Technologies for strengthening immunization coverage in India: a systematic review

Summary Background Immunization coverage varies across India in different settings, geographic areas and populations. Technologies for improving immunization access can reduce disparities in coverage. This systematic review, which follows PRISMA guidelines, aims to examine the technologies for strengthening immunization coverage in India. Methods Studies published between January 1, 2011 and July 31, 2021 were searched in Medline (through PubMed), Cochrane Library and Google Scholar. All observational and experimental studies, except qualitative studies, were included. Studies published in the English language and related to technologies for strengthening immunization, conducted on children, pregnant women, adults, elderly, healthcare personnel, caregivers and vulnerable populations across all Indian settings were included. Non-English articles, protocols, commentaries, letters, abstracts, correspondence, opinion articles, modelling, narrative and systematic reviews were excluded. Two reviewers screened studies independently, extracted data in a standardized sheet and appraised the study quality using the Mixed Methods Appraisal Tool. The primary outcome was technologies that improved immunization coverage. The protocol is registered with OSF (https://osf.io/r42gm). Findings 6592 titles and abstracts were screened, and data extracted from 23 India-specific studies. Quality of 22/23 studies was average or above. Technologies identified included reminder systems, capacity building, community engagement and wearable technologies. Automated incentivised mobile phone reminders, immunization due-list, computerized data tracking, community mobilization and campaigns improved vaccine coverage, although effectiveness of some varied viz., reminder systems, and across states. Newer technologies included the Jyotigram Yojana, Digital Near-field Communication Pendants, “Reaching Every District” Programme and the “My Village My Home” tool. Interpretation Technologies for improving immunization systems, capacity building and community engagement were effective. Newer technologies on vaccine delivery, mapping and cold chain logistics were not evaluated in India or were ineffective. There were limited studies in populations other than children and pregnant women. Future work is needed to evaluate the effectiveness of identified technologies across diverse settings. Funding No funding was received for preparing this manuscript.


Introduction
Immunization is a simple public health intervention that reduces the burden of many vaccine preventable infectious diseases and healthcare expenditure. 1 Through immunization the global mortality of children under 5 years from vaccine-preventable diseases reduced from 5.1 to 1.8 million through 1990-2017. 2eyond infancy and childhood, vaccines save the lives of adolescents, adults, pregnant women, high-risk population (healthcare personnel, immunocompromised individuals, occupationally exposed individuals, migrants, populations living in remote and conflict settings) and the elderly, thus laying the foundations of healthy and productive populations. 3Immunization of adults through catch-up and booster vaccinations provides longstanding protection, thus facilitating healthy ageing and well-being. 4he global immunization coverage for all ages dropped from 86% in 2019 to 81% in 2021. 5While the COVID-19 pandemic has been strongly instrumental in this decline, the importance of raising global coverage to more than 90% remains a priority.Excluding COVID-19 vaccine introductions, only 25 vaccines were introduced globally in 2021.Even though this is an increase from 17 introductions in 2020, when compared to number of vaccines introduced in any year, in the past two decades prior to 2020, this number is quite low.As per the World Health Organization (WHO) data on global immunization coverage, 18.2 million infants missed receiving the first dose of childhood diphtheria, tetanus, pertussis (DTP) vaccine series in 2021, suggesting the impact of COVID-19 on access to immunization and other health services. 5More than 60% of unvaccinated or partially vaccinated children in 2021 were from 10 countries viz., India, Nigeria, Indonesia, Ethiopia, Philippines, Democratic Republic of the Congo, Brazil, Pakistan, Angola, and Myanmar. 5More recently, the introduction of COVID-19 vaccines too was highly variable across countries in 2021, with cumulative number of doses administered per 100 people ranging from 118 in Israel, to less than 0.1 in countries that had just begun vaccination such as Namibia, Mali and Brunei. 6

Research in context
Evidence before this study Evidence on technologies or interventions aimed at improving immunization coverage in India have mainly focused on specific age groups, populations, vaccines, settings, or a specific technology.To our knowledge, so far, no systematic review has focused on technologies used in the Indian context that covers all populations and settings.In this systematic review, we searched three databases, Medline (through PubMed), Cochrane Library and Google Scholar, for published evidence related to technologies that influence immunization coverage in the Indian setting.All observational and experimental studies conducted on all populations across India, published in English-language, between January 1, 2011 and July 31, 2021, were included.Qualitative studies, study protocols, commentaries, letters, correspondence, opinion articles, narrative reviews, systematic reviews, blogs and newspaper articles were excluded.We used the MeSH and Title abstract terms for vaccination and immunization, patient acceptance and vaccine uptake, and for types of technologies.The methodological quality of included studies was appraised using the mixed methods appraisal tool (MMAT).

Added value of this study
This review collates all available evidence on technologies for strengthening immunization coverage in India and covers all age groups, population types (children, adults, elderly, pregnant and lactating women, health care professionals, people with comorbidities and marginal populations) and settings.We summarise the evidence by categorising different technologies under reminder systems, capacity-building initiatives, community engagement initiatives, intersectoral coordination, wearable technology, regulation and monitoring and advocacy.Some technologies were established and successful such as immunization campaigns (including the polio campaign), Mission Indradhanush and Measles-Rubella campaign, while some were relatively new such as digital near-field communication pendants.Studies have also used multi-pronged strategies for strengthening overall immunization programs.Reminder strategies showed variable results.Whether one technology is better than the other remains uncertain.Future studies are required to ascertain the effectiveness and acceptability of single or multiple technologies for overall program improvement in different contexts, populations and geographic locations.

Implications of all the available evidence
Our study identifies multiple technologies that have been successful in the Indian context.These technologies need to be further explored and assessed for possible replication in low-performing districts, different populations, particularly vulnerable or vaccine-hesitant and in hard-toreach areas.This study will provide an evidence base for informing policy decisions on improving immunization programs and strengthening the healthcare system in India.At the same time, this study also highlights the lack of studies on impact of technologies on immunization of populations other than children and pregnant women.There are certain well-established technologies in other countries that have not been studied in India.Future research needs to be directed at studying newer technologies for improving immunization and also assessing the impact of existing successful technologies across other districts of the country.
India faces challenges of underfunded and overstretched health care system, weak surveillance and immunization infrastructure, reduced access to healthcare, lack of awareness and socio-cultural barriers to healthcare utilization. 7Strengthening immunization programs is essential to meet the regional and global disease elimination targets and to achieve the Sustainable Development Goal 3.
A concerted effort is needed to use innovative technologies, digital solutions and other approaches to strengthen the immunization programs so that no person is left behind as part of universal health coverage (UHC). 8ifferent technologies have been used as interventions to address inequitable access, suboptimal uptake and vaccine hesitancy. 9Technology offers significant potential to improve vaccine coverage and could be targeted for health system strengthening, regulation, program monitoring, evaluation, logistics management, capacity building, information and communication etc.The applicability and availability of technology types could vary with the geographical region, target population, context and setting.
11][12][13]18 A comprehensive realworld evaluation of the existing technologies in India, across all populations and settings, are needed for a better understanding of successful interventions for the Indian setting.Considering the diversity of Indian geography and culture, there is a need to adopt locally acceptable and feasible interventions.This systematic review was planned with the primary objective of collating available evidence on technologies that strengthen immunization across all age groups in India.

Search strategy and selection criteria
The protocol of this systematic review was registered in the Open Science Framework (OSF) registries database with a registration ID of osf.io/r42gm and can be accessed from their website (https://doi.org/10.17605/OSF.IO/R42GM). 19It is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines, and was started as a compendium of all evidence related to technologies affecting immunization in all geographical areas across the globe.This manuscript focuses on the evidence specific to the Indian context in the form of a systematic review as part of the Lancet Citizen's Commission's assignment on a collective effort towards generating evidence from India in the realm of health technology, human resources, governance, finance and citizens' engagement for realizing universal health coverage (UHC) in India.

Database search
We searched three databases viz.PubMed, Cochrane Library and Google Scholar, through January 1, 2011 to July 31, 2021, to include evidence from the last decade.The search strategy was designed to cover evidence related to technologies and interventions that affect immunization coverage across all populations and regions of India.The term "Technology" was defined as 'the application of scientific knowledge to practical purposes in any field', 20 which includes methods, techniques, and instrumentation.We used the Boolean operators 'OR' and 'AND' and combined four broad search blocks viz: 1) MeSH and Title abstract terms for 'vaccination' and 'immunization'; 2) MeSH and Title abstract terms for 'patient acceptance' and 'vaccine uptake'; and 3) MeSH and Title abstract terms for types of technologies, interventions and strategies.The details of PubMed search strategy are provided in Supplementary Table S1.The same search terms were used for Cochrane Library.

Study selection
All observational and experimental studies (randomized controlled trials, quasi-experimental studies, cohort studies, case-control studies or cross-sectional studies) from India, which assessed any kind of technology affecting immunization coverage, were included.Studies reporting impact of an intervention, even without a control arm (single-arm trials), were also included in the review in order to cover all possible technologies that play a role in improving immunization coverage.The included studies were conducted across all age groups and population types (pregnant women, caregivers, health care professionals, persons with comorbid conditions, vulnerable populations).We excluded non-English articles, protocols, conference abstracts, narrative reviews, systematic reviews, qualitative studies, modelling studies, letters, correspondence, guidelines, multi-national studies when data from Indian population was unavailable, opinion pieces, commentaries, editorials, blogs and newspaper articles.Unpublished and grey literature sources were not assessed.

Data analysis
The primary outcomes of interest were technologies that affect immunization coverage.Articles retrieved from all three databases were imported into the Dis-tillerSR software.Following removal of duplicates, titles and abstracts were screened for eligibility by two reviewers independently; discrepancies were resolved by mutual dialogue or by consultation with another reviewer.Full texts of eligible articles were retrieved and data extracted in DistillerSR, which included study identification details, study setting, place of study, duration, study design, number and types of vaccines studied, details of the number and types of technologies discussed.No authors were contacted for missing/additional information in the full text articles.The effect size(s) pertaining to the primary endpoint(s) of the study were extracted and presented, as reported in the publication.The findings from the adjusted analysis were presented, wherever available; no pooled analysis was conducted.

Quality assessment
The Mixed Methods Appraisal Tool (MMAT) 2018 was used to appraise the methodological quality of included studies independently by two reviewers in Microsoft Excel. 21Discrepancies in the scores were discussed and resolved, wherever applicable.The assessment included questions related to methodological approach, sampling procedure, response rate, confounders, measurement of outcomes and analysis.All eligible studies were included in the analysis regardless of their quality scores.

Role of the funding source
The Lancet Commission had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Study selection
The study selection details are shown in the PRISMA flow diagram (Fig. 1).The search identified 6809 articles.After removing duplicates (n = 217), 6592 articles were screened for titles and abstracts, of which 6542 articles were excluded.Full texts of 50 India-specific articles were obtained and assessed for eligibility.Twenty-three studies were included in this systematic review, after excluding 27 articles that did not report the primary outcomes including a modelling study which showed impact of community health workers on immunization coverage. 22The reasons for full-text exclusion are presented in Supplement S2.

Study characteristics
The study characteristics and the quality assessment scores of all the 23 included studies (with and without a comparison group) are described in Table 1, whereas those excluding the single-arm trials (17/23) are summarized in Supplementary Table S3.Majority (18/23; 78.26%) were published between 2016 and 2021.2][43][44][45] Three studies were conducted in two or more states. 23,28,41Most (21/23, 91.3%) were community-based; one was school based and one was conducted in a health care centre.Eleven (47.8%) studies reported data from rural settings, six (26.1%) from urban/peri-urban settings, and six (26.1%) from both (rural and urban/peri-urban) settings.A map showing the distribution of study sites is presented in Fig. 2. Almost half of the studies (12/23) were from the Empowered action group (EAG) states (Bihar, Jharkhand, Rajasthan and Uttar Pradesh), which have high fertility, poor socio-demographic and health indicators.There was limited representation from the north-eastern and southern parts of the country.The most common study designs were quasi-experimental studies (10), randomised controlled trials (RCT) (6), cross-sectional studies (3), programme evaluation studies (using secondary data) (2) and mixed methods studies (2).Children were the commonest (19/23; 82.6%) target population, followed by pregnant women (4/23; 17.4%).Fifteen studies assessed multiple vaccines recommended for children, two polio, one measles, one MR, one hepatitis B, while two studied maternal tetanus toxoid, and one maternal influenza vaccine.

Articles Quality assessment of studies
Though qualitative studies were not included, the qualitative component scoring was also provided for two mixed-methods studies as a requirement of MMAT.Almost all (22/23, 95.7%) studies had a consolidated score of three or more; one study had a score of one.No article was excluded from the analysis based on quality.
A detailed assessment of the quality of each study using the MMAT is provided in Supplementary Table S4.

Technologies for strengthening immunization coverage
The technologies identified in the studies were broadly categorised under eight different heads based on the type as shown in Fig. 3.These include the reminder systems, immunization campaigns, sensors and wearable technologies, intersectoral coordination, community mobilization/engagement, capacity building, regulation and monitoring and vaccine advocacy.Four studies reported technologies involving reminder systems which included automated mobile phone reminders with incentives, 29 mHealth application, 27 voice messages (mMitra) 33 and the Kilkari messaging program. 32There was only one study that reported the use of sensors and wearable technology wherein a bead was attached to a thread and worn by the participant. 38This was the digital Near-Field Communication (NFC) pendant which was provided with or without a voice call reminder to the study participants.Five studies reported the use of immunization campaigns as technologies that improved coverage.These included assessment of the impact of national immunization programs or initiatives Fig. 3: Technologies that affect immunization coverage across different settings in India.
like the high-intensity Mission Indradhanush, the Measles-Rubella Campaign, the Polio mass immunization campaigns. 23,40,44ollaborative approaches such as intersectoral coordination were also studied, mostly in the context of the Integrated Child Development Scheme (ICDS), which is a government aided program for early childhood care and development and works by improving community engagement through Anganwadi Centres.Other community mobilisation-related interventions included the involvement of women groups, especially appointed community guardians and home visits by health personnel.Capacity building by training and empowerment of health workers and deployment of staff in increased numbers, were commonly instituted technologies.One study reported the effect of a rural electrification program and showed how a non-health technological intervention had an effect on immunization rates. 28he majority of the technologies showed improvements in coverage or timeliness.The "my village my home" (MVMH) campaign, a simple poster-sized community based tool to record and monitor the vaccination status of every child in the community by the community health workers was promising. 30Assessed in few districts of Jharkhand and Uttar Pradesh in India and Timor Leste, the MVMH tool improved immunization coverage and timeliness.An RCT from Haryana showed enhanced impact of compliance-linked incentive-phone talk time given with automated mobile phone reminders on timeliness compared to the control or automated mobile phone reminder groups. 29A computerised immunization due list as part of the Rural Effective Affordable Comprehensive Health Care (REACH) technology studied in rural Rajasthan was successful in improving coverage. 39This technology used village mapping by GPS and computerised health data tracking.The community level social mobilisation (CLSM) initiative involving mobilisation through community workers and supplementary immunization activities including fixed-booth and house-to-house polio immunization in Uttar Pradesh was unique in countering vaccine hesitancy during the post-polio endemic period. 44The 'Muskaan Ek Abhiyan' (the smile campaign) was an effective multisectoral strategy in Bihar of enhanced intersectoral coordination, awareness generation, increased budgetary support, monitoring and supervision, tracking of beneficiaries and performance-based incentives to service providers. 25ducational interventions to the school children 36,42 and mothers of young children 43 were also encouraging.Some of the newer technologies did not improve coverage such as the digital NFC pendant 38 and the comprehensive RED strategy (Reaching Every District), 24 although they did lead to improvement in program quality.The impact of technologies also varied across states.For example, a high-intensity polio campaign resulted in a higher probability of vaccine uptake in Bihar while lower in Uttar Pradesh. 41

Discussion
The present review highlights the technologies that impact immunization coverage across all ages and populations in India.Twenty-three articles were included and more than half of them were quasiexperimental studies and RCTs.The technologies identified primarily included reminder systems, community mobilisation and capacity building related technologies.Almost all these technologies resulted in an increase in immunization coverage, however, the effectiveness results were variable for some, such as reminder systems; they also differed across states and settings.
Majority (82.6%) of the studies in the present review reported technologies for childhood immunization.The findings were similar to the recent global reviews for this population, wherein educational interventions, implementation of mandatory vaccination in schools, sending timely reminders, provider-directed interventions and financial incentives were found to improve childhood and adolescent vaccination coverage. 46,47Demand generation, modified vaccine delivery approaches, cash transfer programs, health systems strengthening and novel technology usage were also associated with increased immunization coverage of infants from low-and middle-income countries (LMICs). 48We did not find many studies on cash transfer programs and modified delivery approaches in the Indian context, which needs further exploration.Our review also included three studies on pregnant women, all of which assessed mHealth based technologies but showed variable results.Provision of pertussis vaccination by midwives at the place of antenatal care, automated reminders within the electronic medical record and increased provider awareness of recommendations have earlier been shown to be associated with higher maternal vaccine uptake. 49n the present review, we did not find much evidence on populations other than children and pregnant women.This depicts a significant lack of studies in the area of adult immunization, immunization of special/ vulnerable populations and occupational immunization.The dearth of studies in these populations emphasises the need for a life-course approach to immunization, covering individuals as they progress through different stages of life viz.adolescence, adulthood and old age.There is also a lack of disease burden data on the adults and immunocompromised populations.These population groups are often deprived of vaccines due to lack of knowledge about vaccines among public and health care providers, lack of standard guidelines and protocols, and non-inclusion in the Universal Immunization Program (UIP).Integration and intersectoral coordination may, therefore, be necessary for vaccine access among these population groups.
The supply-side technologies identified in this review were mostly directed at capacity building in the forms of teaching and training and increasing the workforce for immunization.The primary processes studied were directed at increasing community engagement.Increasing workforce may not always be a feasible option, given the lack of funding and resources.The review also had limited representation from the northeastern and southern parts of the country.In a country as vast and varied as India, differences in terrain, political interest, health care financing and population dynamics across states can result in certain technologies failing in certain settings.Except for one study, 35 we did not find much evidence of technologies for sensitising healthcare providers about new vaccines, vaccine recommendations and immunization policies for different populations in the Indian context.
In this review, most of the technologies were well established interventions.A new technology identified was the Jyotigram Yojana (JGY): a rural electrification program that resulted in an increased uptake of critical childhood vaccines.A big challenge in LMICs, like India, where the ambient temperatures are high and the electricity supply is unreliable, is the maintenance of cold chain storage for vaccines, 50 which can be improved through rural electrification.Interestingly, India has recently rolled out an electronic vaccine intelligence network (eVIN) system in some states in a phased manner.The eVIN system digitises the vaccine stock management, logistics and temperature tracking at all levels (national to sub-district) of vaccine storage, enabling the real-time monitoring of all the cold chain points.The MVMH-offline tool was found to be promising to track vaccination in communities and has been adapted by several state governments. 30The m-Health education programs of automated voice calls such as Kilkari and mMitra, have been scaled in many states across India, reaching millions of subscribers, suggesting the scalability of mobile based technologies in settings like India.Further, they also contribute to empower mothers.The digital NFC pendant was an innovative technology, although it did not improve the coverage significantly.The RED strategy was assessed in only one study in the present review.Developed in 2002 by WHO, it is a multifaceted strategy aimed at improving immunization services and includes reestablishing outreach services, supportive supervision, monitoring and data usage, improving resource management and increasing community service delivery links. 51It has been shown to strengthen the immunization programs in other countries, 52 although further evaluation is needed in Indian settings.
Very few novel machine-based technologies were evaluated in India, as compared to other countries.The possible reasons could be more emphasis on strengthening of existing capacity building and community engagement efforts for improving immunization coverage, lack of funding to explore newer machine-based technologies and notable differences in effectiveness of a technology due to diversity in the Indian population.
The strengths of this review lies in the fact that we included all study designs and populations, to cover the whole spectrum of technologies.Additionally, the quality of most studies included was above-average.There are, however, certain limitations.First, this review did not include qualitative study designs.Second, our search was limited to the Indian context and it is possible that the inclusion of evidence from countries with settings similar to India could have provided evidence on newer technologies useful for the Indian context.Third, our search was limited to English language publications only; it is possible that studies in regional languages may have been missed.Nonetheless, most of the scientific research from India is published in English-language journals.Additionally, limiting our search to three databases may have resulted in missing certain studies.Fourth, there is a possibility of publication bias, with unpublished studies and those with negative results being missed.A bibliometric analysis of the relevant studies may be considered in the future, which may uncover emerging trends, identify research gaps and help derive novel ideas for further investigation. 53ultiple interventions may be necessary to improve the routine immunization systems in India, as evidenced from multipronged interventions in four studies. 25,26,34,39mproving vaccine access may be a key issue to improve vaccination coverage, especially in marginalized and hardto-reach populations, for which additional human resources dedicated to social mobilization, advocacy, and community engagement will be crucial. 44or districts with the largest number of unimmunized children, the ones with the lowest coverage, better mapping and tracking tools for identifying beneficiaries and geospatial analysis may be useful.Vaccine mandates can be introduced for healthcare workers and occupationally-exposed employees.The UIP in India has introduced many vaccines for children, however, the platform needs to be further expanded to include adults, elderly and high-risk groups. 54Based on the recent success of Co-WIN portal for COVID-19 vaccination, India has initiated a pilot digital universal immunization program to keep the electronic immunization records of new-borns and pregnant mothers with features of reminders, online appointments, tracking on dropouts and digital vaccination certificates.This is suggestive of newer technologies being adopted, based on local experience, acceptance and success.Future research on newer technologies is needed to improve vaccine coverage and timeliness, including cost-effectiveness estimates.Research and development for novel vaccine candidates, multivalent vaccines, and improved vaccine delivery systems (such as microneedle patches) to reduce dependence on needles and cold-chain should be considered.
This review of 23 studies identified several technologies that strengthen immunization programmes in India.Our findings will also benefit other similar countries in the South Asian region and LMICs.The technologies that improve programmatic and health system improvements and strategic planning, such as aiding in the preparation of the immunization-due list, capacity building efforts and engagement of community health workers were found to be effective in improving immunization coverage, although further evaluation in low-performing districts, different population groups, particularly vulnerable or vaccine-hesitant, and hard-toreach areas are needed to ascertain their effectiveness across a range of settings.This will enable policy-makers to identify the most effective technologies for a diverse country like India.Our review had limited representation from populations other than children and pregnant women, which highlights the need for assessing the impact of established technologies in other population groups.Also, expanding the scope of this review to other LMICs, with settings like India, may help identify additional, potentially effective technologies.A multipronged strategy involving the most feasible, accessible, replicable and scalable technologies based on the local needs and perceived barriers, along-with planning and political will is needed to achieve the last mile immunization coverage in India.
Contributors GK conceived the study.ND and TK drafted the study protocol with inputs from MN, SA and RS.ND prepared the screening forms and data extraction sheet with input from all authors.TK, DV, SA, ND, CP and MN performed the article screening and data extraction.TK, CP, SA and MN performed the quality assessment.ND drafted the manuscript with inputs from TK and DV.All authors reviewed the manuscript and provided critical inputs.TK was involved in project administration, software management, coordination, communication, and led the whole review project.RS and GK provided guidance and supervision throughout the review process.We confirm that all authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.ND, TK and DV directly accessed and verified the underlying data reported in the manuscript.

Fig. 1 :
Fig. 1: Study selection.PRISMA Flowchart showing selection and inclusion of the studies in the review.

Fig. 2 :
Fig. 2: Map of India with states showing the location of the studies included in the review.