Sex differences in immune responses that underlie COVID-19 disease outcomes.

There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than among women1-5. However, whether immune responses against severe acute respiratory syndrome coronavirus (SARS-CoV-2) differ between sexes, and whether such differences correlate with the sex difference in the disease course of COVID-19, is currently unknown. Here we examined sex differences in viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. Male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. By contrast, female patients had more robust T cell activation than male patients during SARS-CoV-2 infection. Notably, we found that a poor T cell response negatively correlated with patients' age and was associated with worse disease outcome in male patients, but not in female patients. By contrast, higher levels of innate immune cytokines were associated with worse disease progression in female patients, but not in male patients. These findings provide a possible explanation for the observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of male and female patients with COVID-19.

Longitudinal analyses reveal immunological misfiring in severe COVID-19.

Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4. However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.

Potential Impact of Higher-Valency Pneumococcal Conjugate Vaccines Among Adults in Different Localities in Germany.

Next-generation pneumococcal conjugate vaccines (PCVs) have been approved for use. The serotype distribution of pneumococcal isolates can vary between regions. To understand the potential impacts of new PCVs, we evaluated trends in invasive pneumococcal disease (IPD) among adults in Germany at a local level using Bayesian hierarchical logistic regression. There was little spatial variation in IPD cases caused by PCV13 serotypes, which dropped from 60% of IPD cases in 2006 to 30% in 2018. Over half of IPD cases in 2018 were attributable to serotypes covered by new PCVs (PCV15, PCV20), which suggests they could further reduce the burden of IPD.

Understanding the Factors Influencing Health Care Provider Recommendations about Adolescent Vaccines: A Proposed Framework.

Health care provider recommendations are among the most important factors influencing parents' decisions to vaccinate their adolescents. However, delivery of high-quality health care provider recommendations for vaccination is not universal. There is wide variation in the strength, timeliness and consistency of the delivery of recommendations for all adolescent vaccines. The factors that influence health care providers' recommendations are multi-level and can be conceptualized in much the same way as vaccine acceptance among parents. Health care providers are influenced by their own attitudes and beliefs about a vaccine and also by the patient they are treating and by the community in which they practice as well as state and national level vaccine policy. We propose a multi-level framework for understanding the factors that influence health care providers' recommendations at the individual, interpersonal and community level to both develop and adapt interventions to improve providers' recommendations.

MomsTalkShots, tailored educational app, improves vaccine attitudes: a randomized controlled trial.

BACKGROUND: Many pregnant women and parents have concerns about vaccines. This analysis examined the impact of MomsTalkShots, an individually tailored educational application, on vaccine attitudes of pregnant women and mothers. METHODS: MomsTalkShots was the patient-level component of a multi-level intervention to improve maternal and infant vaccine uptake that also included provider- and practice-level interventions. The impact of these interventions was studied using a two-by-two factorial design, randomizing at both the patient- and the practice-level. Study staff recruited pregnant women from a diverse set of prenatal care practices in Colorado and Georgia between June 2017 and July 2018. All participants (n = 2087) received a baseline survey of maternal and infant vaccine intentions and attitudes, and two follow-up surveys at least 1 month and 1 year after their infant's birth, respectively. Half of participants (n = 1041) were randomly assigned to receive educational videos through MomsTalkShots, algorithmically tailored to their vaccine intentions, attitudes, and demographics. Since the practice/provider intervention did not appear impactful, this analysis focused on MomsTalkShots regardless of the practice/provider intervention. RESULTS: By 1 month post-birth, MomsTalkShots increased perceived risk of maternal influenza disease (61% among MomsTalkShots recipients vs 55% among controls; Odds Ratio: 1.61, 95% Confidence Interval: 1.23-2.09), confidence in influenza vaccine efficacy (73% vs 63%; OR: 1.97, 95%CI: 1.47-2.65), and perceived vaccine knowledge (55% vs 48%; OR: 1.39, 95%CI: 1.13-1.72). Among those intending not to vaccinate at baseline, MomsTalkShots increased perceived risk of maternal influenza disease (38% vs 32%; OR: 2.07, 95%CI: 1.15-3.71) and confidence in influenza vaccine efficacy (44% vs 28%; OR: 2.62, 95%CI: 1.46-4.69). By 1 year post-birth, MomsTalkShots increased perceived vaccine knowledge (62% vs 50%; OR: 1.74, 95%CI: 1.36-2.24) and trust in vaccine information from obstetricians and pediatricians (64% vs 55%; OR: 1.53, 95%CI: 1.17-2.00). Among those uncertain about vaccinating at baseline, MomsTalkShots increased perceived vaccine knowledge (47% vs 12%; OR: 6.89, 95%CI: 1.52-31.25) and reduced infant vaccine safety concerns (71% vs 91%; OR: 0.24, 95%CI: 0.06-0.98). CONCLUSIONS: MomsTalkShots improved pregnant women's and mothers' knowledge and perceptions of maternal and infant vaccines and the diseases they prevent, and offers a scalable tool to address vaccine hesitancy. TRIAL REGISTRATION: Registered at Clinicaltrials.gov on 13/09/2016 (registration number: NCT02898688).

Patterns of recommended vaccine receipt among women ages 24-45 years: a cross-sectional analysis.

BACKGROUND: Vaccine receipt among mid-adults remains low, with only one quarter of adults being up to date for all recommended vaccines. It is important to understand the myriad factors that influence vaccine receipt among mid-adult women to address these low rates. METHODS: We conducted a cross-sectional analysis of data from women ages 24-45 years collected as part of an ongoing case-control study of the effectiveness of HPV vaccine. We examined associations between demographic characteristics and healthcare utilization and receipt of individual vaccines and combinations of multiple vaccines using logistic regression analyses for three routinely recommended vaccines: tetanus, influenza and HPV. RESULTS: Among the 309 women enrolled in the study, only 19 (6.2%) were up to date for all three recommended vaccines and 41 (13.3%) had not received any of the recommended vaccines. A greater number of health care visits in the past year was associated with receipt of influenza (aOR = 6.37, 95% CI = 2.53, 16.1) and tetanus (aOR = 2.17, 95% CI = 1.14, 4.12) vaccines. White women were more likely to have received HPV vaccine (aOR = 2.39, 95% CI = 1.07, 5.36). CONCLUSIONS: Uptake of recommended vaccines is low among young and mid-adult women. There is a need for greater understanding of the underlying factors influencing vaccine receipt in this population.

Human Papillomavirus Vaccination Before 13 and 15 Years of Age: Analysis of National Immunization Survey Teen Data.

Human papillomavirus (HPV) vaccination is suboptimally used in the United States. Vaccination before the 13th birthday is recommended by the Advisory Committee on Immunization Practices and vaccination before the 15th birthday requires only 2 doses. We estimated the proportion of adolescents up to date for HPV vaccine using provider-verified vaccination data from the 2016 National Immunization Survey-Teen. Only 16% of US adolescents completed HPV vaccination before turning 13, and 35% completed HPV vaccination before turning 15. With sexual activity initiation increasing throughout adolescence and higher immunogenicity for younger vaccinees, vaccination before the 13th birthday can provide better protection against HPV-related cancers.

A survey-based study of Zika virus communication preferences among pregnant women in Georgia, United States.

BACKGROUND: Because of the particularly severe perinatal outcomes associated with antenatal Zika virus infection, it is important for prenatal care providers to communicate Zika virus risks and strategies for prevention to their patients. Although face-to-face communication is ideal, clinic visits may not allow for in-depth discussion of all concerns. While previous studies have shown prenatal providers to be pregnant women's most trusted sources of health information, there is little knowledge on what secondary communication modalities pregnant women prefer for receiving information from their providers about an evolving public health emergency. METHODS: A cross-sectional, descriptive anonymous 27-item survey was distributed to pregnant women at four clinics around Atlanta, Georgia from May 5th to June 20th, 2016. The survey assessed women's interest in and communication preferences about prenatal topics, including Zika virus. Descriptive statistics were calculated and chi-square tests were used to evaluate associations between the primary outcomes and patient characteristics. RESULTS: Four-hundred and eight women completed the survey. The most popular resource for obtaining Zika virus information was the Centers for Disease Control and Prevention (CDC) website (73.0%). While their prenatal provider's own website for Zika information ranked 5th among sources currently accessed for Zika information, it ranked third behind educational brochures and emails for ways in which women wanted to receive information. The characteristics of Zika virus information deemed most important were: evidence-based (87.5%), endorsed by the CDC (74.1%), and endorsed by their own provider (67.9%). CONCLUSION: In any public health emergency affecting pregnant women, women are going to seek advice from their obstetric providers. Because providers may lack sufficient time to discuss concerns with every patient, they may consider providing patient education in other ways. For the women included in this study, educational brochures, emails and providers' own practice websites were preferred. Providers should consider taking greater advantage of these modalities to supplement in-person exchanges, particularly during a public health emergency.

Use of Obstetric Practice Web Sites to Distribute Zika Virus Information to Pregnant Women During a Zika Virus Outbreak.

OBJECTIVE: To describe the current use of obstetric practice Web sites to disseminate Zika virus information to patients. DESIGN: Review of 913 randomly selected practice Web sites and associated social media accounts in January and August 2016. SETTING: Obstetric practice Web sites and associated social media accounts, United States of America. PARTICIPANTS: N/A. MAIN OUTCOME MEASURES: Proportion of obstetric practice Web sites and linked social media accounts providing Zika virus information. RESULTS: Twenty-five percent and 35% of obstetric practice Web sites had information posted about Zika virus in January 2016 and August 2016, respectively. Between the 2 time points, the proportion of practices posting Zika virus content on Facebook and Twitter declined (Facebook: 15% in January, 9% in August; Twitter: 12% in January, 8% in August). In August, the most frequently observed Zika virus-related content themes were the use of insect repellent (14%) and travel advisories (14%). At both time points, practices affiliated with large university hospitals were more likely to have posted information on Zika virus than independent OB/GYN-only practices: January: odds ratio (OR) (95% confidence interval [CI]) = 5.68 (3.50-9.20); August: OR (95% CI) = 8.37 (5.31-13.17). Similarly, practices associated with nonuniversity hospitals were more likely to have posted information than independent OB/GYN-only practices: January: OR (95% CI) = 2.71 (1.88-3.92); August: OR (95% CI) = 6.75 (4.75-9.60). CONCLUSION: Obstetric care practices are not fully utilizing their practice Web sites to relay Zika virus information to their patients. Since practitioner-sponsored Web sites have the capacity to directly reach the populations at greatest risk for Zika virus complications, public health professionals should consider adapting their materials and provider outreach campaigns to more easily accommodate Web site-based information dissemination during this type of public health emergency. There must be greater recognition of the value information gains in the eyes of the patient when it is validated by their own provider, especially when that patient is part of the highest-risk population for a given emergency. Public health organizations should strive to minimize the burden it takes for providers to relay useful resources to patients in order to maximize the impact that those resources can have.

Validation of the Vaccination Trust Indicator (VTI) in a multi-country survey of adult vaccination attitudes.

Improved uptake of adult vaccinations could substantially reduce the burden of infectious disease worldwide, however very few countries achieve high coverage of recommended adult vaccinations. Vaccine hesitancy is an important driver of low vaccine uptake among adults but no measure currently exists to capture general vaccination attitudes in this population accurately and efficiently. We utilize data from two surveys of adult vaccine attitudes and uptake conducted in fifteen countries to evaluate the Vaccination Trust Indicator (VTI). The VTI is a six-item measure intended to capture general vaccine attitudes. We utilized multivariable logistic regression to examine the association between VTI scores and self-reported receipt of the seasonal influenza vaccine, receipt of a tetanus toxoid-containing vaccine and intent to receive the flu vaccine in the next season. In the five countries with self-reported vaccine receipt data, we found that a ten-point increase in VTI score was associated with a 50% increase in odds of influenza vaccine receipt (OR = 1.55, 95% CI = 1.48, 1.62) and 25% increase in the odds of tetanus vaccine receipt (OR = 1.26, 95% CI = 1.21, 1.30). Strong associations between VTI score and vaccine receipt were found in each country except China. A strong association between VTI score and intent to receive the influenza vaccine was found in all fifteen countries. The VTI is a promising tool for assessing adult immunization attitudes with clear and immediate uses for immunization programs globally.

Human papillomavirus vaccine effectiveness by age at vaccination: A systematic review.

Human papillomavirus (HPV) vaccines work by preventing infections prior to natural exposure. Thus, it is likely more effective at younger ages, and it is important to understand how effectiveness might be diminished when administered at older ages. We conducted a systematic review of HPV vaccine effectiveness studies published between 2007 and 2022 that included an analysis of effectiveness against vaccine-type HPV infections, anogenital warts, cervical abnormalities and cervical cancer by age at vaccine initiation or completion. Searching multiple databases, 21 studies were included and results were summarized descriptively. Seventeen studies found the highest vaccine effectiveness in the youngest age group. Vaccine effectiveness estimates for younger adolescents ages 9-14 years ranged from approximately 74% to 93% and from 12% to 90% for adolescents ages 15-18 years. These results demonstrate that the HPV vaccine is most effective against HPV-related disease outcomes when given at younger ages, emphasizing the importance of on-time vaccination.

Multi-tiered intervention to increase maternal immunization coverage: A randomized, controlled trial.

OBJECTIVE: To evaluate the impact of a multi-component intervention package of maternal immunization uptake in obstetric care clinics. METHODS: In a multi-level, cluster- and individually-randomized controlled trial we implemented an evidence-based intervention that targeted practice-, provider- and patient-level barriers to vaccine uptake. Obstetric practices were randomized to receive the practice and provider-level interventions or continue their normal standard of care. We enrolled pregnant women at practices in Georgia and Colorado and randomized women into patient-level intervention and control groups, resulting in four study arms. The primary outcomes were receipt of the influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccines during pregnancy. A sample size of 550 women per arm (2200 total) was planned and enrolled to compare the intervention between the four study arms. RESULTS: Between June 2017 and July 2018, 4907 women were screened and 2200 women were randomized, 550 to each of the four study arms. We were unable to follow-up with 108 women, for a final sample size of 2092. Sample characteristics and sample size were similar among study arms. There was no significant increase in Tdap or influenza vaccine uptake overall. Among women who had no intention of or were unsure about receiving the influenza vaccine during pregnancy, those who received just the patient-level intervention were 61% more likely to receive the influenza vaccine than those in the control arm (Relative risk: 1.61; 95% Confidence Interval: 1.18-2.21). There was no significant difference in vaccine uptake for either influenza or tetanus, diphtheria and acellular pertussis between the four arms of the study. CONCLUSIONS: This trial highlights the need for more targeted interventions to improve vaccine uptake. Future work should focus on clinics with low baseline vaccine uptake and the patient-level intervention should be expanded and targeted towards women with low vaccine confidence.

Influenza Vaccination Rates Among Patients With a History of Cancer: Analysis of the National Health Interview Survey.

BACKGROUND: Annual influenza vaccination is recommended for all patients with cancer, but vaccine uptake data by cancer type and time since diagnosis are limited. We sought to estimate vaccination rates across different cancer types in the United States and determine whether rates vary over time since diagnosis. METHODS: Vaccination rates in individuals with solid tumor and hematological malignancies were estimated using data from 59 917 individuals obtained by the 2016 and 2017 National Health Interview Survey conducted by the Centers for Disease Control and Prevention. RESULTS: An average of 64% of the 5053 individuals with self-reported cancer received the influenza vaccine. Vaccination rates in men and women with solid tumors (66.6% and 60.3%, respectively) and hematological malignancies (58.1% and 59.2%, respectively) were significantly higher compared to those without cancer (38.9% and 46.8%, respectively). Lower rates were seen in uninsured patients, those younger than 45 years of age, and in African Americans with hematological malignancies but not with solid tumors. Vaccine uptake was similar regardless of time since cancer diagnosis. CONCLUSIONS: Influenza vaccination rates are higher in men and women with cancer but remain suboptimal, highlighting the need for additional measures to improve vaccine compliance and prevent complications from influenza across all cancer types.

Strategies to increase uptake of maternal pertussis vaccination.

INTRODUCTION: Pertussis is a highly contagious respiratory disease that results in disproportionate morbidity and mortality in infants who have yet to receive the primary diphtheria-tetanus-pertussis vaccine series. In the preceding decades numerous countries began to pursue either prenatal vaccination of pregnant women or postpartum vaccination of caregivers to protect infants. Despite proven benefit, maternal uptake of pertussis vaccine continues to remain suboptimal. AREAS COVERED: Many studies have been conducted to address the suboptimal uptake of maternal pertussis vaccination. This systematic review was undertaken to systematically identify those studies, highlight the most successful strategies and find the knowledge gaps that need to be filled over the coming years to improve vaccine uptake. Twenty-five studies were identified from six different databases. EXPERT OPINION: Five different interventions were shown to be successful in promoting uptake of pertussis vaccination: (1) standing orders, (2) opt-in orders, (3) provider education, (4) on-site vaccination and (5) interactive patient education. Three major knowledge gaps were also identified that need to be filled over the coming years: (1) lack of studies in low- and middle-income countries, (2) lack of studies targeting midwives and/or home birth and (3) lack of studies on the process of vaccine communication.

Vaccine package inserts and prescribing habits of obstetricians-gynecologists for maternal vaccination.

Despite ample evidence of the safety and efficacy of the influenza vaccine and the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine during pregnancy, two-thirds of pregnant women do not receive these vaccines. Providers have a significant role in increasing prenatal vaccine uptake. It is important to understand how different sources of vaccine prescribing information, such as Food and Drug Administration package inserts, influence provider recommendations. We aimed to examine the role of vaccine package inserts in provider recommendations and perceptions of safety and effectiveness of vaccines during pregnancy. A cross-sectional survey was mailed to a random, weighted sample of American College of Obstetricians and Gynecologists Fellows living in the United States in March 2019. Providers were asked about their attitudes toward package inserts, and to evaluate sample package insert statements following two different labeling rules. Their evaluations of each rule were then compared. Of the 321 respondents, the majority (90%, 288/321) recommended and/or administered maternal vaccinations. Few respondents (7.8%, 25/321) read package inserts for information regarding vaccination. Respondents were less likely to recommend sample vaccines with Pregnancy and Lactation Labeling Rule-complying inserts (46.1%, 148/321) than vaccines with Pregnancy Category inserts (87.5%, 282/321). Although most providers did not actively utilize vaccine package inserts to inform recommendations, the previous Pregnancy Categories rule was preferred compared to the Pregnancy and Lactation Labeling Rule. Collaborative efforts to update inserts with current clinical practices for pregnancy would be valuable in reducing apprehensiveness around package inserts to generate safer and more cogent recommendations for pregnant women.

Publishing at any cost: a cross-sectional study of the amount that medical researchers spend on open access publishing each year.

OBJECTIVE: To estimate the financial costs paid by individual medical researchers from meeting the article processing charges (APCs) levied by open access journals in 2019. DESIGN: Cross-sectional analysis. DATA SOURCES: Scopus was used to generate two random samples of researchers, the first with a senior author article indexed in the 'Medicine' subject area (general researchers) and the second with an article published in the ten highest-impact factor general clinical medicine journals (high-impact researchers) in 2019. For each researcher, Scopus was used to identify all first and senior author original research or review articles published in 2019. Data were obtained from Scopus, institutional profiles, Journal Citation Reports, publisher databases, the Directory of Open Access Journals, and individual journal websites. MAIN OUTCOME MEASURES: Median APCs paid by general and high-impact researchers for all first and senior author research and review articles published in 2019. RESULTS: There were 241 general and 246 high-impact researchers identified as eligible for our study. In 2019, the general and high-impact researchers published a total of 914 (median 2, IQR 1-5) and 1471 (4, 2-8) first or senior author research or review articles, respectively. 42% (384/914) of the articles from the general researchers and 29% (428/1471) of the articles from the high-impact medical researchers were published in fully open access journals. The median total APCs paid by general researchers in 2019 was US$191 (US$0-US$2500) and the median total paid by high-impact researchers was US$2900 (US$0-US$5465); the maximum paid by a single researcher in total APCs was US$30115 and US$34676, respectively. CONCLUSIONS: Medical researchers in 2019 were found to have paid between US$0 and US$34676 in total APCs. As journals with APCs become more common, it is important to continue to evaluate the potential cost to researchers, especially on individuals who may not have the funding or institutional resources to cover these costs.

Racial/Ethnic Disparities in Maternal Vaccine Knowledge, Attitudes, and Intentions.

OBJECTIVES: Although disparities in maternal vaccine acceptance among racial/ethnic groups are well documented, the reasons for these disparities are unclear. The objective of this study was to describe differences in pregnant women's knowledge, attitudes, beliefs, intentions, and trust regarding maternal and infant vaccines by race/ethnicity. METHODS: We collected survey data from 1862 pregnant women from diverse prenatal care practices in Georgia and Colorado from June 2017 through July 2018. We performed multiple logistic regressions to determine differences in intentions, knowledge, attitudes, beliefs, and trust by race/ethnicity and calculated odds ratios (ORs) and 95% CIs. RESULTS: Compared with White women, Black and Hispanic women were less confident in vaccine safety and efficacy and less likely to perceive risk of acquiring vaccine-preventable diseases, report provaccine social norms, indicate having enough vaccine knowledge, and trust vaccine information from health care providers and public health authorities. Black women were the least confident in the safety of the maternal influenza vaccine (OR = 0.37; 95% CI, 0.27-0.49); maternal tetanus, diphtheria, and acellular pertussis vaccine (OR = 0.37; 95% CI, 0.27-0.52); and infant vaccines overall (OR = 0.40; 95% CI, 0.28-0.58), and were least likely to intend to receive both maternal vaccines (OR = 0.35; 95% CI, 0.27-0.47) or all infant vaccines on time (OR = 0.45; 95% CI, 0.34-0.61) as compared with White women. CONCLUSIONS: Understanding differences in behavioral constructs integral to vaccine decision making among women of different races/ethnicities can lead to tailored interventions to improve vaccine acceptance.

Mandatory Vaccination in Europe.

BACKGROUND: Mandatory vaccination has been effective in maintaining high vaccination coverage in countries such as the United States. However, there are no peer-reviewed analyses of the association between mandates and both coverage and subsequent incidence of vaccine-preventable disease in Europe. METHODS: Using data from the European Centre for Disease Prevention and Control and the World Health Organization, we evaluated the relationship between country-level mandatory vaccination policies and (1) measles and pertussis vaccine coverage and (2) the annual incidence of these diseases in 29 European countries. Multivariate negative binomial and linear regression models were used to quantify these associations. RESULTS: Mandatory vaccination was associated with a 3.71 (95% confidence interval [CI]: 1.68 to 5.74) percentage point higher prevalence of measles vaccination and a 2.14 (95% CI: 0.13 to 4.15) percentage point higher prevalence of pertussis vaccination when compared with countries that did not have mandatory vaccination. Mandatory vaccination was only associated with decreased measles incidence for countries without nonmedical exemptions (adjusted incidence rate ratio = 0.14; 95% CI: 0.05 to 0.36). We did not find a significant association between mandatory vaccination and pertussis incidence. CONCLUSIONS: Mandatory vaccination and the magnitude of fines were associated with higher vaccination coverage. Moreover, mandatory vaccination was associated with lower measles incidence for countries with mandatory vaccination without nonmedical exemptions. These findings can inform legislative policies aimed at increasing vaccination coverage.