{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T01:32:46Z","timestamp":1782437566134,"version":"3.54.5"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Chromoblastomycosis (CBM) is a chronic disease caused by several species of dematiaceous fungi. In this study, a regional collection of 45 CBM cases was conducted in Guangdong, China, a hyper-endemic area of CBM. Epidemiology findings indicated that the mean age of cases was 61.38 \u00b1 11.20 years, long duration ranged from 3 months to 30 years, and the gender ratio of male to female was 4.6:1. Thirteen cases (29%) declared underlying diseases. Verrucous form was the most common clinical manifestation (<jats:italic>n<\/jats:italic> = 19, 42%). Forty-five corresponding clinical strains were isolated, and 28 of them (62%) were identified as <jats:italic>F. monophora<\/jats:italic>; the remaining 17 (38%) were identified as <jats:italic>F. nubica<\/jats:italic> through ITS rDNA sequence analysis. Antifungal susceptibility tests <jats:italic>in vitro<\/jats:italic> showed low MICs in azoles (PCZ 0.015\u20130.25 \u03bcg\/ml, VCZ 0.015\u20130.5 \u03bcg\/ml, and ITZ 0.03\u20130.5 \u03bcg\/ml) and TRB (0.015\u20131 \u03bcg\/ml). Itraconazole combined with terbinafine was the main therapeutic strategy used for 31 of 45 cases, and 68% (<jats:italic>n<\/jats:italic> = 21) of them improved or were cured. Cytokine profile assays indicated upregulation of IL-4, IL-7, IL-15, IL-11, and IL-17, while downregulation of IL-1RA, MIP-1\u03b2, IL-8, and IL-16 compared to healthy donors (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). The abnormal cytokine profiles indicated impaired immune response to eliminate fungus in CBM cases, which probably contributed to the chronic duration of this disease. In conclusion, we investigated the molecular epidemiological, clinical, and laboratory characteristics of CBM in Guangdong, China, which may assist further clinical therapy, as well as fundamental pathogenesis studies of CBM.<\/jats:p>","DOI":"10.3389\/fcimb.2022.810604","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T06:18:23Z","timestamp":1645165103000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Molecular Characteristics of Regional Chromoblastomycosis in Guangdong, China: Epidemiological, Clinical, Antifungal Susceptibility, and Serum Cytokine Profiles of 45 Cases"],"prefix":"10.3389","volume":"12","author":[{"given":"Hongfang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiufeng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenying","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangxia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenmou","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiying","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Xi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1258\/td.2009.090264","article-title":"Managing Chromoblastomycosis","volume":"40","author":"Ameen","year":"2010","journal-title":"Trop. Doct"},{"key":"B2","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s11046-013-9634-3","article-title":"Chromoblastomycosis Due to Fonsecaea Pedrosoi and F. Monophora in Cuba","volume":"175","author":"Badali","year":"2013","journal-title":"Mycopathologia"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e0006675","DOI":"10.1371\/journal.pntd.0006675","article-title":"Molecular Identification and Antifungal Susceptibility Profiles of Clinical Strains of Fonsecaea Spp. Isolated From Patients With Chromoblastomycosis in Rio De Janeiro, Brazil","volume":"12","author":"Coelho","year":"2018","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"5109","DOI":"10.1073\/pnas.91.11.5109","article-title":"Molecular and Functional Analysis of a Lymphocyte Chemoattractant Factor: Association of Biologic Function With CD4 Expression","volume":"91","author":"Cruikshank","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B5","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1111\/j.1469-0691.2005.01166.x","article-title":"Correlation Between the Procedure for Antifungal Susceptibility Testing for Candida Spp. Of the European Committee on Antibiotic Susceptibility Testing (EUCAST) and Four Commercial Techniques","volume":"11","author":"Cuenca-Estrella","year":"2005","journal-title":"Clin. Microbiol. Infect."},{"key":"B6","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s11046-013-9660-1","article-title":"A Case of Relapsed Chromoblastomycosis Due to Fonsecaea Monophora: Antifungal Susceptibility and Phylogenetic Analysis","volume":"176","author":"Daboit","year":"2013","journal-title":"Mycopathologia"},{"key":"B7","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/myc.12111","article-title":"In Vitro Susceptibility of Chromoblastomycosis Agents to Five Antifungal Drugs and to the Combination of Terbinafine and Amphotericin B","volume":"57","author":"Daboit","year":"2014","journal-title":"Mycoses"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2674","DOI":"10.1128\/JCM.00637-15","article-title":"Fonsecaea Pugnacius, a Novel Agent of Disseminated Chromoblastomycosis","volume":"53","author":"de Azevedo","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1080\/13693780410001661464","article-title":"Molecular Ecology and Pathogenic Potential of Fonsecaea Species","volume":"42","author":"De Hoog","year":"2004","journal-title":"Med. Mycol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1093\/cid\/ciu168","article-title":"Topical Application of Imiquimod as a Treatment for Chromoblastomycosis","volume":"58","author":"de Sousa","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1128\/AAC.02163-13","article-title":"Real-World Experience With Echinocandin MICs Against Candida Species in a Multicenter Study of Hospitals That Routinely Perform Susceptibility Testing of Bloodstream Isolates","volume":"58","author":"Eschenauer","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B12","doi-asserted-by":"publisher","first-page":"45","DOI":"10.4269\/ajtmh.1996.55.45","article-title":"Forty Years of Chromoblastomycosis in Madagascar: A Review","volume":"55","author":"Esterre","year":"1996","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B13","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1093\/mmy\/myw140","article-title":"Molecular Identification of Chromoblastomycosis Clinical Isolates in Guangdong","volume":"55","author":"Fransisca","year":"2017","journal-title":"Med. Mycol."},{"key":"B14","volume-title":"Simulation of Polymer Translocation Through Small Channels: A Molecular Dynamics Study and a New Monte Carlo Approach","author":"Gauthier","year":"2007"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e0005102","DOI":"10.1371\/journal.pntd.0005102","article-title":"Molecular Epidemiology of Agents of Human Chromoblastomycosis in Brazil With the Description of Two Novel Species","volume":"10","author":"Gomes","year":"2016","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1003936","DOI":"10.1371\/journal.ppat.1003936","article-title":"A Polysaccharide Virulence Factor From Aspergillus Fumigatus Elicits Anti-Inflammatory Effects Through Induction of Interleukin-1 Receptor Antagonist","volume":"10","author":"Gresnigt","year":"2014","journal-title":"PLoS Pathog."},{"key":"B17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.pdpdt.2019.02.013","article-title":"Successful Treatment of Chromoblastomycosis Using ALA-PDT in a Patient With Leukopenia","volume":"26","author":"Huang","year":"2019","journal-title":"Photodiagn Photodyn Ther."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0007849","DOI":"10.1371\/journal.pntd.0007849","article-title":"Photodynamic Therapy Combined With Antifungal Drugs Against Chromoblastomycosis and the Effect of ALA-PDT on Fonsecaea In Vitro","volume":"13","author":"Hu","year":"2019","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1093\/mmy\/myx148","article-title":"Melanization of a Meristematic Mutant of Fonsecaea Monophora Increase the Pathogenesis in a BALB\/c Mice Infection Model","volume":"56","author":"Jiang","year":"2018","journal-title":"Med. Mycol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.clindermatol.2006.05.007","article-title":"Chromoblastomycosis","volume":"25","author":"Lopez","year":"2007","journal-title":"Clin. Dermatol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1016\/j.biocel.2003.10.019","article-title":"Macrophage Inflammatory Protein-1","volume":"36","author":"Maurer","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/j.micinf.2005.01.006","article-title":"Cytokines and Lymphocyte Proliferation in Patients With Different Clinical Forms of Chromoblastomycosis","volume":"7","author":"Mazo","year":"2005","journal-title":"Microbes Infect."},{"key":"B23","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1067\/mjd.2001.112220","article-title":"Chromoblastomycosis: A Review of 100 Cases in the State of Rio Grande do Sul, Brazil","volume":"44","author":"Minotto","year":"2001","journal-title":"J. Am. Acad. Dermatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1128\/AAC.01655-09","article-title":"In Vitro Activities of Eight Antifungal Drugs Against 55 Clinical Isolates of Fonsecaea Spp","volume":"54","author":"Najafzadeh","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"B25","doi-asserted-by":"publisher","first-page":"464","DOI":"10.3201\/eid1703.100555","article-title":"Molecular Epidemiology of Fonsecaea Species","volume":"17","author":"Najafzadeh","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1080\/13693780701721856","article-title":"Extensive Chromoblastomycosis Caused by Fonsecaea Pedrosoi Successfully Treated With a Combination of Amphotericin B and Itraconazole","volume":"46","author":"Paniz-Mondolfi","year":"2008","journal-title":"Med. Mycol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2618","DOI":"10.1128\/JCM.40.7.2618-2621.2002","article-title":"Use of the Sensititre Colorimetric Microdilution Panel for Antifungal Susceptibility Testing of Dermatophytes","volume":"40","author":"Pujol","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1128\/CMR.00032-16","article-title":"Chromoblastomycosis","volume":"30","author":"Queiroz-Telles","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"B29","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s11046-013-9648-x","article-title":"Challenges in the Therapy of Chromoblastomycosis","volume":"175","author":"Queiroz-Telles","year":"2013","journal-title":"Mycopathologia"},{"key":"B30","doi-asserted-by":"publisher","first-page":"S466","DOI":"10.1097\/01.ccm.0000186783.34908.18","article-title":"Interleukin-8","volume":"33","author":"Remick","year":"2005","journal-title":"Crit. Care Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/s0090-3019(03)00135-6","article-title":"Cerebral Phaeohyphomycosis Masquerading as a Parafalcian Mass: Case Report","volume":"60","author":"Saberi","year":"2003","journal-title":"Surg. Neurol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1128\/CMR.00093-13","article-title":"Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense","volume":"27","author":"Seyedmousavi","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e3162","DOI":"10.1371\/journal.pntd.0003162","article-title":"In Situ Immune Response in Human Chromoblastomycosis\u2013A Possible Role for Regulatory and Th17 T Cells","volume":"8","author":"Silva","year":"2014","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1023\/a:1006957415346","article-title":"Chromoblastomycosis: A Retrospective Study of 325 Cases on Amazonic Region (Brazil)","volume":"143","author":"Silva","year":"1998","journal-title":"Mycopathologia"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1128\/JCM.00044-17","article-title":"Comparative Evaluation of Sensititre YeastOne and CLSI M38-A2 Reference Method for Antifungal Susceptibility Testing of Aspergillus Spp. Against Echinocandins","volume":"55","author":"Siopi","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.chom.2011.04.005","article-title":"Restoration of Pattern Recognition Receptor Costimulation to Treat Chromoblastomycosis, a Chronic Fungal Infection of the Skin","volume":"9","author":"Sousa","year":"2011","journal-title":"Cell Host Microbe"},{"key":"B37","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1080\/13693780500220373","article-title":"Cerebral Phaeohyphomycosis Caused by Fonsecaea Monophora","volume":"43","author":"Surash","year":"2005","journal-title":"Med. Mycol."},{"key":"B38","first-page":"315","volume-title":"Amplification and Direct Sequencing of Fungal Ribosomal RNA Genes for Phylogenetics","author":"White","year":"1990"},{"key":"B39","volume-title":"Report of the Tenth Meeting of the WHO Strategic and Technical Advisory Group for Neglected Tropical Diseases","year":"2017"},{"key":"B40","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1080\/13693780802468209","article-title":"Molecular Diversity of Fonsecaea (Chaetothyriales) Causing Chromoblastomycosis in Southern China","volume":"47","author":"Xi","year":"2009","journal-title":"Med. Mycol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1111\/j.1439-0507.2007.01383.x","article-title":"Molecular Phylogenetics of Strains Morphologically Identified as Fonsecaea Pedrosoi From Clinical Specimens","volume":"50","author":"Yaguchi","year":"2007","journal-title":"Mycoses"},{"key":"B42","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1093\/mmy\/myx075","article-title":"Chromoblastomycosis in Taiwan: A Report of 30 Cases and a Review of the Literature","volume":"56","author":"Yang","year":"2018","journal-title":"Med. Mycol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s11046-018-0307-0","article-title":"Chromoblastomycosis Caused by Fonsecaea Nubica: First Report in Northern China and Literature Review","volume":"184","author":"You","year":"2019","journal-title":"Mycopathologia"},{"key":"B44","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/s11046-012-9588-x","article-title":"Melanin in a Meristematic Mutant of Fonsecaea Monophora Inhibits the Production of Nitric Oxide and Th1 Cytokines of Murine Macrophages","volume":"175","author":"Zhang","year":"2013","journal-title":"Mycopathologia"},{"key":"B45","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1111\/j.1439-0507.2008.01547.x","article-title":"Successful Treatment for Chromoblastomycosis Caused by Fonsecaea Monophora: A Report of Three Cases in Guangdong, China","volume":"52","author":"Zhang","year":"2009","journal-title":"Mycoses"},{"key":"B46","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1111\/myc.12895","article-title":"In Vitro Susceptibility of Dematiaceous Fungi to Nine Antifungal Agents Determined by Two Different Methods","volume":"62","author":"Zheng","year":"2019","journal-title":"Mycoses"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.810604\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T06:18:30Z","timestamp":1645165110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.810604\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":46,"alternative-id":["10.3389\/fcimb.2022.810604"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.810604","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,18]]},"article-number":"810604"}}