The Lancet Regional Health - Americas

BackgroundThe continued emergence of Salmonella enterica serovar Typhi (S. Typhi) with ever increasing antimicrobial resistance (AMR), necessitates the use of vaccines in endemic countries. A typhoid fever outbreak in Harare, Zimbabwe in 2018 from a multidrug resistant S. Typhi with additional resistance to ciprofloxacin was the catalyst for the introduction of a typhoid conjugate vaccine program. To investigate the historic emergence and evolution of AMR of endemic S. Typhi in Zimbabwe and determined the population structure, gene flux and sequence polymorphisms of strains isolated prior to mass typhoid vaccination to provide a baseline for future evaluation of the effect of the vaccination program. MethodsWe determined the population structure, gene flux and sequence polymorphisms and reconstructed the evolution of AMR. The S. Typhi population structure was investigated in the context the genome sequence of 1904 strains isolated from 65 countries to reconstruct spread of endemic strains into Zimbabwe. FindingsThe population structure of S. Typhi in Zimbabwe is dominated by multidrug resistant genotype 4.3.1.1 (H58) that spread to Zimbabwe from neighboring countries around 2009. Evolution of AMR within Zimbabwe included acquisition of an IncN plasmid carrying a qnrS gene and a mutation in the quinolone resistance determining region of gyrA gene, both implicated in resistance to quinolone antibiotics. A minority population of antimicrobial susceptible S. Typhi genotype 3.3.1 strains was detected in typhoid cases. InterpretationThe currently dominant S. Typhi population is genotype 4.3.1.1 that spread to Zimbabwe and acquired additional AMR though acquisition of a plasmid and mutation of the gyrA gene. This study provides a baseline for future evaluation of the impact of the Typhoid Conjugate Vaccine program in Harare. FundingRAK and GT were supported by Bill and Melinda Gates Foundation project OPP1217121 and the BBSRC Institute Strategic Programme BB/R012504/1 and its constituent project BBS/E/F/000PR10348.

We used a test-negative design to estimate the vaccine effectiveness of Ad26.COV2.S (Janssen) against symptomatic COVID-19 and clinical outcomes in Mato-Grosso do Sul, Brazil. We analyzed 11,817 RT-PCR tests. The mean age was 37 (SD=17) years, 2,308 (20%) of individuals more or equal than 50 years and almost two-thirds of the population was Brown/Pardo. Adjusted effectiveness against symptomatic COVID-19 after 28 days of the single dose was 50.9% (95% CI, 35.5-63.0). Adjusted effectiveness against clinical outcomes was 72.9% (95% CI, 35.1-91.1) for hospitalization, 92.5% (95% CI, 54.9-99.6) for ICU admission, 88.7% (95% CI, 17.9-99.5) for mechanical ventilation and 90.5% (95% CI, 31.5-99.6) for death. Despite lacking precision on some estimates, a single dose of Ad26.COV2.S vaccine continues to protect specially for severe forms of COVID-19 in the context of new variants.

BackgroundPediatric cancer treatment outcomes in low- and middle-income countries (LMICs) significantly lag behind those in high-income countries. One reason for this disparity is high treatment abandonment rates, defined as a failure to start or complete curative-intent therapy after a cancer diagnosis. We conducted a scoping review to describe interventions aimed at reducing treatment abandonment in pediatric cancer patients in LMICs. MethodsStudies identified through systematic database search were included if they met the following criteria: (a) studied an intervention on treatment abandonment; (b) included cancer patients [≤]18 years of age; (c) conducted in LMICs as defined by the World Bank income classification; (d) contained pre- and post-intervention measures of treatment abandonment. We restricted inclusion to English-language publications. Two reviewers independently screened the eligible publications and extracted the data. Interventions were categorized as focusing on socioeconomic support, education/psychosocial support, or clinical care quality and capacity improvements (e.g., care navigation, coordination, or therapeutic/diagnostic expansion). FindingsAmong the 1,808 articles identified in the search, 21 studies met inclusion criteria: four from the WHO African region, nine from the Americas, seven from the South-East Asian, and three from the Western Pacific Region. Sixteen studies (66%) focused on one category for improvement, and eight (34%) were a mixture of two or more categories. All studies demonstrated a decrease in treatment abandonment after the intervention. The median absolute risk reduction (ARR) was 16% (interquartile range [IQR] 10%-24%). The median relative risk reduction was 72% (IQR 60%-82%). The median pre-intervention abandonment rate across full-text studies was 27% (IQR 20%-34%) and decreased to 7% (IQR 3%-12%) after intervention. Interventions with the largest ARR values included components of socioeconomic support, psychosocial support, and clinic care improvements. All of the 10 studies reporting pre- and post-intervention survival outcomes reported increases in survival following the intervention. InterpretationOur scoping review describes interventions that were associated with reduced pediatric cancer treatment abandonment in LMICs. Interventions that combined socioeconomic support, psychosocial support, and clinical care quality/capacity improvements yielded the largest reductions. Despite these encouraging findings, limitations of the evidence, including short study durations, single-center designs, lack of control groups, and likely publication bias, restrict the generalizability of results. These findings suggest that treatment abandonment is a targetable and potentially modifiable challenge in LMICs, and that survival outcomes can improve when health systems adopt multifaceted interventions that support families and strengthen care delivery. FundingNational Institutes of Health, K12CA090433.

Vaccine effectiveness (VE) against emerging SARS-CoV-2 variants is a growing issue. The aim of this work is to evaluate the impact of the COVID-19 additional/booster dose against COVID-19-related symptoms, hospitalization, and death using surveillance data (December 2021-May 2022) from the Italian National Institute of Health (ISS). As of 18 May 2022, for people fully vaccinated with three doses, VE was 87.8% (95% confidence interval (CI): 87.6-88.0), whereas VE decreased from 71.5% (95% CI: 71.0-72.0) in those vaccinated > 120 days to 69.6% (95% CI: 68.3-70.8) within 91-120 days. Results support the importance of receiving a third dose of mRNA COVID-19 vaccine.

Children affected by orphanhood of any cause may benefit from assessment and referral to appropriate services. Timely and accurate data can guide policy. We leveraged new data sources expanding previous reports on national COVID-19-associated orphanhood to estimate national and sub-national numbers of children newly affected by death of parents and co-residing elderly caregivers due to all-causes and to COVID-19-associated causes in 2020-2021 in Brazil. We estimated that 1,300,000 (95% uncertainty interval 1,190,000, 1,430,000) children in Brazil experienced loss of one or multiple parents and/or co-residing caregivers 60+. 673,000 (652,000, 690,000) children were estimated to have lost one or both parents, of which 149,000 (144,000, 154,000) were COVID-19-associated; 635,000 (534,000, 758,000) children were estimated to have lost a co-residing grandparent or other kin, of which 135,000 (85,900, 199,000) were COVID-19-associated. Orphanhood estimates varied across states. The highest all-cause rate of parental orphanhood was in Roraima, at 17.5 (95% uncertainty interval 15.6, 20.6) per 1000 children, and the lowest was in Santa Catarina, at 9.5 (8.7, 10.4) per 1000 children. COVID-19-associated orphanhood was also unevenly distributed, with Mato Grosso experiencing the greatest rate, at 4.4 (3.9, 5.3) per 1000 children, while Para experienced the lowest rate of 1.4 (1.2, 1.8) per 1000 children. We compared our estimates with administrative data for COVID-19-associated orphanhood (from Brazils civil registry offices and manually reviewed death certificates in Campinas) and found that a similar demographic distribution of orphanhood. However, our estimates suggested that administrative sources undercount orphanhood, suggesting that approximately 32% and 56% of total orphanhood was captured in the two datasets, respectively. Our findings highlight the extent of orphanhood in Brazil and the large inequalities between states. Our comparisons with administrative data both validate our model and suggest that strengthening vital registration systems can put children at the center of public health responses globally.

BackgroundAlthough the impact of COVID-19 vaccination is widely documented in the general population, the evidence on its effectiveness in children under 5 years of age is still limited. In this context, the continuation of vaccination programs in this age group has been debated globally. Consequently, we estimated the effectiveness of the 3-dose series of BNT162b2 (Pfizer-BioNTech) in children aged 6 months to 4 years and the complete 2-dose series of CoronaVac (Sinovac) in children aged 3 to 4 in reducing the risk of hospitalizations due to COVID-19-attributed severe acute respiratory infection (SARI) in Brazil. MethodsWe conducted a retrospective cohort study in 24 Brazilian municipalities, using surveillance data. We evaluated vaccine effectiveness in reducing the incidence rate of COVID-19-attributed SARI hospitalizations from July 2023 to December 2024. Covariate adjustments, defined a priori based on a conceptual model represented by a directed acyclic graph (DAG), were implemented using random-effects Poisson regression models. We also analyzed alternative vaccination schedules and obtained age-specific estimates of effectiveness. ResultsThe cohort comprised 37.6 million person-months of follow-up and 1,384 COVID-19-attributed SARI hospitalizations, including 27 associated deaths. The 3-dose series of BNT162b2 vaccine had an effectiveness of 97% (IRR 0.03, 95%CI 0.01-0.10) in the group aged 6 months to 4 years, with no significant differences among age-specific estimates. No deaths occurred among children who completed the 3-dose series, whereas four deaths were observed among those with fewer doses. The effectiveness of CoronaVac was small and not statistically significant (IRR 0.96, 95%CI 0.57-1.62). However, no deaths were recorded among children who received any number of CoronaVac doses, and no COVID-19-attributed SARI hospitalizations were observed among those who received a third dose of this vaccine. ConclusionsThe 3-dose series of the mRNA vaccine (BNT162b2) had high and consistent effectiveness in protecting against severe COVID-19 in children aged 6 months to 4 years. These findings support the maintenance of routine COVID-19 vaccination in this age group.

INTRODUCTIONThe Affordable Care Acts Medicaid expansion aimed to enhance healthcare access for low-income individuals and minority groups, promoting early screening and treatment to improve health equity. OBJECTIVEThis study examines the impact of Medicaid expansion on lung cancer-specific survival (CSM) and overall mortality (OS) by comparing outcomes in Texas (non-expansion of ACA) and California (expansion of ACA). METHODOLOGYWe conducted a retrospective study using data from SEER cancer registry (2007-2021) to evaluate the impact of Medicaid expansion on lung cancer survival in California (expansion) vs. Texas (non-expansion). The study included adults aged 18-64, with periods split into pre-ACA (2007-2013), one-year washout (2014), and post-ACA (2015-2021). We utilized a DID design and adjusted for important covariates. RESULTSAmong 119,937 individuals with Lung cancer, 52.1% were in California (62,521), while 47.8% were in Texas (57,416). The pre-ACA period included 60,010 individuals (53.1% in California and 46.9% in Texas), and 59,927 patients were in the post-ACA period (51.2% in California and 48.8% in Texas). Overall, Medicaid expansion was associated with a 1.12-point (- 1.12, 95% CI -1.46 to -0.77) reduction in the hazard of cancer-specific mortality. The policy was also associated with a 0.81point reduction in the hazard of overall mortality (-0.81, 95% CI -1.06 to -0.57). CONCLUSIONMedicaid expansion was associated with a significant improvement in lung cancer outcomes among individuals with lung cancer in California, which implemented the policy in 2014, compared to Texas, which has not yet implemented the policy.

BackgroundCentral nervous system (CNS) tumors affect over 4,600 children throughout the United States each year. Despite recent trends of increasing incidence of pediatric CNS tumors, the understanding of variations in their incidence between different geographical regions remains incomplete. MethodData used in this study was obtained from the Surveillance, Epidemiology, and End Results (SEER) Program. The SEER database and its built-in operation software was used to generate state-specific incidence data for newly diagnosed CNS tumor diagnoses in children ages 0-19 for the years 2001-2014. Results were organized by tumor type and individual states were clustered into nine geographical regions as defined by the United States Census Bureau. ResultsStatistically significant differences were found in the regional incidence of astrocytoma, primitive neuroectodermal tumor (PNET), and the category of unspecified intracranial and intraspinal neoplasms. However, the magnitude of the difference in incidence ({Delta}I) between specific regions was small, on the order of 0.1 to 0.6 per 100,000 population, representing a nominal 0.05-fold to 0.79-fold change in incidence ({Delta}I/incidence for comparator region) for astrocytoma and for the category of unspecified intracranial and intraspinal neoplasms, and a larger 3.25-fold to 3.75-fold change in incidence for PNET. ConclusionsDifferences in incidence between geographical regions for certain CNS tumor types met the bar for statistical significance. However, these differences are unlikely to be clinically meaningful due to the small effect size.

BackgroundMass vaccination campaigns started in Brazil on January/2021 with CoronaVac followed by ChAdOx1 nCov-19, and BNT162b2 mRNA vaccines. Target populations initially included vulnerable groups such as people older than 80 years, with comorbidities, of indigenous origin, and healthcare workers. Younger age groups were gradually included. MethodsA national cohort of 66.3 million records was compiled by linking registry-certified COVID-19 vaccination records from the Brazilian National Immunization Program with information on severe COVID-19 cases and deaths. Cases and deaths were aggregated by state and age group. Mixed-effects Poisson models were used to estimate the rate of severe cases and deaths among vaccinated and unvaccinated individuals, and the corresponding estimates of vaccine effectiveness by vaccine platform and age group. The study period is from mid-January to mid-July 2021. ResultsEstimates of vaccine effectiveness preventing deaths were highest at 97.9% (95% CrI: 93.5-99.8) among 20-39 years old with ChAdOx1 nCov-19, at 82.7% (95% CrI: 80.7-84.6) among 40-59 years old with CoronaVac, and at 89.9% (87.8--91.8) among 40-59 years old with partial immunization of BNT162b2. For all vaccines combined in the full regimen, the effectiveness preventing severe cases among individuals aged 80+ years old was 35.9% (95% CrI: 34.9-36.9) which is lower than that observed for individuals aged 60-79 years (61.0%, 95% CrI: 60.5-61.5). ConclusionDespite varying effectiveness estimates, Brazils population benefited from vaccination in preventing severe COVID-19 outcomes. Results, however, suggest significant vaccine-specific reductions in effectiveness by age, given by differences between age groups 60-79 years and over 80 years.

BackgroundCoronaVac, an inactivated COVID-19 vaccine, underwent evaluation for its efficacy and safety during the PROFISCOV study conducted in Brazil. MethodsBetween July 21, 2020, and July 29, 2021, 13,166 participants provided informed consent, with 12,688 randomized for the trial. Participants were allocated between vaccine and placebo arms (1:1) and monitored for symptomatic COVID-19 cases, severity of disease, and adverse reactions after two doses given 14 days apart. FindingsThe primary efficacy analysis revealed a vaccine efficacy of 50{square}39% (95% confidence interval [CI], 35{middle dot}26% to 61{middle dot}98%; p=0{middle dot}0049) in preventing symptomatic COVID-19, leading to the issuance of Emergency Use Authorization for CoronaVac in January 2021. Upon completion of follow-up, vaccine efficacy was 44{square}58% [95% CI, 34{middle dot}89% to 52{middle dot}83%; p= 0{middle dot}0023] in preventing COVID-19 and 82{square}14% (95% CI, 64{middle dot}93% to 90{middle dot}90%; p<0{middle dot}0001) in preventing severe COVID-19. Safety data indicated that adverse reactions were more frequent in the vaccine arm, primarily mild to moderate, with pain at the injection site and headache being the most common. InterpretationCoronaVac demonstrated moderate efficacy in preventing symptomatic COVID-19 and high efficacy against severe disease. While reactions were slightly more common in the vaccine group, they were generally mild and manageable. FundingFundacao Butantan, Instituto Butantan, and Sao Paulo Research Foundation (FAPESP; Grants 2020/10127-1 and 2020/06409-1). Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSAt the time of the studys design in 2020, the world was grappling with the COVID- 19 pandemic, with no licensed vaccine available. A global race to develop a safe and effective vaccine was underway, leading to the exploration of several vaccine candidates based on various technologies and mechanisms of action. Among these candidates was CoronaVac, an inactivated vaccine developed by Sinovac Life Sciences. PubMed was searched for pre-clinical and clinical trials using terms "COVID-19", "SARS-CoV-2", "Vaccine", "Vaccine Efficacy", without language or data restrictions. Additionally, information on clinical trials was sought from the ClinicialTrials.gov database and regulatory agencies. The focus was on late-stage clinical trials evaluating the safety, immunogenicity, and efficacy of CoronaVac. Positive safety and immunogenicity results from phase I/II clinical trials in younger and older adults, coupled with expanding pandemic, motivated the design and implementation of this phase III trial in healthcare professionals directly caring for or likely to be in close contact with COVID-19 patients in Brazil. No previous phase III study focusing on the efficacy and safety of CoronaVac in this high-risk population was identified. Added value of this studyBetween July 21, 2020, and July 29, 2021, 12,688 participants were randomized to receive either CoronaVac or placebo. We evaluated symptomatic COVID-19 cases, disease severity, and adverse reactions after two doses given 14 days apart. We found that CoronaVac met the predefined efficacy criteria, providing a moderate efficacy against symptomatic COVID-19 of 50{square}39% (95% CI: 35{middle dot}26-61{middle dot}98) in the primary analysis. Notably, CoronaVac demonstrated high effective against severe disease, with a vaccine efficacy of 82{square}14% (64{middle dot}93-90{middle dot}90) in the final analysis. Regarding safety, CoronaVac was shown to be safe, with most reactions being mild and manageable, albeit more commonly reported in the CoronaVac group. The inclusion of a high-risk study population comprising healthcare workers directly involved in the care of COVID-19 patients in Brazil is a key differentiator of our trial, as other studies of CoronaVac in China, Indonesia, Chile and Turkey at that time were not restricted to healthcare workers. Implications of all the available evidence.The primary efficacy analysis data from this study supported the Emergency Use Authorization issued for CoronaVac in Brazil in January 2021. Subsequently, a national vaccination campaign was initiated, with CoronaVac being the first vaccine to be incorporated in the COVID-19 vaccination program in Brazil. Since then, more than 100 million doses of CoronaVac have been administered in Brazil through the National Health System. The efficacy and safety of two doses of CoronaVac were demonstrated in the final analysis of the study. CoronaVacs ability to prevent severe disease is a crucial attribute that has had a positive impact on pandemic control and public health. It represents a promising option for COVID-19 vaccination, especially in low- or middle-income countries, given its moderate efficacy against symptomatic disease and favorable safety profile, in addition to its lower cost and ease of manufacturing compared to other vaccines available early in the pandemic. The impact on the immunogenicity and safety profile of XBB-updated versions of the vaccine used as a booster vaccination needs to be investigated in future studies.

Pregnant women were excluded from initial clinical trials for COVID-19 vaccines1-2, thus the immunologic response to vaccination in pregnancy and the transplacental transfer of maternal antibodies are just beginning to be studied4-5.

BACKGROUNDVaccination has been effective in ameliorating the impact of COVID-19. However, estimation of vaccine effectiveness (VE) is still unavailable for some widely used vaccines and underrepresented groups. Here, we report on the effectiveness of a nation-wide COVID-19 vaccination program in Mexico. METHODSWe used a test-negative design within a national COVID-19 surveillance system to assess VE of the BNT162b2, mRNA-12732, Gam-COVID-Vac, Ad5-nCoV, Ad26.COV2.S, ChAdOx1 and CoronaVac vaccines, against SARS-CoV-2 infection, COVID-19 related hospitalization and death for adults [&ge;]18 years in Mexico. VE was estimated using Cox proportional hazard models considering time-varying vaccination status in partial and fully vaccinated individuals compared to unvaccinated adults, adjusted by age, sex, comorbidities and municipality. We also estimated VE for adults [&ge;]60 years, for cases with diabetes and comparing periods with predominance of variants B.1.1.519 and B.1.617.2. RESULTSWe assessed 793,487 vaccinated compared to 4,792,338 unvaccinated adults between December 24th, 2020, and September 27th, 2021. VE against SARS-CoV-2 infection was highest for fully vaccinated individuals with mRNA-12732 (91.5%, 95%CI 90.3-92.4) and Ad26.COV2.S (82.2%, 95%CI 81.4-82.9), whereas for COVID-19 related hospitalization were BNT162b2 (84.3%, 95%CI 83.6-84.9) and Gam-COVID-Vac (81.4% 95%CI 79.5-83.1) and for mortality BNT162b2 (89.8%, 95%CI 89.2-90.2) and mRNA-12732 (93.5%, 95%CI 86.0-97.0). VE for all evaluated vaccines was reduced for adults [&ge;]60 years, people with diabetes, and in periods of Delta variant predominance. CONCLUSIONSAll evaluated vaccines were effective against SARS-CoV-2 infection and COVID-19 related hospitalization and death. Mass vaccination campaigns with multiple vaccine products are feasible and effective to maximize vaccination coverage.

Prevalence estimates of autism spectrum disorder (henceforth autism) in Latin America thus far have been limited by a lack of reliable population-level data. We analyzed autism school prevalence across 29 Chilean health service regions for students aged 6-18 years, standardized by age and sex. We validated these results using electronic health records from one of Chiles largest regional health service, the Servicio de Salud Araucania Sur (SSAS). We then projected Bayesian prevalences, reporting nationally, and by health service, ethnicity, immigration background, and rurality. We found a standardized national school autism prevalence of 0.46% (95% CI, 0.46%-0.47%), with boys having six times higher odds of autism than girls (OR 6.10 [95%CI: 5.82-6.41]). The sex - and age-adjusted clinical prevalence in the SSAS trust was 1.22% (95% CI: 1.16%-1.28%) and the projected Bayesian national autism prevalence was 1.31% (95% Credible Interval: 1.25%-1.38%). Our results indicate a higher autism prevalence than previously reported in the south of the Araucania region with observed disparities in prevalence across sex, ethnic groups, and health services.

Congenital heart defects are a leading cause of neonatal morbidity and mortality worldwide. Early diagnosis is essential to enable timely treatment and improve patient outcomes; however, access to early detection and specialized care is unevenly distributed across regions in Argentina. This study describes the prevalence and timing of diagnosis of congenital heart defects and critical congenital heart defects among live births covered by the public health system nationwide. We performed a cross-sectional, descriptive, ecological study including all live births between 2014 and 2019 with a diagnosis of congenital heart defects reported up to five years of age in the National Registry of Congenital Heart Diseases. We calculated prevalence rates and median age at case notification for each province to assess geographic disparities. Out of 2,473,720 live births, 16,150 cases of congenital heart defects (prevalence 65.3 per 10,000 live births) and 3,700 cases of critical congenital heart defects (15.0 per 10,000) were identified. Provincial prevalence ranged widely, from 34.9 to 212.2 per 10,000 for congenital heart defects and from 10.7 to 27.3 per 10,000 for critical cases. The national median age at notification was 75 days for all congenital heart defects and 29 days for critical cases, with notable provincial differences. These findings demonstrate significant provincial variability in both the prevalence of congenital heart defects and the age at which cases are reported to the national health registry. Strengthening early detection efforts and ensuring equitable access to specialized care are crucial to reduce morbidity and mortality associated with these conditions in Argentina and similar settings.

PurposeWilms tumor is a common renal cancer of childhood with long-term survival rates exceeding 80% in high-resource countries, yet survival remains below 50% in the low-resource settings of Africa. We assessed outcomes of a resource-adapted treatment protocol at a Malawian hospital to identify actionable factors affecting survival. MethodsWe assessed clinical outcomes with a single-center retrospective cohort study of children diagnosed between 2016 and 2021 in Lilongwe, Malawi. FindingsWe identified 136 patients with Wilms tumor, most commonly with stage III (25.7%) or IV disease (25.7%). Two-year overall survival (OS) was: Stage I, 78%; Stage II, 27%; Stage III, 62%; Stage IV, 23%, Stage V, 0%. Event-free survival (EFS) was: Stage I, 60%; Stage II, 0%; Stage III, 51%; Stage IV, 13%; Stage V, 0%. After death, treatment abandonment was the most common event comprising EFS, occurring in 26.5% of patients. Among 43% of patients who completed therapy, 2-year OS was 80% and EFS was 69%. Relapse was documented in 9.6% of patients. Radiotherapy was indicated for 40.4% patients, among whom only three received it due to regional unavailability. Factors associated with OS were severe acute malnutrition (Hazard ratio, HR, 1.9), increasing tumor stage (HR, 1.5), and inferior vena cava involvement (HR, 2.7). On multivariable analysis, only tumor stage remained associated with outcome. InterpretationImplementing a curative resource-adapted treatment protocol in an extremely resourced-constrained environment was feasible in Malawi and resulted in relatively favorable outcomes in low-stage disease, particularly among those who completed therapy. However, factors such as late-stage disease, frequent abandonment, and absent radiotherapy represent ongoing implementation barriers that should be the focus of continued research funding and intervention in Africa.

Brazils vast geographic and socioeconomic diversity has contributed to heterogeneous responses to the COVID-19 pandemic, particularly regarding vaccine distribution. This ecological study examined inequality in COVID-19 vaccine administration across 5,568 Brazilian municipalities from 2021 to 2023. Vaccination coverage was estimated using the vaccination coefficient, and inequality was assessed via the Gini index. We further analyzed associations between vaccine distribution inequality and socioeconomic indicators, including the Social Vulnerability Index (SVI), and the national health infrastructure metric PQAVS-03, using beta regression models. Results indicated that northern states such as Roraima, Para, and Amazonas consistently exhibited the highest Gini coefficients, reflecting marked disparities in vaccine allocation, while southern states like Rio Grande do Sul and Espirito Santo demonstrated more equitable distribution. SVI was significantly associated with vaccine inequality in 2021 and 2022 (p < 0.05), but this association weakened in 2023, suggesting a temporal trend toward greater equity. PQAVS-03 showed no statistically significant association in any year. These findings underscore the persistent impact of structural social determinants on vaccine access during public health emergencies, while also highlighting the potential of Brazils public health system to reduce disparities over time.

Real world evidence studies of mass vaccination across health systems have reaffirmed the safety1 and efficacy2,3 of the FDA-authorized mRNA vaccines for COVID-19. However, the impact of vaccination on community transmission remains to be characterized. Here, we compare the cumulative county-level vaccination rates with the corresponding COVID-19 incidence rates among 87 million individuals from 580 counties in the United States, including 12 million individuals who have received at least one vaccine dose. We find that cumulative county-level vaccination rate through March 1, 2021 is significantly associated with a concomitant decline in COVID-19 incidence (Spearman correlation {rho} = -0.22, p-value = 8.3e-8), with stronger negative correlations in the Midwestern counties ({rho} = -0.37, p-value = 1.3e-7) and Southern counties ({rho} = -0.33, p-value = 4.5e-5) studied. Additionally, all examined US regions demonstrate significant negative correlations between cumulative COVID-19 incidence rate prior to the vaccine rollout and the decline in the COVID-19 incidence rate between December 1, 2020 and March 1, 2021, with the US western region being particularly striking ({rho} = -0.66, p-value = 5.3e-37). However, the cumulative vaccination rate and cumulative incidence rate are noted to be statistically independent variables, emphasizing the need to continue the ongoing vaccination roll out at scale. Given confounders such as different coronavirus restrictions and mask mandates, varying population densities, and distinct levels of diagnostic testing and vaccine availabilities across US counties, we are advancing a public health resource to amplify transparency in vaccine efficacy monitoring (https://public.nferx.com/covid-monitor-lab/vaccinationcheck). Application of this resource highlights outliers like Dimmit county (Texas), where infection rates have increased significantly despite higher vaccination rates, ostensibly owing to amplified travel as a "vaccination hub"; as well as Henry county (Ohio) which encountered shipping delays leading to postponement of the vaccine clinics. This study underscores the importance of tying the ongoing vaccine rollout to a real-time monitor of spatio-temporal vaccine efficacy to help turn the tide of the COVID-19 pandemic.

In 2016, the US Food and Drug Administration published guidance for the early development of live biotherapeutic products (LBPs)1. Of particular importance is the characterization of LBP strains and the potential transfer of antimicrobial resistance (AMR) genes to relevant microbial organisms in the recipients microbiota. Van der Lelie et al2, make unsupported claims that the LBP strain VE202-06 encodes a transferable vancomycin resistance element. Here we provide our analysis of the potential transfer of AMR by strain VE202-06. These data indicate that strain VE202-06 has no risk of transferring AMR to relevant microbial organisms.

ObjectivesTo inform efforts to reduce pediatric antibiotic use, we measured cumulative pediatric prescriptions for antibiotics and non-antibiotics and how this varies across geography and patient subgroups. DesignObservational study. SettingUnited States, 2008-2018. Participants207,814 children under age 5 born in the United States between 2008 and 2013 with private medical insurance coverage. InterventionsNone. Main outcome measuresStudy outcomes included (1) the cumulative number of prescriptions received per child by age 5, (2) the proportion of these prescriptions that were attributable to respiratory infections, (3) the proportion of children who received at least one prescription by age 5, and (4) the fraction of total prescriptions received by the top 20% of prescription recipients. ResultsChildren received a mean of 8.21 (95% confidence interval [CI] (8.19, 8.22)) prescriptions for antibiotics and 9.81 (95% CI 9.80, 9.82) prescriptions for non-antibiotics by age five. Most antibiotic prescriptions (64%, 95% CI 63, 65) and many non-antibiotic prescriptions (25%, 95% CI 24, 26) were associated with outpatient visits for respiratory infections. By age 5, 93.8% (95% CI 93.4, 94.2) of children had received at least one antibiotic prescription while 88.3% (95% CI 87.9, 88.7) had received at least one prescription for a non-antibiotic. The top 20% of antibiotic prescription recipients accounted for 50.6% of all antibiotic prescriptions, and the top 20% of non antibiotic prescription recipients accounted for 64.2% of all non-antibiotic prescriptions. Relative to other regions, the South featured higher prescribing rates and earlier time to first prescription. ConclusionsChildren in the US receive a substantial number of antibiotics and other prescription drugs early in their lives, largely related to respiratory infections.

Withdrawal statementThe authors have withdrawn this manuscript because when updating the data analysis, the authors discovered that a data source with vaccination information was incorrectly linked to in the initial dataset used for this analysis. As a result, some individuals that were dropped from our initial analysis due to missing vaccine information should not have been dropped and could therefore impact vaccine effectiveness estimates. We are committed to ensuring the highest standards in our research, and correcting these issues will require substantial revisions and additional analyses. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.