Legionella Pneumophila

by Sean Elliott, MD

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    00:01 <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>

    About the Lecture

    The lecture Legionella Pneumophila by Sean Elliott, MD is from the course Bacteria.

    Included Quiz Questions

    1. C3b receptors
    2. Fcγ receptors
    3. Toll-like receptors
    4. Mac-1 receptors
    5. CD14 receptors
    1. ...aerosols.
    2. contact.
    3. ...fecal-oral route.
    4. ...sexual contact.
    5. ...blood.
    1. Alveolar macrophages
    2. Endothelial cells
    3. Type I pneumocytes
    4. Bronchial epithelial cells
    5. T lymphocytes
    1. ...2–10 days.
    2. ...1–2 days.
    3. ...10–14 days.
    4. ...14–20 days.
    5. ...20–28 days.
    1. Up to 20%
    2. Less than 1%
    3. Less than 10%
    4. Up to 70%
    5. Up to 50%
    1. Hyponatremia
    2. Hypernatremia
    3. Hypercalcemia
    4. Hyperkalemia
    5. Hypomagnesemia

    Author of lecture Legionella Pneumophila

     Sean Elliott, MD

    Sean Elliott, MD

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    i advise everyone to use it
    By Maximec M. on 30. May 2022 for Legionella Pneumophila

    I loved it good explanation . will think of definetly subscribiing . straight to the point

    Very helpful
    By Maria Q. on 15. October 2020 for Legionella Pneumophila

    This lecture is very informative yet concise. Everything that you need to know is here. Thank you