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Unlike ocular or cutaneous pythiosis, the vascular form is defined by arterial wall invasion, long-segment thrombosis, limb ischemia, aneurysmal complications, and high risks of amputation and death. Although\n                    <jats:italic toggle=\"yes\">P. insidiosum<\/jats:italic>\n                    is broadly distributed in freshwater environments, reported human vascular disease remains concentrated in Thailand, indicating that exposure alone is insufficient for disease development. Available evidence supports a multifactorial model centered on repeated freshwater exposure and host susceptibility, particularly hemoglobinopathies and iron dysregulation, while the rarity of comparable vascular disease elsewhere remains unexplained. Because vascular-specific mechanistic data are limited, evidence from animal pythiosis, nonvascular human disease, environmental studies, genomic analyses, and experimental models must be interpreted selectively and linked explicitly to vascular pathogenesis, diagnosis, or management. Infection usually begins at sites of skin disruption after freshwater exposure and progresses through soft tissue and perivascular planes into the arterial wall. Longitudinal intramural extension, rather than typical hematogenous dissemination, explains long-segment arterial occlusion, proximal progression, and relapse after incomplete source control. Diagnosis requires early suspicion, serology, vascular imaging, and tissue-based confirmation. Management depends on prompt and complete surgical removal of infected arterial tissue, supported by adjunctive protein-synthesis\u2013inhibiting antibacterial therapy, particularly when residual disease is suspected. Conventional antifungals have limited activity, and\n                    <jats:italic toggle=\"yes\">Pythium<\/jats:italic>\n                    antigen immunotherapy remains historically important but of uncertain independent benefit. Earlier recognition, better surgical-margin assessment, standardized diagnosis, and prospective treatment data are needed.\n                  <\/jats:p>","DOI":"10.1128\/cmr.00209-25","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:00:10Z","timestamp":1788440410000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Human vascular pythiosis: pathogenesis, diagnosis, and evidence-informed management"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0749-7342","authenticated-orcid":true,"given":"Nitipong","family":"Permpalung","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Johns Hopkins University School of Medicine","place":["Baltimore, 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