Fungal Pathogens as Causes of Acute Respiratory Illness in Hospitalized Veterans: Frequency of Fungal Positive Test Results Using Rapid Immunodiagnostic Assays.

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.

Dietary and socioeconomic risk factors for fumonisin exposure among women of reproductive age in 18 municipalities in Guatemala from 2013 to 2014.

Fumonisin exposure is common in populations where maize is a dietary staple, such as in Guatemala, and has been associated with negative health outcomes including neural tube defects. The objective of this study was to estimate fumonisin B1 (FB1) exposure among Guatemalan reproductive-age women and develop a better understanding of the dietary and sociodemographic risk factors for exposure. A cross-sectional study in 18 municipalities in Guatemala was conducted. Midwives and study nurses enrolled consenting women and collected individual and household demographic and socioeconomic data. A food frequency questionnaire was administered to estimate quantity and types of food products consumed. A urine sample was collected and urinary fumonisin B1 (uFB1) concentration was measured. A univariable analysis was conducted to identify predictors of low/high uFB1. Multivariable logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). In total, 775 women had analyzable urine samples. Higher uFB1 levels were associated with speaking Mayan (OR = 2.33, 95% CI:1.44-3.77), less than high school education (OR = 1.61, 95% CI:1.12-2.30), increasing dietary proportion of maize-based foods (OR = 1.02, 95% CI:1.01-1.03), and consumption of tostadas (fried tortillas) (OR = 1.11, 95% CI:1.02-1.22). Lower uFB1 levels were associated with consumption of highly processed maize-based foods (OR = 0.93, 95% CI:0.87-0.99). Tortillas were the most frequently consumed maize-based food among study participants and significantly associated with high uFB1 exposure in the univariable but not multivariable analysis. Consumption of >4,750 grams/week of maize-based foods, >5,184 g/week of locally produced maize-based foods, and >110 servings/week of tortillas were also significantly associated with high uFB1 exposure in univariable analysis. Populations with low socioeconomic status/education levels and high consumption of maize-based foods had higher fumonisin exposure. Interventions aimed at reducing the risk of exposure to mycotoxins through maize in Guatemala, including the increased consumption of non-maize-based foods, should be further explored.

Factors Influencing Distribution of Coccidioides immitis in Soil, Washington State, 2016.

Coccidioides immitis and Coccidioides posadasii are causative agents of Valley fever, a serious fungal disease endemic to regions with hot, arid climate in the United States, Mexico, and Central and South America. The environmental niche of Coccidioides spp. is not well defined, and it remains unknown whether these fungi are primarily associated with rodents or grow as saprotrophs in soil. To better understand the environmental reservoir of these pathogens, we used a systematic soil sampling approach, quantitative PCR (qPCR), culture, whole-genome sequencing, and soil chemical analysis to identify factors associated with the presence of C. immitis at a known colonization site in Washington State linked to a human case in 2010. We found that the same strain colonized an area of over 46,000 m2 and persisted in soil for over 6 years. No association with rodent burrows was observed, as C. immitis DNA was as likely to be detected inside rodent holes as it was in the surrounding soil. In addition, the presence of C. immitis DNA in soil was correlated with elevated levels of boron, calcium, magnesium, sodium, and silicon in soil leachates. We also observed differences in the microbial communities between C. immitis-positive and -negative soils. Our artificial soil inoculation experiments demonstrated that C. immitis can use soil as a sole source of nutrients. Taken together, these results suggest that soil parameters need to be considered when modeling the distribution of this fungus in the environment. IMPORTANCE Coccidioidomycosis is considered a highly endemic disease for which geographic range is likely to expand from climate change. A better understanding of the ecological niche of Coccidioides spp. is essential for generating accurate distribution maps and predicting future changes in response to the changing environment. Our study used a systematic sampling strategy, advanced molecular detection methods, and soil chemical analysis to identify environmental factors associated with the presence of C. immitis in soil. Our results demonstrate the fungus can colonize the same areas for years and is associated with chemical and microbiological soil characteristics. Our results suggest that in addition to climate parameters, soil characteristics need to be considered when building habitat distribution models for this pathogen.

Using soil survey data to model potential Coccidioides soil habitat and inform Valley fever epidemiology.

Coccidioidomycosis, also known as Valley fever, is a disease that can result in substantial illness and death. It is most common in the southwestern United States and areas of Latin America with arid climates, though reports increasingly suggest its range is wider than previously recognized. The natural habitat of the causative organisms, Coccidioides spp., have been associated with certain soil properties and climatic conditions. Current understanding of its geographic range is primarily defined by skin test studies and outbreak locations. We developed a fuzzy system model to predict suitable soil habitats for Coccidioides across the western United States based on parameters (electrical conductivity, organic matter content, pH, water holding capacity, temperature, and precipitation) from sites where soil sampling has confirmed the presence of Coccidioides. The model identified high coccidioidomycosis incidence areas as having high suitability and identified pockets of elevated suitability corresponding with outbreak locations outside the traditional range. By providing high-resolution estimates of Coccidioides suitability, including areas without public health surveillance for coccidioidomycosis, this model may be able to aid public health and clinical provider decision making. Awareness of possible Coccidioides soil habitats could help mitigate risk during soil-disturbing activities and help providers improve coccidioidomycosis diagnosis and treatment.

Long-term Outcomes of Patients With Fungal Infections Associated With Contaminated Methylprednisolone Injections.

BACKGROUND: The largest health care-associated infection outbreak in the United States occurred during 2012-2013. Following injection of contaminated methylprednisolone, 753 patients developed infection with a dematiaceous mold, Exserohilum rostratum. The long-term outcomes of these infections have not been described. METHODS: This retrospective cohort study of 440 of a total of 753 patients with proven or probable Exserohilum infection evaluated clinical and radiographic findings, antifungal therapy and associated adverse effects, and outcomes at 6 weeks, 3, 6, 9, and 12 months after diagnosis. Patients were grouped into 4 disease categories: meningitis with/without stroke, spinal or paraspinal infections, meningitis/stroke plus spinal/paraspinal infections, and osteoarticular infections. RESULTS: Among the 440 patients, 223 (51%) had spinal/paraspinal infection, 82 (19%) meningitis/stroke, 123 (28%) both, and 12 (3%) osteoarticular infection. Of 82 patients with meningitis/stroke, 18 (22%) died; among those surviving, 87% were cured at 12 months. Only 7 (3%) of 223 patients with spinal/paraspinal infection died, but at 12 months, 68% had persistent or worsening pain and only 47% were cured. For the 123 patients with both meningitis/stroke and spinal/paraspinal infection, 10 (8%) died, pain persisted in 72%, and 52% were cured at 12 months. Only 37% of those with osteoarticular infection were cured at 12 months. Adverse events from antifungal therapy were noted at 6 weeks in 71% of patients on voriconazole and 81% on amphotericin B. CONCLUSIONS: Fungal infections related to contaminated methylprednisolone injections culminated in death in 8% of patients. Persistent pain and disability were seen at 12 months in most patients with spinal/paraspinal infections.

COVID-19 in Correctional and Detention Facilities - United States, February-April 2020.

An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities† on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.

Re-drawing the Maps for Endemic Mycoses.

Endemic mycoses such as histoplasmosis, coccidioidomycosis, blastomycosis, paracoccidioidomycosis, and talaromycosis are well-known causes of focal and systemic disease within specific geographic areas of known endemicity. However, over the past few decades, there have been increasingly frequent reports of infections due to endemic fungi in areas previously thought to be "non-endemic." There are numerous potential reasons for this shift such as increased use of immune suppressive medications, improved diagnostic tests, increased disease recognition, and global factors such as migration, increased travel, and climate change. Regardless of the causes, it has become evident that our previous understanding of endemic regions for these fungal diseases needs to evolve. The epidemiology of the newly described Emergomyces is incomplete; our understanding of it continues to evolve. This review will focus on the evidence underlying the established areas of endemicity for these mycoses as well as new data and reports from medical literature that support the re-thinking these geographic boundaries. Updating the endemic fungi maps would inform clinical practice and global surveillance of these diseases.

Coccidioidomycosis Skin Testing in a Commercially Insured Population, United States, 2014-20171.

Coccidioidomycosis skin testing appears to be uncommon, based on US health insurance claims data. Patient demographic features were consistent with the approval of the test for adults, but few patients had previous coccidioidomycosis diagnosis codes supporting its use for detecting delayed-type hypersensitivity in those with a history of pulmonary coccidioidomycosis.

Suspected Locally Acquired Coccidioidomycosis in Human, Spokane, Washington, USA.

The full geographic range of coccidioidomycosis is unknown, although it is most likely expanding with environmental change. We report an apparently autochthonous coccidioidomycosis patient from Spokane, Washington, USA, a location to which Coccidioides spp. are not known to be endemic.

The detection of Coccidioides from ambient air in Phoenix, Arizona: Evidence of uneven distribution and seasonality.

Coccidioidomycosis is a debilitating fungal disease caused by inhalation of arthroconidia. We developed a novel approach for detection of airborne Coccidioides and used it to investigate the distribution of arthroconidia across the Phoenix, Arizona, metropolitan area. Air filters were collected daily from 21 stationary air-sampling units across the area: the first set collected before, during and after a large dust storm on August 25, 2015, and the second over the 45-day period September 25-November 8, 2016. Analysis of DNA extracted from the filters demonstrated that the day of the dust storm was not associated with increase of Coccidioides in air samples, although evidence of the low-level polymerase chain reaction (PCR) inhibition was observed in DNA extracted from samples collected on the day of the dust storm. Testing over 45 days identified uneven geographic distribution suggesting Coccidioides hot spots. In 2016, highest daily concentration of arthroconidia was observed between September 25-October 20, and only sporadic low levels were detected after that. These results provide evidence of seasonality and uneven spatial distribution of Coccidioides in the air. Our results demonstrate that routine air monitoring for arthroconidia is possible and provides an important tool for Coccidioides surveillance, which can address important questions about environmental exposure and human infection.

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.

Surveillance for Coccidioidomycosis - United States, 2011-2017.

PROBLEM/CONDITION: Coccidioidomycosis (Valley fever) is an infection caused by the environmental fungus Coccidioides spp., which typically causes respiratory illness but also can lead to disseminated disease. This fungus typically lives in soils in warm, arid regions, including the southwestern United States. REPORTING PERIOD: 2011-2017. DESCRIPTION OF SYSTEM: Coccidioidomycosis has been nationally notifiable since 1995 and is reportable in 26 states and the District of Columbia (DC), where laboratories and physicians notify local and state public health departments about possible coccidioidomycosis cases. Health department staff determine which cases qualify as confirmed cases according to the definition established by Council of State and Territorial Epidemiologists and voluntarily submit basic case information to CDC through the National Notifiable Diseases Surveillance System. RESULTS: During 2011-2017, a total of 95,371 coccidioidomycosis cases from 26 states and DC were reported to CDC. The number of cases decreased from 2011 (22,634 cases) to 2014 (8,232 cases) and subsequently increased to 14,364 cases in 2017; >95% of cases were reported from Arizona and California. Reported incidence in Arizona decreased from 261 per 100,000 persons in 2011 to 101 in 2017, whereas California incidence increased from 15.7 to 18.2, and other state incidence rates stayed relatively constant. Patient demographic characteristics were largely consistent with previous years, with an overall predominance among males and among adults aged >60 years in Arizona and adults aged 40-59 years in California. INTERPRETATION: Coccidioidomycosis remains an important national public health problem with a well-established geographic focus. The reasons for the changing trends in reported cases are unclear but might include environmental factors (e.g., temperature and precipitation), surveillance artifacts, land use changes, and changes in the population at risk for the infection. PUBLIC HEALTH ACTION: Health care providers should consider a diagnosis of coccidioidomycosis in patients who live or work in or have traveled to areas with known geographic risk for Coccidioides and be aware that those areas might be broader than previously recognized. Coccidioidomycosis surveillance provides important information about the epidemiology of the disease but is incomplete both in terms of geographic coverage and data availability. Expanding surveillance to additional states could help identify emerging areas that pose a risk for locally acquired infections. In Arizona and California, where most cases occur, collecting systematic enhanced data, such as more detailed patient characteristics and disease severity, could help clarify the reasons behind the recent changes in incidence and identify additional opportunities for focused prevention and educational efforts.

Coccidioidomycosis Among American Indians and Alaska Natives, 2001-2014.

BACKGROUND: American Indians and Alaska Natives (AI/ANs) may be uniquely vulnerable to coccidioidomycosis given the large population residing in the Southwestern United States. We describe coccidioidomycosis-associated hospitalizations and outpatient visits during 2001-2014 in the Indian Health Service (IHS) system and compare hospitalizations with data from the Agency for Healthcare Research and Quality's National (Nationwide) Inpatient Sample (NIS). METHODS: We identified hospitalizations in the IHS and the NIS and outpatient visits in the IHS using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 114.0-114.9. We calculated average annual hospitalization and outpatient visit rates per 1 000 000 population and used Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs). We used multivariable logistic regression to assess factors associated with IHS hospitalization. RESULTS: AI/ANs had the highest average annual hospitalization rate (58.0; 95% CI, 49.5-66.6) of any racial/ethnic group in the NIS, compared with 13.4 (95% CI, 12.7-14.2) for non-Hispanic whites. IHS data showed a hospitalization rate of 37.0; the median length of stay (interquartile range) was 6 (3-10) days. The average annual outpatient visit rate in IHS was 764.2, and it increased from 529.9 in 2001 to 845.9 in 2014. Male sex, age ≥65 years, diabetes, and extrapulmonary or progressive coccidioidomycosis were independently associated with increased risk for hospitalization. Twenty-four percent of patients had ICD-9-CM codes for community-acquired pneumonia in the 3 months before coccidioidomycosis diagnosis. CONCLUSIONS: AI/ANs experience high coccidioidomycosis-associated hospitalization rates, high morbidity, and possible missed opportunities for earlier diagnosis. Yearly trends in IHS data were similar to the general increase in hospitalizations and reported cases nationwide in the same period.

Dengue Knowledge, Attitudes, and Practices Among Arizona Health Care Providers, 2014-2015.

Background: Detection of local dengue transmission requires an aware and engaged medical community, as health care providers are the front line of public health surveillance. To assess the knowledge, attitude, and practice about dengue, an online survey was distributed among Arizona health care providers during 2014 and 2015. Materials and Methods: The survey consisted of a total of 10 knowledge, attitude, and practice questions divided as follows: 5 knowledge questions, 2 attitude questions, and 3 practice questions. The link to the Qualtrics survey was distributed through the Arizona Health Alert Network to a total of 4582 e-mail addresses, of which 335 participants opened the survey, and 196 completed and submitted their responses. Results: Less than half the respondents reported choosing the right dengue diagnostic test (40.4%) or understanding the epidemiology of dengue in Arizona (40.9%). Slightly more than half the respondents reported frequently asking for travel history (59%), and three-fourth of them would notify the local health department on suspicion of a dengue patient (76.1%). Survey score was associated with providers specialized in infectious diseases (1.88, 95% CI: 0.42-3.33, p = 0.01), medical doctors or doctors of osteopathic medicine (1.82, 95% CI: 0.98-2.65, p < 0.0001), and respondents who reported to have heard about the increase in dengue cases in Sonora (Mexico) in fall 2014 (1.51, 95% CI: 0.67-2.34, p = 0.0005), indicating better survey performance. Conclusions: These results indicate that education for health care providers on dengue should be improved particularly among general practice noninfectious disease providers who might be the first point of care for dengue patients. Findings suggest that additional training on clinical management, asking travel history, and notifying the local health department on suspicion of a dengue patient are needed.

Utility of Whole-Genome Sequencing to Ascertain Locally Acquired Cases of Coccidioidomycosis, Washington, USA.

Coccidioidomycosis is an emerging fungal infection in Washington, USA, and the epidemiology of the disease in this state is poorly understood. We used whole-genome sequencing to differentiate locally acquired cases in Washington on the basis of the previously identified phylogeographic population structure of Coccidioides spp. Clinical isolates from coccidioidomycosis cases involving possible Washington soil exposure were included. Of 17 human infections with epidemiologic evidence of possible local acquisition, 4 were likely locally acquired infections and 13 were likely acquired outside Washington. Isolates from locally acquired cases clustered within the previously established Washington clade of C. immitis. Genetic differences among these strains suggest multiple environmental reservoirs of C. immitis in the state.

Update on the Epidemiology of coccidioidomycosis in the United States.

The incidence of reported coccidioidomycosis in the past two decades has increased greatly; monitoring its changing epidemiology is essential for understanding its burden on patients and the healthcare system and for identifying opportunities for prevention and education. We provide an update on recent coccidioidomycosis trends and public health efforts nationally and in Arizona, California, and Washington State. In Arizona, enhanced surveillance shows that coccidioidomycosis continues to be associated with substantial morbidity. California reported its highest yearly number of cases ever in 2016 and has implemented interventions to reduce coccidioidomycosis in the prison population by excluding certain inmates from residing in prisons in high-risk areas. Coccidioidomycosis is emerging in Washington State, where phylogenetic analyses confirm the existence of a unique Coccidioides clade. Additional studies of the molecular epidemiology of Coccidioides will improve understanding its expanding endemic range. Ongoing public health collaborations and future research priorities are focused on characterizing geographic risk, particularly in the context of environmental change; identifying further risk reduction strategies for high-risk groups; and improving reporting of cases to public health agencies.

Interlaboratory agreement of coccidioidomycosis enzyme immunoassay from two different manufacturers.

Coccidioidomycosis, a fungal infection endemic to the Southwestern United States, is challenging to diagnose. The coccidioidomycosis enzyme immunoassay (EIA) test is the least expensive and simplest to perform to detect coccidioidomycosis antibodies in the serum. Concerns regarding falsely positive immunoglobulin (Ig) M EIA test results have led to questions about the agreement of commercially available EIA test kits among laboratories. We sought to evaluate the laboratory agreement of the EIA test at three laboratories using both IMMY and Meridian EIA test kits. Sensitivity and specificity of EIA IgM and IgG were calculated as secondary outcomes. The percent agreement of the EIA IgM and IgG test results among all three laboratories was 90% and 89% for IMMY test kits, respectively, and 67% and 80.5% for Meridian test kits, respectively. Agreement between IgM and IgG combined test results was 85.5% and 70.5%, for IMMY and Meridian, respectively. Combined IgM and IgG assays demonstrated a sensitivity of 68% (62.7%-76%) and a specificity of 99.3% (98%-100%) [IMMY] and a sensitivity of 72.4% (57.3%-87.3%) and a specificity of 91.3% (74%-100%) [Meridian]. In summary, results from the IMMY EIA test kit agreed more often across laboratories than Meridian EIA results, especially for the IgM assay. Isolated positive IgM EIA results using the Meridian test kit should be interpreted with caution and consideration of clinical information and test methodology. Further study of the sensitivity and specificity of coccidioidomycosis EIA test kits is warranted.

Risk Stratification With Coccidioidal Skin Test to Prevent Valley Fever Among Inmates, California, 2015.

Two California state prisons (A and B) have very high rates of coccidioidomycosis (Valley Fever). The prison health care service sought to improve their prevention strategy by risk stratification with a newly available spherulin-based Coccidioides delayed-type hypersensitivity test. Of the 36,789 voluntarily screened inmates, 4.7% experienced adverse reactions. A positive test (8.6% of those tested) was independently associated with (1) incarceration at prisons A and B, (2) admission to prison from a Coccidioides-endemic county, (3) length of stay at prisons A and B, and (4) increasing age. These findings suggest that the test is safe and performing well at risk stratification; the prison system now restricts inmates with negative tests from prisons A and B. This novel use of the test might benefit other coccidioidomycosis prevention programs.

Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study.

BACKGROUND: Fungal infections remain a major contributor to the opportunistic infections that affect people living with HIV. Among them, histoplasmosis is considered neglected, often being misdiagnosed as tuberculosis, and is responsible for numerous deaths in Latin America. The objective of this study was to estimate the burden of HIV-associated histoplasmosis compared with tuberculosis in Latin American countries. METHODS: For this modelling study, we estimated prevalence of previous exposure to Histoplasma capsulatum, HIV-associated histoplasmosis annual incidence, and number of deaths in 2012 in Latin American countries based on historical histoplasmin skin test studies in the general population, with an antigen dilution level of more than 1/10. Studies were identified in a literature search. Data on HIV-associated tuberculosis were extracted from the WHO notifications and outcomes tables and data on people living with HIV were extracted from the UNAIDS report for the year 2012. We systematically propagated uncertainty throughout all the steps of the estimation process. FINDINGS: Among 1310 articles identified as of June 1, 2015, 24 articles were included in the study, representing 129 histoplasmin skin test studies led in the general population of Latin American countries. For the year 2012, we estimated a range of 6710 (95% CI 5680-7867) to 15 657 (13 254-18 357) cases of symptomatic HIV-associated histoplasmosis in Latin America. Hotspot areas for histoplasmosis prevalence (>30%) and incidence (>1·5 cases per 100 people living with HIV) were Central America, the northernmost part of South America, and Argentina. According to realistic scenarios, we estimated a range of 671 (95% CI 568-787) to 9394 (7952-11 014) deaths related to histoplasmosis, compared with 5062 (3777-6405) deaths related to tuberculosis reported in Latin America. INTERPRETATION: Our estimates of histoplasmosis incidence and deaths are high and consistent with published data. For the first time, the burden of histoplasmosis is estimated to be equivalent in incidence and even higher in deaths when compared with tuberculosis among people living with HIV in Latin America. FUNDING: None.