Introduction of the pneumococcal conjugate vaccine in humanitarian and fragile contexts: Perspectives from stakeholders in four African countries.

Childhood pneumonia causes a significant burden of preventable child morbidity and mortality in Chad, Guinea, Somalia/Somaliland, and South Sudan. Leaders from these countries have committed to reducing this burden and are preparing to introduce the pneumococcal conjugate vaccine (PCV) into their immunization programs. To support long-term sustainability for expected PCV introductions in settings afflicted by prolonged humanitarian crises this research explores national stakeholders' perspectives on contextual factors that may influence optimal vaccine implementation. This qualitative study used purposive sampling to identify and interview stakeholders involved in vaccine decision-making. Interview transcripts were analyzed through the framework method, an approach involving charting data into pre-populated matrices. Findings from interviews with 16 key informants from government, partner organizations, and international health agencies fit within the following four overarching themes: (1) population-level vulnerabilities to pneumonia, exacerbated by climatic risks and low levels of maternal education; (2) disease burden and the interest in enhancing surveillance to monitor vaccine impact and integrate disease control efforts; (3) policy processes, including formalizing vaccine decision-making; and (4) vaccine implementation preparation, including the conduct of robust communication campaigns, training, and cold chain upgrades. This research explores perspectives from leaders in these countries which are at pivotal moments in their journeys toward introducing PCV. Widespread commitment among leaders, in addition to financial support, will facilitate vaccine introduction. Further, fostering a shared understanding among partners about context-specific determinants of program success will help build tailored implementation strategies for each country.

Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.

Understanding household-level risk factors for zero dose immunization in 82 low- and middle-income countries.

INTRODUCTION: In 2021, an estimated 18 million children did not receive a single dose of routine vaccinations and constitute the population known as zero dose children. There is growing momentum and investment in reaching zero dose children and addressing the gross inequity in the reach of immunization services. To effectively do so, there is an urgent need to characterize more deeply the population of zero dose children and the barriers they face in accessing routine immunization services. METHODS: We utilized the most recent DHS and MICS data spanning 2011 to 2020 from low, lower-middle, and upper-middle income countries. Zero dose status was defined as children aged 12-23 months who had not received any doses of BCG, DTP-containing, polio, and measles-containing vaccines. We estimated the prevalence of zero-dose children in the entire study sample, by country income level, and by region, and characterized the zero dose population by household-level factors. Multivariate logistic regressions were used to determine the household-level sociodemographic and health care access factors associated with zero dose immunization status. To pool multicountry data, we adjusted the original survey weights according to the country's population of children 12-23 months of age. To contextualize our findings, we utilized United Nations Population Division birth cohort data to estimate the study population as a proportion of the global and country income group populations. RESULTS: We included a total of 82 countries in our univariate analyses and 68 countries in our multivariate model. Overall, 7.5% of the study population were zero dose children. More than half (51.9%) of this population was concentrated in African countries. Zero dose children were predominantly situated in rural areas (75.8%) and in households in the lowest two wealth quintiles (62.7%) and were born to mothers who completed fewer than four antenatal care (ANC) visits (66.5%) and had home births (58.5%). Yet, surprisingly, a considerable proportion of zero dose children's mothers did receive appropriate care during pregnancy (33.5% of zero dose children have mothers who received at least 4 ANC visits). When controlled for other factors, children had three times the odds (OR = 3.00, 95% CI: 2.72, 3.30) of being zero dose if their mother had not received any tetanus injections, 2.46 times the odds (95% CI: 2.21, 2.74) of being zero dose if their mother had not received any ANC visits, and had nearly twice the odds (OR = 1.87, 95% CI: 1.70, 2.05) of being zero dose if their mother had a home delivery, compared to children of mothers who received at least 2 tetanus injections, received at least 4 ANC visits, and had a facility delivery, respectively. DISCUSSION: A lack of access to maternal health care was a strong risk factor of zero dose status and highlights important opportunities to improve the quality and integration of maternal and child health programs. Additionally, because a substantial proportion of zero dose children and their mothers do receive appropriate care, approaches to reach zero dose children should incorporate mitigating missed opportunities for vaccination.

Closing the pneumococcal conjugate vaccine (PCV) introduction gap: an archetype analysis of last-mile countries.

BACKGROUND: Pneumonia remains the leading infectious cause of global childhood deaths, despite the availability of pneumococcal conjugate vaccine (PCV) products and widespread evidence of their safety and efficacy. OBJECTIVE: To map the landscape of countries that are yet to fully include PCV in their National Immunization Programs, we conducted an archetype analysis of country indicators related to barriers and facilitators for PCV decision-making. METHODS: We created a country matrix focused on three key domains - health characteristics, immunisation factors, and policy framework, and identified ten related indicators. We scored countries based on indicator performance and subsequently ranked and grouped them into three archetypes of low-, moderate-, and high-barrier countries with regard to PCV introduction. RESULTS: Our results indicated 39 countries (33 low- and middle-income countries [LMICs] and 6 high-income countries) that are yet to introduce PCV. Among LMICs, 15 countries were classified as 'low-barrier,' indicating factors favourable for PCV introduction such as high immunisation coverage of common childhood vaccines, supportive governments, and substantial disease burden and eligibility for Gavi support. Countries classified in the 'moderate-barrier' (12) and 'high-barrier' (6) archetypes demonstrated adequate capacity in immunisation systems but had competing national priorities and cost barriers that impeded policy decision-making on PCV introduction. CONCLUSIONS: The current health and policy indicator-based categorisation provides an actionable framework to design tailored PCV advocacy within these last-mile countries. Policy approaches emerging from this framework can lead to strengthened decision-making on vaccine introduction and sustained vaccine access that can enhance child survival worldwide.

Healthcare provider perspectives on COVID-19 vaccination for children in India.

BACKGROUND: The rapid development and deployment of effective COVID-19 vaccines have been critical to halt the spread of the pandemic. India started vaccinating children in early 2022, however, vaccine uptake has been suboptimal. METHODS: Between September and November 2022, we conducted an online survey that was disseminated to eligible participants via email, text messages and social media platforms across India. The survey aimed to gather the perspectives of Indian healthcare providers regarding key factors related to the rollout of paediatric COVID-19 vaccines. Descriptive statistics were used to analyse participant demographics and responses on knowledge about paediatric COVID-19 vaccines, perceived risks and benefits, and vaccine rollout strategies. RESULTS: The survey yielded 805 respondents from 23 Indian states; 63.5% were men, 97.3% were paediatricians, median age was 44 years (IQR 25-81). Eighty-one per cent and 65.2% respondents had heard about the most common paediatric COVID-19 vaccines in India, Covaxin and Corbevax, but only 52.9%, 53.7% and 62.1% felt adequately informed about their safety, efficacy and vaccination schedules, respectively. Thirty per cent of respondents were unaware of vaccination guidelines. Eighty-five per cent of respondents felt that vaccines would reduce the incidence of severe disease, hospitalisation and deaths, and 60.6% felt children with comorbidities should be prioritised for vaccination. Perceived supply side barriers included lack of enforcement of guidelines (45.2%) and adverse effects following immunisation monitoring systems (37.6%), and on the demand side, parental vaccine hesitancy (64.4%). Eighty-one per cent believed that school-based vaccination strategies would be highly effective in increasing uptake. CONCLUSIONS: Most respondents were in support of the COVID-19 paediatric vaccination, although just over half did not feel adequately informed. Concerns about vaccine hesitancy among caregivers were the leading reported barrier. Targeted interventions are needed to provide adequate knowledge support to healthcare providers and evidence-based public health messaging to reduce vaccine hesitancy among caregivers.

Leveling the Research Playing Field: Decolonizing Global Health Research Through Web-Based Platforms.

Global health research has traditionally been rooted in colonialism, with some investigators in high-income countries leading and managing research and investigators in low- and middle-income countries serving as implementing partners. The Community Health Worker-Led Intervention for Vaccine Information and Confidence (CIVIC) Project, conducted in India and led jointly by India- and US-based investigators, leveraged web-based platforms to facilitate a more horizontal, inclusive, and balanced approach to partnerships between researchers and the community. Using web-based platforms to conduct research was found to be an effective strategy to engage researchers at all levels and combat systemic barriers associated with in-person activities such as power, economic, social, and gender dynamics. Connecting online for research meetings created a more equitable environment for community members to engage meaningfully with research. Further, by conducting research through web-based platforms, we found that we were able to strengthen the diversity of participants, provide a space for more marginalized groups to speak up, and minimize logistical barriers to attendance. Harnessing web-based approaches in research provides a pathway toward opportunities to promote equity and contribute to the decolonization of global health spaces.

Country ownership as a guiding principle for IA2030: A case study of the measles and rubella elimination programs in Nepal and Nigeria.

Country-owned, as opposed to donor-driven, is a principle within the development sector that recognizes the centrality of countries' leadership, systems, and resources in executing programs and achieving sustainable development. In alignment with this notion, the Immunization Agenda 2030 was developed with country ownership as one of four core principles of the ambitious ten-year plan. This means that the success of immunization programs, including those with eradication and elimination goals such as polio, measles, and rubella, and those with broader equity goals to "leave no one behind" on immunization, would be largely driven by country systems. In this paper we deconstruct country ownership into five operational principles: commitment, coordination, capacity, community participation, and accountability. Through this lens, we illustrate how two countries, Nepal and Nigeria, have exemplified country ownership in their measles and rubella elimination programs and we infer the ways in which country ownership drives system performance and sustains program efforts.

Leading from the frontlines: community-oriented approaches for strengthening vaccine delivery and acceptance.

BACKGROUND: Although immunization is one of the most successful public health interventions, vaccine hesitancy and the COVID-19 pandemic have strained health systems, contributing to global reductions in immunization coverage. Existing literature suggests that involving community members in vaccine interventions has been beneficial, but efforts to facilitate community ownership to motivate vaccine acceptance have been limited. METHODS: Our research leveraged community-based participatory research to closely involve the community from conception to implementation of an intervention to facilitate vaccine acceptance in Mewat District in Haryana, an area in India with extremely low vaccination coverage. Through the development of a community accountability board, baseline data collection on vaccination barriers and facilitators, and two human-centered design workshops, our team co-created a six-pronged intervention with community leaders and community health workers. This intervention included involving religious leaders in vaccine discussions, creating pamphlets of local vaccine champions for dissemination to parent and child caregivers, creating short videos of local leaders advocating for vaccines, implementing communication training exercises for community health workers, and implementing strategies to strengthen coordination between health workers and supervisors. RESULTS: Post-intervention data suggested parents and child caregivers had improvements in knowledge of the purpose of vaccines and side effects of vaccines. They noted that the involvement of religious leaders was beneficial, they were more willing to travel to vaccinate their children, and they had fewer non-logistical reasons to refuse vaccination services. Interviews with community leaders and community health workers who were involved in the creation of the intervention suggested that they experienced higher levels of ownership, they were better equipped to address community concerns, and that vaccine misinformation decreased in the post-intervention period. CONCLUSION: Through this unique intervention to strengthen vaccine uptake that incorporated the needs, interests, and expertise of local community members, we developed a community-driven approach to strengthen vaccine acceptance in a population with low uptake. This comprehensive approach is essential to amplify local voices, identify local concerns and advocates, and leverage bottom-up strategies to co-design successful interventions to facilitate long-term change.

Key factors influencing public health students and curricula in India: Recommendations from a mixed methods analysis.

BACKGROUND: Building on a distinguished history of community medicine training, public health programs have been expanding in India in recent years. The COVID-19 pandemic has brought additional attention to the importance of public health programs and the need for a strong workforce. This paper aims to assess the current capacity for public health education and training in India and provide recommendations for improved approaches to meet current and future public health needs. METHODS: We conducted a desk review of public health training programs via extensive internet searches, literature reviews, and expert faculty consultations. Among those programs, we purposively selected faculty members to participate in in-depth interviews. We developed summary statistics based on the desk review. For qualitative analysis, we utilized a combination of deductive and inductive coding to identify key themes and systematically reviewed the strengths and weaknesses of each theme. RESULTS: The desk review captured 59 institutions offering public health training across India. The majority of training programs were graduate level degrees including Master of Public Health and Master of Science degrees. Key factors impacting these programs included collaborations, mentorship, curriculum standardization, tuition and funding, and student demand for public health education and careers. Collaborations and mentorship were highly valued but varied in quality across institutions. Curricula lacked standardization but also contained substantial flexibility and innovation as a result. Public sector programs were perceived to be affordable though fees and stipends varied across institutions. Further development of career opportunities in public health is needed. CONCLUSION: Public health education and training in India have a strong foothold. There are numerous opportunities for continued expansion and strengthening of this field, to support a robust multi-disciplinary public health workforce that will contribute towards achieving the sustainable development goals.

The effect of the COVID-19 pandemic on routine childhood immunization coverage and timeliness in India: retrospective analysis of the National Family Health Survey of 2019-2021 data.

Background: The COVID-19 pandemic has disrupted health systems globally. We estimated the effect of the pandemic on the coverage and timeliness of routine childhood immunization in India through April 2021. Methods: We used data from India's National Family Health Survey 2019-2021 (NFHS-5), a cross-sectional survey which collected immunization information of under-five children from a nationally representative sample of households between June 2019 and April 2021. We used a mother fixed-effects regression model - accounting for secular trends and confounding factors - to compare COVID-affected children with their COVID-unaffected siblings (n = 59,144). Children who were eligible for a vaccine after January 30, 2020 (date of the first COVID case in India) were considered as the COVID-affected group and those eligible for a vaccine before this date were included in the COVID-unaffected group. Coverage of the following vaccine doses was considered-Bacillus Calmette-Guérin (BCG), hepatitis B birth dose (hepB0), DPT1 (diphtheria, pertussis, and tetanus, first dose), DPT2, DPT3, polio1, polio2, polio3, and measles first dose (MCV1). Indicators of vaccine coverage and vaccine timeliness (defined as receiving a dose within 45 days of minimum eligibility age) were separately examined. Findings: Immunization coverage was lower in COVID-affected children as compared with unaffected children, ranging from 2% lower for BCG and hepB0 to 9% for DPT3 and 10% for polio3. There was no significant difference in MCV1 coverage. Coverage reduction was greater for vaccines doses given in later age groups. The rate of timely receipt of polio and DPT vaccine doses was 3%-5% lower among COVID-affected children relative to unaffected children. Among population subgroups, COVID-affected male children and those from rural areas experienced the highest reduction in vaccine coverage. Interpretation: Children in India experienced lower routine immunization coverage and greater delays in immunization during the COVID-19 pandemic. Funding: The Bill & Melinda Gates Foundation.

Caregiver perceptions of the broader societal benefits of vaccination: A path toward sustainable vaccine advocacy in India.

Over the last decade growing public health evidence suggests that, in addition to health-related benefits, there are also social and economic benefits of vaccination. Research to understand how caregivers in low-and-middle-income countries perceive these social and economic benefits, or if these benefits factor into their vaccination decisions for their children, has been limited. Leveraging qualitative strategies to gain more nuanced insights into caregiver perceptions of vaccination benefits has also been significantly underexplored. We conducted in-depth interviews with 13 caregivers of children, at which point we reached saturation, in Mewat District, Haryana, an area in India with low vaccination coverage. Interview results suggest that caregivers of children associate positive health outcomes with vaccination programs, and some additional social and economic benefits beyond improved health outcomes. Caregivers also shared how local advocacy and gaps in vaccination programs can affect their perceptions of vaccination benefits. Qualitatively exploring the perceived benefits provides a unique understanding of the value that caregivers assign to vaccination and complements existing knowledge on factors that dissuade caregivers from vaccination. These insights will allow researchers to better identify and design context-specific advocacy strategies to strengthen vaccination programs in communities with low vaccine uptake and acceptance.

Vaccine acceptance in rural India: Engaging faith leaders as vaccine ambassadors.

Introduction: Religious faith is a key marker of identity and shapes community perspectives and trust. Faith leader involvement in vaccine campaigns in India have been beneficial to counter misinformation regarding infectious diseases such as polio. Faith leaders are influential stakeholders who bear potential to enhance public confidence in vaccine campaigns. Context: While vaccine coverage has been increasing in India, inequities abound, especially in populations with historically low vaccine confidence. The COVID-19 pandemic has led to major disruptions in delivery of routine immunization services for children. To address these challenges, we co-designed interventions aimed at contextual communication strategies and peer support. Engaging faith leaders was an important part of this intervention. In this report we describe our experience and highlight the perspectives of faith leaders and their expectations of the outcomes for this intervention. Programmatic elements: The CIVIC Project, conducted from January to December 2021 aimed to engage caregivers, community health workers and key stakeholders, particularly, faith leaders in co-designing interventions to address vaccine hesitancy in Mewat. The project, deeply rooted in community based participatory research, used a three-E approach (Exploration of community perspectives, Establishment of vaccine trust and awareness, Engagement in vaccine promotion activities) to successfully engage faith leaders in the design and dissemination of media messages advocating for vaccine acceptance and uptake. Lessons learned: The involvement of faith leaders in the intervention benefited the community in two ways. First, faith leaders were spotlighted via videos, often disseminating advice and personal anecdotes about vaccines, thus reassuring caregivers and community members who previously expressed distrust in vaccines. Second, involvement of trusted faith leaders provided a platform for a two-way dialogue for the community to openly discuss and address myths and misconceptions regarding vaccines. This project provided the learning that co-creating interventions with faith leaders who are often gatekeepers of close-knit communities can lead to the development of vaccine positive messaging that community members relate with, motivating increased vaccine confidence.

Molecular Characterization of the pol Gene of Vertically Transmitted HIV-1 Strains in Children with Virological Failure.

HIV-1 pol gene sequences were analyzed from 77 HIV-1 positive children infected perinatally and exhibiting virological failure (VF). Viral subtyping, phylogenetic analysis, and genotypic drug resistance analysis were carried out on samples collected before start of anti retroviral treatment (ART) (baseline, BL), and at 12 months post-ART initiation (M12). Subtype C was found to be most predominant, seen in 75 of the 77 (97.4%) children. The level of pretreatment drug resistance (PDR) was 14% among these children. At BL, K103N (5), E138A/G (4), and M184V (3) were the most common mutations. At M12 the prevalence of any resistance-associated mutation (RAM) (acquired drug resistance/ADR) was 81.8% (63/77). Dual class resistance mutations were seen in 64% (49/77) of children. M184V/I, K103N/S, and Y181C were the most commonly occurring mutations, seen in 76%, 51%, and 36% children. RAMs to the second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI), etravirine (ETR) and rilpivirine (RPV), were seen in 40.2% (31/77) and 48.05% (37/77) of the children, respectively. Our findings reveal similar prevalence rates of PDR and ADR in children with VF as reported in other studies. Occurrence of ETR and RPV resistance associated mutations (RAMs) is of concern and highlights the need for timely switch of regimens guided by genotypic resistance testing in perinatally infected children from India.

Strengthening institutions for public health education: results of an SWOT analysis from India to inform global best practices.

BACKGROUND: Developing public health educational programs that provide workers prepared to adequately respond to health system challenges is an historical dilemma. In India, the focus on public health education has been mounting in recent years. The COVID-19 pandemic is a harbinger of the increasing complexities surrounding public health challenges and the overdue need to progress public health education around the world. This paper aims to explore strengths and challenges of public health educational institutions in India, and elucidate unique opportunities to emerge as a global leader in reform. METHODS: To capture the landscape of public health training in India, we initiated a web-based desk review of available offerings and categorized by key descriptors and program qualities. We then undertook a series of in-depth interviews with representatives from a purposively sample of institutions and performed a qualitative SWOT analysis. RESULTS: We found that public health education exists in many formats in India. Although Master of Public Health (MPH) and similar programs are still the most common type of public health training outside of community medicine programs, other postgraduate pathways exist including diplomas, PhDs, certificates and executive trainings. The strengths of public health education institutions include research capacities, financial accessibility, and innovation, yet there is a need to improve collaborations and harmonize training with well-defined career pathways. Growing attention to the sector, improved technologies and community engagement all hold exciting potential for public health education, while externally held misconceptions can threaten institutional efficacy and potential. CONCLUSIONS: The timely need for and attention to public health education in India present a critical juncture for meaningful reform. India may also be well-situated to contextualize and scale the types of trainings needed to address complex challenges and serve as a model for other countries and the world.

COVID-19 vaccine acceptance among healthcare workers in India: Results from a cross-sectional survey.

Remarkable scientific progress has enabled expeditious development of effective vaccines against COVID-19. While healthcare workers (HCWs) have been at the frontline of the pandemic response, vaccine acceptance amongst them needs further study. We conducted a web-based survey to assess vaccine acceptance among HCWs in India between January and February 2021, shortly after the launch of India's vaccination campaign. Descriptive statistics were used to examine respondent demographics and Likert scale responses. Binomial logistic regression analyses were used to identify factors associated with vaccine acceptance. The survey yielded 624 respondents from 25 states and five union territories in India; 53.5% were male, and median age was 37 years (IQR 32-46). Amongst all respondents, 84.1% (525/624) supported COVID-19 vaccines, and 63.2% (141/223) of those unvaccinated at the time of survey administration were willing to accept a vaccine. Trust in government sources, healthcare providers or scientific journal articles for COVID-19 related information was reported by 66.8%, while confidence in social media for this information was reported by only 4.5%. Amongst those who had not yet received a COVID-19 vaccine, factors independently associated with vaccine acceptance included age (aOR 3.50 [95% CI, 1.04-11.76] for those above 45 years compared to younger HCWs aged 18-29 years), belief in vaccine effectiveness and safety (aOR 3.78 [95% CI 1.15-12.38]), and provision of free/no-cost vaccine (aOR 2.63 [95% CI, 1.06-6.50]). Most respondents (80%) were confident about their hospital being equipped to efficiently rollout COVID-19 vaccines to the general population. While overall attitudes towards COVID-19 vaccination were positive among HCWs in India, acceptance was lower among healthier and younger HCWs. Data availability on vaccine safety and effectiveness, and cost considerations were important for acceptance. Targeted interventions are needed to improve vaccine acceptance amongst HCWs, since they are critical in promoting vaccine acceptance amongst the general population.

Impact of the SARS-CoV-2 pandemic on routine immunisation services: evidence of disruption and recovery from 170 countries and territories.

BACKGROUND: The SARS-CoV-2 pandemic has revealed the vulnerability of immunisation systems worldwide, although the scale of these disruptions has not been described at a global level. This study aims to assess the impact of COVID-19 on routine immunisation using triangulated data from global, country-based, and individual-reported sources obtained during the pandemic period. METHODS: This report synthesised data from 170 countries and territories. Data sources included administered vaccine-dose data from January to December, 2019, and January to December, 2020, WHO regional office reports, and a WHO-led pulse survey administered in April, 2020, and June, 2020. Results were expressed as frequencies and proportions of respondents or reporting countries. Data on vaccine doses administered were weighted by the population of surviving infants per country. FINDINGS: A decline in the number of administered doses of diphtheria-pertussis-tetanus-containing vaccine (DTP3) and first dose of measles-containing vaccine (MCV1) in the first half of 2020 was noted. The lowest number of vaccine doses administered was observed in April, 2020, when 33% fewer DTP3 doses were administered globally, ranging from 9% in the WHO African region to 57% in the South-East Asia region. Recovery of vaccinations began by June, 2020, and continued into late 2020. WHO regional offices reported substantial disruption to routine vaccination sessions in April, 2020, related to interrupted vaccination demand and supply, including reduced availability of the health workforce. Pulse survey analysis revealed that 45 (69%) of 65 countries showed disruption in outreach services compared with 27 (44%) of 62 countries with disrupted fixed-post immunisation services. INTERPRETATION: The marked magnitude and global scale of immunisation disruption evokes the dangers of vaccine-preventable disease outbreaks in the future. Trends indicating partial resumption of services highlight the urgent need for ongoing assessment of recovery, catch-up vaccination strategy implementation for vulnerable populations, and ensuring vaccine coverage equity and health system resilience. FUNDING: US Agency for International Development.

The Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C.

In a multicentric, observational, investigator-blinded, and longitudinal clinical study of 764 ART-naïve subjects, we identified nine different promoter variant strains of HIV-1 subtype C (HIV-1C) emerging in the Indian population, with some of these variants being reported for the first time. Unlike several previous studies, our work here focuses on the evolving viral regulatory elements, not the coding sequences. The emerging viral strains contain additional copies of the existing transcription factor binding sites (TFBS), including TCF-1α/LEF-1, RBEIII, AP-1, and NF-κB, created by sequence duplication. The additional TFBS are genetically diverse and may blur the distinction between the modulatory region of the promoter and the viral enhancer. In a follow-up analysis, we found trends, but no significant associations between any specific variant promoter and prognostic markers, probably because the emerging viral strains might not have established mono infections yet. Illumina sequencing of four clinical samples containing a coinfection indicated the domination of one strain over the other and establishing a stable ratio with the second strain at the follow-up time points. Since a single promoter regulates viral gene expression and constitutes the master regulatory circuit with Tat, the acquisition of additional and variant copies of the TFBS may significantly impact viral latency and latent reservoir characteristics. Further studies are urgently warranted to understand how the diverse TFBS profiles of the viral promoter may modulate the characteristics of the latent reservoir, especially following the initiation of antiretroviral therapy.

Community perceptions of vaccination among influential stakeholders: qualitative research in rural India.

BACKGROUND: In India and other low- and middle-income countries, multiple family and community members are influential in caregivers' perceptions of vaccination. Existing literature indicates the primary caregiver, typically the mother, is instrumental in vaccine decision-making, but this may vary in contexts. We investigated the role of stakeholders in India who influence caregivers' vaccination perceptions, as this is essential to developing strategies to promote vaccine acceptance and improve uptake. METHODS: This research was conducted in 2019 in Mewat District in Haryana, an area in India with extremely low vaccination coverage. We conducted six focus group discussions with 60 participants in the following categories: fathers of children under-5 years old, expectant mothers, mothers-in-law, community health workers, and community influencers such as locally elected officials and religious leaders. RESULTS: Our results highlighted four themes that influence vaccine uptake. First, while caregivers associated vaccination with reductions in specific diseases, they also noted that vaccination services brought broad health gains, including improved nutrition, antenatal guidance, and social support. Second, community health workers critically influenced, positively or negatively, caregivers' vaccination perceptions. Third, community health workers faced gaps in their education such as limited training on vaccine side-effects, placing them at a disadvantage when dealing with families. Finally, we found that mothers-in-law, fathers, and religious leaders influence caregivers' perceptions of vaccination. CONCLUSIONS: Communication of broader benefits of vaccines and vaccination services by community health workers could be impactful in increasing vaccine acceptance. Vaccine uptake could potentially be improved by facilitating community health workers' ownership over vaccine acceptance and uptake by involving them in the design and implementation of interventions to target mothers and mothers-in-law. A 'bottom-up' approach, leveraging community health workers' knowledge to design interventions, and giving a voice to key members of the household and society beyond mothers alone, may sustain health improvement in low vaccine coverage areas.

Shifting research priorities in maternal and child health in the COVID-19 pandemic era in India: A renewed focus on systems strengthening.

BACKGROUND: The remarkable progress seen in maternal and child health (MCH) in India over the past two decades has been impacted by the COVID-19 pandemic. We aimed to undertake a rapid assessment to identify key priorities for public health research in MCH in India within the context and aftermath of the COVID-19 pandemic. METHODS: A web-based survey was developed to identify top research priorities in MCH. It consisted of 26 questions on six broad domains: vaccine preventable diseases, outbreak preparedness, primary healthcare integration, maternal health, neonatal health, and infectious diseases. Key stakeholders were invited to participate between September and November 2020. Participants assigned importance on a 5-point Likert scale, and assigned overall ranks to each sub-domain research priority. Descriptive statistics were used to examine Likert scale responses, and a ranking analysis was done to obtain an "average ranking score" and identify the top research priority under each domain. RESULTS: Amongst the 84 respondents from across 15 Indian states, 37% were public-health researchers, 25% healthcare providers, 20% academic faculty and 13% were policy makers. Most respondents considered conducting systems strengthening research as extremely important. The highest ranked research priorities were strengthening the public sector workforce (vaccine preventable diseases), enhancing public-health surveillance networks (outbreak preparedness), nutrition support through community workers (primary care integration), encouraging at least 4-8 antenatal visits (maternal health), neonatal resuscitation to reduce birth asphyxia (neonatal health) and screening and treatment of tuberculosis (infectious diseases). Common themes identified through open-ended questions primarily included systems strengthening priorities across domains. CONCLUSIONS: The overall focus for research priorities in MCH in India during the COVID-19 pandemic is on strengthening existing services and service delivery, rather than novel research. Our results highlight pivotal steps within the roadmap for advancing and sustaining maternal and child health gains during the ongoing COVID-19 pandemic and beyond.