王莉莉负责收集数据、撰写及修改文章、文献查找;郭建负责药敏实验以及论文指导、审核。
收稿日期: 2026-03-06
修回日期: 2026-03-31
录用日期: 2026-05-11
网络出版日期: 2026-06-27
基金资助
上海市浦东新区卫健委卫生科技面上项目(PW2024A-02)
Epidemiological status and drug resistance survey of protothecosis in China from 2015 to 2025
Received date: 2026-03-06
Revised date: 2026-03-31
Accepted date: 2026-05-11
Online published: 2026-06-27
目的:无绿藻是一种丧失叶绿素、无法进行光合作用的单细胞微藻,属于小球藻科,其生物学属性介于藻类与真菌之间。无绿藻病多为外源性感染,病原体常经破损的皮肤黏膜接触污染的土壤、水体或有机物而侵入。患者临床表现以皮肤及皮下组织感染和鹰嘴滑囊炎为主。本研究调查2015年至2025年间中国的无绿藻病流行病学特征及抗菌药物敏感性分布,以填补国内无绿藻病流行病学与诊疗规范的空白,为无绿藻病的临床诊疗与防控策略提供依据。方法:2015年至2025年间,回顾性收集由无绿藻病科普与监测联盟收集的84株临床分离的无绿藻菌株,采用微量肉汤稀释法对所有菌株进行体外药物敏感性试验,检测药物涵盖5种唑类、3种棘白菌素类、5-氟胞嘧啶及两性霉素B,并进行CYTB基因测序,构建系统发育分析。结果:2015年至2025年间,我国无绿藻病患者标本分离出的无绿藻临床分离株,以威克汉姆无绿藻为主(79.8%),其次为牛无绿藻(11.9%),其中华东地区的分离株数量最多(45.2%)。无绿藻病患者以中老年人群为主,41~80岁的患者占82.1%。分离部位以皮肤组织最为常见,占59.5%;非皮肤分离部位包括脑脊液、血液、腹水及支气管肺泡灌洗液等。部分唑类药物(伊曲康唑、泊沙康唑和伏立康唑)对无绿藻表现出较强的抗菌活性,抑制50%菌株生长所需的最小抑菌浓度(minimum inhibitory concentration, MIC)即MIC50均为1.000 μg/mL;艾沙康唑活性更优,MIC范围为0.015~1.000 μg/mL。两性霉素B对无绿藻有较强的抗菌活性,MIC50为0.500 μg/ mL。氟康唑、5-氟胞嘧啶及各类棘白菌素类药物对无绿藻无显著抗菌活性。艾沙康唑对威克汉姆无绿藻的抗菌活性显著高于对牛无绿藻和祖菲无绿藻。系统发育分析显示,威克汉姆无绿藻构成最主要的进化分支,且分支结构高度复杂,提示存在显著的种内遗传异质性。结论:我国无绿藻病患者分离获得的菌株以威克汉姆无绿藻为主,感染人群主要为中老年人,分离部位主要为皮肤,但非皮肤感染部位分布广泛。两性霉素B和艾沙康唑对临床分离的无绿藻具有较强的体外抗菌活性,但不同菌种间药物敏感性存在差异。
王莉莉 , 郭建 . 2015年至2025年中国无绿藻病流行现状及耐药调查[J]. 诊断学理论与实践, 2026 , 25(03) : 308 -314 . DOI: 10.16150/j.1671-2870.2026.03.006
Objective Prototheca is a unicellular microalga belonging to the family Chlorellaceae that has lost its chlorophyll and the ability to perform photosynthesis, exhibiting biological characteristics intermediate between algae and fungi. Protothecosis is predominantly an exogenous infection, with pathogens commonly invading through damaged skin or mucous membranes via contact with contaminated soil, water, or organic matter. Clinical manifestations primarily include cutaneous and subcutaneous infections and olecranon bursitis. This study investigates the epidemiological characteristics and antimicrobial susceptibility distribution of protothecosis in China from 2015 to 2025, aiming to bridge the gap in domestic epidemiological data and clinical management guidelines of protothecosis, and to provide a scientific basis for its clinical diagnosis, treatment, and prevention strategies. Methods A total of 84 clinical Prototheca isolates collected by the Protothecosis Science Popularization and Monitoring Consortium (PSPMC) between 2015 and 2025 were retrospectively analyzed. In vitro susceptibility testing was performed for all isolates using the broth microdilution method. The tested agents included five azoles, three echinocandins, 5-flucytosine, and amphotericin B. Additionally, CYTB gene sequencing was conducted, followed by phylogenetic analysis. Results Among the isolates obtained from patients with protothecosis in China between 2015 and 2025, Prototheca wickerhamii was the predominant species (79.8%), followed by Prototheca bovis (11.9%). The highest number of isolates was found in East China (45.2%). The infections predominantly affected middle-aged and elderly individuals, with 82.1% of patients aged between 41 and 80 years. Skin tissue was the most common isolation source, accounting for 59.5% of all clinical isolates. Non-cutaneous sources included cerebrospinal fluid, blood, ascitic fluid, and bronchoalveolar lavage fluid. Azole antifungal agents, such as itraconazole, posaconazole, and voriconazole, demonstrated strong antimicrobial activity against Prototheca, with the minimum inhibitory concentration (MIC) required to inhibit 50% of isolates (MIC50) being 1.000 μg/mL. Isavuconazole exhibited superior activity, with MICs ranging from 0.015 to 1.000 μg/mL. Amphotericin B also showed strong antimicrobial activity (MIC50 = 0.500 μg/mL). Conversely, fluconazole, 5-flucytosine, and echinocandins showed no significant antimicrobial activity against Prototheca. The antimicrobial activity of isavuconazole against P. wickerhamii was significantly higher than against P. bovis and Prototheca zopfii. Phylogenetic analysis indicated that P. wickerhamii constituted the major evolutionary clade with a highly complex structure, suggesting significant intraspecific genetic heterogeneity. Conclusions Prototheca wickerhamii is the predominant species among isolates obtained from patients with protothecosis in China. The infected population mainly consists of middle-aged and elderly individuals. While skin is the main site of infection, non-cutaneous sites are widely distributed. Amphotericin B and isavuconazole demonstrate strong in vitro antimicrobial activity against these clinical Prototheca isolates, although susceptibility varies among different species.
| [1] | THIELE D, BERGMANN A. Protothecosis in human medicine[J]. Int J Hyg Environ Health, 2002, 204(5/6):297-302. |
| [2] | LASS-FLO?RL C, MAYR A. Human protothecosis[J]. Clin Microbiol Rev, 2007, 20(2):230-242. |
| [3] | TODD J R, KING J W, OBERLE A, et al. Protothecosis: Report of a case with 20-year follow-up, and review of previously published cases[J]. Med Mycol, 2012, 50(7):673-689. |
| [4] | TSENG I L, LIU W T. Cutaneous protothecosis[J]. Acad Dermatol Venereol, 2026, 40(5):908-909. |
| [5] | INOUE M, MIYASHITA A, NOGUCHI H, et al. Case report of cutaneous protothecosis caused by Prototheca wickerhamii designated as genotype 2 and current status of human protothecosis in Japan[J]. J Dermatol, 2018, 45(1):67-71. |
| [6] | MATHEW L G, PULIMOOD S, THOMAS M, et al. Disseminated protothecosis[J]. Indian J Pediatr, 2010, 77(2):198-199. |
| [7] | JAGIELSKI T, GAWOR J, BAKU?A Z, et al. cytbas a new genetic marker for differentiation of Prototheca Species[J]. J Clin Microbiol, 2018, 56(10):e00584-e00518. |
| [8] | WANG X, RAN Y, JIA S, et al. Human disseminated protothecosis: The skin is the “window”?[J]. Front Immunol, 2022,13:880196. |
| [9] | SETHURAMAN N, RAO P, RAMANATHAN Y, et al. Disseminated protothecosis caused by Prototheca zopfii in a liver transplant recipient[J]. J Global Infect Dis, 2018, 10(4):228. |
| [10] | JAGIELSKI T, ISKRA M, BAKU?A Z, et al. Occurrence ofProtothecaMicroalgae in aquatic ecosystems with a description of three new species, Prototheca fontanea, Prototheca lentecrescens, and Prototheca vistulensis[J]. Appl Environ Microbiol, 2022, 88(22):e01092-e01022. |
| [11] | MAYORGA J, BARBA-GóMEZ J F, VERDUZCO-MARTíNEZ A P, et al. Protothecosis[J]. Clin Dermatol, 2012, 30(4):432-436. |
| [12] | PROSKURNICKA A, ?UPNIK K, BAKU?A Z, et al. Drug susceptibility profiling of Prototheca Species isolated from cases of human protothecosis[J]. Antimicrob Agents Chemother, 2023, 67(4):e01627-e01622. |
| [13] | JAGIELSKI T, BAKU?A Z, DI MAURO S, et al. A comparative study of the in vitro activity of iodopropynyl butylcarbamate and amphotericin B against Prototheca spp. isolates from European dairy herds[J]. J Dairy Sci, 2017, 100(9):7435-7445. |
| [14] | TORTORANO A M, PRIGITANO A, DHO G, et al. In vitro activity of conventional antifungal drugs and natural essences against the yeast-like Alga Prototheca[J]. J Antimicrob Chemother, 2008, 61(6):1312-1314. |
| [15] | MACESIC N, FLEMING S, KIDD S, et al. Protothecosis in hematopoietic stem cell transplantation: Case report and review of previous cases[J]. Transpl Infect Dis, 2014, 16(3):490-495. |
| [16] | TUOHUTI P, CHEN Y, ZHAO A, et al. Isavuconazole for the treatment of invasive fungal disease in hematology patients: A real-world retrospective study on efficacy and safety[J]. Microorganisms, 2025, 13(12):2677. |
| [17] | áLVAREZ-PéREZ S, ANEGA B, DíAZ-DE-TUESTA J A, et al. Susceptibility testing of Prototheca bovis isolates from cases of bovine mastitis using the CLSI reference broth microdilution method and the Sensititre YeastOne colorimetric panel[J]. Med Mycol, 2021, 59(12):1257-1261. |
| [18] | MASUDA M, JAGIELSKI T, DANESI P, et al. Protothecosis in dogs and cats: New research directions[J]. Mycopathologia, 2021, 186(1):143-152. |
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