BACKGROUND AND OBJECTIVES: Fungal infections cause substantial morbidity and mortality. Monitoring antifungal use is a foundational aspect of antifungal stewardship, particularly as new disease-causing fungi emerge and antifungal resistance spreads. We assessed recent patterns in systemic antifungal medication use among hospitalized patients within a diverse convenience sample of academic medical centres and community hospitals in the USA. METHODS: We conducted a multicentre retrospective cohort study using the Vizient(R) Clinical Data Base. We selected hospitalized patients who received >/=1 dose of systemic antifungal medication during 2018-23 and assessed antifungal days of therapy (DOT) per 1000 patient days. We stratified antifungal DOT by National Comprehensive Cancer Network (NCCN) cancer centre status to compare antifungal use at hospitals with an NCCN-designated cancer centre-some of which also include a main academic medical centre and non-cancer service lines-versus hospitals without an NCCN-designated cancer centre. RESULTS: Among 39 956 873 discharges from 412 hospitals, the proportion of patients who received any systemic antifungal was 4.5%; azoles (3.8%) were the most common antifungal class, followed by echinocandins (0.9%). Overall antifungal DOT were 53.7 per 1000 patient days (114.5 among 25 NCCN hospitals and 43.2 among 387 non-NCCN hospitals). CONCLUSIONS: Substantial antifungal use occurs among hospitalized patients, particularly among those with cancer. The growing population susceptible to fungal infections (e.g. transplants, cancer and other immunosuppressing conditions) warrants consideration of antifungal stewardship and evaluation of appropriateness of antifungal use in the context of increasing resistance.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex, chronic condition affecting the urinary bladder. Symptoms commonly associated with IC/BPS include painful urination, pain during intercourse, a persistent or recurrent sensation of bladder discomfort or pressure that often worsens as the bladder fills and eases after urination, urgency, frequent urination with little warning, nighttime urination disrupting sleep, and burning or other unusual urinary sensations. These symptoms can profoundly impact emotional and mental health, hinder participation in daily activities, disrupt social interactions, and strain personal relationships. OBJECTIVE: This study aimed to compare the experiences of different races and ethnicities with IC/BPS regarding symptoms, diagnosis, treatment status, and treatment methods. We hypothesized that there would be differences in racial and ethnic minority groups. METHODS: A cross-sectional web-based survey was administered between June and August 2022 through the Interstitial Cystitis Association and the Inspire web-based health community. Eligible adults resided in the United States, self-reported IC/BPS symptoms, and completed the survey in English. The instrument gathered demographic information, details regarding age at symptom onset, formal diagnosis status, and treatment use. Validated symptom and problem indices (the O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index) captured symptom severity and quality-of-life impact. Comparative analyses, including Fisher exact and median tests, were conducted across racial or ethnic groups (minority or multiple-race vs White and Hispanic vs non-Hispanic), and multivariable logistic regression assessed predictors of race or ethnicity on IC/BPS diagnosis status and treatment outcomes. RESULTS: In total, 1631 individuals completed the survey. Racial or ethnic minority or multiple-race respondents constituted 11.6% (n=189) of the sample. Although IC/BPS symptom severity (Interstitial Cystitis Symptom Index or Interstitial Cystitis Problem Index scores) did not significantly differ by race or ethnicity, minority or multiple-race respondents were 50% less likely to have a formal medical diagnosis of IC/BPS than White respondents (adjusted odds ratio 0.50, 95% CI 0.30-0.83). Overall, 86.7% (n=1408) of participants reported having received a formal IC/BPS diagnosis, and the single strongest determinant of receiving any form of treatment was having a formal diagnosis (odds ratio 29.67, 95% CI 18.32-48.05). Over 25% (n=385) of all respondents reported using narcotic or opioid medications, indicating the challenging nature of IC/BPS symptom management. CONCLUSIONS: Minority or multiple-race participants were significantly less likely to have ever been diagnosed with IC/BPS by a health care professional, and those who were not diagnosed with IC/BPS were less likely to have used self-care behavioral and nonpharmacological treatments for their symptoms. Streamlining the diagnostic process and public health awareness campaigns outlining treatment options may help individuals manage IC/BPS symptoms.

BACKGROUND: The World Trade Center (WTC) Health Program, a limited federal healthcare program, provides medical monitoring and treatment for WTC-related conditions to eligible Responders and Survivors of the 9/11 terrorist attacks. Free initial health evaluations (IHE) represent the first step towards the Program's goal of providing equitable and timely member access to healthcare. This study aimed to evaluate equity in IHE utilization among Program members to inform the development of targeted interventions. METHODS: This surveillance study used administrative and surveillance data collected from January 2012 through February 2024. It included Program members newly enrolled during 2012-2022 who completed an IHE or were alive for ≥ 1 year after enrollment. We conducted descriptive and multivariable logistic regression analyses. Outcomes of interest included timely IHE utilization (proportion of members completing an IHE within 6 months of enrollment) and any IHE utilization (proportion completing an IHE by February 2024). Factors of interest included member type, sex, age, race/ethnicity, preferred language, and urban/rural residence. RESULTS: 27,379 Responders and 30,679 Survivors were included. Responders were 89% male, 70% 45-64 years old at enrollment and 76% non-Hispanic White. Survivors were 54% male, 54% 45-64 years old at enrollment and 57% non-Hispanic White. Timely IHE utilization remained stable (~ 65%) among Responders, while for Survivors, it increased from 16% among those enrolled in 2017 to 68% in 2021. Timely IHE utilization was lower for younger members (enrolled < 45 years old vs. ≥ 65 years old, adjusted odds ratio [aOR] = 0.71, p < 0.001), rural residents, female Survivors (44% vs. 47% males, aOR = 0.87, p < 0.001), and Survivors who preferred non-English languages (39% vs. 46% who preferred English, aOR = 0.70, p < 0.001). Compared to non-Hispanic White members, non-Hispanic Black members had higher timely/any IHE utilization, while non-Hispanic Asian/Pacific Islander/Native Hawaiian and Hispanic Survivors had lower timely IHE utilization. CONCLUSIONS: This study highlights Program achievements (e.g. increased timely IHE utilization among Survivors over time and higher timely/any IHE utilization among non-Hispanic Black members compared to non-Hispanic White members) and gaps in providing equitable IHE services to its members. The Program can develop tailored strategies to further improve equity in IHE utilization (e.g. working with providers to adopt/expand flexible IHE scheduling and increase non-English language capacity).

Centers for Disease Control and Prevention's (CDC) Project Firstline is a national training collaborative launched during the COVID-19 pandemic to strengthen infection control knowledge among frontline healthcare workers (HCWs). Project Firstline collaborates with multidisciplinary partners to deliver educational resources and promote engagement on infection control topics for the healthcare workforce. In 2021, Project Firstline expanded its focus to include community colleges, where many HCWs are trained. The initiative brought together faculty from varied healthcare professions in a summer intensive program designed to foster peer-to-peer learning and curriculum review while emphasizing the "why" behind infection control practices. CDC learned from participants about the need for flexible approaches, variation in the perceived value of teaching infection control topics across professions, and importance of employer engagement in student education. Ultimately, this effort emphasized the crucial role community colleges play in fostering a culture of infection control expertise across healthcare professions.

INTRODUCTION: An estimated 6,000 preventable cancer deaths - including from colorectal cancer (CRC) - occurred in rural America in 2022. Screening can prevent CRC or identify disease at earlier stages when it is more treatable. However, national estimates for CRC screening lag behind Healthy People 2030 objectives. In rural settings, barriers to screening are unique and persistent. METHODS: We performed a scoping review to describe the types and effectiveness of interventions to increase CRC screening in primarily rural settings. We included US-based studies published during January 2010 through May 2024. Interventions were categorized according to US Community Preventive Services Task Force-recommended strategies for multicomponent interventions. RESULTS: Of 508 unique publications identified, 36 met inclusion criteria. Most studies were multicomponent interventions (n = 34). Most studies were associated with an increase in CRC screening uptake. The most common intervention approaches were client reminders (eg, telephone reminders about screening) (n = 25), small media (eg, pamphlets) (n = 25), and reducing structural barriers to screening (eg, patient navigation) (n = 24). Over half (n = 21) of studies reported using a theory, framework, or research approach to inform intervention development, implementation, or evaluation. Six studies (17%) included cost evaluations. The studies included in this review represented less than half of all US states. CONCLUSION: This scoping review provides insight into CRC screening intervention implementation in rural settings. The limited geographic representation of the interventions included in our review may highlight an opportunity to improve implementation and dissemination of effective CRC screening interventions in rural settings to reduce CRC incidence and death.

BACKGROUND: Fungal meningitis outbreaks are rare and entail high mortality rates. Beginning May 2023, we investigated fungal meningitis caused by Fusarium solani species complex occurring in U.S. patients who received epidural anesthesia in Matamoros, Mexico. METHODS: Early epidemiological information suggested U.S. patients with suspected fungal meningitis had undergone mostly cosmetic procedures under epidural anesthesia performed in two Matamoros clinics. U.S. patients known to have received surgery at these clinics during January 1-May 13, 2023, (clinic closures date) were identified and notified by public health officials. Epidemiological and clinical data were used to update diagnostic and clinical guidance for outbreak response, including use of the experimental antifungal fosmanogepix. Whole genome sequencing was conducted on outbreak isolates. RESULTS: U.S. public health officials attempted to contact 233 potentially exposed U.S. residents who underwent surgeries, mostly cosmetic, in Mexico, reaching 170 (73%). Of those, 104 (61%) reported receiving epidural anesthesia and were therefore considered potentially at risk for fungal meningitis. At least 30/104 (29%) at-risk patients received a diagnostic lumbar puncture; 24 (23 women, 17 Hispanic or Latino) were diagnosed with fungal meningitis, and six were not. Twelve (50%) with fungal meningitis died. All cases involved epidural anesthesia administered by the same anesthesiologist in Mexico. Whole genome sequencing showed that patient isolates of Fusarium from the two implicated clinics in Matamoros, Mexico, were genetically closely related. CONCLUSIONS: Clinicians should maintain suspicion for fungal meningitis in patients with negative bacterial culture, viral culture and molecular testing with a history of epidural anesthesia for any reason.

BACKGROUND: Healthcare workers (HCWs) have been disproportionately affected by coronavirus disease 2019 (COVID-19). This study assessed HCW severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence trends and indicators' effectiveness for infection monitoring in the Philippine healthcare setting during 2021 and 2022-2023. METHODS: We obtained data on HCW demographics at 2 facilities, and COVID-19 symptoms recall and absenteeism at one facility. We collected and tested blood specimens with a SARS-CoV-2 spike and nucleocapsid protein-based serological assay. We calculated crude prevalence ratios (PRs) and 95% confidence intervals (CIs) for risk factors. RESULTS: A total of 253 HCWs were included. Seroprevalence of SARS-CoV-2 infection among HCWs was 34% from September to October 2021 and 92% from October 2022 to April 2023 during the Delta and the Omicron variant surges, respectively, at one facility. At the other facility, seroprevalence was 31% in September-October 2021. Of the 33 seropositive HCWs with questionnaire completed, 14 (42%) did not recall COVID-19-like symptoms in the past year. Serological evidence of SARS-CoV-2 infection was statistically more likely among HCWs who recalled COVID-19-like symptoms in the past year (PR, 2.69 [95% CI: 1.53-4.72]; P < .05). Of the seropositive HCWs, 7 (21%) had no hospital documentation of missed work. Of the 24 HCWs with a positive SARS-CoV-2 test, 12 (50%) tested because of symptoms, 4 (17%) tested after exposure, and 5 (21%) tested following employment screening. CONCLUSIONS: Self-reported symptoms may be used to track SARS-CoV-2 prior infections within resource-limited healthcare settings. Occupational health services should consider these findings when developing infection monitoring strategies among HCWs. Combining surveillance strategies may strengthen infection monitoring.

BACKGROUND: The performance of two piperonyl butoxide (PBO-synergist) insecticide-treated net (ITN) brands, PermaNet(®) 3.0 and Olyset(®) Plus, were evaluated under field conditions in two neighboring districts in Sierra Leone over 36 months to estimate median ITN survival, understand insecticidal efficacy, and identify factors influencing ITN durability. This assessment can help guide future PBO-synergist ITN procurement and replacement strategies. METHODS: This prospective study tracked 370 households and 652 campaign-distributed ITNs from 2020, followed annually for 36 months. Districts were purposefully selected based on shared characteristics. Household surveys were conducted, and 30 ITNs per round were tested for bioefficacy and chemical residue. Key indicators included ITN survival, 24-h mosquito mortality, and chemical content reduction compared to manufacturer targets doses. Cox proportional hazard models identified factors influencing ITN survival. RESULTS: Median useful life was 3.0 (95% CI 2.7-3.5) years for PermaNet(®) 3.0 ITNs in Bo and 2.2 (95% CI 2.0-2.4) years for Olyset(®) Plus ITNs in Moyamba. PermaNet(®) 3.0 ITNs displayed 13% 24-h mortality against pyrethroid-resistant mosquitoes on roof panels, with a 46% reduction in PBO content 34 months post-distribution. Olyset(®) Plus ITNs had 3% f24-hour mortality against pyrethroid-resistant mosquitoes, with a 77% reduction in PBO content. Several factors were associated with improved ITN survival, including cohort ITNs from Bo (adjusted hazard ratio [aHR] = 0.33, p < 0.001), households without children under five (CU5) (aHR = 0.64, p = 0.003), highest socio-economic status tertile (aHR = 0.63, p = 0.016), exposure to social and behaviour change (SBC) messages combined with positive net attitudes (aHR = 0.63, p = 0.008), lack of food storage in sleeping spaces (aHR = 0.56, p = 0.006), exclusive adult use of ITNs (aHR = 0.72, p = 0.048), net folding when not in use (aHR = 0.67, p = 0.015), and drying nets outside (aHR = 0.44, p = 0.008). CONCLUSION: ITNs in Bo outperformed those in Moyamba in both physical and insecticidal performance. However, ITN survival is highly context specific, and further investigation into field performance of new ITN types is necessary across diverse epidemiological settings.

The recognized burden of antimicrobial resistance (AR) is greatest in low- and middle-income countries (LMICs), but limitations in surveillance preclude accurate estimates of AR. We aimed to evaluate colonization in communities and hospitals across six LMICs for two clinically-important pathogens: extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE). Participants in hospitals and communities provided rectal swabs or stool samples for ESCrE and CRE identification. Isolates recovered from selective agars underwent confirmatory identification and antibiotic susceptibility testing (AST) using Vitek(®) 2, MALDI-TOF, and/or disc diffusion testing. ESCrE and CRE were defined based on established breakpoints of phenotypic resistance to third-generation cephalosporins and carbapenems, respectively, to calculate prevalence of colonization. Community prevalence estimates were weighted to account for sampling design differences. A total of 10,139 participants across the 6 countries provided samples; 63% were females with a median age of 35 years (range: 0-99). Colonization with ESCrE in hospitals was high in all sites (range 34-84%). In communities, ESCrE colonization ranged from 22 to 77%. Prevalence of CRE colonization in hospitals ranged from 7 to 36% and in communities ranged from < 1 to 14%. These findings reveal a high burden of AR colonization in LMICs in both communities and hospitals. Cost-effective strategies to reduce AR colonization burden are needed in LMICs.

BACKGROUND: In Africa, for people with HIV on a dolutegravir-based regimen with a viral load of more than 1000 copies per mL despite enhanced adherence counselling, the appropriate course of action is uncertain. We aimed to evaluate the predicted effects of alternative antiretroviral regimen switching options in this population, including consideration of cost-effectiveness. METHODS: We used an existing individual-based model to simulate risk and experience of HIV in 100 000 adults alive between 1989 and 2076. Using sampling of parameter values, we created 1000 setting-scenarios, reflecting the uncertainty in assumptions and a range of settings similar to those seen in eastern, central, southern, and western Africa. For each setting-scenario, we predicted the outcomes from the three alternative policies for people with sustained viral load non-suppression on a dolutegravir-containing regimen from 2026: a switch to a protease inhibitor-based regimen (switch policy), a switch to a protease inhibitor-based regimen only if HIV drug resistance testing beforehand shows integrase inhibitor resistance (resistance test policy), and no switch with no HIV drug resistance test (no switch policy). We considered predicted outcomes over 10-year and 50-year periods from 2026, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted. Ritonavir-boosted darunavir costs $210 per year, and dolutegravir less than $20. We assumed a cost of HIV drug resistance testing of $200 and considered variations around this. For comparing policies, we calculated net DALYs, which account for the health consequences of differences in costs and provide a measure of the impact of a policy on overall population burden of disease. FINDINGS: Across setting-scenarios, there was a mean of 14 480 deaths per year (95% CI 13 750-15 210) over 50 years with a mean annual discounted cost of $103·2 million (95·8-106·5) with the switch policy in the context of having scaled to a setting with an adult population of 10 million in 2024. Compared with the switch policy, the no switch policy was predicted to lead to an overall increased number of DALYs incurred (mean 4400 per year, 95% CI 3200-5500), although it resulted in the lowest overall cost, with a difference in annual discounted costs of $5·1 million (95% CI 4·6-5·6) lower than the switch policy. The resistance test policy led to a similar risk of death and DALYs to the switch policy at a lower overall cost (difference in annual discounted costs $3·5 million per year, 95% CI 3·1-3·9), leading to 6900 (95% CI 5500-8200) fewer net DALYs per year. Net DALYs for the resistance test versus no switch policies were similar (-1000 net DALYs, 95% CI 400 to -2300). The incremental cost-effectiveness ratio when comparing the resistance test policy with the no switch policy was $376 per DALY averted; the switch policy was dominated. INTERPRETATION: Introduction of HIV drug resistance testing for people with sustained viral load non-suppression on dolutegravir-based antiretroviral therapy is likely to be cost-effective. We suggest that exploratory planning for increased access and scale-up of high-quality, low-cost drug resistance testing for the region is undertaken. FUNDING: Gates Foundation as part of the HIV Modelling Consortium.

Shiga-toxin-producing E. coli (STEC) is a leading causing of bacterial foodborne and zoonotic illnesses in the USA. Whole-genome sequencing (WGS) is a powerful tool used in public health and microbiology for the detection, surveillance, and outbreak investigation of STEC. In this study, we applied three WGS-based subtyping methods, high quality single-nucleotide polymorphism (hqSNP) analysis, whole genome multi-locus sequence typing using chromosome-associated loci [wgMLST (chrom)], and core genome multi-locus sequence typing (cgMLST), to isolate sequences from 11 STEC outbreaks. For each outbreak, we evaluated the concordance between subtyping methods using pairwise genomic differences (number of SNPs or alleles), linear regression models, and tanglegrams. Pairwise genomic differences were highly concordant between methods for all but one outbreak, which was associated with international travel. The slopes of the regressions for hqSNP vs. allele differences were 0.432 (cgMLST) and 0.966 wgMLST (chrom); the slope was 1.914 for cgMLST vs. wgMLST (chrom) differences. Tanglegrams comprised of outbreak and sporadic sequences showed moderate clustering concordance between methods, where Baker's Gamma Indices (BGIs) ranged between 0.35 and 0.99 and Cophenetic Correlation Coefficients (CCCs) were ≥0.88 across all outbreaks. The K-means analysis using the Silhouette method showed the clear separation of outbreak groups with average silhouette widths ≥0.87 across all methods. This study validates the use of cgMLST for the national surveillance of STEC illness clusters using the PulseNet 2.0 system and demonstrates that hqSNP or wgMLST can be used for further resolution.

We polled infectious disease specialists about cryptococcal antigen screening for patients initiating HIV antiretroviral therapy. Of 215 respondents, 33% reported typically obtaining screening for patients with CD4 counts <200 cells/mm(3) and 63% for counts <100 CD4 cells/mm(3). Uncertainty about cryptococcal antigen screening benefits and recommendations suggests opportunities for education and increased screening.

INTRODUCTION: Increasing walking for transportation is a strategy to integrate physical activity into daily life. We examined reported environmental, access, and individual reasons for not walking to places near home among US adults, by sociodemographic characteristics and geographic location. METHODS: We used data from the 2022 SummerStyles survey on 3,967 US adults aged 18 years or older. We calculated prevalence of reporting 11 selected reasons for not walking to places within 10 minutes of home, overall and by sex, race or ethnicity, age, education, income, US census region, and metropolitan residence (an area with at least 1 urban area of ≥50,000 inhabitants) versus nonmetropolitan residence. We used Bonferroni-corrected pairwise comparisons and orthogonal polynomial contrasts (ordered groups) to compare prevalence by subgroup. RESULTS: Overall, 79.0% of respondents identified at least 1 reason for not walking to places near home (within 10 minutes). Commonly reported reasons were hot and humid conditions (36.0%), no places to walk within 10 minutes (24.9%), a preference for driving (22.1%), and inconvenience (21.5%). The reasons varied significantly across sociodemographic and geographic subgroups. The prevalence of reporting none of the listed reasons was higher among males than females, higher among non-Hispanic Black and non-Hispanic Asian adults than non-Hispanic White adults, and higher among adults from the Northeast versus the South. CONCLUSION: Eight of 10 US adults reported at least 1 environmental, access, or individual reason for not walking to places near home. Designing communities to make walking for transportation more accessible, convenient, and desirable may help address the leading reasons reported, which may support adults in adding more physical activity to their daily lives.

In April 2024, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was expanded by 1 new order, 1 new family, 6 new subfamilies, 34 new genera and 270 new species. One class, two orders and six species were renamed. Seven families and 12 genera were moved; ten species were renamed and moved; and nine species were abolished. This article presents the updated taxonomy of Negarnaviricota as currently accepted by the ICTV, providing an essential annual update on the classification of members of this phylum that deepen understandings of their evolution, and supports critical public health measures for virus identification and tracking.

Background: Antifungal therapeutic drug monitoring (TDM) is critical for individualized, precision treatment and prevention of fungal infections, but previous research has highlighted low TDM utilization rates, potentially reflecting long turnaround times, complex testing logistics, results interpretation, and cost. Objectives: To inform strategies to increase antifungal TDM use, we assessed TDM-related knowledge, attitudes, and practices among infectious disease (ID) physicians and pharmacists. Methods: We summarized findings from three structured focus group discussions (FGD)—two with six ID physicians each and one with six pharmacists—during March 2024. Open-ended discussions were held regarding awareness of and experiences with fungal infections and TDM, perceptions of antifungal TDM such as potential benefits, barriers, and challenges to conducting antifungal TDM, and information needs about antifungal TDM. We conducted qualitative transcription-based analysis to identify themes. Results: Six themes emerged from FGDs: (1) variable knowledge and experience with antifungal TDM among participants, (2) the importance of close collaboration between physicians and pharmacists during the TDM process, (3) the main motivators driving TDM use were improving treatment outcomes, preventing toxicity, and addressing pharmacokinetic variability, (4) the perception that antifungal resistance was unrelated to TDM, (5) key barriers were a lack of comprehensive clinical guidelines, long lab testing turnaround times, complex testing logistics, and high costs, and (6) a need for additional clinical data on TDM's impact on outcomes. Conclusions: Our findings can inform efforts to increase TDM use by addressing barriers to practice. Development of evidence-based clinical guidelines and improvements in testing infrastructure across practice settings could increase antifungal TDM use. Published 2025. This article is a U.S. Government work and is in the public domain in the USA.

OBJECTIVES: To evaluate the effect of high-dose isoniazid in patients with isoniazid-resistant TB by its bactericidal activity after 1 or more weeks of treatment. SUBJECTS AND METHODS: Using the rapid direct method of phenotypic drug susceptibility testing, we screened persons with positive sputum microscopy results and genotypic drug resistance for isoniazid resistance. Those with no growth at a critical concentration of 2.0 mg/L were invited to participate in a trial of high-dose isoniazid monotherapy lasting 6 days. After 3 days of no treatment, patients received isoniazid 15 mg/kg and were followed with serial quantitative sputum cultures from Days 0 to 6. RESULTS: We enrolled 15 patients after a median of 2 weeks standard first-line treatment. Their median bacillary count on Day 0 was 4.9 log(10) cfu/mL on solid agar, and the time to detection (TTD) was 200 h in liquid medium. Neither metric showed meaningful change in bacillary burden over 6 days, declining by a non-significant 0.08 log(10) cfu/mL/d on solid media and slowing TTD by 23 h. These effects did not differ by degree of isoniazid resistance or specific Inhibin Subunit Alpha (inhA) gene mutations. CONCLUSIONS: The utility of high-dose isoniazid against low-level isoniazid resistance beyond the first 2 weeks of chemotherapy should be reconsidered.

Chromoblastomycosis, a fungal neglected tropical disease, is acquired through traumatic inoculation and is clinically characterized by a chronic granulomatous infection of the skin and subcutaneous tissue. Fonsecaea pedrosoi is the most commonly reported etiologic agent globally. Itraconazole is considered first-line therapy, but successful treatment with terbinafine, voriconazole, and posaconazole has been reported. F. pedrosoi minimum inhibitory concentration (MIC) data are limited, and epidemiological cutoffs (ECVs) are lacking; such data are important to help monitor antifungal resistance trends and guide initial antifungal selection. Thus, we performed antifungal susceptibility testing (AFST) on F. pedrosoi isolates and determined the MIC distributions and ECVs. AFST on Fonsecaea pedrosoi isolates was conducted at six laboratories from October 2023 to June 2024. Species identification was previously confirmed by DNA sequence analysis. AFST was performed by CLSI M38 standard broth microdilution method for itraconazole, voriconazole, posaconazole, isavuconazole, ketoconazole, terbinafine, flucytosine, and amphotericin B. The ECVs were established using the iterative statistical method with ECOFFinder (version 2.1) following CLSI M57 guidelines. We analyzed MIC results from 148 Fonsecaea pedrosoi isolates. The calculated ECVs were itraconazole, 0.5 µg/mL; voriconazole, 0.5 µg/mL; posaconazole, 0.5 µg/mL; isavuconazole, 1 µg/mL; ketoconazole, bimodal, no ECV determined; terbinafine, 0.25 µg/mL; flucytosine, rejected; and amphotericin, 8 µg/mL. These Fonsecaea pedrosoi ECVs, obtained through a multicenter international effort, provide a baseline to better understand the in vitro antifungal susceptibility profile of this species and monitor resistance. Clinicians and researchers can use these values to detect non-wild-type isolates with reduced susceptibility, reevaluate therapeutic options, and investigate potential clinical resistance if treatment failure occurs.IMPORTANCEChromoblastomycosis is a neglected tropical disease caused by an environmental, dematiaceous fungus. This fungal disease is acquired after a break in the skin that allows the fungus to enter, leading to a chronic infection in the skin and subcutaneous tissue. It is difficult to treat and often requires years of antifungal treatment. Fonsecaea pedrosoi is the most reported causative agent globally. Limited antifungal susceptibility data exist for F. pedrosoi making interpreting minimum inhibitory concentration (MIC) results difficult. We performed antifungal susceptibility testing on 148 F. pedrosoi isolates to establish MIC distributions and epidemiologic cutoff values (ECVs) for eight antifungals, including those commonly used to treat chromoblastomycosis. The calculated ECVs for the commonly used antifungals itraconazole and terbinafine were 0.5 and 0.25 µg/mL, respectively. ECVs can be helpful in choosing potential treatment options for F. pedrosoi and monitoring antifungal resistance epidemiology.

Histoplasmosis is a fungal infection that primarily affects the lungs. The condition is caused by Histoplasma organisms, which are often found in soil contaminated with bird or bat droppings. On January 17, 2025, a Georgia infectious disease physician notified CDC of suspected histoplasmosis cases among 12 members of an extended family from households in Georgia, Texas, and Washington. The ill family members included six adults aged 42-49 years and six children aged 8-16 years. They had recently returned from Costa Rica, where they toured a cave linked to a previous histoplasmosis outbreak (1).

In the United States, Shiga toxin-producing Escherichia coli (STEC) outbreaks cause >265,000 infections and cost $280 million annually. We investigated REPEXH01, a persistent strain of STEC O157:H7 associated with multiple sources, including romaine lettuce and recreational water, that has caused multiple outbreaks since emerging in late 2015. By comparing the genomes of 729 REPEXH01 isolates with those of 2,027 other STEC O157:H7 isolates, we identified a highly conserved, single base pair deletion in espW that was strongly linked to REPEXH01 membership. The biological consequence of that deletion remains unclear; further studies are needed to elucidate its role in REPEXH01. Additional analyses revealed that REPEXH01 isolates belonged to Manning clade 8; possessed the toxins stx2a, stx2c, or both; were predicted to be resistant to several antimicrobial compounds; and possessed a diverse set of plasmids. Those factors underscore the need to continue monitoring REPEXH01 and clarify aspects contributing to its emergence and persistence.

Allergic fungal rhinosinusitis (AFRS) is a unique endotype of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite high recurrence rates and often more severe presenting signs compared with other subtypes of CRSwNP, research dedicated to AFRS has been lacking. Diagnostic criteria are outdated, the mechanistic relationship of AFRS to other associated diseases is unclear, and the pathophysiology of disease and risk factors for recurrence have not been well studied. In December 2023, a multidisciplinary group of rhinologists, otolaryngologists, pulmonologists, allergists, immunologists, scientists, and infectious disease experts met at the National Institute of Health to discuss unmet needs for future AFRS research and care, including patient management, diagnostic criteria, severity, pathophysiology, and related conditions. A summary of these clinical and associated research discussions is included below.

SARS-CoV-2 has undergone repeated and rapid evolution to circumvent host immunity. However, outside of prolonged infections in immunocompromised hosts, within-host positive selection has rarely been detected. Here we combine daily longitudinal sampling of individuals with replicate sequencing to increase the accuracy of and lower the threshold for variant calling. We sequenced 577 specimens from 105 individuals in a household cohort during the BA.1/BA.2 variant period. Individuals exhibited extremely low viral diversity, and we estimated a low within-host evolutionary rate. Within-host dynamics were dominated by genetic drift and purifying selection. Positive selection was rare but highly concentrated in spike. A Wright Fisher Approximate Bayesian Computational model identified positive selection at 14 loci with 7 in spike, including S:448 and S:339. This detectable immune-mediated selection is unusual in acute respiratory infections and may be caused by the relatively narrow antibody repertoire in individuals during the early Omicron phase of the SARS-CoV-2 pandemic.

Although lead poisoning can cause detrimental health effects, it is largely preventable. Common exposure sources include contaminated soil, water, and lead-based paint in homes built before the 1978 ban on residential lead-containing paint. In North Carolina, testing for lead is encouraged for all children at ages 1 and 2 years, and is required for children covered by Medicaid. In October 2023, routine pediatric blood lead testing and follow-up investigations conducted by the North Carolina Department of Health and Human Services identified four asymptomatic cases of lead poisoning associated with consumption of cinnamon-containing applesauce packaged in pouches. The Food and Drug Administration (FDA) identified lead in the cinnamon as the source of contamination; chromium was later also detected in the cinnamon. FDA alerted the public on October 28, and the distributor initiated a voluntary recall the following day. To estimate the impact of the event and characterize reported cases, CDC initiated a national call for cases (defined as a blood lead level [BLL] ≥3.5 μg/dL in a person of any age in ≤3 months after consuming a recalled cinnamon-containing applesauce product). During November 22, 2023-April 12, 2024, a total of 44 U.S. states, the District of Columbia, and Puerto Rico reported 566 cases (55% in children aged <2 years, including 20% that were temporally associated with symptoms). The median maximum venous BLL was 7.2 μg/dL (range = 3.5-39.3 μg/dL). The hundreds of children poisoned by this incident highlight the importance of preventing toxic metal contamination of food and promoting routine childhood blood lead testing and follow-up to identify lead exposure sources. Clinicians and public health practitioners should be aware of the potential for exposure to toxic metals from less common sources, including food.

This article assesses the effectiveness of IMC's PDH project by measuring changes in weight-for-age z-score (WAZ) among participating children both during and t 12 months post-implementation. WAZ was the anthropometric indicator of choice, as recommended by PDH guidance (Nutrition Working Group CORE, 2002). This article evaluates changes in nutritional status and seeks to understand caregiver perceptions around implementing promoted practices. Overall, 1,138 children were included in the study (621 Duguna Fango, 517 Damot Woyde), with an average age of 13.5 months (+- 4.8) at enrolment. Within three months of the intervention, 556 (49%) children met the WAZ =-2 criteria. Of the 1,035 children with 12 months of measurements, 472 (46%) achieved normal weight (WAZ =-2) by 12 months of follow-up. The prevalence of severely and moderately underweight children decreased from 36% and 64% (day 1) to 12% and 42% (month 12), respectively. Overall, these findings indicate that weight gain and improvement in WAZ were sustained throughout the 12-month period. Average overall weight gain across the 12 months was 2.55 +- 0.28 kg, with an average change in WAZ of 0.75 +- 0.36 standard deviation. At three months post-intervention, 99% of children met the 0.9 kg weight gain requirement as outlined in PDH protocols. Children who were more severely underweight at enrolment remained underweight by month 12 and had a lag in catch-up growth, compared to those who began the intervention moderately underweight. Although the severely underweight group experienced slightly higher gains over the 12-month period, these gains were often insufficient to reach a normal weight status. This suggests that severely underweight children may require specific, targeted interventions to address their needs.

This cross-sectional study investigates county-level sociodemographic characteristics of patients who use medical cannabis and their authorizing physicians in 7 US states. | eng

BACKGROUND: West Nile virus (WNV) is the most common cause of mosquito-borne disease in the continental USA, with an average of ~1200 severe, neuroinvasive cases reported annually from 2005 to 2021 (range 386-2873). Despite this burden, efforts to forecast WNV disease to inform public health measures to reduce disease incidence have had limited success. Here, we analyze forecasts submitted to the 2022 WNV Forecasting Challenge, a follow-up to the 2020 WNV Forecasting Challenge. METHODS: Forecasting teams submitted probabilistic forecasts of annual West Nile virus neuroinvasive disease (WNND) cases for each county in the continental USA for the 2022 WNV season. We assessed the skill of team-specific forecasts, baseline forecasts, and an ensemble created from team-specific forecasts. We then characterized the impact of model characteristics and county-specific contextual factors (e.g., population) on forecast skill. RESULTS: Ensemble forecasts for 2022 anticipated a season at or below median long-term WNND incidence for nearly all (> 99%) counties. More counties reported higher case numbers than anticipated by the ensemble forecast median, but national caseload (826) was well below the 10-year median (1386). Forecast skill was highest for the ensemble forecast, though the historical negative binomial baseline model and several team-submitted forecasts had similar forecast skill. Forecasts utilizing regression-based frameworks tended to have more skill than those that did not and models using climate, mosquito surveillance, demographic, or avian data had less skill than those that did not, potentially due to overfitting. County-contextual analysis showed strong relationships with the number of years that WNND had been reported and permutation entropy (historical variability). Evaluations based on weighted interval score and logarithmic scoring metrics produced similar results. CONCLUSIONS: The relative success of the ensemble forecast, the best forecast for 2022, suggests potential gains in community ability to forecast WNV, an improvement from the 2020 Challenge. Similar to the previous challenge, however, our results indicate that skill was still limited with general underprediction despite a relative low incidence year. Potential opportunities for improvement include refining mechanistic approaches, integrating additional data sources, and considering different approaches for areas with and without previous cases.

Virus taxonomy, comprising classification and nomenclature, is regulated by the International Committee on Taxonomy of Viruses (ICTV). Taxon names are standardized to facilitate recognition and communication, with defined suffixes for each rank (e.g., the names of orders, families, and genera end in -virales, -viridae, and -virus, respectively). However, until recently, a standard format for species names was lacking. In 2021, following extensive discussion and community consultation, the ICTV decided to adopt a standardized binomial (Linnaean) format for virus species names, consisting of the genus name followed by a "freeform" species epithet. Previously assigned virus species names that were non-compliant with the binomial format have been fully updated. In contrast to taxon names regulated by the ICTV, the names of viruses, or "common" names, such as yellow fever virus or human immunodeficiency virus, are not under the remit of the ICTV and have not been changed.

ARTICLE SUMMARY: Prescribed early physical activity and behavioral management did not improve outcomes in youth following acute concussion compared to the standard of care. OBJECTIVE: To determine the efficacy of early physical activity and behavioral management for acute concussion in pediatric patients. STUDY DESIGN: A multicenter, prospective, 2x2 factorial randomized controlled trial was conducted among patients aged 11-24 years who presented within 72 hours of injury. Participants were randomized into four groups based on early physical activity (or usual care) and behavioral management (or none). The early activity group was encouraged to meet step targets despite symptoms. The primary outcomes were post-concussion symptom severity and quality of life at 14 days post-enrollment. RESULTS: A total of 239 participants were randomized, and 210 completed all study procedures. The early activity group demonstrated higher daily step counts compared with the usual care group. However, no significant differences were observed in post-concussion symptom severity or quality of life at 14 days between groups. The early activity group experienced higher daily post-concussion symptom severity during the first 7 days and took longer to recover compared with the usual care group. Behavioral management showed no effect on outcomes. CONCLUSIONS: Early prescribed physical activity and behavioral management did not improve post-concussion outcomes in the first two weeks following injury. Early prescribed activity despite symptoms was associated with delayed symptom resolution. Clinical trial registration ClinicalTrials.gov NCT03869970.