In the healthcare landscape, diseases such as cancer and HIV/AIDS have benefited from the patient's perspective. For fungal diseases, the patient voice remains absent in critical areas such as policy formulation, funding decisions, and research priorities. Patients affected by fungal disease, along with their caregivers and advocacy groups, possess invaluable insights into the challenges and unmet needs they face. By elevating their voices and experiences, policymakers, funding agencies, and researchers can gain a more comprehensive understanding of the multifaceted nature of fungal disease and the urgency of addressing them. This paper addresses the pressing need for a coordinated effort to elevate the patient voice in advocating for improved policies, increased funding, and enhanced research initiatives regarding fungal disease.

Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host's immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately 80% of fungal diseases [D. W. Denning, Lancet Infect Dis, 24:e428-e438, 2024, https://doi.org/10.1016/S1473-3099(23)00692-8], tend to follow a predictive pattern, while those by occasional opportunists are more variable. For this reason, it is recommended that diseases caused by primary pathogens and the common opportunists are named after the etiologic agent, for example, histoplasmosis and aspergillosis, while this should not be done for occasional opportunists that should be named as [causative fungus] [clinical syndrome], for example, Alternaria alternata cutaneous infection. The addition of a descriptor that identifies the location or clinical type of infection is required, as the general name alone may cover widely different clinical syndromes, for example, "rhinocerebral mucormycosis." A list of major recommended human and animal disease entities (nomenclature) is provided in alignment with their causative agents. Fungal disease names may encompass several genera of etiologic agents, consequently being less susceptible to taxonomic changes of the causative species, for example, mucormycosis covers numerous mucormycetous molds.

During use of sodium hypochlorite bleach, gas-phase hypochlorous acid (HOCl) and chlorine (Cl2) are released, which can react with organic compounds present in indoor air. Reactivity between HOCl/Cl2 and limonene, a common constituent of indoor air, has been observed. The purpose of this study was to characterize the chemical species generated from gas-phase reactions between HOCl/Cl2 and limonene. Gas-phase reactions were prepared in Teflon chambers housing HOCl, Cl2, and limonene. The resulting chemical products were analyzed using gas-phase preconcentration, followed by gas chromatography and high-resolution mass spectrometry. Several chlorinated products were detected, including limonene species containing one, two, and three chlorines and limonene chlorohydrin. Product concentrations and yields were estimated for the most abundant products, and greater than 80% of transformed limonene was represented in the detected products. Temporal sampling of the reactions allowed time courses to be plotted for limonene decay and chlorinated limonene product generation under different conditions, including the treatments of HOCl/Cl2, Cl2 only, high vs low relative humidity, and +/- ozone. These experiments add product speciation, yield estimates, and an understanding of environmental factors affecting product formation to previous studies, further highlighting the chemical transformations initiated by sodium hypochlorite bleach in indoor air.

BACKGROUND: Recently, increasing focus on patient input into research and healthcare improvements has fostered expanded patient-centered advocacy efforts. This first pan-fungal disease summit, part of the MYCology Advocacy, Research, & Education effort, brought together patients, caregivers, and mycology experts to better document patient experiences with invasive fungal disease (IFD) and establish priorities for mycology education, advocacy, and research. METHODS: Patients who had suffered from IFD, their caregivers, clinicians, industry representatives, government officials, and patient advocacy professionals were invited. Patients and caregivers shared their stories and struggles with IFD. Breakout sessions separated mycology experts from patients and caregivers for further discussions to identify commonalities and perceived gaps and to formulate recommendations. The 2 groups then reconvened to develop consensus recommendations. RESULTS: IFD patients and their caregivers shared experiences reflecting the typically lengthy prediagnosis, acute treatment, long-term treatment, and posttreatment recovery stages of IFD. They reported substantial physical, psychological, and financial burdens associated with the IFD experience, particularly related to delayed diagnoses. They reaffirmed a need for coordinated patient-centered education, peer support, and advocacy to document the burden of serious fungal infections. Mycology experts discussed strategies to address gaps in the mycology field, such as insufficient training, inadequate workforce support, and a need to partner more with patient groups. CONCLUSIONS: A summit involving patients with IFD, family caregivers, and mycology experts identified a substantial nonclinical burden of disease associated with IFD. Patients and mycology experts prioritized several goals for education, advocacy, and research to raise awareness of IFD and improve outcomes.

IMPORTANCE: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown. OBJECTIVE: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool. DESIGN, SETTING, AND PARTICIPANTS: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks' gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024. EXPOSURE: Opioid treatment for NOWS and the ESC care approach. MAIN OUTCOMES AND MEASURES: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics. RESULTS: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001). CONCLUSION AND RELEVANCE: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04057820.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) comprises the first 27 N-terminal amino acid residues of E2. It is classically seen as the most heterogeneous region of the HCV genome. In this study, we assessed HVR1 evolution by using ultradeep pyrosequencing for a cohort of treatment-naive, chronically infected patients over a short, 16-week period. Organization of the sequence set into connected components that represented single nucleotide substitution events revealed a network dominated by highly connected, centrally positioned master sequences. HVR1 phenotypes were observed to be under strong purifying (stationary) and strong positive (antigenic drift) selection pressures, which were coincident with advancing patient age and cirrhosis of the liver. It followed that stationary viromes were dominated by a single HVR1 variant surrounded by minor variants comprised from conservative single amino acid substitution events. We present evidence to suggest that neutralization antibody efficacy was diminished for stationary-virome HVR1 variants. Our results identify the HVR1 network structure during chronic infection as the preferential dominance of a single variant within a narrow sequence space. IMPORTANCE: HCV infection is often asymptomatic, and chronic infection is generally well established in advance of initial diagnosis and subsequent treatment. HVR1 can undergo rapid sequence evolution during acute infection, and the variant pool is typically seen to diverge away from ancestral sequences as infection progresses from the acute to the chronic phase. In this report, we describe HVR1 viromes in chronically infected patients that are defined by a dominant epitope located centrally within a narrow variant pool. Our findings suggest that weakened humoral immune activity, as a consequence of persistent chronic infection, allows for the acquisition and maintenance of host-specific adaptive mutations at HVR1 that reflect virus fitness.

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way.

OBJECTIVES: To produce and evaluate a novel virtual reality (VR) training for public health emergency responders. DESIGN: Following a VR training designed to test key public health emergency responder competencies, a prospective cohort of participants completed surveys rating self-assessed skill levels and perceptions of training methods. SETTING: The VR training sessions were administered in a quiet room at the US Centers for Disease Control and Prevention (CDC), Atlanta, Georgia. PARTICIPANTS: All participants volunteered from a list of CDC emergency international surge responders. OUTCOME MEASURES: Perceived impact of the training on responder skills was self-reported via a Likert 5-point scale questionnaire. Assessments were modelled according to the Expanded Technology Acceptance Model measuring participant perceived usefulness of and intention to use the new technology. Inductive coding of qualitative feedback resulted in the identification of central themes. RESULTS: From November 2019 to January 2020, 61 participants were enrolled. Most (98%) participants self-rated above neutral for all skills (mean 4.3; range 1.21-5.00). Regression modelling showed that the perceived ease of use of the VR and ability to produce demonstrable results as likely drivers of further use. Participants agreed that others would benefit from the training (97%), it was representative of actual response scenarios (72%) and they would use lessons learnt in the field (71%). Open-response feedback highlighted feeling being immersed in the training and its utility for public health responders. CONCLUSIONS: At a time when a trained emergency public health workforce is a critical need, VR may be an option for addressing this gap. Participants' impressions and feedback, in the setting of their high skill level and experience, highlighted the utility and benefit of using VR to deliver training. Further research is needed to determine skill acquisition through VR training among a pool of future responders with limited to no response experience.

Pressing challenges in the treatment of invasive fungal infections (IFI) include emerging and rare pathogens, resistant/refractory infections, and antifungal armamentarium limited by toxicity, drug-drug interactions, and lack of oral formulations. Development of new antifungal drugs is hampered by the limitations of the available diagnostics; clinical trial endpoints; prolonged trial duration; difficulties in patient recruitment, including subpopulations (e.g., pediatrics); and heterogeneity of the IFIs. On August 4, 2020, the U.S. Food and Drug Administration convened a workshop that included IFI experts from academia, industry, and other government agencies to discuss the IFI landscape, unmet need, and potential strategies to facilitate the development of antifungal drugs for treatment and prophylaxis. This paper summarizes the key topics presented and discussed during the workshop, such as incentives and research support for drug developers, nonclinical development, clinical trial design challenges, lessons learned from industry, and potential collaborations to facilitate antifungal drug development.

Peracetic acid is a disinfection agent used in medical and food processing facilities, and occupational exposures have been documented. To facilitate characterization of daily occupational exposures, the current work describes the development of a personal sampling technique to quantify the peracetic acid concentration in air samples. Peracetic acid atmospheres were generated in 100 L Teflon chambers, and samples were collected on 350 mg XAD-7 solid sorbent tubes for 4 h at a flow rate of 250 mL/min using a personal sampling pump. Indirect measurement of peracetic acid was achieved by desorption from the sorbent and subsequent treatment with cyclohexene to initiate an epoxidation reaction, formally known as the Prilezhaev reaction. The epoxidation product, cyclohexene oxide, was quantified by gas chromatography-mass spectrometry. The reaction enabled quantification of peracetic acid with high specificity over the common co-contaminants hydrogen peroxide and acetic acid, which were introduced in 10-fold and 100-fold excess to challenge the reaction. The technique also demonstrated an overall estimate of bias and precision of 11 and 8%, respectively, and a limit of detection of 60 ppbv was estimated. Preliminary storage experiments indicate that unreacted peracetic acid is stable on the sorbent tubes for 72 h when stored at -20 °C following collection. Overall, the specificity of the reaction and capability to sample for longer time periods than current methods, in addition to the use of safer personal sampling materials, demonstrate the utility of this technique for peracetic acid measurement in air. © 2022 Elsevier Inc.. All rights reserved.

Mammalian orthoreovirus (MRV) infects many mammalian species including humans, bats, and domestic animals. To determine the prevalence of MRV in bats in the United States, we screened more than 900 bats of different species collected during 2015 to 2019 by a real-time RT-PCR assay; 4.4% bats tested MRV-positive and 13 MRVs were isolated. Sequence and phylogenetic analysis revealed that these isolates belonged to four different strains/genotypes of viruses in serotypes 1 or 2, which contain genes similar to those of MRVs detected in humans, bats, bovine, and deer. Further characterization showed that these four MRV strains replicated efficiently on human, canine, monkey, ferret and swine cell lines. The 40/Bat/USA/2018 strain belonging to the serotype 1 demonstrated the ability to infect and transmit in pigs without prior adaptation. Taken together, this is evidence for different genotypes and serotypes of MRVs circulating in U.S. bats, which can be a mixing vessel of MRVs that may spread to other species, including humans, resulting in cross-species infections. This article is protected by copyright. All rights reserved.

This article shares what was learned from the feasibility assessment of a nurse-led school-based active surveillance (SBAS) pilot to track chronic absenteeism using myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as an exemplar. This pilot encompassed a 3-year period with training and feedback from school nurses (SNs) on data collection and ME/CFS. SNs found that the SBAS process helped them effectively identifying undiagnosed conditions. The assessment revealed the importance of focusing outreach efforts and establishing relationships with the school leadership in developing health policies and programs in the school setting. The pilot data were used to develop a manual to guide SNs for the SBAS process. This can be viewed as a model for SNs in establishing a surveillance to identify and track conditions like ME/CFS. With overlapping symptoms of Long COVID to ME/CFS, this assessment may provide insights for additional efforts to understand the impact of Long COVID on students' education.

Combination antifungal therapy is widely used but not well understood. We analyzed the spectrophotometric readings from a multicenter study conducted by the New York State Department of Health to further characterize the in vitro interactions of the major classes of antifungal agents against Candida spp. Loewe additivity-based fractional inhibitory concentration index (FICi) analysis and Bliss independence-based response surface (BIRS) analysis were used to analyze two-drug inter- and intraclass combinations of triazoles (AZO) (voriconazole, posaconazole), echinocandins (ECH) (caspofungin, micafungin, anidulafungin), and a polyene (amphotericin B) against Candida albicans, C. parapsilosis, and C. glabrata. Although mean FIC indices did not differ statistically significantly from the additivity range of 0.5−4, indicating no significant pharmacodynamic interactions for all of the strain−combinations tested, BIRS analysis showed that significant pharmacodynamic interactions with the sum of percentages of interactions determined with this analysis were strongly associated with the FIC indices (Χ2 646, p < 0.0001). Using a narrower additivity range of 1−2 FIC index analysis, statistically significant pharmacodynamic interactions were also found with FICi and were in agreement with those found with BIRS analysis. All ECH+AB combinations were found to be synergistic against all Candida strains except C. glabrata. For the AZO+AB combinations, synergy was found mostly with the POS+AB combination. All AZO+ECH combinations except POS+CAS were synergistic against all Candida strains although with variable magnitude; significant antagonism was found for the POS+MIF combination against C. albicans. The AZO+AZO combination was additive for all strains except for a C. parapsilosis strain for which antagonism was also observed. The ECH+ECH combinations were synergistic for all Candida strains except C. glabrata for which they were additive; no antagonism was found.

OBJECTIVES: How Right Now (HRN) is an evidence-based, culturally responsive communication campaign developed to facilitate coping and resilience among US groups disproportionately affected by the COVID-19 pandemic. To inform the development of this campaign, we examined patterns in emotional health, stress, and coping strategies among HRN's audiences, focusing on differences among racial and ethnic groups. METHODS: We used a national probability panel, AmeriSpeak, to collect survey data from HRN's priority audience members in English and Spanish at 2 time points (May 2020 and May 2021). We conducted statistical testing to examine differences between time points for each subgroup (Hispanic, non-Hispanic Black, and non-Hispanic White) and differences among subgroups at each time point. RESULTS: We found disparities in COVID-19-related mental health challenges and differences in coping strategies. Non-Hispanic Black respondents were more likely than non-Hispanic White respondents to report challenges related to the social determinants of health, such as affording food and housing (26.4% vs 9.4% in May 2020) and experiencing personal financial loss (46.6% vs 29.2% in May 2020). In May 2021, 30.6% of Hispanic respondents reported being unable to meet basic food or housing needs versus 8.2% of non-Hispanic White respondents, and 51.6% reported personal financial loss versus 26.5% of non-Hispanic White respondents. CONCLUSIONS: Our study further illuminates what is needed to build emotional well-being pathways for people who historically have been economically and socially marginalized. Our findings underscore the need for public health interventions to provide culturally responsive mental health support to populations disproportionately affected by COVID-19 during the pandemic and into the future, with a focus on racial and ethnic disparities.

BACKGROUND: Streptococcus pneumoniae infections cause morbidity and mortality worldwide. A rapid, simple diagnostic method could reduce the time needed to introduce definitive therapy potentially improving patient outcomes. METHODS: We introduce two new methods for diagnosing S. pneumoniae infections by measuring the presence of newly activated, pathogen-specific, circulating Antibody Secreting Cells (ASC). First, ASC were detected by ELISpot assays that measure cells secreting antibodies specific for signature antigens. Second, the antibodies secreted by isolated ASC were collected in vitro in a novel matrix, MENSA (media enriched with newly synthesized antibodies) and antibodies against S. pneumoniae antigens were measured using Luminex immunoassays. Each assay was evaluated using blood from S. pneumoniae and non-S. pneumoniae-infected adult patients. RESULTS: We enrolled 23 patients with culture-confirmed S. pneumoniae infections and 24 controls consisting of 12 non-S. pneumoniae infections, 10 healthy donors and two colonized with S. pneumoniae. By ELISpot assays, twenty-one of 23 infected patients were positive, and all 24 controls were negative. Using MENSA samples, four of five S. pneumoniae-infected patients were positive by Luminex immunoassays while all five non-S. pneumoniae-infected patients were negative. CONCLUSION: Specific antibodies produced by activated ASC may provide a simple diagnostic for ongoing S. pneumoniae infections. This method has the potential to diagnose acute bacterial infections.

In areas where Histoplasma is endemic in the environment, occupations involving activities exposing workers to soil that contains bird or bat droppings may pose a risk for histoplasmosis. Occupational exposures are frequently implicated in histoplasmosis outbreaks. In this paper, we review the literature on occupationally acquired histoplasmosis. We describe the epidemiology, occupational risk factors, and prevention measures according to the hierarchy of controls.

Fungal infections are a rising threat to our immunocompromised patient population, as well as other nonimmunocompromised patients with various medical conditions. However, little progress has been made in the past decade to improve fungal diagnostics. To jointly address this diagnostic challenge, the Fungal Diagnostics Laboratory Consortium (FDLC) was recently created. The FDLC consists of 26 laboratories from the United States and Canada that routinely provide fungal diagnostic services for patient care. A survey of fungal diagnostic capacity among the 26 members of the FDLC was recently completed, identifying the following diagnostic gaps: lack of molecular detection of mucormycosis; lack of an optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of Pneumocystis pneumonia, aspergillosis, candidemia, and endemic mycoses; lack of a standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues; lack of robust databases to enhance mold identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; suboptimal diagnostic approaches for mold blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures for cystic fibrosis patients; inadequate capacity for fungal point-of-care testing to detect and identify new, emerging or underrecognized, rare, or uncommon fungal pathogens; and performance of antifungal susceptibility testing. In this commentary, the FDLC delineates the most pressing unmet diagnostic needs and provides expert opinion on how to fulfill them. Most importantly, the FDLC provides a robust laboratory network to tackle these diagnostic gaps and ultimately to improve and enhance the clinical laboratory's capability to rapidly and accurately diagnose fungal infections.

IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. OBJECTIVE: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. EXPOSURES: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). MAIN OUTCOMES AND MEASURES: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. RESULTS: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). CONCLUSIONS AND RELEVANCE: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

Mammalian orthoreovirus (MRV) infects multiple mammalian species including humans. A United States Midwest swine farm with approximately one thousand 3-month-old pigs experienced an event, in which more than 300 pigs showed neurological signs, like "down and peddling", with approximately 40% mortality. A novel MRV was isolated from the diseased pigs. Sequence and phylogenetic analysis revealed that the isolate was a reassortant virus containing viral gene segments from three MRV serotypes that infect human, bovine and swine. The M2 and S1 segment of the isolate showed 94% and 92% nucleotide similarity to the M2 of the MRV2 D5/Jones and the S1 of the MRV1 C/bovine/Indiana/MRV00304/2014, respectively; the remaining eight segments displayed 93%-94% nucleotide similarity to those of the MRV3 FS-03/Porcine/USA/2014. Pig studies showed that both MRV-infected and native contact pigs displayed fever, diarrhea and nasal discharge. MRV RNA was detected in different intestinal locations of both infected and contact pigs, indicating that the MRV isolate is pathogenic and transmissible in pigs. Seroconversion was also observed in experimentally infected pigs. A prevalence study on more than 180 swine serum samples collected from two states without disease revealed 40-52% positive to MRV. All results warrant the necessity to monitor MRV epidemiology and reassortment as the MRV could be an important pathogen for the swine industry and a novel MRV might emerge to threaten animal and public health.

Reports of bacterial sexually transmitted infections are at the highest levels ever reported in the United States, and state and local budgetary issues are placing specialized sexually transmitted disease (STD) care at risk. This study collected information from 4138 patients seeking care at 26 STD clinics in large metropolitan areas across the United States with high levels of reported STDs to determine patient needs and clinic capabilities. Surveys were provided to patients attending these STD clinics to assess their demographic information as well as reasons for coming to the clinic and surveys were also provided to clinic administrators to determine their operational capacities and services provided by the clinic. For this initial study, we conducted univariate analyses to report all data collected from these surveys. Patients attending STD clinics across the country indicated that they do so because of the relative ease of getting an appointment; including walk-in and same-day appointments as well as the welcoming environment and expertise of the staff at the clinic. Additionally, STD clinics provide specialized care to patients; including HIV testing and counseling as well as on-site, injectable medications for the treatment of gonorrhea and syphilis in an environment that helps to reduce the role of stigma in seeking this kind of care. Sexually transmitted disease clinics continue to play an important role in helping to curb the rising epidemic of sexually transmitted diseases.

Assuring availability of services for patients with lymphedema is required for countries to be validated as having achieved elimination of lymphatic filariasis (LF). A direct inspection protocol (DIP) tool, designed to measure the readiness to provide quality lymphedema management services, has recently been developed. The DIP tool includes 14 indicators across six quality themes: trained staff, case management and education materials, water infrastructure, medications and commodities, patient tracking system, and staff knowledge. We evaluated the use of the tool in Vietnam, where data were needed to inform validation efforts. To apply the tool in Vietnam, we compiled a list of 219 commune health stations (CHS) with known lymphedema patients and conducted a cross-sectional survey in 32 CHS; including 24 in Red River Delta region, 2 in the North Central region, and 6 in the South Central Coast region. The mean facility score, calculated by assigning 1 point per indicator, was 8.8 of 14 points (63%, range 4[29%]-13[93%]). Percentage of surveyed facilities with staff trained in last two years was 0%; availability of lymphedema management guidelines (56%); availability of information, education, and communication materials (16%); reliable improved water infrastructure (94%); availability of antiseptics (81%), antifungals (44%), analgesics or anti-inflammatories (97%), antibiotics (94%); supplies for lymphedema and acute attack management (100%); lymphedema patients recorded in last 12 months (9%); staff knowledge about lymphedema signs/symptoms (63%), lymphedema management strategies (72%), signs/symptoms of acute attacks (81%), and acute attack management strategies (75%). The tool allowed standardized assessment of readiness to provide quality services. Lack of trained health staff, limited patient tracking, and depletion of education materials were identified as challenges and addressed by the national program. Survey data were included in the validation dossier, providing evidence necessary for WHO to validate Vietnam as having eliminated lymphatic filariasis in 2018.

Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC(50) and MIC(90)) values in >400 C. auris isolates were 0.5 μg/mL and 1.0 μg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections.

BACKGROUND: HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. METHODS: We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. FINDINGS: We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. INTERPRETATION: Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores >/=2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).

Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, Setting, and Participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main Outcomes and Measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). Conclusions and Relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.

The Centers for Disease Control and Prevention (CDC) Global Rapid Response Team (GRRT) was launched in June 2015 to strengthen the capacity for international response and to provide an agency-wide roster of qualified surge-staff members who can deploy on short notice and for long durations. To assess GRRT performance and inform future needs for CDC and partners using rapid response teams, we analyzed trends and characteristics of GRRT responses and responders, for deployments of at least 1 day during October 1, 2018, through March 31, 2019. One hundred twenty deployments occurred during the study period, corresponding to 2645 person-days. The median deployment duration was 19 days (interquartile range, 5-30 days). Most deployments were related to emergency response (n = 2367 person-days, 90%); outbreaks of disease accounted for almost all deployment time (n = 2419 person-days, 99%). Most deployments were to Africa (n = 1417 person-days, 54%), and epidemiologists were the most commonly deployed technical advisors (n = 1217 person-days, 46%). This case study provides useful information for assessing program performance, prioritizing resource allocation, informing future needs, and sharing lessons learned with other programs managing rapid response teams. GRRT has an important role in advancing the global health security agenda and should continuously be assessed and adjusted to new needs.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

OBJECTIVE: To investigate whether rates of self-reported Woman's Condom (WC) clinical failure and semen exposure from a functionality study are comparable to results from a contraceptive efficacy substudy. STUDY DESIGN: We structured our comparative analysis to assess whether functionality studies might credibly supplant contraceptive efficacy studies when evaluating new female condom products. Couples not at risk of pregnancy in the functionality (breakage/slippage/invagination/penile misdirection) study and women in the contraceptive efficacy study completed condom self-reports and collected pre and postcoital vaginal samples for up to four uses of the WC. Both studies used nearly identical self-report questions and the same self-sampling procedures and laboratory for prostatic specific antigen (PSA), a well-studied semen biomarker. We compared condom failure and semen exposure proportions using generalized estimating equations methods accounting for within-couple correlation. RESULTS: Ninety-five (95) efficacy substudy participants used 334 WC and 408 functionality participants used 1572 WC. Based on self-report, 19.2% WC (64 condoms) clinically failed in the efficacy substudy compared to 12.3% WC (194 condoms) in the functionality study (p-value=0.030). Of the 207 WC efficacy uses with evaluable post-coital PSA levels, 14.5% (30 uses) resulted in semen exposure compared to 14.2% (184 uses) of the 1293 evaluable WC functionality study uses. CONCLUSIONS: When evaluating the ability of an experimental condom to prevent semen exposure, the rate of clinical condom failure reported by participants risking pregnancy in an efficacy substudy was significantly higher than the rate reported by participants not risking pregnancy in a functionality study. The rate of semen exposure, assessed by an objective biomarker was nearly identical for the two studies. IMPLICATIONS: Our results suggest that an objective marker of semen exposure in functionality studies could provide a reasonable alternative to contraceptive efficacy studies in evaluating risk of unintended pregnancy and inferring protection from sexually transmitted infection than condom failure rates based on self-report.

BACKGROUND: The World Health Organization (WHO) in collaboration with partners is developing a toolkit of resources to guide lymphatic filariasis (LF) morbidity management and disability prevention (MMDP) implementation and evaluation. Direct health facility inspection is the preferred method for documenting the readiness of a country programme to provide quality lymphoedema management services, one of the three MMDP criteria used to demonstrate the elimination of LF as a public health problem. METHODOLOGY/PRINCIPAL FINDINGS: As component of tool development, a Delphi consultation was implemented to gain consensus on six proposed domains and fourteen proposed tracer indicators to measure national programme readiness to provide quality health facility-based lymphoedema management services. A seven-point Likert-type scale was used to rank the importance of proposed domains and tracer indicators. Consensus for inclusion of the indicator was defined a priori as 70% or more of respondents ranking the proposed indicator in the top three tiers (5-7). Purposive sampling was used to select 43 representative experts including country representatives, programme implementers, and technical experts. A 55.8% response rate (n = 24) was achieved for the survey. Analysis of the responses demonstrated that consensus for inclusion had been reached for all proposed domains including trained staff (mean = 6.9, standard deviation (SD) = 0.34), case management and education materials (mean = 6.1, SD = 0.65), water infrastructure (mean = 6.3, SD = 0.81), medications and commodities (mean = 6.3, SD = 0.69), patient tracking system (mean = 6.3, SD = 0.85), and staff knowledge (mean = 6.5, SD = 0.66). SIGNIFICANCE: The Delphi consultation provided an efficient and structured method for gaining consensus among lymphatic filariasis experts around key lymphoedema management quality indicators. The results from this analysis were used to refine the indicators included within the direct inspection protocol tool to ensure its ability to assess health facility readiness to provide quality lymphoedema management services.