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.

Executive Summary: 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.

2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.

Characteristics of patients with mild to moderate primary pulmonary coccidioidomycosis.

In Arizona, USA, primary pulmonary coccidioidomycosis accounts for 15%-29% of community-acquired pneumonia. To determine the evolution of symptoms and changes in laboratory values for patients with mild to moderate coccidioidomycosis during 2010-2012, we conducted a prospective 24-week study of patients with primary pulmonary coccidioidomycosis. Of the 36 patients, 16 (44%) were men and 33 (92%) were White. Median age was 53 years, and 20 (56%) had received antifungal treatment at baseline. Symptom scores were higher for patients who received treatment than for those who did not. Median times from symptom onset to 50% reduction and to complete resolution for patients in treatment and nontreatment groups were 9.9 and 9.1 weeks, and 18.7 and 17.8 weeks, respectively. Median times to full return to work were 8.4 and 5.7 weeks, respectively. One patient who received treatment experienced disseminated infection. For otherwise healthy adults with acute coccidioidomycosis, convalescence was prolonged, regardless of whether they received antifungal treatment.

Pediatric coccidioidomycosis in central California: a retrospective case series.

BACKGROUND: Coccidioidomycosis, an endemic fungal infection seen throughout the southwestern United States, is not well described in children. METHODS: We performed a retrospective observational study of all children admitted to Children's Hospital Central California with coccidioidomycosis from 1 January 2010 to 1 September 2011. RESULTS: Thirty-three children, aged 6 months to 17 years, were hospitalized during the study period. These included patients with pneumonia (n = 28), pleural effusion (n = 13), pleural empyema (n = 4), lung abscess (n = 7), pericarditis (n = 2), osteomyelitis (n = 5), meningitis/cerebritis (n = 2), and vocal cord infection (n = 1). Mediastinitis, with radiographic evidence of purulence and necrotic/abscessed lymph nodes in the mediastinum, was present in 7 patients (21%) and tended to occur more often in younger children (median age, 3 years [range, 0.5-11 years] vs 7 years [range, 0.6-17 years] for non-mediastinitis patients; P = .10). Seven patients were admitted to the intensive care unit and 10 required surgical intervention. One patient died of meningitis. Hospitalizations were longer for patients with mediastinitis (median, 130 days [range, 58-200 days] vs 43 days [range, 3-273 days for non-mediastinitis patients]; P < .01) and those with maximum coccidioidal complement fixing antibody titers ≥1:128 (median, 174 days [range, 53-273 days] vs 33 days [range, 3-200 days] for those with maximum titers <1:128; P < .01). CONCLUSIONS: Coccidioidomycosis causes a substantial disease burden in the children of central California. Mediastinitis is common and tends to occur in younger children. Patients with mediastinitis or elevated coccidioidal complement fixation titers require longer hospitalizations. Further research is needed on the prevention and treatment of this disease.

Pulmonary coccidioidomycosis.

Coccidioidomycosis refers to the spectrum of disease caused by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii. Clinical manifestations vary depending upon both the extent of infection and the immune status of the host. Coccidioidomycosis has been reported to involve almost all organ systems; however, pulmonary disease is the most common clinical manifestation. The incidence of coccidioidomycosis continues to rise, and primary coccidioidal pneumonia accounts for 17 to 29% of all cases of community-acquired pneumonia in endemic regions. The majority of patients with coccidioidomycosis resolve their initial infection without sequelae; however, several patients develop complications of disease ranging in severity from complicated pulmonary coccidioidomycosis to widely disseminated disease with immediately life-threatening manifestations. This review focuses on complications of pulmonary coccidioidomycosis with an emphasis on the management of primary coccidioidal infection, solitary pulmonary nodules, pleural effusions, cavitary disease, acute respiratory distress syndrome (ARDS), miliary disease, and sepsis.

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 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.

Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a).

Coccidioides posadasii spherules stimulate macrophages to make cytokines via TLR-2 and Dectin-1. We used formalin-killed spherules and 1,3-beta-glucan purified from spherules to stimulate elicited peritoneal macrophages and myeloid dendritic cells (mDCs) from susceptible (C57BL/6) and resistant (DBA/2) mouse strains. DBA/2 macrophages produced more TNF-alpha and IL-6 than macrophages from C57BL/6 mice, and the amount of TNF-alpha made was dependent on both TLR2 and Dectin-1. DCs from C57BL/6 mice made more IL-10 and less IL-23p19 and IL-12p70 than did DBA/2 DC. These responses were inhibited by a monoclonal antibody to Dectin-1. DBA/2 mice expressed full-length Dectin-1, whereas C57BL/6 mice spliced out exon 3, which encodes most of the stalk. RAW cells transduced to express the full-length Dectin-1 responded better to FKS than cells expressing truncated Dectin-1. We compared the isoform of Dectin-1 expressed by 34 C57BL/6 X DBA/2 recombinant inbred (BXD RI) lines with their susceptibility to Coccidioides immitis. In 25 of 34 RI lines susceptibility or resistance corresponded to short or full-length isoforms, respectively. These results suggest that alternative splicing of the Dectin-1 gene contributes to susceptibility of C57BL/6 mice to coccidioidomycosis, and affects the cytokine responses of macrophages and mDCs to spherules.

Pleural coccidioidomycosis presenting as spontaneous pneumothorax.

Coccidioides is a fungus endemic to Southwestern USA and Northern Mexico which can be asymptomatic or result in a well-defined clinical syndrome of community-acquired pneumonia. On rare occasion, coccidioidomycosis may have atypical presentations as in our patient, a 25-year-old man admitted with a 2-month history of progressive dyspnoea and cough. He was found to have a large right-sided pneumothorax with exudative pleural effusion which did not resolve following thoracentesis. Decortication was performed which revealed a dense rind of inflammatory tissue covering all lobes of his right lung. Histopathology demonstrated hyphae resembling Aspergillus, but culture and serology confirmed Coccidioides immitis Following several months of antifungal therapy, he achieved complete clinical recovery with near-complete resolution of radiographic findings.

Coccidioides immitis septic knee arthritis.

A 78-year-old man developed right knee pain and swelling without other systemic symptoms. He had travelled frequently to the Central Valley of California. He was diagnosed with coccidioidomycosis based on joint fluid culture. Coccidioidal complement fixation antibody titres were extremely elevated. Arthroscopic debridement and fluconazole therapy did not lead to satisfactory improvement. Subsequent open debridement and change to itraconazole was followed by resolution of clinical signs of infection.

The prevention of recrudescent coccidioidomycosis after solid organ transplantation.

BACKGROUND: Coccidioidomycosis is an endemic fungal infection of the southwestern United States that causes considerable morbidity and mortality in transplant recipients, often as the result of reactivated infection. METHODS: A retrospective review of the medical records of 47 patients with prior coccidioidomycosis who underwent solid organ transplantation (18 liver, 24 kidney, 3 pancreas, and 2 combined organ) at our tertiary care academic medical center. RESULTS: Of 47 transplant recipients with a history of coccidioidomycosis, 44 had quiescent infection at transplantation. Of the three with active coccidioidomycosis at transplantation, two were taking azole prophylaxis and had no further coccidioidal infection after transplantation. One of the three had positive serologic findings identified only on the day of transplantation, and prophylaxis was initiated a few hours after surgery along with immunosuppression; nevertheless, the treatment course was complicated by disseminated coccidioidomycosis. Seven patients did not initiate or self-discontinued prophylaxis; one patient who discontinued prophylaxis experienced recurrent pulmonary infection. CONCLUSIONS: For patients undergoing transplantation in an area endemic for coccidioidomycosis, we recommend routine evaluation for evidence of prior infection and initiation of azole prophylaxis. For our patients with quiescent infection, azoles suppressed any recrudescent coccidioidomycosis after transplantation. The selection of patients who would benefit from prophylaxis and the optimal dose and duration of such prophylaxis should be studied further.

Experimental animal models of coccidioidomycosis.

Experimental models of coccidioidomycosis performed using various laboratory animals have been, and remain, a critical component of elucidation and understanding of the pathogenesis and host resistance to infection with Coccidioides spp., as well as to development of more efficacious antifungal therapies. The general availability of genetically defined strains, immunological reagents, ease of handling, and costs all contribute to the use of mice as the primary laboratory animal species for models of this disease. Five types of murine models are studied and include primary pulmonary disease, intraperitoneal with dissemination, intravenous infection emulating systemic disease, and intracranial or intrathecal infection emulating meningeal disease. Each of these models has been used to examine various aspects of host resistance, pathogenesis, or antifungal therapy. Other rodent species, such as rat, have been used much less frequently. A rabbit model of meningeal disease, established by intracisternal infection, has proven to model human meningitis well. This model is useful in studies of host response, as well as in therapy studies. A variety of other animal species including dogs, primates, and guinea pigs have been used to study host response and vaccine efficacy. However, cost and increased needs of animal care and husbandry are limitations that influence the use of the larger animal species.

Cutaneous Coccidiomycosis Masquerading as an Epidermoid Cyst: Case Report and Review of the Literature.

OBJECTIVES: To present a challenging case of inoculatory fungal mycosis mimicking an epidermoid cyst, which may have been easily overlooked by the pathologist. METHODS: We present a case report of a 29-year-old male with a nodule on the right lower back, which was surgically excised and submitted to pathology as a ruptured epidermoid cyst. RESULTS: Histopathologic sections revealed detached soft tissue fragments containing polymorphic granulomas with abscess and suspicious-appearing spherical structures ranging in size from 50 to 200 µm. Some spherules were located within different types of multinucleated giant cells and most were located in close proximity to abscess. Periodic acid-Schiff fungal stain highlighted these structures and a presumptive diagnosis of coccidiomycosis was rendered. Serologic testing was performed which confirmed exposure to Coccidioides immitis, and extensive work-up for evidence of disseminated disease was negative. Subsequently, additional clinical history was garnered which revealed recent travel history to El Paso, Texas, of many weeks duration for military training, conducted mostly outdoors, subjectively with several encounters of being stuck by vegetation during these exercises. CONCLUSION: This interesting case highlights important diagnostic histologic clues to consider when evaluating "routine" cyst specimens and highlights the importance of thorough clinicopathologic correlation, even in the "routine."

Central nervous system coccidioidomycosis: a clinicopathologic study of treatment with and without amphotericin B.

The clinical and pathologic findings in 32 patients with central nervous system (CNS) coccidioidomycosis were studied. Seventeen patients had received more than 1.5 g of amphotericin B (AMB), chiefly intravenously, during treatment periods of up to eight years. Eight patients had received 246 mg to 1.3 g of AMB, and three patients had received only brief treatment (one to three days; total dose, no more than 100 mg). Fifteen patients had not received AMB. Significant clinical differences between the patients treated with and without AMB were longer survival time following diagnosis of illness (P less than 0.05) and more frequent cranial nerve signs in the treated patients (P = 0.089). The wide spectrum of macroscopic and microscopic lesions in the CNS included meningitis, ventriculitis, hydrocephalus, and cerebritis. Long-standing infections were associated with disseminated discrete foci of gliosis and infarcts in the brain, particularly in the basal ganglia and deep white matter, related to endarteritis obliterans in basilar meninges. In contrast to patients with CNS and systemic mycoses treated with amphotericin B methyl ester (J Infect Dis 146:125, 1982), no diffuse lesions of white matter were found in patients treated with or without AMB. Histopathologic patterns observed in this study included leptomeningitis alone, leptomeningitis with cerebritis, leptomeningitis with cerebritis and infarcts, and the unusual pattern of disseminated miliary granulomas. The frequency and extent of CNS lesions in the groups treated with and without AMB were not significantly different. It is concluded that AMB therapy, while prolonging survival, does not alter the spectrum of pathologic findings in CNS coccidioidomycosis infection.

Cutaneous manifestations of systemic mycoses.

Systemic fungal diseases are primary pulmonary diseases caused by the dimorphic fungal pathogens, Blastomyces dermatitides, Coccidioides immitis. Histoplasma capsulatum, or Paracoccidioides brasiliensis. Infection occurs after inhalation of the infectious form of the fungus and may be acute, self-limited, or subclinical. Primary cutaneous infection occurs only after traumatic implantation of the fungus and is unusual. Erythema nodosum or erythema multiforme may accompany the acute form of the disease. Other cutaneous manifestations represent disseminated disease and, as such, require systemic antifungal therapy. Because cutaneous lesions have occurred coincidentally with other cutaneous pathologies, emphasis should be placed on a complete clinical history, physical examination, and diagnosis by histopathology and culture.

Clinical manifestations of pulmonary fungal infections.

Coccidioidomycosis, histoplasmosis, cryptococcosis, and blastomycosis are the most common deep pulmonary fungal infections encountered by the clinician. Each has a particular environmental habitat. As world travel increases, exposure to these infections becomes increasingly more common. The article reviews the microbiology, natural history, and clinical and laboratory findings of these diseases. Treatment options for these infections also are discussed.