兽研腐霉病是一种由腐霉属致病性卵菌引起的严重疾病，传统上与热带和亚热带气候及淡水环境相关(1,2)。该病主要影响人、马和犬，通常与接触停滞或流动缓慢的淡水生境有关，这些生境支持感染性游动孢子的产生。大多数哺乳动物感染涉及Pythium insidiosum复合群，尽管偶尔有报道提及其他致病性卵菌(3,4)。
来自传统公认流行区以外地区（包括美国北部和日本）的报告不断增加，提示腐霉病的全球分布范围更广(2)。然而，欧洲的受影响情况仍极为特殊。最近的一项系统综述确定西班牙是欧洲唯一有本地获得性人类腐霉病病例记录的国家(2,5)。2023年，我们报告了意大利2例本土犬皮肤腐霉病病例，这些病例与反复接触意大利中部的布拉恰诺湖有关(6)。这些初步观察提示可能存在有利于致病性腐霉属物种的局部生态位。我们随后又确定了2021-2024年间诊断的5例犬病例，使意大利已确认的本地获得性犬病例总数达到7例。所有犬在发病前均未离开过意大利，支持本地获得性感染的观点。
所有犬均有反复接触自然淡水环境的病史。报告的接触地点包括布拉恰诺湖（5例）、博尔塞纳湖（1例）和意大利北部的维韦罗内湖（1例）（图1）。与布拉恰诺湖相关的不同病例从2021年至2024年陆续被确认，提示有利于致病性腐霉属物种的局部环境条件持续存在。此外，与维韦罗内湖相关的一例病例的确认将已确认接触地点的地理范围扩大了>300 km。尽管环境调查不在本研究范围内，但所有涉及的地点均具有近岸浅水区的特征，这些区域在夏季月份经历显著季节性升温。此类条件可能有利于致病性腐霉属物种的持续存在或增殖(1)。综合考虑所有因素，我们认为我们的发现支持意大利不同地区存在可能适合致病性卵菌的生态位，尽管缺乏传统公认的热带气候条件。
[图：与本土犬类腐霉病病例相关的淡水地点，用于一项本土犬类腐霉病关联研究]
7只感染犬中有6只为德国牧羊犬。尽管病例数仍然有限，但这种优势值得注意，提示除环境暴露外的因素可能参与疾病的发生。来自流行区的已发表犬系列显示品种分布不一，提示疾病出现可能反映了环境暴露、宿主相关因素和临床识别模式之间的多因素相互作用。临床表现主要为皮肤型，以慢性结节、斑块、溃疡和引流窦道为特征（图2）；1只犬后来出现胃肠道受累。研究人员已描述了世界其他地区犬腐霉病中类似的皮肤和胃肠道表现(7-9)。本系列中皮肤型表现占优势可能反映了通过受损皮肤暴露的途径或识别偏倚，因为胃肠道疾病可能较难诊断。在数例病例中，初始临床表现提示炎症性或细菌性疾病，经验性治疗以及在某些病例中反复手术先于明确诊断（附录）。
[图：犬类腐霉病的代表性皮肤表现，用于一项与淡水相关的本土犬类腐霉病关联研究]
我们通过细胞学、组织病理学、培养和测序的组合建立了诊断（附录）。细胞学和组织学检查显示与脓性肉芽肿性炎症相关的宽大、不规则、稀疏分隔的菌丝样结构。6例病例获得了内转录间隔区序列数据，这些分离株聚集在P. insidiosum复合群进化枝IV内，对应于目前指定为Pythium periculosum的谱系。(10)我们使用涵盖该复合群内已确认的4个主要进化枝的代表性参考序列进行了系统发育分析（附录图）。来自意大利的所有序列均归入进化枝IV，与该进化枝先前观察到的更广泛的非美洲代表性一致(10)。另有一例仅获得大亚基序列数据的病例，显示与先前归入同一谱系的分离株相似性最高。来自意大利的序列彼此间也显示出有限的分化，并在进化枝IV框架内显得密切相关，提示存在地理相关的聚集。
我们的发现进一步证明，犬腐霉病可发生于传统公认流行区以外的温带环境。与淡水暴露相关病例的反复识别提示，尽管缺乏典型热带气候条件，意大利多个地区可能存在适宜的环境生态位。从“同一健康”视角看，犬可作为与多种宿主相关的环境暴露风险哨兵，并有助于识别先前未被充分认识、有利于致病性卵菌的生态位。提高兽医和人类医疗保健专业人员的认识，对于在欧洲更早识别这一新发疾病具有重要意义。
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Pythiosis is a severe disease caused by pathogenic oomycetes of the genus Pythium and is classically associated with tropical and subtropical climates and freshwater environments (1,2). The disease affects mainly humans, horses, and dogs and is typically linked to exposure to stagnant or slow-moving freshwater habitats that support production of infective zoospores. Most mammalian infections involve the Pythium insidiosum complex, although there have been occasional reports citing additional pathogenic oomycetes (3,4).
Increasing reports from regions outside traditionally recognized endemic areas, including northern areas of the United States and Japan, suggest a broader global distribution of pythiosis (2). Europe, however, remains exceptionally affected. A recent systematic review identified Spain as the only country in Europe in which locally acquired human pythiosis cases had been documented (2,5). In 2023, we reported 2 autochthonous canine cutaneous pythiosis cases in Italy, which were linked to recurrent exposure to Lake Bracciano in central Italy (6). Those initial observations suggested the possible presence of a local ecologic niche favorable to pathogenic Pythium species. We subsequently identified 5 additional canine cases diagnosed during 2021–2024, bringing the total number of recognized locally acquired canine cases in Italy to 7. None of the dogs had traveled outside Italy before disease onset, supporting the notion of locally acquired infection.
All dogs had histories of repeated exposure to natural freshwater environments. Reported sites included Lake Bracciano (5 cases), Lake Bolsena (1 case), and Lake Viverone in northern Italy (1 case) (Figure 1). Distinct cases linked to Lake Bracciano were recognized from 2021 through 2024, suggesting persistent local environmental conditions favorable to pathogenic Pythium species. In addition, identification of a case associated with Lake Viverone expands the geographic range of recognized exposure sites by >300 km. Although environmental investigations were outside the scope of this study, all implicated sites feature shallow, near-shore areas that undergo marked seasonal warming during summer months. Such conditions may favor persistence or proliferation of pathogenic Pythium species (1). All factors considered, we believe that our findings support the presence of ecologic niches potentially suitable for pathogenic oomycetes in different regions of Italy despite the absence of traditionally recognized tropical climatic conditions.
[图：Freshwater sites associated with autochthonous canine pythiosis cases for a study of autochthonous canine pythiosis link]
Six of the 7 infected dogs were German shepherds. Although the number of cases remains limited, this predominance is noteworthy and suggest that factors beyond environmental exposure alone might contribute to disease occurrence. Published canine series from endemic regions show variable breed distributions, suggesting that disease emergence likely reflects a multifactorial interplay between environmental exposure, host-related factors, and clinical recognition patterns. Clinical manifestations were predominantly cutaneous and characterized by chronic nodules, plaques, ulceration, and draining tracts (Figure 2); 1 dog later developed gastrointestinal involvement. Researchers have described similar cutaneous and gastrointestinal manifestations in canine pythiosis occurring in other regions of the world (7–9). The predominance of cutaneous presentations in our series may reflect route of exposure through damaged skin or recognition bias, because gastrointestinal disease may be less readily diagnosed. In several cases, the initial clinical manifestation suggested inflammatory or bacterial disorders, and empirical treatment and, in some cases, repeated surgery preceded definitive diagnosis (Appendix).
[图：Representative cutaneous manifestations of canine pythiosis for a study of autochthonous canine pythiosis linked with fr]
We established diagnosis by combinations of cytology, histopathology, culture, and sequencing (Appendix). Cytologic and histologic examination showed broad, irregular, sparsely septate, hyphae-like structures associated with pyogranulomatous inflammation. Internal transcribed spacer sequence data were available for 6 cases, and those isolates clustered within clade IV of the P. insidiosum complex, corresponding to the lineage currently designated Pythium periculosum. (10) We conducted phylogenetic analysis using representative reference sequences spanning the 4 major clades recognized within the complex (Appendix Figure). All sequences from Italy grouped within clade IV, consistent with the broader extra-American representation previously observed for this clade (10). One additional case, for which only large subunit sequence data were available, showed highest similarity to isolates previously assigned to the same lineage. The sequences from Italy also showed limited divergence from one another and appeared closely related within the clade IV framework, suggesting a geographically related cluster.
Our findings provide further evidence that canine pythiosis can occur in temperate settings outside traditionally recognized endemic areas. Recurrent identification of cases associated with freshwater exposure suggests that suitable environmental niches may exist in multiple regions of Italy despite the absence of classically tropical climatic conditions. From a One Health perspective, dogs may act as sentinels of environmental exposure risk relevant to multiple hosts and may contribute to recognition of previously underappreciated ecologic niches favorable to pathogenic oomycetes. Increased awareness among veterinary and human healthcare professionals will be important for earlier recognition of this emerging disease in Europe.
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