Enablers and barriers to rotavirus vaccine coverage in Assam, India- A qualitative study.

Background: Estimates suggest that 78,000 children died due to rotavirus gastroenteritis annually between 2011 and 2013 in India. The north eastern state of Assam reported 38.4% pediatric diarrheal admissions testing positive for rotavirus. Rotavirus vaccine (RVV) was introduced in Assam in 2017 following which the National Family Health Survey-5 (NFHS-5) (2019) revealed low RVV coverage in Assam with wide variation between the districts. the current study was conceptualized and undertaken to capture the enablers and barriers to RVV coverage in Assam. Methods: Qualitative study conducted in 5 randomly selected districts in Assam. Participants (key informants) were recruited by purposive sampling at each level of the health system including healthcare officials, service providers and caregivers based on availability. Thirty-five in-depth interviews (IDIs) and five focus group discussions (FGDs) were conducted. Interviews were tape recorded and transcribed. Data was coded and analyzed using the thematic framework approach. Results: Findings from the qualitative data collection were collated and analyzed under 7 identified themes. Difficult terrain, limited service provider availability and no catch-up training for new recruits were some of the barriers to RVV coverage. In contrast, Information, Education & Communication (IEC) in vernacular language, RVV safety profile, development partner support and adequate RVV supply were identified as some of the enablers of RVV coverage. Conclusion: Few broad recommendations to overcome identified barriers include comprehensive inter-sectoral coordination, regular monitoring and frequent refresher training sessions. There is a need for a future study utilizing existing coverage data and larger sample size to triangulate the findings of this study.

Health impact and cost-effectiveness of expanding routine immunization coverage in India through Intensified Mission Indradhanush.

Many children do not receive a full schedule of childhood vaccines, yet there is limited evidence on the cost-effectiveness of strategies for improving vaccination coverage. Evidence is even scarcer on the cost-effectiveness of strategies for reaching "zero-dose children," who have not received any routine vaccines. We evaluated the cost-effectiveness of periodic intensification of routine immunization (PIRI), a widely applied strategy for increasing vaccination coverage. We focused on Intensified Mission Indradhanush (IMI), a large-scale PIRI intervention implemented in India in 2017-2018. In 40 sampled districts, we measured the incremental economic cost of IMI using primary data, and used controlled interrupted time-series regression to estimate incremental vaccination doses delivered. We estimated deaths and disability-adjusted life years (DALYs) averted using the Lives Saved Tool and reported cost-effectiveness from immunization program and societal perspectives. We found that, in sampled districts, IMI had an estimated incremental cost of 2021US$13.7 (95% uncertainty interval: 10.6 to 17.4) million from an immunization program perspective and increased vaccine delivery by an estimated 2.2 (-0.5 to 4.8) million doses over a 12-month period, averting an estimated 1,413 (-350 to 3,129) deaths. The incremental cost from a program perspective was $6.21 per dose ($2.80 to dominated), $82.99 per zero-dose child reached ($39.85 to dominated), $327.63 ($147.65 to dominated) per DALY averted, $360.72 ($162.56 to dominated) per life-year saved, and $9,701.35 ($4,372.01 to dominated) per under-five death averted. At a cost-effectiveness threshold of 1x per-capita GDP per DALY averted, IMI was estimated to be cost-effective with 90% probability. This evidence suggests IMI was both impactful and cost-effective for improving vaccination coverage, though there is a high degree of uncertainty in the results. As vaccination programs expand coverage, unit costs may increase due to the higher costs of reaching currently unvaccinated children.

Using freeze-preventive cold boxes in rural Nepal: A study of equipment performance, acceptability, system fit, and cost.

We conducted a field evaluation using qualitative and quantitative methods to assess freeze prevention of vaccines transported and stored in a recently developed, World Health Organization-prequalified freeze-preventive cold box (FPCB) as compared to currently used standard cold boxes (SCBs). The study assessed the FPCB's practical use, health worker acceptance, health system fit (including cost considerations), and challenges faced by health workers in variable conditions and geographical settings. The evaluation took place in five health facilities across hilly and plains districts of Nepal in two phases: Phase 1 involved FPCBs in simulated use alongside SCBs. In Phase 2, actual vaccines were used in the FPCBs. The study gathered quantitative data from logbooks and electronic temperature monitors placed inside and outside the cold boxes. Qualitative data were collected from health workers, cold chain personnel, and immunization program managers involved in the vaccine cold chain at multiple levels. No damage, durability issues, or freezing incidents were observed when using FPCBs, but two incidents of freezing occurred when using SCBs. FPCBs also took longer to cool down than SCBs. Participants mostly found the FPCB to be safe and user friendly for vaccine transportation and short-term storage. Advantages of the FPCB as compared to the SCB include its ability to minimize vaccine wastage, to keep freeze-sensitive vaccines safe (the average value of freeze-sensitive vaccines transported per shipment was $1,704), and to ease preparation through elimination of the need to condition ice packs. Procurement price ranges for FPCBs overlap those for SCBs. Disadvantages of the FPCB include its greater size and weight, which require more personnel and vehicles during transportation. This suggests that lighter and smaller FPCBs would be more effective and acceptable for the Nepal immunization program and other, similar immunization programs conducted globally.

Using new cold chain technologies to extend the vaccine cold chain in India: Equipment performance, acceptability, systems fit, and costs.

This study evaluated the performance, acceptability, costs, and systems fit of three new cold chain devices in India: a second-generation ice-lined refrigerator (ILR), a solar direct drive (SDD) refrigerator, and a long-term passive device (LTPD). The evaluation was conducted over 15 months during 2016-2017. Sites were selected for their diversity in climate, terrain, and grid electrical supply, and 31 cold chain devices were deployed, 1 to each site. Results showed that all three technologies maintained correct temperatures. The SDD refrigerators had no malfunctions, whilst the ILRs had at least one malfunction, mostly due to the printed circuit board's sensitivity to the erratic power supply. The LTPD temperature display panel caused challenges initially that required replacement of all solar panels with lithium batteries. Yet the devices' long holdovers helped ensure vaccine potency. One challenge, particularly with the ILRs and SDD refrigerators, was condensation. The passively cooled LTPD was valued in settings with smaller populations and unreliable or no power; however, some its features, including the need to condition ice blocks, made it challenging to operate. In addition, the acceptable temperature range for the LTPD, as for all passively cooled devices (greater than 0 °C and less than + 10 °C), was confusing for some health workers due to the decades-long emphasis on maintaining temperatures at + 2 °C to + 8 °C. The greatest system-related benefit was establishment of new cold chain points (CCPs) at locations with intermittent or no grid electricity, bringing immunisation services closer to hard-to-reach areas. A key limitation of all three devices was the inability to freeze ice packs, which are required for vaccine carriers, somewhat restricting the potential of these technologies to reach underserved populations. Moreover, establishing new CCPs added costs to the health system. Results from this study, including costing data, can help guide decision-making.

Enablers and Barriers to the Scaling Up of Pneumococcal Conjugate Vaccine in India During the COVID-19 Pandemic: A Qualitative Study.

Background: Pneumonia is one of the leading causes of death in under-5 children in India. This led the Ministry of Health & Family Welfare (MoHFW) in India to decide for the nationwide roll-out of the Pneumococcal Conjugate Vaccine (PCV). However, the introduction of PCV became more complex in the face of unprecedented challenges set forth by the COVID-19 pandemic. The study aims to assess enablers and barriers to the introduction of PCV in India during the pandemic. Methodology: Qualitative research approach involving key-informant interviews from John Snow India (JSI), the lead technical agency that supported MoHFW in the PCV expansion was employed to delineate the enablers and barriers. Principle of saturation was employed to derive the sample size. Thematic analysis using inductive approach was based on the modified World Health Organization (WHO) framework for new vaccine introduction impact on the Immunization and Health Systems, using NVIVO 12 qualitative data analysis software. Results: A total of 11 key informants (4 national-level program managers and 7 state technical officers) were telephonically interviewed. The study found social acceptance, lower cost of the vaccine, and intensive communication activities as potential enablers. Other enablers for PCV introduction included a robust vaccine supply-chain system, ample cold-chain space availability, and strong political commitment, despite the ongoing second wave. Further, the identified barriers included poor physical access, insufficient social mobilization, and limited advocacy along with a stretched workforce. Conclusion: The study delineated several enablers and barriers to introducing PCV in the country during the pandemic. The existing barriers in the PCV roll-out prompted the need to address these gaps, making key program-based recommendations to improve future new vaccine introductions during the pandemic.

Improving Equity in Urban Immunization in Low- and Middle-Income Countries: A Qualitative Document Review.

INTRODUCTION: As the world continues to urbanize, particularly in low- and middle-income countries, understanding the barriers and effective interventions to improve urban immunization equity is critical to achieving both Immunization Agenda 2030 targets and the Sustainable Development Goals. Approximately 25 million children missed one or more doses of the diphtheria, tetanus and pertussis (DTP3) vaccine in 2021 and it is estimated that close to 30% of the world's children missing the first dose of DTP, known as zero-dose, live in urban and peri-urban settings. METHODS: The aim of this research is to improve understanding of urban immunization equity through a qualitative review of mixed method studies, urban immunization strategies and funding proposals across more than 70 urban areas developed between 2016 and 2020, supported by Gavi, the Vaccine Alliance. These research studies and strategies created a body of evidence regarding the barriers to vaccination in urban settings and potential interventions relevant to low- and middle-income countries (LMICs) with a focus on the vaccination of urban poor, populations of concern and residents of informal settlements. Through the document review we identified common challenges to achieving equitable coverage in urban areas and mapped proposed interventions. RESULTS: We identified 70 documents as part of the review and categorized results across (1) social determinants of health, (2) immunization service-delivery barriers and (3) quality of services. Barriers and solutions identified in the documents were categorized in these thematic areas, drawing information from results in more than 21 countries. CONCLUSION: Populations of concern such as migrants, refugees, residents of informal settlements and the urban poor face barriers to accessing care which include poor availability and quality of service. Example solutions proposed to these challenges include tailored delivery strategies, improved use of digital data collection and child-friendly services. More research is required on the efficacy of the proposed interventions identified and on gender-specific dynamics in urban poor areas affecting equitable immunization coverage.

Critical factors in the successful expansion of Pneumococcal Conjugate Vaccine in India during the COVID-19 pandemic.

India had decided to roll out PCV in India in 2015, but successful implementation of any new vaccine introduction mandates an enormous effort. PCV was scaled up during the COVID-19 pandemic, which posed new, unprecedented challenges in the vaccine rollout. However, India successfully expanded PCV in the country in record time across all states and Union Territories. During the pandemic, supply-side restrictions, delayed vaccine shipments, staff shortages, and restrictions in conducting training negatively affected the roll-out of PCV across the country. However, despite the ongoing pandemic, India successfully rolled out PCV across the country in 7 months. In this review, the authors have conducted a narrative review to delineate the crucial factors that helped in the successful expansion of PCV.

Achieving the IA2030 Coverage and Equity Goals through a Renewed Focus on Urban Immunization.

The 2021 WHO and UNICEF Estimates of National Immunization Coverage (WUENIC) reported approximately 25 million under-vaccinated children in 2021, out of which 18 million were zero-dose children who did not receive even the first dose of a diphtheria-tetanus-pertussis-(DPT) containing vaccine. The number of zero-dose children increased by six million between 2019, the pre-pandemic year, and 2021. A total of 20 countries with the highest number of zero-dose children and home to over 75% of these children in 2021 were prioritized for this review. Several of these countries have substantial urbanization with accompanying challenges. This review paper summarizes routine immunization backsliding following the COVID-19 pandemic and predictors of coverage and identifies pro-equity strategies in urban and peri-urban settings through a systematic search of the published literature. Two databases, PubMed and Web of Science, were exhaustively searched using search terms and synonyms, resulting in 608 identified peer-reviewed papers. Based on the inclusion criteria, 15 papers were included in the final review. The inclusion criteria included papers published between March 2020 and January 2023 and references to urban settings and COVID-19 in the papers. Several studies clearly documented a backsliding of coverage in urban and peri-urban settings, with some predictors or challenges to optimum coverage as well as some pro-equity strategies deployed or recommended in these studies. This emphasizes the need to focus on context-specific routine immunization catch-up and recovery strategies to suit the peculiarities of urban areas to get countries back on track toward achieving the targets of the IA2030. While more evidence is needed around the impact of the pandemic in urban areas, utilizing tools and platforms created to support advancing the equity agenda is pivotal. We posit that a renewed focus on urban immunization is critical if we are to achieve the IA2030 targets.

An Equity Analysis of Zero-Dose Children in India Using the National Family Health Survey Data: Status, Challenges, and Next Steps.

Background While immunization programs across the world have made considerable progress, children and communities continue to be beyond the reach of healthcare services. Globally, they are now referred to as zero-dose (ZD) children (those who have not received a single dose of diphtheria, pertussis, and tetanus-containing vaccine). Pre-COVID-19 pandemic analyses suggest that nearly 50% of vaccine-preventable deaths occur among ZD children. Two-thirds of these children live in extremely poor households suffering from multiple deprivations including lack of access to reproductive health services, water, and sanitation. Hence, ZD children have now been prioritized as a key cohort for identification and integration with the health systems as we build back from the pandemic. Methodology Extracting data from the last two National Family Health Survey (NFHS) rounds (NFHS 4, 2015-2016 and NFHS 5, 2019-2021), this study aims to ascertain the status of ZD children aged 12-23 months in India, the challenges, and the necessary action agenda going forward. Data were analyzed for equity determinants such as gender, place of residence, religion, birth order, caste, and mother's schooling. Key determinants included the change in ZD prevalence at the national, state, and district levels; variations across equity parameters and states with maximum improvements; and disparity across these indicators. A correlation analysis was also conducted to understand the nature of the association between ZD prevalence and critical maternal and child health indicators. Results The overall ZD prevalence between the two rounds was reduced by 4.1% (10.5-6.4%). A total of 26 states in the country reported a ZD prevalence of <10% in NFHS 5 compared to 18 in NFHS 4. In total, 324 districts reported a ZD prevalence of <5%, and 145 districts reported a prevalence of >10%. The equity parameters reflected a slow-footed reduction among ZD for girl children, across urban geographies, firstborn children, mothers with 12 or more years of schooling, and children in families with the highest wealth quintiles. A negative correlation accentuated between the two NFHS rounds was established between first-trimester registration, four or more antenatal visits, institutional deliveries, and ZD prevalence. Conclusions The findings point toward sustained improvement across key equity parameters, however, challenges do exist. Moreover, the impact of the pandemic on immunization programs across the globe and in India is bound to halt and reverse the progress and potentiate further inequities. It is thus imperative that continued and augmented efforts are continued to identify, integrate, and immunize ZD children, families, and communities.

Using long-range freeze-preventive vaccine carriers in Nepal: A study of equipment performance, acceptability, systems fit, and cost.

Preventing vaccine freezing is one of the biggest challenges in vaccine management. Until 2018, vaccine carriers used in the immunization program lacked features to prevent vaccine freezing. Freeze-preventive vaccine carriers (FPVCs) have an engineered liner that buffers vaccines from direct exposure to frozen ice packs. A field evaluation of three FPVCs was conducted in 24 health posts in eastern Nepal. The objective was to evaluate the FPVCs' performance, acceptability, systems fit, and cost, to inform prequalification and introduction planning. The study was carried out in two phases: in the first phase, FPVCs containing dummy vaccines (labeled "Not for Human Use") were transported to outreach sessions along with a standard vaccine carrier (SVC); in the second phase, the FPVCs were used for transporting vaccines taken to outreach sessions and used for vaccinating eligible children. The study gathered quantitative and qualitative data from health workers, logbooks, and electronic temperature monitors placed inside and outside the FPVCs. Results indicate the FPVCs successfully prevented temperatures below 0 °C more than 99% of the time-except at one site, where ambient temperatures were below the minimum rated testing temperature specified by the World Health Organization. Internal cool-down times for the FPVCs were highly variable, as were mean kinetic temperatures, possibly driven by the wide range of ambient temperatures and higher-than-expected variations in freezer performance, which, along with the need to transport ice packs to some locations, affected ice-pack temperatures. Almost all health workers requested smaller, lighter-weight FPVCs but appreciated the FPVCs' ability to prevent vaccines from freezing while avoiding undue heat exposure. FPVCs had benefit-cost ratios greater than 1 and hence good value for money. Results point to the importance of understanding the intended environment of use and the need for smaller, short-range as well as long-range carriers.

Public finance of universal routine childhood immunization in India: district-level cost estimates.

India's Universal Immunization Programme (UIP) is among the largest routine childhood vaccination programmes in the world. However, only an estimated 65% of Indian children under the age 2 years were fully vaccinated in 2019. We estimated the cost of raising childhood vaccination coverage to a minimum of 90% in each district in India. We obtained vaccine price data from India's comprehensive multi-year strategic plan for immunization. Cost of vaccine delivery by district was derived from a 2018 field study in 24 districts. We used propensity score matching methods to match the remaining Indian districts with these 24, based on indicators from the National Family Health Survey (2015-16). We assumed the same unit cost of vaccine delivery in matched pair districts and estimated the total and incremental cost of providing routine vaccines to 90% of the current cohort of children in each district. The estimated national cost of providing basic vaccinations-one dose each of Bacillus Calmette-Guerin (BCG) and measles vaccines, and three doses each of oral polio (OPV) and diphtheria, pertussis and tetanus vaccines-was $784.91 million (2020 US$). Considering all childhood vaccines included in UIP during 2018-22 (one dose each of BCG, hepatitis B and measles-rubella; four doses of OPV; two doses of inactivated polio; and three doses each of rotavirus, pneumococcal and pentavalent vaccines), the estimated national cost of vaccines and delivery to 90% of target children in each district was $1.73 billion. The 2018 UIP budget for vaccinating children, pregnant women and adults was $1.17 billion (2020 US$). In comparison, $1.73 billion would be needed to vaccinate 90% of children in all Indian districts with the recommended schedule of routine childhood vaccines. Additional costs for infrastructural investments and communication activities, not incorporated in this study, may also be necessary.

Cost of conducting Measles-Rubella vaccination campaign in India.

A Measles-Rubella (MR) vaccination campaign was launched in India in a phased manner in February 2017 to cover children aged 9 months to 15 years. As evidence on campaign vaccine delivery costs is limited, the delivery cost for MR campaign from a government provider perspective was estimated in four Indian states, namely, Assam, Gujarat, Himachal Pradesh, and Uttar Pradesh. Costs were calculated in top-down and bottom-up approaches using data collected from 84 sites at different administrative levels and immunization partners in the study states from August 2019 to March 2020. All costs were presented in 2019 US$ and Indian Rupee (INR). The financial cost per dose of the MR campaign including all partner support ranged from US$0.16 (INR 10.95) in Uttar Pradesh to US$0.34 (INR 24.13) in Gujarat. In Uttar Pradesh, the full economic cost per dose was US$0.87 (INR 61.39). The key financial cost drivers were incentives related to service delivery and supervision, the printing of reporting formats for record-keeping, social mobilization, and advocacy. The financial delivery cost per dose estimated was higher than the government pre-fixed budget per child for the MR campaign, probably indicating an insufficient budget. However, the study found underutilization of MR budget in two states and use of other sources of funding for the campaign indicating the need for proper utilization of the campaign budgets by the states. Unit cost information generated from this study will be useful for planning, cost projections, and economic analysis of future vaccination campaigns in India.

Strengthening the immunization supply chain: A time-to-supply based approach to cold chain network optimization & extension in Madhya Pradesh.

Expansion of immunization coverage is dependent in part on delivering potent vaccines in an equitable and timely manner to immunization outreach session sites from Cold Chain Points (CCPs). When duration of travel between the last CCP and the session site (Time-to-Supply) is too long, three consequences may arise: decreased potency due to exposure to heat and freezing, beneficiary dropouts due to delayed session starts, and, increased operational costs for the Health Facility (HF) conducting the outreach sessions. Guided by the Government of India's recommendation on cold chain point expansion to ensure that all session sites are within a maximum of 60 min from the last CCP, CHAI and the State Routine Immunization Cell in the state of Madhya Pradesh collaborated to pilot a novel approach to cold chain network optimization and expansion in eight districts of Madhya Pradesh. Opportunities for realignment of remote sub-health centers (SHCs) and corresponding session sites to alternative existing CCPs or to HFs which could be converted to new CCPs were identified, and proposed using a greedy adding algorithm-based optimization which relied on health facility level geo-location data. Health facility geo-coordinates were collected through tele-calling and site visits, and a Microsoft Excel based optimization tool was developed. This exercise led to an estimated reduction in the number of remote SHCs falling beyond the permissible travel time from CCPs by 56.89 percent (132 remote sites), from 232 to 100. The 132 resolved sites include 73 sites realigned to existing CCPs, and 59 sites to be attached to 22 newly proposed CCPs. Both the network optimization approach and the institutional capacity built during this project will continue to be useful to India's immunization program. The approach is replicable and may be leveraged by developing countries facing similar challenges due to geographical, institutional, and financial constraints.

A Conserved Role for Asrij/OCIAD1 in Progenitor Differentiation and Lineage Specification Through Functional Interaction With the Regulators of Mitochondrial Dynamics.

Mitochondria are highly dynamic organelles whose activity is an important determinant of blood stem and progenitor cell state. Mitochondrial morphology is maintained by continuous fission and fusion and affects stem cell proliferation, differentiation, and aging. However, the mechanism by which mitochondrial morphology and dynamics regulate cell differentiation and lineage choice remains incompletely understood. Asrij/OCIAD1 is a conserved protein that governs mitochondrial morphology, energy metabolism and human embryonic stem cell (hESC) differentiation. To investigate the in vivo relevance of these properties, we compared hESC phenotypes with those of Drosophila hematopoiesis, where Asrij is shown to regulate blood progenitor maintenance by conserved mechanisms. In concordance with hESC studies, we found that Drosophila Asrij also localizes to mitochondria of larval blood cells and its depletion from progenitors results in elongated mitochondria. Live imaging of asrij knockdown hemocytes and of OCIAD1 knockout hESCs showed reduced mitochondrial dynamics. Since key regulators of mitochondrial dynamics actively regulate mitochondrial morphology, we hypothesized that mitochondrial fission and fusion may control progenitor maintenance or differentiation in an Asrij-dependent manner. Knockdown of the fission regulator Drp1 in Drosophila lymph gland progenitors specifically suppressed crystal cell differentiation whereas depletion of the fusion regulator Marf (Drosophila Mitofusin) increased the same with concomitant upregulation of Notch signaling. These phenotypes were stronger in anterior progenitors and were exacerbated by Asrij depletion. Asrij is known to suppress Notch signaling and crystal cell differentiation. Our analysis reveals that synergistic interactions of Asrij with Drp1 and Marf have distinct impacts on lymph gland progenitor mitochondrial dynamics and crystal cell differentiation. Taken together, using invertebrate and mammalian model systems we demonstrate a conserved role for Asrij/OCIAD1 in linking mitochondrial dynamics and progenitor differentiation. Our study sets the stage for deciphering how regulators of mitochondrial dynamics may contribute to functional heterogeneity and lineage choice in vertebrate blood progenitors.

Assessment of the knowledge, preferences and concern regarding the prospective COVID-19 vaccine among adults residing in New Delhi, India - A cross-sectional study.

BACKGROUND: Understanding the perception and concerns of people about COVID-19 vaccine in developing and populous country like India will help in understanding demand for the vaccine and further tailoring out public health information and education activities. The study was carried out to assess the present state of knowledge people have about the probable vaccine for COVID-19, to know the preferences of respondents about this vaccine and to learn the expectations and apprehensions of people about features of this prospective COVID-19 vaccine residing in the capital city of India. METHODS: This cross-sectional study was conducted amongst the residents of Delhi, India from July to October 2020. Both offline and online interview method was used to collect date from 513 participants representing various occupational strata. Data were collected on sociodemographic variable, vaccine acceptance and concerns regarding COVID-19 vaccine. RESULTS: Among the study population, 79.5% said they will take the vaccine while 8.8% said they were not going to take the vaccine and remaining 11.7% had not yet decided about it. More than 50% were willing to pay for the vaccine and 72% felt vaccine should first be given to health workers and high-risk group. CONCLUSION: The following study has helped to understand the percentage of people who are hesitant to take the vaccine and also the concerns regarding the vaccine. Also since half of the population is willing to pay for the vaccine, a strategic approach considering the various economical classes of people could be applied in a developing country like India.

The incremental cost of improving immunization coverage in India through the Intensified Mission Indradhanush programme.

Intensified Mission Indradhanush (IMI) was a strategic endeavour launched by the Government of India aiming to achieve 90% full immunization coverage in the country by 2018. The basic strategy of this special drive involved identifying missed children and vaccinating them in temporary outreach sites for 1 week over consecutive 4-month period starting from October 2017. This study estimated the incremental economic and financial cost of conducting IMI in India from a government provider perspective. Five states-Assam, Bihar, Maharashtra, Rajasthan and Uttar Pradesh were purposefully selected because of high concentration of IMI activities. The stratified random sample of 40 districts, 90 sub-districts and 289 sub-centres were included in this study. Cost data were retrospectively collected at all levels from administrative records, financial records and staff interviews involved in IMI. The weighted incremental economic cost per dose (including vaccine costs) was lowest in Uttar Pradesh (US$3.45) and highest in Maharashtra (U$12.23). Incremental economic cost per IMI dose was found to be higher than a recent routine immunization costing study by Chatterjee and colleagues in 2018, suggesting that it requires additional resources to immunize children through an intensified push in hard-to-reach areas. Incremental financial cost of the IMI programme estimated in this study will be helpful for the government for any future planning of such special initiative. The reasons for variation of unit costs of IMI across the study districts are not known, but lower baseline coverage, high population density, migration, geography and terrain and vaccinating small numbers of children per session could account for the range of findings. Further analysis is required to understand the determinants of cost variations of the IMI programme, which may aid in better planning and more efficient use of resources for future intensified efforts.

Impact of campaign-style delivery of routine vaccines: a quasi-experimental evaluation using routine health services data in India.

The world is not on track to achieve the goals for immunization coverage and equity described by the World Health Organization's Global Vaccine Action Plan. Many countries struggle to increase coverage of routine vaccination, and there is little evidence about how to do so effectively. In India in 2016, only 62% of children had received a full course of basic vaccines. In response, in 2017-18 the government implemented Intensified Mission Indradhanush (IMI), a nationwide effort to improve coverage and equity using a campaign-style strategy. Campaign-style approaches to routine vaccine delivery like IMI, sometimes called 'periodic intensification of routine immunization' (PIRI), are widely used, but there is little robust evidence on their effectiveness. We conducted a quasi-experimental evaluation of IMI using routine data on vaccine doses delivered, comparing districts participating and not participating in IMI. Our sample included all districts that could be merged with India's 2016 Demographic and Health Surveys data and had available data for the full study period. We used controlled interrupted time-series analysis to estimate the impact of IMI during the 4-month implementation period and in subsequent months. This method assumes that, if IMI had not occurred, vaccination trends would have changed in the same way in the participating and not participating districts. We found that, during implementation, IMI increased delivery of 13 infant vaccines, with a median effect of 10.6% (95% confidence interval 5.1% to 16.5%). We did not find evidence of a sustained effect during the 8 months after implementation ended. Over the 12 months from the beginning of implementation, we estimated reductions in the number of under-immunized children that were large but not statistically significant, ranging from 3.9% (-6.9% to 13.7%) to 35.7% (-7.5% to 77.4%) for different vaccines. The largest effects were for the first doses of vaccines against diphtheria-tetanus-pertussis and polio: IMI reached approximately one-third of children who would otherwise not have received these vaccines. This suggests that PIRI can be successful in increasing routine immunization coverage, particularly for early infant vaccines, but other approaches may be needed for sustained coverage improvements.

Typhoid in India: An Age-old Problem With an Existing Solution.

Enteric fever continues to impact millions of people who lack adequate access to clean water and sanitation. The typhoid and paratyphoid fever burden in South Asia is broadly acknowledged, but current estimates of incidence, severity, and cost of illness from India are lacking. This supplement addresses this gap in our knowledge, presenting findings from two years of surveillance, conducted at multiple sites between October 2017 and February 2020, in the Surveillance for Enteric Fever in India (SEFI) network. Results provide contemporaneous evidence of high disease burden and cost of illness-the latter borne largely by patients in the absence of universal healthcare coverage in India. Against a backdrop of immediate priorities in the COVID-19 pandemic, these data are a reminder that typhoid, though often forgotten, remains a public health problem in India. Typhoid conjugate vaccines, produced by multiple Indian manufacturers, and recommended for use in high burden settings, ensure that the tools to tackle typhoid are an immediately available solution to this public health problem.

Oral cholera vaccine delivery strategy in India: Routine or campaign?-A scoping review.

Oral Cholera Vaccine (OCV) has been recognized as an adjunct tool for prevention and control of cholera. However, policy directions are currently unavailable in India to guide the vaccine delivery. We conducted a scoping review to inform the policy about the scopes and challenges of different strategic choices of OCV delivery in India in light of current evidences, highlighting the scope of new research. METHODS: Adopting the Arksey and O'Malley Framework for review, we searched for literatures on "efficacy", "effectiveness", and "cost" of oral cholera vaccine delivery through different strategies in Pubmed and Scopus. RESULTS: We found that the protective efficacy of OCV depends on its coverage. Evidence on effectiveness of OCV are available for both reactive and pre-vaccination campaigns. Reactive high-risk vaccination is more effective than reactive ring and mass vaccination. Pre-vaccination campaigns are more effective than reactive vaccination when vaccine availability is adequate. Pre-vaccination through school campaigns in 1-14 years age group have been cost effective in India. Vaccination campaigns in under-5 children are also cost effective in spite of low efficacy due to the scope of averting a higher number of cases. However, no evidence is available regarding efficacy and effectiveness of OCV in children <1 year as well as the effectiveness of delivering OCV through routine immunization. CONCLUSION: Little evidence exist to depict mass-campaign as more economic and effective than routine expanded programme on immunization (EPI) session for delivery of OCV. Considering operational feasibility, it needs to be explored whether OCV delivery strategy is compatible with India's current EPI, if it can be introduced in routine immunization at measles containing vaccine age-schedule, optionally preceded by a campaign in targeted hot-spots in the 1-14 year age-group. Safety and efficacy data of OCV during infancy as well as hot-spot surveillance are pre-requisites for formulation of such EPI policy.

Introducing rotavirus vaccine in the Universal Immunization Programme in India: From evidence to policy to implementation.

BACKGROUND: In 2016, India became one of the first countries in Asia to introduce an indigenously manufactured rotavirus vaccine. However, any new vaccine introduction needs to be meticulously planned to allow for strengthening of the existing immunization systems instead of burdening them. METHODS: The process of rotavirus vaccine introduction in India started with the establishment of National Rotavirus Surveillance Network in 2005 which generated relevant evidence to inform policy level decisions to introduce the vaccine. The preparatory activities started with assessment of health systems and closing any gaps. This was followed by development of vaccine specific training packages and cascade training for programme managers and health workers. The introduction was complemented with strong communications systems and media involvement to allow for good acceptability of the vaccine on the ground. Each step of introduction was led by the government and technically supported by development partners. RESULTS: India introduced rotavirus vaccine in a phased wise manner. In the first two phases the vaccine has been introduced in nine states of the country accounting for nearly 35% of the annual birth cohort of the country. From March 2016 to November 2017, approximately 13,260,000 rotavirus vaccine doses were administered in the country. The vaccine was well accepted by both the health workers and parents/caregivers. CONCLUSION: Rotavirus vaccine introduction in India is an excellent example of how government stewardship with well-defined roles for development partners can allow a new vaccine introduction to be used as a system strengthening activity.