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<b>Legionella Pneumophila.</b>
<b>Now, before we talk a little bit more about Legionella,</b>
<b>it’s important to talk about why it is called Legionella.</b>
<b>This is one case where the organism was discovered after the</b>
<b> disease for which it is named happened.</b>
<b>In fact, there was Legionnaires' conference where a large </b>
<b>number of the attendees</b>
<b>developed an atypical pneumonia and a point source was </b>
<b>finally discovered</b>
<b>and the name of the disease, Legionnaires disease, now is </b>
<b>going to describe Legionella, the organism.</b>
<b>So without further ado, the organism named for the </b>
<b>Legionnaires,</b>
<b>Legionella pneumophila, is a gram-negative coccobacillus;</b>
<b>facultatively intracellular, growing within a cell; and it </b>
<b>is a very poorly-staining organism.</b>
<b>So, as we'll talk about later on in the session,</b>
<b>its identification measures are typically done through other</b>
<b> methods than looking at it under a Gram stain.</b>
<b>So where does Legionella live?</b>
<b>It, in retrospect, now it’s known to occupy pretty much any </b>
<b>environmental water source.</b>
<b>This could be an industrial level air conditioner or </b>
<b>potentially hot water tanks,</b>
<b>or certainly lakes, but also hospital-based water system</b>
<b>which is unfortunate for those patients who are </b>
<b>immunocompromised and even municipal or city water supplies.</b>
<b>In fact, most large towns up to full size cities in the </b>
<b>world,</b>
<b>that are able to will screen for the presence of Legionella </b>
<b>to see not if it’s present but how much of it is present.</b>
<b>Transmission is via aerosolized water which is important </b>
<b>although so important</b>
<b>as well is that person to person transmission is not known </b>
<b>to occur</b>
<b>even in those immunocompromised patients who may have a </b>
<b>productive cough.</b>
<b>How does the pathogenesis occur?</b>
<b>The first component is that Legionella binds to its target </b>
<b>cell,</b>
<b>in this case the alveolar macrophage,</b>
<b>but it does so by adopting part of the normal immune system </b>
<b>sort of getting</b>
<b>under the wire, as it will, so the organism itself binds to </b>
<b>the normal receptor for compliment 3b</b>
<b>and in place of the compliment being internalized,</b>
<b>the Legionella itself is internalized into the alveolar </b>
<b>macrophage -</b>
<b>but, it also is able to produce a factor which prevents </b>
<b>binding of the lysosome with the phagosome.</b>
<b>Keeping in mind the phagosome is the collection of an </b>
<b>ingested material,</b>
<b>the lysosome is that enzyme-rich, many times acidic, </b>
<b>enzyme-rich environment</b>
<b>which is supposed to bind, fuse with the phagosome and </b>
<b>destroy anything within it</b>
<b>but in this case, that process is prevented by Legionella </b>
<b>itself - so it’s catching a free ride,</b>
<b>which is quite lovely. It is then free to duplicate itself, </b>
<b>multiply itself,</b>
<b>and then when it’s ready it releases degradative enzymes, in</b>
<b> effect killing the alveolar macrophage</b>
<b>and releasing itself into the world to go about its business</b>
<b> and do more fun stuff.</b>
<b>So there are two commonly recognized forms of disease </b>
<b>associated with Legionella.</b>
<b>The most commonly recognized is Legionnaires disease, </b>
<b>although this is the least common.</b>
<b>The more common but the least well-known is Pontiac fever - </b>
<b>go figure.</b>
<b>Infection rate for Legionnaires disease is less than 5% but </b>
<b>when it does occur,</b>
<b>it’s typically in an epidemic and sporadic fashion due to a </b>
<b>point source -</b>
<b>witness the Legionnaire’s conference, witness clusters of </b>
<b>diseases in infected hospitals, et cetera.</b>
<b>Pontiac fever is epidemic, present potentially all the time,</b>
<b> with a high infection rate.</b>
<b>Legionnaires disease clinically is an atypical pneumonia</b>
<b>but a very severe one so this means that it could be </b>
<b>multiple lobes of the lung</b>
<b>which are affected or could be a single lobe.</b>
<b>Patients typically have high fevers with rigors,</b>
<b>with chills and they have a dry, nonproductive cough.</b>
<b>They may actually progress to have severe gastrointestinal</b>
<b>and central nervous system symptoms.</b>
<b>Whereas those with Pontiac fever have at the most a mild </b>
<b>flu-like illness</b>
<b>without any focal pneumonia whatsoever. Timing of onset.</b>
<b>Well, as noted before, Legionnaires disease in association </b>
<b>with a point water source</b>
<b>typically is going to occur in summer and fall -</b>
<b>times when somebody might most often be using air </b>
<b>conditioning, water cooling, etc.</b>
<b>However disease can occur throughout the year if it’s </b>
<b>related to an internal source like a hospital water supply </b>
<b>or etc.</b>
<b>Pontiac fever though can occur throughout the year just </b>
<b>simply due to any waterborne exposure.</b>
<b>Incubation period of Legionnaires disease up to 10 days, </b>
<b>most commonly 4 to 5 days;</b>
<b>Pontiac fever it’s very rapid incubation period only one to </b>
<b>two days.</b>
<b>Legionnaires disease, obviously, as we’ve talked about the </b>
<b>more severe</b>
<b>and therefore antibiotic therapy is necessary to get past </b>
<b>this, Pontiac fever similar to mild flu,</b>
<b>is self-limited - it resolves on its own.</b>
<b>The mortality rate, again this won’t be a surprise but </b>
<b>untreated Legionnaires disease,</b>
<b>especially in those who are infirm or have a compromised </b>
<b>immune system,</b>
<b>can be quite severe and up to a 20% mortality rate has been </b>
<b>described.</b>
<b>Pontiac fever - self-limited; mild, mild flu like; has a </b>
<b>very low mortality rate less than 1%.</b>
<b>Lab diagnosis, and again, remember that the organism does </b>
<b>not gram stain well,</b>
<b>so one can use other stain such as the silver stain or </b>
<b>florescent stain.</b>
<b>One can use a very special culture keeping in mind that </b>
<b>Legionella grows within cells</b>
<b>and so to actually get it to grow and culture requires </b>
<b>adding lots of external support</b>
<b>such as charcoal, yeast, buffering it with iron, cysteine, </b>
<b>etc.</b>
<b>The most commonly used diagnostic method to detect </b>
<b>Legionella pneumophila is the urine antigen test.</b>
<b>This is an immunofluorescence test which will detect the </b>
<b>presence of those toxin antigens released by Legionella</b>
<b>and it is typically excreted into the first morning urine -</b>
<b>meaning that one wants the urine to sort of pool overnight</b>
<b>then capture the first urine as the patient wakes up, </b>
<b>transport it, still warm to the laboratory,</b>
<b>so the lab can then do the antigen. Why warm?</b>
<b>Because the antigen decomposes very or deteriorates very </b>
<b>rapidly</b>
<b>and allowing the urine to cool meaning temperature </b>
<b>sensitive,</b>
<b>will disorder and disintegrate the antigen giving a false </b>
<b>negative test.</b>
<b>Patients with Legionnaires disease also are found to have </b>
<b>hyponatremia, why might that be?</b>
<b>In large part it’s due to vascular leakage and water,</b>
<b>osmotic shifting during the acute pneumonia</b>
<b>which then has a secondary effect of giving one </b>
<b>hyponatremia.</b>
<b>This slide shows a summary</b>
<b>of the laboratory diagnosis for Legionella</b>
<b>PCR as the preferred diagnostic test</b>
<b>for Legionella pneumonia.</b>
<b>It's highly accurate</b>
<b>and a text all Legionella serogroups.</b>
<b>However, one may need an induced sputum</b>
<b>or even better,</b>
<b>a bronchoalveolar lavage specimen</b>
<b>to increase the yield.</b>
<b>Urinary antigen testing is a second line</b>
<b>testing strategy if PCR is unavailable.</b>
<b>It can give you rapid results</b>
<b>and has high specificity, but</b>
<b>a sensitivity is only about 75%, and also</b>
<b>it only detects Legionella type one.</b>
<b>Culture, then, is the gold standard</b>
<b>for confirmation</b>
<b>for either of the first types</b>
<b>of testing strategy.</b>
<b>But it takes three to five days</b>
<b>for a result and its sensitivity</b>
<b>is only ten to up to 80%.</b>
<b>This also will have a higher yield</b>
<b>if one could provide an induced sputum</b>
<b>or a bronchoalveolar lavage specimen.</b>
<b>Treatment. Antibiotics are the preferred treatment and </b>
<b>specific one’s including the macrolides -</b>
<b>the erythromycin, azithromycin are the drugs of choice for </b>
<b>Legionella.</b>
<b>The fluoroquinolones such as ciprofloxacin also will work, </b>
<b>but there are other choices as well for patients</b>
<b>who may be sensitized either due to gastrointestinal </b>
<b>distress or other issues.</b>
<b>Rifampin and doxycycline can be alternatives.</b>
<b>Unfortunately, there is a fair amount of resistance among </b>
<b>Legionella to all of the beta lactam antibiotics,</b>
<b>so the penicillins, the cephalosporins, the carbapenems -</b>
<b>none of those will have significant or predictable effect in</b>
<b> this case.</b>
<b>Prevention. This is perhaps the most difficult part because </b>
<b>it would be the most ideal.</b>
<b>If we could prevent Legionella from being in a common water </b>
<b>supply</b>
<b>and making it into the patient that would be best,</b>
<b>unfortunately, it is notoriously difficult.</b>
<b>City water supplies will have Legionella, it’s just a fact </b>
<b>of where the organism grows</b>
<b>and therefore it will enter into medical settings,</b>
<b>into the homes of patients who are immunocompromised or at </b>
<b>risk of developing Legionella disease.</b>
<b>Things that have been tried to reduce the burden of </b>
<b>Legionella are hyperchlorinating the water</b>
<b>and we’re not talking just like a swimming pool </b>
<b>hyperchlorination</b>
<b>but the point of doing a significant percentage of the water</b>
<b> being chlorine-based,</b>
<b>also meaning the patient should not be drinking, showering, </b>
<b>etc.</b>
<b>with that water during the time of hyperchlorination.</b>
<b>Also, heating the water supply - here is another example of </b>
<b>some is enough, too much is even better.</b>
<b>So parts of the world which have normally warm municipal </b>
<b>water supplies</b>
<b>have a higher organism load of Legionella because it grows </b>
<b>better in those warmer areas,</b>
<b>but exceeding that temperature by going up to super heat </b>
<b>level,</b>
<b>so well-passed the normal body temperature would be </b>
<b>appropriate to get rid of Legionella</b>
<b>but it’s not very effective if you are trying to do so for </b>
<b>an entire hospital system.</b>
<b>Hot water system, fine; cold water system, big challenge.</b>
<b>So a evolving intermediate approach because </b>
<b>hyperchlorination is difficult for patients</b>
<b>to tolerate and it’s difficult on pipes,</b>
<b>it is to use various ions such as copper silver treatments</b>
<b>which also will limit growth and persistence of the </b>
<b>Legionella in the cold water systems.</b>
<b>Regardless the step, this is an ongoing area of discovery</b>
<b>to maximize the prevention of Legionella from water pipes </b>
<b>and from exposure to patients at risk.</b>
<b>So going from an organism that got its name from the </b>
<b>disease, talking about the disease,</b>
<b>which thankfully is still somewhat rare but does occur </b>
<b>occasionally in epidemics</b>
<b>and always in association with some exposure to aerosolized </b>
<b>water, this is our friend - Legionella.</b>