IMPORTANCE: Antimicrobial resistance is a major public health problem in the US. Estimating national rates of antimicrobial-resistant infections commonly associated with health care can aid in targeted public health efforts. OBJECTIVE: To determine the national incidence rates of 6 pathogens over time: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp (VRE), extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella spp (excluding Klebsiella aerogenes) (ESCR-EK), carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Acinetobacter spp (CRAsp), and multidrug-resistant (MDR) Pseudomonas aeruginosa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2012 to 2022 on inpatient hospitalizations, clinical cultures, and facility-level characteristics. Hospital-months were included in the dynamic cohort if the hospital reported at least 1 culture with microbial growth accompanied by antimicrobial susceptibility testing (AST) results in the month. Data from the PINC-AI and Becton Dickinson Insights databases were used, and cases were defined as incident nonsurveillance cultures yielding an organism of interest with sufficient AST results for a phenotype of interest. Data were collected from January 2012 to December 2022 and analyzed from April 2023 to June 2024. EXPOSURE: Inpatient hospitalizations with a discharge date in an included hospital month. MAIN OUTCOMES AND MEASURES: National annual antimicrobial-resistant cases per 10 000 hospitalizations were obtained using weights based on facility-level characteristics. Cases were defined as community-onset if collected on or before day 3 of hospitalization and hospital-onset if obtained on day 4 or later. RESULTS: This study cohort included 332 to 606 hospitals per year between 2012 to 2022 and 7 158 139 cultures. Antimicrobial-resistant pathogens accounted for an estimated 569 749 (95% CI, 475 949-663 548) cases and 179.6 (95% CI, 163.1-196.1) cases per 10 000 hospitalizations in 2022. Of these cases, 77% (437 657; 95% CI, 364 529-510 785) were community-onset and 23% (132 092; 95% CI, 108 241-155 943) were hospital-onset. MRSA (44% [251 854; 95% CI, 209 558-294 150]) and ESCR-EK (35% [200 884; 95% CI, 163 692-238 077]) made up the largest proportions of total infections in 2022, respectively. Rates of hospital-onset MRSA, VRE, CRE, CRAsp, and MDR P aeruginosa had periods of decline from 2012 to 2019; however, all pathogens experienced an increase in hospital-onset rates in 2020 and 2021. Community-onset ESCR-EK rates increased from 2012 to 2022, while community-onset rates of MRSA, VRE, and MDR P aeruginosa declined. CONCLUSIONS AND RELEVANCE: While antimicrobial resistance rates have experienced uneven declines in the US from 2012 to 2022, the burden of resistance remains substantial. These findings suggest that more effective strategies to reduce antimicrobial resistance are needed.

Long-term effects of COVID-19 on multiple organ systems have been reported. Indigenous persons experienced disproportionate morbidity and mortality from COVID-19; however, Post-COVID-19 Conditions (PCC) have not been well described in this population. We conducted a longitudinal cohort study among Indigenous persons living in the Navajo Nation or White Mountain Apache Tribal lands in the Southwest United States who tested positive for SARS-CoV-2 between February 1, 2021 and August 31, 2022. Participants were enrolled during their acute illness and followed for three months. PCC was defined as the presence of any self-reported symptom and/or any sequelae or new condition recorded in the electronic health record at the 3-month visit. Risk factors for PCC were evaluated using Poisson regression with robust standard errors. The analysis included 258 adults and 84 children. Most participants (98.4% of adults, 90.5% of children) experienced a mild, symptomatic acute illness. Over half of adults (57.8%) and a third (39.3%) of children experienced six or more symptoms during the acute illness. Three months post-acute COVID-19, 39.8% of adults and 15.9% of children had symptoms consistent with PCC. Commonly reported symptoms were fatigue/tiredness, cough, headache, runny nose, and myalgia. Among adults enrolled during Omicron predominance, older age and hospitalization for COVID-19 were significantly associated with an increased risk of PCC, and COVID-19 vaccination was significantly associated with a decreased risk of PCC in univariable analysis. In a multivariable analysis, COVID-19 vaccination (risk ratio: 0.56; 95% confidence interval: 0.34, 0.90) remained significantly associated with a decreased risk of PCC. In this cohort of Indigenous persons in the Southwest US, PCC at three months post-acute COVID-19 illness were common, including among individuals with mild acute illness. While the absence of a control group is a limitation, these findings highlight the potential ongoing healthcare needs related to PCC in Indigenous populations.

BACKGROUND: Understanding virus-virus interactions is important for evaluating disease transmission and severity. Positive interactions suggest concurrent circulation, while negative interactions indicate reduced transmission of one virus when another is prevalent. This study examines interactions among seven respiratory viruses using a Bayesian approach that accounts for seasonality and long-term trends. METHODS: We analyzed data from 43,385 acute febrile illness cases in the Sentinel Enhanced Dengue Surveillance System in Puerto Rico (2013-2023). Viruses studied included influenza A (IAV), influenza B (IBV), respiratory syncytial virus (RSV), human parainfluenza viruses 1 and 3 (HPIV-1, HPIV-3), human adenovirus (HAdV), and human metapneumovirus (HMPV). Wavelet coherence analysis investigated synchronous or asynchronous viral co-variation, while a Bayesian hierarchical model estimated pairwise interactions. RESULTS: Among 43,385 participants, 26.0% tested positive for at least one virus, with IAV (9.5%), HAdV (4.1%), RSV (3.6%), and IBV (3.6%) being most frequent. Coinfections occurred in 0.5% of cases, often involving HAdV. Wavelet coherence identified significant synchronization among RSV/HMPV, HPIV-1/HMPV, and other virus pairs, with minimal coherence during the COVID-19 pandemic. Bayesian modeling suggested five virus-virus associations: four positive (RSV/HPIV-3, HMPV/HPIV-1, IBV/HAdV, IBV/HMPV) and one negative (IAV/HAdV). However, when restricting the analysis to the pre-pandemic period, fewer associations remained statistically credible. CONCLUSIONS: Respiratory viruses in Puerto Rico demonstrate patterns of co-circulation that may reflect complex interactions, but these associations appear context-dependent. Findings highlight the need for continued surveillance to better understand virus-virus dynamics and their implications for public health interventions.

BACKGROUND: Hepatitis E virus (HEV) is endemic in many resource-poor countries. Despite an available vaccine, data on HEV-associated mortality are scarce, hindering informed decisions. This study aims to estimate the population-based rate of HEV-specific mortality in Bangladesh. METHODS: During December 2014-September 2017, we conducted surveillance in six tertiary hospitals in Bangladesh. Patients aged ≥14 years with acute jaundice were recruited, tested for IgM anti-HEV, and followed up post-discharge. A mortality survey in the hospital catchment areas identified deaths associated with acute jaundice, including maternal, stillbirths and neonatal deaths delivered by a mother with acute jaundice during pregnancy, confirmed by two independent physicians reviewing verbal autopsy data. RESULTS: Out of 1,925 patients with acute jaundice identified and enrolled in the surveillance hospitals, 302 died, with 28 (9%) testing positive for IgM anti-HEV. In the hospital catchment areas, the team identified 587 jaundice-associated deaths, including 25 maternal deaths. Combining hospital-based surveillance and mortality survey data, the study estimated 986 (95% CI: 599-1338) HEV-associated deaths annually among individuals aged ≥14 years in Bangladesh, including 163 (95% CI: 57-395) maternal deaths. Additionally, 279 (95% CI: 101-664) stillbirths and 780 (95% CI: 365-1,297) neonatal deaths were attributed to HEV infection annually. CONCLUSIONS: Prior Global Burden of Disease studies presented wildly varying modeling estimates of HEV-associated annual deaths, ranging from 50,000 in 2013 to 1,932 in 2019. This study is the first to directly measure population-based estimates of mortality in Bangladesh, which can be used to determine the cost-effectiveness of hepatitis E vaccination and other interventions.

BACKGROUND: Evaluation of optimal dosing has generally been inadequate during TB drug development. Fluoroquinolones are central to TB treatment. We aimed to determine the dose of levofloxacin needed to achieve maximal efficacy and acceptable safety and tolerability as part of a multidrug TB regimen. METHODS: Opti-Q was an international, multi-center, randomized, placebo-controlled, phase II trial. Eligible participants with TB resistant to isoniazid and rifampicin but susceptible to fluoroquinolones (MDR-TB) were randomized to receive one of four weight-adjusted once-daily doses of levofloxacin given for 24 weeks(168 doses): 11mg/kg(750mg), 14mg/kg(750mg/1000mg), 17 mg/kg(1000mg/1250mg) or 20mg/kg(1250mg/1500mg) alongside a multidrug regimen. The primary efficacy outcome was time to sputum culture conversion and the primary safety outcome was grade 3 or higher adverse events. FINDINGS: 111 participants were randomized from three sites in South Africa and Peru. 83(75%) had cavities on chest x-ray, 55(50%) had a smear grading of 3+, median BMI was 20.4 kg/m(2). Median levofloxacin AUC/MIC was 573, 633, 918 and 1343 across the four treatment arms. There was no difference in time to culture conversion on solid or liquid media by treatment arm (stratified log-rank p=0.282), by tertile of AUC/MIC (p=0.350), or by dose received (p=0.723); 69.3%, 74.8%, 70.6% and 78.3% achieved culture conversion after 8 weeks on solid media respectively across the treatment arms; 64.6%, 69.5%, 52.6% and 69.6% in liquid culture. More participants experienced a grade 3-5 adverse event by dose (37.0% and 16.0% in the highest and lowest dose groups respectively, p=0.042, Cochran-Armitage test for trend) and by tertile of AUC (p=0.011). INTERPRETATION: As part of a multidrug regimen, doses of levofloxacin above 1000mg resulted in greater exposures and increased frequency of adverse events but did not result in faster time to sputum culture conversion. A dose of 1000mg daily can achieve the target exposure in nearly all adults and was well tolerated. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT01918397.

BACKGROUND: Centers for Disease Control and Prevention recommends test-of-cure (TOC) for persons with pharyngeal gonorrhea (GC) 7-14 days after treatment. We investigated the yield and feasibility of routine pharyngeal GC TOC to detect treatment failures. METHODS: During May 2021-July 2022, four U.S. STD clinics implemented pharyngeal GC TOC. Sites collected demographic, clinical, and behavioral data on all treated pharyngeal GC and positive TOC cases. Cases were dispositioned with the suspected reason for positive TOC. To assess perceived feasibility, sites participated in qualitative interviews. RESULTS: During the study period, 1,968 pharyngeal GC infections were diagnosed. Among 1,829 treated cases, 97.3% (n = 1,777) received ceftriaxone and 45.7% (n = 836) returned for TOC, varying by site (range: 35.5%- 70.8%). Among those with TOC, 4.7% (n = 39) were positive by NAAT. Of these, 48.7% had culture attempted; six positive TOC (15.4%) were also positive by culture. Most positive TOC (66.7%) were attributed to re-infection (n = 13) or false-positive results (n = 13). Six (15.4%) were treatment failures. Four failed recommended treatment and had a positive culture: two were susceptible to ceftriaxone and two did not have antimicrobial susceptibility results. Seven positive TOC (17.9%) had insufficient data to disposition. Sites perceived TOC to be feasible, though substantial resources were required.ConclusionRoutine pharyngeal GC TOC yielded 5% positivity, though treatment failure was rare (<1%), and no cases of cephalosporin-resistant GC were identified. Low TOC return rates, limited culture collection, and limited culture yield highlight challenges to determining the cause of a positive TOC and the limitations of TOC in identifying cephalosporin resistance.

In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV) was introduced to the childhood immunization programme in 2006 and replaced by the 10-valent PCV (PCV10, GSK) in 2011. To describe invasive pneumococcal disease in the era of childhood PCV vaccination on pneumococcal bacteraemia across all ages, we collected and sequenced 979 pneumococcal blood isolates from consecutive patients with pneumococcal bacteraemia in the Gelderland area, the Netherlands, between 2000 and 2020. In total, 58% of the bacteraemia cases (n=563/979) occurred in the elderly population. Compared to the pre-PCV period (2000-2005), the odds ratio for non-PCV10 bacteraemia was 17.5 (CI 9.9-31.6; P<0.001) in the late-PCV10 period, showing an overall increase in the proportion of bacteraemia cases being caused by non-vaccine serotype pneumococci (2016-2020). The increase in non-PCV10 serotypes is mainly driven by an expansion of lineage global pneumococcal sequencing cluster 3 (GPSC3) expressing serotype 8, alongside the emergence of serotype 12F that was mediated by multiple lineages (GPSC32/GPSC26/GPSC55). Both serotypes 8 and 12F were included in the latest PCV20 formulation that is licensed to be used in children and adults in Europe. Over 20 years, we observed a low prevalence of antimicrobial resistance (AMR) as predicted by genome data. There were no significant changes in AMR prevalence after vaccine introduction (P>0.05 for all comparisons). We saw a stably low prevalence of reduced penicillin susceptibility, which was observed in multiple pneumococcal lineages, with GPSC10 being the most common in the Gelderland collection, whilst GPSC1 and GPSC6 were common among the penicillin-resistant pneumococcal blood culture isolates provided by the Netherlands Reference Laboratory for Bacterial Meningitis. Comparison to global collections of GPSC10, GPSC1 and GPSC6 isolates favored the likelihood of separate introductions of penicillin-resistant isolates rather than cloncal expansion. Genomic surveillance of pneumococcal bacteraemia in this unbiased population sample in the Netherlands supports the use of higher valency PCVs, such as PCV20, especially in adults, to prevent future bacteraemia cases caused by Streptococcus pneumoniae in the Gelderland area, the Netherlands, while maintaining a low prevalence of AMR in the pneumococcal population.

BACKGROUND: Nanomedicine offers a number of innovative strategies to address major public health burdens, including complex respiratory illnesses. In this work, we introduce a multi-drug nanoparticle fabricated using femtosecond laser ablation for the treatment of influenza, SARS-CoV-2, and their co-infections. METHODS: The SARS-CoV-2 antiviral, remdesivir; the influenza antiviral, baloxavir marboxil; and the anti-inflammatory, dexamethasone, were co-crystalized and then ablated in aqueous media using a femtosecond pulsed laser and subsequently surface modified with the cationic polymer, chitosan, or poly-d-lysine. Physical and chemical properties were then characterized using multiple complimentary techniques. Finally, a clinically relevant in vitro primary mouse trachea epithelial cell-air-liquid interface culture model was used to analyze the antiviral effect of our nanoparticles against Influenza Virus A. RESULTS: Our final nanoparticle exhibited a positive zeta potential with a diameter of ~73 nm. Remdesivir, baloxavir marboxil, and dexamethasone were all present in the nanoparticle suspension at a 1:1:1 ratio. Notably, these particles exhibited a potent anti-influenza effect, decreasing the viral titer by ≈ 4 logs in comparison to vehicle controls. CONCLUSION: Overall, these findings demonstrate great promise both for the use of laser ablation to generate multi-drug nanoparticles and for the anti-viral effects of our nanoformulation against respiratory illness.

The Egyptian rousette bat (ERB) is a natural reservoir for Marburg virus (MARV; family Filoviridae), a putative reservoir for Sosuga virus (SOSV; family Paramyxoviridae), and a vertebrate reservoir for Kasokero virus (KASV; family Orthonairoviridae); however, the effect of naturally occurring coinfection by those viruses on MARV shedding and spillover potential is unknown. To answer this question, we experimentally infected one cohort of captive-bred ERBs with SOSV+MARV (n=12 bats) or MARV only (n=12 bats) and a second cohort with KASV+MARV (n=12 bats) or MARV only (n=12 bats), and then collected blood, oral swab, and rectal swab specimens throughout the course of infection to monitor viral shedding. Compared to the MARV-monoinfected bat group, the SOSV+MARV-coinfected bat group exhibited a significantly shortened duration of MARV oral shedding and a significantly decreased anti-MARV IgG response, which may increase the capacity for MARV reinfection. In contrast, relative to the MARV-monoinfected bat group, the KASV+MARV-coinfected bat group exhibited significantly increased peak magnitudes and durations of MARV viremia and oral shedding, as well as a significantly increased anti-MARV IgG response. Correspondingly, cumulative MARV shedding loads, a measure of infectiousness, were significantly higher in the KASV+MARV-coinfected bat group than the MARV-monoinfected bat group. Four of the KASV+MARV-coinfected bats were classified as MARV supershedders, together accounting for 72.5% of the KASV-MARV experimental cohort's total shedding. Our results demonstrate that SOSV+MARV and KASV+MARV coinfection of ERBs differentially modulates MARV shedding and anti-MARV IgG responses, thereby implicating MARV coinfection as playing a critical role in bat-to-bat MARV transmission dynamics and spillover potential.

BACKGROUND: Brain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute brain infections at 13 hospitals in Brazil, India, and Malawi. METHODS: With hospital stakeholders, policy makers, and patient and public representatives, we co-designed a multifaceted clinical and laboratory intervention, informed by an evaluation of routine practice. The intervention, tailored for each setting, included a diagnostic and management algorithm, a lumbar puncture pack, a testing panel, and staff training. We used multivariable logistic regression and interrupted time series analysis to compare the coprimary outcomes-the percentage of patients achieving a syndromic diagnosis and the percentage achieving a microbiological diagnosis before and after the intervention. The study was registered at ClinicalTrials.gov (NCT04190303) and is complete. FINDINGS: Between Jan 5, 2021, and Nov 30, 2022, we screened 10 462 patients and enrolled a total of 2233 patients at 13 hospital sites connected to the four study centres in Brazil, India, and Malawi. 1376 (62%) were recruited before the intervention and 857 (38%) were recruited after the intervention. 2154 patients (96%) had assessment of the primary outcome (1330 [62%] patients recruited pre-intervention and 824 [38%] recruited post-intervention). The median age across centres was 23 years (IQR 6-44), with 1276 (59%) being adults aged 16 years or older and 888 (41%) children aged between 29 days and 15 years; 1264 (59%) patients were male and 890 (41%) were female. Data on race and ethnicity were not recorded. 1020 (77%) of 1320 patients received a syndromic diagnosis before the intervention, rising to 701 (86%) of 813 after the intervention (adjusted odds ratio [aOR] 1·81 [95% CI 1·40-2·34]; p<0·0001). A microbiological diagnosis was made in 294 (22%) of 1330 patients pre-intervention, increasing to 250 (30%) of 824 patients post-intervention (aOR 1·46 [95% CI 1·18-1·79]; p=0·00040). Interrupted time series analysis confirmed that these increases exceeded a modest underlying trend of improvement over time. The percentage receiving a lumbar puncture, time to appropriate therapy, and functional outcome also improved. INTERPRETATION: Diagnosis and management of patients with suspected acute brain infections improved following introduction of a simple intervention package across a diverse range of hospitals on three continents. The intervention is now being implemented in other settings as part of the WHO Meningitis Roadmap and encephalitis control initiatives. FUNDING: UK National Institute for Health and Care Research.

BACKGROUND: Evidence shows that isoniazid preventive therapy (IPT) reduces tuberculosis (TB) incidence among people with human immunodeficiency virus (HIV) with additive benefit beyond antiretroviral therapy alone, but its effectiveness in settings with high multidrug-resistant TB (MDR-TB) burden is unclear. We assessed the relationship between IPT and TB incidence among people with HIV (PWH) in Ukraine, a high-burden (32.6%) MDR-TB setting, and whether its effectiveness is maintained among virologically suppressed persons. METHODS: We analyzed national surveillance data for HIV and TB collected between 2018 and 2022. Complete IPT (n = 40 733) was defined as receipt of ≥146 days of therapy and no IPT (n = 91 022) as <28 days of therapy. We modeled TB incidence and death using Poisson regression adjusting for covariates related to receipt of IPT and TB incidence. The secondary outcome was multidrug resistance, and sensitivity analyses explored the influence of virologic suppression. RESULTS: Of 131 755 PWH who met inclusion criteria, 9089 (5.5%) died. Unadjusted TB incidence was 1.91 cases per 100 person-years in the No IPT group and 1.01 cases per 100 person-years in the Complete IPT group (adjusted incidence rate ratio [aIRR], 1.99). MDR-TB occurred in 29.1% and 30.7% of TB cases in the Complete and No IPT groups, respectively. Among virologically suppressed PWH, persons with no IPT had a higher TB incidence (aIRR, 1.38) than those who completed IPT. CONCLUSIONS: Completing IPT as part of a public health intervention can significantly reduce TB incidence among PWH, even in settings with high-burden MDR-TB and among the virologically suppressed.

BACKGROUND: Assessing the impact of influenza epidemics provides useful information to assess both population and healthcare system burden and can inform prevention and control measures for seasonal epidemics, such as vaccination and antivirals. Furthermore, it is an important component of pandemic preparedness. METHODS: We assessed and compared three influenza impact parameters: influenza-associated excess respiratory mortality, hospitalizations and ICU admissions, under the World Health Organization Pandemic Influenza Severity Assessment framework. We used a generalized additive model to estimate these parameters from 1998 through 2019 in Hong Kong based on historical mortality, hospitalization, ICU admission and influenza surveillance data. Intensity thresholds by influenza type were estimated using quantiles from the distribution of peak values of the parameters from 1998 through 2017 and were compared to the real-time estimates of excess parameters in 2018-2019. Influenza death and hospitalization data were used for validation. FINDINGS: There was good agreement between the different impact parameters after comparing the 2018-2019 data to the thresholds. The 2019 influenza A epidemic was characterized as having moderate impact overall and in all age groups, except 0-64 years for whom the excess ICU impact was high; whereas the 2018 influenza B epidemic was characterized as having very high impact overall and in all age groups. INTERPRETATION: The impact of influenza epidemics can vary from year to year. The PISA framework facilitates the impact assessment of seasonal influenza epidemics using different data sources and can be implemented in both real-time or at the end of seasons as policy makers and public health officials prepare for the next seasonal epidemic.

IMPORTANCE: Stimulants are increasingly prescribed for US adults. Whether such prescribing is associated with misuse and prescription stimulant use disorder (PSUD) is less understood. OBJECTIVES: To examine (1) sex- and age-specific trends in the number of persons dispensed stimulants and trends in dispensed prescription stimulants by prescriber specialty in 2019 through 2022; (2) prevalence of misuse and PSUD by use of prescription amphetamine-type stimulants (hereafter referred to as amphetamines) and methylphenidate; and (3) PSUD prevalence and sociodemographic and behavioral health correlates among persons using prescription stimulants with and without prescription stimulant misuse. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study used the 2019-2022 IQVIA Total Patient Tracker and National Prescription Audit New to Brand databases and the 2021-2022 National Surveys on Drug Use and Health (NSDUH) (community-dwelling 18- to 64-year-old individuals). Data analysis was performed from March to April 2024. EXPOSURE: Past-year use of prescription stimulants. MAIN OUTCOMES AND MEASURES: PSUD using DSM-5 criteria. RESULTS: Of the sampled 83 762 adults aged 18 to 64 years, 33.8% (unweighted) were aged 18 to 25 years, 53.0% (unweighted) were aged 26 to 49 years, and 56.0% (unweighted) were women. Among those using prescription stimulants, 25.3% (95% CI, 23.8%-26.8%) reported misuse, and 9.0% (95% CI, 8.0%-10.0%) had PSUD. Among those with PSUD, 72.9% (95% CI, 68.3%-77.6%) solely used their own prescribed stimulants, 87.1% (95% CI, 82.3%-90.8%) used amphetamines, 42.5% (95% CI, 36.6%-48.5%) reported no misuse, and 63.6% (95% CI, 56.8%-69.8%) had mild PSUD. Individuals using amphetamines, compared with those using methylphenidate, had higher prevalence ratios of misuse (3.1 [95% CI, 2.2-4.3]) and PSUD (2.2 [95% CI, 1.3-3.8]). The largest increase in the number of individuals dispensed prescription stimulants was among women aged 35 to 64 years, from 1.2 million in quarter 1 of 2019 to 1.7 million in quarter 4 of 2022 (average quarterly percentage change, 2.6% [95% CI, 2.1%-3.1%]). The prevalence of prescription stimulant misuse was lower among women aged 35 to 64 years using these medications (13.7% [95% CI, 11.1%-16.8%]) than other sex- and age-specific subgroups (ranging from 22.0% [95% CI, 17.9%-26.7%] for men aged 35-64 years to 36.8% [95% CI, 32.6%-41.2%] for women aged 18-25 years). CONCLUSIONS AND RELEVANCE: High prevalence of prescription stimulant misuse and PSUD (regardless of misuse status) suggests the importance of ensuring clinically appropriate use and of screening for and treating PSUD among all adults prescribed stimulants, especially those using amphetamines. Findings may suggest potential progress in addressing the mental health care gap for middle-aged women and the need for evidence-based clinical guidance and training on benefits and risks of prescription stimulants for adults.

BACKGROUND: Information on the status of insecticide resistance in malaria vectors is critical for implementing effective malaria vector control. The Sierra Leone National Malaria Control Programme, in collaboration with the PMI VectorLink project, assessed the resistance status to insecticides commonly used in public health, and associated resistance mechanisms in Anopheles gambiae, the main vector of malaria in Sierra Leone. METHODS: The susceptibility of An. gambiae against pyrethroids with and without piperonyl butoxide (PBO), chlorfenapyr, clothianidin, bendiocarb and pirimiphos-methyl was evaluated in four districts of Sierra Leone in 2018 and 2019 using WHO and CDC bottle bioassay protocols. A subset of samples that were exposed to the insecticides were screened for molecular markers of insecticide resistance, knock-down resistance (kdr) L1014F, 1014S and N1575Y, and (ace-1-G119S). RESULTS: Anopheles gambiae from all sites were resistant to the diagnostic doses of three pyrethroids: deltamethrin, permethrin and alpha-cypermethrin. Intensity of resistance to all three pyrethroids was high, with less than 95% mortality at 10X concentration. However, pre-exposure of An. gambiae to PBO increased overall mortality by 41.6%, 50.0% and 44.0% for deltamethrin, permethrin and alpha-cypermethrin, respectively. The vector was susceptible to chlorfenapyr, clothianidin and pirimiphos-methyl, while bendiocarb showed possible resistance. The frequency of kdr alleles was 98.2% for L1014F, 2.1% for 1014S and 8.9% for N1575Y, while the frequency of the Ace-1 G119S allele was 13.6%. Significant deviation from the Hardy-Weinberg equilibrium and deficiency of heterozygotes was detected only at the G119S locus of An. gambiae (p < 0.0001). Of the 191 An. gambiae sensu lato that were molecularly identified to the species level, 81.7% were An. gambiae sensu stricto (95% CI 75.3-86.7), followed by Anopheles coluzzii (17.8%, 95% CI (12.8-24.1) with one hybrid of An. gambiae/An. coluzzii 0.5%, 95% CI (0.03-3.3). CONCLUSION: Malaria vectors were highly resistant to pyrethroids but exposure to PBO partially restored susceptibility in An. gambiae s.l. in Sierra Leone. Malaria vectors were susceptible to chlorfenapyr, clothianidin and pirimiphos-methyl with possible resistance to bendiocarb. These data informed the selection and distribution of ITN PBO in Sierra Leone's mass campaigns in 2020 and selection of clothianidin for indoor residual spraying in 2021.

A recent article published in Science urges mandatory indoor air quality (IAQ) standards in public spaces, focusing on protecting public health, especially against diseases such as COVID-19, but also IAQ in general (1). Given the significance of this topic to our society, this short communication aims to provide commentary on the article and further discuss the importance of establishing IAQ standards. Citing a lack of legislated standards globally, the authors (1) propose numerical limits for four IAQ parameters: particulate matter (PM(2.5)), carbon dioxide (CO(2)), carbon monoxide (CO), and ventilation rate (VR). While recognizing that most of the countries do not have any mandatory IAQ standards, it is also noteworthy that IAQ regulations or guidelines exist in more than 40 countries. We like to emphasize that successful IAQ management requires recognizing, sharing, and reviewing openly available, existing regulations and guidelines, while adapting them to regional characteristics.

BACKGROUND: Household transmission of respiratory viruses may drive community spread. Few recent studies have examined household respiratory syncytial virus (RSV) transmission in the United States. METHODS: We conducted a prospective community-based cohort study from 1 June 2022 to 31 May 2023. Participants had blood samples collected and completed nasal swabs and surveys at least weekly, irrespective of symptoms. We tested serum for RSV antibody, nasal swabs by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and performed whole genome sequencing. We evaluated secondary RSV transmission and associated risk factors based on a log-linear Poisson regression model. RESULTS: RSV was detected among 310 (10%) participants within 200 (20%) households. Most (94%) index cases were symptomatic. We identified 37 cases of potential secondary transmission within 14 days of a distinct index case (10%, 95% confidence interval [CI]: 7%, 14%); median age of index and secondary cases were 6 (interquartile range [IQR]: 3-10) and 35 (7-41) years, respectively, with 89% (24/27) of index cases aged 6 months to 12 years. Factors associated with increased risk of RSV transmission included index case viral detection ≥1 week and contact age ≤12 years. Of 120 sequenced specimens, the main lineages represented were A.d.5.2 (n = 37) and A.d.1 (n = 30). Sequenced viruses from households with ≥2 RSV infections were similar when occurring within ≤14 days (mean pairwise difference 4 [range 0-13], n = 17 households), compared to those >14 days (137 [37-236], n = 2). CONCLUSIONS: Most RSV household transmission occurs from infants and young children to adults. Viral genome sequencing demonstrated that multiple household infections within a 14-day period are likely due to within-household transmission.

BACKGROUND: Although numerous studies have demonstrated the effectiveness of interventions delivered by disease intervention specialists (DIS), relatively few studies have assessed their economic outcomes. We performed a systematic literature review of the cost, cost-effectiveness, and cost-benefit of DIS-delivered interventions for sexually transmitted infections (STIs) in the United States. METHODS: Building on a recent systematic review of the effectiveness of DIS-delivered interventions, we reviewed economic outcomes associated with these interventions for STIs. We searched articles indexed in MEDLINE, Web of Science, CINAHL, and ProQuest from 2000 through December 2022, using these inclusion criteria: addressed an intervention of DIS-delivered interventions for STIs including partner services; United States setting; and included estimates for program cost, cost-effectiveness, or cost-benefit. Findings were summarized through narrative synthesis. RESULTS: Seven studies met the inclusion criteria. Overall, DIS-delivered interventions including STI partner services can be a cost-effective use of public health resources. In some scenarios, the cost of these interventions can be completely offset by averted medical costs. Cost and cost-effectiveness estimates of DIS-delivered interventions can vary across geographic settings and under different epidemiologic conditions. CONCLUSIONS: Although scarce, the available evidence suggests DIS-delivered interventions including STI partner services are an efficient use of public health resources. Health economic modeling studies are needed to facilitate conversion of intermediate cost-effectiveness outcomes (e.g., cost per syphilis case identified and treated) into standard cost-effectiveness outcomes (e.g., cost per quality-adjusted life year [QALY] gained).

Understanding vaccine uptake and related factors among health care workers is critical to successful vaccination programs. A cross-sectional survey was conducted in central, provincial, district hospitals and health centers among health workers in Lao People's Democratic Republic (PDR) in November 2023 to assess health workers' experience with influenza and COVID-19 vaccination, vaccination uptake, intended uptake, and intention to recommend both vaccinations to patients in the future. Logistic regression was used to identify factors associated with these practices. Among 1228 surveyed health workers in six provinces, 55 % were nurses, assistant nurses, or midwives; 32 % were doctors or assistant doctors; and 14 % had other occupations. Overall, 77 % of respondents were female, and the median age was 34 years (interquartile range 29-42 years). Current influenza vaccination and receipt of COVID-19 booster doses were 70 % (95 % confidence interval [CI]: 62-78 %) and 90 % (95 % CI: 87-92 %), respectively. If vaccines were available for free in the future, approximately 94 % and 92 % of health workers would receive influenza and COVID-19 vaccination, respectively. Nearly all health workers would recommend influenza (98 %) and COVID-19 (95 %) vaccination to their patients. Health workers who had received influenza vaccination prior to the COVID-19 pandemic were more likely to have received current influenza vaccination (adjusted odds ratio [aOR], 95 % CI: 3.7, 2.8-4.9) and to intend to receive influenza vaccination in the future (aOR 2.7, 95 % CI: 1.1-6.8). Health workers who were vaccinated for influenza in the current season were more likely to receive COVID-19 booster doses and to intend to receive future booster doses (aOR, 95 % CI: 2.2, 1.3-3.7 and 2.5, 1.2-5.1, respectively). Intention to recommend influenza vaccination to patients was associated with the intention to recommend COVID-19 vaccination to patients, and vice versa. High acceptance for influenza and COVID-19 vaccination among health workers can support a successful vaccination program in Lao PDR.

Road traffic deaths are preventable but remain a major public health problem. Crashes cause more than 40,000 deaths annually in the United States, and traffic-related pedestrian deaths have increased rapidly. To examine change in pedestrian and overall traffic death rates (deaths per 100,000 population) within an international context, CDC analyzed 2013-2022 data from the United States and 27 other high-income countries in the International Road Traffic and Accident Database, as well as early 2023 U.S. estimates. Between 2013 and 2022, U.S. pedestrian death rates increased 50% (from 1.55 to 2.33 per 100,000 population), while other countries generally experienced decreases (median decrease = 24.7%). During this period, overall U.S. traffic death rates increased 22.5% (from 10.41 to 12.76), but decreased by a median of 19.4% in 27 other high-income countries. Among all countries examined, the United States had the highest pedestrian death rates overall and among persons aged 15-24 and 25-64 years. Projected 2023 U.S. estimates suggest a potential decline in pedestrian (2%) and overall traffic (4%) deaths, compared with those in 2022. Accelerated adoption of a Safe System approach, focused on creating safer roadways and vehicles, establishing safer speeds, supporting safer road users, and improving post-crash care, can help reduce U.S. pedestrian and overall traffic deaths.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular diseases (CVD). Recent clinical guidelines recommend measuring Lp(a); however, the lack of Lp(a) assay standardization presents challenges to using common clinical decision points. Assay standardization may minimize inter-assay variability. This improves consistency in CVD risk assessment and evaluations of Lp(a) therapeutic efficacy. Genetically determined size variations in the defining apolipoprotein(a) [apo(a)] protein contribute to inter-individual Lp(a) heterogeneity. Individuals who express 2 apo(a) isoforms have 2 sizes of apo(a) in circulation, further contributing to Lp(a) heterogeneity. OBJECTIVE: The Centers for Disease Control and Prevention's Clinical Standardization Programs (CDC CSP) recently launched an Lp(a) standardization program based on the International Federation of Clinical Chemistry endorsed liquid-chromatography mass spectrometry-based reference measurement procedure (RMP). As part of this program, CDC CSP conducted an interlaboratory comparison study to evaluate current Lp(a) inter-assay variability and to investigate potential factors contributing to measurement variability. METHODS: Eight clinical laboratories measured Lp(a) in 40 individual donor serum samples and 3 serum pools. Serum samples were immunophenotyped by Western blot analysis to determine Lp(a) isoform sizes. Sample concentrations were measured in duplicate over 2 independent runs. RESULTS: Assay-specific Lp(a) measurements demonstrated good linear correlation with the RMP. Lp(a) inter-assay measurement variations ranged from 3.3% to 69.1% across individual samples; however, Lp(a) inter-assay coefficients of variation did not increase in a concentration-dependent manner and were not correlated with Lp(a) isoform sizes. CONCLUSION: This study provides new insights into Lp(a) inter-assay variability and assay performance in clinical laboratories that will guide future standardization efforts.

Newborn screening (NBS) is one of the United States' largest, most successful preventative public health initiatives, improving outcomes for newborns with inborn errors of metabolism. Most disorders on the Recommended Uniform Screening Panel are screened using triple-quadrupole mass spectrometry and flow injection analysis. While these methods are sensitive and well suited for high-throughput quantitative applications, the breadth of measured analytes is limited to a relatively small number of biomarkers, which often have considerable overlaps between healthy and diseased populations. High-resolution liquid chromatography-mass spectrometry (LC-MS)-based metabolomics is now capable of profiling thousands of metabolites, making it well suited for exploratory and biomarker discovery studies. To this end, we developed a robust workflow for performing nontargeted LC-MS analysis on dried bloodspot (DBS) specimens with coverage across many metabolic pathways relevant to NBS. HILIC chromatography enabled quantitation of amino acid and acylcarnitine species while also retaining lipid species, such as lyso-phosphatidylcholines. We analyzed 810 newborn-derived DBS samples across a wide range of newborn birthweights, identifying correlations with metabolites that help to better account for the lower accuracy observed for some NBS markers (e.g., isovalerylcarnitine). Additionally, we leveraged this nontargeted workflow to capture new biomarkers and metabolic phenotypes in newborns associated with parenteral nutrition administration and maternal nicotine exposure. Two critical biomarkers were identified as useful additions to targeted screening panels: N-acetyltyrosine as a qualitative marker for parenteral nutrition administration and N-acetylputrescine as a quantitative marker for controlling birthweight variability.

INTRODUCTION: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, complex illness. No diagnostic tests exist; illness evaluation relies on medical history, physical exam, and laboratory tests. While more is known about ME/CFS in adults, it can affect children and adolescents as a chronic condition. METHODS: We implemented an ME/CFS pediatric educational activity (diagnosis, management, and communication) with medical, physician assistant, and nursing students at one university and with medical students at a second university. Pretests, two videos and slides, and posttests were completed in approximately 40 minutes. Evaluation included quantitative and qualitative measures for knowledge, attitudes, beliefs, confidence, and clinical information about ME/CFS. RESULTS: The first group included 31 students who reported low familiarity and clinical exposure to ME/CFS. At posttest, 25 students (81%) recognized ME/CFS as a medical condition compared to seven (23%) at pretest. Using 0-5 scales, mean pretest-to-posttest ability to diagnose increased from 1.0 to 3.5, and confidence to communicate increased from 1.4 to 3.9. The second group, including 26 students pretest and 19 posttest, also reported low familiarity and clinical exposure The posttest showed increased self-rated ability to diagnose (pretest M: 0.6, posttest M: 3.3) and confidence to communicate (pretest M: 1.4, posttest M: 3.7). Qualitative feedback for this group showed understanding of pediatric ME/CFS symptoms, management, and communication. DISCUSSION: This educational activity increased knowledge of ME/CFS as self-reported ability to make a diagnosis and increased confidence to communicate about pediatric ME/CFS. Participating students showed changes in attitudes towards ME/CFS as a medical condition.

BACKGROUND: Dentists, dental hygienist, and veterinary technicians using drills, scalers and polishers are at risk of developing sensorineural deficits in the fingers and hands. The goal of this study was to determine whether exposure to high-frequency vibration contributed to changes in sensory function. METHODS: The tails of rats were exposed to vibration at 1250 Hz (constant acceleration of 49 m/s2) for 4 hours per day, for 10 days. The effects on sensory nerve function, and vascular function were measured. RESULTS: Vibration increased sensitivity to applied pressure and to transcutaneous electrical stimulation at 2000 and 250 Hz. It also resulted in a reduction in blood flow and myogenic tone. CONCLUSIONS: Exposure to high-frequency vibration has detrimental effects on both peripheral sensorineural and vascular function.

Background: The tick-borne pathogens, Bourbon virus (BRBV) and Heartland virus (HRTV) are the cause of febrile illnesses that may progress to severe and fatal diseases. Materials and Methods: As a preliminary effort to determine if these viruses were enzootic in Texas, ticks and blood samples were collected from feral swine (Sus scrofa) and white-tailed deer (Odocoileus virginianus) (WTD) killed by gunning as part of an abatement program during 2019-2021 in Travis County, Texas. Ticks were collected from these animals by hand and blood samples were obtained by cardiac puncture using 22-gauge needles and 5 mL syringes. Information was recorded for each animal, including date, sex, and location. The species of ticks were identified morphologically using a taxonomic key, and serum samples were tested for neutralizing antibodies to BRBV and HRTV. Results: A total of 83 Ixodes scapularis and 58 Amblyomma americanum ticks were collected from feral swine, and 196 I. scapularis and 11 Dermacentor albipictus from WTD. Although A. americanum, the implicated vector of both viruses was collected from feral swine, neutralizing antibody was not detected to BRBV, but 12% (9/75) had antibody to HRTV as evidence of a previous infection. Of the serum samples obtained from WTD, all were negative for BRBV neutralizing antibody, but 6.6%% (5/75) were positive for HRTV antibody. Conclusion: These preliminary results indicated that HRTV was enzootic in Travis, County, Texas and further studies are warranted to determine the specific tick vectors and the possible role of WTD and feral swine in the maintenance and transmission cycle of this virus.