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      Coccidioidomycosis: A Contemporary Review

      review-article
      Infectious Diseases and Therapy
      Springer Healthcare
      Coccidioidomycosis, Coccidioides, Valley fever, Endemic mycosis, Review

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          Abstract

          Coccidioidomycosis, colloquially known as Valley Fever, is an invasive dimorphic fungal infection caused by Coccidioides immitis and  C. posadasii. The fungi are found in the arid desert soils of the southwestern US, as well as in parts of Mexico and Central and South America. Acquisition is typically via inhalation of arthroconidia which become airborne after both natural (e.g., earthquakes, dust storms, and fires) and human-related events (e.g., military maneuvers, recreational activities, agriculture, and construction). The incidence of infection in increasing likely a result of both climatic and populational changes. Further, the recognized geographic distribution of Coccidioides spp. is expanding, as cases are being diagnosed in new areas (e.g., eastern Washington, Oregon, and Utah). Most coccidioidal infections are asymptomatic (60%); however, approximately one-third develop a pulmonary illness which is a leading cause of community-acquired pneumonia in highly endemic areas. Uncommonly (0.5–2% of cases), the infection disseminates to extrapulmonary locations (e.g., skin, bones/joints, and the central nervous system), and is most commonly seen among persons with cellular immunodeficiencies (e.g., transplant recipients, HIV, and pregnancy) and non-Caucasian races (especially African Americans and Filipinos). The diagnosis of coccidioidomycosis requires astute clinical suspicion and laboratory findings, including positive serology, cultures, and/or histopathology results. Treatment is warranted among persons with pneumonia who have risk factors for complicated disease and among those with extrapulmonary disease. Novel antifungals with improved fungicidal activity and rapidity of action with fewer side effects and drug interactions are needed. Preventive strategies (e.g., education regarding the disease, dust avoidance, mask wearing, including among select groups, antifungal prophylaxis, and surveillance laboratory testing) are advised for residents and travelers to endemic areas. Currently, no preventive vaccine is available. Coccidioidomycosis has been recognized for over a century, and an expanding wealth of knowledge has been gained regarding this emerging infectious disease which will be reviewed here.

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          Most cited references159

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          Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes.

          Voriconazole is the therapy of choice for aspergillosis and a new treatment option for candidiasis. Liver disease, age, genetic polymorphism of the cytochrome CYP2C19, and comedications influence voriconazole metabolism. Large variations in voriconazole pharmacokinetics may be associated with decreased efficacy or with toxicity. This study was conducted to assess the utility of measuring voriconazole blood levels with individualized dose adjustments. A total of 181 measurements with high-pressure liquid chromatography were performed during 2388 treatment days in 52 patients. A large variability in voriconazole trough blood levels was observed, ranging from 5.5 mg/L (a level possibly associated with toxicity) in 31% of cases. Lack of response to therapy was more frequent in patients with voriconazole levels 1 mg/L (15 [12%] of 39 patients; P=.02). Blood levels >1 mg/L were reached after increasing the voriconazole dosage, with complete resolution of infection in all 6 cases. Among 16 patients with voriconazole trough blood levels >5.5 mg/L, 5 patients (31%) presented with an encephalopathy, including 4 patients who were treated intravenously with a median voriconazole dosage of 8 mg/kg per day, whereas none of the patients with levels
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            Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives.

            While most Ascomycetes tend to associate principally with plants, the dimorphic fungi Coccidioides immitis and Coccidioides posadasii are primary pathogens of immunocompetent mammals, including humans. Infection results from environmental exposure to Coccidiodies, which is believed to grow as a soil saprophyte in arid deserts. To investigate hypotheses about the life history and evolution of Coccidioides, the genomes of several Onygenales, including C. immitis and C. posadasii; a close, nonpathogenic relative, Uncinocarpus reesii; and a more diverged pathogenic fungus, Histoplasma capsulatum, were sequenced and compared with those of 13 more distantly related Ascomycetes. This analysis identified increases and decreases in gene family size associated with a host/substrate shift from plants to animals in the Onygenales. In addition, comparison among Onygenales genomes revealed evolutionary changes in Coccidioides that may underlie its infectious phenotype, the identification of which may facilitate improved treatment and prevention of coccidioidomycosis. Overall, the results suggest that Coccidioides species are not soil saprophytes, but that they have evolved to remain associated with their dead animal hosts in soil, and that Coccidioides metabolism genes, membrane-related proteins, and putatively antigenic compounds have evolved in response to interaction with an animal host.
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              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.
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                Author and article information

                Contributors
                nancy32red@yahoo.com
                Journal
                Infect Dis Ther
                Infect Dis Ther
                Infectious Diseases and Therapy
                Springer Healthcare (Cheshire )
                2193-8229
                2193-6382
                1 March 2022
                1 March 2022
                : 1-30
                Affiliations
                GRID grid.419722.b, ISNI 0000 0004 0392 9464, Infectious Diseases Department, , Scripps Health System, ; San Diego, CA USA
                Article
                606
                10.1007/s40121-022-00606-y
                8887663
                35233706
                a1f6cca6-4380-4b10-8f24-01698148afcf
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 25 January 2022
                : 4 February 2022
                Categories
                Review

                coccidioidomycosis,coccidioides,valley fever,endemic mycosis,review

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