|Year : 2019 | Volume
| Issue : 3 | Page : 243-250
Epidemiology of rotavirus gastroenteritis and need of high rotavirus vaccine coverage with early completion of vaccination schedule for protection against rotavirus diarrhea in India: A narrative review
Bhaskar Raju1, Raunak P Parikh2, Volker V Vetter3, Shafi Kolhapure4
1 Head of Department, Department of PED GE, Dr. Mehta Children's Hospital, Chennai, Tamil Nadu, India
2 Senior Medical Advisor, Medical Affairs (Vaccines), GSK, Mumbai, India
3 Director, Global Medical Affairs Rotavirus Vaccines, GSK, Wavre, Belgium
4 Head of Department, Medical Affairs (Vaccines), GSK, Mumbai, India
|Date of Web Publication||20-Sep-2019|
Raunak P Parikh
Dr. Annie Besant Road, Worli, Mumbai - 400 030, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Rotavirus is a leading cause of severe pediatric diarrhea worldwide, with about 199,000 childhood deaths in 2015, of which 90% in low-income countries. India alone accounts for 22% of the global rotavirus gastroenteritis (RVGE)-related deaths among children below 5 years of age. The World Health Organization recommends introducing rotavirus vaccines (RVVs) as a priority in developing countries where high rates of RVGE are observed. To have the desired impact, RVV should be administered the earliest possible, ideally before the first episode of RVGE. In India, four RVVs are available for use in infants ≥6 weeks of age: the single-strain, two-dose, live-attenuated human RVV Rotarix; the five-strain, three-dose, human-bovine reassortant RVV Rotateq; the single-strain, three-dose, naturally reassortant human-bovine RVV Rotavac; and the five-strain, three-dose, human-bovine RVV Rotasiil; all of them proven to be efficacious and well tolerated. Whereas Rotarix and Rotateq have shown high efficacy/effectiveness against severe RVGE in developed countries (≥90%), they have been observed to be lower in developing countries (~40%–70%). Rotavac and Rotasiil have shown similar efficacy in low-income settings, but further studies are needed to assess their effectiveness. Rotarix and Rotateq have not shown increased intussusception (IS) risk in clinical trials. Postmarketing surveillances were able to show a very tiny increased risk of IS after the first dose of vaccine, but the extensive benefits of rotavirus vaccination far outweigh the low-level risk of IS. In India, where the disease is a major problem and occurs in very early months of life, RVVs should have high coverage and vaccination schedule should be completed as early as possible (≥6 weeks of age) to maximize the vaccine impact.
Keywords: Coverage, early vaccination, India, rotavirus
|How to cite this article:|
Raju B, Parikh RP, Vetter VV, Kolhapure S. Epidemiology of rotavirus gastroenteritis and need of high rotavirus vaccine coverage with early completion of vaccination schedule for protection against rotavirus diarrhea in India: A narrative review. Indian J Public Health 2019;63:243-50
|How to cite this URL:|
Raju B, Parikh RP, Vetter VV, Kolhapure S. Epidemiology of rotavirus gastroenteritis and need of high rotavirus vaccine coverage with early completion of vaccination schedule for protection against rotavirus diarrhea in India: A narrative review. Indian J Public Health [serial online] 2019 [cited 2020 Aug 8];63:243-50. Available from: http://www.ijph.in/text.asp?2019/63/3/243/267216
| Introduction|| |
Rotavirus gastroenteritis disease
Rotavirus is a highly contagious virus, almost every child worldwide would be exposed to the virus by 5 years of age, causing acute gastroenteritis (AGE) often associated with severe dehydration and rarely even convulsion. While it is primarily transmitted via fecal–oral route by person-to-person contact, it has been postulated that spread also occurs through respiratory secretions and contaminated environmental surfaces, which can explain the rapid acquisition of anti-rotavirus antibody in the first 3 years of life regardless of hygiene and sanitary conditions. It is the leading cause of severe pediatric diarrhea worldwide, with about 199,000 childhood deaths in 2015, representing 40% of diarrheal deaths in under-five children. It is estimated that 2 million hospitalizations worldwide in children <5 years of age are due to rotaviral infections.
Therapy is symptomatic, often treated with fluid and salt replacement and oral zinc, but the lack of access to parenteral therapy/health care in developing countries results in a high rotavirus gastroenteritis (RVGE)-associated mortality. Further, the high incidence of severe vomiting in rotaviral diarrhea reduces the efficacy of oral rehydration salts, resulting in hospitalization for parental therapy. Hence, the most efficient option to protect children currently is to prevent the disease.
Natural rotavirus infection is associated with protection against severe rotavirus disease, though infection still occurs. While both cell-mediated and humoral immunities are important, it has been seen that the first infection with rotavirus elicits a predominantly homotypic and serum neutralizing antibody response to the virus while subsequent infections elicit a broader and heterotypic response. Protection is greatest against the moderate-to-severe disease after the first two infections, and severity of the disease is reduced in subsequent infections. Velázquez et al. have previously shown complete protection against moderate-to-severe RVGE after two infections.
Protection induced by rotavirus vaccines (RVVs) is effective in preventing rotavirus-related morbidity/mortality, and the World Health Organization (WHO) has recommended RVVs to be included in all national immunization programs (NIPs) particularly in countries with high RVGE-associated mortality rates. While RVVs have been effective in the prevention of RVGE, vaccine effectiveness (VE) does vary in developing versus developed countries. Through this narrative review, we have tried to provide an overview of the epidemiology of RVGE diseases, available vaccines conferring protective immunity against RVGE, and implementation challenges for a rotavirus vaccination program in India and also argued in favor of early completion of vaccination schedule with high coverage RVVs in a community. A comprehensive search of electronic databases in English was undertaken with broad overview of topic-related area in PubMed and Embase with keywords “rotavirus gastroenteritis,” “rotavirus vaccination” “immunogenicity,” “impact,” “effectiveness,” “coverage,” “compliance,” “developing countries,” and “India” used alone or in combination. Relevant information from government and WHO websites were also considered.
Particularities of rotavirus gastroenteritis in India
India has the highest RVGE-associated mortality, accounting for 22% of all RVGE-related deaths among children under-5 years of age in the world. Studies estimate that 11.37 million episodes of RVGE occur each year in India, among them, 872,000 requiring a hospitalization. Rotavirus-associated mortality in India is estimated to be 78,000/year.
Rotavirus epidemiology in low-income countries is characterized by one or more periods of intense virus circulation, in a year-round transmission context. While the disease remains high throughout the year in India, with rotavirus positivity of ~40% among children hospitalized with AGE, disease positivity is highest in December–February (56% of AGE) and lowest in June–August (21%).
RVGE is uncommon in neonates, likely due to protection due to transplacentally acquired rotavirus-specific IgG. If the disease does occur, it is asymptomatic or mild. In addition, breastfeeding may provide some protection, but due to inconsistencies across studies, this is more controversial. While neonates have some protection against RVGE, the disease is common in young infants in low-income countries. In a study from India, rotavirus positivity among hospitalized children with AGE was 17.4% and 27.4% in children aged <3 and <6 months, respectively.
Five rotavirus strains account for about 90% of all rotavirus infections worldwide: G1P, G2P, G3P, G4P, and G9P. G1P is the most prevalent strain worldwide and was the identified strain in 62.7% of hospitalized RVGE in India.
| Rotavirus Vaccination|| |
As of August 2018, 98 countries have introduced RVVs. Limitations to more widespread implementation of WHO recommendations on RVV introduction have included lack of funding, lack of political will, and recognition of the potential benefits of vaccination. Research from countries that have introduced RVV in NIP has found that vaccination reduced rotavirus-related hospitalizations substantially, in developed as well as developing countries, although the impact varied with settings. In addition, rotavirus vaccination is also a very cost-effective intervention. A study that evaluated that impact of vaccination in 72 countries that account for 95% of rotavirus-related mortality over period 2011–2030 projected cost per disability-adjusted life year (DALY) averted of US$42, with cost-effectiveness ratios less than the per capita gross domestic product in all WHO regions. Vaccination was the most cost-effective and had the greatest impact in regions with high rotavirus mortality. Similarly, RVV introduction in Indian NIP would be a very cost-effective at 1 US$ per dose with an estimated cost per DALY averted of US$ 21–56, which is less than the country's per capita gross domestic product., While vaccine cost does affect the cost-effectiveness, rotavirus vaccination remains cost-effective even at 7 US$ per dose in Indian NIP.
The Ministry of Health and Family Welfare (MoHFW), Government of India, introduced rotavirus vaccination in the NIP in a phased manner in 2016. Initial implementation challenges have included timely availability of supply, 30%–35% wastage with multidose vial, partial national introduction with need to vaccinate children from border districts, mix-up with oral polio vaccine (OPV) dropper, and how to handle infants with partial series (infants who have received at least 1 dose of a RVV but not completed the vaccination schedule) in private sector with regard to the lack of interchangeability data. Currently, there are two RVVs (Rotavac [Bharat Biotech International]), and (Rotasiil [Serum Institute of India Ltd]) in NIP in different states. Mixed RVV implementation has additional potential implementation challenges as all licensed RVVs have differences in terms of cold chain, storage, vaccine vial monitor, wastage, doses per vial, volume per dose, and training material.
In Indian NIP, RVV will be given to all new births, co-administered with pentavalent vaccine, polio vaccine (oral/inactivated), and pneumococcal vaccine. RVVs have been extensively evaluated in co-administration studies with pneumococcal- and diphtheria, tetanus, and pertussis (DTP)-containing vaccines with no significant interference of protective immune responses of the respective vaccines. OPV may have an inhibitory effect to the first dose of RVV; this does not persist after administration of subsequent doses of RVV.
To have the desired impact, the RVV should be administrated as early as optimally possible, ideally before natural RVGE occurs. Consistent with WHO recommendation to initiate rotavirus vaccination as soon as possible after 6 weeks of age (concomitant with the first dose of DTP), the MoHFW recommends the first dose to be administered along with other NIP vaccines at 6 weeks of age. The manufacturers recommend initiating the rotavirus vaccination to children of 6 weeks of age, with an interval of 4 weeks between two doses, making schedule completion possible by 10 weeks of age or 14 weeks of age, for two- and three-dose schedule vaccines, respectively. In the poorest rural settings where the mortality rates of RVGE are the highest, it appears that exposure to rotavirus happens early and that the level of vaccine protection is the lowest. Given that extensive evidence exists that natural rotavirus infection occurs early in developing countries, vaccination schedule should be completed as early as possible in infancy in developing countries.
Besides effectiveness and timeliness, the impact of rotavirus vaccination also depends on coverage. A study in Europe has shown that vaccination impact was higher in countries with high coverage (Austria, Belgium, and Finland) compared to countries with lower vaccination coverage (France, Germany, and Spain). In Austria, 70%–84% RVGE hospitalization reduction was seen in <1 year of age with coverage of 72%–84%. With over 90% coverage, 65%–80% RVGE hospitalization reduction in <2 years of age was seen in Belgium and 80% in <1 year of age was seen in Finland. In contrast, in France and Spain where rotavirus is not part of a national vaccination program with coverage rates between 38% and 47%, RVGE hospitalization reduction in <2 years of age has been 43%–51%. Similarly, in Germany where RVV is included in 5 of 16 federal state immunization programs, RVGE hospitalization reduction of 25%–36% in <2 years of age has been seen with coverage rates of 22%–58%. In Malawi, concomitant with increasing vaccination coverages (74.6% in 2013, 92.4% in 2014, and 95.1% in 2015), reduction in incidence of rotavirus hospitalization per 100,000 population has been demonstrated (268.7 in 2012, 152.5 in 2014, and 123.1 in 2015).
In order to ensure maximum benefit, it is crucial to ensure high vaccination coverage and timely completion of schedule. A recent meta-analysis has also highlighted the need to complete the recommended vaccination schedule, as completed schedules (2 or 3 doses, based on the vaccines) offered higher VE (81% VE; 95% confidence interval [CI]: 75; 86%) than partial schedule (62% VE; 95% CI: 55; 69%, P < 0.001).
The MoHFW recommends RVV in NIP initiation up to 1 year of age, and WHO recommends RVV for children up to 2 years of age, which differs from the recommendation of manufacturers (completion by 24 or 32 weeks of age) [Table 1]. The expanded age group for vaccination is relevant in low-income countries as delays in vaccination are common, and upper age restriction could lead to exclusion of a substantial number of children from vaccination and lower coverage.
|Table 1: Available vaccines in India - Summary of product characteristics|
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In India where rotavirus vaccination was introduced in 2016 in four states, in a phased manner, a 73% coverage has been reported in 2018. This is encouraging, but there is a need to further increase coverage as well as to ensure early completion of vaccination schedule. It should be noted that while there is evidence of herd protection in high-income countries, there are limited data on indirect benefits in unvaccinated populations in low- and middle-income countries. This further re-enforces the need to achieve high coverage among at-risk populations in countries such as India.
| Vaccines|| |
Vaccines available in India
Table 1 presents the characteristics of the vaccines available in India. Four orally administered live attenuated vaccines are available in India, of which Rotarix (GSK), and Rotateq (Merck and Co. Inc.) are licensed worldwide, while Rotavac and Rotasiil are licensed are available in India only. These vaccines have different characteristics in terms of biology, behavior, and mechanism of protection. Design wise, Rotarix is the only available two-dose human RVV and acts like an attenuated natural rotavirus infection. The other cited vaccines are human-bovine reassortant strains, occurring either naturally or produced in laboratory.
Vaccine efficacy and effectiveness in developed and developing countries
Many studies worldwide have shown that Rotarix is immunogenic and effective in preventing severe RVGE. Rotarix has demonstrated to have efficacy against RVGE of G1P and other heterotypic strains with nonvaccine G-type strains, for example, G8 or G12, or P-type strains, for example, P or P. In European efficacy trials, 95.8% (95% CI: 89.6; 98.7%) reduction against severe RVGE in infants <1 year of age was demonstrated, with sustained efficacy of 90.4% of efficacy (95% CI: 85.1; 94.1%) in the 2nd year of life. In the efficacy trial conducted in South Africa and Malawi, vaccine efficacy against severe RVGE was 61.2% (95% CI: 44.0; 73.2%). Subsequent effectiveness of 64% and 68% against any severity and severe disease, respectively, has been seen in Malawi. A single natural rotavirus infection, either symptomatic or asymptomatic, is thought to provide protective immunity against subsequent severe disease, irrespective of serotype. Similarly, with Rotarix, partial protection is apparent from the first dose itself. Initial immunogenicity studies with similar antigen content to the marketed formulation have suggested high seroconversion after the first dose (88%), with the second dosing having a catch-up rather than a booster effect (96% seroconversion). The subsequent European efficacy study also demonstrated that vaccine efficacy of 89.8% (95% CI: 8.9; 99.8%) against any episode of RVGE was seen for the period between dose 1 and dose 2. This is a boon in settings where the second dose may sometimes not be completed and in developing countries where rotaviral infection occurs earlier in infancy.
Rotateq has shown efficacy with a reduction of RVGE incidence in infants of 98.0% (95% CI: 88.3; 100.0%) in the USA and Finland 1 year postvaccination. Efficacy was demonstrated against RVGE of genotypes G1P, G2P, G3P, G4P, G9P, and G12P. In addition, efficacy against other nonvaccine G-type strains, for example, G8 or G9, or P-type strains, for example, P or P has also been demonstrated. The efficacy of Rotateq has been shown to be lower in some developing countries of the world with 39.3% (95% CI: 19.1; 54.7%) in Africa and 48.3% (95% CI: 22.3; 66.1%) in Asia.,
Rotavac and Rotasiil have been evaluated in Phase III studies done during a 2-year follow-up period in India [Table 2]. Rotavac has demonstrated an efficacy of 55.1% (95% CI: 39.9; 66.4%) and 36.4% (95% CI: 26.0; 45.3%) against severe RVGE and RVGE any severity, respectively. The highest efficacy was observed against severe RVGE of children in the 1st year of life (56.4%; 95% CI: 36.6; 70.1%), when the disease is most serious. Efficacy against heterotypic G1P, G2P, G12P, and G12P rotavirus strains and partially heterotypic G9P strain has also been demonstrated in Phase III trials for Rotavac vaccine, although with a lower efficacy toward G1P. Rotasiil has demonstrated efficacies of 32.9% (95% CI: 11.6; 49.1%) and 22.6% (95% CI: 12.9; 31.3%) against severe RVGE and RVGE of any severity, respectively.
|Table 2: Efficacy and effectiveness of available rotavirus vaccines against severe rotavirus gastroenteritis, rotavirus gastroenteritis of any severity, and hospitalizations in developing countries (low-and low-middle income countries according to the World Bank data)|
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While RVVs have had a significant impact on reduction in severe RVGE in developing countries, the vaccine efficacy/effectiveness in these countries has been lower than that seen in the developed world (~40%–70% vs. ≥90%). The reasons for this are not clearly understood, several factors have been considered with no conclusive evidence. Factors that have been evaluated include malnutrition, deficiencies of zinc, Vitamin A and D, more diverse and variable gut microbiota in children from the developing world, coinfections with other enteric pathogens, genetic differences that may affect susceptibility to infection (e.g., Lewis-negative secretor-positive children), and presence of maternal antibodies (transplacental or via breast milk)., It has been hypothesized that high transplacentally acquired rotavirus-specific immunoglobulin G (IgG) or breast milk rotavirus-specific IgA may result in reduced seroconversion. The limited data available on the role of transplacentally-acquired IgG are mixed, some studies indicate reduced seroconversion and others report no effect. In studies where breastfeeding was withheld at the time of vaccination, there was no effect on seroconversion indicating that breastfeeding does not impair response to vaccination. While breast milk rotavirus-specific IgA may be associated with lower seroconversion, breastfeeding does not seem to significantly impair seroconversion and withholding it at the time of vaccination is not recommended.
Other licensed vaccines and vaccines in development
Other licensed vaccines include Rotavin-M1 (PolyVac) in Vietnam and Lanzhou Lamb Rotavirus (LLR, Lanzhou Institute of Biological Products) in China. Rotavin-M1 is a two-dose live attenuated human RVV G1P, while LLR vaccine is a five-dose live attenuated lamb rotavirus strain G10P).
While several oral live attenuated animal-human reassortment vaccines are in Phase III of development, novel types are also being evaluated. These include RV3, a live oral human RVV G3P strain isolated from neonates, that is able to replicate in neonatal gut in the presence of maternal antibodies. It has been found to be immunogenic and efficacious in schedules that include a birth dose. Another vaccine candidate being developed by the National Institutes of Health, USA, and PATH is an intramuscular subunit vaccine with truncated VP8 of P, P, and P.
Both the globally marketed RVVs have been proven, in large prelicensure clinical trials including up to 70,000 infants, to be well tolerated. The overall safety profile of those vaccines is encouraging. The most common adverse events may include diarrhea, irritability, and abdominal pain. A very rare but serious adverse event is intussusception (IS), an intestinal condition that causes bowel obstruction and can be fatal if not promptly diagnosed/treated. While no increased risk of IS has been associated with either Rotateq or Rotarix in Phase III clinical trials, it was identified as a very rare adverse event in postlicensure safety studies. A self-controlled risk interval analysis reported a persistent clustering of reported IS events to the Vaccine Adverse Event Reporting System (a national passive surveillance system to receive adverse events after vaccination in the USA) 3–6 days (risk period) compared to 0–2 days (nonrisk or control period) after Rotateq vaccination (daily reporting ratio [DRR]: 3.75, 95% CI: 1.9; 7.39). With the use of DRR, it was possible to identify IS events in risk and nonrisk period and clustering and excess IS events in risk versus nonrisk period. A similar study led with the Rotarix vaccine has shown a DRR of 7.5 (95% CI: 2.3; 24.6) within 3–6 days compared to 0–2 days postdose 1, which translates in an excess risk of IS of 1.6 (95% CI: 0.3; 5.8) per 100,000 vaccinations.
A recent meta-analysis also identified a risk of IS following dose 2 but lesser extent than with dose 1. The relative risk of IS was 5.4 (95% CI: 3.9; 7.4) and 5.5 (95% CI: 3.3; 9.3) 7 days after the first dose of Rotarix and Rotateq, respectively. After 7 days postdose 2, the RR of IS was 1.8 (95% CI: 1.3; 2.5) for Rotarix and 1.7 (95% CI: 1.1; 2.6) for Rotateq. IS could be considered a class effect.
Data related to risk of IS with Rotavac and Rotasiil are limited. Their safety profiles have been evaluated in their respective clinical trials where no difference between vaccine and placebo groups could be observed.,, However, the subject range was too small (6799–7500 children) to detect this potential side effect. At this point, no postlicensure safety-marketing surveillance data are available for Indian vaccines. Studies should be set in place to be able to draw a conclusion regarding the safety profiles of these vaccines.
The potential benefits of a vaccine must be weighed against the potential risk of undesirable outcomes (adverse events) occurring after administration, including IS. A very small increased risk of IS was identified with RVVs, but the extensive benefits to health of rotavirus vaccination far outweigh the low-level risk of IS, especially when vaccine is administered before 3 months of age, as the natural risk of IS increases afterward.
| Conclusion|| |
RVGE is a major disease burden in low-income countries and particularly in India. RVVs have been available for use in private medical practice for nearly a decade, and the Indian Academy of Pediatricians has been recommending rotavirus vaccination in routine immunization schedules. More recently, RVV has also been included in the NIP. Internationally marketed vaccines Rotarix and Rotateq have undergone extensive clinical development programs with demonstrated efficacy/effectiveness in diverse settings and have established safety profile. Despite the relatively lower efficacy/effectiveness in developing countries, given the high burden of disease, vaccination still reduces substantially the RVGE-related morbidity and mortality. Rotavac and Rotasiil have demonstrated similar efficacy compared to the internationally marketed vaccines in developing countries.
In India like in other developing countries, the epidemiology of RVGE can influence the optimal vaccination schedule. In India, 17% of infants 0–8 weeks of age hospitalized with AGE are rotavirus positive, and ~20% of RVGE admissions take place by 12 weeks of age. This indicates that rotavirus disease occurs early in India, and this warrants early initiation and completion of RVV in India. While all RVVs are indicated for use in infants 6 weeks of age and above, the two-dose vaccine offers potential benefits of earlier completion of schedule compared to three-dose vaccines. In addition, higher compliance can be expected for two-dose than three-dose, as some children may not receive the third dose.
RVGE is a major health problem in India. Effective vaccines against RVGE are available for use, and there is an opportunity to reduce <5 years of age diarrheal morbidity with rotavirus vaccination in India. It is important to initiate vaccination as early as possible along with other vaccines at 6 weeks of age and ensure early completion of the schedule.
The authors would like to thank Business and Decision Life Sciences platform for editorial assistance and publications coordination, on behalf of GSK. Amandine Radziejwoski coordinated publication development and editorial support and Sarah Fico provided medical writing support.
Financial support and sponsorship
GlaxoSmithKline Biologicals SA funded the study and costs associated with the development of the present manuscript.
Conflicts of interest
Raunak Parikh, Volker Vetter, and Shafi Kolhapure are employees of the GSK group of companies. Bhaskar Raju declares no conflict of interest.
| References|| |
Centers for Disease Control and Prevention. In: Hamborsky J, Kroger A, Wolfe S, editors. Epidemiology and Prevention of Vaccine-Preventable Diseases. Washington D.C: Public Health Foundation; 2015. Available from: https://www.cdc.gov/vaccines/pubs/pinkbook/rota.html
. [Last accessed on 2019 Sep 01].
Crawford SE, Ramani S, Tate JE, Parashar UD, Svensson L, Hagbom M, et al.
Rotavirus infection. Nat Rev Dis Primers 2017;3:17083.
GBD Diarrhoeal Diseases Collaborators. Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: A systematic analysis for the global burden of disease study 2015. Lancet Infect Dis 2017;17:909-48.
Parashar UD, Hummelman EG, Bresee JS, Miller MA, Glass RI. Global illness and deaths caused by rotavirus disease in children. Emerg Infect Dis 2003;9:565-72.
World Health Organization. Rotavirus vaccines. WHO position paper January 2013. Wkly Epidemiol Rec 2013;88:49-64.
Dennehy PH. Rotavirus vaccines: An overview. Clin Microbiol Rev 2008;21:198-208.
Velázquez FR, Matson DO, Calva JJ, Guerrero L, Morrow AL, Carter-Campbell S, et al.
Rotavirus infection in infants as protection against subsequent infections. N Engl J Med 1996;335:1022-8.
Tate JE, Burton AH, Boschi-Pinto C, Parashar UD, World Health Organization–Coordinated Global Rotavirus Surveillance Network. Global, regional, and national estimates of rotavirus mortality in children 5 years of age, 2000-2013. Clin Infect Dis 2016;62 Suppl 2:S96-105.
John J, Sarkar R, Muliyil J, Bhandari N, Bhan MK, Kang G, et al.
Rotavirus gastroenteritis in India, 2011-2013: Revised estimates of disease burden and potential impact of vaccines. Vaccine 2014;32 Suppl 1:A5-9.
Mehendale S, Venkatasubramanian S, Kumar CP, Kang G, Gupte MD, Arora R, et al.
Expanded Indian national rotavirus surveillance network in the context of rotavirus vaccine introduction. Indian Pediatr 2016;53:575-81.
Plenge-Bönig A, Soto-Ramírez N, Karmaus W, Petersen G, Davis S, Forster J, et al.
Breastfeeding protects against acute gastroenteritis due to rotavirus in infants. Eur J Pediatr 2010;169:1471-6.
Kumar A, Basu S, Vashishtha V, Choudhury P. Burden of rotavirus diarrhea in under five indian children. Indian Pediatr 2016;53:607-17.
O'Ryan M. Rotavirus vaccines: A story of success with challenges ahead. F1000Res 2017;6:1517.
Tate JE, Parashar UD. Rotavirus vaccines in routine use. Clin Infect Dis 2014;59:1291-301.
Atherly DE, Lewis KD, Tate J, Parashar UD, Rheingans RD. Projected health and economic impact of rotavirus vaccination in GAVI-eligible countries: 2011-2030. Vaccine 2012;30 Suppl 1:A7-14.
Rose J, Homa L, Meropol SB, Debanne SM, Bielefeld R, Hoyen C, et al.
Health impact and cost-effectiveness of a domestically-produced rotavirus vaccine in India: A model based analysis. PLoS One 2017;12:e0187446.
Esposito DH, Tate JE, Kang G, Parashar UD. Projected impact and cost-effectiveness of a rotavirus vaccination program in India, 2008. Clin Infect Dis 2011;52:171-7.
Payne DC. Remaining Programmatic Challenges for the Implementation of Rotavirus Vaccines: Interchangeability in RVV Products. Minsk, Belarus: 13th
International Rotavirus Symposium; 2018.
Cherian T, Wang S, Mantel C. Rotavirus vaccines in developing countries: The potential impact, implementation challenges, and remaining questions. Vaccine 2012;30 Suppl 1:A3-6.
Karafillakis E, Hassounah S, Atchison C. Effectiveness and impact of rotavirus vaccines in Europe, 2006-2014. Vaccine 2015;33:2097-107.
Bar-Zeev N, Jere KC, Bennett A, Pollock L, Tate JE, Nakagomi O, et al.
Population impact and effectiveness of monovalent rotavirus vaccination in urban Malawian children 3 years after vaccine introduction: Ecological and case-control analyses. Clin Infect Dis 2016;62 Suppl 2:S213-9.
Hungerford D, Smith K, Tucker A, Iturriza-Gómara M, Vivancos R, McLeonard C, et al.
Population effectiveness of the pentavalent and monovalent rotavirus vaccines: A systematic review and meta-analysis of observational studies. BMC Infect Dis 2017;17:569.
Bhandari N, Rongsen-Chandola T, Bavdekar A, John J, Antony K, Taneja S, et al.
Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: A randomised, double-blind, placebo-controlled trial. Lancet 2014;383:2136-43.
Vesikari T, Karvonen A, Prymula R, Schuster V, Tejedor JC, Cohen R, et al.
Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: Randomised, double-blind controlled study. Lancet 2007;370:1757-63.
Naik SP, Zade JK, Sabale RN, Pisal SS, Menon R, Bankar SG, et al.
Stability of heat stable, live attenuated rotavirus vaccine (ROTASIIL®). Vaccine 2017;35:2962-9.
Madhi SA, Cunliffe NA, Steele D, Witte D, Kirsten M, Louw C, et al.
Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med 2010;362:289-98.
Bar-Zeev N, Kapanda L, Tate JE, Jere KC, Iturriza-Gomara M, Nakagomi O, et al.
Effectiveness of a monovalent rotavirus vaccine in infants in malawi after programmatic roll-out: An observational and case-control study. Lancet Infect Dis 2015;15:422-8.
Vesikari T, Karvonen A, Korhonen T, Espo M, Lebacq E, Forster J, et al.
Safety and immunogenicity of RIX4414 live attenuated human rotavirus vaccine in adults, toddlers and previously uninfected infants. Vaccine 2004;22:2836-42.
Armah GE, Sow SO, Breiman RF, Dallas MJ, Tapia MD, Feikin DR, et al.
Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Sub-Saharan Africa: A randomised, double-blind, placebo-controlled trial. Lancet 2010;376:606-14.
Zaman K, Dang DA, Victor JC, Shin S, Yunus M, Dallas MJ, et al.
Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: A randomised, double-blind, placebo-controlled trial. Lancet 2010;376:615-23.
Madhi SA, Kirsten M, Louw C, Bos P, Aspinall S, Bouckenooghe A, et al.
Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in south african children over two consecutive rotavirus-seasons: A randomized, double-blind, placebo-controlled trial. Vaccine 2012;30 Suppl 1:A44-51.
Patel MM, Patzi M, Pastor D, Nina A, Roca Y, Alvarez L, et al
. Effectiveness of monovalent rotavirus vaccine in Bolivia: Case-control study. BMJ 2013;346:f3726.
Msimang VM, Page N, Groome MJ, Moyes J, Cortese MM, Seheri M, et al.
Impact of rotavirus vaccine on childhood diarrheal hospitalization after introduction into the South African public immunization program. Pediatr Infect Dis J 2013;32:1359-64.
Jiang V, Jiang B, Tate J, Parashar UD, Patel MM. Performance of rotavirus vaccines in developed and developing countries. Hum Vaccin 2010;6:532-42.
Gastañaduy PA, Contreras-Roldán I, Bernart C, López B, Benoit SR, Xuya M, et al.
Effectiveness of monovalent and pentavalent rotavirus vaccines in Guatemala. Clin Infect Dis 2016;62 Suppl 2:S121-6.
Patel M, Pedreira C, De Oliveira LH, Tate J, Leshem E, Mercado J, et al.
Effectiveness of pentavalent rotavirus vaccine against a diverse range of circulating strains in Nicaragua. Clin Infect Dis 2016;62 Suppl 2:S127-32.
Bhandari N, Rongsen-Chandola T, Bavdekar A, John J, Antony K, Taneja S, et al.
Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in indian children in the second year of life. Vaccine 2014;32 Suppl 1:A110-6.
Kulkarni PS, Desai S, Tewari T, Kawade A, Goyal N, Garg BS, et al.
A randomized phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants. Vaccine 2017;35:6228-37.
Isanaka S, Guindo O, Langendorf C, Matar Seck A, Plikaytis BD, Sayinzoga-Makombe N, et al.
Efficacy of a low-cost, heat-stable oral rotavirus vaccine in Niger. N Engl J Med 2017;376:1121-30.
Burnett E, Parashar U, Tate J. Rotavirus vaccines: Effectiveness, safety, and future directions. Paediatr Drugs 2018;20:223-33.
Desselberger U. Differences of rotavirus vaccine effectiveness by country: Likely causes and contributing factors. Pathogens 2017;6:E65.
Mwila K, Chilengi R, Simuyandi M, Permar SR, Becker-Dreps S. Contribution of maternal immunity to decreased rotavirus vaccine performance in low-and middle-income countries. Clin Vaccine Immunol 2017;24:e00405-16.
Bines JE, At Thobari J, Satria CD, Handley A, Watts E, Cowley D, et al.
Human neonatal rotavirus vaccine (RV3-BB) to target rotavirus from birth. N Engl J Med 2018;378:719-30.
Haber P, Patel M, Pan Y, Baggs J, Haber M, Museru O, et al.
Intussusception after rotavirus vaccines reported to US VAERS, 2006-2012. Pediatrics 2013;131:1042-9.
Haber P, Parashar UD, Haber M, DeStefano F. Intussusception after monovalent rotavirus vaccine United States, vaccine adverse event reporting system (VAERS), 2008-2014. Vaccine 2015;33:4873-7.
Rosillon D, Buyse H, Friedland LR, Ng SP, Velázquez FR, Breuer T, et al.
Risk of intussusception after rotavirus vaccination: Meta-analysis of postlicensure studies. Pediatr Infect Dis J 2015;34:763-8.
Parashar UD, Cortese MM, Payne DC, Lopman B, Yen C, Tate JE, et al.
Value of post-licensure data on benefits and risks of vaccination to inform vaccine policy: The example of rotavirus vaccines. Vaccine 2015;33 Suppl 4:D55-9.
Yung CF, Chong CY, Thoon KC. Age at first rotavirus vaccination and risk of intussusception in infants: A public health modeling analysis. Drug Safety 2016;39:745-8.
[Table 1], [Table 2]