Evaluation of BNT162b2 Covid-19 Vaccine in Children Younger than 5 Years of Age.

BACKGROUND: Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children. METHODS: We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2-3 safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present results for children 6 months to less than 2 years of age and those 2 to 4 years of age through the data-cutoff dates (April 29, 2022, for safety and immunogenicity and June 17, 2022, for efficacy). In the phase 2-3 trial, participants were randomly assigned (in a 2:1 ratio) to receive two 3-µg doses of BNT162b2 or placebo. On the basis of preliminary immunogenicity results, a third 3-µg dose (≥8 weeks after dose 2) was administered starting in January 2022, which coincided with the emergence of the B.1.1.529 (omicron) variant. Immune responses at 1 month after doses 2 and 3 in children 6 months to less than 2 years of age and those 2 to 4 years of age were immunologically bridged to responses after dose 2 in persons 16 to 25 years of age who received 30 µg of BNT162b2 in the pivotal trial. RESULTS: During the phase 1 dose-finding study, two doses of BNT162b2 were administered 21 days apart to 16 children 6 months to less than 2 years of age (3-µg dose) and 48 children 2 to 4 years of age (3-µg or 10-µg dose). The 3-µg dose level was selected for the phase 2-3 trial; 1178 children 6 months to less than 2 years of age and 1835 children 2 to 4 years of age received BNT162b2, and 598 and 915, respectively, received placebo. Immunobridging success criteria for the geometric mean ratio and seroresponse at 1 month after dose 3 were met in both age groups. BNT162b2 reactogenicity events were mostly mild to moderate, with no grade 4 events. Low, similar incidences of fever were reported after receipt of BNT162b2 (7% among children 6 months to <2 years of age and 5% among those 2 to 4 years of age) and placebo (6 to 7% among children 6 months to <2 years of age and 4 to 5% among those 2 to 4 years of age). The observed overall vaccine efficacy against symptomatic Covid-19 in children 6 months to 4 years of age was 73.2% (95% confidence interval, 43.8 to 87.6) from 7 days after dose 3 (on the basis of 34 cases). CONCLUSIONS: A three-dose primary series of 3-µg BNT162b2 was safe, immunogenic, and efficacious in children 6 months to 4 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age.

BACKGROUND: Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age. METHODS: A phase 1, dose-finding study and an ongoing phase 2-3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-µg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed. RESULTS: During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 µg, 20 µg, or 30 µg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 µg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3). CONCLUSIONS: A Covid-19 vaccination regimen consisting of two 10-µg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

Adjusting Incidence Estimates with Laboratory Test Performances: A Pragmatic Maximum Likelihood Estimation-Based Approach.

Understanding the incidence of disease is often crucial for public policy decision-making, as observed during the COVID-19 pandemic. Estimating incidence is challenging, however, when the definition of incidence relies on tests that imperfectly measure disease, as in the case when assays with variable performance are used to detect the SARS-CoV-2 virus. To our knowledge, there are no pragmatic methods to address the bias introduced by the performance of labs in testing for the virus. In the setting of a longitudinal study, we developed a maximum likelihood estimation-based approach to estimate laboratory performance-adjusted incidence using the expectation-maximization algorithm. We constructed confidence intervals (CIs) using both bootstrapped-based and large-sample interval estimator approaches. We evaluated our methods through extensive simulation and applied them to a real-world study (TrackCOVID), where the primary goal was to determine the incidence of and risk factors for SARS-CoV-2 infection in the San Francisco Bay Area from July 2020 to March 2021. Our simulations demonstrated that our method converged rapidly with accurate estimates under a variety of scenarios. Bootstrapped-based CIs were comparable to the large-sample estimator CIs with a reasonable number of incident cases, shown via a simulation scenario based on the real TrackCOVID study. In more extreme simulated scenarios, the coverage of large-sample interval estimation outperformed the bootstrapped-based approach. Results from the application to the TrackCOVID study suggested that assuming perfect laboratory test performance can lead to an inaccurate inference of the incidence. Our flexible, pragmatic method can be extended to a variety of disease and study settings.

Emerging and re-emerging pediatric viral diseases: a continuing global challenge.

The twenty-first century has been marked by a surge in viral epidemics and pandemics, highlighting the global health challenge posed by emerging and re-emerging pediatric viral diseases. This review article explores the complex dynamics contributing to this challenge, including climate change, globalization, socio-economic interconnectedness, geopolitical tensions, vaccine hesitancy, misinformation, and disparities in access to healthcare resources. Understanding the interactions between the environment, socioeconomics, and health is crucial for effectively addressing current and future outbreaks. This scoping review focuses on emerging and re-emerging viral infectious diseases, with an emphasis on pediatric vulnerability. It highlights the urgent need for prevention, preparedness, and response efforts, particularly in resource-limited communities disproportionately affected by climate change and spillover events. Adopting a One Health/Planetary Health approach, which integrates human, animal, and ecosystem health, can enhance equity and resilience in global communities. IMPACT: We provide a scoping review of emerging and re-emerging viral threats to global pediatric populations This review provides an update on current pediatric viral threats in the context of the COVID-19 pandemic This review aims to sensitize clinicians, epidemiologists, public health practitioners, and policy stakeholders/decision-makers to the role these viral diseases have in persistent pediatric morbidity and mortality.

Lessons From a House on Fire-From Smallpox to Polio.

Global burden of disease morbidity and mortality has shifted dramatically in the last 30 years from infectious to non-communicable diseases, leading to major improvements in global child survival and enhanced life expectancy for all age groups. Vaccination efforts worldwide have been key to this achievement, but with a reduction in vaccine preventable diseases, anti-vaccine sentiments have concurrently increased. Eradication of smallpox in 1977 is a testament to vaccination impacts on human health. Despite this historic success, recent increases in infectious disease outbreaks, such as polio and measles, especially among poorly vaccinated populations, have underscored the risks of resurgence of diseases once thought eliminated in the United States and elsewhere. Engaging governments, community leaders, and the public will be critical to continuing the advancement of global health through elimination of vaccine preventable diseases.

Symptoms, viral loads, and rebound among COVID-19 outpatients treated with nirmatrelvir/ritonavir compared to propensity score matched untreated individuals.

BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes among patients with COVID-19; however, rebound after treatment has been reported. We compared symptom and viral dynamics in community-based individuals with COVID-19 who completed N/R and similar untreated individuals. METHODS: We identified symptomatic participants who tested SARS-CoV-2 positive and were N/R eligible from a COVID-19 household transmission study: index cases from ambulatory settings and their households were enrolled, collecting daily symptoms, medication use, and respiratory specimens for quantitative PCR for 10 days, March 2022-May 2023. Participants who completed N/R (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R completion or, if untreated, seven days after symptom onset. RESULTS: Treated (n=130) and untreated participants (n=241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; p=0.009) and VL rebound (27% vs 7%; p<0.001). Average daily symptoms were lower among treated participants compared to untreated participants without symptom rebound (1.0 vs 1.6; p<0.01), but not statistically lower with symptom rebound (3.0 vs 3.4; p=0.5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; p<0.01), but not statistically lower with VL rebound (4.8 vs 5.1; p=0.7). CONCLUSIONS: Individuals who completed N/R experienced fewer symptoms and lower VL but were more likely to have rebound compared to untreated individuals. Providers should still prescribe N/R, when indicated, and communicate possible increased rebound risk to patients.

Infectious Diseases-Related Hospitalizations During Oral Polio Vaccine (OPV) and Non-OPV Immunization Periods: An Empirical Evaluation of all Hospital Discharges in California (1985-2010).

BACKGROUND: Live attenuated vaccines such as oral polio vaccine (OPV) can stimulate innate immunity and may have off-target protective effects on other pathogens. We aimed to address this hypothesis by examining changes in infectious diseases (ID)-related hospitalizations in all hospital discharges in California during OPV (1985-1996) and non-OPV immunization periods (2000-2010). METHODS: We searched the Office of Statewide Health Planning and Development database for all hospital discharges with any ID-related discharge diagnosis code during 1985-2010. We compared the proportion of ID-related hospitalizations (with at least 1 ID-related discharge diagnosis) among total hospitalizations during OPV immunization (1985-1996) versus non-OPV immunization (2000-2010) periods. RESULTS: There were 19 281 039 ID-related hospitalizations (8 464 037 with an ID-related discharge diagnosis as the principal discharge diagnosis for the hospitalization) among 98 117 475 hospitalizations in 1985-2010; 9 520 810 ID hospitalizations/43 456 484 total hospitalizations in 2000-2010 versus 7 526 957/43 472 796 in 1985-1996. The risk ratio for ID-related hospitalizations in 2000-2010 versus 1985-1996 was 1.27 (95% confidence interval [CI], 1.26-1.27) for all diagnoses and 1.15 (95% CI: 1.15-1.16) for principal diagnoses. Increases also existed in the proportion of lower respiratory and gastrointestinal infections. DISCUSSION: The proportion of ID-related hospitalizations was lower in the OPV immunization period compared to the period after OPV was discontinued. When focused only on hospitalizations with ID as the principal discharge diagnosis, the signal remained significant but was smaller. These findings require replication in additional studies.

Incidence and Prevalence of Coronavirus Disease 2019 Within a Healthcare Worker Cohort During the First Year of the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic.

BACKGROUND: Preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2_ infections in healthcare workers (HCWs) is critical for healthcare delivery. We aimed to estimate and characterize the prevalence and incidence of coronavirus disease 2019 (COVID-19) in a US HCW cohort and to identify risk factors associated with infection. METHODS: We conducted a longitudinal cohort study of HCWs at 3 Bay Area medical centers using serial surveys and SARS-CoV-2 viral and orthogonal serological testing, including measurement of neutralizing antibodies. We estimated baseline prevalence and cumulative incidence of COVID-19. We performed multivariable Cox proportional hazards models to estimate associations of baseline factors with incident infections and evaluated the impact of time-varying exposures on time to COVID-19 using marginal structural models. RESULTS: A total of 2435 HCWs contributed 768 person-years of follow-up time. We identified 21 of 2435 individuals with prevalent infection, resulting in a baseline prevalence of 0.86% (95% confidence interval [CI], .53%-1.32%). We identified 70 of 2414 incident infections (2.9%), yielding a cumulative incidence rate of 9.11 cases per 100 person-years (95% CI, 7.11-11.52). Community contact with a known COVID-19 case was most strongly correlated with increased hazard for infection (hazard ratio, 8.1 [95% CI, 3.8-17.5]). High-risk work-related exposures (ie, breach in protective measures) drove an association between work exposure and infection (hazard ratio, 2.5 [95% CI, 1.3-4.8). More cases were identified in HCWs when community case rates were high. CONCLUSIONS: We observed modest COVID-19 incidence despite consistent exposure at work. Community contact was strongly associated with infections, but contact at work was not unless accompanied by high-risk exposure.

Long-Term Accuracy of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Interferon-γ Release Assay and Its Application in Household Investigation.

BACKGROUND: An immunodiagnostic assay that sensitively detects a cell-mediated immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed for epidemiological investigation and for clinical assessment of T- cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses. METHODS: The performance of a whole blood interferon-gamma (IFN-γ) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific T cells was evaluated in coronavirus disease 2019 (COVID-19) convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen. RESULTS: The overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI]: 79.0-89.0) and 86.6% (123/142; 95% CI: 80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI: 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI: 64.4-89.2) at 10 months post-infection (P < .01). The IFN-γ response remained relatively robust at 10 months post-infection (3.8 vs 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of + 50% (95% CI: +25.4 to +74.6) and +21.7% (95% CI: +9.23 to +42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts. CONCLUSIONS: The SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.

Favipiravir for Treatment of Outpatients With Asymptomatic or Uncomplicated Coronavirus Disease 2019: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

BACKGROUND: Favipiravir, an oral, RNA-dependent RNA polymerase inhibitor, has in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite limited data, favipiravir is administered to patients with coronavirus disease 2019 (COVID-19) in several countries. METHODS: We conducted a phase 2, double-blind, randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV-2 reverse-transcription polymerase chain reaction assay (RT-PCR) within 72 hours of enrollment. Participants were randomized to receive placebo or favipiravir (1800 mg twice daily [BID] day 1, 800 mg BID days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 amplicon-based sequencing, we assessed favipiravir's impact on mutagenesis. RESULTS: We randomized 149 participants with 116 included in the mITT cohort. The participants' mean age was 43 years (standard deviation, 12.5 years) and 57 (49%) were women. We found no difference in time to shedding cessation overall (hazard ratio [HR], 0.76 favoring placebo [95% confidence interval {CI}, .48-1.20]) or in subgroups (age, sex, high-risk comorbidities, seropositivity, or symptom duration at enrollment). We detected no difference in time to symptom resolution (initial: HR, 0.84 [95% CI, .54-1.29]; sustained: HR, 0.87 [95% CI, .52-1.45]) and no difference in transition mutation accumulation in the viral genome during treatment. CONCLUSIONS: Our data do not support favipiravir at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher favipiravir doses are effective and safe for patients with COVID-19. CLINICAL TRIALS REGISTRATION: NCT04346628.

Promoting COVID-19 vaccine acceptance: recommendations from the Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA.

Since the first case of COVID-19 was identified in the USA in January, 2020, over 46 million people in the country have tested positive for SARS-CoV-2 infection. Several COVID-19 vaccines have received emergency use authorisations from the US Food and Drug Administration, with the Pfizer-BioNTech vaccine receiving full approval on Aug 23, 2021. When paired with masking, physical distancing, and ventilation, COVID-19 vaccines are the best intervention to sustainably control the pandemic. However, surveys have consistently found that a sizeable minority of US residents do not plan to get a COVID-19 vaccine. The most severe consequence of an inadequate uptake of COVID-19 vaccines has been sustained community transmission (including of the delta [B.1.617.2] variant, a surge of which began in July, 2021). Exacerbating the direct impact of the virus, a low uptake of COVID-19 vaccines will prolong the social and economic repercussions of the pandemic on families and communities, especially low-income and minority ethnic groups, into 2022, or even longer. The scale and challenges of the COVID-19 vaccination campaign are unprecedented. Therefore, through a series of recommendations, we present a coordinated, evidence-based education, communication, and behavioural intervention strategy that is likely to improve the success of COVID-19 vaccine programmes across the USA.

The Impact of Unconscious Bias in Healthcare: How to Recognize and Mitigate It.

The increasing diversity in the US population is reflected in the patients who healthcare professionals treat. Unfortunately, this diversity is not always represented by the demographic characteristics of healthcare professionals themselves. Patients from underrepresented groups in the United States can experience the effects of unintentional cognitive (unconscious) biases that derive from cultural stereotypes in ways that perpetuate health inequities. Unconscious bias can also affect healthcare professionals in many ways, including patient-clinician interactions, hiring and promotion, and their own interprofessional interactions. The strategies described in this article can help us recognize and mitigate unconscious bias and can help create an equitable environment in healthcare, including the field of infectious diseases.

The 2016 California policy to eliminate nonmedical vaccine exemptions and changes in vaccine coverage: An empirical policy analysis.

BACKGROUND: Vaccine hesitancy, the reluctance or refusal to receive vaccination, is a growing public health problem in the United States and globally. State policies that eliminate nonmedical ("personal belief") exemptions to childhood vaccination requirements are controversial, and their effectiveness to improve vaccination coverage remains unclear given limited rigorous policy analysis. In 2016, a California policy (Senate Bill 277) eliminated nonmedical exemptions from school entry requirements. The objective of this study was to estimate the association between California's 2016 policy and changes in vaccine coverage. METHODS AND FINDINGS: We used a quasi-experimental state-level synthetic control analysis and a county-level difference-in-differences analysis to estimate the impact of the 2016 California policy on vaccination coverage and prevalence of exemptions to vaccine requirements (nonmedical and medical). We used publicly available state-level data from the US Centers for Disease Control and Prevention on coverage of measles, mumps, and rubella (MMR) vaccination, nonmedical exemption, and medical exemption in children entering kindergarten. We used county-level data individually requested from state departments of public health on overall vaccine coverage and exemptions. Based on data availability, we included state-level data for 45 states, including California, from 2011 to 2017 and county-level data for 17 states from 2010 to 2017. The prespecified primary study outcome was MMR vaccination in the state analysis and overall vaccine coverage in the county analysis. In the state-level synthetic control analysis, MMR coverage in California increased by 3.3% relative to its synthetic control in the postpolicy period (top 2 of 43 states evaluated in the placebo tests, top 5%), nonmedical exemptions decreased by 2.4% (top 2 of 43 states evaluated in the placebo tests, top 5%), and medical exemptions increased by 0.4% (top 1 of 44 states evaluated in the placebo tests, top 2%). In the county-level analysis, overall vaccination coverage increased by 4.3% (95% confidence interval [CI] 2.9%-5.8%, p < 0.001), nonmedical exemptions decreased by 3.9% (95% CI 2.4%-5.4%, p < 0.001), and medical exemptions increased by 2.4% (95% CI 2.0%-2.9%, p < 0.001). Changes in vaccination coverage across counties after the policy implementation from 2015 to 2017 ranged from -6% to 26%, with larger increases in coverage in counties with lower prepolicy vaccine coverage. Results were robust to alternative model specifications. The limitations of the study were the exclusion of a subset of US states from the analysis and the use of only 2 years of postpolicy data based on data availability. CONCLUSIONS: In this study, implementation of the California policy that eliminated nonmedical childhood vaccine exemptions was associated with an estimated increase in vaccination coverage and a reduction in nonmedical exemptions at state and county levels. The observed increase in medical exemptions was offset by the larger reduction in nonmedical exemptions. The largest increases in vaccine coverage were observed in the most "high-risk" counties, meaning those with the lowest prepolicy vaccine coverage. Our findings suggest that government policies removing nonmedical exemptions can be effective at increasing vaccination coverage.

Achieving Speaker Gender Equity at the SIR Annual Scientific Meeting: The Effect of Female Session Coordinators.

PURPOSE: To examine the impact of targeted efforts to increase the number of female speakers at the Society of Interventional Radiology (SIR) Annual Scientific Meeting (ASM) by reporting gender trends for invited faculty in 2017/2018 vs 2016. MATERIALS AND METHODS: Faculty rosters for the 2016, 2017, and 2018 SIR ASMs were stratified by gender to quantify female representation at plenary sessions, categorical courses, symposia, self-assessment modules, and "meet-the-expert" sessions. Keynote events, scientific abstract presentations, and award ceremonies were excluded. In 2017, the SIR Annual Meeting Committee issued requirements for coordinators to invite selected women as speakers. Session coordinators are responsible for issuing speaker invitations, and invited speakers have the option to decline. RESULTS: Years 2017 and 2018 showed increases in female speaker representation, with women delivering 13% (89 of 687) and 14% (85 of 605) of all assigned presentations, compared with 9% in 2016 (46 of 514; P = .03 and P = .01, respectively). Gender diversity correlated with the gender of the session coordinator(s). When averaged over a 3-year period, female speakers constituted 7% of the speaker roster (112 of 1,504 presentations) for sessions led by an all-male coordinator team, compared with 36% (108 of 302) for sessions led by at least 1 female coordinator (P < .0001). Results of the linear regression model confirmed the effect of coordinator team gender composition (P < .0001). CONCLUSIONS: Having a woman as a session coordinator increased female speaker participation, which suggests that the inclusion of more women as coordinators is one mechanism for achieving gender balance at scientific meetings.

Untapped Resources: Attaining Equitable Representation for Women in IR.

PURPOSE: To investigate the current state of gender diversity among invited coordinators at the Society of Interventional Radiology (SIR) Annual Scientific Meeting and to compare the academic productivity of female interventional radiologists to that of invited male coordinators. MATERIALS AND METHODS: Faculty rosters for the SIR Annual Scientific Meetings from 2015 to 2017 were stratified by gender to quantify female representation among those asked to lead and coordinate podium sessions. To quantify academic productivity and merit, H-index, publications, and authorship by females over a 6-year period (2012-2017) were statistically compared to that of recurring male faculty. RESULTS: From 2015 to 2017, women held 7.1% (9/126), 4.3%, (8/188), and 13.7% (27/197) of the available coordinator positions for podium sessions, with no representation at the plenary sessions, and subject matter expertise was concentrated in economics and education. Academic productivity of the top quartile of published female interventional radiologists was statistically similar to that of the invited male faculty (H-index P = .722; total publications P = .689; and authorship P = .662). CONCLUSIONS: This study found that senior men dominate the SIR Annual Scientific Meeting, with few women leading or coordinating the podium sessions, despite their established academic track record.

Pediatric HIV Infection and Decreased Prevalence of OPV Point Mutations Linked to Vaccine-associated Paralytic Poliomyelitis.

Background: Mutations associated with prolonged replication of the attenuated polioviruses found in oral poliovirus vaccine (OPV) can lead to vaccine-derived poliovirus (VDPV) and cause paralysis indistinguishable from that caused by wild poliovirus. In response, the World Health Organization has initiated the transition to exclusive use of inactivated poliovirus vaccine (IPV), with OPV administration in cases of outbreak. However, it is currently unclear how IPV-only vaccination, well known to provide humoral but not mucosal immunity, will impact the development of paralysis causing OPV variants. Children infected with human immunodeficiency virus (HIV) have been documented to show decreased mucosal immunity following OPV vaccination. Thus, HIV-infected children vaccinated with OPV may serve as proxy for children with IPV-only vaccination. Methods: We conducted a prospective study of Zimbabwean infants receiving OPV as part of their routine vaccination schedule. Stool samples collected from OPV-vaccinated children serially until age 24 months were tested for OPV serotypes using a real-time polymerase chain reaction protocol that quantifies the amount of mutant OPV variants found in each sample. Results: Out of 2130 stool samples collected from 402 infants 365 stool samples were OPV positive: 313 from 212 HIV-noninfected (HIV-) infants and 52 from 34 HIV-infected (HIV+) infants. HIV- infants showed significantly higher proportions of OPV mutants when compared to HIV+ infants. Conclusions: HIV infection is associated with a reduced proportion of OPV vaccine associated paralytic polio mutants. These results suggest that OPV administered to individuals previously vaccinated only with IPV will show decreased propensity for OPV mutations.

Assessing the Risk of Vaccine-derived Outbreaks After Reintroduction of Oral Poliovirus Vaccine in Postcessation Settings.

Background: The Polio Eradication and Endgame Strategic Plan 2013-2018 calls for the gradual withdrawal of oral poliovirus vaccine (OPV) from routine immunization. We aimed to quantify the transmission potential of Sabin strains from OPV when it is reintroduced, accidentally or deliberately, in a community vaccinated with inactivated poliovirus vaccine alone. Methods: We built an individual-based stochastic epidemiological model that allows independent spread of 3 Sabin serotypes and differential transmission rates within versus between households. Model parameters were estimated by fitting to data from a prospective cohort in Mexico. We calculated the effective reproductive number for the Mexico cohort and simulated scenarios of Sabin strain resurgence under postcessation conditions, projecting the risk of prolonged circulation, which could lead to circulating vaccine-derived poliovirus (cVDPV). Results: The estimated effective reproductive number for naturally infected individuals was about 1 for Sabin 2 and Sabin 3 (OPV2 and OPV3) in a postcessation setting. Most transmission events occurred between households. We estimated the probability of circulation for >9 months to be (1) <<1% for all 3 serotypes when 90% of children <5 years of age were vaccinated in a hypothetical outbreak control campaign; (2) 45% and 24% for Sabin 2 and Sabin 3, respectively, when vaccine coverage dropped to 10%; (3) 37% and 8% for Sabin 2 and Sabin 3, respectively, when a single active shedder appeared in a community. Conclusions: Critical factors determining the risk of cVDPV emergence are the scale at which OPV is reintroduced and the between-household transmission rate for poliovirus, with intermediate values posing the greatest risk.

Spatial Analyses of Oral Polio Vaccine Transmission in an Community Vaccinated With Inactivated Polio Vaccine.

Background: Understanding the spatial dynamics of oral polio vaccine (OPV) transmission will improve resource targeting. Mexico provides a natural laboratory, as it uses inactivated polio vaccine routinely as well as OPV bi-annually. Methods: Using geospatial maps, we measured the distance and density of OPV vaccinees' shedding in the areas nearest to unvaccinated households in 3 Mexican villages. Comparison of transmission to unvaccinated households utilized a mixed effects logistic regression with random effects for household and time, adjusted for age, gender, area, and running water. Results: The median distance from an unvaccinated household to its nearest OPV-shedding household was 85 meters (interquartile range, 46-145) and the median number of vaccinees shedding OPV within 200 m was 3 (2-6). Transmission to unvaccinated households occurred by day 1. There was no association (odds ratio [OR] 1.04; 95% credible interval [CrI] 0.92-1.16) between the distance from OPV shedding and the odds of transmission. The number of OPV vaccinees shedding within 200 m came close to a significant association with unvaccinated transmission (OR 0.93; CrI 0.84-1.01), but this was not the case for households 100 or 500 m apart. Results were consistent across the 3 villages. Conclusions: Geospatial analysis did not predict community transmission from vaccinated to unvaccinated households, because OPV use resulted in rapid, low transmission levels. This finding supports the global cessation of OPV.