Current Challenges in Coccidioidomycosis

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 11138

Special Issue Editors


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Guest Editor
UCSF Fresno MEP, University of California-San Francisco, Fresno, CA, USA
Interests: fungal lung disease; critical care; asthma; acute lung injury; decision support; sepsis; chronic obstructive lung disease; lung cancer; lung nodules; coccidioidomycosis

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Guest Editor
1. Quantitative and Systems Biology Graduate Program, University of California Merced, Merced, CA 95343, USA
2. Department of Molecular and Cell Biology, School of Natural Sciences, University of California Merced, Merced, CA 95343, USA
3. Health Sciences Research Institute, University of California Merced, Merced, CA 95343, USA
Interests: immunological tolerance and autoimmune disease; cellular and molecular interplay between lymphocytes and dendritic cells

Special Issue Information

Dear Colleagues,

Coccidioidomycosis, often termed valley fever, is an orphan disease caused by the inhalation of the fungi Coccidioides immitis and Coccidioides posadasii in airborne dust. Efforts to reduce the impact of valley fever have been limited by a lack of understanding around its transmission, a lack of a definitive and rapid diagnostic, and an insufficient understanding of the factors that predict which patients will develop severe, even fatal, disseminated disease or prolonged systemic symptoms. Coccidioidomycosis is a potentially fatal fungal infection and is considered an emergent fungal disease due to the increasing incidence of infections. Infection begins in the lungs, and in 1–4% of cases disseminates to other tissues, including meninges, bones, joints, and skin. The tissue-specific exploration of the disease is vastly understudied within the primary site of infection and within other tissues during disseminated disease. This Special Issue focuses on the basic biology of the disease within the pulmonary and extrapulmonary tissues, as well as the specialized diagnosis and clinical treatment of it in pulmonary and extrapulmonary infection.

Prof. Dr. Michael W. Peterson
Dr. Katrina K. Hoyer
Guest Editors

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Keywords

  • Coccidioides
  • pulmonary
  • meningitis
  • joints/bone
  • dissemination
  • inflammatory response

Published Papers (5 papers)

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Research

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10 pages, 1679 KiB  
Article
Spinal Arachnoiditis in Patients with Coccidioidomycosis Meningitis—Analysis of Clinical and Imaging Features
by Geetha Sivasubramanian, Saurin Kadakia, Jani M. Kim, Sarah Pervaiz, Yueqi Yan and Robert Libke
J. Fungi 2022, 8(11), 1180; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8111180 - 8 Nov 2022
Cited by 1 | Viewed by 1838
Abstract
Background: Coccidioidomycosis meningitis (CM) is the most aggressive form of coccidioidomycosis, requiring lifelong antifungal treatment and often cerebrospinal fluid (CSF) diversion. Long-standing CM can be associated with spinal complications such as arachnoiditis. However, studies describing the frequency, clinical, and imaging characteristics of arachnoiditis [...] Read more.
Background: Coccidioidomycosis meningitis (CM) is the most aggressive form of coccidioidomycosis, requiring lifelong antifungal treatment and often cerebrospinal fluid (CSF) diversion. Long-standing CM can be associated with spinal complications such as arachnoiditis. However, studies describing the frequency, clinical, and imaging characteristics of arachnoiditis in patients with CM are limited. Methods: We identified 133 patients with CM based on CSF culture, PCR, or serology between January 2010 and December 2020. Of these, 37 patients underwent spinal imaging. Data on demographics, risk factors, symptoms, antifungal therapy, surgical management, follow-up visits, adherence, serological trends, and imaging findings were reviewed. Results: Abnormal findings were observed in 30 of the 37 patients with CM who underwent spinal imaging. The imaging abnormalities noted in our study included leptomeningeal enhancement (53%), arachnoiditis (53%), syringomyelia (23%), cord signal abnormalities (10%), and osteomyelitis (7%). Of the 30 patients, 90% had symptoms, such as weakness, numbness, or urinary retention. The incidence of arachnoiditis in the present study was 12%. Higher initial CSF protein levels and intra cranial pressure were associated with a higher risk of developing arachnoiditis/syringomyelia. Management of CM was challenging, as evidenced by shunt failure (46%), medication non-compliance (57%), and lack of adequate follow-up (60%). Persistent disabilities were noted in 62% of the patients. Conclusions: Patients with CM develop spinal complications such as arachnoiditis, or syringomyelia. Many cases may go undetected due to lack of symptoms in early stages. CM management challenges such as shunt failure, lack of follow-up care, and medication noncompliance, were frequent. Full article
(This article belongs to the Special Issue Current Challenges in Coccidioidomycosis)
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Review

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15 pages, 752 KiB  
Review
Coccidioidomycosis Osteoarticular Dissemination
by Benedicte M. Moni, Barton L. Wise, Gabriela G. Loots and Dina R. Weilhammer
J. Fungi 2023, 9(10), 1002; https://0-doi-org.brum.beds.ac.uk/10.3390/jof9101002 - 11 Oct 2023
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Abstract
Valley fever or coccidioidomycosis is a pulmonary infection caused by species of Coccidioides fungi that are endemic to California and Arizona. Skeletal coccidioidomycosis accounts for about half of disseminated infections, with the vertebral spine being the preferred site of dissemination. Most cases of [...] Read more.
Valley fever or coccidioidomycosis is a pulmonary infection caused by species of Coccidioides fungi that are endemic to California and Arizona. Skeletal coccidioidomycosis accounts for about half of disseminated infections, with the vertebral spine being the preferred site of dissemination. Most cases of skeletal coccidioidomycosis progress to bone destruction or spread to adjacent structures such as joints, tendons, and other soft tissues, causing significant pain and restricting mobility. Manifestations of such cases are usually nonspecific, making diagnosis very challenging, especially in non-endemic areas. The lack of basic knowledge and research data on the mechanisms defining susceptibility to extrapulmonary infection, especially when it involves bones and joints, prompted us to survey available clinical and animal data to establish specific research questions that remain to be investigated. In this review, we explore published literature reviews, case reports, and case series on the dissemination of coccidioidomycosis to bones and/or joints. We highlight key differential features with other conditions and opportunities for mechanistic and basic research studies that can help develop novel diagnostic, prognostic, and treatment strategies. Full article
(This article belongs to the Special Issue Current Challenges in Coccidioidomycosis)
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Other

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7 pages, 1352 KiB  
Brief Report
Serologic Rebound after Stopping Azoles for Primary Pulmonary Coccidioidomycosis: A Case-Controlled Observational Study
by Priyal J. Shah, Neil M. Ampel, Marlene E. Girardo and Janis E. Blair
J. Fungi 2023, 9(9), 901; https://0-doi-org.brum.beds.ac.uk/10.3390/jof9090901 - 1 Sep 2023
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Abstract
Background: We sought to characterize the outcomes of patients with primary pulmonary coccidioidomycosis whose post-treatment complement fixation (CF) titer increased by more than 2 dilutions (serologic rebound) after discontinuation of antifungal treatment. Methods. We conducted a retrospective chart review of patients with primary [...] Read more.
Background: We sought to characterize the outcomes of patients with primary pulmonary coccidioidomycosis whose post-treatment complement fixation (CF) titer increased by more than 2 dilutions (serologic rebound) after discontinuation of antifungal treatment. Methods. We conducted a retrospective chart review of patients with primary pulmonary coccidioidomycosis and identified immunocompetent, non-pregnant adults who received antifungal treatment and then experienced a serologic rebound after treatment discontinuation. We compared these to matched controls similarly treated who did not have serologic rebound. Results. Fifty-eight patients experienced serologic rebound. Thirty (52%) of these were associated with symptoms. Nine were associated with radiographic progression. The median time to serologic rebound was 3.5 months. Antifungal treatment was reinitiated in 37 (63.7%) patients. Four of the 58 (6.9%) with rebounded serology subsequently developed extra-thoracic dissemination. Compared with matched controls, patients with rebounded serology were more likely to have post-treatment symptoms, reinitiation of antifungal therapy, and a longer duration of clinical follow-up. However, they were not more likely to experience extra-thoracic dissemination. Conclusion: Serological rebound, manifested in at least 2-dilution rise of CF titer following antifungal treatment of primary pulmonary coccidioidomycosis, was uncommon, but resulted in longer clinical follow-up. Continued monitoring of such patients is important to identify the patients who develop subsequent symptoms, as well as extra-thoracic dissemination. Full article
(This article belongs to the Special Issue Current Challenges in Coccidioidomycosis)
9 pages, 3200 KiB  
Brief Report
Differentiating Lung Nodules Due to Coccidioides from Those Due to Lung Cancer Based on Radiographic Appearance
by Michael W. Peterson, Ratnali Jain, Kurt Hildebrandt, William Keith Carson and Mohamed A. Fayed
J. Fungi 2023, 9(6), 641; https://0-doi-org.brum.beds.ac.uk/10.3390/jof9060641 - 1 Jun 2023
Cited by 1 | Viewed by 4816
Abstract
Background: Coccidioidomycosis (cocci) is an endemic fungal disease that can cause asymptomatic or post-symptomatic lung nodules which are visible on chest CT scanning. Lung nodules are common and can represent early lung cancer. Differentiating lung nodules due to cocci from those due to [...] Read more.
Background: Coccidioidomycosis (cocci) is an endemic fungal disease that can cause asymptomatic or post-symptomatic lung nodules which are visible on chest CT scanning. Lung nodules are common and can represent early lung cancer. Differentiating lung nodules due to cocci from those due to lung cancer can be difficult and lead to invasive and expensive evaluations. Materials and Methods: We identified 302 patients with biopsy-proven cocci or bronchogenic carcinoma seen in our multidisciplinary nodule clinic. Two experienced radiologists who were blinded to the diagnosis read the chest CT scans and identified radiographic characteristics to determine their utility in differentiating lung cancer nodules from those due to cocci. Results: Using univariate analysis, we identified several radiographic findings that differed between lung cancer and cocci infection. We then entered these variables along with age and gender into a multivariate model and found that age, nodule diameter, nodule cavitation, presence of satellite nodules and radiographic presence of chronic lung disease differed significantly between the two diagnoses. Three findings, cavitary nodules, satellite nodules and chronic lung disease, have sufficient discrimination to potentially be useful in clinical decision-making. Conclusions: Careful evaluation of the three obtained radiographic findings can significantly improve our ability to differentiate benign coccidioidomycosis infection from lung cancer in an endemic region for the fungal disease. Using these data may significantly reduce the cost and risk associated with distinguishing the cause of lung nodules in these patients by preventing unnecessary invasive studies. Full article
(This article belongs to the Special Issue Current Challenges in Coccidioidomycosis)
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5 pages, 211 KiB  
Brief Report
Case Series of End-Stage Liver Disease Patients with Severe Coccidioidomycosis
by Daniel Ho, Kristen D. Kelley, Satya Dandekar, Stuart H. Cohen and George R. Thompson III
J. Fungi 2023, 9(3), 305; https://0-doi-org.brum.beds.ac.uk/10.3390/jof9030305 - 27 Feb 2023
Cited by 3 | Viewed by 1446
Abstract
Liver disease causes relative compromise of the host immune system through multiple overlapping mechanisms and is an established risk factor for invasive fungal diseases including candidiasis and cryptococcosis. This immunologic derangement also leads to rapid progression of disease with resultant increases in morbidity [...] Read more.
Liver disease causes relative compromise of the host immune system through multiple overlapping mechanisms and is an established risk factor for invasive fungal diseases including candidiasis and cryptococcosis. This immunologic derangement also leads to rapid progression of disease with resultant increases in morbidity and mortality. We describe severe coccidioidomycosis cases in the setting of liver dysfunction. Collaborative multi-center epidemiologic studies should be performed to determine the incidence of severe coccidioidomycosis in patients with concurrent liver disease. Full article
(This article belongs to the Special Issue Current Challenges in Coccidioidomycosis)
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