Legionnaires' Disease: causes, effects, and a lot of questions

For the past several months New York City news outlets have closely covered the outbreak of Legionnaires' disease in the South Bronx.  This outbreak, though claiming few lives, has sickened a large number of people, and the causative agent of this disease has been detected in the cooling systems of apartment complexes, hospitals, a mall, and even a high school.   This is, in effect, a disease of summer.  The bacteria that causes Legionnaires' live in warm aquatic reservoirs (like industrial cooling towers and hot tubs), and are dispersed by aerosolization.  In other words – those a/c vents to which you want to cling during a heatwave might actually be blowing a cool mist of disease-causing bacteria in your face.   While not directly related to chemical ecology, we figured discussion of this disease – its causative agent, environmental requirements, risk-factors and current treatments – is certainly topical – and hopefully even thought-provoking.

The history of Legionnaires' disease is actually quite interesting.  It was first discovered after the outbreak of a mysterious pneumonia-like illness at a meeting of the American Legion in Philadelphia in 1976.  At first this outbreak did not seem notable - as the symptoms resembled those of pneumonia or influenza – diseases at which it seemed obvious to point a finger.  This disease, however, did not respond to the frequently prescribed beta-lactam antibiotics (like penicillin) – and ultimately 29 of the 182 patients at the American Legion Meeting died.   It took several months for scientists to determine that the causative agent of this disease was a genus of bacteria called Legionella (named after the conference that it terrorized).  In fact, it turned out that this bacteria had even been isolated before but it had just never been characterized or studied, and was certainly not suspected of being a human threat.

While new bacterial species are likely discovered daily, it’s not that often that we come across a completely unknown pathogenic agent that can cause such mayhem.  So maybe it’s worth it to think, just for a second, about how terrifying it would be to combat an organism about which absolutely nothing is known.    Determining effective treatments for infectious diseases generally requires the ability to grow the organism in a lab - but this process can take months of optimization to establish appropriate growth conditions (on a related side-note, the causative agent of leprosy – Mycobacterium leprae – has never been successfully cultivated in a lab).   Additionally, in order to deal with an outbreak, the source of the infectious agent must be identified.   So how do you secure a treatment when you can’t even grow the organism in the lab?  and how do you prevent further infections if you don’t even know the source?  These were obviously pressing questions for the CDC in 1976, and luckily it was not too long before researchers were able to culture Legionella, figure out which antibiotics were somewhat effective in fighting Legionella infections, and even determine that it was aerosolization of bacteria, rather than human-human contact,  that mediated the rapid spread of the disease. 

Legionella pneumophila, which is probably the best-studied species of this bacterial family, infects animal macrophages – immune cells that basically hunt and degrade foreign agents in the body.  Legionella, however, like Mycobacteria (the causative agent of tuberculosis and leprosy), manage to evade degradation by these cells, and even replicate and thrive within them.   Infections of this nature can be difficult to treat because not only do these bacteria successfully evade their host immune system, they can utilize the host cell as a sort of secondary armor making them less susceptible (or accessible) to antibiotic treatment.  Fascinatingly, Legionella are know to infect other types of cells besides animal cells and are believed to often reside and replicate within amoeba – a eukaryotic single-celled organism that are often abundant in the same types of aqueous environments as Legionella.  This observation about the environmental lifestyle of Legionella may help explain why this bacteria has adapted to colonize human macrophages – which in many ways are highly similar to amoebal cells – and also indicates a method by which this organism can evade water treatments by sequestering themselves within the cell body of the much heartier amoeba.  

In their non-human habitat, Legionella have also been known to form expansive biofilms, which are large aggregations of bacterial cells that are stuck together in a gooey matrix.  In short, biofilms are a real menace; they can form on many surfaces – including in the lung (cystic fibrosis) or on teeth (plaque), on the hulls of ships (apparently this slows the ship down?!?!), on hospital equipment (bad for obvious reasons) and a whole slew of other stuff.   Biofilm formation is yet another mechanism by which bacteria can become more resistant to antibiotics and the ability to break up or penetrate biofilms is an important focus in antibiotic research.  The propensity of Legionella to form these structures has made treatment of these infections more difficult and has likely made them much less susceptible to standard treatments (chlorine etc.) of our water supply. 

Outbreaks of Legionnaires' disease are unlikely to go away.  While Legionella are present in most fresh water sources, they are usually low in number and thus do not pose a threat.  Reservoirs such as hot tubs, humidifiers, cooling towers, those mist-sprayers they have over the vegetables at the grocery store, etc., present these bacteria with environmental factors that increase their growth and dissemination:  warm temperatures and aerosolization.  This sort of terrifying fact implies that urban infrastructure is actually selecting for the rapid growth and efficient dissemination of this bacteria.  That being said - it seems sort of strange that Legionnaires' outbreaks seem particularly common this summer seeing as air conditioners, hot tubs, cooling towers etc. have been around for quite a while.  Is it merely increased media coverage?  Or perhaps many previous outbreaks have been attributed to influenza or pneumonia?  The low mortality rate and unremarkable symptoms make this an infection that is probably commonly over-looked or not even reported.  

Luckily Legionnaires' is a treatable disease and a low percentage of infected people are likely to die from an infection.  However, while many strides have been made in understanding Legionella infections since the Legionnaires' outbreak in the late 1970s, there are certainly weaknesses in how we diagnose and deal with this disease.  As with almost all bacterial diseases, antibiotic resistance has presented a problem in the treatment of Legionella infections, so we must continue to be vigilant in discovering new ways to kill these bacteria.  Additionally, currently-used methods for detecting Legionella in a patient or in a water source lack either efficiency or sensitivity.  The gold standard of detection requires cultivation of the bacteria, which can be quite slow, whereas DNA-amplification-based methods, which have the potential to be both sensitive and efficient are not currently in use in the United States.  The development of a cheap diagnostic for detecting Legionella in the environment could be a critical advance  in preventing future outbreaks.  

The recent Legionnaires' outbreak in New York City and subsequent outbreaks in San Quentin Prison and western Illinois, have certainly captured the attention of the public and hopefully has highlighted the need for improvement in how to manage and prevent these outbreaks in major cities.   For obvious reasons, further identifying the underlying biological processes mediating Legionella infections in humans will improve treatments for this disease in patients.  However, understanding the ecological behavior of this organism (like biofilm formation or amoebal infection) could unveil new drug targets or diagnostic approaches that would minimize dissemination of this resourceful (and summer-ruining) bacterium.

- AMC