IMPORTANCE: Evidence is needed on the economic favorability of a 2023-2024 COVID-19 vaccination program to support policy decisions on recommendations for COVID-19 vaccination. OBJECTIVE: To measure the cost-effectiveness of vaccination with a 2023-2024 COVID-19 mRNA vaccine in adults aged 18 years or older compared with no updated vaccination (with a 2023-2024 vaccine). DESIGN, SETTING, AND PARTICIPANTS: This decision analytic modeling study used a simulation model to compare outcomes for hypothetical cohorts of vaccinated and unvaccinated, immunocompetent adults stratified by age (18-49 years, 50-64 years, and >/=65 years). Parameters were drawn from primary and published data to represent characteristics of the US adult population. The interventions included vaccination with a 2023-2024 mRNA vaccine against COVID-19-associated illness compared with no updated vaccination (with a 2023-2024 vaccine) using a 1-year analytic time frame. A phase 2 analysis also considered an intervention strategy of vaccination with an additional dose of 2023-2024 COVID-19 mRNA vaccine. MAIN OUTCOME AND MEASURE: The incremental cost-effectiveness ratio as reported in 2023 US dollars per quality-adjusted life-year. RESULTS: Vaccination averted substantial numbers of cases, hospitalizations, intensive care unit stays, and deaths across age groups. For adults aged 18 to 49 years and 50 to 64 years, vaccination yielded incremental cost-effectiveness ratios of $115 588 and $25 787 per quality-adjusted life-year gained, respectively. For individuals aged 65 years or older, vaccination was cost saving. Sensitivity analyses indicated that the results were most sensitive to the cost per vaccine dose, vaccine effectiveness, and probability of hospitalization. In phase 2 analyses, an additional dose strategy was only economically favorable in higher-risk scenarios for individuals aged 65 years or older. CONCLUSIONS AND RELEVANCE: In this modeling study, economic favorability of COVID-19 vaccination varied by age. Cost-effectiveness results for individuals in the 2 older age groups were favorable and generally robust to changes in parameter inputs, while results for the younger age group were sensitive to parameter input changes. As the evidence base for COVID-19 vaccination and burden of illness evolves, it may be important to continue to update and revise the economic evaluation of vaccination. The Advisory Committee on Immunization Practices considered these results in its decision to recommend vaccination with the 2023 to 2024 COVID-19 mRNA vaccines.

INTRODUCTION: Community-acquired pneumonia (CAP) is an important cause of hospitalisation among older adults. Assessing costs of CAP hospitalisation aids in economic evaluation of preventive interventions and guides policy decisions. METHODS: We estimated resource utilisation rates and costs from a societal perspective among adults aged >60 years admitted with CAP in eight public and eight private hospitals in four Indian cities (ie, National Capital Region-Delhi, Kolkata, Pune and Chennai) from December 2018 to March 2020. We interviewed patients, reviewed medical records and bills to estimate resources used, direct medical cost of diagnosis and treatment; direct non-medical cost of travel, lodging and food; and indirect cost of patients and caregivers' lost income from admission to discharge. Mean costs with SD by hospital type, age group, chronic condition, critical care (intensive care unit, ICU) and virus detection are presented in US dollars (US$). Linear regression after log transformation was conducted to identify determinants of total cost. RESULTS: We analysed data from 1009 CAP patients in private (63%) and public (37%) hospitals with a median age of 68 (IQR: 63-75) years. Influenza was detected in 121 (12%) and respiratory syncytial virus (RSV) in 21 (2%). Mean length of stay was 6.2 (SD 4.8) days; 37% required ICU admission. Antibiotics and antivirals were used in 96% and 23% of admissions, respectively. Mean (SD) CAP hospitalisation cost was US$305 (244) in public and US$1210 (1019) in private hospitals; US$1024 (1095) in influenza and US$943 (778) in RSV-associated CAP. Regression analysis showed that cost was higher in hospitalisation in private hospitals, those requiring ICU care and among persons with comorbid conditions. CONCLUSIONS: Substantial resources were used, and costs were incurred during CAP hospitalisation among older adults. The findings could aid in cost-benefit analyses of interventions to reduce pneumonia burden, including influenza, RSV or pneumococcal vaccination in older adults.

BACKGROUND: Understanding the population dynamics and geographical range of Aedes aegypti is critically important for arbovirus vector surveillance and control. Little is known about the current distribution and seasonality of Ae. aegypti in Grand Lomé, Togo. We developed an investigation to determine whether Ae. aegypti was present across Lomé communes during a 1-year collection period. METHODS: Mosquito ovitraps (n = 70) were deployed across the 13 communes in the Grand Lomé health region and were examined between May 2022 and April 2023. Generalized linear mixed models (GLMMs) were applied to investigate the relationship between larval collections and seasonality. The European Space Agency (ESA) WorldCover 10 m 2020 product was used to represent different land cover classes and to determine whether sites with higher larval numbers differed from sites with lower numbers. RESULTS: A total of 52,768 Ae. aegypti larvae were collected across the 13 communes of Grand Lomé. The highest incidence of Ae. aegypti larvae was observed in the commune of Bè-Ouest (= 122.74 per 1000 population). Agoè-Nyivé was the commune with the lowest incidence over the entire study period. There was a statistically significant difference in Ae. aegypti larval counts between the rainy and dry seasons. Eight land-use classes were represented by the ESA 10 m product in Grand Lomé, with the built-up category being the most common. We found a significant relationship between larval abundance categories and land cover classes. CONCLUSIONS: This study shows that Ae. aegypti larvae can be found across all communes of the Grand Lomé region in both the rainy and dry seasons, especially in ovitraps surrounded by built-up land cover category. The results of this study could be useful in guiding disease vector surveillance and control efforts due to the potential imminent risk of upcoming dengue outbreaks.

Nirsevimab is a long-acting monoclonal antibody that protects infants and young children against severe respiratory syncytial virus (RSV) disease. Children are eligible for one 50 mg dose, one 100 mg dose, or two 100 mg doses of nirsevimab based on age, weight, time of year, maternal vaccination, and risk of severe disease. In winter 2023/2024, we developed a model to project the number of nirsevimab doses needed to immunize all eligible U.S. children during the 2024/2025 season. We grouped all births from March 2023 through March 2025 into weekly cohorts, partitioned those cohorts based on eligibility criteria, and computed eligibility for each partition. In the absence of maternal RSV vaccination, we estimated U.S. children would be eligible to receive 4.3 million nirsevimab doses in 2024/2025, of which 48% would be 100 mg doses. Projections of total eligibility can be used to inform production goals and avoid shortages of nirsevimab.

During 2020-2023, we sequenced Bayou virus from 2 patients in Louisiana, USA, with hantavirus cardiopulmonary syndrome. Direct virus sequencing demonstrated an inferred evolutionary relationship to previous cases. Our findings demonstrate that separate virus spillovers cause isolated cases and probable wide distribution of Bayou hantavirus in rodents across Louisiana.

BACKGROUND AND OBJECTIVES: Respiratory syncytial virus (RSV) causes substantial hospitalization in US infants. The Advisory Committee on Immunization Practices recommended nirsevimab in infants younger than 8 months born during or entering their first RSV season and for children aged 8 to 19 months at increased risk of RSV hospitalization in their second season. This study's objective was to evaluate the cost-effectiveness of nirsevimab in all infants in their first RSV season and in high-risk children in their second season. METHODS: We simulated healthcare utilization and deaths from RSV with and without nirsevimab among infants aged 0 to 7 months and those 8 to 19 months old over a single RSV season. Data came from published literature, US Food and Drug Administration approval documents, and epidemiologic surveillance data. We evaluated societal outcomes over a lifetime discounting at 3% and reporting in 2022 US dollars. Sensitivity and scenario analyses identified influential variables. RESULTS: We estimated that 107 253 outpatient visits, 38 204 emergency department visits, and 14 341 hospitalizations could be averted each year if half of the US birth cohort receives nirsevimab. This would cost $153 517 per quality-adjusted life year (QALY) saved. Nirsevimab in the second season for children facing a 10-fold higher risk of hospitalization would cost $308 468 per QALY saved. Sensitivity analyses showed RSV hospitalization costs, nirsevimab cost, and QALYs lost from RSV disease were the most influential parameters with cost-effectiveness ratios between cost-saving and $323 788 per QALY saved. CONCLUSIONS: Nirsevimab for infants may be cost-effective, particularly among those with higher risks and costs of RSV.

BACKGROUND AND OBJECTIVES: Respiratory syncytial virus (RSV) commonly causes hospitalization among US infants. A maternal vaccine preventing RSV in infants, RSV bivalent prefusion F maternal vaccine (RSVpreF), was approved by the US Food and Drug Administration and recommended by the Advisory Committee on Immunization Practices. Our objective was to evaluate the health benefits and cost-effectiveness of vaccinating pregnant persons in the United States using RSVpreF. METHODS: We simulated RSV infection and disease with and without seasonal RSVpreF vaccination in half of the pregnant persons in the annual US birth cohort during weeks 32 through 36 of gestation. Model inputs came from peer-reviewed literature, Food and Drug Administration records, and epidemiological surveillance databases. The results are reported using a societal perspective in 2022 US dollars for a 1-year time frame, discounting future health outcomes and costs at 3%. Sensitivity and scenario analyses were performed. RESULTS: Year-round maternal vaccination with RSVpreF would prevent 45 693 outpatient visits, 15 866 ED visits, and 7571 hospitalizations among infants each year. Vaccination had a societal incremental cost of $396 280 per quality-adjusted life-year (QALY) saved. Vaccination from September through January cost $163 513 per QALY saved. The most influential inputs were QALYs lost from RSV disease, the cost of the vaccine, and RSV-associated hospitalization costs; changes in these inputs yielded outcomes ranging from cost-saving to $800 000 per QALY saved. CONCLUSIONS: Seasonal maternal RSV vaccination designed to prevent RSV lower respiratory tract infection in infants may be cost-effective, particularly if administered to pregnant persons immediately before or at the beginning of the RSV season.

The antiviral drug tecovirimat* has been used extensively to treat U.S. mpox cases since the start of a global outbreak in 2022. Mutations in the mpox viral protein target (F13 or VP37) that occur during treatment can result in resistance to tecovirimat(†) (1,2). CDC and public health partners have conducted genetic surveillance of monkeypox virus (MPXV) for F13 mutations through sequencing and monitoring of public databases. MPXV F13 mutations associated with resistance have been reported since 2022, typically among severely immunocompromised mpox patients who required prolonged courses of tecovirimat (3-5). A majority of patients with infections caused by MPXV with resistant mutations had a history of tecovirimat treatment; however, spread of tecovirimat-resistant MPXV was reported in California during late 2022 to early 2023 among persons with no previous tecovirimat treatment (3). This report describes a second, unrelated cluster of tecovirimat-resistant MPXV among 18 persons with no previous history of tecovirimat treatment in multiple states.

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two subunit RSV vaccines (Arexvy [GSK] and Abrysvo [Pfizer]) received approval from the U.S. Food and Drug Administration (FDA). In June 2023, ACIP recommended that adults aged ≥60 years may receive a single dose of RSV vaccine, using shared clinical decision-making. In support of development of this policy, our objective was to assess the cost-effectiveness of RSV vaccination in the general population in this age group. We used a decision-analytical model of RSV over a two-year timeframe using data from published literature, FDA documents, epidemiological databases, and manufacturer data. We tracked RSV-associated outpatient, emergency department, inpatient healthcare utilization, RSV-attributable deaths, quality-adjusted life-years lost (QALYs), and societal costs. The societal cost per QALY saved from RSV vaccination depended on age group and product: adults aged ≥60 years, $196,842 for GSK's vaccine and $176,557 for Pfizer's vaccine; adults ≥65 years, $162,138 for GSK and $146,543 for Pfizer; adults 60- <65 years, $385,829 for GSK and $331,486 for Pfizer. Vaccine efficacy, incidence of RSV hospitalization, and vaccine cost had the greatest influence on cost per QALY. Cost per QALY saved decreased as the age of those vaccinated increased. Inputs such as long-term efficacy are uncertain. RSV vaccination in adults aged ≥60 years may be cost-effective, particularly in those of more advanced age. Lower vaccine acquisition costs and persistent efficacy beyond two RSV seasons would render RSV vaccination more cost-effective for a broader target population. PRIMARY FUNDING SOURCE: US Centers for Disease Control and Prevention.

While costs of norovirus acute gastroenteritis (AGE) to healthcare systems have been estimated, out-of-pocket and indirect costs incurred by households are not well documented in community settings, particularly in developing countries. We conducted active surveillance for AGE in two communities in Peru: Puerto Maldonado (October 2012-August 2015) and San Jeronimo (April 2015-April 2019). Norovirus AGE events with PCR-positive stool specimens were included. Data collected in follow-up interviews included event-related medical resource utilization, associated out-of-pocket costs, and indirect costs. There were 330 norovirus-associated AGE events among 3,438 participants from 685 households. Approximately 49% of norovirus events occurred among children <5 years of age and total cost to the household per episode was highest in this age group. Norovirus events cost a median of US $2.95 (IQR $1.04-7.85) in out-of-pocket costs and $12.58 (IQR $6.39-25.16) in indirect costs. Medication expenses accounted for 53% of out-of-pocket costs, and productivity losses accounted for 59% of the total financial burden on households. The frequency and associated costs of norovirus events to households in Peruvian communities support the need for prevention strategies including vaccines. Norovirus interventions targeting children <5 years of age and their households may have the greatest economic benefit.

Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 10-25 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 16-23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers' serogroup B-containing vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.

OBJECTIVE: To assess medical costs of hospitalizations and emergency department (ED) care associated with respiratory syncytial virus (RSV) disease in children enrolled in the New Vaccine Surveillance Network. STUDY DESIGN: We used accounting and prospective surveillance data from six pediatric health systems to assess direct medical costs from laboratory-confirmed RSV-associated hospitalizations (n=2,007) and ED visits (n=1,267) from 2016 through 2019 among children aged <5 years. We grouped costs into categories relevant to clinical care and administrative billing practices. We examined RSV-associated medical costs by care setting using descriptive and bivariate analyses. We assessed associations between known RSV risk factors and hospitalization costs and length of stay (LOS) using chi-square tests of association. RESULTS: The median cost was $7,100 (IQR: $4,006-$13,355) per hospitalized child and $503 (IQR: $387-$930) per ED visit. Eighty percent (n=2,628) of our final sample were children aged <2 years. Fewer weeks' gestational age (GA) was associated with higher median costs in hospitalized children [p<0.001, ≥37 weeks' GA: $6,840 ($3,905-$12,450); 29-36 weeks' GA: $7,721 ($4,362-$15,274); <29 w weeks' GA: $9,131 ($4,518-$19,924)]. Full-term infants accounted for 70% of the total expenditures in our sample. Almost three quarters of the healthcare dollars spent originated in children under 12 months of age; the primary age group targeted by recommended RSV prophylactics. CONCLUSIONS: Reducing the cost burden for RSV-associated medical care in young children will require prevention of RSV in all young children, not just high-risk infants. Newly available maternal vaccine and immunoprophylaxis products could substantially reduce RSV-associated medical costs.

INTRODUCTION: Advocacy for the provision of public health resources, including vaccine for the prevention of acute respiratory illnesses (ARIs) among older adults in India, needs evidence on costs and benefits. Using a cohort of community-dwelling adults aged 60 years and older in India, we estimated the cost of ARI episode and its determinants. METHODS: We enrolled 6016 participants in Ballabgarh, Chennai, Kolkata and Pune from July 2018 to March 2020. They were followed up weekly to identify ARI and classified them as acute upper respiratory illness (AURI) or pneumonia based on clinical features based on British Thoracic Society guidelines. All pneumonia and 20% of AURI cases were asked about the cost incurred on medical consultation, investigation, medications, transportation, food and lodging. The cost of services at public facilities was supplemented by WHO-Choosing Interventions that are Cost-Effective(CHOICE) estimates for 2019. Indirect costs incurred by the affected participant and their caregivers were estimated using human capital approach. We used generalised linear model with log link and gamma family to identify the average marginal effect of key determinants of the total cost of ARI. RESULTS: We included 2648 AURI and 1081 pneumonia episodes. Only 47% (range 36%-60%) of the participants with pneumonia sought care. The mean cost of AURI episode was US$13.9, while that of pneumonia episode was US$25.6, with indirect costs comprising three-fourths of the total. The cost was higher among older men by US$3.4 (95% CI: 1.4 to 5.3), those with comorbidities by US$4.3 (95% CI: 2.8 to 5.7) and those who sought care by US$17.2 (95% CI: 15.1 to 19.2) but not by influenza status. The mean per capita annual cost of respiratory illness was US$29.5. CONCLUSION: Given the high community disease and cost burden of ARI, intensifying public health interventions to prevent and mitigate ARI among this fast-growing older adult population in India is warranted.

Meningococcal disease describes the spectrum of infections caused by Neisseria meningiditis, including meningitdis, bacteremia, and bacteremic pneumonia. Two quadrivalent meningococcal polysaccharide-protein conjugate vaccines that provide protection against meningococcal serogroups A, C, W, and Y (MenACWY-D [Menactra, manufactured by Sanofi Pasteur, Inc., Swiftwater, Pennsylvania] and MenACWY-CRM [Menveo, manufactured by Novartis Vaccines, Cambridge, Massachusetts]) are licensed in the United States for use among persons aged 2 through 55 years. MenACWY-D also is licensed for use among infants and toddlers aged 9 through 23 months. Quadrivalent meningococcal polysaccharide vaccine (MPSV4 [Menommune, manufactured by sanofi pasteur, Inc., Swiftwater, Pennsylvania]) is the only vaccine licensed for use among persons aged ≥56 years. A bivalent meningococcal polysaccharide protein conjugate vaccine that provides protection against meningococcal serogroups C and Y along with Haemophilus influenzae type b (Hib) (Hib-MenCY-TT [MenHibrix, manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium]) is licensed for use in children aged 6 weeks through 18 months. This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of meningococcal disease in the United States, specifically the changes in the recommendations published since 2005 (CDC. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2005;54 [No. RR-7]). As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians as a resource. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination for persons at increased risk for meningococcal disease (i.e., persons who have persistent complement component deficiencies, persons who have anatomic or functional asplenia, microbiologists who routinely are exposed to isolates of N. meningitidis, military recruits, and persons who travel to or reside in areas in which meningococcal disease is hyperendemic or epidemic). Guidelines for antimicrobial chemoprophylaxis and for evaluation and management of suspected outbreaks of meningococcal disease also are provided.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. Nirsevimab (Bevfortus, Sanofi and AstraZeneca) is recommended to prevent RSV-associated lower respiratory tract infection (LRTI) in infants. In August 2023, the Food and Drug Administration (FDA) approved RSVpreF vaccine (Abrysvo, Pfizer Inc.) for pregnant persons as a single dose during 32-36 completed gestational weeks (i.e., 32 weeks and zero days' through 36 weeks and 6 days' gestation) to prevent RSV-associated lower respiratory tract disease in infants aged <6 months. Since October 2021, CDC's Advisory Committee on Immunization Practices (ACIP) RSV Vaccines Pediatric/Maternal Work Group has reviewed RSV epidemiology and evidence regarding safety, efficacy, and potential economic impact of pediatric and maternal RSV prevention products, including RSVpreF vaccine. On September 22, 2023, ACIP and CDC recommended RSVpreF vaccine using seasonal administration (i.e., during September through end of January in most of the continental United States) for pregnant persons as a one-time dose at 32-36 weeks' gestation for prevention of RSV-associated LRTI in infants aged <6 months. Either maternal RSVpreF vaccination during pregnancy or nirsevimab administration to the infant is recommended to prevent RSV-associated LRTI among infants, but both are not needed for most infants. All infants should be protected against RSV-associated LRTI through use of one of these products.

BACKGROUND: Vaccine effectiveness (VE) estimates vary by population characteristics and circulating variants. North America and Europe have generated many COVID-19 VE estimates but relied heavily on mRNA vaccines. Fewer estimates are available for non-mRNA vaccines and from Latin America. We aimed to estimate the effectiveness of several COVID-19 vaccines in preventing SARS-CoV-2-associated severe acute respiratory infection (SARI) in Paraguay from May 2021 to April 2022. METHODS: Using sentinel surveillance data from four hospitals in Paraguay, we conducted a test-negative case-control study to estimate COVID-19 vaccine effectiveness against SARI by vaccine type/brand and period of SARS-CoV-2 variant predominance (Gamma, Delta, Omicron). We used multivariable logistic regression adjusting for month of symptom onset, age group, and presence of ≥1 comorbidity to estimate the odds of COVID-19 vaccination in SARS-CoV-2 test-positive SARI case-patients compared to SARS-CoV-2 test-negative SARI control-patients. RESULTS: Of 4,229 SARI patients, 2,381 (56%) were SARS-CoV-2-positive case-patients and 1,848 (44%) were SARS-CoV-2-negative control-patients. A greater proportion of case-patients (73%; 95% CI: 71-75) than of control-patients (40%; 95% CI: 38-42) were unvaccinated. During the Gamma variant-predominant period, VE estimates for partial vaccination with mRNA vaccines and Oxford/AstraZeneca Vaxzevria were 90.4% (95% CI: 66.4-97.6) and 52.2% (95% CI: 25.0-69.0), respectively. During the Delta variant-predominant period, VE estimates for complete vaccination with mRNA vaccines, Oxford/AstraZeneca Vaxzevria, or Gamaleya Sputnik V were 90.4% (95% CI: 74.3-97.3), 83.2% (95% CI: 67.8-91.9), and 82.9% (95% CI: 53.0-95.2), respectively. The effectiveness of all vaccines declined substantially during the Omicron variant-predominant period. CONCLUSIONS: This study contributes to our understanding of COVID-19 VE in Latin America and to global understanding of vaccines that have not been widely used in North America and Europe. VE estimates from Paraguay can parameterize models to estimate the impact of the national COVID-19 vaccination campaign in Paraguay and similar settings.

The extent to which the 2022 mpox outbreak has affected persons without a recent history of male-to-male sexual contact (MMSC) is not well understood. During November 1-December 14, 2022, CDC partnered with six jurisdictional health departments to characterize possible exposures among mpox patients aged ≥18 years who did not report MMSC during the 3 weeks preceding symptom onset. Among 52 patients included in the analysis, 14 (27%) had a known exposure to a person with mpox, including sexual activity and other close intimate contact (eight) and household contact (six). Among 38 (73%) patients with no known exposure to a person with mpox, self-reported activities before illness onset included sexual activity and other close intimate contact (17; 45%), close face-to-face contact (14; 37%), attending large social gatherings (11; 29%), and being in occupational settings involving close skin-to-skin contact (10; 26%). These findings suggest that sexual activity remains an important route of mpox exposure among patients who do not report MMSC.

The COVID-19 pandemic presents global health, welfare, and economic concerns. The agricultural workforce has experienced adverse effects, placing the U.S. food supply at risk. Agricultural workers temporarily travel to the United States on H-2A visas to supplement the agricultural workforce. Approximately 300,000 agricultural workers enter the United States with H-2A visas each year; over 90.0% are from Mexico. During February-May 2021, a COVID-19 testing pilot was performed with Clínica Médica Internacional (CMI), a clinic that performs medical examinations for US-bound immigrants, to determine the SARS-CoV-2 infection status of H-2A agricultural workers in Mexico before entry to the US. The CerTest VIASURE Real Time PCR Detection Kit was used. Participants' demographic information, test results, and testing turnaround times were collected. Workers who tested positive for SARS-CoV-2 completed isolation before US entry. During the pilot, 1195 H-2A workers were tested; 15 (1.3%) tested positive. Average reporting time was 31 h after specimen collection. This pilot demonstrated there is interest from H-2A employers and agents in testing the H-2A community before US entry. Testing for SARS-CoV-2 can yield public health benefit, is feasible, and does not delay entry of temporary agricultural workers to the US.

Respiratory syncytial virus (RSV) is a major cause of respiratory illness and hospitalization in older adults during fall and winter in the United States. The 2023-2024 RSV season was the first during which RSV vaccination was recommended for U.S. adults aged ≥60 years, using shared clinical decision-making. On June 26, 2024, the Advisory Committee on Immunization Practices voted to update this recommendation as follows: a single dose of any Food and Drug Administration-approved RSV vaccine (Arexvy [GSK]; Abrysvo [Pfizer]; or mResvia [Moderna]) is now recommended for all adults aged ≥75 years and for adults aged 60-74 years who are at increased risk for severe RSV disease. Adults who have previously received RSV vaccine should not receive another dose. This report summarizes the evidence considered for these updated recommendations, including postlicensure data on vaccine effectiveness and safety, and provides clinical guidance for the use of RSV vaccines in adults aged ≥60 years. These updated recommendations are intended to maximize RSV vaccination coverage among persons most likely to benefit, by clarifying who is at highest risk and by reducing implementation barriers associated with the previous shared clinical decision-making recommendation. Continued postlicensure monitoring will guide future recommendations.

Background Norovirus outbreaks are notoriously explosive, with dramatic symptomology and rapid disease spread. Children are particularly vulnerable to infection and drive norovirus transmission due to their high contact rates with each other and the environment. Despite the explosive nature of norovirus outbreaks, attack rates in schools and daycares remain low with the majority of students not reporting symptoms.Methods We explore immunologic and epidemiologic mechanisms that may underlie epidemic norovirus transmission dynamics using a disease transmission model. Towards this end, we compared different model scenarios, including innate resistance and acquired immunity (collectively denoted ‘immunity’), stochastic extinction, and an individual exclusion intervention. We calibrated our model to daycare and school outbreaks from national surveillance data.Results Recreating the low attack rates observed in daycare and school outbreaks required a model with immunity. However, immunity alone resulted in shorter duration outbreaks than what was observed. The addition of individual exclusion (to the immunity model) extended outbreak durations by reducing the amount of time that symptomatic people contribute to transmission. Including both immunity and individual exclusion mechanisms resulted in simulations where both attack rates and outbreak durations were consistent with surveillance data.Conclusions The epidemiology of norovirus outbreaks in daycare and school settings cannot be well described by a simple transmission model in which all individuals start as fully susceptible. Interventions should leverage population immunity and encourage more rigorous individual exclusion to improve venue-level control measures.Competing Interest StatementDr. Lopman reports personal fees from Takeda Pharmaceuticals, CDC Foundation, and Hall Booth Smith, P.C. outside the submitted work.Funding StatementThis Study was funded by the Joint Initiative for Vaccine Economics, Phase 5, a cooperative agreement between the University of Michigan and the Centers for Disease Control and Prevention (U01IP000965). Additionally, this study was funded by the National Institute of General Medical Sciences (U01GM110712). Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe surveillance datasets are available from the Centers for Disease Control and Prevention upon request and application. Computing code available from the corresponding author upon reasonable request.

BACKGROUND: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. METHODS: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. RESULTS: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. CONCLUSIONS: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

In mid-June 2021, B.1.671.2 (Delta) became the predominant variant of SARS-CoV-2, the virus that causes COVID-19, circulating in the United States. As of July 2021, the Delta variant was responsible for nearly all new SARS-CoV-2 infections in the United States.* The Delta variant is more transmissible than previously circulating SARS-CoV-2 variants (1); however, whether it causes more severe disease in adults has been uncertain. Data from the CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system for COVID-19-associated hospitalizations, were used to examine trends in severe outcomes in adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 during periods before (January-June 2021) and during (July-August 2021) Delta variant predominance. COVID-19-associated hospitalization rates among all adults declined during January-June 2021 (pre-Delta period), before increasing during July-August 2021 (Delta period). Among sampled nonpregnant hospitalized COVID-19 patients with completed medical record abstraction and a discharge disposition during the pre-Delta period, the proportion of patients who were admitted to an intensive care unit (ICU), received invasive mechanical ventilation (IMV), or died while hospitalized did not significantly change from the pre-Delta period to the Delta period. The proportion of hospitalized COVID-19 patients who were aged 18-49 years significantly increased, from 24.7% (95% confidence interval [CI] = 23.2%-26.3%) of all hospitalizations in the pre-Delta period, to 35.8% (95% CI = 32.1%-39.5%, p<0.01) during the Delta period. When examined by vaccination status, 71.8% of COVID-19-associated hospitalizations in the Delta period were in unvaccinated adults. Adults aged 18-49 years accounted for 43.6% (95% CI = 39.1%-48.2%) of all hospitalizations among unvaccinated adults during the Delta period. No difference was observed in ICU admission, receipt of IMV, or in-hospital death among nonpregnant hospitalized adults between the pre-Delta and Delta periods. However, the proportion of unvaccinated adults aged 18-49 years hospitalized with COVID-19 has increased as the Delta variant has become more predominant. Lower vaccination coverage in this age group likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including those aged <50 years who have relatively low vaccination rates compared with older adults.

OBJECTIVES: Seasonal influenza vaccines protect against 3 (trivalent influenza vaccine [IIV3]) or 4 (quadrivalent influenza vaccine [IIV4]) viruses. IIV4 costs more than IIV3, and there is a trade-off between incremental cost and protection. This is especially the case in low- and middle-income countries (LMICs) with limited budgets; previous reviews have not identified studies of IIV4-IIV3 comparisons in LMICs. We summarized the literature that compared health and economic outcomes of IIV4 and IIV3, focused on LMICs. METHODS: We systematically searched 5 databases for articles published before October 6, 2021, that modeled health or economic effects of IIV4 versus IIV3. We abstracted data and compared findings among countries and models. RESULTS: Thirty-eight studies fit our selection criteria; 10 included LMICs. Most studies (N = 31) reported that IIV4 was cost-saving or cost-effective compared with IIV3; we observed no difference in health or economic outcomes between LMICs and other countries. Based on cost differences of influenza vaccines, only one study compared coverage of IIV3 with IIV4 and reported that the maximum IIV4 price that would still yield greater public health impact than IIV3 was 13% to 22% higher than IIV3. CONCLUSIONS: When vaccination coverage with IIV4 and IIV3 is the same, IIV4 tends to be not only more effective but more cost-effective than IIV3, even with relatively high price differences between vaccine types. Alternatively, where funding is limited as in most LMICs, higher vaccine coverage can be achieved with IIV3 than IIV4, which could result in more favorable health and economic outcomes.

Broadly neutralizing antibodies against SARS-CoV-2 variants are sought to curb COVID-19 infections. Here we produced and characterized a set of mouse monoclonal antibodies (mAbs) specific for the ancestral SARS-CoV-2 receptor binding domain (RBD). Two of them, 17A7 and 17B10, were highly potent in microneutralization assay with 50% inhibitory concentration (IC(50) ) ≤ 135 ng/ml against infectious SARS-CoV-2 variants, including G614, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Kappa, Lambda, B.1.1.298, B.1.222, B.1.5 and R.1. Both mAbs (especially 17A7) also exhibited strong in vivo efficacy in protecting K18-hACE2 transgenic mice from the lethal infection with G614, Alpha, Beta, Gamma and Delta viruses. Structural analysis indicated that 17A7 and 17B10 target the tip of the receptor binding motif (RBM) in the RBD-up conformation. A third RBD-reactive mAb (3A6) although escaped by Beta and Gamma, was highly effective in cross-neutralizing Delta and Omicron BA.1 variants in vitro and in vivo. In competition experiments, antibodies targeting epitopes similar to these 3 mAbs were rarely enriched in human COVID-19 convalescent sera or post-vaccination sera. These results are helpful to inform new antibody/vaccine design and these mAbs can be useful tools for characterizing SARS-CoV-2 variants and elicited antibody responses. This article is protected by copyright. All rights reserved.

Generations of medical educators have recommended including public and population health (PPH) content in the training of U.S. physicians. The COVID-19 pandemic, structural racism, epidemic gun violence, and the existential threats caused by climate change are currently unsubtle reminders of the essential nature of PPH in medical education and practice. To assess the state of PPH content in medical education, the authors reviewed relevant guidance, including policies, standards, and recommendations from national bodies that represent and oversee medical education for physicians with MD degrees. Findings confirm that guidance across the medical education continuum, from premedical education to continuing professional development, increasingly includes PPH elements that vary in specificity and breadth. Graduate medical education policies present the most comprehensive approach in both primary care and subspecialty fields. Behavioral, quantitative, social, and systems sciences are represented, although not uniformly, in guidance for every phase of training. Quantitative PPH skills are frequently presented in the context of research, but not in relation to the development of population health perspectives (e.g., evidence-based medicine, quality improvement, policy development). The interdependence between governmental public health and medical practice, environmental health, and the impact of structural racism and other systems of oppression on health are urgent concerns, yet are not consistently or explicitly included in curricular guidance. To prepare physicians to meet the health needs of patients and communities, educators should identify and address gaps and inconsistencies in PPH curricula and related guidance. Re-examinations of public health and health care systems in the wake of the COVID-19 pandemic support the importance of PPH in physician training and practice, as physicians can help to bridge clinical and public health systems. This review provides an inventory of existing guidance (presented in the appendices) to assist educators in establishing PPH as an essential foundation of physician training and practice.

Here we interrogate the factors responsible for SARS-CoV-2 breakthrough infections in a K18-hACE2 transgenic mouse model. We show that Delta and the closely related Kappa variant cause viral pneumonia and severe lung lesions in K18-hACE2 mice. Human COVID-19 mRNA post-vaccination sera after the 2(nd) dose are significantly less efficient in neutralizing Delta/Kappa than early 614G virus in vitro and in vivo. By 5 months post-vaccination, ≥50% of donors lack detectable neutralizing antibodies against Delta and Kappa and all mice receiving 5-month post-vaccination sera die after the lethal challenges. Although a 3(rd) vaccine dose can boost antibody neutralization against Delta in vitro and in vivo, the mean log neutralization titers against the latest Omicron subvariants are 1/3-1/2 of those against the original 614D virus. Our results suggest that enhanced virulence, greater immune evasion and waning of vaccine-elicited protection account for SARS-CoV-2 variants caused breakthrough infections.

The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health. JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States. Although the safety and immunogenicity of JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second vaccine dose. Participants with no prior history of smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-neutralizing antibody in response to JYNNEOS vaccination. Finally, even though total OPXV-specific IgG titers and neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region. MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation.

BACKGROUND: The aim of this study was to evaluate the health and economic impact of the varicella vaccination program on varicella disease in the United States (US), 1996-2020. METHODS: Analysis was conducted using the Centers for Disease Control and Prevention or published annual population-based varicella incidence, and varicella-associated hospitalization, outpatient visit, and mortality rates in the US population aged 0-49 years during 1996-2020 (range, 199.5-214.2 million persons) compared to before vaccination (1990-1994). Disease costs were estimated using the societal perspective. Vaccination program costs included costs of vaccine, administration, postvaccination adverse events, and travel and work time lost to obtain vaccination. All costs were adjusted to 2020 US dollars using a 3% annual discount rate. The main outcome measures were the number of varicella-associated cases, hospitalizations, hospitalization days, and premature deaths prevented; life-years saved; and net societal savings from the US varicella vaccination program. RESULTS: Among US persons aged 0-49 years, during 1996-2020, it is estimated that more than 91 million varicella cases, 238 000 hospitalizations, 1.1 million hospitalization days, and almost 2000 deaths were prevented and 118 000 life-years were saved by the varicella vaccination program, at net societal savings of $23.4 billion. CONCLUSIONS: Varicella vaccination has resulted in substantial disease prevention and societal savings for the US over 25 years of program implementation.

OBJECTIVES: This study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices. METHODS: Hematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses. RESULTS: Base-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79000/QALY among persons living with human immunodeficiency virus, and $208000/QALY among persons with selected autoimmune and inflammatory conditions. CONCLUSIONS: Generally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.

Identification of the emerging multidrug-resistant yeast Candida auris is challenging. Here, we describe the role of the Mexico national reference laboratory Instituto de Diagnóstico y Referencia Epidemiológicos Dr. Manuel Martínez Báez (InDRE) and the Mexican national laboratory network in the identification of C. auris. Reference identification of six suspected isolates was done based on phenotypic and molecular laboratory methods, including growth in special media, evaluation of isolate micromorphology, and species-specific PCR and pan-fungal PCR and sequencing. The four C. auris isolates identified were able to grow on modified Sabouraud agar with 10% NaCl incubated at 42 °C. With one exception, isolates of C. auris were spherical to ovoid yeast-like cells and blastoconidia, with no hyphae or pseudohyphae on cornmeal agar. C. auris isolates were resistant to fluconazole. Species-specific and pan-fungal PCR confirmed isolates as C. auris. Sequence analysis revealed the presence of two different C. auris clades in Mexico, clade I (South Asia) and clade IV (South America).