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Fifty years after Legionnaires’ disease was first recognized, major outbreaks such as the 2026 New York City cluster still occur because environmental microbiology, clinical diagnosis, and building engineering operate in silos. This review aims to bridge these separated fields and establish a proactive, system-wide framework for water safety. Through a purposive synthesis of experimental research, epidemiological surveillance, and public-health investigations through August 2026, we trace the complete pathway linking protozoan hosts, biofilms, and building water dynamics with clinical recognition, genomic attribution, and regulatory policy. Our findings clarify why bacterial presence and human disease often diverge. Buildings act as dynamic microbial incubators where water stagnation, pipe chemistry, and net-zero heating designs shape Legionella persistence. Furthermore, rising case notifications are heavily influenced by broader molecular testing rather than expanding environmental hazards alone, whereas weather effects vary substantially across local water systems. Although culture, polymerase chain reaction assays, and whole-genome sequencing capture different biological states, their public-health impact relies on coordinated interpretation and rapid action. Highlighting novel operational strategies, we propose a parallel-track outbreak model that pairs immediate exposure control with simultaneous genomic and epidemiological source attribution. Finally, we advocate shifting prevention from isolated test compliance to sustained system performance by integrating continuous temperature monitoring, testing-adjusted surveillance, and shared accountability between water utilities and building operators. Ultimately, the next breakthrough in preventing Legionnaires’ disease depends on connecting existing capabilities, judging water safety by durable reductions in hazardous conditions, recurring operational failures, and human illness.
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Wu et al. (2026) studied this question.
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