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.

Disseminated coccidioidomycosis in a patient with juvenile idiopathic arthritis receiving infliximab.

BACKGROUND: Coccidioides immitis is a dimorphic fungus endemic to the arid climates of the Southwest United States, Mexico and parts of Central and South America. Human infection occurs through inhalation of spores with less than half of exposures progressing to a symptomatic state that primarily consists of pulmonary manifestations. Disseminated coccidioidomycosis is exceedingly rare, occurring in fewer than 1 % of symptomatic infections. Through hematogenous spread, the fungus can infect most organ systems and may be fatal without systemic antifungal treatment. Individuals with impaired cell-mediated immunity either from primary immunodeficiency disorders or secondary to immunosuppression with medications such as tumor necrosis factor alpha (TNF-α) inhibitors have increased risk of disseminated coccidioidomycosis and previous cases of coccidioidomycosis have been reported with biologic therapy. CASE PRESENTATION: We present a case of disseminated coccidioidomycosis in a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) being treated with prednisone, methotrexate, and infliximab. The patient presented with symptoms of meningeal irritation, bilateral choroidal lesions, and necrotizing peripheral pneumonia. Her infection was thought to be a reactivation of coccidioidomycosis given her history of resolved pneumonia that occurred after traveling to Arizona, New Mexico, and El Paso one year prior to presentation. Following diagnosis, she improved with discontinuation of her immunosuppressive medications and two weeks of intravenous amphotericin B and fluconazole with plans for lifetime treatment with fluconazole while immunosuppressed. Due to worsening arthritis, she will begin tofacitinib and continue close monitoring of chest x-rays and coccidioides antibody. CONCLUSIONS: Patients undergoing immunosuppressive therapy for rheumatological conditions are at increased risk of disseminated coccidioidomycosis and should be evaluated with high suspicion when presenting with atypical symptoms and history of travel to endemic regions.

Coccidioidomycosis.

Coccidioidomycosis, caused by the dimorphic pathogenic fungi Coccidioides immitis and Coccidioides posadassi, is endemic to the southwestern United states and Central and South America. The incidence of coccidioidomycosis continues to increase. Coccidioidomycosis is typically a self-limiting influenza-like respiratory illness; however, it can lead to disseminated disease outside of the lungs. Not all nondisseminated cases require therapy, but antifungal therapy is typically beneficial requiring treatment ranging from months to lifelong. Clinical factors related to treatment decisions include severity of symptoms, radiography, coccidioidomycosis serologic results, and concurrent medical problems including immunosuppression. This review summarizes the epidemiology, clinical manifestations, and treatment options.

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.

Application of laser capture microdissection and PCR sequencing in the diagnosis of Coccidioides spp. infection: A case report and literature review in China.

Coccidioidomycosis is endemic to California, Arizona, and Mexico. In recent years, the reported cases of coccidioidomycosis have increased in nonendemic regions. Here, we reported a case of imported pulmonary coccidioidomycosis in a Chinese patient. A 63-year-old man presented with dry cough and fatigue for 6 months, and a computed tomography scan revealed a solitary nodule in the right lower lung and small nodules in both lungs. The diagnosis of coccidioidomycosis was initially confirmed by histopathologic examination. The pathogen Coccidioides spp. was identified by laser capture microdissection (LCM) combined with subsequent molecular techniques based on the positive histopathologic features. Additionally, we reviewed 47 reported cases of coccidioidomycosis in China. The number of reported cases is increasing, and the incidence of disseminated infection has exhibited a trend of shifting towards healthy young adults in China. Since clinical presentations and imaging findings lack specificity, a majority of domestic cases of coccidioidomycosis were initially misdiagnosed as tumours or tuberculosis. Moreover, the diagnosis of endemic mycoses may be challenging because of their rarity and the limited availability of diagnostic tests. The diagnosis was mainly confirmed by histopathological examination. The species involved were identified based on positive cultures in only 4 cases. To our knowledge, this is the first study to use LCM and molecular techniques to identify Coccidioides spp. in the histopathologically positive but uncultivable specimen. Comparing with previous reported studies, LCM combined with nucleic acid amplification techniques improve the ability of species identification for the timely diagnosis of coccidioidomycosis.

Systemic coccidioidomycosis in a llama cria native to Missouri.

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.

Case Report: Severe Craniofacial Coccidioidomycosis in a Pregnant Woman.

Coccidioidomycosis is a systemic fungal disease caused by Coccidioides immitis and Coccidioides posadasii. The lungs are the most common and often the initial site of involvement, and the non-pulmonary presentation is infrequent. We describe an unusual case of primary craniocutaneous coccidioidomycosis in a pregnant woman with infected bilateral periorbital nodules, intense pain at paranasal sinuses, and several osteolytic skull lesions. The analysis of 54 cases available in the literature makes us suggest that the area between the United States and Mexico is a risk zone for primary cutaneous coccidioidomycosis.

Disseminated Coccidioidomycosis Presenting as Polyarticular Septic Arthritis: A Case Report.

Coccidioidomycosis a fungal infection endemic to southwestern United States. It is caused by inhalation of spores of Coccidioides immitis. Sixty percent of infections are asymptomatic; the remaining 40% are primarily pulmonary disease. In <1% of infections, dissemination can occur. Dissemination usually affects those with impaired cellular immunity and pregnant women, and can involve bones, joints, meninges, and skin. We present the case of a 29-year-old Hispanic male who presented to the emergency department (ED) complaining of pain and swelling of right wrist and ankle as well as left knee for 2 months. He was referred to rheumatology clinic but returned to the ED as he developed spontaneous purulent drainage from his wrist. In the ED, an arthrocentesis of 2 of the joints showed total nucleated cells of 520 000/cm2 and 90 000/cm2 with 61% and 93% neutrophils, respectively. Fungal culture eventually grew Coccidioides immitis from his wrist and knee. Coccidioidomycosis complement fixation titer came back >1:512. Bone scan showed uptake of adjacent bones in the affected joints. Superimposed bacterial infection of the wrist complicated the treatment course and delayed the start of liposomal amphotericin B. Eventually patient received 12 weeks of intravenous liposomal amphotericin-B with slow clinical improvement and then switched to oral isavuconazonium for maintenance therapy. This case shows that although disseminated polyarthritis coccidioidomycosis is very rare, clinicians should keep the diagnosis of disseminated synovial coccidioidomycosis in mind in patients with risk factors.

Disseminated Coccidioidomycosis Following Insufficient Treatment at Initial Presentation: Case Report.

A 35-year-old male presented to our university hospital with night sweats, fevers, ulcerated skin lesions to the lower mouth and posterior neck, shortness of breath, and an enlarging cervical lymph node. The patient was evaluated 2 months prior for respiratory symptoms, cervical lymphadenopathy, and skin lesions resulting in a diagnosis of primary pulmonary coccidioidomycosis and was treated with a 4-week course of fluconazole. On presentation to our hospital, initial laboratory test results revealed leukocytosis, increased liver enzymes, elevated inflammatory markers, and hypercalcemia. Computed tomography scan of the chest revealed lung nodules in a miliary pattern and prominent mediastinal lymphadenopathy. Magnetic resonance imaging revealed multiple vertebral and iliac bone lesions, as well as bilateral psoas muscle lesions. Serum ELISA (enzyme linked immunosorbent assay) detected elevated serological markers against coccidioides, and sputum culture revealed coccidioides arthroconidia, confirming the presence of an acute coccidioides infection. Biopsy of the right iliac crest and cervical lymph node revealed spherules resembling coccidioides, escalating the diagnosis to disseminated coccidioidomycosis. The patient's hospital course was complicated by septic shock, acute respiratory distress syndrome requiring several days of mechanical ventilation, and acute kidney injury. He was ultimately treated with several weeks of voriconazole and liposomal amphotericin-B. He made a full recovery and was discharged on an extended course of oral voriconazole. Our case highlights the importance of recognition and appropriate treatment duration of disseminated coccidioidomycosis at initial presentation. Failure to do so may lead to increased morbidity and mortality.

Coccidioidal meningitis in non-AIDS patients. A case series at a Mexican neurological referral center.

BACKGROUND: Coccidioidal meningitis is a life-threatening condition and a diagnostic challenge in cases of chronic meningitis. It is associated to severe complications, like basal arachnoiditis, hydrocephalus, and secondary vasculitis. OBJECTIVE: To present a 20-year retrospective clinical series of coccidioidal meningitis cases at a Mexican neurological referral center. RESULTS: The clinical records of 11 patients, predominantly males, were retrieved. Weight loss and night sweats were observed in 64 % of cases. Neurological signs included intracranial hypertension in 91 % of cases, altered alertness and meningeal syndrome in 72 %, and neuropsychiatric symptoms in 64 %. Mean CSF glucose levels were 30 ± 25 mg/dL, and pleocytosis ranged from 0 to 2218 cells/mm3. The diagnosis was confirmed by coccidioidal antigen latex agglutination in 91 % of cases. Radiological findings were hepatomegaly in 55 % of cases and pneumonia in 45 %. Neuroimaging findings included leptomeningitis in 73 % of cases, pachymeningitis in 45 %, and vascular involvement in 91 %. Less common findings included spinal cord lesion and mycotic aneurism, found in 18 % of cases. A molecular coccidioidal DNA test confirmed the predominance of Coccidioides immitis, detected in 64 % of cases. With respect to the clinical outcome, 46 % of patients died. The survivors suffered from sequels like chronic headache, cognitive alterations, and depression. CONCLUSIONS: Coccidioidal meningitis is an entity with high mortality rates. More than one half of patients suffered disseminated disease. Although meningeal signs are not frequent in chronic meningitis, more than two-thirds of our patients showed mild nuchal rigidity. In addition, cerebral and cerebellar volume loss, associated with cognitive impairment and depression, was often observed in surviving patients during the clinical-radiological follow-up.

Primary Cutaneous Coccidioidomycosis: An Update.

Coccidioidomycosis is an endemic mycosis of the southern United States, Northern Mexico, and South America. Primary cutaneous coccidioidomycosis, despite being a very rare clinical presentation, has shown an increasing incidence. An extensive literature search for cutaneous coccidioidomycosis cases was performed using the OLDMEDLINE, PubMed, Cochrane, LILACS and Google Scholar databases for studies published from January 1927 through December 21, 2019. Forty-two observational studies were included totaling 82 cases of primary cutaneous coccidioidomycosis. Narrative reviews, systematic reviews, and meta-analyses were also included. Additionally, an original case was included. Patients with primary cutaneous coccidioidomycosis share the same geographical and epidemiological characteristics as those with pulmonary or disseminated coccidioidomycosis. Most of the imported cases came from endemic areas. A large portion of cases had prior local skin trauma. Tissue culture is still the leading diagnostic method; nevertheless, molecular techniques such as polymerase chain reaction (PCR) are currently relevant to differentiate between species. First-line treatment consists of azoles; however, it has an excellent prognosis even without treatment. Primary cutaneous coccidioidomycosis should be considered a differential diagnosis of unusual infections or neoformations in any part of the body in resident populations of endemic areas or in patients with a previous history of travel to these areas.

Simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient: A case report and literature review.

Advances in solid organ transplantation have improved the survival of end-stage organ disease at the expense of an increased risk for opportunistic infections. Unusual clinical presentations and the possibility of concurrent infections make diagnosing invasive fungal infection (IFI) more difficult. Here, we present a case of simultaneous vertebral infection caused by Coccidioides immitis-posadasii and subcutaneous phaeohyphomycosis due to Nigrograna mackinnonii in a kidney transplant recipient. The diagnosis of both infections required invasive procedures to obtain tissue and a high index of suspicion that more than one IFI could be present. A multidisciplinary team approach for the management of immunocompromised patients with suspected or diagnosed IFI is warranted.

Bicavitary eosinophilic effusion in a dog with coccidioidomycosis.

This is a case of coccidioidomycosis in a dog, examined for vomiting and labored breathing. Physical examination and thoracic and abdominal imaging revealed pleural and peritoneal effusions, both of which exhibited neutrophilic inflammation with a substantial eosinophilic component. The dog had positive IgM and IgG coccidioidomycosis titers at initial evaluation. The eosinophilic component of the inflammation was attributed to coccidioidomycosis. The dog underwent approximately 6 months of fluconazole treatment, with both effusions and clinical signs improving after 6 weeks. Three months after cessation of antifungal treatment, the dog developed a mid-diaphyseal lytic and proliferative lesion in the left radius caused by Coccidioides spp. This case illustrates the importance of consideration of coccidioidomycosis when an eosinophilic cavitary effusion is present in dogs that live in or have traveled to endemic regions.

Opportunistic coinfection with Pneumocystis jirovecii and Coccidioides immitis associated with idelalisib treatment in a patient with chronic lymphocytic leukaemia.

We describe a case of opportunistic coinfections with Coccidioides immitis and Pneumocystis jirovecii following treatment with idelalisib, a phosphoinositide 3-kinase inhibitor, for chronic lymphocytic leukaemia. This is the first case of pulmonary coccidioidomycosis reported in association with idelalisib. We review challenges related to diagnosis of opportunistic infections in this context. This report illustrates (1) the uncommon occurrence of two opportunistic infections concurrently or in rapid succession, (2) the importance of maintaining a broad differential diagnosis in the setting of an atypical imaging finding, slow clinical response or when immunomodulatory drugs are used, and (3) the challenges associated with non-invasive serological testing in individuals with haematological malignancy on immunomodulatory therapy.

Disseminated Coccidioidomycosis to the Gallbladder.

Coccidioidomycosis is an infection caused by inhalation of arthroconidia produced by dimorphic fungi in the genus Coccidioides. Forty percent of patients will develop an influenza-like illness with symptoms suggestive of a mild and self-limited respiratory infection; however, 5% of these individuals will develop extrapulmonary disseminated disease. An immunocompromised patient presented with right upper quadrant pain, ultrasound with pericholecystic fluid, in which a percutaneous cholecystostomy contained biliary fluid that grew the fungus Coccidioides immitis. Patient was initiated on intravenous amphotericin therapy and was followed closely with postoperative bile drainage with eventual laparoscopic cholecystectomy. We present a very rare case of disseminated coccidioidomycosis to the gallbladder.

Risk factors and outcomes of culture-proven acute Coccidioides spp. infection in San Diego, California, United States.

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.

Environmental factors affecting ecological niche of Coccidioides species and spatial dynamics of valley fever in the United States.

Coccidioidomycosis is an understudied infectious disease acquired by inhaling fungal spores of Coccidioides species. While historically connected to the southwestern United States, the endemic region for this disease is not well defined. This study's objective was to estimate the impact of climate, soil, elevation and land cover on the Coccidioides species' ecological niche. This research used maximum entropy ecological niche modeling based on disease case data from 2015 to 2016. Results found mean temperature of the driest quarter, and barren, shrub, and cultivated land covers influential in characterizing the niche. In addition to hotspots in central California and Arizona, the Columbia Plateau ecoregion of Washington and Oregon showed more favorable conditions for fungus presence than surrounding areas. The identification of influential spatial drivers will assist in future modeling efforts, and the potential distribution map generated may aid public health officials in watching for potential hotspots, assessing vulnerability, and refining endemicity.

Pulmonary Coccidioidomycosis.

Coccidioidomycosis is an infection caused by the geographically restricted dimorphic fungus, Coccidioides. Coccidioidomycosis occurs endemically in the southwestern and western United States, mainly in focused regions of Arizona and California where the incidence is highest, and in Central and South America. Patients with impaired immunity, especially those with impaired cellular immunity, are at higher risk of severe and disseminated disease. In this review, we describe the fungal ecology and mycology, epidemiology, pathophysiology, and normal immune defenses to Coccidioides as well as address current concepts in diagnosis, treatment, and continued care of patients with pulmonary coccidioidomycosis. We also present and answer our most frequently asked questions regarding patients with primary pulmonary coccidioidomycosis.