Genomics and metagenomics of Madurella mycetomatis, a causative agent of black grain mycetoma in Sudan.

Madurella mycetomatis is one of the main causative agents of mycetoma, a debilitating neglected tropical disease. Improved understanding of the genomic diversity of the fungal and bacterial causes of mycetoma is essential to advances in diagnosis and treatment. Here, we describe a high-quality genome assembly of M. mycetomatis and results of the whole genome sequence analysis of 26 isolates from Sudan. We demonstrate evidence of at least seven genetically diverse lineages and extreme clonality among isolates within these lineages. We also performed shotgun metagenomic analysis of DNA extracted from mycetoma grains and showed that M. mycetomatis reads were detected in all sequenced samples with the average of 11,317 reads (s.d. +/- 21,269) per sample. In addition, 10 (12%) of the 81 tested grain samples contained bacterial reads including Streptococcus sp., Staphylococcus sp. and others.

Clinical Characteristics, Health Care Utilization, and Outcomes Among Patients in a Pilot Surveillance System for Invasive Mold Disease-Georgia, United States, 2017-2019.

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.

Surveillance practices and air-sampling strategies to address healthcare-associated invasive mold infections in Society for Healthcare Epidemiology of America (SHEA) Research Network hospitals-United States, 2020.

With this survey, we investigated healthcare-associated invasive mold infection (HA-IMI) surveillance and air sampling practices in US acute-care hospitals. More than half of surveyed facilities performed HA-IMI surveillance and air sampling. HA-IMI surveillance was more commonly performed in academic versus nonacademic facilities. HA-IMI case definitions and sampling strategies varied widely among respondents.

Patient notification about suspected hospital-associated outbreaks of invasive mold infections: Considerations for public health and hospital personnel.

A common type of fungal disease investigation involves hospital-associated clusters of invasive mold infections (IMIs), which typically occur among immunocompromised patients. Responding to IMI clusters can be challenging for public health and hospital personnel for several reasons such as difficulty of confirming the existence of an outbreak, difficulty of determining source. Although many resources exist to guide patient notification about healthcare incidents (eg, bloodborne exposures, disease outbreaks), IMI clusters involve special considerations related to the complex diseases, uncertain exposures, and differential benefits and risks of notification. Early, nuanced communication about hospital-associated IMI clusters is almost always the best course of action to help reduce risks to patients' health and foster trust between patients and hospitals.

Trends in Agricultural Triazole Fungicide Use in the United States, 1992-2016 and Possible Implications for Antifungal-Resistant Fungi in Human Disease.

BACKGROUND: The fungus Aspergillus fumigatus (A. fumigatus) is the leading cause of invasive mold infections, which cause severe disease and death in immunocompromised people. Use of triazole antifungal medications in recent decades has improved patient survival; however, triazole-resistant infections have become common in parts of Europe and are emerging in the United States. Triazoles are also a class of fungicides used in plant agriculture, and certain triazole-resistant A. fumigatus strains found causing disease in humans have been linked to environmental fungicide use. OBJECTIVES: We examined U.S. temporal and geographic trends in the use of triazole fungicides using U.S. Geological Survey agricultural pesticide use estimates. DISCUSSION: Based on our analysis, overall tonnage of triazole fungicide use nationwide was relatively constant during 1992-2005 but increased >4-fold during 2006-2016 to 2.9 million kg in 2016. During 1992-2005, triazole fungicide use occurred mostly in orchards and grapes, wheat, and other crops, but recent increases in use have occurred primarily in wheat, corn, soybeans, and other crops, particularly in Midwest and Southeast states. We conclude that, given the chemical similarities between triazole fungicides and triazole antifungal drugs used in human medicine, increased monitoring for environmental and clinical triazole resistance in A. fumigatus would improve overall understanding of these interactions, as well as help identify strategies to mitigate development and spread of resistance. https://doi.org/10.1289/EHP7484.

Development of the Global Mycetoma Working Group.

The Global Mycetoma Working Group (GMWG) was formed in January 2018 in response to the declaration of mycetoma as a neglected tropical disease (NTD) by the World Health Assembly. The aim of the working group is to connect experts and public health practitioners around the world to accelerate mycetoma prevention activities and reduce the impact of mycetoma on patients, healthcare providers and society in the endemic regions. The working group has made tangible contributions to mycetoma programming, awareness and coordination among scientists, clinicians and public health professionals. The group's connectivity has enabled rapid response and review of NTD documents in development, has created a network of public health professionals to provide regional mycetoma expertise and has enabled mycetoma to be represented within broader NTD organizations. The GMWG will continue to serve as a hub for networking and building collaborations for the advancement of mycetoma clinical management and treatment, research and public health programming.

Ventilator-associated pneumonia involving Aspergillus flavus in a patient with coronavirus disease 2019 (COVID-19) from Argentina.

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, emerged in Wuhan, China, in December 2019 and rapidly spread around the world. Invasive aspergillosis has been reported as a complication of severe influenza pneumonia among intensive care patients. Similarities between COVID-19 and influenza pneumonia, together with limited published case series, suggest that aspergillosis may be an important complication of COVID-19. This report describes a case of ventilator-associated pneumonia involving Aspergillus flavus in a patient with COVID-19 from Buenos Aires, Argentina.

A One Health Approach to Combatting Sporothrix brasiliensis: Narrative Review of an Emerging Zoonotic Fungal Pathogen in South America.

Cat-transmitted sporotrichosis caused by Sporothrix brasiliensis has become a major public health concern and presents a distinct divergence from the traditional epidemiology of sporotrichosis. This emerging fungal pathogen spreads readily among cat populations, and human infections occur exclusively via zoonotic transmission. While sporotrichosis is an implantation mycosis that typically manifests as cutaneous lesions in humans and cats, severe extracutaneous manifestations are more common with S. brasiliensis than other Sporothrix species infections. Rapid diagnosis and appropriate treatment regimens are critical for successful clinical resolution of sporotrichosis in both cats and humans. Species-level identification of Sporothrix is possible with molecular diagnostics and necessary for tracking the geographic expansion of S. brasiliensis and better understanding its epidemiology. Combatting cat-transmitted sporotrichosis requires a One Health approach to successfully implement public health control measures.

Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.

Does Pulmonary Aspergillosis Complicate Coronavirus Disease 2019?

OBJECTIVES: Aspergillus coinfection in coronavirus disease 2019 patients has rarely been described but may be occurring among coronavirus disease 2019 patients admitted to ICUs. Previous reports of viral coinfections with Aspergillus, including influenza-associated pulmonary aspergillosis, suggest that coronavirus disease 2019-associated aspergillosis is plausible. This report aims to summarize what is known about coronavirus disease 2019 complicated by Aspergillus, introduces coronavirus disease 2019-associated pulmonary aspergillosis as a possible clinical entity, and describes reasons clinical suspicion of Aspergillus is warranted in the critical care setting. DATA SOURCES: We summarize the available evidence suggesting the existence of Aspergillus coinfection among severe coronavirus disease 2019 patients. This includes published coronavirus disease 2019 patient case series, a case description, and a review of potential biologic mechanisms. STUDY SELECTION: Reports of coronavirus disease 2019 patient attributes were selected if they included clinical, microbiologic, or radiologic signs of invasive fungal infection. DATA EXTRACTION: Data included in summary tables were identified through a literature search for coronavirus disease 2019-associated pulmonary aspergillosis. DATA SYNTHESIS: We present descriptive data extracted from coronavirus disease 2019-associated pulmonary aspergillosis case series current at the time of article submission. DISCUSSION: Pulmonary aspergillosis is known to occur among influenza patients requiring intensive care and is associated with increased mortality. If Aspergillus coinfections are occurring among coronavirus disease 2019 patients, early clinical suspicion and testing are needed to understand the epidemiology of these infections and prevent associated mortality. As the coronavirus disease 2019 pandemic unfolds, reports on the existence of this coinfection are needed, and opportunities to contribute cases of Aspergillus coinfection among coronavirus disease 2019 patients to an ongoing registry are described.

Use of whole-genome sequencing to detect an outbreak of Malassezia pachydermatis infection and colonization in a neonatal intensive care unit-California, 2015-2016.

Whole-genome sequencing confirmed the presence of a Malassezia pachydermatis outbreak among neonates in a neonatal intensive care unit. This technology supports the importance of adhering to infection prevention measures.

Presumed ocular histoplasmosis syndrome in a commercially insured population, United States.

PURPOSE: To describe epidemiologic features of patients with presumed ocular histoplasmosis syndrome (POHS) in the United States using insurance claims data and compare POHS patients with and without choroidal neovascularization (CNV). DESIGN: Retrospective cohort study. METHODS: Patients with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for histoplasmosis retinitis on an outpatient claim in the 2014 IBM® MarketScan® Commercial Database and the Medicare Supplemental Database who were enrolled for at least 2 years after the POHS code. MAIN OUTCOME MEASURES: Data related to testing, treatment, and direct medical costs. RESULTS: Among >50 million total MarketScan enrollees, 6,678 (13 per 100,000) had a POHS diagnosis code. Of those, 2,718 were enrolled for 2 years; 698 (25%) of whom had a CNV code. Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers. CNV patients had significantly more eye care provider visits (mean 8.8 vs. 3.2, p<0.0001), more ophthalmic imaging tests, higher rates of treatment with anti-vascular endothelial growth factor injections (45% vs. 4%, p<0.0001), and incurred higher mean total yearly costs ($1,251.83 vs. $251.36, p<0.0001) than POHS patients without CNV. CONCLUSIONS: Although the relationship between Histoplasma and POHS remains controversial, geographic patterns of POHS patient residence were consistent with the traditionally reported range of the fungus. CNV in the context of POHS was associated with additional healthcare use and costs. Further research to understand POHS etiology, risk factors, prevalence, and complications is needed, along with early diagnosis and treatment strategies.

Knowledge of Infectious Disease Specialists Regarding Aspergillosis Complicating Influenza, United States.

In an online survey, we found that nearly one fifth of physicians in the United States who responded had seen or heard about a case of invasive pulmonary aspergillosis after severe influenza at their institution. However, <10% routinely used galactomannan testing to test for this fungus in patients with severe influenza.

Antibiotic and antifungal treatment among persons with confirmed coccidioidomycosis - Southern California, 2011.

We investigated coccidioidomycosis testing and treatment patterns among persons in an integrated healthcare delivery system to identify gaps in diagnosis and treatment. Coccidioidomycosis diagnosis delays were common. Among persons who tested positive, 70% were prescribed antibiotics before positive coccidioidomycosis tests. Antibiotic treatment decreased and antifungal treatment increased after positive testing.

Histoplasmosis-related Healthcare Use, Diagnosis, and Treatment in a Commercially Insured Population, United States.

BACKGROUND: Infections with Histoplasma can range from asymptomatic to life-threatening acute pulmonary or disseminated disease. Histoplasmosis can be challenging to diagnose and is widely underrecognized. We analyzed insurance claims data to better characterize histoplasmosis testing and treatment practices and its burden on patients. METHODS: We used the IBM MarketScan Research Databases to identify patients with histoplasmosis (International Classification of Diseases, Ninth Revision, Clinical Modification codes 115.00-115.99) during 2012-2014. We analyzed claims in the 3 months before to the 1 year after diagnosis and examined differences between patients with probable (hospitalized or >1 outpatient visit) and suspected (1 outpatient visit) histoplasmosis. RESULTS: Among 1935 patients (943 probable, 992 suspected), 54% had codes for symptoms or findings consistent with histoplasmosis and 35% had ≥2 healthcare visits in the 3 months before diagnosis. Overall, 646 (33%) had any fungal-specific laboratory test: histoplasmosis antibody test (n = 349 [18%]), Histoplasma antigen test (n = 349 [18%]), fungal smear (n = 294 [15%]), or fungal culture (n = 223 [12%]); 464 (24%) had a biopsy. Forty-nine percent of probable patients and 10% of suspected patients were prescribed antifungal medication in the outpatient setting. In total, 19% were hospitalized. Patients' last histoplasmosis-associated healthcare visits occurred a median of 6 months after diagnosis. CONCLUSIONS: Some histoplasmosis patients experienced severe disease, apparent diagnostic delays, and prolonged illness, whereas other patients lacked symptoms and were likely diagnosed incidentally (eg, via biopsy). Low rates of histoplasmosis-specific testing also suggest incidental diagnoses and low provider suspicion, highlighting the need for improved awareness about this disease.

A Guide to Investigating Suspected Outbreaks of Mucormycosis in Healthcare.

This report serves as a guide for investigating mucormycosis infections in healthcare. We describe lessons learned from previous outbreaks and offer methods and tools that can aid in these investigations. We also offer suggestions for conducting environmental assessments, implementing infection control measures, and initiating surveillance to ensure that interventions were effective. While not all investigations of mucormycosis infections will identify a single source, all can potentially lead to improvements in infection control.

Hurricane-Associated Mold Exposures Among Patients at Risk for Invasive Mold Infections After Hurricane Harvey - Houston, Texas, 2017.

In August 2017, Hurricane Harvey caused unprecedented flooding and devastation to the Houston metropolitan area (1). Mold exposure was a serious concern because investigations after Hurricanes Katrina and Rita (2005) had documented extensive mold growth in flood-damaged homes (2,3). Because mold exposure can cause serious illnesses known as invasive mold infections (4,5), and immunosuppressed persons are at high risk for these infections (6,7), several federal agencies recommend that immunosuppressed persons avoid mold-contaminated sites (8,9). To assess the extent of exposure to mold and flood-damaged areas among persons at high risk for invasive mold infections after Hurricane Harvey, CDC and Texas health officials conducted a survey among 103 immunosuppressed residents in Houston. Approximately half of the participants (50) engaged in cleanup of mold and water-damaged areas; these activities included heavy cleanup (23), such as removing furniture or removing drywall, or light cleanup (27), such as wiping down walls or retrieving personal items. Among immunosuppressed persons who performed heavy cleanup, 43% reported wearing a respirator, as did 8% who performed light cleanup. One participant reported wearing all personal protective equipment (PPE) recommended for otherwise healthy persons (i.e., respirator, boots, goggles, and gloves). Immunosuppressed residents who are at high risk for invasive mold infections were exposed to mold and flood-damaged areas after Hurricane Harvey; recommendations from health care providers to avoid exposure to mold and flood-damaged areas could mitigate the risk to immunosuppressed persons.

Estimation of Direct Healthcare Costs of Fungal Diseases in the United States.

BACKGROUND: Fungal diseases range from relatively-minor superficial and mucosal infections to severe, life-threatening systemic infections. Delayed diagnosis and treatment can lead to poor patient outcomes and high medical costs. The overall burden of fungal diseases in the United States is challenging to quantify, because they are likely substantially underdiagnosed. METHODS: To estimate the total, national, direct medical costs associated with fungal diseases from a healthcare payer perspective, we used insurance claims data from the Truven Health MarketScan 2014 Research Databases, combined with hospital discharge data from the 2014 Healthcare Cost and Utilization Project National Inpatient Sample and outpatient visit data from the 2005-2014 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. All costs were adjusted to 2017 dollars. RESULTS: We estimate that fungal diseases cost more than $7.2 billion in 2017, including $4.5 billion from 75055 hospitalizations and $2.6 billion from 8993230 outpatient visits. Hospitalizations for Candida infections (n = 26735, total cost $1.4 billion) and Aspergillus infections (n = 14820, total cost $1.2 billion) accounted for the highest total hospitalization costs of any disease. Over half of outpatient visits were for dermatophyte infections (4981444 visits, total cost $802 million), and 3639037 visits occurred for non-invasive candidiasis (total cost $1.6 billion). CONCLUSIONS: Fungal diseases impose a considerable economic burden on the healthcare system. Our results likely underestimate their true costs, because they are underdiagnosed. More comprehensive estimates of the public health impact of these diseases are needed to improve their recognition, prevention, diagnosis, and treatment.

Multidrug-Resistant Aspergillus fumigatus Carrying Mutations Linked to Environmental Fungicide Exposure - Three States, 2010-2017.

The environmental mold Aspergillus fumigatus is the primary cause of invasive aspergillosis. In patients with high-risk conditions, including stem cell and organ transplant recipients, mortality exceeds 50%. Triazole antifungals have greatly improved survival (1); however, triazole-resistant A. fumigatus infections are increasingly reported worldwide and are associated with increased treatment failure and mortality (2). Of particular concern are resistant A. fumigatus isolates carrying either TR34/L98H or TR46/Y121F/T289A genetic resistance markers, which have been associated with environmental triazole fungicide use rather than previous patient exposure to antifungals (3,4). Reports of these triazole-resistant A. fumigatus strains have become common in Europe (2,3), but U.S. reports are limited (5). Because of the risk posed to immunocompromised patients, understanding the prevalence of such isolates in patients is important to guide clinical and public health decision-making. In 2011, CDC initiated passive laboratory monitoring for U.S. triazole-resistant A. fumigatus isolates through outreach to clinical laboratories. This system identified five TR34/L98H isolates collected from 2016 to 2017 (6), in addition to two other U.S. isolates collected in 2010 and 2014 and reported in 2015 (5). Four of these seven isolates were reported from Pennsylvania, two from Virginia, and one from California. Three isolates were collected from patients with invasive pulmonary aspergillosis, and four patients had no known previous triazole exposure. A. fumigatus resistant to all triazole medications is emerging in the United States, and clinicians and public health personnel need to be aware that resistant infections are possible even in patients not previously exposed to these medications.