Abram Luther Wagner

Background: Influenza vaccines have seen many changes over recent years in terms of both policy recommendations and product types. Immune responses and vaccine effectiveness vary by vaccine strain composition and product type. This study aimed to explore this variation on a regional level through examining spatial and temporal autocorrelations of vaccine uptake of different product types within Michigan from 2017 to 2021. Methods: Influenza vaccine administration data from the 2017/18 to 2021/22 seasons were obtained from the Michigan Care Improvement Registry. Population size estimates for 2017 and 2019 were obtained from the Michigan Department of Health and Human Services. Age-standardized and age-stratified vaccination rates were computed. Disparate county-level vaccine uptake clusters were constructed using spatial autocorrelation indicators and spatiotemporal clusters were identified using scan statistics. Linear mixed effect models were used to study the impact of social vulnerability and urbanicity level on seasonal influenza vaccination rate. Results: Vaccination incidence rates for adjuvanted, recombinant, and nasal sprays vaccines and for any vaccines increased significantly through the study period. County-level spatiotemporal clusters of type-specific uptake rates were identified. Most notably, we identified an emerging cluster with high uptake of adjuvanted vaccine radiating from Ottawa County, located in suburban Grand Rapids, and the disappearance of high uptake cluster for high-dose vaccine uptake in the area. Vaccination rates by any product type were found to vary seasonally and showed weak negative association with more rural regions. The overall vaccination rates appear to be lower among counties with higher social vulnerability in certain urbanicity levels, but social vulnerability and urbanicity were not significantly associated with overall vaccination rate during the study period. Conclusions: Vaccine type-specific uptake was spatially and temporally diverse in Michigan between 2017 and 2022. Mid and Northern Michigan had consistently relatively lower vaccination rate compared to other regions in Michigan.

Difficulties ascertaining the true burden of infection and mortality from SARS-CoV-2 hindered disease surveillance and healthcare resource allocation throughout the COVID-19 pandemic. Although all-cause excess mortality estimates have long been deployed to avoid the challenges of case detection when testing availability is variable, aggregation of mortality by cause of death and spatial unit may mask underlying patterns and hide underlying associations with social factors. Furthermore, some non-infectious causes of death may have decreased during the pandemic, resulting in all-cause excess mortality capturing a net pandemic effect rather than the direct burden of Covid-19. Using mortality data in the state of Michigan from January 2015 – November 2019, we calculated the expected mortality for December 2019 – November 2022 using negative binomial regression. Comparing these estimates to the observed mortality, we calculated the burden of excess mortality during the winter 2019 influenza season and COVID-19 pandemic, as divided into 7 distinct periods based on dominant viral strain and pharmaceutical and non-pharmaceutical interventions implemented. All analyses were performed with the data aggregated by cause of death and to the county level and repeated at both the county and census tract level disaggregated into two crude cause of death categories: acute respiratory infections (ARIs) and all other causes (non-acute respiratory infections, non-ARIs). We examined spatial heterogeneity of excess mortality by cause using the Theil index to determine if variation in excess mortality was driven by differences between or within counties. The excess mortality rate from ARI peaked in the first phase of the pandemic, with a ratio of 10.7 observed to expected deaths (95% CrI: 10.3 – 11.1). However, the all- cause excess mortality rate rose only to 1.20 excess deaths per expected (95% CrI: 1.17 – 1.22) and the non- ARI excess mortality rate was unchanged. Comparing ARI excess mortality rates calculated at the county vs. census tract level demonstrated large and unpredictable variation, with county level estimates ranging from 0.42 to 1.2 times the tract level estimates. However, county level estimates of non-ARI and all- cause excess mortality ratios were consistently closer to tract level estimates. Within county variation of ARI mortality decreased during the pandemic and slowly returned to reference levels, suggesting spatial patterning of ARI mortality became more similar across census tracts as rates rose statewide. Social vulnerability was associated with an increased ARI excess mortality rate ratio at the census tract level during the first pandemic phase (EMRR: 1.1, 95% CrI: 1.08 - 1.13), but this effect was attenuated when aggregated to all-cause mortality or to the county level. Our findings indicate that using county-level all-cause excess mortality as a proxy for ARI excess mortality obscured the burden of ARI death, particularly during the most acute phases of the COVID-19 pandemic. Relying on aggregated metric of all-cause mortality limits the power to detect large shifts in cause-specific mortality, and that limitation can be mitigated by even using coarse categories such as ARI vs. non-ARI deaths. Similarly, finer scale spatial units allow for the detection of local trends necessary to identify associated social factors.

As Valley fever (coccidioidomycosis) vaccine candidates progress towards human trials, a challenge to their eventual introduction is understanding vaccine demand and addressing vaccine hesitancy. We assessed intent to accept a Valley fever vaccine for humans and dogs in two populations living in highly endemic regions: employees at Kern Medical (KM) in Bakersfield, California (N = 103) and members of the public in West Texas (N = 230). We compared the weighted proportions of each population willing to vaccinate themselves and their dogs by demographic and coccidioidomycosis risk factors and assessed the importance of vaccine-related factors on vaccine uptake in each population. We found that 42% (95% confidence interval (CI): 34–49%) of West Texas residents and 76% (95% CI: 63–85%) of KM employees were willing to accept a coccidioidal vaccine, while 49% (95% CI: 41–58%) of West Texas residents and 74% (95% CI: 58–86%) of KM employees were willing to vaccinate their dogs. Among West Texas residents, vaccination willingness was significantly higher among those with prior awareness of Valley fever (adjusted odds ratio (aOR): 3.83, 95% CI: 1.73, 8.49). Across both study populations, absence of side effects was the most important condition that would increase vaccination willingness. Our results indicate substantial interest in a Valley fever vaccine while suggesting that increased Valley fever awareness and minimal vaccine side effects may be important for increased uptake.

Introduction: Social distancing and wearing a face mask are highly recommended to mitigate the transmission of coronavirus disease 2019 (COVID-19). However, the success of these strategies relies on individuals’ adherence and public compliance. This study was conducted to assess the level of belief in social distancing and face mask practices in communities in low- and middle-income countries (LMICs) and to identify their possible determinants. Methods: A cross-sectional study was conducted in ten LMICs countries in Asia, Africa, and South America from February to May 2021. A questionnaire was used to assess the belief, practice, and their plausible determinants. Identification of the associated determinants was performed using a logistic regression model. Results: Our data revealed that only 62.6% and 66.9% of the participants had good beliefs in social distancing and good face mask practices, respectively. Residing in the Americas, having a healthcare-related job, knowing people in immediate social environment who are or have been infected and exposure to information of COVID-19 cases on social media or TV were factors significantly associated with good belief in social distancing. Residing country, gender, monthly household income, type of job and exposure to information of COVID-19 cases were significantly associated with face mask wearing practice. Conclusion: The proportion of participants having good beliefs in social distancing and good face mask practices is relatively low (<75%). Hence, sustained health campaigns regarding social distancing benefits and face mask-wearing practices during COVID-19 are critical in LMICs.

Background: Despite advancements in child immunization, inadequate immunization rates in low- and middle-income countries persist due to inadequate health infrastructure, challenges in vaccine supply and distribution, insufficient healthcare provider training, and low levels of community trust in vaccines. Aceh, a religiously conservative province in Indonesia, has low pediatric vaccination coverage and exemplifies the need for innovative vaccine delivery models. Evidence suggests interventions should target both logistical barriers (e.g., distance or clinic wait times) and societal factors, including misinformation, that contribute towards vaccine hesitancy. Methods: The trial “TABRIE” will measure the impact of two strategies on children’s vaccination rates and parental attitudes towards vaccines in Banda Aceh and Aceh Besar, Indonesia, compared to current outreach strategies. The two strategies being tested are (a) an informational conference with religious leaders who work in specific clinics and (b) a mobile vaccine clinic staffed with community health workers conducting a variety of outreach events. We will execute a stepped wedge cluster randomized design with baseline measures and a cross-sectional sampling structure. Twelve districts ( Kecamatan ) will be randomized into one of the two strategies. In year 1, three districts from each strategy will implement the intervention, with the other three districts implementing the strategy in the second year. We will conduct cross-sectional surveys in September 2023 (baseline), September 2024 (year 1), and September 2025 (year 2). The primary outcome is the proportion of fully vaccinated children aged 1–5 years for bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), polio, and measles. Secondary outcomes include the proportion of children aged 1–5 years with at least one dose of DTP and measles vaccines, the proportion of vaccine-hesitant parents, social norms surrounding vaccination, parental trust in community health workers to administer vaccines, the proportion of parents experiencing distance barriers to vaccination, the proportion of parents reporting that their religious leader encourages vaccination, and the proportion of parents receiving vaccination information from their religious leader. Discussion: This study will conduct a stepped wedge cluster randomized trial to separately estimate the effects of religious conferences and mobile vaccine clinics on pediatric vaccination rates and parental attitudes towards vaccination. It will offer a novel paradigm in vaccination delivery by inserting vaccination from clinics into social spaces that provide alternative, community-centered policy solutions to vaccine hesitancy. Trial registration: ClinicalTrials.gov NCT06160999. Registered on December 14, 2023.

Background: Aceh, the westernmost province in Indonesia, was granted autonomous status, allowing the area to officially practice Sharia law, making the region religiously conservative. The province has the lowest measles vaccination rates in the country, with only 54% coverage. This study aims to quantify the contribution of concerns or structural barriers on non-vaccination. Methods: In a 2022 cross-sectional population-based study, 899 parents reported religious vaccine concerns, concerns about side effects, and whether they encountered structural barriers. The degree to which religious concerns impact the first dose of measles-rubella (MR1) and pentavalent (Penta1) vaccination was quantified through population-attributable fractions (PAF). Results: Among respondents, 62% reported their child had received MR1 and 63% Penta1. In total, 60% of parents expressed religious concerns about vaccination and 75% about vaccine side effects. The PAF for MR1 non-vaccination was 36% (95% CI: 21%, 52%) for religious concerns and 35% (95% CI: 16%, 51%) for concerns about side effects. For Penta1, the PAF was 42% (95% CI: 24%, 59%) for concerns about side effects and 28% (95% CI: 13%, 44%) for religious concerns. Structural barriers like stockouts, cost, or inconvenient clinic hours were less frequently cited and contributed minimally to non-vaccination. Conclusions: While concerns can overlap, evidence suggests that religious concerns are distinct and influence vaccination rates more than structural barriers. Understanding barriers to vaccination is a precursor to developing tailored interventions, like encouraging religious leaders to act as a trusted source of vaccine guidelines or promoting the use of a halal vaccine, that can mitigate hesitancy.