巴西东北部某州首府首次出现人畜共患孢子丝菌病的临床流行病学概况:猫驱动的城市新发疫情证据。 机翻

First clinical-epidemiological profile of zoonotic sporotrichosis in a state capital of Northeast Brazil: evidence of an emerging feline-driven urban epidemic.

中文关键词(术语机标,非人工翻译):实验室检查

期刊Revista do Instituto de Medicina Tropical de Sao Paulo
发表日期2026-10-19
物种猫
DOI10.1590/s1678-9946202668069
PMID42912015

摘要

Zoonotic sporotrichosis has expanded in Brazil as an urban, cat-associated mycosis, but its human clinical-epidemiological profile remains poorly characterized in Maranhao State, Brazil. This study describes a hospital-based cohort from Greater Sao Luis and defines a regional profile not previously established in the state. We conducted an observational study combining retrospective and prospective data from 2022 to 2025 at a reference hospital for infectious diseases in Sao Luis municipality, Maranhao State, Brazil. Confirmed cases were defined by culture and/or compatible histopathological findings supported by clinical-epidemiological criteria. Demographic, exposure, clinical, laboratory, therapeutic, and outcome variables were analyzed using descriptive statistics and appropriate statistical tests. A total of 189 confirmed cases were analyzed. Cases increased sharply after 2022 and peaked in 2024, with 82 cases. Most patients lived in Sao Luis municipality (84.7%), were female (67.2%), and were aged 30-59 years (47.1%). Feline-associated exposure predominated: 70.9% reported having household cats and 81.5% reported scratches or contact with feline lesions or secretions. The lymphocutaneous form was the main presentation (61.9%), followed by fixed cutaneous disease (29.1%); upper limbs were the most frequently affected sites (73.0%). Culture was positive for Sporothrix spp. in 62.2% of tested samples, and suppurative granulomas were frequent findings on histopathological examination. Itraconazole was the first-line therapy in 92.0% of treated patients. Greater Sao Luis shows the profile of an emerging urban epidemic of zoonotic sporotrichosis of feline origin. These findings provide local evidence to guide surveillance, early diagnosis, integration between human and veterinary health services, and One Health-based control strategies in Maranhao State.

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第1页,共7页 本文为开放获取文章,依据知识共享署名许可协议条款发布。Rev Inst Med Trop São Paulo. 2026;68:e69 第1页,共7页 原创论文 https://doi.org/10.1590/S1678-9946202668069 1 马拉尼昂联邦大学,健康科学研究生项目,巴西马拉尼昂州圣路易斯 2 马拉尼昂联邦大学,Presidente Dutra大学医院,巴西马拉尼昂州圣路易斯 3 Cedro实验室,巴西马拉尼昂州圣路易斯 4 马拉尼昂联邦大学,医学院,巴西马拉尼昂州圣路易斯 5 Rede D'Or,D'Or研究与教学研究所,巴西马拉尼昂州圣路易斯 通讯作者:Thiago Dutra Mendonça 马拉尼昂联邦大学,健康科学研究生项目,Av. dos Portugueses, 1966, Vila Bacanga, CEP 65080-805, São Luís, MA, Brazil 电话:+55 98 98185-5206 电子邮箱:thiago.dm@ufma.br 收稿日期:2026年5月19日 接受日期:2026年8月3日 编辑:Gil Benard

巴西东北部某州首府人兽共患孢子丝菌病首个临床-流行病学特征:猫驱动的新发城市流行证据 Thiago Dutra Mendonça 1 , Rayssa de Sousa Silva 1 , Sirlei Garcia Marques 2,3 , Gustavo Silva Santos de Sousa 4 , Bianca de Fátima Assunção Sodré 4 , Ayrton Rocha Lima 4 , Guilherme Alencar de Medeiros 3 , Daniel Wagner de Castro Lima Santos 2,5 , Conceição de Maria Pedrozo e Silva de Azevedo 1 摘要 人兽共患孢子丝菌病作为一种与猫相关的城市真菌病在巴西不断扩大,但其在巴西马拉尼昂州的人类临床-流行病学特征仍鲜有描述。本研究描述了来自大圣路易斯地区的医院队列,并界定了该州此前尚未建立的区域特征。我们开展了一项观察性研究,结合2022年至2025年在巴西马拉尼昂州圣路易斯市一家传染病参考医院收集的回顾性和前瞻性数据。确诊病例定义为培养和/或符合组织病理学发现并得到临床-流行病学标准支持的病例。采用描述性统计和适当的统计学检验分析人口学、暴露、临床、实验室、治疗和结局变量。共分析189例确诊病例。病例在2022年后急剧增加,并于2024年达到峰值,共82例。大多数患者居住在圣路易斯市(84.7%),为女性(67.2%),年龄30–59岁(47.1%)。猫相关暴露占主导:70.9%报告家中有猫,81.5%报告有抓伤或接触猫病变或分泌物。淋巴皮肤型为主要表现(61.9%),其次为固定皮肤型(29.1%);上肢是最常受累部位(73.0%)。在受检样本中,62.2%培养出孢子丝菌属阳性,组织病理学检查中化脓性肉芽肿为常见发现。92.0%接受治疗的患者以伊曲康唑为一线治疗。大圣路易斯地区呈现出猫源性人兽共患孢子丝菌病新发城市流行的特征。这些发现为马拉尼昂州的监测、早期诊断、人医与兽医卫生服务整合以及基于“同一健康”的控制策略提供了本地证据。 关键词:孢子丝菌病。人兽共患病。猫。孢子丝菌属。流行病学。公共卫生。 引言 孢子丝菌病是由孢子丝菌属温度双相真菌引起的植入性真菌病。尽管传统上认为其与来自土壤、植物残体和职业暴露的创伤性接种有关,但随着猫传播疾病的增多,其流行病学在巴西已发生显著变化1,2。在此背景下,受感染的猫作为高效的放大器,因为其病变可能含有高真菌负荷,且传播可通过抓伤、咬伤或接触发生

Mendonça 等,Rev Inst Med Trop São Paulo. 2026;68:e69 第2页/共7页,伴渗出物2,3。其他传播途径,包括腐生性暴露、污染污染物以及感染猫的呼吸道传播,也已有报道,在监测和预防策略中应予以考虑4,5。巴西目前是全球人畜共患孢子丝菌病最重要的地区,尤其是因为该国与猫相关的传播与Sporothrix brasiliensis密切相关,这是一种高毒力菌种,已推动重大城市暴发1,2。首次大规模城市流行描述于里约热内卢市,那里猫与人间持续传播使孢子丝菌病从偶发的植入性真菌病转变为城市公共卫生问题3。后续报告记录了向巴西其他地区的地理扩散,包括系统人类数据仍有限的地区4,6-8。巴西东北部地区孢子丝菌病报告频率不断增加,但该病的人类负担和临床特征仍记录不均7。在马拉尼昂州,近期兽医和实验室证据提示Sporothrix spp.在圣路易斯市都市区循环;然而,足以界定受影响人群、主要暴露、临床表现、诊断模式和治疗反应的人类数据仍然匮乏。这一空白限制了监测规划、临床怀疑以及人-动物-环境一体化控制措施的实施4,9,10。因此,本研究旨在描述2022年至2025年巴西马拉尼昂州圣路易斯市一家参考医院治疗的经确认人畜共患孢子丝菌病病例的临床流行病学特征、诊断发现和治疗特点。通过在一个此前特征描述不足的地区界定本地特征,本研究为该州的公共卫生行动和One Health策略提供证据。伦理 本研究经马拉尼昂联邦大学研究伦理委员会批准,伦理审查证书编号Nº 84202724.9.0000.5087。所有程序均遵循巴西涉及人类研究的伦理标准。对于回顾性数据,因数据取自病历,豁免知情同意。对于前瞻性数据,已获得参与者或其法定代理人的书面知情同意。已获得患者对发表图2面部图像的书面知情同意。为保护隐私,眼部已遮挡。材料与方法 研究设计与场所 这是一项观察性研究,结合2022年1月至2023年12月的回顾性数据和2024年1月至2025年12月的前瞻性数据。研究在巴西马拉尼昂州圣路易斯市一家传染病和寄生虫病参考医院进行,该院接收来自首都及周边市的患者。研究人群与病例定义 研究人群包括研究期间治疗的经确认孢子丝菌病患者。病例资格依据符合巴西孢子丝菌病监测指南的临床流行病学和实验室标准确定11。符合条件的病例至少满足以下标准之一:Sporothrix spp.培养阳性;组织病理学发现符合孢子丝菌病,包括化脓性肉芽肿性炎症,伴或不伴星状体或酵母样结构;或符合的临床流行病学表现并有实验室或组织病理学证据支持。符合的临床表现包括单个或多个丘疹、结节、结节溃疡性、皮肤或黏膜病变,伴或不伴淋巴管扩散,并与既往接触猫、创伤性接种、接触有机物或其他合理暴露途径相关。诊断不确定或数据不足以分析的病例被排除。数据收集 数据取自病历和医院通知表。变量包括性别、年龄、居住市、诊断年份、接触猫、抓伤或接触猫病变或分泌物、园艺或土壤暴露、临床型、病变部位、真菌培养、组织病理学发现、抗真菌治疗、治疗持续时间以及可获得的临床结局。实验室诊断 真菌学检查在马拉尼昂州中央公共卫生实验室和Cedro实验室进行。临床样本,包括脓液、病变渗出物和活检碎片,接种于补充氯霉素的沙氏葡萄糖琼脂上,并

Rev Inst Med Trop São Paulo. 2026;68:e69 巴西东北部某州首府人畜共患孢子丝菌病的首次临床-流行病学特征分析 第3页,共7页 放线菌酮(Mycosel型选择性培养基)并在25 °C和37 °C下培养。所有回顾性样本的商业生产商详细信息并不一致可得。推定鉴定遵循常规实验室标准,基于与孢子丝菌属(Sporothrix spp.)相符的菌落生长和微形态特征;然而,并非所有分离株均有详细的大体和微形态描述符以及37 °C下酵母相转化的系统记录。对固定在10%福尔马林并石蜡包埋的皮肤活检碎片进行组织病理学检查。3–5 μm厚的切片用苏木精和伊红染色进行形态学分析;必要时,使用Grocott六胺银染色和过碘酸-雪夫染色检测真菌结构。统计分析 分类变量以绝对频率和相对频率汇总。连续变量根据数据分布以均数和标准差或中位数描述。分类变量之间的关联使用统计检验进行评估。统计显著性定义为p<0.05。分析使用SPSS(26.0版,IBM Corp.,Armonk,NY,USA)进行。结果 共分析189例确诊的人畜共患孢子丝菌病病例。年度分布显示研究期间显著增加,其中2024年病例数最高(82例),其次是2023年和2025年(图1)。大多数患者居住在São Luís市,为女性,且为30–59岁的成年人。平均年龄为43.7岁(标准差,17岁)。人口学分布汇总于表1。猫相关暴露是主要的流行病学模式。189例有可用数据的患者中,134例(70.9%)报告有与猫的家庭接触,154例(81.5%)报告有抓伤或接触猫病变或分泌物。这些暴露变量并非互斥,在记录了直接接触猫病变或分泌物的记录中,家猫常被描述为患病。园艺或土壤暴露不常见,仅7例患者(3.7%)报告。淋巴皮肤型是最常见的临床表现,其次是固定型皮肤病变。播散型及其他表现,包括黏膜和骨关节受累,较少见。数据集中记录了10例播散型病例;其中1例累及眶后区域,伴视交叉受压和永久性视力后遗症。代表性临床表现见图2。临床特征和暴露变量见表2。表1 - 巴西马拉尼昂州大São Luís地区2022–2025年确诊孢子丝菌病病例的人口学特征和年度分布。特征 n % 诊断年份 2022 13 6.9 2023 57 30.2 2024 82 43.4 2025 37 19.6 性别 女性 127 67.2 男性 62 32.8 年龄组,岁 0–19 28 14.8 20–29 30 15.9 30–59 89 47.1 ≥60 42 22.2 平均年龄,岁(SD)43.7(17.0)居住城市 São Luís 160 84.7 马拉尼昂州其他城市 29 15.3 SD = 标准差;百分比基于189例确诊病例估算。图1 图1 - 巴西马拉尼昂州医院队列中2022–2025年确诊孢子丝菌病病例的时间分布。

Mendonça 等,Rev Inst Med Trop São Paulo. 2026;68:e69 第4页,共7页。在135例接受真菌培养的患者中,84例(62.2%)为孢子丝菌属阳性。60例患者有组织病理学资料,其中40例(66.7%)发现化脓性肉芽肿。多核巨细胞和急性炎症浸润常见,部分病例可见真菌结构。92.1%的受治患者使用了伊曲康唑,189例受治患者中有174例(92.0%)使用;少数病例记录了替代方案,包括碘化钾和特比萘芬。大多数疗程持续三个月。住院情况、标准化结局评估及治疗调整的详细原因在病历中未一致记录,因此无法进行可靠分析。表3显示了诊断和治疗数据。讨论 本研究描述了大圣路易斯、马拉尼昂州、巴西的人兽共患孢子丝菌病的临床-流行病学特征,并支持该病作为该地区猫源性城市真菌病正在扩展的解释。2022年至2024年病例增加,加上猫相关暴露和局限性皮肤型的 predominance,与巴西其他受猫传播孢子丝菌病影响的城市中心报告的模式相似2,7。病例集中在圣路易斯市表明该首府可能是重要的传播或诊断焦点。这一发现可能反映了多种因素的综合作用,包括人口密度、人与家猫或流浪猫的密切接触、表2 - 确诊病例的流行病学暴露和临床特征。特征 n/N % 流行病学暴露 家猫 134/189 70.9 抓伤或接触猫病变/分泌物 154/189 81.5 园艺或土壤接触 7/189 3.7 临床类型 淋巴皮肤型 117/189 61.9 固定皮肤型 55/189 29.1 播散型 10/189 5.3 其他类型(黏膜或骨关节)7/189 3.7 病变部位 上肢 138/189 73.0 下肢 30/189 15.9 面部/颈部 15/189 7.9 躯干 6/189 3.2 图2 - 人兽共患孢子丝菌病的临床和组织病理学谱:(A)固定皮肤型孢子丝菌病,表现为手和腕背侧溃疡性结痂斑块;(B)淋巴皮肤型孢子丝菌病,特征为沿上肢淋巴引流途径分布的多个结节性病变;(C)播散性皮肤受累,面部多发病变累及鼻、口周和下巴区域;眼部为编辑和伦理保护而匿名化;(D)组织病理学切片显示淋巴组织细胞性肉芽肿性炎症浸润,伴中性粒细胞和坏死灶;(E)更高倍放大组织病理学切片显示中性粒细胞性炎症,炎症浸润中散布真菌结构;(F)组织病理学切片显示肉芽肿性炎症,伴淋巴组织细胞性和中性粒细胞性成分及组织坏死区域。苏木精-伊红染色(D–F)。图2

Rev Inst Med Trop São Paulo. 2026;68:e69 巴西东北部某州首府人畜共患孢子丝菌病首次临床-流行病学特征分析 第5页/共7页 更便捷的转诊医院可及性以及更高的临床识别度。然而,增幅之大提示该现象不能仅用转诊偏倚来解释,值得在医院检测之外开展结构化监测。女性 predominance 与孢子丝菌病历史上的职业性形式形成对比,后者经典地与农村或农业暴露相关。然而,这与巴西观察到的当代人畜共患特征一致,其中女性作为家庭环境中病猫的照护者可能具有更大的暴露风险 2,3,12。30–59岁成年人的 predominance 也提示涉及经济活跃人群,可能对生产力、家庭日常和照护动态产生影响。流行病学发现支持猫传播的作用。超过三分之二的患者报告家中有猫,超过80%报告有抓伤或接触猫病变或分泌物。相比之下,园艺或土壤暴露罕见。这一对比突显了研究环境中从腐生性或职业性孢子丝菌病向主要城市人畜共患病的转变 1,2,13。在马拉尼昂州,这一区分很重要,因为控制不能仅依赖针对土壤暴露的个体防护;它需要感染猫的早期诊断和治疗、负责任的宠物饲养、病动物的安全处理,以及人类与兽医卫生服务之间的协调监测。临床模式也与猫相关接种一致。淋巴皮肤型和固定皮肤型的 predominance,加上频繁的上肢受累,提示直接创伤性接种后局部或淋巴播散。播散性表现不常见但具有临床相关性,特别是眶后受累并遗留永久性视觉后遗症的病例。尽管大多数皮肤孢子丝菌病病例不危及生命,严重表现强调了对复杂疾病早期识别、充分治疗和转诊路径的需求。合并症和免疫状态信息不完整,这妨碍了对该队列中播散性表现的深入解读 4,14。培养仍是诊断确认的核心,但组织病理学在该队列中有用。化脓性肉芽肿性炎症、中性粒细胞浸润和偶见真菌结构符合活动性真菌感染。这些发现在培养或分子鉴定不广泛可及的环境中尤其相关,尽管组织病理学应结合临床和流行病学证据解读。已发表的孢子丝菌病组织病理学敏感性估计通常不高,我们的发现应在转诊中心队列和选择性提交活检的背景下解读,而非作为诊断敏感性的直接测量 4,5。伊曲康唑是主要治疗药物,与国际对固定皮肤型和淋巴皮肤型孢子丝菌病的推荐一致 4,14。三个月疗程的 predominance 可能提示许多患者早期诊断和良好反应。然而,根据推荐,治疗理想上应在临床缓解后继续,而复发、依从性、药物可及性、住院和失访无法在该数据集中系统评估,应在未来研究中调查。局限性 本研究存在局限性。其基于医院的设计可能过度代表获得专科诊疗的患者,而低估在其他地方治疗或社区未诊断的轻症病例。回顾性部分依赖于病历和通知表的完整性,导致某些分析中分母可变,以及住院、免疫状态、标准化结局和治疗调整指征信息不完整。完整的 georeferenced 居住数据也不可用,限制了更详细的空间分析。并非所有分离株都具备物种水平的分子确认;因此,巴西孢子丝菌在巴西人畜共患背景和当地猫证据下被讨论为最可能的物种,但 表3 - 孢子丝菌病患者的诊断发现和治疗特征。特征 n/N % 真菌培养 孢子丝菌属阳性 84/135 62.2 阴性 51/135 37.8 组织病理学 化脓性肉芽肿 40/60 66.7 其他发现 20/60 33.3 使用药物 伊曲康唑 174/189 92.0 碘化钾 10/189 5.3 特比萘芬 5/189 2.7 治疗时长 3个月 109/189 57.7 4–6个月 60/189 31.7 >6个月 20/189 10.6

Mendonça等。Rev Inst Med Trop São Paulo. 2026;68:e69 第6页,共7页 并非作为所有人类病例的确认物种。尽管存在这些局限性,本研究仍为一个特征描述不足的地区提供了本地证据,并具有直接的公共卫生意义。大圣路易斯地区需要对人类和猫的孢子丝菌病进行综合监测,在受感染猫只所在地区主动发现病例,开展专业培训以实现早期诊断,对患病动物进行兽医诊断和治疗,对患者进行安全接触动物的教育,以及采取跨部门“同一健康”策略以阻断传播。这些措施应与系统化报告、公众沟通和猫群管理政策相结合。结论 大圣路易斯地区的人兽共患孢子丝菌病呈现出猫源性城市新发流行病的特征,其特点是病例数不断增加、以成年女性为主、家庭内与猫密切接触、频繁被抓伤或接触猫病变部位,以及主要累及上肢的淋巴皮肤型疾病。据我们所知,本医院队列研究首次提供了该地区人类孢子丝菌病的区域临床流行病学特征描述,并为监测和控制提供了可操作的证据。研究结果支持迫切需要采取“同一健康”策略,整合人类医疗保健、兽医诊断和治疗、猫群管理、健康教育、系统化报告和协调监测,以遏制孢子丝菌病在马拉尼昂州和巴西东北部的扩散。利益冲突 无。数据可用性 由于伦理限制,作者不会提供额外数据。资助 本研究部分由巴西高等教育人员改进协调组织(CAPES)资助,资助代码001。参考文献 1. Rodrigues AM, Della Terra PP, Gremião ID, Pereira SA, Orofino-Costa R, Camargo ZP. 新发和再发致病性孢子丝菌属物种的威胁。Mycopathologia. 2020;185:813-42. 2. Gremião ID, Miranda LH, Reis EG, Rodrigues AM, Pereira SA. 孢子丝菌病人兽共患流行病:猫到人的传播。PLoS Pathog. 2017;13:e1006077. 3. Barros MB, Schubach AO, Valle AC, Galhardo MC, Conceição-Silva F, Schubach TM, 等。巴西里约热内卢由猫传播的孢子丝菌病流行:一系列病例的描述。Clin Infect Dis. 2004;38:529-35. 4. Rodrigues AM, Gonçalves SS, Carvalho JA, Borba-Santos LP, Rozental S, Camargo ZP. 孢子丝菌病流行病学、诊断和治疗的最新进展及其未来趋势。J Fungi (Basel). 2022;8:776. 5. Orofino-Costa R, Freitas DF, Bernardes-Engemann AR, Rodrigues AM, Talhari C, Ferraz CE, 等。人类孢子丝菌病:巴西皮肤病学会关于临床、诊断和治疗管理的建议。An Bras Dermatol. 2022;97:757-77. 6. Gremião ID, Oliveira MM, Miranda LH, Freitas DF, Pereira SA. 孢子丝菌病在巴西的地理扩散。Emerg Infect Dis. 2020;26:621-4. 7. Silva CE, Valeriano CA, Ferraz CE, Neves RP, Oliveira MM, Silva JC, 等。巴西东北部伯南布哥州孢子丝菌病的流行病学特征和地理扩散。Future Microbiol. 2021;16:1371-9. 8. Cognialli RC, Cáceres DH, Bastos FA, Cavassin FB, Lustosa BP, Vicente VA, 等。巴西库里蒂巴巴西孢子丝菌感染发病率上升,2011-2022年。Emerg Infect Dis. 2023;29:1330-9. 9. Barros AF, Vitor JS, Esposito YR, Oliveira NS, Silva EM, Souza IM, 等。巴西马拉尼昂州圣路易斯岛猫孢子丝菌病分离的巴西孢子丝菌系统发育分析。Pesq Vet Bras. 2025;45:e07581. 10. 巴西。卫生部。健康与环境监测秘书处。传染病司。人兽共患病和媒介传播疾病监测总协调处。技术说明第60/2023-CGZV/DEDT/SVSA/MS号:关于巴西动物孢子丝菌病监测的建议。[引用日期2026年8月10日]。可从以下网址获取:https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/notas-tecnicas/2023/nota-tecnica-no-60-2023-cgzv-dedt-svsa-ms/view 11. 巴西。卫生部。健康与环境监测秘书处。流行病学和健康与环境监测战略行动司。健康监测指南:第3卷。第6版修订。巴西利亚:卫生部;2024年。[引用日期2026年8月10日]。可从以下网址获取:https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/svsa/vigilancia/guia-de-vigilancia-em-saude-volume-3-6a-edicao/ 12. Chakrabarti A, Bonifaz A, Gutierrez-Galhardo MC, Mochizuki

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Page 1 of 7 This is an open-access article distributed under the terms of the Creative Commons Attribution License. Rev Inst Med Trop São Paulo. 2026;68:e69 Page 1 of 7 ORIGINAL ARTICLE https://doi.org/10.1590/S1678-9946202668069 1 Universidade Federal do Maranhão, Programa de Pós-Graduação em Ciências da Saúde, São Luís, Maranhão, Brazil 2 Universidade Federal do Maranhão, Hospital Universitário Presidente Dutra, São Luís, Maranhão, Brazil 3 Laboratório Cedro, São Luís, Maranhão, Brazil 4 Universidade Federal do Maranhão, Faculdade de Medicina, São Luís, Maranhão, Brazil 5 Rede D’Or, Instituto D’Or de Pesquisa e Ensino, São Luís, Maranhão, Brazil Correspondence to: Thiago Dutra Mendonça Universidade Federal do Maranhão, Programa de Pós-Graduação em Ciências da Saúde, Av. dos Portugueses, 1966, Vila Bacanga, CEP 65080-805, São Luís, MA, Brazil Tel: +55 98 98185-5206 E-mail: thiago.dm@ufma.br Received: 19 May 2026 Accepted: 3 August 2026 Editor: Gil Benard

First clinical-epidemiological profile of zoonotic sporotrichosis in a state capital of Northeast Brazil: evidence of an emerging feline-driven urban epidemic Thiago Dutra Mendonça 1 , Rayssa de Sousa Silva 1 , Sirlei Garcia Marques 2,3 , Gustavo Silva Santos de Sousa 4 , Bianca de Fátima Assunção Sodré 4 , Ayrton Rocha Lima 4 , Guilherme Alencar de Medeiros 3 , Daniel Wagner de Castro Lima Santos 2,5 , Conceição de Maria Pedrozo e Silva de Azevedo 1 ABSTRACT Zoonotic sporotrichosis has expanded in Brazil as an urban, cat-associated mycosis, but its human clinical-epidemiological profile remains poorly characterized in Maranhao State, Brazil. This study describes a hospital-based cohort from Greater Sao Luis and defines a regional profile not previously established in the state. We conducted an observational study combining retrospective and prospective data from 2022 to 2025 at a reference hospital for infectious diseases in Sao Luis municipality, Maranhao State, Brazil. Confirmed cases were defined by culture and/or compatible histopathological findings supported by clinicalepidemiological criteria. Demographic, exposure, clinical, laboratory, therapeutic, and outcome variables were analyzed using descriptive statistics and appropriate statistical tests. A total of 189 confirmed cases were analyzed. Cases increased sharply after 2022 and peaked in 2024, with 82 cases. Most patients lived in Sao Luis municipality (84.7%), were female (67.2%), and were aged 30–59 years (47.1%). Feline-associated exposure predominated: 70.9% reported having household cats and 81.5% reported scratches or contact with feline lesions or secretions. The lymphocutaneous form was the main presentation (61.9%), followed by fixed cutaneous disease (29.1%); upper limbs were the most frequently affected sites (73.0%). Culture was positive for Sporothrix spp. in 62.2% of tested samples, and suppurative granulomas were frequent findings on histopathological examination. Itraconazole was the first-line therapy in 92.0% of treated patients. Greater Sao Luis shows the profile of an emerging urban epidemic of zoonotic sporotrichosis of feline origin. These findings provide local evidence to guide surveillance, early diagnosis, integration between human and veterinary health services, and One Health-based control strategies in Maranhao State. KEYWORDS: Sporotrichosis. Zoonoses. Cats. Sporothrix. Epidemiology. Public health. INTRODUCTION Sporotrichosis is an implantation mycosis caused by thermodimorphic fungi of the genus Sporothrix. Although it was traditionally associated with traumatic inoculation from soil, plant debris, and occupational exposure, its epidemiology has changed substantially in Brazil with the rise of cat-transmitted disease 1,2 . In this setting, infected felines act as efficient amplifiers because their lesions may contain high fungal burden, and transmission can occur through scratches, bites, or contact

Mendonça et al. Rev Inst Med Trop São Paulo. 2026;68:e69 Page 2 of 7 with exudates 2,3 . Additional transmission routes, including sapronotic exposure, contaminated fomites, and respiratory transmission from infected cats, have also been reported and should be considered in surveillance and prevention strategies 4,5 . Brazil is currently the most relevant global setting for zoonotic sporotrichosis, particularly because felineassociated transmission in the country has been strongly linked to Sporothrix brasiliensis, a highly virulent species that has driven major urban outbreaks 1,2 . The first large urban epidemic was described in Rio de Janeiro city, where sustained transmission among cats and humans transformed sporotrichosis from an occasional implantation mycosis into an urban public health issue 3 . Subsequent reports have documented geographic spread to other Brazilian regions, including areas where systematic human data remain limited 4,6-8 . Sporotrichosis has been reported with increasing frequency in the northeastern region of Brazil, but the human burden and clinical profile of the disease remain unevenly documented 7 . In Maranhao State, recent veterinary and laboratory evidence suggests circulation of Sporothrix spp. in the metropolitan area of Sao Luis municipality; however, human data sufficient to define the affected population, main exposures, clinical presentations, diagnostic patterns, and therapeutic response are still scarce. This gap limits surveillance planning, clinical suspicion, and the implementation of integrated human-animalenvironment control measures 4,9,10 . Therefore, this study aims to describe the clinicalepidemiological profile, diagnostic findings, and therapeutic characteristics of confirmed cases of zoonotic sporotrichosis treated at a reference hospital in Sao Luis municipality, Maranhao State, Brazil, from 2022 to 2025. By defining a local profile in a previously undercharacterized region, the study provides evidence for public health action and One Health strategies in the state. Ethics The study was approved by the Research Ethics Committee of the Universidade Federal do Maranhao under Certificate of Presentation for Ethical Appraisal Nº 84202724.9.0000.5087. All procedures followed Brazilian ethical standards for research involving human beings. For retrospective data, informed consent was waived because data were collected from medical records. For prospective data, written informed consent was obtained from participants or their legal guardians. Written informed consent for publication of the facial image in Figure 2 was obtained from the patient. The eyes were obscured for privacy. MATERIALS AND METHODS Study design and setting This was an observational study combining retrospective data from January 2022 to December 2023 and prospective data from January 2024 to December 2025. The study was conducted at a reference hospital for infectious and parasitic diseases in Sao Luis municipality, Maranhao State, Brazil, which receives patients from the capital and surrounding municipalities. Study population and case definition The study population comprised patients with confirmed sporotrichosis treated during the study period. Case eligibility was established based on compatible clinicalepidemiological and laboratory criteria, in line with Brazilian surveillance guidance for sporotrichosis 11 . Eligible cases met at least one of the following criteria: positive culture for Sporothrix spp.; histopathological findings compatible with sporotrichosis, including suppurative granulomatous inflammation, with or without asteroid bodies or yeast-like structures; or a compatible clinicalepidemiological presentation supported by laboratory or histopathological evidence. Compatible clinical presentations included single or multiple papular, nodular, nodular-ulcerative, cutaneous, or mucosal lesions, with or without lymphatic spread, associated with previous contact with cats, traumatic inoculation, contact with organic material, or other plausible exposure routes. Cases with inconclusive diagnosis or insufficient data for analysis were excluded. Data collection Data were obtained from medical records and hospital notification forms. Variables included sex, age, municipality of residence, year of diagnosis, contact with cats, scratches or contact with feline lesions or secretions, gardening or soil exposure, clinical form, lesion site, mycological culture, histopathological findings, antifungal treatment, treatment duration, and clinical outcome when available. Laboratory diagnosis Mycological investigation was performed at the Central Public Health Laboratory of Maranhao State and at Cedro Laboratory. Clinical samples, including pus, lesion exudate, and biopsy fragments, were cultured on Sabouraud dextrose agar supplemented with chloramphenicol and

Rev Inst Med Trop São Paulo. 2026;68:e69 First clinical-epidemiological profile of zoonotic sporotrichosis in a state capital of Northeast Brazil Page 3 of 7 cycloheximide (Mycosel-type selective medium) and incubated at 25 °C and 37 °C. Detailed information on the commercial manufacturers was not consistently available for all retrospective samples. Presumptive identification followed routine laboratory criteria based on colony growth and micromorphological features compatible with Sporothrix spp.; however, detailed macro- and micromorphological descriptors and systematic documentation of yeast conversion at 37 °C were not available for all isolates. Histopathological examination was performed on skin biopsy fragments fixed in 10% formalin and embedded in paraffin. Sections 3–5 μm thick were stained with hematoxylin and eosin for morphological analysis; when indicated, Grocott methenamine silver and periodic acid–Schiff stains were used to detect fungal structures. Statistical analysis Categorical variables were summarized as absolute and relative frequencies. Continuous variables were described as means and standard deviations or medians, according to data distribution. Associations between categorical variables were evaluated using statistical tests. Statistical significance was defined as p<0.05. Analyses were performed using SPSS (version 26.0, IBM Corp., Armonk, NY, USA). RESULTS A total of 189 confirmed cases of zoonotic sporotrichosis were analyzed. The annual distribution showed a marked increase during the study period, with 2024 accounting for the highest number (82 cases), followed by 2023 and 2025 (Figure 1). Most patients lived in Sao Luis municipality, were female, and were adults aged 30–59 years. The mean age was 43.7 years (standard deviation, 17 years). The demographic distribution is summarized in Table 1. Feline-associated exposure was the dominant epidemiological pattern. Household contact with cats was reported by 134 of 189 patients with available data (70.9%), and scratches or contact with feline lesions or secretions were reported by 154 of 189 patients (81.5%). These exposure variables were not mutually exclusive, and household cats were frequently described as sick in records that documented direct contact with feline lesions or secretions. Gardening or soil exposure was uncommon, reported by only seven patients (3.7%). The lymphocutaneous form was the most frequent clinical presentation, followed by fixed cutaneous disease. Disseminated forms and other presentations, including mucosal and osteoarticular involvement, were less common. Ten disseminated cases were recorded in the dataset; among them, one involved the retro-orbital region, with optic chiasm compression and permanent visual sequelae. Representative clinical presentations are shown in Figure 2. Clinical characteristics and exposure variables are presented in Table 2. Table 1 - Demographic profile and annual distribution of confirmed sporotrichosis cases in Greater Sao Luis, Maranhao State, Brazil, 2022–2025. Characteristicn% Year of diagnosis 2022136.9 20235730.2 20248243.4 20253719.6 Sex Female12767.2 Male6232.8 Age group, years 0–192814.8 20–293015.9 30–598947.1 ≥604222.2 Mean age, years (SD)43.7 (17.0) Municipality of residence Sao Luis16084.7 Other municipalities in Maranhao State 2915.3 SD = standard deviation; percentages estimated based on 189 confirmed cases. FIG1 Figure 1 - Temporal distribution of confirmed sporotrichosis cases in the hospital-base cohort, Maranhao State, Brazil, 2022–2025.

Mendonça et al. Rev Inst Med Trop São Paulo. 2026;68:e69 Page 4 of 7 Among 135 patients who underwent mycological culture, 84 (62.2%) were positive for Sporothrix spp. Histopathology was available for 60 patients, and suppurative granulomas were found in 40 (66.7%). Multinucleated giant cells and acute inflammatory infiltrates were frequent, and fungal structures were observed in selected cases. Itraconazole was used in 92.1% of treated patient, used in 174 of 189 treated patients (92.0%); alternative regimens recorded in a minority of cases included potassium iodide and terbinafine. Most regimens lasted three months. Hospitalization, standardized outcome assessment, and detailed reasons for treatment modification were not consistently documented in the medical records and therefore could not be robustly analyzed. Table 3 shows diagnostic and therapeutic data. DISCUSSION This study defines a clinical-epidemiological profile of zoonotic sporotrichosis in Greater Sao Luis, Maranhao State, Brazil, and supports the interpretation that the disease is expanding as an urban mycosis of feline origin in the region. The increase in cases from 2022 to 2024, together with the predominance of cat-related exposure and localized cutaneous forms, resembles the pattern reported in other Brazilian urban centers affected by feline-transmitted sporotrichosis 2,7 . The concentration of cases in Sao Luis municipality indicates that the capital may represent an important focus of transmission or diagnosis. This finding may reflect a combination of factors, including population density, close contact between humans and domestic or stray cats, Table 2 - Epidemiological exposure and clinical characteristics of confirmed sporotrichosis cases. Characteristicn/N% Epidemiological exposure Household cats134/18970.9 Scratches or contact with feline lesions/secretions 154/18981.5 Gardening or soil contact7/1893.7 Clinical form Lymphocutaneous117/18961.9 Fixed cutaneous55/18929.1 Disseminated10/1895.3 Other forms (mucosal or osteoarticular)7/1893.7 Lesion location Upper limbs138/18973.0 Lower limbs30/18915.9 Face/neck15/1897. 9 Trunk6/1893.2 Figure 2 - Clinical and histopathological spectrum of zoonotic sporotrichosis: (A) fixed cutaneous sporotrichosis presenting as an ulcerated and crusted plaque on the dorsal aspect of the hand and wrist; (B) lymphocutaneous sporotrichosis characterized by multiple nodular lesions distributed along the lymphatic drainage pathway of the upper limb; (C) disseminated cutaneous involvement with multiple facial lesions affecting the nasal, perioral, and chin regions; the eyes were anonymized for editorial and ethical protection; (D) histopathological section showing a lymphohistiocytic granulomatous inflammatory infiltrate with neutrophils and foci of necrosis; (E) higher-magnification histopathological section showing neutrophilic inflammation with fungal structures interspersed within the inflammatory infiltrate; (F) histopathological section demonstrating granulomatous inflammation with lymphohistiocytic and neutrophilic components and areas of tissue necrosis. Hematoxylin and eosin staining (D–F). FIG2

Rev Inst Med Trop São Paulo. 2026;68:e69 First clinical-epidemiological profile of zoonotic sporotrichosis in a state capital of Northeast Brazil Page 5 of 7 better access to a reference hospital, and greater clinical recognition. Nevertheless, the magnitude of the increase suggests that the phenomenon cannot be explained solely by referral bias and deserves structured surveillance beyond hospital detection. Female predominance contrasts with the historical occupational form of sporotrichosis, classically associated with rural or agricultural exposure. However, it is consistent with the contemporary zoonotic profile observed in Brazil, in which women may have greater exposure as caregivers of sick cats in the household environment 2,3,12 . The predominance among adults aged 30–59 years also suggests involvement of the economically active population, with possible effects on productivity, family routines, and caregiving dynamics. The epidemiological findings support the role of feline transmission. More than two-thirds of patients reported having household cats, and more than 80% reported scratches or contact with feline lesions or secretions. In contrast, gardening or soil exposure was rare. This contrast highlights the transition from sapronotic or occupational sporotrichosis to a predominantly urban zoonosis in the studied setting 1,2,13 . In Maranhao State, this distinction is important because control cannot rely only on individual protection against soil exposure; it requires early diagnosis and treatment of infected cats, responsible pet ownership, safe handling of sick animals, and coordinated surveillance between human and veterinary health services. The clinical pattern was also consistent with feline-associated inoculation. The predominance of lymphocutaneous and fixed cutaneous forms, together with frequent upper-limb involvement, suggests direct traumatic inoculation followed by local or lymphatic spread. Disseminated presentations were uncommon but clinically relevant, particularly the case with retro-orbital involvement and permanent visual sequelae. Although most cutaneous sporotrichosis cases are not life-threatening, severe presentations reinforce the need for early recognition, adequate treatment, and referral pathways for complicated disease. Information on comorbidities and immune status was incomplete, which hinders deeper interpretation of disseminated presentations in this cohort 4,14 . Culture remains central for diagnostic confirmation, but histopathology was useful in this cohort. Suppurative granulomatous inflammation, neutrophilic infiltrates, and occasional fungal structures were compatible with active fungal infection. These findings are particularly relevant in settings where culture or molecular identification is not widely available, although histopathology alone should be interpreted together with clinical and epidemiological evidence. Published sensitivity estimates for histopathology in sporotrichosis are often modest, and our findings should be interpreted in the context of a referral-center cohort and selective submission of biopsies rather than as a direct measure of diagnostic sensitivity 4,5 . Itraconazole was the main therapeutic agent, consistent with international recommendations for fixed cutaneous and lymphocutaneous sporotrichosis 4,14 . The predominance of three-month treatments may indicate early diagnosis and favorable response in many patients. However, according to recommendations, treatment should ideally continue beyond clinical resolution, and recurrence, adherence, access to medication, hospitalization, and loss to follow-up could not be systematically evaluated in this dataset and should be investigated in future studies. Limitations This study has limitations. Its hospital-based design may overrepresent patients who accessed specialized care and underrepresent mild cases treated elsewhere or not diagnosed in the community. The retrospective component depended on the completeness of medical records and notification forms, resulting in variable denominators in some analyses and incomplete information on hospitalization, immune status, standardized outcomes, and indications for treatment modification. Full georeferenced residential data were also unavailable, limiting a more detailed spatial analysis. Molecular confirmation at the species level was not available for all isolates; therefore, Sporothrix brasiliensis is discussed as the most plausible species in the Brazilian zoonotic context and in light of local feline evidence, but Table 3 - Diagnostic findings and therapeutic characteristics of patients with sporotrichosis. Characteristicn/N% Mycological culture Positive for Sporothrix spp.84/13562.2 Negative51/13537.8 Histopathology Suppurative granuloma40/6066.7 Other findings20/6033.3 Medication used Itraconazole174/18992.0 Potassium iodide10/1895.3 Terbinafine5/1892.7 Treatment duration 3 months109/18957.7 4–6 months60/18931.7 >6 months20/18910.6

Mendonça et al. Rev Inst Med Trop São Paulo. 2026;68:e69 Page 6 of 7 not as a confirmed species for all human cases. Despite these limitations, this study provides local evidence from a poorly characterized area and has immediate public health implications. Greater Sao Luis requires integrated surveillance of human and feline sporotrichosis, active case finding in areas with infected cats, professional training for early diagnosis, veterinary diagnosis and treatment of sick animals, patient education on safe animal handling, and intersectoral One Health strategies to interrupt transmission. These measures should be coupled with systematic notification, public communication, and feline population management policies. CONCLUSION Zoonotic sporotrichosis in Greater Sao Luis has the profile of an emerging urban epidemic of feline origin, marked by an increasing number of cases, predominance among adult women, intense household exposure to cats, frequent scratches or contact with feline lesions, and predominantly lymphocutaneous disease affecting the upper limbs. To the best of our knowledge, this hospital-based cohort provides the first regional clinicalepidemiological characterization of human sporotrichosis in this setting and offers actionable evidence for surveillance and control. The findings support the urgent need for One Health strategies integrating human healthcare, veterinary diagnosis and treatment, feline population management, health education, systematic notification, and coordinated surveillance to contain the expansion of sporotrichosis in Maranhao State and the Brazilian Northeast. CONFLICT OF INTERESTS None. DATA AVAILABILITY The authors will not make additional data available due to ethical restrictions. FUNDING This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil, Finance Code 001. REFERENCES 1. Rodrigues AM, Della Terra PP, Gremião ID, Pereira SA, Orofino-Costa R, Camargo ZP. The threat of emerging and re-emerging pathogenic Sporothrix species. Mycopathologia. 2020;185:813-42. 2. Gremião ID, Miranda LH, Reis EG, Rodrigues AM, Pereira SA. Zoonotic epidemic of sporotrichosis: cat to human transmission. PLoS Pathog. 2017;13:e1006077. 3. Barros MB, Schubach AO, Valle AC, Galhardo MC, Conceição- Silva F, Schubach TM, et al. Cat-transmitted sporotrichosis epidemic in Rio de Janeiro, Brazil: description of a series of cases. Clin Infect Dis. 2004;38:529-35. 4. Rodrigues AM, Gonçalves SS, Carvalho JA, Borba-Santos LP, Rozental S, Camargo ZP. Current progress on epidemiology, diagnosis, and treatment of sporotrichosis and their future trends. J Fungi (Basel). 2022;8:776. 5. Orofino-Costa R, Freitas DF, Bernardes-Engemann AR, Rodrigues AM, Talhari C, Ferraz CE, et al. Human sporotrichosis: recommendations from the Brazilian Society of Dermatology for clinical, diagnostic and therapeutic management. An Bras Dermatol. 2022;97:757-77. 6. Gremião ID, Oliveira MM, Miranda LH, Freitas DF, Pereira SA. Geographic expansion of sporotrichosis, Brazil. Emerg Infect Dis. 2020;26:621-4. 7. Silva CE, Valeriano CA, Ferraz CE, Neves RP, Oliveira MM, Silva JC, et al. Epidemiological features and geographical expansion of sporotrichosis in the state of Pernambuco, northeastern Brazil. Future Microbiol. 2021;16:1371-9. 8. Cognialli RC, Cáceres DH, Bastos FA, Cavassin FB, Lustosa BP, Vicente VA, et al. Rising incidence of Sporothrix brasiliensis infections, Curitiba, Brazil, 2011-2022. Emerg Infect Dis. 2023;29:1330-9. 9. Barros AF, Vitor JS, Esposito YR, Oliveira NS, Silva EM, Souza IM, et al. Phylogenetic analysis of Sporothrix brasiliensis isolated from feline sporotrichosis on São Luís Island, Maranhão, Brazil. Pesq Vet Bras. 2025;45:e07581. 10. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Departamento de Doenças Transmissíveis. Coordenação-Geral de Vigilância de Zoonoses e Doenças de Transmissão Vetorial. Nota Técnica nº 60/2023-CGZV/DEDT/ SVSA/MS: a respeito das recomendações sobre a vigilância da esporotricose animal no Brasil. [cited 2026 Aug 10]. Available from: https://www.gov.br/saude/pt-br/centrais-de-conteudo/ publicacoes/notas-tecnicas/2023/nota-tecnica-no-60-2023- cgzv-dedt-svsa-ms/view 11. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Departamento de Ações Estratégicas de Epidemiologia e Vigilância em Saúde e Ambiente. Guia de vigilância em saúde: volume 3. 6ª ed. rev. Brasília: Ministério da Saúde; 2024. [cited 2026 Aug 10]. Available from: https://www. gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/svsa/ vigilancia/guia-de-vigilancia-em-saude-volume-3-6a-edicao/ 12. Chakrabarti A, Bonifaz A, Gutierrez-Galhardo MC, Mochizuki

Rev Inst Med Trop São Paulo. 2026;68:e69 First clinical-epidemiological profile of zoonotic sporotrichosis in a state capital of Northeast Brazil Page 7 of 7 T, Li S. Global epidemiology of sporotrichosis. Med Mycol. 2015;53:3-14. 13. Etchecopaz A, Toscanini MA, Gisbert A, Mas J, Scarpa M, Iovannitti CA, et al. Sporothrix brasiliensis: a review of an emerging South American fungal pathogen, its related disease, presentation and spread in Argentina. J Fungi (Basel). 2021;7:170. 14. Kauffman CA, Bustamante B, Chapman SW, Pappas PG. Clinical practice guidelines for the management of sporotrichosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45:1255-65.

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