Early detection of emerging SARS-CoV-2 variants is critical to guiding rapid risk assessments, providing clear and timely communication messages, and coordinating public health action. CDC identifies and monitors novel SARS-CoV-2 variants through diverse surveillance approaches, including genomic, wastewater, traveler-based, and digital public health surveillance (e.g., global data repositories, news, and social media). The SARS-CoV-2 variant BA.2.86 was first sequenced in Israel and reported on August 13, 2023. The first U.S. COVID-19 case caused by this variant was reported on August 17, 2023, after a patient received testing for SARS-CoV-2 at a health care facility on August 3. In the following month, eight additional U.S. states detected BA.2.86 across various surveillance systems, including specimens from health care settings, wastewater surveillance, and traveler-based genomic surveillance. As of October 23, 2023, sequences have been reported from at least 32 countries. Continued variant tracking and further evidence are needed to evaluate the full public health impact of BA.2.86. Timely genomic sequence submissions to global public databases aided early detection of BA.2.86 despite the decline in the number of specimens being sequenced during the past year. This report describes how multicomponent surveillance and genomic sequencing were used in real time to track the emergence and transmission of the BA.2.86 variant. This surveillance approach provides valuable information regarding implementing and sustaining comprehensive surveillance not only for novel SARS-CoV-2 variants but also for future pathogen threats.

Coccidioidomycosis, histoplasmosis, and blastomycosis are underrecognized and frequently misdiagnosed fungal infections that can clinically resemble bacterial and viral community-acquired pneumonia (CAP). This guidance is intended to help clinicians in outpatient settings test for these fungal diseases in patients with CAP to reduce misdiagnoses, unnecessary antibacterial use, and poor outcomes.

Fungal infections can cause severe disease and death and impose a substantial economic burden on healthcare systems. Public health research requires a multidisciplinary approach and is essential to help save lives and prevent disability from fungal diseases. In this manuscript, we outline the main public health research priorities for fungal diseases, including the measurement of the fungal disease burden and distribution and the need for improved diagnostics, therapeutics, and vaccines. Characterizing the public health, economic, health system, and individual burden caused by fungal diseases can provide critical insights to promote better prevention and treatment. The development and validation of fungal diagnostic tests that are rapid, accurate, and cost-effective can improve testing practices. Understanding best practices for antifungal prophylaxis can optimize prevention in at-risk populations, while research on antifungal resistance can improve patient outcomes. Investment in vaccines may eliminate certain fungal diseases or lower incidence and mortality. Public health research priorities and approaches may vary by fungal pathogen.

Drowned organ donors can be exposed to environmental molds through the aspiration of water; transplantation of exposed organs can cause invasive mold infections in recipients. We describe 4 rapidly fatal cases of potentially donor-derived invasive mold infections in the United States, highlighting the importance of maintaining clinical suspicion for these infections in transplant recipients.

Fungal respiratory illnesses caused by endemic mycoses can be nonspecific and are often mistaken for viral or bacterial infections. We performed fungal testing on serum specimens from patients hospitalized with acute respiratory illness (ARI) to assess the possible role of endemic fungi as etiologic agents. Patients hospitalized with ARI at a Veterans Affairs hospital in Houston, Texas, during November 2016-August 2017 were enrolled. Epidemiologic and clinical data, nasopharyngeal and oropharyngeal samples for viral testing (PCR), and serum specimens were collected at admission. We retrospectively tested remnant sera from a subset of patients with negative initial viral testing using immunoassays for the detection of Coccidioides and Histoplasma antibodies (Ab) and Cryptococcus, Aspergillus, and Histoplasma antigens (Ag). Of 224 patient serum specimens tested, 49 (22%) had positive results for fungal pathogens, including 30 (13%) by Coccidioides immunodiagnostic assays, 19 (8%) by Histoplasma immunodiagnostic assays, 2 (1%) by Aspergillus Ag, and none by Cryptococcus Ag testing. A high proportion of veterans hospitalized with ARI had positive serological results for fungal pathogens, primarily endemic mycoses, which cause fungal pneumonia. The high proportion of Coccidioides positivity is unexpected as this fungus is not thought to be common in southeastern Texas or metropolitan Houston, though is known to be endemic in southwestern Texas. Although serological testing suffers from low specificity, these results suggest that these fungi may be more common causes of ARI in southeast Texas than commonly appreciated and more increased clinical evaluation may be warranted.

Fungal diseases are frequently coded as "unspecified mycoses" in data sets used to estimate disease burden. In a large administrative database, 50.9% of unspecified mycosis hospitalizations during 2019-2021 had positive fungal laboratory testing, most commonly Candida (79.1%), highlighting a potential need for improved coding practices and greater fungal laboratory testing.

OBJECTIVE: Indoor mold after flooding poses health risks including rare but serious invasive mold infections. The purpose of this study was to evaluate use of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes for mold infection and mold exposure in Houston, Texas during the year before and the year after Hurricane Harvey. METHODS: This study used data from MarketScan, a large health insurance claims database. RESULTS: The incidence of invasive mold infections remained unchanged in the year after Hurricane Harvey; however, the incidence of diagnosis codes for mold exposure nearly doubled compared with the year before the hurricane (6.3 vs. 11.0 per 100,000 enrollees, rate ratio: 1.7, 95% confidence interval 1.0-3.1). CONCLUSIONS: Diagnosis codes alone may not be sufficiently sensitive to detect changes in invasive mold infection rates within this population and timeframe, demonstrating the need for more comprehensive studies.

BACKGROUND: Candida auris is an emerging fungal threat that has been spreading in the United States since it was first reported in 2016. OBJECTIVE: To describe recent changes in the U.S. epidemiology of C auris occurring from 2019 to 2021. DESIGN: Description of national surveillance data. SETTING: United States. PATIENTS: Persons with any specimen that was positive for C auris. MEASUREMENTS: Case counts reported to the Centers for Disease Control and Prevention by health departments, volume of colonization screening, and antifungal susceptibility results were aggregated and compared over time and by geographic region. RESULTS: A total of 3270 clinical cases and 7413 screening cases of C auris were reported in the United States through 31 December 2021. The percentage increase in clinical cases grew each year, from a 44% increase in 2019 to a 95% increase in 2021. Colonization screening volume and screening cases increased in 2021 by more than 80% and more than 200%, respectively. From 2019 to 2021, 17 states identified their first C auris case. The number of C auris cases that were resistant to echinocandins in 2021 was about 3 times that in each of the previous 2 years. LIMITATION: Identification of screening cases depends on screening that is done on the basis of need and available resources. Screening is not conducted uniformly across the United States, so the true burden of C auris cases may be underestimated. CONCLUSION: C auris cases and transmission have risen in recent years, with a dramatic increase in 2021. The rise in echinocandin-resistant cases and evidence of transmission is particularly concerning because echinocandins are first-line therapy for invasive Candida infections, including C auris. These findings highlight the need for improved detection and infection control practices to prevent spread of C auris. PRIMARY FUNDING SOURCE: None.

BACKGROUND: Characterizing invasive mold infection (IMI) epidemiology in the context of large flooding events is important for public health planning and clinical decision making. METHODS: We assessed IMI incidence (per 10 000 healthcare encounters) 1 year before and after Hurricane Harvey at 4 hospitals in Houston, Texas. Potential IMI cases were assigned as proven or probable cases using established definitions, and surveillance cases using a novel definition. We used rate ratios to describe IMI incidence and multivariable logistic regression to examine patient characteristics associated with IMI case status. RESULTS: IMI incidence was significantly higher posthurricane (3.69 cases) than prehurricane (2.50 cases) (rate ratio, 1.48 [95% confidence interval, 1.10-2.00]), largely driven by surveillance IMI cases. Aspergillus was the most common species cultured (33.5% prehurricane and 39.9% posthurricane). About one-quarter (25.8%) of IMI patients lacked classical IMI risk factors such as hematologic malignancy and transplantations. Overall, 45.1% of IMI patients received intensive care, and in-hospital all-cause mortality was 24.2%. CONCLUSIONS: IMI incidence likely increased following Hurricane Harvey and outcomes for IMI patients were severe. Patient and clinician education on IMI prevention and identification is warranted, particularly as the frequency of extreme weather events increases due to climate change.

Vulvovaginal candidiasis (VVC) is a common infection, and high-quality studies report that misdiagnosis is frequent, with diagnostic testing needed to distinguish it from other causes of vaginitis and avoid inappropriate empiric treatment. However, few recent studies have evaluated U.S. healthcare providers' testing practices for VVC in detail. We evaluated healthcare providers' self-reported testing practices for VVC and treatment outcomes as part of a nationwide online survey in order to identify potential opportunities for improving VVC testing and treatment in the United States. Among 1,503 providers surveyed, 21.3% reported "always" (7.4%) or "usually" (13.9%) ordering diagnostic testing for patients with suspected VVC; this proportion was higher among gynecologists (36.0%) compared with family practitioners (17.8%) and internists (15.8%). Most providers (91.2%) reported that patients' VVC "always" (6.4%) or "usually" (84.9%) responds to initial treatment. Whether the symptom resolution reported in this survey was truly related to VVC is unclear given high rates of misdiagnosis and known widespread empiric prescribing. With only about one-in-five providers reporting usually or always performing diagnostic testing for VVC despite guidelines recommending universal use, research is needed to address barriers to proper testing.

BACKGROUND: Candidemia is a common healthcare-associated infection with high mortality. Estimates of recurrence range from 1% to 17%. Few studies have focused on those with recurrent candidemia, who often experience more severe illness and greater treatment failure. We describe recurrent candidemia trends and risk factors. METHODS: We analyzed population-based candidemia surveillance data collected during 2011-2018. Persons with >1 episode (defined as the 30-day period after a positive Candida species) were classified as having recurrent candidemia. We compared factors during the initial episode between those who developed recurrent candidemia and those who did not. RESULTS: Of the 5428 persons identified with candidemia, 326 (6%) had recurrent infection. Recurrent episodes occurred 1.0 month to 7.6 years after any previous episode. In multivariable logistic regression controlling for surveillance site and year, recurrent candidemia was associated with being 19-44 years old (vs ≥65 years; adjusted odds ratio [aOR], 3.05 [95% confidence interval {CI}, 2.10-4.44]), being discharged to a private residence (vs medical facility; aOR, 1.53 [95% CI, 1.12-2.08]), hospitalization in the 90 days prior to initial episode (aOR, 1.66 [95% CI, 1.27-2.18]), receipt of total parenteral nutrition (aOR, 2.08 [95% CI, 1.58-2.73]), and hepatitis C infection (aOR, 1.65 [95% CI, 1.12-2.43]). CONCLUSIONS: Candidemia recurrence >30 days after initial infection occurred in >1 in 20 persons with candidemia. Associations with younger age and hepatitis C suggest injection drug use may play a modifiable role. Prevention efforts targeting central line care and total parenteral nutrition use may help reduce the risk of recurrent candidemia.

BACKGROUND: Outbreaks of healthcare-associated mucormycosis (HCM), a life-threatening fungal infection, have been attributed to multiple sources, including contaminated healthcare linens. In 2020, staff at Hospital A in Arkansas alerted public health officials of a potential HCM outbreak. METHODS: We collected data on patients at Hospital A who had invasive mucormycosis during January 2017-June 2021 and calculated annual incidence of HCM (defined as mucormycosis diagnosed within ≥7 days after hospital admission). We performed targeted environmental assessments, including linen sampling at the hospital, to identify potential sources of infection. RESULTS: During the outbreak period (June 2019-June 2021), 16 patients had HCM; clinical features were similar between HCM patients and non-HCM patients. Hospital-wide HCM incidence (per 100 000 patient-days) increased from 0 in 2018 to 3 in 2019 and 6 in 2020. For the 16 HCM patients, the most common underlying medical conditions were hematologic malignancy (56%) and recent traumatic injury (38%); 38% of HCM patients died in-hospital. Healthcare-associated mucormycosis cases were not epidemiologically linked by common procedures, products, units, or rooms. At Hospital A and its contracted offsite laundry provider, suboptimal handling of laundered linens and inadequate environmental controls to prevent mucormycete contamination were observed. We detected Rhizopus on 9 (9%) of 98 linens sampled at the hospital, including on linens that had just arrived from the laundry facility. CONCLUSIONS: We describe the largest, single-center, HCM outbreak reported to date. Our findings underscore the importance of hospital-based monitoring for HCM and increased attention to the safe handling of laundered linens.

Equitable access to COVID-19 therapeutics is a critical aspect of the distribution program led by the U.S. Department of Health and Human Services (HHS).* Two oral antiviral products, nirmatrelvir/ritonavir (Paxlovid)(†) and molnupiravir (Lagevrio),(§) received emergency use authorization (EUA) from the Food and Drug Administration (FDA) in December 2021, to reduce the risk for COVID-19-associated hospitalization and death for those patients with mild to moderate COVID-19 who are at higher risk for severe illness (1,2). HHS has been distributing these medications at no cost to recipients since their authorization. Data collected from provider sites during December 23, 2021-May 21, 2022, indicated substantial disparities in the population-adjusted dispensing rates in high social vulnerability (high-vulnerability) zip codes compared with those in medium- and low-vulnerability zip codes (3). Specifically, dispensing rates for the 4-week period during April 24-May 21, 2022, were 122 per 100,000 residents (19% of overall population-adjusted dispensing rates) in high-vulnerability zip codes compared with 247 (42%) in medium-vulnerability and 274 (39%) in low-vulnerability zip codes. This report provides an updated analysis of dispensing rates by zip code-level social vulnerability and highlights important intervention strategies.

As SARS-CoV-2, the virus that causes COVID-19, continues to circulate globally, high levels of vaccine- and infection-induced immunity and the availability of effective treatments and prevention tools have substantially reduced the risk for medically significant COVID-19 illness (severe acute illness and post-COVID-19 conditions) and associated hospitalization and death (1). These circumstances now allow public health efforts to minimize the individual and societal health impacts of COVID-19 by focusing on sustainable measures to further reduce medically significant illness as well as to minimize strain on the health care system, while reducing barriers to social, educational, and economic activity (2). Individual risk for medically significant COVID-19 depends on a person's risk for exposure to SARS-CoV-2 and their risk for developing severe illness if infected (3). Exposure risk can be mitigated through nonpharmaceutical interventions, including improving ventilation, use of masks or respirators indoors, and testing (4). The risk for medically significant illness increases with age, disability status, and underlying medical conditions but is considerably reduced by immunity derived from vaccination, previous infection, or both, as well as timely access to effective biomedical prevention measures and treatments (3,5). CDC's public health recommendations change in response to evolving science, the availability of biomedical and public health tools, and changes in context, such as levels of immunity in the population and currently circulating variants. CDC recommends a strategic approach to minimizing the impact of COVID-19 on health and society that relies on vaccination and therapeutics to prevent severe illness; use of multicomponent prevention measures where feasible; and particular emphasis on protecting persons at high risk for severe illness. Efforts to expand access to vaccination and therapeutics, including the use of preexposure prophylaxis for persons who are immunocompromised, antiviral agents, and therapeutic monoclonal antibodies, should be intensified to reduce the risk for medically significant illness and death. Efforts to protect persons at high risk for severe illness must ensure that all persons have access to information to understand their individual risk, as well as efficient and equitable access to vaccination, therapeutics, testing, and other prevention measures. Current priorities for preventing medically significant illness should focus on ensuring that persons 1) understand their risk, 2) take steps to protect themselves and others through vaccines, therapeutics, and nonpharmaceutical interventions when needed, 3) receive testing and wear masks if they have been exposed, and 4) receive testing if they are symptomatic, and isolate for ≥5 days if they are infected.

BACKGROUND: Widespread inappropriate antibiotic prescribing is a major driver of resistance. Little is known about antifungal prescribing practices in the United States, which is concerning given emerging resistance in fungi, particularly to azole antifungals. OBJECTIVE: We analyzed outpatient U.S. antifungal prescribing data to inform stewardship efforts. DESIGN: Descriptive analysis of outpatient antifungal prescriptions dispensed during 2018 in the IQVIA Xponent database. METHODS: Prescriptions were summarized by drug, sex, age, geography, and healthcare provider specialty. Census denominators were used to calculate prescribing rates among demographic groups. RESULTS: Healthcare providers prescribed 22.4 million antifungal courses in 2018 (68 prescriptions per 1,000 persons). Fluconazole was the most common drug (75%), followed by terbinafine (11%) and nystatin (10%). Prescription rates were higher among females vs. males (110 vs. 25 per 1,000) and adults vs. children (82 vs. 27 per 1,000). Prescription rates were highest in the South (81 per 1,000 persons) and lowest in the West (48 per 1,000 persons). Nurse practitioners and family practitioners prescribed the most antifungals (43% of all prescriptions), but the highest prescribing rates were among obstetrician-gynecologists (84 per provider). CONCLUSIONS: Prescribing of antifungal drugs in the outpatient setting was common, with enough courses dispensed for one in every 15 U.S. residents in 2018. Fluconazole use patterns suggest vulvovaginal candidiasis as a common indication. Regional prescribing differences could reflect inappropriate use or variations in disease burden. Further study of higher antifungal use in the South could help target antifungal stewardship practices.

BACKGROUND: Cryptococcosis is a serious opportunistic fungal disease, and the proportion of cases among patients with immunosuppressive conditions other than HIV or organ transplant has increased. Understanding laboratory testing patterns for cryptococcosis is useful for estimating its true burden and developing testing guidance. METHODS: We identified cryptococcosis tests (cryptococcal antigen [CrAg], cryptococcal antibody, and fungal cultures) performed at a major national commercial laboratory ordered during March 1, 2019-October 1, 2021, and analyzed test results, patient and provider features, reasons for testing, geography, and temporal trends. RESULTS: Among 29 180 serum CrAg tests, 4422 (15.2%) were positive, and among 10 724 cerebrospinal fluid (CSF) CrAg tests, 492 (4.6%) were positive. Frequent reasons for serum CrAg testing in nonhospital settings (10 882 tests) were HIV (44.6%) and cryptococcosis (17.0%); other underlying conditions were uncommonly listed (<10% total). Serum CrAg positivity declined from 25.6% in October 2019 to 11.3% in September 2021. The South had the highest positivity for serum CrAg tests (16.6%), CSF CrAg tests (4.7%), and fungal cultures (0.15%). Among 5009 cryptococcal antibody tests, 5 (0.1%) were positive. CONCLUSIONS: Few outpatient serum CrAg tests were performed for patients with immunocompromising conditions other than HIV, suggesting potential missed opportunities for early detection. Given the high positive predictive value of CrAg testing, research is needed to improve early diagnosis, particularly in patients without HIV. Conversely, the low yield of antibody testing suggests that it may be of low value. The decline in CrAg positivity during the COVID-19 pandemic warrants further investigation.

BACKGROUND: Frozen foods have rarely been linked to Listeria monocytogenes illness. We describe an outbreak investigation prompted both by hospital clustering of illnesses and product testing. METHODS: We identified outbreak-associated listeriosis cases using whole-genome sequencing (WGS), product testing results, and epidemiologic linkage to cases in the same Kansas hospital. We reviewed hospital medical and dietary records, product invoices, and molecular subtyping results. Federal and state officials tested product and environmental samples for L. monocytogenes. RESULTS: Kansas officials were investigating five cases of listeriosis at a single hospital when, simultaneously, unrelated sampling for a study in South Carolina identified L. monocytogenes in Company A ice cream products made in Texas. Isolates from four patients and Company A products were closely related by WGS, and the four patients with known exposures had consumed milkshakes made with Company A ice cream while hospitalized. Further testing identified L. monocytogenes in ice cream produced in a second Company A production facility in Oklahoma; these isolates were closely related by WGS to those from five patients in three other states. These ten illnesses, involving three deaths, occurred from 2010 through 2015. Company A ultimately recalled all products. CONCLUSION: In this U.S. outbreak of listeriosis linked to a widely distributed brand of ice cream, WGS and product sampling helped link cases spanning five years to two production facilities, indicating longstanding contamination. Comprehensive sanitation controls and environmental and product testing for L. monocytogenes, with regulatory oversight, should be implemented for ice cream production.

BACKGROUND: Invasive mold diseases (IMDs) cause severe illness, but public health surveillance data are lacking. We describe data collected from a laboratory-based, pilot IMD surveillance system. METHODS: During 2017-2019, the Emerging Infections Program conducted active IMD surveillance at 3 Atlanta-area hospitals. We ascertained potential cases by reviewing histopathology, culture, and Aspergillus galactomannan results and classified patients as having an IMD case (based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [MSG] criteria) or a non-MSG IMD case (based on the treating clinician's diagnosis and use of mold-active antifungal therapy). We described patient features and compared patients with MSG vs non-MSG IMD cases. RESULTS: Among 304 patients with potential IMD, 104 (34.2%) met an IMD case definition (41 MSG, 63 non-MSG). The most common IMD types were invasive aspergillosis (n=66 [63.5%]), mucormycosis (n=8 [7.7%]), and fusariosis (n=4 [3.8%]); the most frequently affected body sites were pulmonary (n=66 [63.5%]), otorhinolaryngologic (n=17 [16.3%]), and cutaneous/deep tissue (n=9 [8.7%]). Forty-five (43.3%) IMD patients received intensive care unit-level care, and 90-day all-cause mortality was 32.7%; these outcomes did not differ significantly between MSG and non-MSG IMD patients. CONCLUSIONS: IMD patients had high mortality rates and a variety of clinical presentations. Comprehensive IMD surveillance is needed to assess emerging trends, and strict application of MSG criteria for surveillance might exclude over one-half of clinically significant IMD cases.

To the Editor: Onychomycosis, a fungal nail infection most frequently caused by dermatophytes, is an underrecognized public health problem, particularly given the global emergence of terbinafine resistance.1,2 We estimated onychomycosis prevalence, described risk factors, and assessed adherence to American Academy of Dermatology (AAD) guidelines that recommend confirmatory testing (eg, direct microscopy, histopathology, fungal culture) before prescribing oral antifungal therapy.3

The COVID-19 pandemic has highlighted and exacerbated long-standing inequities in the social determinants of health (1-3). Ensuring equitable access to effective COVID-19 therapies is essential to reducing health disparities. Molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid) are oral antiviral agents effective at preventing hospitalization and death in patients with mild to moderate COVID-19 who are at high risk* for progression to severe COVID-19 when initiated within 5 days of symptom onset. These medications received Emergency Use Authorization from the Food and Drug Administration (FDA) in December 2021() and were made available at no cost to recipients through the U.S. Department of Health and Human Services (HHS) on December 23, 2021. Beginning March 7, 2022, a series of strategies was implemented to expand COVID-19 oral antiviral access, including the launch of the Test to Treat initiative.() Data from December 23, 2021-May 21, 2022, were analyzed to describe oral antiviral prescription dispensing overall and by week, stratified by zip code social vulnerability. Zip codes represented areas classified as low, medium, or high social vulnerability; approximately 20% of U.S. residents live in low-, 31% in medium-, and 49% in high-social vulnerability zip codes.() During December 23, 2021-May 21, 2022, a total of 1,076,762 oral antiviral prescriptions were dispensed (Lagevrio = 248,838; Paxlovid = 827,924). Most (70.3%) oral antivirals were dispensed during March 7-May 21, 2022. During March 6, 2022-May 21, 2022, the number of oral antivirals dispensed per 100,000 population increased from 3.3 to 77.4 in low-, from 4.5 to 70.0 in medium-, and from 7.8 to 35.7 in high-vulnerability zip codes. The number of oral antivirals dispensed rose substantially during the overall study period, coincident with the onset of initiatives to increase access. However, by the end of the study period, dispensing rates in high-vulnerability zip codes were approximately one half the rates in medium- and low-vulnerability zip codes. Additional public health, regulatory, and policy efforts might help decrease barriers to oral antiviral access, particularly in communities with high social vulnerability.

BACKGROUND: COVID-19-associated fungal infections cause severe illness, but comprehensive data on disease burden are lacking. We analyzed US National Vital Statistics System (NVSS) data to characterize disease burden, temporal trends, and demographic characteristics of persons dying from fungal infections during the COVID-19 pandemic. METHODS: Using NVSS's January 2018-December 2021 Multiple Cause of Death Database, we examined numbers and age-adjusted rates (per 100,000 population) of fungal deaths by fungal pathogen, COVID-19 association, demographic characteristics, and year. RESULTS: Numbers and age-adjusted rates of fungal deaths increased from 2019 (n = 4,833, rate 1.2, 95% confidence interval [CI]    1.2-1.3) to 2021 (n = 7,199, rate: 1.8, 95% CI = 1.8-1.8); of 13,121 fungal deaths during 2020-2021, 2,868 (21.9%) were COVID-19-associated. Compared with non-COVID-19-associated fungal deaths (n = 10,253), COVID-19-associated fungal deaths more frequently involved Candida (n = 776 [27.1%] versus n = 2,432 [23.7%]) and Aspergillus (n = 668 [23.3%] versus n = 1,486 [14.5%]) and less frequently involved other specific fungal pathogens. Fungal death rates were generally highest in non-White and non-Asian populations. Death rates from Aspergillus infections were approximately two times higher in the Pacific US census division compared with most other divisions. CONCLUSIONS: Fungal deaths increased during 2020-2021 compared with previous years, primarily driven by COVID-19-associated fungal deaths, particularly those involving Aspergillus and Candida. Our findings may inform efforts to prevent, identify, and treat severe fungal infections in COVID-19 patients, especially in certain racial/ethnic groups and geographic areas.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common gynecologic problem in the United States but estimates of its true incidence and prevalence are lacking. We estimated self-reported incidence and lifetime prevalence of healthcare provider-diagnosed VVC and recurrent VVC (RVVC), assessed treatment types, and evaluated demographic and health-related risk factors associated with VVC. METHODS: An online survey sent to 4548 U.S. adults; data were weighted to be representative of the population. We conducted descriptive and bivariate analyses to examine demographic characteristics and health related factors associated with having VVC in the past year, lifetime prevalence of VVC, and over-the-counter (OTC) and prescription antifungal treatment use. We conducted multivariate analyses to assess features associated with 1) having VVC in the past year, 2) number of VVC episodes in the past year, and 3) lifetime prevalence of VVC. RESULTS: Among the subset of 1869 women respondents, 98 (5.2%) had VVC in the past year; of those, 5 (4.7%) had RVVC. Total, 991 (53%) women reported healthcare provider-diagnosed VVC in their lifetime. Overall, 72% of women with VVC in the past year reported prescription antifungal treatment use, 40% reported OTC antifungal treatment use, and 16% reported both. In multivariate analyses, odds of having VVC in the past year were highest for women with less than a high school education (aOR = 6.30, CI: 1.84-21.65), with a child/children under 18 years old (aOR = 3.14, CI: 1.58-6.25), with diabetes (aOR = 2.93, CI: 1.32-6.47), who were part of a couple (aOR = 2.86, CI: 1.42-5.78), and with more visits to a healthcare provider for any reason (aOR = 2.72, CI: 1.84-4.01). Similar factors were associated with increasing number of VVC episodes in the past year and with lifetime prevalence of VVC. CONCLUSION: VVC remains a common infection in the United States. Our analysis supports known clinical risk factors for VVC and suggests that antifungal treatment use is high, underscoring the need to ensure appropriate diagnosis and treatment.

BACKGROUND: In the United States, the true geographic distribution of the environmental fungus Histoplasma capsulatum remains poorly understood but appears to have changed since it was first characterized. Histoplasmosis is caused by inhalation of the fungus and can range in severity from asymptomatic to life-threatening. Due to limited public health surveillance and under detection of infections, it is challenging to directly use reported case data to characterize spatial risk. METHODS: Using monthly and yearly county-level public health surveillance data and various environmental and socioeconomic characteristics, we use a spatio-temporal occupancy model to estimate latent, or unobserved, presence of H. capsulatum, accounting for imperfect detection of histoplasmosis cases. RESULTS: We estimate areas with higher probabilities of the presence of H. capsulatum in the East North Central states around the Great Lakes, reflecting a shift of the endemic region to the north from previous estimates. The presence of H. capsulatum was strongly associated with higher soil nitrogen levels. CONCLUSIONS: In this investigation, we were able to mitigate challenges related to reporting and illustrate a shift in the endemic region from historical estimates. This work aims to help inform future surveillance needs, clinical awareness, and testing decisions for histoplasmosis.

Vulvovaginal candidiasis (VVC) is a common cause of vaginitis, but the national burden is unknown, and clinical diagnosis without diagnostic testing is often inaccurate. We aimed to calculate rates and evaluate diagnosis and treatment practices of VVC and recurrent vulvovaginal candidiasis (RVVC) in the United States. We used the 2018 IBM® MarketScan® Research Databases, which include health insurance claims data on outpatient visits and prescriptions for >28 million people. We used diagnosis and procedure codes to examine underlying conditions, vaginitis-related symptoms and conditions, diagnostic testing, and antibacterial and antifungal treatment among female patients with VVC. Among 12.3 million female patients in MarketScan, 149,934 (1.2%) had a diagnosis code for VVC; of those, 3.4% had RVVC. The VVC rate was highest in the South census region (14.3 per 1,000 female patients) and lowest in the West (9.9 per 1000). Over 60% of patients with VVC did not have codes for any diagnostic testing, and microscopy was the most common test type performed in 29.5%. Higher rates of diagnostic testing occurred among patients who visited an OB/GYN (53.4%) compared with a family practice or internal medicine provider (24.2%) or other healthcare provider types (31.9%); diagnostic testing rates were lowest in the South (34.0%) and highest in the Midwest (41.0%). Treatments on or in the 7 days after diagnosis included systemic fluconazole (70.0%), topical antifungal medications (19.4%), and systemic antibacterial medications (17.2%). The low frequencies of diagnostic testing for VVC and high rates of antifungal and antibacterial use suggest substantial empiric treatment, including likely overprescribing of antifungal medications and potentially unnecessary antibacterial medications. These findings support a need for improved clinical care for VVC to improve both patient outcomes and antimicrobial stewardship, particularly in the South and among non-OB/GYN providers.

We conservatively estimated the US economic burden of fungal diseases as $11.5 billion in 2019: direct medical costs ($7.5 billion), productivity loss due to absenteeism ($870 million), and premature deaths ($3.2 billion). An alternative "value of statistical life" approach yielded >$48 billion. These are likely underestimates given underdiagnosis and underreporting.

OBJECTIVES: Extensive floodwater damage following hurricane Harvey raised concerns of increase in invasive mould infections (IMIs), especially in immunocompromised patients. To more comprehensively characterize the IMI landscape pre- and post- Harvey, we used a modified, less restrictive clinical IMI (mcIMI) definition by incorporating therapeutic-intent antifungal drug prescriptions combined with an expanded list of host and clinical features. METHODS: We reviewed 103 patients at MD Anderson Cancer Center (Houston, Texas), who lived in Harvey-affected counties and had mould-positive cultures within 12 months pre-/post-Harvey (36 and 67 patients, respectively). Cases were classified as proven or probable IMI (EORTC/MSG criteria), mcIMI, or colonization/ contamination. We also compared in-hospital mortality and 42- day survival outcomes of patients with mcIMI pre-/ post- Harvey. RESULTS: The number of patients with mould- positive cultures from Harvey- affected counties almost doubled from 36 pre- Harvey to 67 post- Harvey (p < 0.01). In contrast, no significant changes in (mc) IMI incidence post- Harvey nor changes in the etiological mould genera were noted. However, patients with mcIMIs from flood affected areas had significantly higher in- hospital mortality (p = 0.01). CONCLUSIONS: We observed increased colonization but no excess cases of (mc)IMIs in immunosuppressed cancer patients from affected areas following a large flooding event such as hurricane Harvey.

Although the availability of effective vaccines raises optimism for the control of SARS-CoV-2 transmission in the USA, public health systems must prepare to respond to all COVID-19 health impacts, particularly post-COVID conditions (PCCs).1,2 PCCs consist of new, returning, or ongoing health problems diagnosed in people with a history of SARS-CoV-2 infection, typically present at least 4 weeks after infection.3 While PCCs are still being defined and characterized, PCCs could potentially affect millions of Americans.1,2

IMPORTANCE: New symptoms and conditions can develop following SARS-CoV-2 infection. Whether they occur more frequently among persons with SARS-CoV-2 infection compared with those without is unclear. OBJECTIVE: To compare the prevalence of new diagnoses of select symptoms and conditions between 31 and 150 days after testing among persons who tested positive vs negative for SARS-CoV-2. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed aggregated electronic health record data from 40 health care systems, including 338 024 persons younger than 20 years and 1 790 886 persons aged 20 years or older who were tested for SARS-CoV-2 during March to December 2020 and who had medical encounters between 31 and 150 days after testing. MAIN OUTCOMES AND MEASURES: International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes were used to capture new symptoms and conditions that were recorded 31 to 150 days after a SARS-CoV-2 test but absent in the 18 months to 7 days prior to testing. The prevalence of new symptoms and conditions was compared between persons with positive and negative SARS-CoV-2 tests stratified by age (20 years or older and young than 20 years) and care setting (nonhospitalized, hospitalized, or hospitalized and ventilated). RESULTS: A total of 168 701 persons aged 20 years or older and 26 665 younger than 20 years tested positive for SARS-CoV-2, and 1 622 185 persons aged 20 years or older and 311 359 younger than 20 years tested negative. Shortness of breath was more common among persons with a positive vs negative test result among hospitalized patients (≥20 years: prevalence ratio [PR], 1.89 [99% CI, 1.79-2.01]; <20 years: PR, 1.72 [99% CI, 1.17-2.51]). Shortness of breath was also more common among nonhospitalized patients aged 20 years or older with a positive vs negative test result (PR, 1.09 [99% CI, 1.05-1.13]). Among hospitalized persons aged 20 years or older, the prevalence of new fatigue (PR, 1.35 [99% CI, 1.27-1.44]) and type 2 diabetes (PR, 2.03 [99% CI, 1.87-2.19]) was higher among those with a positive vs a negative test result. Among hospitalized persons younger than 20 years, the prevalence of type 2 diabetes (PR, 2.14 [99% CI, 1.13-4.06]) was higher among those with a positive vs a negative test result; however, the prevalence difference was less than 1%. CONCLUSIONS AND RELEVANCE: In this cohort study, among persons hospitalized after a positive SARS-CoV-2 test result, diagnoses of certain symptoms and conditions were higher than among those with a negative test result. Health care professionals should be aware of symptoms and conditions that may develop after SARS-CoV-2 infection, particularly among those hospitalized after diagnosis.

BACKGROUND: Blastomycosis, coccidioidomycosis, and histoplasmosis cause various symptoms and syndromes, which may present similarly to other infections such as bacterial or viral community-acquired pneumonia, influenza, and tuberculosis. METHODS: We used the IBM MarketScan Research Databases to identify adult outpatients with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), diagnosis codes during 2016-2017 for blastomycosis, coccidioidomycosis, histoplasmosis, pneumonia (viral, bacterial, Streptococcus pneumoniae, and unspecified pneumonia), influenza; tuberculosis, and other lower and upper respiratory infections. We compared symptoms on and in the 90 days before diagnosis between patients with these diagnosis codes. RESULTS: Fever was less common in blastomycosis (2.6%), histoplasmosis (5.3%), and coccidioidomycosis (9.4%) than in patients with influenza (18.5%) or pneumonia (12.6-16.3%). Fungal diseases resembled bacterial, viral, and unspecified pneumonias for many pulmonary symptoms. However, cough was more common with coccidioidomycosis (31.4%) and less common with histoplasmosis (14.0%) and blastomycosis (13.1%) versus influenza (20.2%). Although less frequent, solitary pulmonary nodule (5.2-14.4%), enlarged lymph nodes (3.7-9.0%), hyperhidrosis (<2%), and erythema nodosum (<2%) were particularly suggestive of fungal diseases. CONCLUSIONS: Despite limitations inherent in administrative coding, this analysis of symptom codes across disease types suggests that fungal diseases may be difficult to clinically distinguish from other causes of pneumonia except when certain uncommon symptoms are present. Healthcare providers caring for patients with pneumonia, especially if nonresponsive to conventional treatment, should consider fungal diseases as possible etiologies.

On July 15, 2021, the Secretary of Health of Honduras (SHH) was notified of an unexpected number of mucormycosis cases among COVID-19 patients. SHH partnered with the Honduras Field Epidemiology Training Program, the Executive Secretariat of the Council of Ministers of Health of Central America and the Dominican Republic (SE-COMISCA), Pan American Health Organization (PAHO), and CDC to investigate mucormycosis cases at four geographically distinct hospitals in Honduras. | | Mucormycosis is a severe, often fatal disease caused by infection with angioinvasive molds belonging to the order Mucorales. Risk factors for mucormycosis include certain underlying medical conditions (e.g., hematologic malignancy, stem cell or solid organ transplantation, or uncontrolled diabetes) and the use of certain immunosuppressive medications (1). COVID-19 might increase mucormycosis risk because of COVID-19–induced immune dysregulation or associated medical treatments, such as systemic corticosteroids and other immunomodulatory drugs (e.g., tocilizumab), which impair the immune response against mold infections (2). In India, an apparent increase in mucormycosis cases (which was referred to by the misnomer “black fungus”) was attributed to COVID-19 (3).