Facilitators and barriers for use of rotavirus vaccine amongst various stakeholders and its implications for Indian context – A systematic review

ABSTRACT

Background: We performed a systematic review to evaluate factors affecting uptake of rotavirus vaccine amongst physicians, parents and health system.

Methods: We identified 15 studies that met the inclusion criteria from 790 screened studies published between Jan 2005 to Jan 2016.

Results: Perceived severity of rotavirus disease, efficacy of vaccine and recommendation by health authorities positively influenced uptake of vaccine amongst health care providers. Routine and timely vaccination with routine vaccines and availability of rotavirus vaccine in public health programme facilitated uptake. Family income, parental education and employment status positively influenced the decision to vaccinate by parents. Concerns about safety, high cost, additional workload and logistic problems in acquiring vaccine stocks were perceived as barriers.

Conclusion: Improved awareness regarding the rotavirus vaccination amongst public and scientific community and strengthening of public health system for better and timely immunisation coverage are important factors to maximize uptake of rotavirus vaccine in India.

KEYWORDS:

• Rotavirus disease
• vaccine
• uptake
• factors
• acceptability

Introduction

Rotavirus is the most common cause of vaccine-preventable severe diarrhoea, responsible for 28% childhood cases worldwide.¹ Rotavirus disease was responsible for 197000 deaths in under-five population in the year 2011 which indicates that 23 children die due to this condition every hour.² In India, Rotavirus infection was found to be responsible for 34% of total deaths due to diarrhoea in under-five population with an estimated mortality of 4.14 deaths per 1000 live births in 2005.³

To reduce the burden of rotavirus disease, WHO and other international organisations with support from GAVI have prioritized development of rotavirus vaccine and its introduction into immunisation schedules over the last decade.⁴ Introduction of rotavirus vaccine into the national immunisation schedule of Europe and Americas was recommended by WHO in 2006.⁵ This recommendation was extended worldwide in April 2009 after review of clinical trials conducted in Africa and Asia.⁶ The efficacy of Rotateq as well as Rotarix is demonstrated to be more than 90% in high-income countries in West, but is found to be moderate to low in low and middle income countries.^7–8 Despite the lower efficacy in Asian and African countries, the vaccine has substantial potential for disease prevention in these countries due to a high infection rate and round-the-year transmission of the rotavirus.

In India, rotavirus vaccines are being used by paediatricians in the private sector since last few years. An indigenously developed vaccine – Rotavac [Bharat Biotech] has been demonstrated to have protection against rotavirus disease comparable to the protection offered by other rota virus vaccines in high income countries.⁹ Presently, Rotavac vaccine is being introduced in few states of India as a part of the public-health system driven universal immunisation programme.¹⁰

As with any new service or product introduced in healthcare, introduction of a new vaccine is likely to encounter challenges. Crucially, there have been both positive and negative opinions regarding the need and usefulness of rotavirus vaccination amongst policy makers and health care providers.^11,12 Risk of intussusception associated with the earlier rotavirus vaccine, modest efficacy of rotavirus vaccines in developing countries, presence of co-infections and role of WASH interventions in prevention of morbidity and mortality due to diarrhoea are potential factors that influence the decision for rotavirus vaccine use.¹¹ Issues related to provider as well as user perceptions and acceptability can be crucial in the success of the vaccine introduction. Additionally, readiness of the health system infrastructure and availability of resources can be potential influencers of vaccine uptake.

These and many other factors lead to the question about how rotavirus vaccine can systematically and effectively be introduced into the national immunisation program at scale. Some answers to this can be obtained from an analysis facilitators and barriers for uptake of rotavirus vaccine from available literature worldwide. With this context, we performed a systematic review of factors affecting uptake of rotavirus vaccine amongst parents, health care providers and health system.

Methods

This systematic review protocol was registered at PROSPERO with registration no CRD42016033742 and can be accessed at http://www.crd.york.ac.uk/PROSPERO. We included studies that assessed awareness, attitudes and perceptions of physicians and parents regarding rotavirus vaccination, intention to vaccinate, perceived facilitators and barriers, compliance to recommendation for rotavirus vaccination. We also included operational research studies evaluating reasons for poor or incomplete vaccination with rotavirus. Studies related to clinical trials, immunisation policies, mass immunisation, were excluded as they were not relevant for the review.

The search strategy utilised various combinations of non-MeSH terms including ‘uptake’, ‘coverage’, ‘factors’, ‘access, ‘barrier’, ‘challenges’ and MeSH as well as non-MeSH terms for rotavirus vaccine. Literature search was conducted using United States National Library of Medicine, IndMed and Cochrane Database. The search strategy shown in Table 1S was used for search in United States National Library of medicine (Pubmed) database. Similar strategy was used for search in other databases. Original articles published from 1st Jan 2005 to 31st Jan 2016 were included. Apart from the published literature, reports from workshops, conferences were searched through given databases, Google and reference lists of the published papers. Studies published in languages other than English and animal studies were excluded. We did not include post-introduction evaluations of rotavirus vaccine as they mainly assessed vaccine effectiveness. One author independently screened titles and abstracts of the studies to select potentially relevant articles. Full texts of all the selected articles were obtained and were then screened by two authors independently based on predefined eligibility criteria for inclusion.

Table 1. Health care provider-related factors affecting uptake of rota viral vaccine.

Health care provider-related factors	References	Proportions of health care providers	RR or OR for behaviours significantly associated with likelihood for vaccination^$	Correlation with intention to vaccinate (r)
Being a paediatrician vs. family practitioner	^Citation14–Citation16^,^Citation18	70-88% (P); 46.1-55% (FP)	1.13 for P Ref: FP
Disease severity and need for vaccination
Perceived severity of the disease	^Citation14^,^Citation18^,^Citation19	55.6-83% (P); 46.1% (FP)	1.51-1.84
Experience of severe gastroenteritis during medical practice	^Citation19	84% (P)
Significant economic burden due to disease	^Citation19	62% (P)
Perceived need for vaccination	^Citation16^,^Citation18^,^Citation19	66- 83% (P); 28% (FP)	5.81
Perceived efficacy of vaccine	^Citation14^,^Citation16^,^Citation18^,^Citation19	45.1 -89% (P)	1.45 -4.13	0.54
Recommendation by health authorities	^Citation14^,^Citation16^,^Citation18	41-91.4% (P); 44% (FP)
Did not perceive need for vaccination	^Citation16^,^Citation18	12-16.3% (P); 33% (FP)	0.14-0.34
Vaccine-related factors
Knowledge about the vaccine and its schedule	^Citation18^,^Citation19	59-62% (P);32% (FP)
Complexity of recommendations for timing of rota vaccine doses	^Citation18	29% (P) 40% (FP)	0.59
Mode of administration of the vaccine	^Citation19	85% (P)		0.40
Logistic factors
Availability in public health system	^Citation14^,^Citation19	59% – 92.2% (P)
Unwarranted burden of work	^Citation18		0.34
Obtaining adequate supplies	^Citation18		0.65
Adding vaccine to already overloaded schedule	^Citation16^,^Citation18	8 -29% (P);50% (FP)	0.17 -0.47
Time taken to discuss vaccine safety with parents	^Citation16	14.5% (P)	0.10-0.64
Upfront cost to purchase vaccine	^Citation16^,^Citation18^,^Citation19	49.2-60% (P)	0.48	-0.22
Lack of reimbursement /adequate reimbursement	^Citation16^,^Citation18	75-81% (P)	0.42
Vaccine safety
Reluctance to vaccinate due to withdrawal of previous rota vaccine	^Citation16^,^Citation18	68% (P)	0.38, 0.45
Perception of vaccine safety	^Citation14^,^Citation16^,^Citation19	45.5 – 75.5% (P)	0.22 – 0.72
The fact that it's a new vaccine	^Citation19	44% (P)		-0.29

P – Paediatrician, FP – Family practitioner, ^{$ –} risk ratios of odd's ratios representing association of certain behaviours with the likelihood of vaccination as compared to all others.

Data extraction was completed for all the eligible studies using standardised data extraction form in Microsoft Excel. Factors related to uptake of rotavirus vaccination were captured under following four headings: Health provider related, parent related, health system related and vaccine related factors. In addition, limitations of the study were also captured. The data extraction was independently carried out by one author and was reviewed by a senior author. We used New Castle Ottawa Scale (NOS) for assessment of quality and bias.¹³ Two reviewers independently assessed the quality of studies. In case of dispute, opinion of third reviewer was taken. As most of the identified relevant studies were qualitative in nature and reported minimum quantitative data, we did not attempt to conduct a meta-analysis.

Factors that affected uptake of rotavirus vaccine from the perspective of physician, parents or health system were considered as variables of interest. The variables were expressed as range of proportions, risk ratio and correlation co-efficient.

Results

A total of 775 titles and abstracts were screened through searching various databases out of which 71 full text articles were screened for eligibility and 15 studies were identified based on the predefined inclusion criteria. Figure 1 shows PRISMA flow chart for selection of studies. The descriptions of included studies is given in Table 2S.

Figure 1. PRISMA 2009 Flow Diagram.

Table 2. Health system -related factors for uptake of rota viral vaccine.

Health System-related factors	References	Proportion of stakeholders recommending/using vaccine	RR or OR for systems associated with significant likelihood for rota vaccination*	Correlation coefficient (r)
Practice setting	^Citation16^,^Citation18		HMO/HP/Clinic 1.36- 2.97 CHC/HBP 1.85 PP Ref
No of providers in practice	^Citation18		10 or more – 1.91 1to 3 -Ref
Type of primary care provider	^Citation15^,^Citation17	82% (P) 70.9% (FP)	P – 1.13; FP – Ref FP – 0.14; P -0.699; WBC – Ref
Availability of the vaccine in public health system or UIP	^Citation19^,^Citation20	59% paediatricians	Availability in public health system – 8.5 – 29.3
Coverage of routine immunisation (esp DTaP)	^Citation15	80.3% in infants receiving at least one dose of DTaP vs 62.2% in infants not receiving DTaP	≥ 1 dose of DTaP – 1.26 No DTaP – Ref
Routine vaccination with PCV	^Citation14		Received PCV -13.2 Not received PCV – Ref
Receiving DTaP vaccination within 24 or 32 weeks	^Citation22		DTaP<24 or 32 wks -17.8 DTap> 24 or 32 wks -Ref
Delay during pentavalent vaccination	^Citation21	Dose 1: 78.3% after age limit; 94.7% before age limit Dose 2: 64.1% after age limit; 87.7% before age limit	Dose 1: After age limit – 0.2 Before age limit – Ref. Dose 2: After age limit – 0.1 Before age limit -Ref
Delay in receiving DTP-HiB vaccine	^Citation23	Dose 1: 99.0% for DTP-Hib1 Vs 95.2% for Rota1 (3.8% difference) – 9.5% receiving dose 1 after 14 weeks Dose 2: 98.4% for DTP-Hib2 Vs 83.0% for Rota2 (15.4% difference) – 16.6% receiving dose 2 after 24 weeks		0.82, p = 0.09 0.90, p = 0.04
Vaccine being given with other routine immunisation	^Citation20		Given with routine vaccine – 4.3 Not given with routine vaccine – Ref

HMO – Health management organization; HP – Hospital, CHC – community health centre, HBP – Hospital based practice; UIP – universal immunisation program; P – paediatrician, FP – Family Physician; * – Ref is all others wherever not mentioned.

Eight of these studies were questionnaire surveys, either internet-based or telephonic, conducted amongst physicians or parents of the children. The rest were retrospective observational cohort studies, cross-sectional surveys and a prospective study. Six of these studies were conducted in United states, 3 in Canada, one in India, China, United Kingdom, Belgium, El Salvador, and Brazil each.

Quality assessment

The potential risk of bias assessment for included studies has been described in Table 3S-5S. Most of the cross sectional studies did not demonstrate comparability of non-respondents. Two out of three of the case control studies had controls selected from hospitals thus inducing a selection bias as the controls were not true representative of healthy population. All the included studies had well-defined study question or objective, defined target population, clearly described methods and analysis, description of limitations and major conclusions.

Table 3. Parent-related factors affecting uptake of rota viral vaccine.

Parent-related factors	References	Proportions of parents	OR or RR for parental factors/behaviours associated with significant likelihood for vaccination*	Correlation with intention to vaccinate
Proportion of parents recommending/vaccinating	^Citation17^,^Citation20^,^Citation4	67-92.2%	9.78
Education of fathers	^Citation17		Bachelor degree – 5.88 Master degree – 3.33 Primary education – Ref
Employment status of fathers	^Citation17		Unemployed -0.21 Fully salaried – ref
Employment status of mothers	^Citation17		Unemployed – 0.30 Fully salaried – ref
Household income	^Citation24^,^Citation17		> 75K $ – 2.24 <75K $ – ref EUR 2–3K – 2.63 EUR 3–4K – 3.125 > EUR 4 K – 5.55 ≤ EUR 2 K – Ref	0.11
Maternal age	^Citation15	< 25 yrs - 73.9% 30–35 yrs – 81.5%	0.91
Single parent	^Citation24			-0.06
Personal normative belief	^Citation20^,^Citation24		4.59 – 9.9	0.42
Subjective norm	^Citation20^,^Citation24		0.6 -2.5	0.24
Recommendation by doctors	^Citation20^,^Citation24		1.13 – 21.1
Recommendation by national advisory committee	^Citation20		21.7- 22.7
Information by media	^Citation20		0.54, 0.5

Personal normative belief – parents’ perceptions of the moral correctness of having their child vaccinated; Subjective norm – parents’ perceptions that significant others will approve rotavirus vaccination, * – Ref is all others wherever not mentioned.

We have broadly classified the factors into provider, user and system related.

Health care provider-related factors

There were five studies that evaluated perceptions of physicians regarding rotavirus vaccination. In four of these studies, the vaccine was better accepted among paediatricians (recommended by 70–88%) as compared to family physicians (46.1-55%).^14–15 A greater proportion of paediatricians (66-83%) perceived a need for vaccination with rotavirus vaccine as compared to family physicians (28%).^15,16,18 Knowledge about the vaccine schedule was also greater in paediatricians as compared to family physicians. In one study conducted in Belgium, the risk of incomplete vaccination with rotavirus vaccine was found to be greater when the vaccine was being prescribed by family physicians as compared to paediatricians (OR 6.67 vs.1.43).¹⁷

As shown in Table 1, perceived need for vaccination (RR = 5.81) and perceived efficacy of vaccine (RR = 1.45-4.13) were found to be strong factors influencing use of rotavirus vaccine amongst health care providers in Canadian, American as well as Indian studies.^14–18,19 Health care providers who perceive that rotavirus vaccine is a severe disease and had experience of treating severe gastroenteritis in their practice were more likely to prescribe rotavirus vaccine. Recommendation by health authorities was considered important for decision making by health care providers in three of the included studies.^14–16

On the other hand, barriers perceived by health care providers while using rotavirus vaccine were mainly related to logistic or vaccine safety issues – complexity of recommendations by health authorities, upfront cost to purchase vaccine and lack of reimbursement.^15,17 These factors are pertinent to vaccine being available in the private health system in industrialised countries and may not be applicable if the vaccine becomes available in the public health system of LMIC and is available of free of cost. Adding another vaccine to already overburdened schedule of vaccines (OR = 0.17-0.47), unwarranted burden of work (OR = 0.34) and obtaining adequate supplies of vaccines (OR = 0.65) were logistic issues found in two American studies. Additionally, withdrawal of RotaShield from US market due to associated risk of intussusception (OR = 0.38-0.45) and time taken to discuss safety with parents was considered as barriers for use of rotavirus vaccine by providers in US.^15,16

There was one study conducted in Indian paediatricians which reflected the perceptions of health providers in India regarding the use of rotavirus vaccine. In this study, 91.4% paediatricians relied upon the recommendations by Indian Academy of Paediatrics for prescribing rotavirus vaccine. Availability of rotavirus vaccine in the public health system was considered as a major facilitator as 92.2% paediatricians said that they would routinely prescribe the vaccine if it is available in the public health system. Concerns about vaccine safety were expressed by 45.5% of paediatricians in this study.¹⁴

Health system-related factors

Health system-related factors were evaluated based on studies conducted amongst health care providers and studies analysing one or more factors influencing uptake of rotavirus vaccine (Table 2).

In US, the vaccine was almost 1.5 to 2 times more likely to be administered in health maintenance organisations, hospital-based practices and community health centres as compared to private practice. Practices with 10 or more providers were 1.9 times more likely to administer rota vaccine as compared to practices with 3 or less providers^15,16 indicating possibility that institutes with large number of providers follow certain uniform recommendations for rotavirus vaccination. The vaccine was most likely to be prescribed in Well-Baby clinics followed by paediatricians as compared to family physicians in two studies. In Canadian study,¹⁹ 59% of the paediatricians said that introduction of the vaccine into the public health system would be useful. In another American study, 73.5% pregnant women indicated that their babies would receive all vaccines that are available in the public health system (RR = 29.3).²⁰ These findings underline the importance of inclusion of rotavirus vaccine in universal immunization for its public health impact.

Coverage and timeliness of routine vaccination was found to have an impact on coverage of rotavirus vaccine. In two observational study conducted in US and El Salvador, coverage of rotavirus vaccine was found to be associated with coverage of routine vaccination.^21,15 In Indian study, increased coverage of pneumococcal vaccine was found to be associated with increased uptake of rotavirus vaccine (RR = 13.2).¹⁴ In a retrospective study based on vaccination data in US, children who received DTaP immunization within 24 to 32 weeks of age were 17.8 times more likely to receive vaccination with rotavirus vaccine as compared to children who received it after this age limit.²² In a Brazilian study, coverage of rotavirus vaccine correlated with the timeliness of routine immunisation with DTP-HiB and difference in the coverage of rotavirus vaccine and DTP-HiB correlated with delay in DTP-HiB.²³ This is because rotavirus vaccine is not routinely recommended beyond 6–8months of age due to increased risk of intussusception.^22,23

Parent-related factors

As seen in Table 3, the parent-related factors were reported in 3 studies conducted in Belgium, Canada and US. In an American study, 67% parents expressed a positive intention to vaccinate their children with rotavirus vaccine and it was associated with 9.78 more likelihood of the chid receiving rotavirus vaccine.²⁴ In two other studies conducted in Canada and Belgium, 74% and 92.2% parents recommended and vaccinated their children with rotavius vaccine.^17–20 Education status of fathers and employment status of both parents were found to be associated with increased likelihood of the child receiving rotavirus vaccine in Belgium study.¹⁷

Canadian and Belgian studies showed that children in families with high income had greater odds of receiving rotavirus vaccination. However, these are studies from high income countries and in both these studies; the vaccine was not included in public funded programme. The findings are likely to be replicated in private sector of LMIC as well where uptake is largely decided by affordability of the vaccine. The type of residence in metro, urban, semi-urban or rural setup was not found to influence coverage of rotavirus vaccine in studies conducted in United States and China.^15,25

In the American and Canadian studies, personal normative beliefs (parents’ perceptions of the moral correctness of having their child vaccinated) positively impacted parents’ decision to vaccinate whereas subjective norms (parents’ perceptions that significant others will approve rotavirus vaccination) was not consistently associated with positive intention of parents to vaccinate.^19,20 Recommendation by health care providers and health authorities was found to be associated with increased parents’ intention to vaccinate children with rotavirus vaccine. In Canadian study, information about rota virus vaccine from media which were internet websites mainly acted was associated with reduced intention to vaccinate by parents.

Other factors

Oral mode of administration was found to be a facilitating factor in both parent as well as physician surveys.^19,20,23 In both types of studies, 49.2 to 60% of respondents considered cost to purchase the vaccine as a barrier to vaccinate.

Among child-related factors, first child in the family was more likely to be vaccinated as compared to children with 3 or more siblings.^15,17,20,23 In the Belgian study, attendance at a professional daycare in the first year of life was associated with increased the likelihood of vaccination.¹⁷ Race and gender of the child were not found to influence the intention to vaccinate (Table 4).

Table 4. Vaccine-related and social/family-related factors for uptake of rota viral vaccine.

Factors	References	Proportions	RR or OR for factors associated with significant likelihood for vaccination	Correlation with intention to vaccinate	Beta associated with intention to vaccinate against rota
Vaccine-related factors
Mode of administration of the vaccine	^Citation19^,^Citation20^,^Citation4	85% health care providers	0.93 -2.5	0.40
Cost of the vaccine	^Citation16^,^Citation18^,^Citation19	49.2%-60% health care providers	0.48	-0.22
Social/family-related factors
First child	^Citation15^,^Citation20	46.2% vs. 28.7%	First child – 2.3 Birth order of 2 or more – ref
More than one child in the family	^Citation15^,^Citation17^,^Citation24	3 or more siblings in the family 58% vs. 71.2% for no sibling for at least one vaccination	3 or more siblings - 0.19- 0.89 No sibling/only child – Ref		-0.09
Gender	^Citation22^,^Citation25		Females – 0.99-1.02 Males – ref
Race	^Citation22		Black – 0.96 Hispanic – 0.98 White – ref
Daycare attendance	^Citation17		Professional daycare -2.17 No daycare – Ref

In a small prospective study conducted in NICU settings, coverage of rota vaccine was 33% as compared to 80–87% coverage for all other routine immunisation due to the policy of rota vaccination at discharge for NICU infants. This was to prevent nosocomial transmission of rota vaccine virus.²⁶ Another study was conducted by Jaque et alin NICU settings to evaluate if administration of rota virus vaccine is a standard practice in NICU. In this study, 45 out of 56 NICUs had the standard practice of administering rotavirus vaccine. Lack of standard guidelines for controlling risk of infection transmission following rotavirus immunisation in NICU was found to a barrier.²⁷

Discussion

The review addresses many contextual, individual as well rotavirus vaccine specific determinants of rotavirus vaccine uptake from various global studies. Although only two of the studies were conducted in LMIC and a majority of these studies are from developed countries, the have some implications in the context of LMICs, including India. These studies have been conducted within few years after introduction of rotavirus vaccine in the country, but not all countries have rotavirus vaccine as part of public health program.

Studies conducted amongst parents indicate that positive attitude towards rotavirus vaccine, recommendation by health authorities, doctors and media plays major influence on decision making by parents regarding rotavirus vaccination. This is in consensus with recent literature on overall childhood vaccine uptake from developed countries.^28,29 Parental education and socioeconomic status is found to affect vaccine uptake positively as well as negatively in different parts of the world. In developing countries like India and Bangladesh, parental education and socioeconomic status have been found to have positive influence on vaccine uptake.³⁰ Our findings suggest positive effect of parental education and high income on uptake of rotavirus vaccine. This may indicate better health seeking behaviour by educated and high income families. However, the issue of affordability for parents may be less important for public health immunisation program in India as the vaccine is made available free of cost to the families. None-the-less, this emphasizes need for large scale public awareness campaigns through media regarding the benefits of rotavirus vaccination.

Studies amongst health care providers indicate that awareness regarding rotavirus disease burden and vaccination physicians including need for vaccination, schedule and health authority recommendations is potential influencer for vaccine uptake. These findings may be more applicable for health care providers in private sector and before introduction of the vaccine in public health system. Indian health system is a mix of public and private service providers.. While immunization is a priority program for the public health system, due to large number of people accessing the private health sector, health care providers from private sector also play important role in overall success of immunisation.³¹ However, awareness regarding need for rotavirus vaccination and vaccine schedule is also important for frontline health workers in public health system who are responsible for vaccination coverage at grass root level.³² Thus, there is need for effective communication methods regarding rotavirus vaccination amongst all cadres of health care providers and frontline workers.

Although availability of rotavirus vaccine in public health system has been found to facilitate overall uptake of the vaccine amongst health care providers and parents in various studies; this also adds to the burden of existing vaccinations and logistic difficulties in vaccine supply and cold chain maintenance especially in remote rural places.³³ In a country like India, although the national coverage for basic vaccination is 62%, the coverage varies from state to state with lowest coverage in India's largest central states.^34,35 Based on distributional impact of rotavirus vaccination in 25 GAVI countries, simply introduction of new rotavirus vaccine into the existing system would target the investments towards high income groups with good vaccination coverage.³⁶ Considering the higher mortality risk and better cost effectiveness of rotavirus immunisation in low income regions,³⁶ strengthening of the framework for national immunisation is necessary to maximize the health benefits due to rotavirus immunisation.

Timely coverage of routine immunisation is an important correlate of uptake of rotavirus vaccine given the criteria for age restriction.^22,21 A modelling study by Patel et al, showed that the additional lives saved by removing age restrictions for rotavirus vaccination would in fact outnumber the potential excess vaccine-associated intussusception deaths.³⁷ Due to further evidence in this regard, the age restriction for rotavirus vaccine has been relaxed by WHO. Despite this, in India, IAP continues to use of age restriction of 8 months.³⁵ Delayed childhood vaccination is a known challenge in India.³⁸ In view of this, scaling up of routine immunisation and improved coverage of routine immunisation will increase opportunity to provide rotavirus vaccine to maximum number of children.³⁹

Concerns about safety of rotavirus vaccine and its association with intussusception was expressed by health care providers and parents in few studies probably in view of withdrawal of first Rotavirus vaccine in US.^16,19,14 Post-marketing studies on the newer vaccines have shown favourable risk benefit ratio of introduction of the vaccine in routine vaccination.^40,41 This is despite the lower efficacy of vaccine in low and middle income countries. An extended cost effectiveness analysis by Verguet et al shows that public finance of rotavirus vaccine in India, can still offer financial risk protection amongst poor considering the reduction in mortality and herd immunity acquired by mass community vaccination.⁴² Since risk of intussusception with Indian vaccine, Rotavac, is unknown; presently, sentinel surveillance for intussusception is being carried out in some parts of country [ongoing study]. Indian Council for Medical Research plans to utilise national rotavirus surveillance network for monitoring safety and impact of Rotavac in the health system.⁴³

Overall, certain facilitators and barriers identified in this review may not be specific for rotavirus vaccine per se but may be applicable for introduction of any new vaccine. At the same time, certain factors such as age restriction, issues related to vaccine safety are specific for rotavirus vaccine.

Although most of the included studies are from developed nations and there is dearth of such studies from low and middle income countries, we have attempted to draw conclusions which may be applicable in India. There is scope for more research in this regard in LMIC. The review does not include studies only assessing coverage of rotavirus vaccine and reviews from various expert groups in this regard. These are some of the limitations of this review.

None the less, the review gives an insight into certain important factors which may influence health care providers as well as parents’ decision to use rotavirus vaccine and determine uptake of rotavirus vaccine in health system. Lessons learnt from the available literature can inform policy makers and can help in successful introduction of rotavirus vaccine in India.

Conclusion

As India prepares to introduce rotavirus vaccine in routine vaccination, creating public and health care community awareness regarding rotavirus vaccination, strengthening of public health system in for timely and adequate coverage of routine immunisation, maintaining uninterrupted vaccine supply, training of human resources are essential steps to reap optimum benefits from rotavirus vaccination.

Abbreviations

ASHA	=	Accredited Social Health Activist
DTaP	=	Diphtheria, Tetanus, acellular pertussis
DTP-HiB	=	Diphtheria Pertussis Tetanus- Hemophilus Influenza B
GAVI	=	Global Alliance for Vaccines and Immunisation
IAP	=	Indian Association of Paediatricians
LMIC	=	Lower-Middle Income Countries
NICU	=	Neonatal intensive care unit
NTAGI	=	National Technical Advisory Group on Immunisation
PRISMA	=	Preferred reporting items for systematic review and meta-analysis
PCV	=	Pneumococcal vaccine
SAGE	=	Strategic advisory group of Experts
UIP	=	Universal Immunisation Schedule
WHO	=	World health organisation
WASH	=	Water sanitation and hygiene

Disclosure of potential conflicts of Interest

The authors declare that they have no conflict of interest.

Acknowledgments

The authors are thankful to Dr. Jose Martines, Scientific Coordinator, CISMAC, University of Bergen , Centre for International Health for critically reviewing the manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.