Carlos R. Oliveira

Unvetted scientific claims about vaccines can spread rapidly and undermine decades of progress in immunization and public trust. A recent non-peer-reviewed analysis, promoted at political hearings, in the documentary “An Inconvenient Study,” and on social media, has been used to suggest that vaccinated children experience higher rates of chronic illness than unvaccinated peers. Despite standard regression models, critical flaws - uncontrolled confounding, exposure misclassification, unequal follow-up, and outcome multiplicity, invalidate causal inference. An independent group of international experts critically appraises this analysis and contrast its claims with the consistent evidence confirming vaccine safety and effectiveness. We also show how poorly designed studies can distort public discourse, amplify misinformation, and fuel vaccine hesitancy. We outline actions to strengthen research integrity, such as transparent data sharing, labeling of non-peer-reviewed content, and evidence-based communication. Safeguarding public health demands that vaccine evidence be methodologically sound, reviewed, and interpreted by qualified experts.

Neonatal echovirus 11 (E11) infection can be fulminant and fatal, yet no antiviral is approved. Recent outbreaks with recombinant variants have renewed concern about E11. We report a neonate with severe E11 infection treated with pocapavir, an investigational capsid inhibitor. Treatment was associated with viral clearance and favorable long-term outcomes.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection and hospitalization in infants and young children worldwide. Clinical management in infants remains primarily supportive, and natural infection provides incomplete and transient immunity. For decades, prophylaxis was limited to monthly palivizumab for selected high-risk infants. Recent advances in prefusion F structural biology, antibody engineering, and maternal immunization have transformed RSV prevention. This review summarizes the biologic and clinical rationale for preventing RSV disease in pediatric populations, with emphasis on currently licensed long-acting monoclonal antibodies and maternal RSVpreF vaccination. We integrate a meta-analysis of real-world effectiveness data and discuss implementation of these novel immunoprophylactic strategies in clinical practice. Across 43 observational studies, pooled effectiveness against RSV-associated hospitalization was 80.9% for nirsevimab and 79.1% for maternal RSVpreF vaccination, demonstrating substantial real-world protection during early infancy. Success now depends on optimizing implementation and achieving equitable access.

Background: Nirsevimab has been widely administered in the United States since 2023 to protect infants and young children from severe disease caused by respiratory syncytial virus (RSV). Although early post-licensure studies have shown high effectiveness against medically attended RSV infection, uncertainty remains about the durability of protection, effectiveness beyond the first RSV season, and the extent to which changing RSV seasonality influences real-world effectiveness. Objective: To estimate the effectiveness of nirsevimab against medically attended RSV infection across three consecutive RSV seasons and to examine how effectiveness varies by season and time since immunization. Methods: We conducted a test-negative case-control study utilizing electronic health records of infants and young children tested for RSV by polymerase chain reaction in outpatient and inpatient settings within the Yale New Haven Health System between October 1, 2023, and March 1, 2026. Effectiveness of nirsevimab was estimated using multivariable logistic regression, adjusting for age, weekly RSV activity, pre-existing risk factors, and other potential confounders. Variation in effectiveness was examined by season, encounter setting, and time since immunization up to 24 months. Results: Overall, 17,755 infants and young children were tested for RSV infection, of whom 2,388 (13.4%) were cases and 15,367 (86.6%) were controls. The overall effectiveness of nirsevimab was 67.3% (95% confidence interval [CI]: 59.8, 73.3%) against all medically-attended RSV infections, 60.2% (95% CI: 49.6, 68.5%) against RSV-associated outpatient visits, and 88.9% (95% CI: 82.3, 93.0%) against RSV-associated hospitalization. Effectiveness against medically attended RSV infection declined across seasons, from 76.7% (95% CI: 60.5, 86.3%) in 2023/24 to 54.4% (95% CI: 33.0, 68.9%) in 2025/26. Lower season-specific effectiveness in later seasons corresponded with progressively delayed RSV activity over. Protection against RSV-associated hospitalization declined with increasing time since immunization, from 92.5% (95% credible interval [CrI]: 85.9, 96.4%) at 1 month, to 77.2% (95% CrI: 60.4, 87.6%) at 6 months, and 39.9% (95% CrI: 2.4, 63.3%) at 12 months post-immunization, after which effectiveness plateaued. Conclusions: Nirsevimab remained effective against RSV-associated hospitalization through 6 to 12 months after immunization. Delayed RSV activity was associated with lower effectiveness, highlighting the importance of aligning administration with local RSV circulation.

Importance: Religious vaccine exemptions remain central to debates over school-entry immunization mandates, but evidence on exemption repeal outside outbreak-driven policy responses and across communities with different religious contexts remains limited. Objective: To estimate changes in kindergarten vaccination coverage associated with Connecticut’s 2021 repeal of religious vaccine exemptions, examine variation by school type and local religious congregation density, and compare trends with states that retained exemptions. Design/Setting/Participants: Interrupted time series analysis using kindergarten vaccination data from 2012-2025. Vaccine coverage trends in Connecticut were compared to Arizona, Louisiana, and Oregon, which retained religious exemptions during the study period. Intervention: The intervention studied was Public Act 21-6, which eliminated religious vaccine exemptions from school-entry immunization requirements. Main Outcomes and Measures: Outcomes included annual coverage for measles-mumps-rubella (MMR), varicella, diphtheria-tetanus-acellular pertussis (DTaP), polio, and hepatitis B vaccines. Models estimated pre-policy trends, immediate level changes, and post-policy slope changes. Analyses were stratified by public and private schools and by county-level religious congregation density. Results: Before policy implementation, kindergarten vaccination coverage in Connecticut declined across all vaccines by 0.16-0.20% per year (p < 0.001). Repeal of the religious exemptions occurred during a period of increasing religious congregation density and was associated with improved school-entry vaccination coverage, with annual coverage increasing 0.88-1.02% per year (p < 0.001). Coverage increased in both public and private schools, with larger post-policy gains in private schools. Coverage increases did not differ significantly between high- and low-religiosity counties. In segmented regression analyses, Connecticut’s post-policy MMR slope was significantly higher than those of Arizona, Oregon, and Louisiana by 1.36, 1.71, and 1.15 percentage points per year, respectively (p < 0.001). By 2024/25, Connecticut MMR coverage reached 98.2%, exceeding coverage in comparison states by 5.6-9.6%. Cumulatively, the model-estimated policy impact represented an estimated 2,579 additional kindergarteners immunized against MMR compared with the no-policy counterfactual. Conclusions and Relevance: Connecticut’s repeal of religious vaccine exemptions was associated with increases in kindergarten vaccination coverage across public and private schools, independent of local religious congregation density. These findings suggest that removal of religious vaccine exemptions may be an effective policy approach to improve childhood immunization coverage. KEY POINTS: Question: How does Connecticut’s repeal of religious vaccine exemptions affect kindergarten vaccination coverage in the context of local religious and nationwide coverage trends? Findings: An interrupted time series analysis using data from 2012-2025 revealed that repeal of religious vaccine exemptions was followed by a reversal of declining kindergarten vaccination coverage trends. Coverage increases did not differ significantly between high- and low-religiosity counties. Compared with states that retained religious exemptions, Connecticut had significantly greater post-policy increases in vaccination coverage. Meaning: Repeal of religious vaccine exemptions may improve school-entry vaccination coverage even during a period of increasing religious congregation density and may reduce disparities between public and private schools.

Respiratory syncytial virus (RSV) disproportionately causes severe infections among infants and older adults, yet the key age group responsible for viral spread to other age groups remains poorly defined. While current immunization approaches effectively reduce disease severity among the most vulnerable, identifying the core drivers of infection is essential to effectively disrupt population-level transmission. By generating 910 whole-genome viral sequences of RSV from all age groups (<1 to 65+ years) in Connecticut, we identified that children aged 12-35 months are the primary drivers of viral transmission to other age groups. This group significantly shapes the genetic diversity of circulating strains. Furthermore, we found that RSV is introduced into the community through frequent and independent entries from other US regions throughout the year, rather than through a single explosive seasonal introduction or long-term local persistence. Ultimately, our findings justify prevention strategies that expand beyond reducing disease burden to actively prioritizing the reduction of transmission and infection.

Introduction Respiratory syncytial virus (RSV) is a leading cause of hospitalisation in infants worldwide. New immunoprophylactic products, including long-acting monoclonal antibodies and maternal vaccines, have demonstrated high efficacy in prelicensure clinical trials. Understanding how these interventions perform outside controlled trials, and how viral evolution or host factors influence protection, is essential for sustaining confidence in RSV prevention programmes. Methods and analysis We will conduct a 5-year, test-negative case–control study among infants ≤12 months of age who present with acute respiratory illness (ARI) within a large healthcare delivery network serving a demographically diverse population. Cases will be infants testing positive for RSV by PCR, and controls will be RSV-negative infants meeting the same ARI criteria. Data will be obtained from electronic health records, structured caregiver surveys and state immunization registries to ensure accurate classification of exposures and covariates. Vaccine effectiveness will be estimated using multivariable logistic regression controlling for potential confounding. RSV-positive specimens will undergo full-genome sequencing to identify variant lineages and potential immune-escape mutations. A subset of participants will provide acute and convalescent blood samples for single-cell immune profiling to define innate and adaptive responses associated with breakthrough infection. Ethics and dissemination The study protocol has been approved by the Yale Human Investigation Committee (HIC #2000036550). Written informed consent will be obtained from all parents or legal guardians prior to participation. Study findings will be disseminated through peer-reviewed publications, scientific meetings and public repositories, with fully de-identified participant data to protect privacy and confidentiality. Viral genomic data will be shared in accordance with the National Institutes of Health Genomic Data Sharing Policy, and analytical code will be made publicly available to ensure reproducibility. Trial registration number NCT06172660.

Summary: Reduced vaccine coverage has led to a resurgence of vaccine-preventable diseases, threatening decades of public health progress. This perspective explores the rise in measles cases and outlines how the pediatric infectious disease community can rebuild vaccine confidence to reverse this trend.

Objective Congenital cytomegalovirus (cCMV) is a leading cause of potentially treatable non-genetic hearing loss, but many cases are missed at birth. In 2016, Connecticut mandated hearing-targeted cCMV screening for all newborns who fail their initial hearing test. We evaluated its impact on diagnosis rates and long-term outcomes by comparing the 3 years of no screening with the subsequent eight years of mandated screening. Methods We conducted a retrospective interrupted time series study (2013–2023) within a health system serving ∼60% of Connecticut’s population. Confirmed cases were defined as positive CMV testing within 21 days of life. Annual diagnosis rates were modeled before and after mandate implementation. Long-term audiologic and neurodevelopmental outcomes were tracked through June 2025. Results Among 197,177 births, 48 infants had confirmed cCMV. The screening mandate was associated with a 3.6-fold increase in diagnoses (IRR 3.58; 95% CI 1.17–11.0), peaking at 4.09 per 10,000 births. Prior to the mandate, all detected cases were moderately to severely symptomatic. Afterward, 11 clinically inapparent cases were identified, 73% of whom were later found to have significant sequelae. Among those with sensorineural hearing loss at birth, 81% worsened over time. Developmental delays occurred in 61% of children with follow-up. Conclusion Hearing-targeted screening increased cCMV case detection and identified infants with clinically meaningful disease who would otherwise have been missed. However, many infections likely remain undetected, underscoring both the value and limitations of targeted approaches and highlighting the need to consider universal screening.