<sec><title>BACKGROUND</title>Chemotherapy to prevent TB is a core component of care for persons living with HIV (PLHIV). There are few reports describing adherence to TB prevention under programmatic conditions in high TB burden settings.</sec><sec><title>METHODS</title>We measured adherence to daily isoniazid (INH) preventive treatment (IPT) using a commercially available colourimetric assay to detect urine INH metabolites among PLHIV who self-reported INH ingestion within the preceding 24 h. Enrollee characteristics associated with non-adherence despite self-reported INH ingestion were identified in multivariate log-binomial regression. Interoperator reliability for the detection of INH metabolites was calculated among three independent operators.</sec><sec><title>RESULTS</title>Self-reported INH ingestion and metabolite data were known for 300 PLHIV. INH metabolite was detected in 112 (68.7%) of 163 PLHIV who self-reported INH ingestion in the preceding 24 h. The prevalence of alcohol consumption was significantly higher among INH-non-adherent PLHIV compared with INH-adherent PLHIV (adjusted prevalence ratio 2.43, 95% CI 1.16-5.12). Two-way interoperator reliability ranged from κ 0.86 to κ 0.94.</sec><sec><title>CONCLUSIONS</title>Compared with self-reported 24-h INH ingestion in a high TB-HIV-incidence programmatic setting, biometric adherence to IPT was suboptimal in this sample of PLHIV. Alcohol consumption was the only potentially modifiable risk factor significantly associated with INH non-adherence. Colourimetric interpretation reliability across three operators was moderate/strong.</sec>.

IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) is an uncommon but severe hyperinflammatory illness that occurs 2 to 6 weeks after SARS-CoV-2 infection. Presentation overlaps with other conditions, and risk factors for severity differ by patient. Characterizing patterns of MIS-C presentation can guide efforts to reduce misclassification, categorize phenotypes, and identify patients at risk for severe outcomes. OBJECTIVE: To characterize phenotypic clusters of MIS-C and identify clusters with increased clinical severity. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, MIS-C phenotypic clusters were inferred using latent class analysis applied to the largest cohort to date of cases from US national surveillance data from 55 US public health jurisdictions. Cases reported to the Centers for Disease Control and Prevention MIS-C national surveillance program as of April 4, 2023, with symptom onset on or before December 31, 2022, were retrospectively analyzed. Twenty-nine clinical signs and symptoms were selected for clustering after excluding variables with 20% or more missingness and 10% or less or 90% or more prevalence. A total of 389 cases missing 10 or more variables were excluded, and multiple imputation was conducted on the remaining cases. MAIN OUTCOMES AND MEASURES: Differences by cluster in prevalence of each clinical sign and symptom, percentage of patients admitted to the intensive care unit (ICU), length of hospital and ICU stay, mortality, and relative frequency over time. RESULTS: Among 8944 included MIS-C cases (median [IQR] patient age, 8.7 [5.0-12.5] years; 5407 [60.5%] male), latent class analysis identified 3 clusters characterized by (1) frequent respiratory findings primarily affecting older children (respiratory cluster; 713 cases [8.0%]; median [IQR] age, 12.7 [6.3-16.5] years), (2) frequent shock and/or cardiac complications (shock and cardiac cluster; 3359 cases [37.6%]; median [IQR] age, 10.8 [7.7-14.0] years), and (3) remaining cases (undifferentiated cluster; 4872 cases [54.5%]; median [IQR] age, 6.8 [3.6-10.3] years). The percentage of patients with MIS-C admitted to the ICU was highest for the shock and cardiac cluster (82.3% [2765/3359]) followed by the respiratory (49.5% [353/713]) and undifferentiated clusters (33.0% [1609/4872]). Among patients with data on length of stay available, 129 of 632 hospitalizations (20.4%) and 54 of 281 ICU stays (19.2%) in the respiratory cluster lasted 10 or more days compared with 708 of 3085 (22.9%) and 157 of 2052 (7.7%), respectively, in the shock and cardiac cluster and 293 of 4467 (6.6%) and 19 of 1220 (1.6%), respectively, in the undifferentiated cluster. The proportion of cases in both the respiratory cluster and the shock and cardiac cluster decreased after emergence of the Omicron variant in the US. CONCLUSIONS AND RELEVANCE: In this cohort study, MIS-C cases clustered into 3 subgroups with distinct clinical phenotypes, severity, and distribution over time. Use of clusters in future studies may support efforts to evaluate surveillance case definitions and identify groups at highest risk for severe outcomes.

During 2023, the Centers for Disease Control and Prevention (CDC) recommended the first respiratory syncytial virus (RSV) immunizations intended for widespread use in the United States to prevent severe RSV illness in infants and older adults. CDC, in collaboration with federal, public health, and academic partners, is conducting evaluations of real-world effectiveness of recommended RSV immunization products in the United States. Similar frameworks for evaluation are being applied to RSV vaccines and nirsevimab, a long-acting preventative monoclonal antibody, to estimate product effectiveness. The overall goal of CDC's RSV immunization effectiveness program is to generate timely and robust evidence through observational studies to inform immunization product policy decisions and other measures related to RSV prevention and control. CDC is evaluating effectiveness through high-quality, well-controlled observational studies leveraging a variety of platforms that provide robust data to inform policy decisions.

IMPORTANCE: Respiratory syncytial virus (RSV) infection can cause severe illness in adults. However, there is considerable uncertainty in the burden of RSV-associated hospitalizations among adults prior to RSV vaccine introduction. OBJECTIVE: To describe the demographic characteristics of adults hospitalized with laboratory-confirmed RSV and to estimate annual rates and numbers of RSV-associated hospitalizations, intensive care unit (ICU) admissions, and in-hospital deaths. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the RSV Hospitalization Surveillance Network (RSV-NET), a population-based surveillance platform that captures RSV-associated hospitalizations in 58 counties in 12 states, covering approximately 8% of the US population. The study period spanned 7 surveillance seasons from 2016-2017 through 2022-2023. Included cases from RSV-NET were nonpregnant hospitalized adults aged 18 years or older residing in the surveillance catchment area and with a positive RSV test result. EXPOSURE: Laboratory-confirmed RSV-associated hospitalization, defined as a positive RSV test result within 14 days before or during hospitalization. MAIN OUTCOMES AND MEASURES: Hospitalization rates per 100 000 adult population, stratified by age group. After adjusting for test sensitivity and undertesting for RSV in adults hospitalized with acute respiratory illnesses, rates were extrapolated to the US population to estimate annual numbers of RSV-associated hospitalizations. Clinical outcome data were used to estimate RSV-associated ICU admissions and in-hospital deaths. RESULTS: From the 2016 to 2017 through the 2022 to 2023 RSV seasons, there were 16 575 RSV-associated hospitalizations in adults (median [IQR] age, 70 [58-81] years; 9641 females [58.2%]). Excluding the 2020 to 2021 and the 2021 to 2022 seasons, when the COVID-19 pandemic affected RSV circulation, hospitalization rates ranged from 48.9 (95% CI, 33.4-91.5) per 100 000 adults in 2016 to 2017 to 76.2 (95% CI, 55.2-122.7) per 100 000 adults in 2017 to 2018. Rates were lowest among adults aged 18 to 49 years (8.6 [95% CI, 5.7-16.8] per 100 000 adults in 2016-2017 to 13.1 [95% CI, 11.0-16.1] per 100 000 adults in 2022-2023) and highest among adults 75 years or older (244.7 [95% CI, 207.9-297.3] per 100 000 adults in 2022-2023 to 411.4 [95% CI, 292.1-695.4] per 100 000 adults in 2017-2018). Annual hospitalization estimates ranged from 123 000 (95% CI, 84 000-230 000) in 2016 to 2017 to 193 000 (95% CI, 140 000-311 000) in 2017 to 2018. Annual ICU admission estimates ranged from 24 400 (95% CI, 16 700-44 800) to 34 900 (95% CI, 25 500-55 600) for the same seasons. Estimated annual in-hospital deaths ranged from 4680 (95% CI, 3570-6820) in 2018 to 2019 to 8620 (95% CI, 6220-14 090) in 2017 to 2018. Adults 75 years or older accounted for 45.6% (range, 43.1%-48.8%) of all RSV-associated hospitalizations, 38.6% (range, 36.7%-41.0%) of all ICU admissions, and 58.7% (range, 51.9%-67.1%) of all in-hospital deaths. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of adults hospitalized with RSV before the 2023 introduction of RSV vaccines, RSV was associated with substantial burden of hospitalizations, ICU admissions, and in-hospital deaths in adults, with the highest rates occurring in adults 75 years or older. Increasing RSV vaccination of older adults has the potential to reduce associated hospitalizations and severe clinical outcomes.

BACKGROUND: The objective of this study was to identify antibiotic stewardship (AS) opportunities in Latin American medical-surgical intensive care units (MS-ICUs) and general wards (Gral-wards). METHODS: We conducted serial cross-sectional point prevalence surveys in MS-ICUs and Gral-wards in 41 Latin American hospitals between March 2022 and February 2023. Patients >18 years of age in the units of interest were evaluated for antimicrobial use (AU) monthly (MS-ICUs) or quarterly (Gral-wards). Antimicrobial data were collected using a standardized form by the local AS teams and submitted to the coordinating team for analysis. RESULTS: We evaluated AU in 5780 MS-ICU and 7726 Gral-ward patients. The hospitals' median bed size (interquartile range) was 179 (125-330), and 52% were nonprofit. The aggregate AU prevalence was 53.5% in MS-ICUs and 25.5% in Gral-wards. Most (88%) antimicrobials were prescribed to treat infections, 7% for surgical prophylaxis and 5% for medical prophylaxis. Health care-associated infections led to 63% of MS-ICU and 38% of Gral-ward AU. Carbapenems, piperacillin-tazobactam, intravenous (IV) vancomycin, and ampicillin-sulbactam represented 50% of all AU to treat infections. A minority of IV vancomycin targeted therapy was associated with documented methicillin-resistant Staphylococcus aureus infection or therapeutic drug monitoring. In both units, 17% of antibiotics prescribed as targeted therapy represented de-escalation, while 24% and 15% in MS-ICUs and Gral-wards, respectively, represented an escalation of therapy. In Gral-wards, 32% of antibiotics were used without a microbiologic culture ordered. Half of surgical prophylaxis antibiotics were prescribed after the first 24 hours. CONCLUSIONS: Based on this cohort, areas to improve AU in Latin American hospitals include antibiotic selection, de-escalation, duration of therapy, and dosing strategies.

BACKGROUND: Screening for SARS-CoV-2 infection among hospital admissions made interpretation of COVID-19 hospitalization data challenging as SARS-CoV-2-positive persons with mild or asymptomatic infection may be incorrectly identified as COVID-19-associated hospitalizations. The study objective is to estimate the proportion of hospitalizations likely attributable to COVID-19 among SARS-CoV-2-positive hospitalized patients. METHODS: A sample of laboratory-confirmed SARS-CoV-2-positive hospitalizations from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) from June 2020 to September 2023 was analyzed, with a focus on July 2022 to September 2023. Likely COVID-19-attributable hospitalizations were defined as hospitalizations among SARS-CoV-2-positive non-pregnant adults ages ≥ 18 years with COVID-19-related presenting complaint, treatment, or discharge diagnosis. RESULTS: Among 44,816 sampled hospitalizations, 90% met the definition of likely COVID-19-attributable. Among the 9866 admissions occurring during July 2022 to September 2023, 86% were likely COVID-19-attributable; 87% had a COVID-19-related presenting complaint, 64% received steroids or COVID-19-related treatment, 47% had respiratory- and 10% had coagulopathy-related discharge diagnoses, and 39% had COVID-19 as the principal discharge diagnosis code. More than 70% met ≥ 2 criteria. Compared with likely COVID-19-attributable hospitalizations, SARS-CoV-2-positive patients who did not meet the case definition were more likely to be ages 18-49 years (27% vs. 13%), have no underlying medical conditions (14% vs. 4%), or be asymptomatic for COVID-19 upon admission (46% vs. 10%) (all p < 0.05). CONCLUSIONS: Most hospitalizations among SARS-CoV-2-positive adults in a recent period were likely attributable to COVID-19. COVID-19-attributable hospitalizations are less common among younger SARS-CoV-2-positive hospitalized adults but still account for nearly three quarters of all admissions among SARS-CoV-2-positive adults in this age group.

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.

BACKGROUND: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. METHODS: HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March-April 2023. FINDINGS: Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% "other"). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term "antibiotic stewardship". Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (< 30%) or AMR (< 50%) were a problem in their HCF. Lack of access to antibiogram and to locally endorsed guidelines was reported by 51% and 34% of HCWs, respectively. Among prescribers, 53% did not consider non-physicians' opinions to make antibiotic-related decisions, 22% reported not receiving education on how to select antibiotics based on culture results and 60% stated patients and families influence their antibiotic decisions. CONCLUSIONS: Although HCWs perceived improving AU as a priority, they did not perceive AU or AMR as a problem in their HCF. AS opportunities include improved access to guidelines, access to AMR/AU data, teamwork, and education on AS for HCWs and patients and families.

IMPORTANCE: Respiratory syncytial virus (RSV) infection can cause severe respiratory illness in older adults. Less is known about the cardiac complications of RSV disease compared with those of influenza and SARS-CoV-2 infection. OBJECTIVE: To describe the prevalence and severity of acute cardiac events during hospitalizations among adults aged 50 years or older with RSV infection. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed surveillance data from the RSV Hospitalization Surveillance Network, which conducts detailed medical record abstraction among hospitalized patients with RSV infection detected through clinician-directed laboratory testing. Cases of RSV infection in adults aged 50 years or older within 12 states over 5 RSV seasons (annually from 2014-2015 through 2017-2018 and 2022-2023) were examined to estimate the weighted period prevalence and 95% CIs of acute cardiac events. EXPOSURES: Acute cardiac events, identified by International Classification of Diseases, 9th Revision, Clinical Modification or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification discharge codes, and discharge summary review. MAIN OUTCOMES AND MEASURES: Severe disease outcomes, including intensive care unit (ICU) admission, receipt of invasive mechanical ventilation, or in-hospital death. Adjusted risk ratios (ARR) were calculated to compare severe outcomes among patients with and without acute cardiac events. RESULTS: The study included 6248 hospitalized adults (median [IQR] age, 72.7 [63.0-82.3] years; 59.6% female; 56.4% with underlying cardiovascular disease) with laboratory-confirmed RSV infection. The weighted estimated prevalence of experiencing a cardiac event was 22.4% (95% CI, 21.0%-23.7%). The weighted estimated prevalence was 15.8% (95% CI, 14.6%-17.0%) for acute heart failure, 7.5% (95% CI, 6.8%-8.3%) for acute ischemic heart disease, 1.3% (95% CI, 1.0%-1.7%) for hypertensive crisis, 1.1% (95% CI, 0.8%-1.4%) for ventricular tachycardia, and 0.6% (95% CI, 0.4%-0.8%) for cardiogenic shock. Adults with underlying cardiovascular disease had a greater risk of experiencing an acute cardiac event relative to those who did not (33.0% vs 8.5%; ARR, 3.51; 95% CI, 2.85-4.32). Among all hospitalized adults with RSV infection, 18.6% required ICU admission and 4.9% died during hospitalization. Compared with patients without an acute cardiac event, those who experienced an acute cardiac event had a greater risk of ICU admission (25.8% vs 16.5%; ARR, 1.54; 95% CI, 1.23-1.93) and in-hospital death (8.1% vs 4.0%; ARR, 1.77; 95% CI, 1.36-2.31). CONCLUSIONS AND RELEVANCE: In this cross-sectional study over 5 RSV seasons, nearly one-quarter of hospitalized adults aged 50 years or older with RSV infection experienced an acute cardiac event (most frequently acute heart failure), including 1 in 12 adults (8.5%) with no documented underlying cardiovascular disease. The risk of severe outcomes was nearly twice as high in patients with acute cardiac events compared with patients who did not experience an acute cardiac event. These findings clarify the baseline epidemiology of potential cardiac complications of RSV infection prior to RSV vaccine availability.

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two RSV vaccines were approved for prevention of RSV lower respiratory tract disease in adults aged ≥60 years. In June 2023, CDC recommended RSV vaccination for adults aged ≥60 years, using shared clinical decision-making. Using data from the Respiratory Syncytial Virus-Associated Hospitalization Surveillance Network, a population-based hospitalization surveillance system operating in 12 states, this analysis examined characteristics (including age, underlying medical conditions, and clinical outcomes) of 3,218 adults aged ≥60 years who were hospitalized with laboratory-confirmed RSV infection during July 2022-June 2023. Among a random sample of 1,634 older adult patients with RSV-associated hospitalization, 54.1% were aged ≥75 years, and the most common underlying medical conditions were obesity, chronic obstructive pulmonary disease, congestive heart failure, and diabetes. Severe outcomes occurred in 18.5% (95% CI = 15.9%-21.2%) of hospitalized patients aged ≥60 years. Overall, 17.0% (95% CI = 14.5%-19.7%) of patients with RSV infection were admitted to an intensive care unit, 4.8% (95% CI = 3.5%-6.3%) required mechanical ventilation, and 4.7% (95% CI = 3.6%-6.1%) died; 17.2% (95% CI = 14.9%-19.8%) of all cases occurred in long-term care facility residents. These data highlight the importance of prioritizing those at highest risk for severe RSV disease and suggest that clinicians and patients consider age (particularly age ≥75 years), long-term care facility residence, and underlying medical conditions, including chronic obstructive pulmonary disease and congestive heart failure, in shared clinical decision-making when offering RSV vaccine to adults aged ≥60 years.

We analyzed multisystem inflammatory syndrome in children cases by reported COVID-19 vaccination status (2-dose primary series vs. no vaccination). A total of 46% vaccinated versus 58% unvaccinated persons received intensive care unit-level care (P = 0.02); the risk of intensive care unit admission was 23% higher (adjusted relative risk: 1.23; 95% confidence interval: 1.03-1.48) among unvaccinated patients; 21 unvaccinated persons died. Multisystem inflammatory syndrome in children occurs after SARS-CoV-2 infection in vaccinated persons, but may be less severe.

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.

Objective: U.S. healthcare utilization declined during the COVID-19 pandemic, potentially leading to spurious drops in disease incidence recorded in administrative healthcare datasets used for public health surveillance. We used time series modeling to characterize the magnitude and duration of the COVID-19 pandemic's impact on claims-based monthly incidence of 12 symptomatic conditions among Medicare beneficiaries aged >=65 years. Method(s): Time series of observed monthly incidence of each condition were generated using Medicare claims data from January 2016-May 2021. Incidence time series were decomposed through seasonal and trend decomposition using Loess, resulting in seasonal, trend, and remainder components. We fit a non-linear mixed effects model to remainder time series components and used it to estimate underlying incidence and number of unrecorded cases of each condition during the pandemic period. Result(s): Observed incidence of all 12 conditions declined steeply in March 2020 with nadirs in April 2020, generally followed by return to pre-pandemic trends. The relative magnitude of the decrease varied by condition, but month of onset and duration did not. Estimated unrecorded cases during March 2020-May 2021 ranged from 9,543 (95% confidence interval [CI]: 854-15,703) for herpes zoster to 236,244 (95% CI: 188,583-292,369) for cataracts. Conclusion(s): Due to reduced healthcare utilization during the COVID-19 pandemic, claims-based data underestimate incidence of non-COVID-19 conditions. Time series modeling can be used to quantify this underestimation, facilitating longitudinal analyses of disease incidence pre- and post-pandemic. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Respiratory syncytial virus (RSV) is a cause of severe respiratory illness in older adults. In May 2023, the Food and Drug Administration approved the first vaccines for prevention of RSV-associated lower respiratory tract disease in adults aged ≥60 years. Since May 2022, the Advisory Committee on Immunization Practices (ACIP) Respiratory Syncytial Virus Vaccines Adult Work Group met at least monthly to review available evidence regarding the safety, immunogenicity, and efficacy of these vaccines among adults aged ≥60 years. On June 21, 2023, ACIP voted to recommend that adults aged ≥60 years may receive a single dose of an RSV vaccine, using shared clinical decision-making. This report summarizes the body of evidence considered for this recommendation and provides clinical guidance for the use of RSV vaccines in adults aged ≥60 years. RSV vaccines have demonstrated moderate to high efficacy in preventing RSV-associated lower respiratory tract disease and have the potential to prevent substantial morbidity and mortality among older adults; postmarketing surveillance will direct future guidance.

BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability.

BACKGROUND: The diagnosis of SARS-CoV-2-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute COVID-19 and may impact clinical management. METHODS: In this retrospective cohort study, we applied the U.S. Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at six academic medical centers during March 1, 2020-December 31, 2021. MIS-A patients were matched on age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts. RESULTS: Through medical record review of 10,223 patients hospitalized with SARS-CoV-2-associated illness, we identified 53 MIS-A cases. Compared with 106 matched COVID-19 patients, MIS-A patients were more likely to be non-Hispanic Black and less likely to be non-Hispanic White. MIS-A patients more likely had laboratory-confirmed COVID-19 ≥ 14 days prior to hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, MIS-A patients had higher neutrophil-to-lymphocyte ratio, C-reactive protein, ferritin, procalcitonin and D-dimer, compared with COVID-19 patients. MIS-A patients had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. Mortality was 6% in both cohorts. CONCLUSIONS: Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management.

BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.

Ongoing symptoms might follow acute COVID-19. Using electronic health information, we compared pre‒ and post‒COVID-19 diagnostic codes to identify symptoms that had higher encounter incidence in the post‒COVID-19 period as sequelae. This method can be used for hypothesis generation and ongoing monitoring of sequelae of COVID-19 and future emerging diseases.

THIS REPORT SUMMARIZES THE EVIDENCE AND RATIONALE SUPPORTING THE COMPONENTS OF THE CSTE/CDC MIS-C SURVEILLANCE CASE DEFINITION AND DESCRIBES THE METHODS USED TO DEVELOP THE DEFINITION. THESE METHODS INCLUDED CONVENING MIS-C CLINICAL EXPERTS (I.E., CONSULTANTS): regarding identification of MIS-C and its distinction from other pediatric conditions, a review of available literature comparing MIS-C phenotype with that of pediatric COVID-19 and other hyperinflammatory syndromes, and retrospective application of different criteria to data from MIS-C cases previously reported to CDC.

To describe the impact of the US varicella vaccination program on severe varicella outcomes, we analyzed varicella hospitalizations using the National Inpatient Sample 1993-2019 and varicella deaths using the National Center for Health Statistics data 1990-2019. Over 25 years of vaccination program (1995-2019), varicella hospitalizations, and deaths declined 94% and 97%, respectively, among persons aged <50 years. Most of the decline (90%) occurred during the 1-dose period (through 2006/2007) by attaining and maintaining high vaccination coverage; additional declines occurred during the 2-dose period, especially in the age groups covered by the 2-dose recommendation. The greatest decline for both hospitalizations and deaths (97% and >99%, respectively) was among persons aged <20 years, born during the varicella vaccination program. In the <20 age group, varicella hospitalization has become a rare event, and varicella deaths have been practically eliminated in the United States. A total of >10 500 varicella hospitalizations and 100 varicella deaths are now prevented annually in the United States as a direct result of vaccination and reduction in varicella-zoster virus circulation.

Rocky Mountain spotted fever (RMSF) is a life-threatening tick-borne disease documented in North, Central, and South America. In California, RMSF is rare; nonetheless, recent fatal cases highlight ecological cycles of the two genera of ticks, Dermacentor and Rhipicephalus, known to transmit the disease. These ticks occur in completely different habitats (sylvatic and peridomestic, respectively) resulting in different exposure risks for humans. This study summarizes the demographic, exposure, and clinical aspects associated with the last 40 years of reported RMSF cases to the California Department of Public Health (CDPH). Seventy-eight RMSF cases with onsets from 1980 to 2019 were reviewed. The incidence of RMSF has risen in the last 20 years from 0.04 cases per million to 0.07 cases per million (a two-fold increase in reports), though the percentage of cases that were confirmed dropped significantly from 72% to 25% of all reported cases. Notably, Hispanic/Latino populations saw the greatest rise in incidence. Cases of RMSF in California result from autochthonous and out-of-state exposures. During the last 20 years, more cases reported exposure in Southern California or Mexico than in the previous 20 years. The driver of these epidemiologic changes is likely the establishment and expansion of Rhipicephalus sanguineus sensu lato ticks in Southern California and on-going outbreaks of RMSF in northern Mexico. Analysis of available electronically reported clinical data from 2011 to 2019 showed that 57% of reported cases presented with serious illness requiring hospitalization with a 7% mortality. The difficulty in recognizing RMSF is due to a non-specific clinical presentation; however, querying patients on the potential of tick exposure in both sylvatic and peridomestic environments may facilitate appropriate testing and treatment.

OBJECTIVE: Two cohort studies in patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated contrasting results regarding the benefit of initial immunomodulatory treatment with intravenous immunoglobulin (IVIG) alone versus IVIG and glucocorticoids. We sought to determine whether application of different MIS-C definitions and differing disease severity between cohorts underlay discrepant results. METHODS: The Overcoming COVID-19 Public Health Surveillance Registry (OC-19) included patients meeting the US Centers for Disease Control and Prevention (CDC) MIS-C definition, whereas the Best Available Treatment Study (BATS) applied the World Health Organization (WHO) definition. We applied the WHO definition to the OC-19 cohort and the CDC definition to the BATS cohort and determined the proportion that did not meet the alternate definition. We compared illness severity indicators between cohorts. RESULTS: Of 349 OC-19 patients, 9.5% did not meet the WHO definition. Of 350 BATS patients, 10.3% did not meet the CDC definition. Most organ system involvement was similar between the cohorts, but more OC-19 patients had WHO-defined cardiac involvement (87.1% vs 79.4%, P = 0.008). OC-19 patients were more often admitted to intensive care (61.0% vs 44.8%, P < 0.001) and more often received vasopressors or inotropes (39.5% vs 22.9%, P < 0.001) before immunomodulatory treatment. CONCLUSION: Greater illness severity and cardiovascular involvement in the OC-19 cohort compared with the BATS cohort, and not use of different MIS-C case definitions, may have contributed to differing study conclusions about optimal initial treatment for MIS-C. Disease severity should be considered in future MIS-C study designs and treatment recommendations to identify patients who would benefit from aggressive immunomodulatory treatment.

Recent mumps outbreaks among highly vaccinated populations, including college students, have called into question the vaccine effectiveness (VE) of routine two-dose measles, mumps, and rubella (MMR2) immunization. We aimed to estimate the VE required for a novel vaccination strategy (e.g., MMR booster dose, novel vaccine) to prevent large mumps outbreaks on college campuses. Using mumps college outbreak data reported to the U.S. Centers for Disease Control and Prevention during 2016-2017, we estimated current MMR2 VE using the screening method and implemented a compartmental model of mumps transmission. We performed 2000 outbreak simulations, following introduction of an infectious person to a population of 10,000, over ranges of MMR2 vaccine coverage (VC) and VE (30.0-99.0%). We compared the impact of varying VC and VE on mumps and mumps orchitis case counts and determined VE thresholds that ensured < 5.0% and < 2.0% of the outbreak simulations exceeded 20 and 100 mumps cases. Median estimated MMR2 VE in reported mumps outbreaks was 60.5% and median reported MMR2 VC was 97.5%. Simulated mumps case count was more sensitive to changes in VE than in VC. The opposite was true for simulated mumps orchitis case count, though orchitis case count was small (mean <10 cases across simulations for VE near 60.5% and VC near 97.5%). At 97.5% VC, 73.1% and 78.2% VE were required for < 5.0% and < 2.0% of outbreaks, respectively, to exceed 100 mumps cases. Maintaining 97.5% VC, 82.4% and 85.9% VE were required for < 5.0% and < 2.0% of outbreaks, respectively, to exceed 20 cases. We conclude that maintaining current levels of MMR2 VC, a novel vaccination strategy aimed at reducing mumps transmission must achieve at least 73.1-85.9% VE among young adults to prevent large mumps outbreaks on college campuses.

We describe 2,116 multisystem inflammatory syndrome in children (MIS-C) cases reported to CDC during Delta and Omicron circulation from July 2021-January 2022. Half of MIS-C patients were aged 5-11 years, 52% received ICU-level care, and 1.1% died. Only 3.0% of eligible patients were fully vaccinated prior to MIS-C onset.

BACKGROUND: Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population. METHODS: We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily. FINDINGS: Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement. INTERPRETATION: Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further. FUNDING: This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a severe condition temporally associated with SARS-CoV-2 infection. METHODS: In this retrospective cohort study, we applied the U.S. Centers for Disease Control and Prevention (CDC) case definition to identify diagnosed and undiagnosed MIS-A cases among adults discharged April 2020-January 2021 from four Atlanta, Georgia hospitals affiliated with a single medical center. Non-MIS-A COVID-19 hospitalizations were identified using International Classification of Diseases, Tenth Revision encounter code U07.1. We calculated the ratio of MIS-A to COVID-19 hospitalizations, compared demographic characteristics of the two cohorts, and described clinical characteristics of MIS-A patients. RESULTS: We identified 11 MIS-A cases, none of which were diagnosed by the treatment team, and 5,755 COVID-19 hospitalizations (ratio 1: 523). Compared with patients with COVID-19, patients with MIS-A were more likely to be younger than 50 years (72.7% vs. 26.1%, p < 0.01) and to be non-Hispanic Black persons (81.8% vs. 50.0%, p = 0.04). Ten patients with MIS-A (90.9%) had at least one underlying medical condition. Two MIS-A patients (18.2%) had a previous episode of laboratory-confirmed COVID-19, occurring 37 and 55 days prior to admission. All MIS-A patients developed left ventricular systolic dysfunction. None had documented mucocutaneous involvement. All required intensive care, all received systemic corticosteroids, eight (72.7%) required mechanical ventilation, two (18.2%) required mechanical cardiovascular circulatory support, and none received intravenous immunoglobulin. Two (18.2%) died or were discharged to hospice. CONCLUSIONS: MIS-A is severe but likely underrecognized complication of SARS-CoV-2 infection. Improved recognition of MIS-A is needed to quantify its burden and identify populations at highest risk.

In mid-December 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, surpassed the B.1.617.2 (Delta) variant as the predominant strain in California.() Initial reports suggest that the Omicron variant is more transmissible and resistant to vaccine neutralization but causes less severe illness compared with previous variants (1-3). To describe characteristics of patients hospitalized with SARS-CoV-2 infection during periods of Delta and Omicron predominance, clinical characteristics and outcomes were retrospectively abstracted from the electronic health records (EHRs) of adults aged 18 years with positive reverse transcription-polymerase chain reaction (RT-PCR) SARS-CoV-2 test results admitted to one academic hospital in Los Angeles, California, during July 15-September 23, 2021 (Delta predominant period, 339 patients) and December 21, 2021-January 27, 2022 (Omicron predominant period, 737 patients). Compared with patients during the period of Delta predominance, a higher proportion of adults admitted during Omicron predominance had received the final dose in a primary COVID-19 vaccination series (were fully vaccinated) (39.6% versus 25.1%), and fewer received COVID-19-directed therapies. Although fewer required intensive care unit (ICU) admission and invasive mechanical ventilation (IMV), and fewer died while hospitalized during Omicron predominance, there were no significant differences in ICU admission or IMV when stratified by vaccination status. Fewer fully vaccinated Omicron-period patients died while hospitalized (3.4%), compared with Delta-period patients (10.6%). Among Omicron-period patients, vaccination was associated with lower likelihood of ICU admission, and among adults aged 65 years, lower likelihood of death while hospitalized. Likelihood of ICU admission and death were lowest among adults who had received a booster dose. Among the first 131 Omicron-period hospitalizations, 19.8% of patients were clinically assessed as admitted for non-COVID-19 conditions. Compared with adults considered likely to have been admitted because of COVID-19, these patients were younger (median age=38 versus 67 years) and more likely to have received at least one dose of a COVID-19 vaccine (84.6% versus 61.0%). Although 20% of SARS-CoV-2-associated hospitalizations during the period of Omicron predominance might be driven by non-COVID-19 conditions, large numbers of hospitalizations place a strain on health systems. Vaccination, including a booster dose for those who are fully vaccinated, remains critical to minimizing risk for severe health outcomes among adults with SARS-CoV-2 infection.

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes.

Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory illness related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The characteristics of patients with this syndrome and the frequency with which it occurs among patients hospitalised after SARS-CoV-2 infection are unclear. Using the Centers for Disease Control and Prevention case definition for MIS-A, we created ICD-10-CM code and laboratory criteria to identify potential MIS-A patients in the Premier Healthcare Database Special COVID-19 Release, a database containing patient-level information on hospital discharges across the United States. Modified MIS-A criteria were applied to hospitalisations with discharge from March to December 2020. The proportion of hospitalisations meeting electronic health record criteria for MIS-A and descriptive statistics for patients in the potential MIS-A cohort were calculated. Of 34 515 SARS-CoV-2-related hospitalisations with complete clinical and laboratory data, 53 met modified criteria for MIS-A (0.15%). The median age was 62 years (IQR 52-74). Most patients met the severe cardiac illness criterion through either myocarditis (66.0%) or new-onset heart failure (35.8%). A total of 79.2% of patients required ICU admission, while 43.4% of patients in the cohort died. MIS-A appears to be a rare but severe outcome of SARS-CoV-2 infection. Additional studies are needed to investigate how this syndrome differs from severe coronavirus disease 2019 (COVID-19) in adults.