Coccidioides and Coccidioidomycosis, 2nd Edition

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: 31 August 2024 | Viewed by 6256

Special Issue Editor


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Guest Editor
School of Medicine, University of California, San Diego, CA, USA
Interests: coccidioidomycosis; primary pathogenic fungi; pathogenesis; immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Interest in coccidioidomycosis has increased dramatically over the past several years as the number of cases has increased and more genetic information has become available. There are 900 papers about Coccidioidomycosis within the past ten years indexed in PubMed. It is now recognized that coccidioidomycosis is a common cause of serious infections in Southern California and Southern Arizona, including the heavily populated Phoenix area. The endemic area of the organism is much larger than previously recognized and there have been several studies of the ecology and phylogenetics of these species. Our understanding of the conversion from mycelia to spherules is also growing. There has continued to be much interest in the immune response to the organism and novel studies of diagnostic tests and potential therapies have also been done. This Special Issue will showcase papers from several disciplines on Coccidioides spp. and coccidioidomycosis.

Dr. Theo N. Kirkland
Guest Editor

Manuscript Submission Information

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Keywords

  • Coccidioides spp.
  • coccidioidomycosis
  • genomics
  • fungal biology
  • ecology
  • phylogenetics
  • immunology
  • diagnostic tests
  • anti-fungal drugs

Published Papers (6 papers)

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Research

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9 pages, 1095 KiB  
Communication
Discovery of a Unique Set of Dog-Seroreactive Coccidioides Proteins Using Nucleic Acid Programmable Protein Array
by Megan A. Koehler, Lusheng Song, Francisca J. Grill, Lisa F. Shubitz, Daniel A. Powell, John N. Galgiani, Marc J. Orbach, Edward J. Robb, Yunro Chung, Stacy A. Williams, Vel Murugan, Jin-gyoon Park, Joshua LaBaer, Douglas F. Lake and D. Mitchell Magee
J. Fungi 2024, 10(5), 307; https://doi.org/10.3390/jof10050307 - 24 Apr 2024
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Abstract
Valley Fever (VF), caused by fungi in the genus Coccidioides, is a prevalent disease in southwestern and western parts of the United States that affects both humans and animals, such as dogs. Although the immune responses to infection with Coccidioides spp. are [...] Read more.
Valley Fever (VF), caused by fungi in the genus Coccidioides, is a prevalent disease in southwestern and western parts of the United States that affects both humans and animals, such as dogs. Although the immune responses to infection with Coccidioides spp. are not fully characterized, antibody-detection assays are used in conjunction with clinical presentation and radiologic findings to aid in the diagnosis of VF. These assays often use Complement Fixation (CF) and Tube Precipitin (TP) antigens as the main targets of IgG and IgM reactivity, respectively. Our group previously reported evidence of over 800 genes expressed at the protein level in C. posadasii. However, antibody reactivity to the majority of these proteins has never been explored. Using a new, high-throughput screening technology, the Nucleic Acid Programmable Protein Array (NAPPA), we screened serum specimens from dogs against 708 of these previously identified proteins for IgG reactivity. Serum from three separate groups of dogs was analyzed and revealed a small panel of proteins to be further characterized for immuno-reactivity. In addition to CF/CTS1 antigen, sera from most infected dogs showed antibody reactivity to endo-1,3-betaglucanase, peroxisomal matrix protein, and another novel reactive protein, CPSG_05795. These antigens may provide additional targets to aid in antibody-based diagnostics. Full article
(This article belongs to the Special Issue Coccidioides and Coccidioidomycosis, 2nd Edition)
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14 pages, 3511 KiB  
Article
Galleria mellonella Model of Coccidioidomycosis for Drug Susceptibility Tests and Virulence Factor Identification
by Matthew Mendoza Barker, Sarah Saeger, Althea Campuzano, Jieh-Juen Yu and Chiung-Yu Hung
J. Fungi 2024, 10(2), 131; https://doi.org/10.3390/jof10020131 - 5 Feb 2024
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Abstract
Coccidioidomycosis (CM) can manifest as respiratory and disseminated diseases that are caused by dimorphic fungal pathogens, such as Coccidioides species. The inhaled arthroconidia generated during the saprobic growth phase convert into multinucleated spherules in the lungs to complete the parasitic lifecycle. Research on [...] Read more.
Coccidioidomycosis (CM) can manifest as respiratory and disseminated diseases that are caused by dimorphic fungal pathogens, such as Coccidioides species. The inhaled arthroconidia generated during the saprobic growth phase convert into multinucleated spherules in the lungs to complete the parasitic lifecycle. Research on coccidioidal virulence and pathogenesis primarily employs murine models typically associated with low lethal doses (LD100 < 100 spores). However, the Galleria model has recently garnered attention due to its immune system bearing both structural and functional similarities to the innate system of mammals. Our findings indicate that Coccidioides posadasii can convert and complete the parasitic cycle within the hemocoel of the Galleria larva. In Galleria, the LD100 is between 0.5 and 1.0 × 106 viable spores for the clinical isolate Coccidioides posadasii C735. Furthermore, we demonstrated the suitability of this model for in vivo antifungal susceptibility tests to validate the bioreactivity of newly discovered antifungals against Coccidioides. Additionally, we utilized this larva model to screen a Coccidioides posadasii mutant library showing attenuated virulence. Similarly, the identified attenuated coccidioidal mutants displayed a loss of virulence in a commonly used murine model of coccidioidomycosis. In this study, we demonstrated that Galleria larvae can be applied as a model for studying Coccidioides infection. Full article
(This article belongs to the Special Issue Coccidioides and Coccidioidomycosis, 2nd Edition)
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Review

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21 pages, 9381 KiB  
Review
The Known and Unknown “Knowns” of Human Susceptibility to Coccidioidomycosis
by Amy P. Hsu
J. Fungi 2024, 10(4), 256; https://doi.org/10.3390/jof10040256 - 28 Mar 2024
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Abstract
Coccidioidomycosis occurs after inhalation of airborne spores of the endemic, dimorphic fungus, Coccidioides. While the majority of individuals resolve the infection without coming to medical attention, the fungus is a major cause of community-acquired pneumonia in the endemic region, and chronic pulmonary [...] Read more.
Coccidioidomycosis occurs after inhalation of airborne spores of the endemic, dimorphic fungus, Coccidioides. While the majority of individuals resolve the infection without coming to medical attention, the fungus is a major cause of community-acquired pneumonia in the endemic region, and chronic pulmonary and extrapulmonary disease poses significant personal and economic burdens. This review explores the literature surrounding human susceptibility to coccidioidomycosis, including chronic pulmonary and extrapulmonary dissemination. Over the past century of study, themes have emerged surrounding factors impacting human susceptibility to severe disease or dissemination, including immune suppression, genetic susceptibility, sex, pregnancy, and genetic ancestry. Early studies were observational, frequently with small numbers of cases; several of these early studies are highly cited in review papers, becoming part of the coccidioidomycosis “canon”. Specific genetic variants, sex, and immune suppression by TNF inhibitors have been validated in later cohort studies, confirming the original hypotheses. By contrast, some risk factors, such as ABO blood group, Filipino ancestry, or lack of erythema nodosum among black individuals, are repeated in the literature despite the lack of supporting studies or biologic plausibility. Using examination of historical reports coupled with recent cohort and epidemiology studies, evidence for commonly reported risk factors is discussed. Full article
(This article belongs to the Special Issue Coccidioides and Coccidioidomycosis, 2nd Edition)
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24 pages, 3280 KiB  
Review
The Host Response to Coccidioidomycosis
by Theo N. Kirkland, Chiung-Yu Hung, Lisa F. Shubitz, Sinem Beyhan and Joshua Fierer
J. Fungi 2024, 10(3), 173; https://doi.org/10.3390/jof10030173 - 25 Feb 2024
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Abstract
Coccidioidomycosis is an important fungal disease that is found in many desert regions of the western hemisphere. The inhaled organisms are highly pathogenic, but only half of infected, immunologically intact people develop symptomatic pneumonia; most symptomatic infections resolve spontaneously, although some resolve very [...] Read more.
Coccidioidomycosis is an important fungal disease that is found in many desert regions of the western hemisphere. The inhaled organisms are highly pathogenic, but only half of infected, immunologically intact people develop symptomatic pneumonia; most symptomatic infections resolve spontaneously, although some resolve very slowly. Furthermore, second infections are very rare and natural immunity after infection is robust. Therefore, the host response to this organism is very effective at resolving the infection in most cases and immunizing to prevent second infections. People who are immunocompromised are much more likely to develop disseminated infection. This is a comprehensive review of the innate and acquired immune responses to Coccidioides spp., the genetics of resistance to severe infection, and the search for an effective vaccine. Full article
(This article belongs to the Special Issue Coccidioides and Coccidioidomycosis, 2nd Edition)
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Other

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9 pages, 1133 KiB  
Brief Report
Evaluation of the Analytical Performance of a Lateral Flow Assay for the Detection of Anti-Coccidioides Antibodies in Human Sera—Argentina
by Mariana N. Viale, Diego H. Caceres, Patricia E. Mansilla, María C. Lopez-Joffre, Flavia G. Vivot, Andrea N. Motter, Adriana I. Toranzo and Cristina E. Canteros
J. Fungi 2024, 10(5), 322; https://doi.org/10.3390/jof10050322 - 28 Apr 2024
Viewed by 530
Abstract
Coccidiomycosis is a potentially life-threatening fungal infection endemic to certain regions of Argentina. The infection is caused by Coccidioides spp. and is primarily diagnosed by Coccidioides antibody (Ab) detection. Access to rapid, highly accurate diagnostic testing is critical to ensure prompt antifungal therapy. [...] Read more.
Coccidiomycosis is a potentially life-threatening fungal infection endemic to certain regions of Argentina. The infection is caused by Coccidioides spp. and is primarily diagnosed by Coccidioides antibody (Ab) detection. Access to rapid, highly accurate diagnostic testing is critical to ensure prompt antifungal therapy. The sōna Coccidioides Ab Lateral Flow Assay (LFA) performs faster and requires less laboratory infrastructure and equipment compared with other Ab detection assays, potentially providing a substantial improvement for rapid case screening in coccidioidomycosis-endemic regions; however, validation of this test is needed. Thus, we aimed to evaluate the analytical performance of the sōna Coccidioides Ab (LFA) and compare agreement with anti-Coccidioides Ab detection assays. A total of 103 human sera specimens were tested, including 25 specimens from patients with coccidioidomycosis and 78 from patients without coccidioidomycosis. The sōna Coccidioides Ab Lateral Flow Assay (LFA) was performed with a sensitivity of 88%, and specificity and accuracy of 87%. Furthermore, the Coccidioides Ab LFA had good agreement with other anti-Coccidioides Ab detection assays. Our findings suggest the sōna Coccidioides Ab LFA has satisfactory performance and may be useful for diagnosing coccidioidomycosis in endemic regions. Full article
(This article belongs to the Special Issue Coccidioides and Coccidioidomycosis, 2nd Edition)
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10 pages, 926 KiB  
Brief Report
Examining Miliary Disease Etiology in a Coccidioides-Endemic Center: A Retrospective Cohort Study
by Ashley M. Scott, James Ray Lim, Reubender Randhawa, Jason Lee, Kavitha Yaddanapudi, Brooke Rabe and Joshua Malo
J. Fungi 2024, 10(1), 29; https://doi.org/10.3390/jof10010029 - 31 Dec 2023
Viewed by 1174
Abstract
Background: A miliary pattern on chest imaging is often attributed to tuberculosis (TB) infection. However, a myriad of conditions can cause a miliary pattern, many of which are imminently life-threatening. Research Question: The primary aim of our study is to elucidate the potential [...] Read more.
Background: A miliary pattern on chest imaging is often attributed to tuberculosis (TB) infection. However, a myriad of conditions can cause a miliary pattern, many of which are imminently life-threatening. Research Question: The primary aim of our study is to elucidate the potential causes of miliary chest imaging patterns to improve workup and empiric therapy selection. The secondary aims are to discern the predictors of miliary disease etiology and to determine whether appropriate empiric antimicrobial therapies were given. Study Design and Methods: In this retrospective cohort study, we searched a radiology database for patients with chest imaging studies described by the word “miliary”. Subjects were excluded if they were under 18 years of age and if there were insufficient objective data to support a miliary disease etiology. A radiologist independently reviewed all imaging studies, and studies that did not appear to have a true miliary pattern were excluded. The collected data include patient demographics, immunocompromising risk factors, conditions associated with miliary disease, β-D-glucan levels, serum eosinophil count, and empiric therapies received. Results: From our 41-patient cohort, 22 patients (53.7%) were clinically diagnosed with coccidioidomycosis, 8 (19.5%) with TB, 7 (17.1%) with metastatic solid cancer, 1 (2.4%) with lymphoma, 1 (2.4%) with other (Mycobacterium simiae), and 3 (7.3%) with unknown diseases (the sum equals 42 patients because one individual was diagnosed with both coccidioidomycosis and TB). All six patients with greater than 500 eosinophils/μL were diagnosed with coccidioidomycosis. Of the 22 patients diagnosed with coccidioidomycosis, 20 (90.91%) were empirically treated with an antifungal regimen. Of the eight patients with TB, six were empirically treated for TB. Interpretation: Based on our data from a Coccidioides-endemic region with close proximity to tuberculosis-endemic areas, the leading cause of miliary disease is coccidioidomycosis, although TB and cancer are also common etiologies. Serum eosinophilia and elevated β-D-glucan levels were strongly predictive of coccidioidomycosis in our patient cohort with a miliary chest imaging pattern. Full article
(This article belongs to the Special Issue Coccidioides and Coccidioidomycosis, 2nd Edition)
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