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We present a case of Coccidioides posadasii infection which was contracted during study abroad. This coccidioidomycosis showed atypical manifestations and was diagnosed by a combination of tissue biopsy, metagenomic next–generation sequencing, internal transcribed spacer sequencing and culture. Initial treatment with fluconazole was not effective. Antifungal therapy was switched to voriconazole based on drug sensitivity results with good result. This case demonstrates the clinical significance of combining multiple diagnostic methods.

The National Reference Laboratory in Clinical Mycology of Argentina conducted a retrospective review of human coccidioidomycosis cases diagnosed by the National Mycology Laboratory Network of Argentina between 2010 and 2022 to determine the burden of the disease in the country. A total of 100 human coccidioidomycosis cases were documented, with a higher prevalence in male patients (male-to-female ratio of 1.9:1), with a median age of 41 years. Comparing the number of cases between two 10-year periods (2000–2009 and 2010–2019), the increase was 36.51% (from 63 to 86 cases). Among the 100 recorded cases, 79 tested positive using the double immunodiffusion test. Spherules were observed in 19 cases through histopathology or direct microscopic examination and the fungus was isolated in 39 cases. Thirty-six isolates were identified as Coccidioides posadasii through partial sequencing of the Ag2/PRA gene. Catamarca province had the highest number of cases, comprising 64% of the total, with an incidence rate above 1.0–2.5/100,000 inhabitants until 2018. However, there has been a recent downward trend in the region from 2018 to 2022. It is concerning that more than half of diagnosed cases were chronic pulmonary or disseminated forms, indicating a lack of early disease detection. To rectify this issue, it is imperative to conduct targeted training programs for healthcare personnel and enhance public awareness within the endemic area. This will contribute to a better understanding of the true burden of coccidioidomycosis and enable the implementation of appropriate sanitary control measures. [ABSTRACT FROM AUTHOR]

Coccidioides immitis and posadasii are closely related fungal species that cause coccidioidomycosis. These dimorphic organisms cause disease in immunocompetent as well as immunocompromised individuals and as much as 40% of the population is infected in the endemic area. Although most infections resolve spontaneously, the infection can be prolonged and, in some instances, fatal. Coccidioides has been studied for more than 100 years and many aspects of the organism and the disease it causes have been investigated. There are over 500 manuscripts concerning Coccidioides (excluding clinical articles) referenced in PubMed over the past 50 years, so there is a large body of evidence to review. We reviewed the most accurate and informative basic research studies of these fungi including some seminal older studies as well as an extensive review of current research. This is an attempt to gather the most important basic research studies about this fungus into one publication. To focus this review, we will discuss the mycology of the organism exclusively rather than the studies of the host response or clinical studies. We hope that this review will be a useful resource to those interested in Coccidioides and coccidioidomycosis.

Takashi Abe,1,* Fumihiro Yamaguchi,1,* Shunsuke Sakakura,1 Yo Shiratori,1 Ayaka Mase,1 Toshitaka Funaki,1 Yoshito Kamio,2 Takashi Suzuki,2 Yusuke Shikama,1 Yasutaka Hoshino3 1Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan; 2Departments of Thoracic Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan; 3Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan*These authors contributed equally to this workCorrespondence: Fumihiro Yamaguchi, Department of Respiratory Medicine, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, 227-8501, Japan, Tel +81-45-971-1151, Email f_y@med.showa-u.ac.jpAbstract: Coccidioidomycosis is an endemic disease that is particularly prevalent in the United States. However, its geographic distribution is becoming widespread. Here, we present a Japanese male who resided in the United States for 1 year, where he was diagnosed with pulmonary coccidioidomycosis that was accompanied by cavity formation. He did not tolerate antifungal therapy and consequently underwent partial resection of the upper lobe of his left lung upon his return to Japan. The patient’s symptoms improved after surgery. The trend toward global networking and logistics means that a diagnosis of coccidioidomycosis should be considered in routine practice in nonendemic areas. Due to the rarity of surgical treatment for this disease, prolonged follow-up is necessary. During the last follow-up, the patient was symptom-free.Keywords: coccidioidomycosis, Coccidioides immitis, Coccidioides posadasii, endemic disease

Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis in many arid regions of the Americas. One of these regions is bordered by the Caribbean Sea, and the surrounding landscape may play an important role in the dispersion of C. posadasii across South America through southeastern Mexico, Honduras, Guatemala, and Venezuela. Comparative phylogenomic analyses of C. posadasii reveal that clinical strains from Venezuela are genetically distinct from the North American populations found in (i) Arizona and (ii) Texas, Mexico, and the rest of South America (TX/MX/SA). We find evidence for admixture between the Venezuela and the North American populations of C. posadasii in Central America. Additionally, the proportion of Venezuelan alleles in the admixed population decreases as latitude (and distance from Venezuela) increases. Our results indicate that the population in Venezuela may have been subjected to a recent bottleneck and shows a strong population structure. This analysis provides insight into potential for Coccidioides spp. to invade new regions.IMPORTANCE Valley Fever is a fungal disease caused by two species of fungi: Coccidioides immitis and C. posadasii These fungi are found throughout the arid regions of North and South America; however, our understanding of genetic diversity and disease in South America is limited. In this report, we analyze 10 new genomes of Coccidioides posadasii from regions bordering the Caribbean Sea. We show that these populations are distinct and that isolates from Venezuela are likely a result of a recent bottleneck. These data point to patterns that might be observed when investigating recently established populations.

AbstractCoccidioides spp. are dimorphic, pathogenic fungi that can cause severe human and animal disease. Like the other primary fungal pathogens, animal infection results in a morphologic transformation from the environmental mycelial phase to a tissue phase, known as a spherule. The sequencing and annotation of Coccidioides spp. and the genomes of several nonpathogenic Onygenales species allows comparisons that provide clues about the Coccidioides spp. genes that might be involved in pathogenesis. The analysis in this study is a gene by gene orthology comparison. Although there were few differences in the size of genes families in the Coccidioides spp.-specific group compared to the genes shared by Coccidioides spp. and nonpathogenic Onygenales, there were a number of differences in the characterization of the two types of genes. Many more Coccidioides spp.-specific genes are up-regulated expression in spherules. Coccidioides spp.-specific genes more often lacked functional annotation and were more often classified as orphan genes. Analysis by random forest machine learning confirmed that high numbers of orthologs and high levels of expression in hyphae were predictive of common genes, while high levels of expression in spherules and more nonsynonymous predicted Coccidioides spp.-specific genes. Review of individual genes in the Coccidioides spp.-specific group identified a histidine kinase, two thioredoxin genes, a calmodulin gene and ureidoglycolate hydrolase. Hopefully, identification of these genes will be useful for pursuing potential Coccidioides spp. virulence genes in the future.

Coccidioidomycosis is a fungal disease caused by either Coccidioides immitis or Coccidioides posadasii. Anecdotal evidence suggests that camelids are particularly susceptible to this disease and that a relatively large percentage of pneumonias in these animals are caused by Coccidioides spp. In a search of 21 y (1992-2013) of records from the California Animal Health and Food Safety Laboratory, we found 79 cases of coccidioidomycosis diagnosed in camelids; 66 (84%) had pneumonia and 13 (16%) had lesions only in organs other than the lungs. The organs most frequently affected were lung (84%) and liver (78%). Coccidioides spp. were the cause of pneumonia in 66 of 362 (18%) camelid cases during the study period. The lesions in affected organs were multifocal-to-coalescing pyogranulomas, which in most cases were visible grossly. Ten of the 12 formalin-fixed, paraffin-embedded lung samples tested by a universal Coccidioides spp. PCR assay were positive (4 C. immitis, 2 C. posadasii); the species could not be determined in 4 of the 10 cases positive by PCR. Coccidioidomycosis is an important cause of pneumonia in camelids in California, and can be caused by either C. immitis or C. posadasii.

We present a case of Coccidioides posadasii infection which was contracted during study abroad. This coccidioidomycosis showed atypical manifestations and was diagnosed by a combination of tissue biopsy, metagenomic next-generation sequencing, internal transcribed spacer sequencing and culture. Initial treatment with fluconazole was not effective. Antifungal therapy was switched to voriconazole based on drug sensitivity results with good result. This case demonstrates the clinical significance of combining multiple diagnostic methods., (© 2024 The Authors. Published by Elsevier B.V. on behalf of International Society for Human and Animal Mycology.)

On the basis of a 1957 geographic Coccidioides seropositivity survey, 3 counties in southwestern Utah, USA, were considered coccidioidomycosis-endemic, but there has been a paucity of information on the disease burden in Utah since. We report findings from a recent clinical and epidemiologic study of coccidioidomycosis in Utah. To describe clinical characteristics, we identified all coccidioidomycosis cases in an integrated health system in the state during 2006–2015. For epidemiologic analysis, we used cases reported to the Utah Department of Health during 2009–2015. Mean state incidence was 1.83 cases/100,000 population/year. Washington County, in southwestern Utah, had the highest incidence, 17.2 cases/100,000 population/year. In a generalized linear model with time as a fixed effect, mean annual temperature, population, and new construction were associated with regional variations in incidence. Using these variables in a spatiotemporal model, we estimated the adjusted regional variation by county to predict areas where Coccidioides infections might increase.

Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of Coccidioides spp. This neglected disease has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S., Mexico, Central and South America. The incidence of this infection in California and Arizona has been increasing over the past fifteen years. Several large cities are within the endemic region in the U.S. Coccidioidomycosis accounts for 25,000 hospital admissions per year in California. While most cases of coccidioidomycosis resolve spontaneously, up to 40% are severe enough to require anti-fungal treatment, and a significant number disseminate beyond the lungs. Disseminated infection involving the meninges is fatal without appropriate treatment. Infection with Coccidioides spp. is protective against a second infection, so vaccination seems biologically plausible. This review of efforts to develop a vaccine against coccidioidomycosis focuses on vaccine approaches and the difficulties in identifying protein antigen/adjuvant combinations that protect in experimental mouse models. Although the quest for a vaccine is still in the early stage, scientific efforts for vaccine development may pave the way for future success.

Background: Coccidioidomycosis represents an endemic and challenging disease, with rare extrapulmonary manifestations. The present review of all published cases of core and extremities osseous coccidioidomycosis aims to describe epidemiology, patients' characteristics, symptoms as well as medical and surgical treatment options and their effectiveness. Methods: A thorough review of all published skeletal core and extremity infections due to Coccidioides species was conducted. Information regarding demographics, causative fungus, antifungal treatment (AFT), surgical management as well as the infection outcome was recorded. Results: A total of 92 cases of Coccidioides spp. skeletal infections were recorded in 87 patients. The patients' mean age was 35.3 years. The most common site of infection was the spine (82.6%), followed by the foot (6.5%), while the predominant symptom upon presentation was pain (29.9%). Immunosuppressive conditions and/or medications were observed in 21 patients (24.1%). Regarding imaging methods, indicating diagnosis, plain X-rays or CT scans were performed in most patients (50.6%), followed by magnetic resonance imaging (MRI) (47.1%). Most cases were diagnosed through histopathology (62; 71.3%), followed by serology testing (36; 42.4%) and by cultures (35; 40.2%). In 32 cases (36.8%), Coccidioides immitis was cultured, while in the remaining 55 cases (63.2%) the fungus was not further characterized. Regarding AFT, amphotericin B was the preferred agent (52.9%), followed by fluconazole (43.3%). In most cases (78.2%) surgical treatment was also performed. Treatment was successful in 80.5% of cases. Conclusions: Skeletal core and extremity infections due to Coccidioides spp. represent a severe disease. With the available data, the combination of prolonged proper AFT with surgical intervention seems to be the optimal current therapeutic approach. [ABSTRACT FROM AUTHOR]

On the basis of a 1957 geographic Coccidioides seropositivity survey, 3 counties in southwestern Utah, USA, were considered coccidioidomycosis-endemic, but there has been a paucity of information on the disease burden in Utah since. We report findings from a recent clinical and epidemiologic study of coccidioidomycosis in Utah. To describe clinical characteristics, we identified all coccidioidomycosis cases in an integrated health system in the state during 2006-2015. For epidemiologic analysis, we used cases reported to the Utah Department of Health during 2009-2015. Mean state incidence was 1.83 cases/100,000 population/year. Washington County, in southwestern Utah, had the highest incidence, 17.2 cases/100,000 population/year. In a generalized linear model with time as a fixed effect, mean annual temperature, population, and new construction were associated with regional variations in incidence. Using these variables in a spatiotemporal model, we estimated the adjusted regional variation by county to predict areas where Coccidioides infections might increase. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is a fungal, respiratory disease caused by Coccidioides immitis and Coccidioides posadasii. The host immune responses that define disease outcome during infection are largely unknown, although T helper responses are required. Adaptive immunity is influenced by innate immunity as antigen-presenting cells activate and educate adaptive responses. Macrophage and dendritic cell (DC) recognition of pathogen surface molecules are critical for Coccidioides clearance. We characterize the broad innate immune responses to Coccidioides by analyzing macrophage and dendritic cell responses to Coccidioides arthroconidia using avirulent, vaccine Coccidioides strain NR-166 (Dcts2/Dard1/Dcts3), developed from parental virulent strain C735. We developed a novel flow cytometry-based method to analyze macrophage phagocytosis to complement traditional image-scoring methods. Our study found that macrophage polarization is blocked at M0 phase and activation reduced, while DCs polarize into proinflammatory DC1s, but not anti-inflammatory DC2, following interaction with Coccidioides. However, DCs exhibit a contact-dependent reduced activation to Coccidioides as defined by co-expression of MHC-II and CD86. In vivo, only modest DC1/DC2 recruitment and activation was observed with avirulent Coccidioides infection. In conclusion, the vaccine Coccidioides strain recruited a mixed DC population in vivo, while in vitro data suggest active innate immune cell inhibition by Coccidioides. [ABSTRACT FROM AUTHOR]

Abstract Background Coccidioides spp. are dimorphic fungi endemic to Central America, regions of South America and southwestern USA. Two species cause most human disease: Coccidioides immitis (primarily California isolates) and Coccidioides posadasii. Coccidioidomycosis is typically acquired through inhalation of soil or dust containing spores. Coccidioidal meningitis (CM), most common in the immunocompromised host, can also affect immunocompetent hosts. Case presentation We report a case of C. posadasii meningoencephalitis in a previously healthy 42-year-old Caucasian male who returned to Canada after spending time working in New Mexico. He presented with a 3-week history of headache, malaise and low-grade fevers. He developed progressive confusion and decreasing level of consciousness following hospitalization. Evidence of hydrocephalus and leptomeningeal enhancement was demonstrated on magnetic resonance imaging (MRI) of his brain. Serologic and PCR testing of the patient's CSF confirmed Coccidioides posadasii. Despite appropriate antifungal therapy he continues to have significant short-term memory deficits and has not returned to his full baseline functional status. Conclusions Travel to endemic regions can result in disease secondary to Coccidioides spp. and requires physicians in non-endemic areas to have a high index of suspicion. Effective therapeutic options have reduced the mortality rate of CM, however, it is still associated with significant morbidity and requires life-long therapy.

The genus Coccidioides consists of two species: C. immitis and C. posadasii. Prior to 2000, all disease was thought to be caused by a single species, C. immitis. The organism grows in arid to semiarid alkaline soils throughout western North America and into Central and South America. Regions in the United States, with highest prevalence of disease, include California, Arizona, and Texas. The Mexican states of Baja California, Coahuila, Sonora, and Neuvo Leon currently have the highest skin test positive results. Central America contains isolated endemic areas in Guatemala and Honduras. South America has isolated regions of high endemicity including areas of Colombia, Venezuela, Argentina, Paraguay, and Brazil. Although approximately 15,000 cases per year are reported in the United States, actual disease burden is estimated to be in the hundreds of thousands, as only California and Arizona have dedicated public health outreach, and report and track disease reliably. In this review, we survey genomics, epidemiology, ecology, and summarize aspects of disease, diagnosis, prevention, and treatment.

Coccidioides immitis and posadasii are closely related fungal species that cause coccidioidomycosis. These dimorphic organisms cause disease in immunocompetent as well as immunocompromised individuals and as much as 40% of the population is infected in the endemic area. Although most infections resolve spontaneously, the infection can be prolonged and, in some instances, fatal. Coccidioides has been studied for more than 100 years and many aspects of the organism and the disease it causes have been investigated. There are over 500 manuscripts concerning Coccidioides (excluding clinical articles) referenced in PubMed over the past 50 years, so there is a large body of evidence to review. We reviewed the most accurate and informative basic research studies of these fungi including some seminal older studies as well as an extensive review of current research. This is an attempt to gather the most important basic research studies about this fungus into one publication. To focus this review, we will discuss the mycology of the organism exclusively rather than the studies of the host response or clinical studies. We hope that this review will be a useful resource to those interested in Coccidioides and coccidioidomycosis.

Endemic mycoses remain a significant cause of morbidity and mortality among immunocompromised patients. As the number of immunosuppressed individuals increases worldwide, the incidence of endemic mycoses is also expected to rise. In immunocompromised patients, endemic mycoses can present in atypical fashion, cause more severe and/or disseminated disease, and result in higher mortality. Despite several noteworthy advances over the past decade, significant challenges remain with regard to the prevention, diagnosis, and therapy of endemic mycoses in immunocompromised hosts. This review highlights important developments related to the epidemiology, diagnosis, treatment, and prevention of commonly encountered endemic mycoses. We also discuss emerging topics, knowledge gaps, and areas of future research.

A 3-mo-old male llama was examined because of a 4-wk history of lethargy and ill thrift. Clinical examination revealed subcutaneous masses in the left prescapular and right inguinal regions, mild ataxia, a slight head tilt to the right, and right ear droop. The cria died before clinical workup was complete. At autopsy, there was generalized lymphadenomegaly, a hepatic nodule, a midbrain mass causing rostral compression of the cerebellum, and internal hydrocephalus. Microscopic findings included pyogranulomatous lymphadenitis, meningoencephalitis, hepatitis, and bronchopneumonia. Intralesional fungal spherules, most consistent with Coccidioides spp., were identified in the lymph nodes, lung, and brain. Fungal culture, single-nucleotide variation genotyping real-time PCR, and DNA sequencing confirmed Coccidioides posadasii. The dam of the cria was native to Arizona and had been moved to Missouri ~2.5 y previously. Agar gel immunodiffusion assay of the herd revealed that only the dam was positive for Coccidioides spp.; 6 herdmates were negative. Computed tomography of the dam revealed multiple nodules within the lungs and liver, which were presumed to be an active coccidioidomycosis infection. This case of systemic coccidioidomycosis in a llama native to Missouri was presumably acquired by vertical transmission from the dam. [ABSTRACT FROM AUTHOR]

Background: Coccidioidomycosis represents an endemic and challenging disease, with rare extrapulmonary manifestations. The present review of all published cases of core and extremities osseous coccidioidomycosis aims to describe epidemiology, patients’ characteristics, symptoms as well as medical and surgical treatment options and their effectiveness. Methods: A thorough review of all published skeletal core and extremity infections due to Coccidioides species was conducted. Information regarding demographics, causative fungus, antifungal treatment (AFT), surgical management as well as the infection outcome was recorded. Results: A total of 92 cases of Coccidioides spp. skeletal infections were recorded in 87 patients. The patients’ mean age was 35.3 years. The most common site of infection was the spine (82.6%), followed by the foot (6.5%), while the predominant symptom upon presentation was pain (29.9%). Immunosuppressive conditions and/or medications were observed in 21 patients (24.1%). Regarding imaging methods, indicating diagnosis, plain X-rays or CT scans were performed in most patients (50.6%), followed by magnetic resonance imaging (MRI) (47.1%). Most cases were diagnosed through histopathology (62; 71.3%), followed by serology testing (36; 42.4%) and by cultures (35; 40.2%). In 32 cases (36.8%), Coccidioides immitis was cultured, while in the remaining 55 cases (63.2%) the fungus was not further characterized. Regarding AFT, amphotericin B was the preferred agent (52.9%), followed by fluconazole (43.3%). In most cases (78.2%) surgical treatment was also performed. Treatment was successful in 80.5% of cases. Conclusions: Skeletal core and extremity infections due to Coccidioides spp. represent a severe disease. With the available data, the combination of prolonged proper AFT with surgical intervention seems to be the optimal current therapeutic approach.

Coccidioidomycosis is a fungal, respiratory disease caused by Coccidioides immitis and Coccidioides posadasii. This emerging infectious disease ranges from asymptomatic to pulmonary disease and disseminated infection. Most infections are cleared with little to no medical intervention whereas chronic disease often requires life-long medication with severe impairment in quality of life. It is unclear what differentiates hosts immunity resulting in disease resolution versus chronic infection. Current understanding in mycology-immunology suggests that chronic infection could be due to maladaptive immune responses. Immunosuppressed patients develop more severe disease and mouse studies show adaptive Th1 and Th17 responses are required for clearance. This is supported by heightened immunosuppressive regulatory responses and lowered anti-fungal T helper responses in chronic Coccidioides patients. Diagnosis and prognosis is difficult as symptoms are broad and overlapping with community acquired pneumonia, often resulting in misdiagnosis and delayed treatment. Furthermore, we lack clear biomarkers of disease severity which could aid prognosis for more effective healthcare. As the endemic region grows and population increases in endemic areas, the need to understand Coccidioides infection is becoming urgent. There is a growing effort to identify fungal virulence factors and host immune components that influence fungal immunity and relate these to patient disease outcome and treatment. This review compiles the known immune responses to Coccidioides spp. infection and various related fungal pathogens to provide speculation on Coccidioides immunity.

ABSTRACT Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis in many arid regions of the Americas. One of these regions is bordered by the Caribbean Sea, and the surrounding landscape may play an important role in the dispersion of C. posadasii across South America through southeastern Mexico, Honduras, Guatemala, and Venezuela. Comparative phylogenomic analyses of C. posadasii reveal that clinical strains from Venezuela are genetically distinct from the North American populations found in (i) Arizona and (ii) Texas, Mexico, and the rest of South America (TX/MX/SA). We find evidence for admixture between the Venezuela and the North American populations of C. posadasii in Central America. Additionally, the proportion of Venezuelan alleles in the admixed population decreases as latitude (and distance from Venezuela) increases. Our results indicate that the population in Venezuela may have been subjected to a recent bottleneck and shows a strong population structure. This analysis provides insight into potential for Coccidioides spp. to invade new regions. IMPORTANCE Valley Fever is a fungal disease caused by two species of fungi: Coccidioides immitis and C. posadasii. These fungi are found throughout the arid regions of North and South America; however, our understanding of genetic diversity and disease in South America is limited. In this report, we analyze 10 new genomes of Coccidioides posadasii from regions bordering the Caribbean Sea. We show that these populations are distinct and that isolates from Venezuela are likely a result of a recent bottleneck. These data point to patterns that might be observed when investigating recently established populations.

Coccidioidomycosis is a fungal, respiratory disease caused by Coccidioides immitis and Coccidioides posadasii. This emerging infectious disease ranges from asymptomatic to pulmonary disease and disseminated infection. Most infections are cleared with little to no medical intervention whereas chronic disease often requires life-long medication with severe impairment in quality of life. It is unclear what differentiates hosts immunity resulting in disease resolution versus chronic infection. Current understanding in mycology-immunology suggests that chronic infection could be due to maladaptive immune responses. Immunosuppressed patients develop more severe disease and mouse studies show adaptive Th1 and Th17 responses are required for clearance. This is supported by heightened immunosuppressive regulatory responses and lowered anti-fungal T helper responses in chronic Coccidioides patients. Diagnosis and prognosis is difficult as symptoms are broad and overlapping with community acquired pneumonia, often resulting in misdiagnosis and delayed treatment. Furthermore, we lack clear biomarkers of disease severity which could aid prognosis for more effective healthcare. As the endemic region grows and population increases in endemic areas, the need to understand Coccidioides infection is becoming urgent. There is a growing effort to identify fungal virulence factors and host immune components that influence fungal immunity and relate these to patient disease outcome and treatment. This review compiles the known immune responses to Coccidioides spp. infection and various related fungal pathogens to provide speculation on Coccidioides immunity. [ABSTRACT FROM AUTHOR]

Summary: Background: Coccidioides spp. are dimorphic fungi endemic to parts of the United States, Mexico, Central and South America. Infection can cause a range of disease from self‐limited acute pneumonia to severe disseminated disease. Methods: We performed a retrospective chart review of medical records of cases of culture‐proven acute coccidioidomycosis at the University of California San Diego between 1 April 2015 and 31 December 2019 and described the demographics, risk factors and outcomes of these cases. Results: Over the study period, fifteen evaluable cases of culture‐proven acute coccidioidomycosis were identified. Of these, 87% (13/15) had traditional risk factors for coccidioidomycosis infection while two lacked known risk factors, including one patient with cirrhosis and one with chronic hepatitis C infection. Seven of fifteen (47%) had primary coccidioidomycosis of the lungs without dissemination and 7/15 (47%) disseminated disease. Of those with disseminated disease, 6/7 (86%) had either high‐risk ethnicity or blood type as their only risk factor. At 90 days, 11/15 (73%) were alive, 3/15 (20%) deceased and 1/15 (7%) lost to follow‐up. Of those not alive at 90 days, 1/3 (33%) had disseminated disease and 2/3 (67%) primary coccidioidomycosis, both on immunosuppressive therapy. Discussion: Coccidioides spp. infection occurs in a variety of hosts with varying underlying risk factors, with the majority in our cohort overall and 86% with disseminated disease lacking traditional risk factors for invasive fungal infection other than ethnicity and/or blood phenotype. Clinicians should be aware of these non‐traditional risk factors in patients with coccidioidomycosis infection. [ABSTRACT FROM AUTHOR]

The genus Coccidioides consists of two species: C. immitis and C. posadasii. Prior to 2000, all disease was thought to be caused by a single species, C. immitis. The organism grows in arid to semiarid alkaline soils throughout western North America and into Central and South America. Regions in the United States, with highest prevalence of disease, include California, Arizona, and Texas. The Mexican states of Baja California, Coahuila, Sonora, and Neuvo Leon currently have the highest skin test positive results. Central America contains isolated endemic areas in Guatemala and Honduras. South America has isolated regions of high endemicity including areas of Colombia, Venezuela, Argentina, Paraguay, and Brazil. Although approximately 15,000 cases per year are reported in the United States, actual disease burden is estimated to be in the hundreds of thousands, as only California and Arizona have dedicated public health outreach, and report and track disease reliably. In this review, we survey genomics, epidemiology, ecology, and summarize aspects of disease, diagnosis, prevention, and treatment. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis (Valley Fever) is a fungal infection found in the southwestern United States, northern Mexico, and some places in Central and South America. The fungi that cause it (Coccidioides immitis and Coccidioides posadasii) are normally soil dwelling, but, if disturbed, become airborne and infect the host when their spores are inhaled. It is thus natural to surmise that weather conditions, which foster the growth and dispersal of Coccidioides, must have an effect on the number of cases in the endemic areas. This article reviews our attempts to date at quantifying this relationship in Kern County, California (where C. immitisis endemic). We have examined the effect on incidence resulting from precipitation, surface temperature, and wind speed. We have performed our studies by means of a simple linear correlation analysis, and by a generalized autoregressive moving average model. Our first analysis suggests that linear correlations between climatic parameters and incidence are weak; our second analysis indicates that incidence can be predicted largely by considering only the previous history of incidence in the county—the inclusion of climate- or weather-related time sequences improves the model only to a relatively minor extent. Our work therefore suggests that incidence fluctuations (about a seasonally varying background value) are related to biological and/or anthropogenic reasons, and not so much to weather or climate anomalies.

Coccidioidomycosis is a fungal, respiratory disease caused by Coccidioides immitis and Coccidioides posadasii. The host immune responses that define disease outcome during infection are largely unknown, although T helper responses are required. Adaptive immunity is influenced by innate immunity as antigen-presenting cells activate and educate adaptive responses. Macrophage and dendritic cell (DC) recognition of pathogen surface molecules are critical for Coccidioides clearance. We characterize the broad innate immune responses to Coccidioides by analyzing macrophage and dendritic cell responses to Coccidioides arthroconidia using avirulent, vaccine Coccidioides strain NR-166 (Δcts2/Δard1/Δcts3), developed from parental virulent strain C735. We developed a novel flow cytometry-based method to analyze macrophage phagocytosis to complement traditional image-scoring methods. Our study found that macrophage polarization is blocked at M0 phase and activation reduced, while DCs polarize into proinflammatory DC1s, but not anti-inflammatory DC2, following interaction with Coccidioides. However, DCs exhibit a contact-dependent reduced activation to Coccidioides as defined by co-expression of MHC-II and CD86. In vivo, only modest DC1/DC2 recruitment and activation was observed with avirulent Coccidioides infection. In conclusion, the vaccine Coccidioides strain recruited a mixed DC population in vivo, while in vitro data suggest active innate immune cell inhibition by Coccidioides.

Coccidioides is a primary pathogenic fungus, which infects humans through highly infectious arthroconidia, causing substantial morbidity including life-threatening disseminated infections. Due to the low infectious dose, laboratory personnel might become infected during diagnostic procedures. Accordingly, coccidioidomycosis is reported as the most frequent laboratory-acquired systemic mycosis worldwide. This risk is aggravated in non-endemic countries, where the diagnosis may not be suspected. We report on an inadvertent exposure of 44 persons to Coccidioides posadasii in a clinical microbiology laboratory in Chile, the measures of containment after rapid diagnosis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the lessons learnt in a non-endemic setting. [ABSTRACT FROM AUTHOR]

The fungal genus Coccidioides is composed of two species, Coccidioides immitis and Coccidioides posadasii. These two species are the causal agents of coccidioidomycosis, a pulmonary disease also known as valley fever. The two species are thought to have shared genetic material due to gene exchange in spite of their long divergence. To quantify the magnitude of shared ancestry between them, we analyzed the genomes of a population sample from each species. Next, we inferred what is the expected size of shared haplotypes that might be inherited from the last common ancestor of the two species and find a cutoff to find what haplotypes have conclusively been exchanged between species. Finally, we precisely identified the breakpoints of the haplotypes that have crossed the species boundary and measure the allele frequency of each introgression in this sample. We find that introgressions are not uniformly distributed across the genome. Most, but not all, of the introgressions segregate at low frequency. Our results show that divergent species can share alleles, that species boundaries can be porous, and highlight the need for a systematic exploration of gene exchange in fungal species. [ABSTRACT FROM AUTHOR]

During the past 20 years, a general picture of the genetic diversity and population structure of Coccidioides, the causal agent of coccidioidomycosis (Valley fever), has emerged. The genus consists of 2 genetically diverse species, C. immitis and C. posadasii, each of which contains 1 or more distinct populations with limited gene flow. Genotypic data indicate that C. immitis is divided into 2 subpopulations (central and southern California populations) and C. posadasii is divided into 3 subpopulations (Arizona, Mexico, and Texas/South America populations). However, admixture within and among these populations and the current paucity of environmental isolates limit our understanding of the population genetics of Coccidioides. We assessed population structure of Coccidioides in Arizona by analyzing 495 clinical and environmental isolates. Our findings confirm the population structure as previously described and indicate a finer scale population structure in Arizona. Environmental isolates appear to have higher genetic diversity than isolates from human patients.

Endemic mycoses represent a growing public health challenge in North America. We describe the epidemiology of 1,392 microbiology laboratory-confirmed cases of blastomycosis, histoplasmosis, and coccidioidomycosis in Ontario during 1990-2015. Blastomycosis was the most common infection (1,092 cases; incidence of 0.41 cases/100,000 population), followed by histoplasmosis (211 cases) and coccidioidomycosis (89 cases). Incidence of blastomycosis increased from 1995 to 2001 and has remained elevated, especially in the northwest region, incorporating several localized hotspots where disease incidence (10.9 cases/100,000 population) is 12.6 times greater than in any other region of the province. This retrospective study substantially increases the number of known endemic fungal infections reported in Canada, confirms Ontario as an important region of endemicity for blastomycosis and histoplasmosis, and provides an epidemiologic baseline for future disease surveillance. Clinicians should include blastomycosis and histoplasmosis in the differential diagnosis of antibiotic-refractory pneumonia in patients traveling to or residing in Ontario. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is a systemic fungal infection for which a vaccine has been sought for over fifty years. The avirulent Coccidioides posadasii strain, Δcps1 , which is missing a 6 kb gene, showed significant protection in mice. These studies explore conditions of protection in mice and elucidate the immune response. Mice were vaccinated with different doses and viability states of Δcps1 spores, challenged with virulent C. posadasii , and sacrificed at various endpoints, dependent on experimental objectives. Tissues from vaccinated mice were harvested for in vitro elucidation of immune response. Vaccination with viable Δcps1 spores was required for protection from lethal challenge. Viable spore vaccination produced durable immunity, lasting at least 6 months, and prolonged survival (≥6 months). The C. posadasii vaccine strain also protected mice against C. immitis (survival ≥ 6 months). Cytokines from infected lungs of vaccinated mice in the first four days after Cp challenge showed significant increases of IFN-γ, as did stimulated CD4 + spleen cells from vaccinated mice. Transfer of CD4 + cells, but not CD8 + or B cells, reduced fungal burdens following challenge. IFN-γ from CD4 + cells in vaccinated mice indicates a Th1 response, which is critical for host control of coccidioidomycosis. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infections, including those caused by yeasts, moulds and endemic organisms, can be significant causes of morbidity and mortality in immunocompromised hosts, those with multiple comorbidities and occasionally immunocompetent hosts. Current antifungal agents are often limited by drug toxicities, drug interactions or the development of resistance. VT-1598 is a novel tetrazole that has greater specificity for fungal Cyp51 than currently available triazoles and thus the potential for clinically significant drug interactions is reduced. We measured the in vitro activity of VT-1598 against clinical isolates of Candida and Cryptococcus species, endemic fungi, including Coccidioides, Blastomyces and Histoplasma, Aspergillus species and Rhizopus arrhizus.Methods: Antifungal susceptibility testing was performed by broth microdilution or macrodilution methods per CLSI standards. Clinical isolates of each species were used and clinically available antifungal agents were tested against each isolate.Results: VT-1598 demonstrated in vitro activity against yeasts and moulds that was similar to or greater than that of clinically available antifungal agents, including amphotericin B, fluconazole, caspofungin, voriconazole and posaconazole. The in vitro activity of VT-1598 was also maintained against resistant isolates, including fluconazole-resistant Candida isolates. In vitro activity was also observed against endemic fungi, including Blastomyces, Histoplasma and both Coccidioides immitis and Coccidioides posadasii.Conclusions: VT-1598 demonstrated in vitro activity against yeasts, moulds and endemic fungi, which was maintained against isolates that had reduced susceptibility to other antifungals. Further studies are warranted to evaluate the in vivo efficacy of VT-1598 against various fungal pathogens. [ABSTRACT FROM AUTHOR]

Coccidioides immitis and C. posadasii are two highly pathogenic dimorphic fungal species that are endemic in the arid areas of the new world, including the region from west Texas to southern and central California in the USA that cause coccidioidomycosis (also known as Valley Fever). In highly endemic regions such as southern Arizona, up to 50% of long term residents have been infected. New information about fungal population genetics, ecology, epidemiology, and host-pathogen interactions is becoming available. However, our understanding of some aspects of coccidioidomycosis is still incomplete, including the extent of genetic variability of the fungus, the genes involved in virulence, and how the changes in gene expression during the organism's dimorphic life cycle are related to the transformation from a free-living mold to a parasitic spherule. Unfortunately, efforts to develop an effective subunit vaccine have not yet been productive, although two potential live fungus vaccines have been developed. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis, commonly known as valley fever, is a disease caused by two species of fungi, Coccidioides immitis and Coccidioides posadasii . Coccidioidomycosis is often self-limiting; however, in some patients, the disease can rapidly progress to a severe and potentially life-threatening illness. Proper diagnostics for coccidioidomycosis are important because acute disease can manifest as community-acquired pneumonia, and can be misdiagnosed as a viral or bacterial infection. Improper diagnosis can lead to unnecessary antibacterial therapy and may encourage extra-pulmonary proliferation of the fungus, which then requires longer antifungal therapy. Although coccidioidomycosis is caused by two different species, in terms of symptoms, disease progression, or clinical diagnostics, there are no known differences between the species. Additionally, recent work has revealed that the distribution of the organism in the environment may be changing and that the organism exists in the environment beyond the region of high endemicity. Overall, disease incidence has risen, and it is not known if this represents a better reporting and diagnosis infrastructure, increased environmental load, or increasing pathogenicity. Discussed here are the most common approaches to diagnose coccidioidomycosis, as well as recent advances in our understanding of the changing epidemiology of the disease and the causative organism. [ABSTRACT FROM AUTHOR]

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Two novel family 18 chitinases, chiA and chiH , were identified and cloned from the transcriptome of H. sinensis based on the transcriptome sequence data. The recombinant chitinases were overexpressed in Escherichia coli BL21, subsequently purified and functionally characterized. The optimal temperature and pH for chiA were 55 °C and 5.0, respectively, and those for chiH were 50 °C and 5.0, respectively. The highest enzyme activities of 11.5 U/mg and 8.1 U/mg were obtained for chiA and chiH, respectively, when colloidal chitin was used as the substrate with Ba 2+ . chiA exhibited higher V max of 1.94 μmol/μg/h and k cat of 1.443 S −1 than those of chiH with V max of 1.63 μmol/μg/h and k cat of 1.175 S −1 , and both were efficient towards colloidal chitin compared with other typical family 18 chitinases. Substrate specificity and gene expression analyses indicated that chiA and chiH preferred substrates containing N -acetyl groups, such as colloidal chitin and glycol chitin, while no activity was detected toward laminarin, cellobiose, carboxymethyl cellulose and starch. The work presented here would aid in the understanding and performance of future studies on the infection mechanism of H. sinensis . [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is a systemic disease induced by dimorphic fungi Coccidioides and C. posadasii. Its causative agents - primary pathogens - are endemic for American states. However introduced cases of the disease can be traced in some other world regions too. This paper contains summarized foreign literature data on the issue. Presented are the results of our own investigations on the problem of Coccidioidomycosis diagnostics. Discussed are also problems and prospective of the development of a diagnostic preparations designed to detect and identify Coccidioides spp.

The aim of the present study was to evaluate the effect of cotrimoxazole on the in vitro susceptibility of Coccidioides posadasii strains to antifungals. A total of 18 strains of C. posadasii isolated in Brazil were evaluated in this study. The assays were performed in accordance with the Clinical and Laboratory Standards Institute guidelines and the combinations were tested using the checkerboard method. The minimum inhibitory concentrations were reduced by 11, 2.4, 4.3 and 3.5 times for amphotericin B, itraconazole, fluconazole and voriconazole, respectively. Moreover, it was seen that cotrimoxazole itself inhibited C. posadasii strains in vitro. The impairment of folic acid synthesis may be a potential antifungal target for C. posadasii.