants followed until age five. Infection risk depended on the degree of viral shedding in the population. Infection risk and severity were influenced by age, number of previous infections, and vaccination history. Probabilities of inpatient and outpatient health services utilization depended on symptom severity. With the model, we compared a strategy of nationwide 116E vaccination to one of no vaccination. Costs were considered from the perspective of all payers (including families) and from the societal perspective.ResultsWe estimated that an established 116E vaccination program would reduce symptomatic rotavirus infection by 13.0%, while reducing population-wide rotavirus mortality by 34.6% (over 34,000 lives annually). Rotavirus outpatient visits would decline by 21.3%, and hospitalization would decline by 28.1%. The cost per disability-adjusted life year (DALY) averted was estimated at 3,429 Rupees (approximately $56). Predicted mortality reduction in children born during the first five years of vaccination implementation was nearly identical to that in children born in later years (34.4% versus 34.6%).Conclusions116E vaccination of Indian infants would likely substantially reduce rotavirus-related morbidity, mortality, and utilization at a cost considered highly cost-effective by standard criteria. Nearly the entire mortality reduction benefit of vaccination was attributable to direct protection of those vaccinated, as opposed to indirect “herd immunity” effects.

Rotavirus gastroenteritis among children less than 5 years of age in private outpatient setting in urban India

Burden of rotavirus gastroenteritis (RVGE) in outpatient setting in India is not fully understood. A prospective study was undertaken to describe RVGE among Indian children less than 5 years of age presenting in outpatient departments with acute gastroenteritis (AGE). This study was conducted at 11 outpatient departments (OPDs) of private pediatric clinics in urban areas of India. A total of 605 eligible children were enrolled at OPDs. Stool samples of the subjects were collected and tested for presence of rotavirus antigen by enzyme immune assay (EIA) and were typed by reverse-transcriptase polymerase chain reaction (RT-PCR). Physician examined the children and documented the disease particulars. In addition, parents/guardians were interviewed for AGE related symptoms, health care utilization and cost incurred due to AGE, and parental stress associated with AGE. After OPD, parents/guardians completed diary cards and questionnaires to capture the information for 14 days following the enrollment.Complete data for analysis including stool sample results was available from 552 subjects. 23% (127/552; [CI 19.5, 26.5]) of stool samples were rotavirus (RV) positive. RT-PCR was done for 85.8% (109/127) of RV positive samples. G1, G2, G9, and G12 types were identified in 34.9% (38/109), 37.6% (41/109), 8.3% (9/109), and 6.4% (7/109) stool samples, respectively. P[4] and P[8] were identified in 36.7% (40/109) stool samples each, followed by P[6] identified in 15.6% (17/109) stool samples.At the time of enrollment, all three symptoms (vomiting, diarrhea, and fever) were observed concurrently in higher proportion of RV positive subjects compared to RV negative subjects (60.6% [77/127] vs. 42.8% [182/425], p=0.0004). Healthcare resource utilization, costs incurred due to disease, and parental stress were higher for RV positive subjects compared to RV negative subjects.In conclusion, RVGE was found to be a definite burden in AGE cases attending pediatric outpatient clinics in urban areas and it was associated with substantial economic and psychological burden. Introduction of rotavirus vaccine in India may help in reducing this disease burden.

Active surveillance for intussusception in a phase III efficacy trial of an oral monovalent rotavirus vaccine in India

BackgroundPost licensure studies have identified an increased risk of intussusception following vaccination with currently licensed rotavirus vaccines, raising safety concerns generic to all rotavirus vaccines. We describe the surveillance for intussusception in a phase III clinical trial with an oral monovalent rotavirus vaccine developed from the neonatal 116E strain. MethodsUsing broad screening criteria and active surveillance, the incidence of intussusception between 6 weeks and 2 years of age was measured in 4532 children who received three doses of vaccine and 2267 children who received a placebo in the clinical trial. Possible intussusceptions were evaluated with a screening ultrasonogram. An independent intussusception case adjudication committee reviewed all intussusceptions and graded them on Brighton Collaboration criteria for diagnostic certainty. ResultsWe identified twenty-three intussusceptions on ultrasound from 1361 evaluated sentinel events. Eleven were of level 1 diagnostic certainty as determined by the independent intussusception case adjudication committee. None required surgical intervention, and the earliest identified intussusception was at 36 days following the third dose in a placebo recipient. Among vaccine recipients the first event of intussusception occurred 112 days after the third dose. The incidence of ultrasound-diagnosed intussusception was 200/100,000 child-years (95% CI, 120, 320) among those receiving the vaccine and 141/100,000 child-years (95% CI, 50, 310) among those receiving the placebo. The incidence rate of confirmed intussusception among vaccine recipients was 94/100,000 child-years (95% CI, 41, 185) and 71/100,000 child-years (95% CI, 15, 206) among those receiving the placebo. ConclusionIn this licensure study, 23 cases of intussusception were identified through an active surveillance system, but there was no temporal association with rotavirus vaccination. The use of active surveillance with broad criteria intended for ensuring safety of children participating in a trial, identified several transient intussusceptions that were of doubtful clinical significance.

Analysis of the Universal Immunization Programme and introduction of a rotavirus vaccine in India with IndiaSim

Background and objectivesIndia has the highest under-five death toll globally, approximately 20% of which is attributed to vaccine-preventable diseases. India's Universal Immunization Programme (UIP) is working both to increase immunization coverage and to introduce new vaccines. Here, we analyze the disease and financial burden alleviated across India's population (by wealth quintile, rural or urban area, and state) through increasing vaccination rates and introducing a rotavirus vaccine. MethodsWe use IndiaSim, a simulated agent-based model (ABM) of the Indian population (including socio-economic characteristics and immunization status) and the health system to model three interventions. In the first intervention, a rotavirus vaccine is introduced at the current DPT3 immunization coverage level in India. In the second intervention, coverage of three doses of rotavirus and DPT and one dose of the measles vaccine are increased to 90% randomly across the population. In the third, we evaluate an increase in immunization coverage to 90% through targeted increases in rural and urban regions (across all states) that are below that level at baseline. For each intervention, we evaluate the disease and financial burden alleviated, costs incurred, and the cost per disability-adjusted life-year (DALY) averted. ResultsBaseline immunization coverage is low and has a large variance across population segments and regions. Targeting specific regions can approximately equate the rural and urban immunization rates. Introducing a rotavirus vaccine at the current DPT3 level (intervention one) averts 34.7 (95% uncertainty range [UR], 31.7–37.7) deaths and $215,569 (95% UR, $207,846–$223,292) out-of-pocket (OOP) expenditure per 100,000 under-five children. Increasing all immunization rates to 90% (intervention two) averts an additional 22.1 (95% UR, 18.6–25.7) deaths and $45,914 (95% UR, $37,909–$53,920) OOP expenditure. Scaling up immunization by targeting regions with low coverage (intervention three) averts a slightly higher number of deaths and OOP expenditure. The reduced burden of rotavirus diarrhea is the primary driver of the estimated health and economic benefits in all intervention scenarios. All three interventions are cost saving. ConclusionImproving immunization coverage and the introduction of a rotavirus vaccine significantly alleviates disease and financial burden in Indian households. Population subgroups or regions with low existing immunization coverage benefit the most from the intervention. Increasing coverage by targeting those subgroups alleviates the burden more than simply increasing coverage in the population at large.

Team science and the creation of a novel rotavirus vaccine in India: a new framework for vaccine development

Team science and the creation of a novel rotavirus vaccine in India: a new framework for vaccine development

High Cost Is the Primary Barrier Reported by Physicians Who Prescribe Vaccines Not Included in India's Universal Immunization Program

Haemophilus influenzae type B (Hib) vaccine, pneumococcal conjugate vaccine (PCV) and rotavirus (RV) vaccine are available in the private market in India, but, except for Hib in eight states, are not included in India's Universal Immunization Program (UIP). Pediatricians were surveyed about administering non-UIP vaccines. Most give these vaccines to some of their patients (73-83%, depending on vaccine), but few give them to all patients (7-18%). High cost was the most frequently cited barrier (93-96%). Only 10-12% of respondents had concerns about the efficacy of PCV or RV vaccine, and concerns about Hib vaccine efficacy or any vaccine safety issues were rare (1-3%). Practice varied by type of healthcare facility, with pediatricians at government hospitals least likely to administer non-UIP vaccines. Support for the inclusion of all three in the UIP was high (83-95%). Including Hib vaccine, PCV and RV vaccine in India's UIP would be supported by pediatricians and help eliminate the current barrier of high cost of these immunizations.

Extended CEA of rotavirus vaccine in India and Ethiopia

Extended CEA of rotavirus vaccine in India and Ethiopia

Rotavirus vaccine in India faces controversy

A new pediatric vaccine for rotavirus that apparently showed 56% efficacy in a phase III clinical trial has run into controversy, according to an expert who points to the need for more safety data and questions the rationale for including it in routine immunization. The vaccine, ROTAVAC, was

Consensus recommendations on immunization and IAP immunization timetable 2012

Vaccinology today is a rapidly changing specialty of medical science where new developments are regularly taking place. There is a need to review/revise recommendations about existing vaccines in the light of recent information. Following an IAPCOI meeting in December 2011, a draft statement was prepared and circulated among the meeting participants to arrive at a consensus. To review and issue recommendations on the recent contentious issues pertaining to rotavirus, Hib, and pneumococcal conjugate vaccines, and to revise recommendations for 2012 Immunization timetable for pediatricians in office practice. IAPCOI abolished the earlier categorization of vaccines in four categories. On rotavirus, the committee stresses the need of having more data on disease burden in India. Further, there is a need to optimize use of rotavirus vaccines in India to achieve higher yields in term of protective efficacy. For the want of adequate data, the committee is not able to issue any specific recommendation on the suitability of a particular rotavirus vaccine (monovalent vs multivalent) for the country. The committee also acknowledges a small risk of acute intussusception following use of current generation of rotavirus vaccines and recommends inclusion of the history of intussusception in the past as an absolute contraindication. The committee concludes that there are no safety concerns of Hib vaccines as reported frequently in lay media. On the disease burden of pneumococcal diseases, the committee concludes that there is a need of conducting more community based studies to gather more evidence. Similarly, the data on prevalence of different pneumococcal serotypes in the country is sparse and limited to few hospital based studies. There is need of establishing real-time multisite pneumococcal disease surveillance in the country. Due to scarcity of data on the prevalence of pneumococcal serotypes and non-typeable hemophilus influenza (NTHi) in India, it is difficult to comment on the superiority of one pneumococcal conjugate vaccine over other. The committee also revised the recommendations for the year 2012.

Key statements of IAPCOI and IAP Immunization Timetable for year 2012

Abstract Vaccinology today is a rapidly changing specialty of medical science where new developments are regularly taking place at short intervals. There is a need to review/revise recommendations about existing vaccines in light of recent information. Following an IAPCOI meeting in December 2011, a draft statement was prepared and circulated among the meeting participants to arrive at a consensus. Objectives To review and issue recommendations on the recent contentious issues pertaining to rotavirus, Hib, and pneumococcal conjugate vaccines and to revise recommendations for 2012 Immunization timetable for pediatricians in office practice. Recommendations IAPCOI abolished the earlier categorization of vaccines in four categories. On rotavirus, the committee stresses the need of having more data on disease burden in India. Further, there is a need to optimize use of rotavirus vaccines in India to achieve higher yields in term of protective efficacy. In the want of adequate data, the committee is not able to issue any specific recommendation on the suitability of a particular rotavirus vaccine (monovalent Vs multivalent) for the country. The committee also acknowledges a small risk of acute intussusceptions following use of current generation of rotavirus vaccines and recommends inclusion of the history of intussusception in the past as an absolute contraindication. The committee concludes there is no safety concerns of Hib vaccines as reported frequently in lay media. On the disease burden of pneumococcal diseases (PD), the committee concludes that there is need of conducting more community based studies to gather more evidence. Similarly, the data on prevalence of different pneumococcal serotypes in the country is sparse and limited to few hospital based studies. There is need of establishing real-time multi-site pneumococcal disease surveillance in the country. Due to scarcity of data on the prevalence of pneumococcal serotypes and non-typeable hemophilus influenzae (NTHi) in India, it is difficult to comment on the superiority of one pneumococcal conjugate vaccine over other. The committee also revised the recommendations for the year 2012.

Projecting Vaccine Efficacy

Researchers must often make assumptions about the efficacy of an intervention in a target population without the benefit of trial data specific to that population. Such assumptions may be particularly tenuous with models of vaccination strategies, since the distribution of pathogen strains in target populations may differ substantially from the strain distributions in trial sites. We describe a technique for projecting expected vaccine efficacy in settings where applying unadjusted trial-based efficacy data may overestimate the benefits of immunization. This simple method uses data describing setting-specific strain distributions of pathogens and strain-specific vaccine efficacies to generate a weighted overall efficacy. An example of estimating the expected efficacy of a new rotavirus vaccine in India is used to illustrate the technique. The method is shown to perform very well in a validation population for whom actual efficacy had been observed and can therefore aid those in the international health community in determining the optimal uses of scarce resources.

Development of Candidate Rotavirus Vaccines Derived from Neonatal Strains in India

The need for a rotavirus vaccine in India is based on the enormous burden associated with the >100,000 deaths due to rotavirus diarrhea that occur annually among Indian children. Two rotavirus strains identified during nosocomial outbreaks of rotavirus infection in New Delhi and Bangalore, India, more than a decade ago are being developed as live oral vaccines. Infected newborns had no symptoms, shed virus for up to 2 weeks after infection, mounted a robust immune response, and demonstrated protection against severe rotavirus diarrhea after reinfection. The 2 strains are naturally occurring bovine-human reassortants. The New Delhi strain, 116E, is characterized as having a P[11],G9 genotype, and the Bangalore strain, I321, is characterized as having a P[11],G10 genotype. The strains have been prepared as pilot lots for clinical trials to be conducted in New Delhi. This unique project, which is developing a new rotavirus vaccine in India with the use of Indian strains, an Indian manufacturer, and an Indian clinical development program, aims to expedite introduction of rotavirus vaccines in India.