Of Time and the River: How Our Understanding of Legionellosis Has Changed Since 1976.

It has been >40 years since an outbreak of legionellosis occurred at the iconic Bellevue-Stratford Hotel in Philadelphia [1]. Legionnaires’ disease made its initial documented appearance at a state legionnaires’ convention (hence the name); the Centers for Disease Control and Prevention had isolated Legionella pneumophila by 1977 [1] and had also identified this pathogen retrospectively as having caused outbreaks of relatively mild febrile illness (ie, Pontiac fever) [2]. Since then, >40 species of Legionella, with varying pathogenicity, have been identified [3]. Large outbreaks of legionellosis, classically associated with cooling towers, misters, fountains, or other sources of aerosol, can affect hundreds of individuals, with high case-fatality rates, and may be alarming to communities. Nosocomial outbreaks occur, as well. The epidemiology of legionellosis appears to be quite dynamic, with marked increases in case counts described throughout the United States over a 15-year period [4]. Legionella species, including L. pneumophila, are environmentally abundant, which can make environmental investigations during such outbreaks perplexing: Legionella species may be found, but they might be genotypically distinct from those causing the outbreak [5]. Indeed, I would suggest that one fundamental paradox of legionellosis epidemiology is that if these microbes are environmentally abundant so that exposure must be almost ubiquitous, why is disease uncommon? What are we missing? Part of the puzzle must relate to host factors, including relative immune compromise (long associated with Legionella species other than L. pneumophila) and age-related immunosenescence, as the risk of recognized legionellosis appears to increase exponentially with age [4, 6]. Legionellosis epidemiology might also be a matter of “seek and ye shall find”: urine antigen testing identifies only a single serogroup of L. pneumophila (LP1), culture and direct fluorescent antigen testing are technically challenging, and clinicians may not test individuals with nonsevere pneumonia or without immune compromise for legionellosis. Perhaps if we sought this disease more widely, we would find more of it: a German study evaluated the fraction of pneumonia attributable to LP1 in both hospitalized patients and ambulatory patients with so-called walking pneumonia, and they found that approximately 4% of both groups had legionellosis [7]. We evaluated the relationship between legionellosis testing and positive test results in the Canadian province of Ontario (where almost all legionellosis testing was centralized at a single laboratory) and found a positive feedback loop, whereby the occurrence of legionellosis seemed to spur higher levels of subsequent testing (and, consequently, case identification) by clinicians [8]. Find and ye shall seek. However, given the environmental abundance of Legionella species and the impact of physical factors such as water temperatures and sediments on Legionella proliferation, it seems likely that the physical environment is also an important component of the legionellosis puzzle. Understanding such relationships becomes particularly important in the context of accelerating global climate change [9]. Cassell et al, in the current issue of The Journal of Infectious Diseases, have made an important contribution to our understanding of the physical environment and legionellosis risk [10]. These authors have demonstrated that, in Connecticut (a state documented to have seen the largest increase in legionellosis in the United States since the 1990s), local hydrological influences, in the form of both rainfall and river flows, appeared to predict legionellosis risk from 1999 to 2015. Such risk was also clustered near major watersheds, even after adjustment for population density and housing characteristics. The authors’ elegant combination of both spatial and temporal analytic tools paints a convincing case. This work also adds to a growing body of work suggesting that hot, wet weather somehow drives legionellosis risk in North America, Europe, and Asia [9– 14]. We also found an association between local hydrologic characteristics (ie, watershed levels and lake temperatures) and legionellosis risk in Toronto (although no association with rainfall or temperature) [15], but to my knowledge, this is the first study to demonstrate the impact of multiple hydrological influences on legionellosis risk in a single jurisdiction. E D I T O R I A L C O M M E N T A R Y