BACKGROUND: For settings with low tuberculosis incidence, disease elimination is a long-term goal. We investigated pathways to tuberculosis pre-elimination (incidence <1·0 cases per 100 000 people) and elimination (incidence <0·1 cases per 100 000 people) in the USA, where incidence was estimated at 2·9 per 100 000 people in 2023. METHODS: Using a mathematical modelling framework, we simulated how US tuberculosis incidence could be affected by changes in tuberculosis services in the countries of origin for future migrants to the USA, as well as changes in tuberculosis services inside the USA. To do so, we used a linked set of transmission dynamic models, calibrated to demographic and epidemiological data for each setting. We constructed intervention scenarios representing improvements in tuberculosis services internationally and within the USA, individually and in combination, plus a base-case scenario representing continuation of current services. We simulated health and economic outcomes until 2100, using a Bayesian approach to quantify uncertainty in these outcomes. FINDINGS: Under the base-case scenario, US tuberculosis incidence was projected to decline to 1·8 cases per 100 000 (95% uncertainty interval [UI] 1·5-2·1) in the total population by 2050. Intervention scenarios produced substantial reductions in tuberculosis incidence, with the combination of all domestic and international interventions projected to achieve pre-elimination by 2033 (95% UI 2031-2037). Compared with the base-case scenario, this combination of interventions could avert 101 000 tuberculosis cases (95% UI 84 000-120 000) and 13 300 tuberculosis deaths (95% UI 10 500-16 300) in the USA from 2025 to 2050. Tuberculosis elimination was not projected before 2100. INTERPRETATION: Strengthening tuberculosis services domestically, promoting the development of more effective technologies and interventions, and supporting tuberculosis programmes in countries with a high tuberculosis burden are key strategies for accelerating progress towards tuberculosis elimination in the USA. FUNDING: US Centers for Disease Control and Prevention.

Advances in pediatric TB care are promising, the result of decades of advocacy, operational and clinical trials research, and political will by national and local TB programs in high-burden countries. However, implementation challenges remain in linking policy to practice and scaling up innovations for prevention, diagnosis, and treatment of TB in children, especially in resource-limited settings. There is both need and opportunity to strengthen clinician confidence in making a TB diagnosis and managing the various manifestations of TB in children, which can facilitate the translation of evidence to action and expand access to new tools and strategies to address TB in this population. This review aims to summarize existing guidance and best practices for clinicians and health care providers in low-resource, TB-endemic settings and identify resources with more detailed and actionable information for decision-making along the clinical cascade to prevent, find, and cure TB in children.

Infections cause substantial morbidity and mortality among patients receiving care in outpatient hemodialysis facilities. We describe comprehensive infection prevention assessments by US public health departments using standardized interview and observation tools. Results demonstrated how facility layouts can undermine infection prevention and that clinical practices often fall short of policies.

BACKGROUND: Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step towards informing better infection prevention and control practices and improving public health response. METHODS: Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1-December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. RESULTS: Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly bla(OXA-23) or bla(OXA-24/40); however, an isolate with bla(NDM) was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). CONCLUSIONS: Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP.

Currently, tuberculosis (TB) is the leading cause of death from a single infectious agent and accounts for over one-third of all HIV-related deaths. However, research and programmatic funding have lagged far behind investments for many other diseases. For about a century, the current Bacillus Calmette-Guérin vaccine has been the only effective vaccine and is only effective in preventing severe disease in children; the first new therapeutic drug for TB in over 40 years was brought to market a few years ago; and until 10 years ago, diagnosis of TB depended on a century-old testing technique. This paper relates TB to neglected tropical diseases (NTDs) and highlights shared characteristics. The aim is to elevate awareness of TB within the framework of NTDs and gain insights from successes in addressing NTDs and how these lessons can be applied to help global health programs change the trajectory of the TB epidemic. A literature review was conducted to compare TB to NTDs and highlight lessons learned from NTD control that can be applied to the TB epidemic. Common features of NTDs include underlying burden of disease, influence and effect on poverty and development, and neglect through political will and funding. There are overarching principles for the design and implementation of NTD control programs that could be applied to ending TB.

BACKGROUND: Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) are extensively drug resistant bacteria. We investigated the source of a multistate CP-CRPA outbreak. METHODS: Cases were defined as a U.S. patient's first isolation of P. aeruginosa sequence type 1203 with the carbapenemase gene blaVIM-80 and cephalosporinase gene blaGES-9 from any specimen source collected and reported to CDC between January 1, 2022-May 15, 2023. We conducted a 1:1 matched case-control study at the post-acute care facility with the most cases, assessed exposures associated with case status for all case-patients, and tested products for bacterial contamination. RESULTS: We identified 81 case-patients from 18 states, 27 of whom were identified through surveillance cultures. Four (7%) of 54 case-patients with clinical cultures died within 30 days of culture collection, and four (22%) of 18 with eye infections underwent enucleation. In the case-control study, case-patients had increased odds of receiving artificial tears compared to controls (crude matched OR: 5.0, 95% CI: 1.1, 22.8). Overall, artificial tears use was reported by 61 (87%) of 70 case-patients with information; 43 (77%) of 56 case-patients with brand information reported use of Brand A, an imported, preservative-free, over-the-counter (OTC) product. Bacteria isolated from opened and unopened bottles of Brand A were genetically related to patient isolates. FDA inspection of the manufacturing plant identified likely sources of contamination. CONCLUSIONS: A manufactured medical product serving as the vehicle for carbapenemase-producing organisms is unprecedented in the U.S. The clinical impacts from this outbreak underscore the need for improved requirements for U.S. OTC product importers.

The flavivirus envelope protein is a class II fusion protein that drives flavivirus-cell membrane fusion. The membrane fusion process is triggered by the conformational change of the E protein from dimer in the virion to trimer, which involves the rearrangement of three domains, EDI, EDII, and EDIII. The movement between EDI and EDII initiates the formation of the E protein trimer. The EDI-EDII hinge region utilizes four motifs to exert the hinge effect at the interdomain region and is crucial for the membrane fusion activity of the E protein. Using West Nile virus (WNV) NY99 strain derived from an infectious clone, we investigated the role of eight flavivirus-conserved hydrophobic residues in the EDI-EDII hinge region in the conformational change of E protein from dimer to trimer and viral entry. Single mutations of the E-A54, E-I130, E-I135, E-I196, and E-Y201 residues affected infectivity. Importantly, the E-A54I and E-Y201P mutations fully attenuated the mouse neuroinvasive phenotype of WNV. The results suggest that multiple flavivirus-conserved hydrophobic residues in the EDI-EDII hinge region play a critical role in the structure-function of the E protein and some contribute to the virulence phenotype of flaviviruses as demonstrated by the attenuation of the mouse neuroinvasive phenotype of WNV. Thus, as a proof of concept, residues in the EDI-EDII hinge region are proposed targets to engineer attenuating mutations for inclusion in the rational design of candidate live-attenuated flavivirus vaccines.

Recent advances in technology can be leveraged to enhance public health research and practice. This study aimed to assess the effects of mobility and policy changes on COVID-19 case growth and the effects of policy changes on mobility using data from Google Mobility Reports, information on public health policy, and COVID-19 testing results. Multiple bivariate regression analyses were conducted to address the study objectives. Policies designed to limit mobility led to decreases in mobility in public areas. These policies also decreased COVID-19 case growth. Conversely, policies that did not restrict mobility led to increases in mobility in public areas and led to increases in COVID-19 case growth. Mobility increases in public areas corresponded to increases in COVID-19 case growth, while concentration of mobility in residential areas corresponded to decreases in COVID-19 case growth. Overall, restrictive policies were effective in decreasing COVID-19 incidence in the Dominican Republic, while permissive policies led to increases in COVID-19 incidence.

Background HIV preexposure prophylaxis (PrEP) could reduce the disparities in HIV incidence among black men who have sex with men (BMSM) compared to white MSM (WMSM), but this may depend on progression through the PrEP care continuum.Methods We expanded our network-based mathematical model of HIV transmission for MSM, which simulates PrEP based on CDC’s clinical practice guidelines, to include race-stratified transitions through the PrEP continuum steps of awareness, access, prescription, adherence, and retention. Continuum parameters were estimated based on published incidence cohorts and PrEP open-label studies. Counterfactuals included a no-PrEP reference scenario, and intervention scenarios in which the BMSM continuum step parameters were modified.Results Implementing PrEP according to the observed BMSM continuum was projected to result in 8.4% of all BMSM on PrEP at year 10, yielding a 23% decline in incidence (HR = 0.77). On an absolute scale, the racial disparity in incidence in this scenario was 4.95 per 100 person-years at risk (PYAR), a 19% decline from the 6.08 per 100 PYAR disparity in the reference scenario. If BMSM continuum parameters were equal to WMSM values, 17.7% of BMSM would be on PrEP, yielding a 47% decline in incidence (HR = 0.53) and a disparity of 3.30 per 100 PYAR (a 46% decline in the disparity).Conclusions PrEP could lower HIV incidence overall and reduce absolute racial disparities between BMSM and WMSM. Interventions addressing the racial gaps in the PrEP continuum will be needed to further decrease these HIV disparities.

Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of bla(KPC)-carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention's Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of bla(KPC)-carrying Klebsiella pneumoniae ST258, and clonal expansion of bla(KPC)-carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of bla(KPC)-carrying Enterobacter and Klesbiella, with evidence that most derived from the local acquisition of bla(KPC) plasmids circulating in an interconnected regional health care network. Thus, the underlying processes driving KPC-CRE burden can differ substantially across regions and can be discerned through regional genomic surveillance. This study provides proof of concept that integrating genomic data with information on interfacility patient transfers can provide insights into locations and drivers of regional KPC-CRE burden that can enable targeted interventions.

Primary amebic meningoencephalitis (PAM) is a rare and lethal infection caused by Naegleria fowleri. We report an epidemiological and environmental investigation relating to a case of PAM in a previously healthy boy age 8 years. An interview of the patient's family was conducted to determine the likely exposure site and to assess risk factors. Data from the United States Geological Survey site at Waterloo, NE, on the Elkhorn River were used to estimate water temperature and streamflow at the time and site of exposure. Data from the National Weather Service were used to estimate precipitation and ambient air temperature at the time and site of exposure. Despite conventional treatment, the patient died 2 days after hospital admission. The patient participated in recreational water activities in the Elkhorn River in northeastern Nebraska 5 days before symptom onset. In the week before exposure, water and ambient air high temperatures reached annual highs, averaging 32.4°C and 35.8°C, respectively. The day before infection, 2.2 cm of precipitation was reported. Streamflow was low (407 ft3/s). Infections in several northern states, including Nebraska, suggest an expanding geographic range of N. fowleri transmission, which may lead to increased incidence of PAM in the United States. Similar environmental investigations at suspected exposure sites of future cases will allow data aggregation, enabling investigators to correlate environmental factors with infection risk accurately.

BACKGROUND: Most multicenter studies of US pediatric sepsis epidemiology use administrative data or focus on pediatric intensive care units. We conducted a detailed medical record review to describe sepsis epidemiology in children and young adults. METHODS: In a convenience sample of hospitals in 10 states, patients aged 30 days-21 years, discharged during 1 October 2014-30 September 2015, with explicit diagnosis codes for severe sepsis or septic shock, were included. Medical records were reviewed for patients with documentation of sepsis, septic shock, or similar terms. We analyzed overall and age group-specific patient characteristics. RESULTS: Of 736 patients in 26 hospitals, 442 (60.1%) had underlying conditions. Most patients (613 [83.3%]) had community-onset sepsis, although most community-onset sepsis was healthcare associated (344 [56.1%]). Two hundred forty-one patients (32.7%) had outpatient visits 1-7 days before sepsis hospitalization, of whom 125 (51.9%) received antimicrobials ≤30 days before sepsis hospitalization. Age group-related differences included common underlying conditions (<5 years: prematurity vs 5-12 years: chronic pulmonary disease vs 13-21 years: chronic immunocompromise); medical device presence ≤30 days before sepsis hospitalization (1-4 years: 46.9% vs 30 days-11 months: 23.3%); percentage with hospital-onset sepsis (<5 years: 19.6% vs ≥5 years: 12.0%); and percentage with sepsis-associated pathogens (30 days-11 months: 65.6% vs 13-21 years: 49.3%). CONCLUSIONS: Our data suggest potential opportunities to raise sepsis awareness among outpatient providers to facilitate prevention, early recognition, and intervention in some patients. Consideration of age-specific differences may be important as approaches are developed to improve sepsis prevention, risk prediction, recognition, and management.

BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6-97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3-65·6) of causes, whereas bacteria accounted for 27·3% (23·3-31·6) and Mycobacterium tuberculosis for 5·9% (3·9-8·3). Viruses were less common (54·5%, 95% CrI 47·4-61·5 vs 68·0%, 62·7-72·7) and bacteria more common (33·7%, 27·2-40·8 vs 22·8%, 18·3-27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4-34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND AND OBJECTIVES: The Food and Drug Administration expanded Emergency Use Authorization for use of Pfizer-BioNTech (BNT-162b2) coronavirus disease 2019 vaccine to include people ages 12 years and older on May 10, 2021. We describe adverse events observed during the first full year of the US coronavirus disease 2019 vaccination program for adolescents ages 12 to 17 years. METHODS: We conducted descriptive analyses using data from 2 complementary US vaccine safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health impacts, and the Vaccine Adverse Event Reporting System (VAERS), the national spontaneous reporting system. We reviewed reports and calculated adverse event reporting rates using vaccine administration data. RESULTS: Among 172 032 adolescents ages 12 to 17 years enrolled in v-safe, most reported reactions following BNT-162b2 were mild to moderate, most frequently reported on the day after vaccination, and more common after dose 2. VAERS received 20 240 adverse event reports; 91.5% were nonserious. Among adverse events of interest, we verified 40 cases of multisystem inflammation syndrome in children (1.2 cases per million vaccinations), 34 (85%) of which had evidence of prior severe acute respiratory syndrome coronavirus 2 infection; and 570 cases of myocarditis (17.7 cases per million vaccinations), most of whom (77%) reported symptom resolution at the time of report. CONCLUSIONS: During the first year BNT-162b2 was administered to adolescents ages 12 to 17 years, most reported adverse events were mild and appeared self-limited. Rates of myocarditis were lower than earlier reports. No new serious safety concerns were identified.

Multisystem inflammatory syndrome in children (MIS-C) is a complication of SARS-CoV-2 infection; in the U.S., reporting of MIS-C after COVID-19 vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5-11 years on October 29, 2021. Covering a period when ∼7 million children received vaccine, surveillance for MIS-C ≤90 days post-vaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence. During a period with extensive SARS-CoV-2 circulation, MIS-C illness in children after COVID-19 vaccination who lacked evidence of SARS-CoV-2 infection was rare (<1 per million vaccinated children).

Data on monkeypox in children and adolescents aged <18 years are limited (1,2). During May 17-September 24, 2022, a total of 25,038 monkeypox cases were reported in the United States,(dagger) primarily among adult gay, bisexual, and other men who have sex with men (3). During this period, CDC and U.S. jurisdictional health departments identified Monkeypox virus (MPXV) infections in 83 persons aged <18 years, accounting for 0.3% of reported cases. Among 28 children aged 0-12 years with monkeypox, 64% were boys, and most had direct skin-to-skin contact with an adult with monkeypox who was caring for the child in a household setting. Among 55 adolescents aged 13-17 years, most were male (89%), and male-to-male sexual contact was the most common presumed exposure route (66%). Most children and adolescents with monkeypox were non-Hispanic Black or African American (Black) (47%) or Hispanic or Latino (Hispanic) (35%). Most (89%) were not hospitalized, none received intensive care unit (ICU)-level care, and none died. Monkeypox in children and adolescents remains rare in the United States. Ensuring equitable access to monkeypox vaccination, testing, and treatment is a critical public health priority. Vaccination for adolescents with risk factors and provision of prevention information for persons with monkeypox caring for children might prevent additional infections.

OBJECTIVES: To describe COVID-19-related pediatric hospitalizations during a period of B.1.617.2 (Delta) variant predominance and to determine age-specific factors associated with severe illness. PATIENTS AND METHODS: We abstracted data from medical charts to conduct a cross-sectional study of patients aged <21 years hospitalized at 6 US children's hospitals during July-August 2021 for COVID-19 or with an incidental positive SARS-CoV-2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation. RESULTS: Of 947 hospitalized patients, 759 (80.1%) had COVID-19, of whom 287 (37.8%) had severe illness. Factors associated with severe illness included coinfection with RSV (PR 3.64) and bacteria (PR 1.88) in infants; RSV coinfection in patients aged 1-4 years (PR 1.96); and obesity in patients aged 5-11 (PR 2.20) and 12-17 years (PR 2.48). Having ≥2 underlying medical conditions was associated with severe illness in patients aged <1 (PR 1.82), 5-11 (PR 3.72), and 12-17 years (PR 3.19). CONCLUSIONS: Among patients hospitalized for COVID-19, factors associated with severe illness included RSV coinfection in those aged <5 years, obesity in those aged 5-17 years, and other underlying conditions for all age groups <18 years. These findings can inform pediatric practice, risk communication, and prevention strategies, including vaccination against COVID-19.

Child and adolescent tuberculosis (TB) has been long neglected by TB programs but there have been substantive strides in prioritizing TB among these populations in the past two decades. Yet, gaps remain in translating evidence and policy to action at the primary care level, ensuring access to novel tools and approaches to diagnosis, treatment, and prevention for children and adolescents at risk of TB disease. This article describes the progress that has been made and the gaps that remain in addressing TB among children and adolescents while also highlighting pragmatic approaches and the role of multisectoral partnerships in facilitating integration of innovations into routine program practice. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Seventy percent of tuberculosis (TB) cases in the United States occur among non-US-born persons; cases usually result from reactivation of latent TB infection (LTBI) likely acquired before the person's US arrival. We conducted a prospective study among US immigrant visa applicants undergoing the required overseas medical examination in Vietnam. Consenting applicants >15 years of age were offered an interferon-γ release assay (IGRA); those 12-14 years of age received an IGRA as part of the required examination. Eligible participants were offered LTBI treatment with 12 doses of weekly isoniazid and rifapentine. Of 5,311 immigrant visa applicants recruited, 2,438 (46%) consented to participate; 2,276 had an IGRA processed, and 484 (21%) tested positive. Among 452 participants eligible for treatment, 304 (67%) initiated treatment, and 268 (88%) completed treatment. We demonstrated that using the overseas medical examination to provide voluntary LTBI testing and treatment should be considered to advance US TB elimination efforts.

During June 2021, the highly transmissible(†) B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States. U.S. pediatric COVID-19-related hospitalizations increased during July-August 2021 following emergence of the Delta variant and peaked in September 2021.(§) As of May 12, 2021, CDC recommended COVID-19 vaccinations for persons aged ≥12 years,(¶) and on November 2, 2021, COVID-19 vaccinations were recommended for persons aged 5-11 years.** To date, clinical signs and symptoms, illness course, and factors contributing to hospitalizations during the period of Delta predominance have not been well described in pediatric patients. CDC partnered with six children's hospitals to review medical record data for patients aged <18 years with COVID-19-related hospitalizations during July-August 2021.(††) Among 915 patients identified, 713 (77.9%) were hospitalized for COVID-19 (acute COVID-19 as the primary or contributing reason for hospitalization), 177 (19.3%) had incidental positive SARS-CoV-2 test results (asymptomatic or mild infection unrelated to the reason for hospitalization), and 25 (2.7%) had multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition associated with COVID-19.(§§) Among the 713 patients hospitalized for COVID-19, 24.7% were aged <1 year, 17.1% were aged 1-4 years, 20.1% were aged 5-11 years, and 38.1% were aged 12-17 years. Approximately two thirds of patients (67.5%) had one or more underlying medical conditions, with obesity being the most common (32.4%); among patients aged 12-17 years, 61.4% had obesity. Among patients hospitalized for COVID-19, 15.8% had a viral coinfection(¶¶) (66.4% of whom had respiratory syncytial virus [RSV] infection). Approximately one third (33.9%) of patients aged <5 years hospitalized for COVID-19 had a viral coinfection. Among 272 vaccine-eligible (aged 12-17 years) patients hospitalized for COVID-19, one (0.4%) was fully vaccinated.*** Approximately one half (54.0%) of patients hospitalized for COVID-19 received oxygen support, 29.5% were admitted to the intensive care unit (ICU), and 1.5% died; of those requiring respiratory support, 14.5% required invasive mechanical ventilation (IMV). Among pediatric patients with COVID-19-related hospitalizations, many had severe illness and viral coinfections, and few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions.

RATIONALE: Approximately two-thirds of new cases of tuberculosis (TB) in the United States are among non-U.S.-born persons. Culture-based overseas TB screening in U.S.-bound immigrants and refugees has substantially reduced the importation of TB into the United States, but it is unclear to what extent this program prevents the importation of multidrug-resistant TB (MDR-TB). OBJECTIVES: To study the epidemiology of MDR-TB in U.S.-bound immigrants and refugees, and to evaluate effect of culture-based overseas TB screening in U.S.-bound immigrants and refugees on reducing the importation of MDR-TB into the United States. METHODS: We analyzed data of immigrants and refugees who completed overseas treatment for culture-positive TB during 2015-2019. We also compared mean annual number of MDR-TB cases in non-U.S.-born persons within 1 year of arrival in the United States between 1996-2006 (when overseas screening followed a smear-based algorithm) and 2014-2019 (after full implementation of a culture-based algorithm). RESULTS: Of 3,300 culture-positive TB cases prevented by culture-based overseas TB screening in immigrants and refugees during 2015-2019, 122 (3.7%, 95% confidence interval (CI) 3.1-4.1) had MDR-TB, 20 (0.6%, 95% CI 0.3-0.9) had rifampicin-resistant TB, 382 (11.6%, 95% CI 10.5-12.7) had isoniazid-resistant TB, and 2,776 (84.1%, 95% CI 82.9-85.4) had rifampicin- and isoniazid-susceptible TB. None were diagnosed with extensively drug-resistant TB (XDR-TB). Culture-based overseas TB screening in U.S.-bound immigrants and refugees prevented 24.4 MDR-TB cases per year from arriving in the United States, 18.2 cases more than smear-based overseas TB screening. Mean annual number of MDR-TB cases among non-U.S.-born persons within 1 year of arrival in the United States decreased from 34.6 cases in 1996-2006 to 19.5 cases in 2014-2019 (difference of 15.1, p<0.001). CONCLUSIONS: Culture-based overseas TB screening in U.S.-bound immigrants and refugees substantially reduced the importation of MDR-TB into the United States.

INTRODUCTION: Providing more convenient and patient-centred options for service delivery is a priority within global HIV programmes. These efforts improve patient satisfaction and retention and free up time for providers to focus on new HIV diagnoses or severe illness. Recently, the coronavirus disease 2019 (COVID-19) pandemic precipitated expanded eligibility criteria for these differentiated service delivery (DSD) models to decongest clinics and protect patients and healthcare workers. This has resulted in dramatic scale-up of DSD for antiretroviral therapy, cotrimoxazole and tuberculosis (TB) preventive treatment. While TB treatment among people living with HIV (PLHIV) has traditionally involved frequent, facility-based management, TB treatment can also be adapted within DSD models. Such adaptations could include electronic tools to ensure appropriate clinical management, treatment support, adherence counselling and adverse event (AE) monitoring. In this commentary, we outline considerations for DSD of TB treatment among PLHIV, building on best practices from global DSD model implementation for HIV service delivery. DISCUSSION: In operationalizing TB treatment in DSD models, we consider the following: what activity is being done, when or how often it takes place, where it takes place, by whom and for whom. We discuss considerations for various programme elements including TB screening and diagnosis; medication dispensing; patient education, counselling and support; clinical management and monitoring; and reporting and recording. General approaches include multi-month dispensing for TB medications during intensive and continuation phases of treatment and standardized virtual adherence and AE monitoring. Lastly, we provide operational examples of TB treatment delivery through DSD models, including a conceptual model and an early implementation experience from Zambia. CONCLUSIONS: COVID-19 has catalysed the rapid expansion of differentiated patient-centred service delivery for PLHIV. Expanding DSD models to include TB treatment can capitalize on existing platforms, while providing high-quality, routine treatment, follow-up and patient education and empowerment.

BACKGROUND: Pneumonia remains the leading cause of death among children <5 years of age beyond the neonatal period in Thailand. Using data from the Pneumonia Etiology Research for Child Health (PERCH) Study, we provide a detailed description of pneumonia cases and etiology in Thailand to inform local treatment and prevention strategies in this age group. METHODS: PERCH, a multi-country case-control study, evaluated the etiology of hospitalized cases of severe and very severe pneumonia among children 1-59 months of age. The Thailand site enrolled children for 24 consecutive months during January 2012-February 2014 with staggered start dates in 2 provinces. Cases were children hospitalized with pre-2013 WHO-defined severe or very severe pneumonia. Community controls were randomly selected from health services registries in each province. Analyses were restricted to HIV-negative cases and controls. We calculated adjusted odds ratios (ORs) and 95% CIs comparing organism prevalence detected by nasopharyngeal/oropharyngeal (NP/OP) polymerase chain reaction between cases and controls. The PERCH Integrated Analysis (PIA) used Bayesian latent variable analysis to estimate pathogen-specific etiologic fractions and 95% credible intervals. RESULTS: Over 96% of both cases (n = 223) and controls (n = 659) had at least 1 organism detected; multiple organisms were detected in 86% of cases and 88% of controls. Among 98 chest Radiograph positive (CXR+) cases, respiratory syncytial virus (RSV) had the highest NP/OP prevalence (22.9%) and the strongest association with case status (OR 20.5; 95% CI: 10.2, 41.3) and accounted for 34.6% of the total etiologic fraction. Tuberculosis (TB) accounted for 10% (95% CrI: 1.6-26%) of the etiologic fraction among CXR+ cases. DISCUSSION: More than one-third of hospitalized cases of severe and very severe CXR+ pneumonia among children 1-59 months of age in Thailand were attributable to RSV. TB accounted for 10% of cases, supporting evaluation for TB among children hospitalized with pneumonia in high-burden settings. Similarities in pneumonia etiology in Thailand and other PERCH sites suggest that global control strategies based on PERCH study findings are relevant to Thailand and similar settings.

BACKGROUND: TB is the leading cause of mortality among people living with HIV (PLHIV), for whom isoniazid preventive therapy (IPT) has a proven mortality benefit. Despite WHO recommendations, countries have been slow in scaling up IPT. This study describes processes, challenges, solutions, outcomes and lessons learned during IPT scale-up in Kenya.METHODS: We conducted a desk review and analyzed aggregated Ministry of Health (MOH) IPT enrollment data from 2014 to 2018 to determine trends and impact of program activities. We further analyzed IPT completion reports for patients initiated from 2015 to 2017 in 745 MOH sites in Nairobi, Central, Eastern and Western Kenya.RESULTS: IPT was scaled up 75-fold from 2014 to 2018: the number of PLHIV covered increased from 9,981 to 749,890. The highest percentage increases in the cumulative number of PLHIV on IPT were seen in the quarters following IPT pilot projects in 2014 (49%), national launch in 2015 (54%), and HIV treatment acceleration in 2016 (158%). Among 250,069 patients initiating IPT from 2015 to 2017, 97.5% completed treatment, 0.2% died, 0.8% were lost to follow-up, 1.0% were not evaluated, and 0.6% discontinued treatment.CONCLUSIONS: IPT can be scaled up rapidly and effectively among PLHIV. Deliberate MOH efforts, strong leadership, service delivery integration, continuous mentorship, stakeholder involvement, and accountability are critical to program success.

The World Health Organization (WHO) recommends providing tuberculosis preventive treatment (TPT) to all persons living with HIV and to all household contacts of persons with bacteriologically confirmed pulmonary tuberculosis disease. Regrettably, the absence of a harmonized data collection and management approach to TPT indicators has contributed to programmatic challenges at local, national, and global levels. However, in April 2020, the WHO launched the Consolidated HIV Strategic Information Guidelines, with an updated set of priority indicators. These guidelines recommend that Ministries of Health collect, report, and use data on TPT completion in addition to TPT initiation. Both indicators are reflected in the WHO's list of 15 core indicators for program management and are also required by the US President's Emergency Plan for AIDS Relief's Monitoring, Evaluation, and Reporting (MER) guidance. Although not perfectly harmonized, both frameworks now share essential indicator characteristics. Aligned indicators are necessary for robust strategic and operational planning, resource allocation, and data communication. "Collect once, use many times" is a best practice for strategic information management. Building harmonized and sustainable health systems will enable countries to successfully maintain essential HIV, tuberculosis, and other health services while combatting new health threats.

IMPORTANCE: Controlling antimicrobial resistance in health care is a public health priority, although data describing antimicrobial use in US nursing homes are limited. OBJECTIVE: To measure the prevalence of antimicrobial use and describe antimicrobial classes and common indications among nursing home residents. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional, 1-day point-prevalence surveys of antimicrobial use performed between April 2017 and October 2017, last survey date October 31, 2017, and including 15 276 residents present on the survey date in 161 randomly selected nursing homes from selected counties of 10 Emerging Infections Program (EIP) states. EIP staff reviewed nursing home records to collect data on characteristics of residents and antimicrobials administered at the time of the survey. Nursing home characteristics were obtained from nursing home staff and the Nursing Home Compare website. EXPOSURES: Residence in one of the participating nursing homes at the time of the survey. MAIN OUTCOMES AND MEASURES: Prevalence of antimicrobial use per 100 residents, defined as the number of residents receiving antimicrobial drugs at the time of the survey divided by the total number of surveyed residents. Multivariable logistic regression modeling of antimicrobial use and percentages of drugs within various classifications. RESULTS: Among 15 276 nursing home residents included in the study (mean [SD] age, 77.6 [13.7] years; 9475 [62%] women), complete prevalence data were available for 96.8%. The overall antimicrobial use prevalence was 8.2 per 100 residents (95% CI, 7.8-8.8). Antimicrobial use was more prevalent in residents admitted to the nursing home within 30 days before the survey date (18.8 per 100 residents; 95% CI, 17.4-20.3), with central venous catheters (62.8 per 100 residents; 95% CI, 56.9-68.3) or with indwelling urinary catheters (19.1 per 100 residents; 95% CI, 16.4-22.0). Antimicrobials were most often used to treat active infections (77% [95% CI, 74.8%-79.2%]) and primarily for urinary tract infections (28.1% [95% CI, 15.5%-30.7%]). While 18.2% (95% CI, 16.1%-20.1%) were for medical prophylaxis, most often use was for the urinary tract (40.8% [95% CI, 34.8%-47.1%]). Fluoroquinolones were the most common antimicrobial class (12.9% [95% CI, 11.3%-14.8%]), and 33.1% (95% CI, 30.7%-35.6%) of antimicrobials used were broad-spectrum antibiotics. CONCLUSIONS AND RELEVANCE: In this cross-sectional survey of a cohort of US nursing homes in 2017, prevalence of antimicrobial use was 8.2 per 100 residents. This study provides information on the patterns of antimicrobial use among these nursing home residents.

IMPORTANCE: Hospital antimicrobial consumption data are widely available; however, large-scale assessments of the quality of antimicrobial use in US hospitals are limited. OBJECTIVE: To evaluate the appropriateness of antimicrobial use for hospitalized patients treated for community-acquired pneumonia (CAP) or urinary tract infection (UTI) present at admission or for patients who had received fluoroquinolone or intravenous vancomycin treatment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included data from a prevalence survey of hospitalized patients in 10 Emerging Infections Program sites. Random samples of inpatients on hospital survey dates from May 1 to September 30, 2015, were identified. Medical record data were collected for eligible patients with 1 or more of 4 treatment events (CAP, UTI, fluoroquinolone treatment, or vancomycin treatment), which were selected on the basis of common infection types reported and antimicrobials given to patients in the prevalence survey. Data were analyzed from August 1, 2017, to May 31, 2020. EXPOSURE: Antimicrobial treatment for CAP or UTI or with fluoroquinolones or vancomycin. MAIN OUTCOMES AND MEASURES: The percentage of antimicrobial use that was supported by medical record data (including infection signs and symptoms, microbiology test results, and antimicrobial treatment duration) or for which some aspect of use was unsupported. Unsupported antimicrobial use was defined as (1) use of antimicrobials to which the pathogen was not susceptible, use in the absence of documented infection signs or symptoms, or use without supporting microbiologic data; (2) use of antimicrobials that deviated from recommended guidelines; or (3) use that exceeded the recommended duration. RESULTS: Of 12 299 patients, 1566 patients (12.7%) in 192 hospitals were included; the median age was 67 years (interquartile range, 53-79 years), and 864 (55.2%) were female. A total of 219 patients (14.0%) were included in the CAP analysis, 452 (28.9%) in the UTI analysis, 550 (35.1%) in the fluoroquinolone analysis, and 403 (25.7%) in the vancomycin analysis; 58 patients (3.7%) were included in both fluoroquinolone and vancomycin analyses. Overall, treatment was unsupported for 876 of 1566 patients (55.9%; 95% CI, 53.5%-58.4%): 110 of 403 (27.3%) who received vancomycin, 256 of 550 (46.6%) who received fluoroquinolones, 347 of 452 (76.8%) with a diagnosis of UTI, and 174 of 219 (79.5%) with a diagnosis of CAP. Among patients with unsupported treatment, common reasons included excessive duration (103 of 174 patients with CAP [59.2%]) and lack of documented infection signs or symptoms (174 of 347 patients with UTI [50.1%]). CONCLUSIONS AND RELEVANCE: The findings suggest that standardized assessments of hospital antimicrobial prescribing quality can be used to estimate the appropriateness of antimicrobial use in large groups of hospitals. These assessments, performed over time, may inform evaluations of the effects of antimicrobial stewardship initiatives nationally.

Objective: To examine the association between the Centers for Disease Control and Prevention (CDC)'s Social Vulnerability Index (SVI) and COVID-19 incidence among Louisiana census tracts. Methods: An ecological study comparing the CDC SVI and census tract-level COVID-19 case counts was conducted. Choropleth maps were used to identify census tracts with high levels of both social vulnerability and COVID-19 incidence. Negative binomial regression with random intercepts was used to compare the relationship between overall CDC SVI percentile and its four sub-themes and COVID-19 incidence, adjusting for population density. Results: In a crude stratified analysis, all four CDC SVI sub-themes were significantly associated with COVID-19 incidence. Census tracts with higher levels of social vulnerability were associated with higher COVID-19 incidence after adjusting for population density (adjusted RR: 1.52, 95% CI: 1.41-1.65). Conclusions: The results of this study indicate that increased social vulnerability is linked with COVID-19 incidence. Additional resources should be allocated to areas of increased social disadvantage to reduce the incidence of COVID-19 in vulnerable populations.

Rationale: U.S. health departments routinely conduct post-arrival evaluation of immigrants and refugees at risk for tuberculosis (TB), but this important intervention has not been thoroughly studied.Objectives: To assess outcomes of the post-arrival evaluation intervention.Methods: We categorized at-risk immigrants and refugees as having had recent completion of treatment for pulmonary TB disease overseas (including in Mexico and Canada); as having suspected TB disease (chest radiograph/clinical symptoms suggestive of TB) but negative culture results overseas; or as having latent TB infection (LTBI) diagnosed overseas. Among 2.1 million U.S.-bound immigrants and refugees screened for TB overseas during 2013-2016, 90,737 were identified as at risk for TB. We analyzed a national data set of these at-risk immigrants and refugees and calculated rates of TB disease for those who completed post-arrival evaluation.Results: Among 4,225 persons with recent completion of treatment for pulmonary TB disease overseas, 3,005 (71.1%) completed post-arrival evaluation within 1 year of arrival; of these, TB disease was diagnosed in 22 (732 cases/100,000 persons), including 4 sputum culture-positive cases (133 cases/100,000 persons), 13 sputum culture-negative cases (433 cases/100,000 persons), and 5 cases with no reported sputum-culture results (166 cases/100,000 persons). Among 55,938 with suspected TB disease but negative culture results overseas, 37,089 (66.3%) completed post-arrival evaluation; of these, TB disease was diagnosed in 597 (1,610 cases/100,000 persons), including 262 sputum culture-positive cases (706 cases/100,000 persons), 281 sputum culture-negative cases (758 cases/100,000 persons), and 54 cases with no reported sputum-culture results (146 cases/100,000 persons). Among 30,574 with LTBI diagnosed overseas, 18,466 (60.4%) completed post-arrival evaluation; of these, TB disease was diagnosed in 48 (260 cases/100,000 persons), including 11 sputum culture-positive cases (60 cases/100,000 persons), 22 sputum culture-negative cases (119 cases/100,000 persons), and 15 cases with no reported sputum-culture results (81 cases/100,000 persons). Of 21,714 persons for whom treatment for LTBI was recommended at post-arrival evaluation, 14,977 (69.0%) initiated treatment and 8,695 (40.0%) completed treatment.Conclusions: Post-arrival evaluation of at-risk immigrants and refugees can be highly effective. To optimize the yield and impact of this intervention, strategies are needed to improve completion rates of post-arrival evaluation and treatment for LTBI.