Who gets vaccinated in a measles-rubella campaign in Nepal?: results from a post-campaign coverage survey.

BACKGROUND: Following the 2015 earthquake, a measles-rubella (MR) supplementary immunization activity (SIA), in four phases, was implemented in Nepal in 2015-2016. A post-campaign coverage survey (PCCS) was then conducted in 2017 to assess SIA performance and explore factors that were associated with vaccine uptake. METHODS: A household survey using stratified multi-stage probability sampling was conducted to assess coverage for a MR dose in the 2015-2016 SIA in Nepal. Logistic regression was then used to identify factors related to vaccine uptake. RESULTS: Eleven thousand two hundred fifty-three households, with 4870 eligible children provided information on vaccination during the 2015-2016 MR SIA. Overall coverage of measles-rubella vaccine was 84.7% (95% CI: 82.0-87.0), but varied between 77.5% (95% CI: 72.0, 82.2) in phase-3, of 21 districts vaccinated in Feb-Mar 2016, to 97.7% (CI: 95.4, 98.9) in phase-4, of the last seven mountainous districts vaccinated in Mar-Apr 2016. Coverage in rural areas was higher at 85.6% (CI: 81.9, 88.8) than in urban areas at 79.0% (CI: 75.5, 82.1). Of the 4223 children whose caregivers knew about the SIA, 96.5% received the MR dose and of the 647 children whose caregivers had not heard about the campaign, only 1.8% received the MR dose. CONCLUSIONS: The coverage in the 2015-2016 MR SIA in Nepal varied by geographical region with rural areas achieving higher coverage than urban areas. The single most important predictor of vaccination was the caregiver being informed in advance about the vaccination campaign. Enhanced efforts on social mobilization for vaccination have been used in Nepal since this survey, notably for the most recent 2020 MR campaign.

Gridded population survey sampling: a systematic scoping review of the field and strategic research agenda.

INTRODUCTION: In low- and middle-income countries (LMICs), household survey data are a main source of information for planning, evaluation, and decision-making. Standard surveys are based on censuses, however, for many LMICs it has been more than 10 years since their last census and they face high urban growth rates. Over the last decade, survey designers have begun to use modelled gridded population estimates as sample frames. We summarize the state of the emerging field of gridded population survey sampling, focussing on LMICs. METHODS: We performed a systematic scoping review in Scopus of specific gridded population datasets and "population" or "household" "survey" reports, and solicited additional published and unpublished sources from colleagues. RESULTS: We identified 43 national and sub-national gridded population-based household surveys implemented across 29 LMICs. Gridded population surveys used automated and manual approaches to derive clusters from WorldPop and LandScan gridded population estimates. After sampling, some survey teams interviewed all households in each cluster or segment, and others sampled households from larger clusters. Tools to select gridded population survey clusters include the GridSample R package, Geo-sampling tool, and GridSample.org. In the field, gridded population surveys generally relied on geographically accurate maps based on satellite imagery or OpenStreetMap, and a tablet or GPS technology for navigation. CONCLUSIONS: For gridded population survey sampling to be adopted more widely, several strategic questions need answering regarding cell-level accuracy and uncertainty of gridded population estimates, the methods used to group/split cells into sample frame units, design effects of new sample designs, and feasibility of tools and methods to implement surveys across diverse settings.

ω-3 and ω-6 Fatty Acid Supplementation May Reduce Autism Symptoms Based on Parent Report in Preterm Toddlers.

Background: Children born preterm are at increased risk of autism spectrum disorder (ASD). n-3 (ω-3) Combined with n-6 (ω-6) fatty acids including γ-linolenic acid (GLA) may benefit children born preterm showing early signs of ASD. Previous trials have reported that docosahexaenoic acid (DHA) promotes cognitive development in preterm neonates and n-3 fatty acids combined with GLA improve attention-deficit-hyperactivity disorder. Objectives: The objectives of the pilot Preemie Tots Trial were 1) to confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms and 2) to explore the effects of supplementation on parent-reported ASD symptoms and related behaviors. Methods: This was a 90-d randomized, fully blinded, placebo-controlled trial in 31 children 18-38 mo of age who were born at ≤29 wk of gestation. One group was assigned to daily Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA), and the other group received canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid). Mixed-effects regression analyses followed intent-to-treat analysis and explored effects on parent-reported ASD symptoms and related behaviors. Results: Of 31 children randomly assigned, 28 had complete outcome data. After accounting for baseline scores, those assigned to treatment exhibited a greater reduction in ASD symptoms per the Brief Infant Toddler Social Emotional Assessment ASD scale than did those assigned to placebo (difference in change = - 2.1 points; 95% CI: - 4.1, - 0.2 points; standardized effect size = - 0.71). No other outcome measure reflected a similar magnitude or a significant effect. Conclusions: This pilot trial confirmed adequate numbers of children enrolled and participated fully in the trial. No safety concerns were noted. It also found clinically-significant improvements in ASD symptoms for children randomly assigned to receive Omega-3-6-9 Junior, but effects were confined to one subscale. A future full-scale trial is warranted given the lack of effective treatments for this population. This trial was registered at www.clinicaltrials.gov as NCT01683565.

Using Serum IgE Antibodies to Predict Esophageal Eosinophilia in Children.

OBJECTIVES: Symptoms of eosinophilic esophagitis are variable and can be nonspecific. Food-specific serum immunoglobulin E (IgE) antibodies are frequently found in patients with eosinophilic esophagitis and are obtained using a widely available blood test. Our objective was to evaluate the ability of food-specific IgE antibodies to predict the presence of esophageal eosinophilia. METHODS: We reviewed 144 medical records for pediatric patients having esophageal biopsy and serum analysis for IgE antibodies to food (exploratory group). We performed logistic regression using sex and number of positive food-specific IgE tests to develop a model that predicts ≥15 eosinophils/high-power field (hpf) in the esophagus. We tested the model using 142 additional patients (validation group). RESULTS: The probability of having ≥15 eosinophils/hpf in the esophagus was higher in boys and increased with the number of positive food-specific IgE tests from 12% (95% confidence interval 4.8-26) in girls with 0 foods positive to 86% (95% confidence interval 71-94) for boys with 4 or 5 foods positive. The statistical model using sex and number of positive IgE tests to predict patients having ≥15 eosinophils/hpf showed acceptable discriminative ability (area under the receiver operating characteristic curve 0.80). The performance metrics for the model to predict ≥15 eosinophils/hpf in the validation group were similar (area under the receiver operating characteristic curve 0.75). CONCLUSIONS: Requiring only a blood test and a simple algorithm, analysis for IgE antibodies to food may expedite an esophagogastroduodenoscopy and decrease delays in the diagnosis and treatment of patients with nonspecific gastrointestinal symptoms who have increased eosinophils in the esophagus.

Determinants of immunization in polio super high-risk union councils of Pakistan.

BACKGROUND: The current polio epidemiology in Pakistan poses a unique challenge for global eradication as the country is affected by ongoing endemic poliovirus transmission. Across the country, 40 union councils (UCs) which serve as core reservoirs for poliovirus with continuous incidences of polio cases are categorized as super-high-risk union councils (SHRUCs). METHODOLOGY: A cross-sectional survey was conducted in 39 SHRUCs using a two-stage stratified cluster sampling technique. 6,976 children aged 12-23 months were covered. A structured questionnaire was used for data collection. Data were analyzed using STATA version 17. RESULTS: Based on both vaccination records and recall, 48.3% of children were fully-, 35.4 % were partially-, and 16.3% were non-vaccinated in the SHRUC districts. A child is considered fully vaccinated when h/she completed vaccination for BCG, OPV0, OPV 1-3, Penta 1-3, PCV 1-3, IPV, and MCV1. Vaccination cards were seen for over half of the children in the SHRUC districts of Khyber Pakhtunkhwa (KP) and the majority of the SHRUC districts in Sindh, except for the SHRUC district of Malir the districts of Balochistan. Results for polio vacancies show that 60.9% of children from the SHRUC districts were vaccinated with at least three doses of OPV and one dose of IPV, while 20.4% were vaccinated with any OPV doses or IPV and 18.7% of children did not receive any polio vaccines. The dropout rate between vaccine visits was higher than the WHO-recommended cutoff point of 10% for all vaccine doses in the SHRUC districts. The likelihood of being fully vaccinated was higher among the children of educated parents. Full vaccination was found significant among the children of any SHRUC districts compared to district Killa Abdullah. CONCLUSION: Context-specific strategies with more focus on community engagement and targeted mobilization, along with robust monitoring mechanisms, would help address the underlying challenges of under-immunization in the SHRUCs.

Evaluating Scope and Bias of Population-Level Measles Serosurveys: A Systematized Review and Bias Assessment.

BACKGROUND: Measles seroprevalence data have potential to be a useful tool for understanding transmission dynamics and for decision making efforts to strengthen immunization programs. In this study, we conducted a systematized review and bias assessment of all primary data on measles seroprevalence in low- and middle-income countries (as defined by World Bank 2021 income classifications) published from 1962 to 2021. METHODS: On 9 March 2022, we searched PubMed for all available data. We included studies containing primary data on measles seroprevalence and excluded studies if they were clinical trials or brief reports, from only health-care workers, suspected measles cases, or only vaccinated persons. We extracted all available information on measles seroprevalence, study design, and seroassay protocol. We conducted a bias assessment based on multiple categories and classified each study as having low, moderate, severe, or critical bias. This review was registered with PROSPERO (CRD42022326075). RESULTS: We identified 221 relevant studies across all World Health Organization regions, decades, and unique age ranges. The overall crude mean seroprevalence across all studies was 78.0% (SD: 19.3%), and the median seroprevalence was 84.0% (IQR: 72.8-91.7%). We classified 80 (36.2%) studies as having severe or critical overall bias. Studies from country-years with lower measles vaccine coverage or higher measles incidence had higher overall bias. CONCLUSIONS: While many studies have substantial underlying bias, many studies still provide some insights or data that could be used to inform modelling efforts to examine measles dynamics and programmatic decisions to reduce measles susceptibility.

Measuring coverage in MNCH: design, implementation, and interpretation challenges associated with tracking vaccination coverage using household surveys.

Vaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low- and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis.

Measuring coverage in MNCH: total survey error and the interpretation of intervention coverage estimates from household surveys.

Nationally representative household surveys are increasingly relied upon to measure maternal, newborn, and child health (MNCH) intervention coverage at the population level in low- and middle-income countries. Surveys are the best tool we have for this purpose and are central to national and global decision making. However, all survey point estimates have a certain level of error (total survey error) comprising sampling and non-sampling error, both of which must be considered when interpreting survey results for decision making. In this review, we discuss the importance of considering these errors when interpreting MNCH intervention coverage estimates derived from household surveys, using relevant examples from national surveys to provide context. Sampling error is usually thought of as the precision of a point estimate and is represented by 95% confidence intervals, which are measurable. Confidence intervals can inform judgments about whether estimated parameters are likely to be different from the real value of a parameter. We recommend, therefore, that confidence intervals for key coverage indicators should always be provided in survey reports. By contrast, the direction and magnitude of non-sampling error is almost always unmeasurable, and therefore unknown. Information error and bias are the most common sources of non-sampling error in household survey estimates and we recommend that they should always be carefully considered when interpreting MNCH intervention coverage based on survey data. Overall, we recommend that future research on measuring MNCH intervention coverage should focus on refining and improving survey-based coverage estimates to develop a better understanding of how results should be interpreted and used.

Understanding COVID-19 Vaccine Acceptance among Latin American Health Workers: Implications for Designing Interventions.

Health workers (HWs) have a key role in promoting vaccine acceptance. This study draws on the Behavioral and Social Drivers of Vaccination (BeSD) model and our team's investigation of vaccine hesitancy in a sample of 1197 HWs across 14 Caribbean countries in 2021. We conducted a cross-sectional Internet survey of 6718 HWs across 16 countries in Latin America in spring 2022, after the COVID-19 vaccine had recently become widely available in the region. The survey assessed HWs' attitudes regarding COVID-19 vaccines and vaccines in general. As a proxy measure of COVID-19 vaccine acceptance, we used the willingness to recommend the COVID-19 vaccine to eligible people. Ninety-seven percent of respondents were COVID-19 vaccine acceptant. Although nearly all respondents felt that the COVID-19 vaccine was safe and effective, 59% expressed concerns about potential adverse effects. Despite uniformly high acceptance of the COVID-19 vaccine overall and across Latin American subregions, acceptance differed by sex, HW profession, and COVID-19 history. Social processes, including actions and opinions of friends, family, and colleagues; actions and opinions of religious leaders; and information seen on social networks shaped many respondents' opinions of vaccines, and the magnitude of these effects differed across both demographic and geographic subgroups. Information campaigns designed for HWs should underscore the importance of vaccine safety. Messages should be tailored to specific audiences according to the information source each is most likely to consult and trust.

Routine Immunization Coverage and Immunization Card Retention in Pakistan: Results From a Cross-sectional National Survey.

BACKGROUND: Immunization is one of the most successful public health interventions available, saving millions of lives from death and disability each year. Therefore, improving immunization coverage is a high priority for the Government of Pakistan and essential to progress toward universal health coverage. This survey reports the national and provincial/regional coverage and determinants of fully, partially, and not-vaccinated children 12-23 months of age, antigen-wise coverage, percentage of home-based vaccination records (HBR) retention, and reasons for nonretention; dropout, timeliness, and prevalence of missed opportunities for simultaneous vaccination (MOSV). METHODS: The survey was a descriptive cross-sectional national household survey carried out across Pakistan. The survey included 110,790 children 12-23 months old and their caregivers. A World Health Organization (WHO)-Expanded Program on Immunization (EPI) Survey questionnaire was adapted to collect information. Data were analyzed using the WHO Vaccination Coverage Quality Indicators (VCQI) software and Stata version 17. RESULTS: Nationally excluding Azad Jammu and Kashmir (AJK) and Gilgit Baltistan (GB), the coverage of fully vaccinated children was 76.5%. The likelihood of being fully vaccinated was higher among children of educated parents who belonged to higher wealth quintiles and resided in any province/region other than Balochistan. The main reasons for unimmunization were no faith in immunization, rumors about vaccines, and distance to the facility. About two-thirds (66.2%) of the children had their HBR available, and the main reasons for not having a card were never visiting a health facility and having no awareness about the importance of a card. Dropout was discernible for later doses of vaccines compared with earlier ones. Higher proportions of children received the last doses late by more than two months. Of the 218,002 vaccination visits documented on HBR in the provinces, MOSVs occurred in 17.6% of the visits. CONCLUSION: The immunization coverage rates provide a direction to strategize the progress to improve the vaccination rates in Pakistan. The country needs to outline the immediate and long-term actions to combat vaccine-preventable diseases, such as escalating integrated immunization campaigns and outreach activities, provision of mobility support, and deploying behavioral interventions as a cross-cutting strategy to improve awareness and reduce misconceptions.

A Practical Guide to Pilot Testing Community-Based Vaccination Coverage Surveys.

Pilot testing is crucial when preparing any community-based vaccination coverage survey. In this paper, we use the term pilot test to mean informative work conducted before a survey protocol has been finalized for the purpose of guiding decisions about how the work will be conducted. We summarize findings from seven pilot tests and provide practical guidance for piloting similar studies. We selected these particular pilots because they are excellent models of preliminary efforts that informed the refinement of data collection protocols and instruments. We recommend survey coordinators devote time and budget to identify aspects of the protocol where testing could mitigate project risk and ensure timely assessment yields, credible estimates of vaccination coverage and related indicators. We list specific items that may benefit from pilot work and provide guidance on how to prioritize what to pilot test when resources are limited.

Randomized double-blind placebo-controlled proof-of-concept trial of resveratrol for outpatient treatment of mild coronavirus disease (COVID-19).

Resveratrol is a polyphenol that has been well studied and has demonstrated anti-viral and anti-inflammatory properties that might mitigate the effects of COVID-19. Outpatients (N = 105) were recruited from central Ohio in late 2020. Participants were randomly assigned to receive placebo or resveratrol. Both groups received a single dose of Vitamin D3 which was used as an adjunct. The primary outcome measure was hospitalization within 21 days of symptom onset; secondary measures were ER visits, incidence of pneumonia, and incidence of pulmonary embolism. Five patients chose not to participate after randomization. Twenty-one-day outcome was determined of all one hundred participants (mean [SD] age 55.6 [8.8] years; 61% female). There were no clinically significant adverse events attributed to resveratrol. Outpatients in this phase 2 study treated with resveratrol had a lower incidence compared to placebo of: hospitalization (2% vs. 6%, RR 0.33, 95% CI 0.04-3.10), COVID-19 related ER visits (8% vs. 14%, RR 0.57, 95% CI 0.18-1.83), and pneumonia (8% vs. 16%, RR 0.5, 95% CI 0.16-1.55). One patient (2%) in each group developed pulmonary embolism (RR 1.00, 95% CI: 0.06-15.55). This underpowered study was limited by small sample size and low incidence of primary adverse events consequently the results are statistically similar between treatment arms. A larger trial could determine efficacy.Trial Registrations: ClinicalTrials.gov NCT04400890 26/05/2020; FDA IND #150033 05/05/2020.

Concerns, attitudes, and intended practices of Caribbean healthcare workers concerning COVID-19 vaccination: A cross-sectional study.

BACKGROUND: The Caribbean has a long history of being a global leader in immunization, and one factor contributing to this success has been the commitment of healthcare workers in promoting the benefits of vaccines. Healthcare workers play a critical role in building trust between the public and the immunization program and are generally cited as the most trusted source of information on vaccination. Healthcare workers themselves, therefore, must be confident in vaccination as a public health good and able to transmit this confidence to those who trust them. However, just as with the general public, healthcare workers develop confidence at different rates and may be susceptible to misinformation about vaccines. METHODS: During April and May 2021, the Pan American Health Organization (PAHO) conducted a mixed-methods survey to assess vaccination attitudes, opinions, and reasoning of 1197 healthcare workers across 14 Caribbean countries. FINDINGS: Seventy-seven percent of respondents expressed clear intention to be vaccinated for COVID-19 as soon as possible. Intention to be vaccinated as soon as possible was expressed by lower proportions of nurses (66%) and allied health professionals (62%) than physicians (85%) and by younger respondents than older ones (64% vs. 85%, respectively; p < 0.001 for all these comparisons). Across 32 questions about attitudes and opinions, vaccine hesitancy was consistently expressed by higher proportions of nurses and allied health professionals than physicians and by younger respondents than older ones. INTERPRETATION: Insights from the survey are helping PAHO address healthcare worker concerns with informative messages and supporting countries in policy development to increase vaccine confidence and coverage among Caribbean healthcare workers. FUNDING: This work has been sponsored by the World Health Organization/Pan American Health Organization, the Government of Germany and The Gavi Alliance.

Multilevel analysis of predictors of multiple indicators of childhood vaccination in Nigeria.

BACKGROUND: Substantial inequalities exist in childhood vaccination coverage levels. To increase vaccine uptake, factors that predict vaccination coverage in children should be identified and addressed. METHODS: Using data from the 2018 Nigeria Demographic and Health Survey and geospatial data sets, we fitted Bayesian multilevel binomial and multinomial logistic regression models to analyse independent predictors of three vaccination outcomes: receipt of the first dose of Pentavalent vaccine (containing diphtheria-tetanus-pertussis, Hemophilus influenzae type B and Hepatitis B vaccines) (PENTA1) (n = 6059) and receipt of the third dose having received the first (PENTA3/1) (n = 3937) in children aged 12-23 months, and receipt of measles vaccine (MV) (n = 11839) among children aged 12-35 months. RESULTS: Factors associated with vaccination were broadly similar for documented versus recall evidence of vaccination. Based on any evidence of vaccination, we found that health card/document ownership, receipt of vitamin A and maternal educational level were significantly associated with each outcome. Although the coverage of each vaccine dose was higher in urban than rural areas, urban residence was not significant in multivariable analyses that included travel time. Indicators relating to socio-economic status, as well as ethnic group, skilled birth attendance, lower travel time to the nearest health facility and problems seeking health care were significantly associated with both PENTA1 and MV. Maternal religion was related to PENTA1 and PENTA3/1 and maternal age related to MV and PENTA3/1; other significant variables were associated with one outcome each. Substantial residual community level variances in different strata were observed in the fitted models for each outcome. CONCLUSION: Our analysis has highlighted socio-demographic and health care access factors that affect not only beginning but completing the vaccination series in Nigeria. Other factors not measured by the DHS such as health service quality and community attitudes should also be investigated and addressed to tackle inequities in coverage.

Leveraging a national biorepository in Zambia to assess measles and rubella immunity gaps across age and space.

High-quality, representative serological surveys allow direct estimates of immunity profiles to inform vaccination strategies but can be costly and logistically challenging. Leveraging residual serum samples is one way to increase their feasibility. We subsampled 9854 residual sera from a 2016 national HIV survey in Zambia and tested these specimens for anti-measles and anti-rubella virus IgG antibodies using indirect enzyme immunoassays. We demonstrate innovative methods for sampling residual sera and analyzing seroprevalence data, as well as the value of seroprevalence estimates to understand and control measles and rubella. National measles and rubella seroprevalence for individuals younger than 50 years was 82.8% (95% CI 81.6, 83.9%) and 74.9% (95% CI 73.7, 76.0%), respectively. Despite a successful childhood vaccination program, measles immunity gaps persisted across age groups and districts, indicating the need for additional activities to complement routine immunization. Prior to vaccine introduction, we estimated a rubella burden of 96 congenital rubella syndrome cases per 100,000 live births. Residual samples from large-scale surveys can reduce the cost and challenges of conducting serosurveys, and multiple pathogens can be tested. Procedures to access quality specimens, ensure ethical approvals, and link sociodemographic data can improve the timeliness and value of results.

Studies with staggered starts: multiple baseline designs and group-randomized trials.

OBJECTIVES: Multiple baseline designs (MBDs) have been suggested as alternatives to group-randomized trials (GRT). We reviewed structural features of MBDs and considered their potential effectiveness in public health research. We also reviewed the effect of staggered starts on statistical power. METHODS: We reviewed the MBD literature to identify key structural features, recent suggestions that MBDs be adopted in public health research, and the literature on power in GRTs with staggered starts. We also computed power for MBDs and GRTs. RESULTS: The features that have contributed to the success of small MBDs in some fields are not likely to translate well to public health research. MBDs can be more powerful than GRTs under some conditions, but those conditions involve assumptions that require careful evaluation in practice. CONCLUSIONS: MBDs will often serve better as a complement of rather than as an alternative to GRTs. GRTs may employ staggered starts for logistical or ethical reasons, but this will always increase their duration and will often increase their cost.

Cutoff designs for community-based intervention studies.

Public health interventions are often designed to target communities defined either geographically (e.g. cities, counties) or socially (e.g. schools or workplaces). The group randomized trial (GRT) is regarded as the gold standard for evaluating these interventions. However, community leaders may object to randomization as some groups may be denied a potentially beneficial intervention. Under a regression discontinuity design (RDD), individuals may be assigned to treatment based on the levels of a pretest measure, thereby allowing those most in need of the treatment to receive it. In this article, we consider analysis, power, and sample size issues in applying the RDD and related cutoff designs in community-based intervention studies. We examine the power of these designs as a function of intraclass correlation, number of groups, and number of members per group and compare results to the traditional GRT.

Randomized Double-blind Placebo-controlled Proof-of-concept Trial of Resveratrol for Outpatient Treatment of Mild Coronavirus Disease (COVID-19).

Resveratrol is a polyphenol that has been well studied and has demonstrated anti-viral and anti-inflammatory properties that might mitigate the effects of COVID-19. Outpatients (N=105) were recruited from central Ohio in late 2020. Participants were randomly assigned to receive placebo or resveratrol. Both groups received a single dose of Vitamin D3 which was used as an adjunct. The primary outcome measure was hospitalization within 21 days of symptom onset; secondary measures were ER visits, incidence of pneumonia and pulmonary embolism. Five patients chose not to participate after randomization. Twenty-one day outcome was determined of all one hundred participants (mean [SD] age 55.6 [8.8] years; 61% female) (or their surrogates). There were no clinically significant adverse events attributed to resveratrol. Outpatients in this phase 2 study treated with resveratrol had a lower incidence compared to placebo of: hospitalization (2% vs. 6%, RR 0.33, 95% CI 0.04-3.10), COVID-related ER visits (8% vs. 14%, RR 0.57, 95% CI 0.18-1.83), and pneumonia (8% vs. 16%, RR 0.5, 95% CI 0.16-1.55). One patient (2%) in each group developed pulmonary embolism (RR 1.00, 95% CI: 0.06-15.55). This underpowered study was limited by small sample size and low incidence of primary adverse events. A larger trial could determine efficacy. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT04400890 26/05/2020; FDA IND #150033 05/05/2020.

Pairs of independent nationally representative vaccination coverage surveys conducted within one year of each other: A global overview covering 2000-2019.

BACKGROUND: Population-based surveys play an important role in measuring vaccination coverage. Surveys measuring vaccination coverage may be commissioned by the Expanded Programme on Immunization (EPI surveys) or part of multi-domain non-EPI surveys such as Demographic and Health Surveys (DHS) or Multiple Indicator Cluster Surveys (MICS). Surveys conducted too close in time to each other may not only be an inefficient use of resources but may also create problems for programme staff when results suggest inconsistent patterns of programme performance for similar time periods. OBJECTIVE: To summarize the occurrence of vaccination coverage surveys conducted close in time during 2000-2019 and compare results of EPI and non-EPI coverage surveys when the surveys were conducted within one year of each other. METHODS: Using a database of published national-level vaccination coverage survey results compiled by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF), the authors abstracted information on survey field work dates, sample size, percentage of children with documented history of vaccination and the percent coverage, as well as published uncertainty intervals from DHS and MICS, for the first and third doses of diphtheria-tetanus toxoid-pertussis containing vaccine (DTP1, DTP3) and first dose of measles containing vaccine (MCV1). Survey results of EPI and non-EPI surveys were compared. RESULTS: The authors identified 646 surveys with final reports and estimates of national-level vaccination coverage for DTP1, DTP3, or MCV1 from a total of 687 surveys with data collection start date from 2000 to 2019. Of the 140 countries with at least one vaccination coverage survey, a median of four surveys was observed. Most countries were Gavi-eligible and located in the WHO Africa Region. Sixty-six survey dyads were identified where an EPI survey occurred within one year of a non-EPI survey. For the 66 dyads, in 49 of 59 with information available, EPI surveys reported higher proportion of documented evidence of vaccination and EPI survey results tended to suggest higher levels of vaccination coverage compared to the non-EPI surveys; quite often, differences were substantial. Surveys that found higher proportions of children with documented vaccination evidence tended to also find higher proportions of children who had been vaccinated. SUMMARY: Opportunities exist to improve overall planning of vaccination coverage measurement in population-based household surveys so that both EPI and non-EPI surveys are more comparable and survey coverage estimates are more appropriately spaced in time. When surveys occur too close in time, careful attention is warranted to ensure comparability and assess sources of documented evidence of vaccination and related coverage differences.

Using Household Surveys to Assess Missed Opportunities for Simultaneous Vaccination: Longitudinal Examples from Colombia and Nigeria.

One important strategy to increase vaccination coverage is to minimize missed opportunities for vaccination. Missed opportunities for simultaneous vaccination (MOSV) occur when a child receives one or more vaccines but not all those for which they are eligible at a given visit. Household surveys that record children's vaccination dates can be used to quantify occurrence of MOSVs and their impact on achievable vaccination coverage. We recently automated some MOSV analyses in the World Health Organization's freely available software: Vaccination Coverage Quality Indicators (VCQI) making it straightforward to study MOSVs for any Demographic & Health Survey (DHS), Multi-Indicator Cluster Survey (MICS), or Expanded Programme on Immunization (EPI) survey. This paper uses VCQI to analyze MOSVs for basic vaccine doses among children aged 12-23 months in four rounds of DHS in Colombia (1995, 2000, 2005, and 2010) and five rounds of DHS in Nigeria (1999, 2003, 2008, 2013, and 2018). Outcomes include percent of vaccination visits MOSVs occurred, percent of children who experienced MOSVs, percent of MOSVs that remained uncorrected (that is, the missed vaccine had still not been received at the time of the survey), and the distribution of time-to-correction for children who received the MOSV dose at a later visit.