Hello. So, I have some ringing in my ears, but I don't know why. I'm going to be very brief about this. The handout is in the site. I'm waiting for the rest of that. Okay, so I'm going to be talking about laboratory-associated infections, and this is an occupational global health issue of growing concern. Some of it has to do with the gain-of-function research that you've heard about. A lot of it has to do with the increased studying of select agents and emerging diseases, and it's interesting that I originally chose a case presentation to lead into the discussion of laboratory-associated infections, and it turns out that two weeks ago, the Infectious Disease Society of America notified all their members, which I'm an infectious disease specialist, that there was a outbreak of a recurring emerging disease that hadn't been present in the U.S. for 50 years, and so I think that it's probably, you're going to get some questions about this probably from your clients or in your institution, so it might be worthwhile to at least read over my discussion. So, I have nothing to disclose, though I will state that I'm a consultant for about 150 biotech companies in the Washington metropolitan area for the past couple of decades. I don't have any investments in any of them. So, the case presentation is a febrile 55-year-old insulin-dependent white male who presented to his primary care provider in Frederick, Maryland, due to a two-week history of increasing painful mass in the left axilla. On March 16th, the patient's PCP gave the patient an intramuscular injection of ceftriaxone, started him on 10 days of cefalexin. Chest x-ray, urine, blood cultures were all unrevealing. In April, despite completing the therapy, episodes of fever increased, and the patient experienced marked fatigue, malaise, night sweats, weight loss. The patient's PCP then began a 10-day course of clarithromycin, which improved the symptoms and coincided with resolution of the left axillary mass. However, four days later, after completing the regimen, the patient's symptoms returned. He continued to have some weight loss, experienced mid-epigastric abdominal pain. Multiple blood cultures were obtained and were negative. Six weeks from the onset, a CT scan of the patient's abdomen revealed multiple hepatic and splenic lesions consistent with abscesses. Due to his hyperglycemia, diabetic ketoacidosis, and increased abdominal pain, the patient was admitted to Frederick Memorial Hospital where he had an ultrasound-guided fine needle aspirate of the lesions, which revealed purulent-appearing material. Blood cultures again were obtained, and the patient was placed on piperacillin-tazobactam. On day two of that hospitalization, he developed respiratory arrest, requiring mechanical ventilatory support, and was transferred to Johns Hopkins for further treatment. At the time of the transfer, Frederick Memorial Hospital identified and reported small bipolar, weakly staining, gram-negative rods in the culture of the liver abscess fluid. On arrival to Johns Hopkins, the diagnosis was made by a fourth-year medical student. The medical student obtained a work history and found that the patient was a microbiologist who did research at USAMRID on several pathogenic bacteria, including Bacoldria malari, a causative agent of glanders. The next day, the automatic bacterial detection system at Frederick Memorial initially identified a bacteria that it was pseudomonas putatum. So once they knew what they were dealing with, I'll just say the patient got better. So the purpose of this was to emphasize the fact that I wasn't clinically involved in the case. I did know the infectious disease specialist, did know the primary care provider. These were good physicians. This person didn't feel the need to tell them what he did, nor did they ask the patient what he did. And so it was essentially a fourth-year medical student who made the diagnosis. So this is the disease that has been reported by IDSA that is now recurring in the U.S. It because of global change, climate change, the environment has been ripe for it to spread up from South America into the Gulf area, and so the Gulf states are reporting cases. So you may find that this is something that you're going to have to deal with. I can go through glanders. The handout pretty much describes it. It's a pseudomonas-like agent, multi-drug resistant. If you don't think about it, your patient is dead shortly. It's a lot like meningococcemia. I saw it in the soldiers coming back from Vietnam. It's in the soil. It was in the wounds of these individuals. It usually presents as a pneumonia. So the the key thing about this particular agent, and I'll go down to the the key thing, is that it's a great manicur. And so it isn't it's going to look like TB or it's going to look like typhoid. And more importantly, the host is the key thing. And in my years of working in biotechnology, when somebody tells me that they're working with a detenuated strain of an agent, it's only attenuated if the host is immunocompetent. So we have certainly seen attenuated plague kill researcher in Chicago and various agents that we are usually not very pathogenic actually create serious disease in our immunocompromised. So one of the key things I do in the pre-employment and periodic physicals is ask them, has there been anything that has affected your immune system? Are you on a targeted biologic, you know, for some condition? Or have you received chemotherapy, etc., etc.? But in this case, what made this individual susceptible was one, he was working with it improperly. Two, he was an altered host. And so the presence of any predisposing condition without proper PPE, such as diabetes, chronic liver, kidney disease, alcohol abuse, long-term steroids, any of these conditions will put an individual at risk of getting the disease compared to his co-worker right next to him who may be doing exactly the same thing. So this was the notification that IDSA was making us aware of. They started to isolate meleodosis in the Mississippi area in the soil, and it really has a rather global footprint, mainly in the tropics. And at the same time, it has been creeping up because of climate change into Central America and now is back into the United States where it hadn't been for 50 years. So this is sort of the progression of the occasional cases they would see. Most of the cases they saw, those cases came from areas or had visited areas where meleodosis was endemic. But then they started getting autochthonous cases, cases that were where the individual had no travel history. All right. And then there was kind of an epidemic with an imported aromatherapy spray that was contaminated with it. So they're starting to see more and more cases now. They seem to be more homebound. They did some ecological studies and found that really the entire Southeast U.S. is susceptible to this particular disease. So talking about, this was the lead-in, talking about laboratory-associated infections. And it's kind of appropriate that we're talking about it now because, in reality, this is the 200th anniversary of the birth of Pasteur and Koch. These were the fathers of microbiology, germ theory, and, in my opinion, modern medicine. But at the same time that they discovered these agents, within a matter of months to years, there were laboratory accidents that led to infections with these agents. And every one of these great microbiologists that are in the books had staff or themselves suffer from the diseases that they discovered. So laboratory-associated infections have been with us forever. And the development of a biological safety cabinet was done because we're not perfect. We don't do things in a perfect way. We don't follow protocols. We get complacent. And so biosafety cabinets have, in many ways, reduced the amount of infections over the years. But nevertheless, there's been a wide number of, a large number of laboratory-associated infections, and they've been reported all the way back to the period of Pasteur. I won't go through a lot of this because I think the point I'm trying to make here is that you can get it from a variety, you can get it from whatever you're studying. If it's in any way zoonotic infection or human infection, at the same time you can get it by needle stick or splash. But the biggest concern we have is aerosol. And so when you're dealing with this in a lab, when you're dealing with an agent in the lab, you really are focusing on what are the aerosol-generating procedures that you're doing, and what type of personal protection are you giving your staff, and what type, are you using a biosafety cabinet, or at what level of control are you using. So let me just go. So when we're talking about these lab exposures, one example that I like to give is a laboratory exposure that occurred in 2004, and it was SARS. And it was in a laboratory, they were transferring the agent from a BSL-3 to a BSL-2, and there were two laboratory-acquired infections. The first lab worker infected two people, mother and a nurse, and the second lab worker infected two people, one of them died. And then the other one went on to cause tertiary transmission to five other people. So a total 11 people were infected by this laboratory-associated infection. So obviously there's a lot of statistics showing who's at risk, and certainly laboratory workers, health care workers, medical pathologists have been found to be at high risk. Most of the agents in the world that are being reported are primarily bacterial, but you see a number of viral, rickettsial, fungal, and parasitic infections depending on what people are studying. Again, aerosol is a very common way that it's transmitted, and oftentimes the unclear sources that are reported here are oftentimes actually aerosol. So I'm trying to go a little bit through this. When we talk about, I think it's important to know how we can engineer some of the controls here, and so BSL 1, 2, 3, and 4 are what is used. So BSL 1 is used when you have a well-characterized agent, not known to consistently cause disease in healthy adults, and minimal potential hazard for the laboratory personnel and further spread into the environment. So dissecting frogs in high school, you know, typical procedures like that. BSL 2 agents are moderate potential hazard to personnel and the environment, moderate to low individual and community risk, but no aerosol transmission. So BSL 2 is oftentimes what you see in hospital settings. The only BSL 3 you might see in a hospital would be maybe the TB area where they're isolating fungus, coccidioides, or TB, where they will have a biosafety cabinet. BSL 3, which is where most of my laboratory's clients that are dealing with select agents and various emerging diseases, they'll be working in this type of facility, which is essentially for indigenous or exotic agents that cause serious or potentially lethal disease with aerosol transmission potential and high individual and community risk. Effective treatment and prevention usually is available. So when it isn't available, then you move into BSL 4. And there's about 13 BSL 4 facilities in the United States, and these are major usually federal institutions, like USAMRID, like Homeland Security, but you'll see it in Boston and Galveston, Plum Island, move their operation to Manhattan, Kansas, and they deal with all of the serious animal pathogens that can wipe out our livestock. So these are, again, primarily readily transmitted, dangerous, exotic agents that pose high individual or community risk of aerosol transmission and life-threatening disease. Usually there is no effective treatment or prevention. So I wanted to sort of put it in perspective. Another aspect of why someone might take a BSL 2 agent and raise it up to a BSL 3 has to do with volume. Are you ginning up, fermenting a whole bunch of bacteria beyond just a small amount? For agents that are very, very hard to get out of the environment, prions are almost impossible to decontaminate from surfaces. So you can easily contaminate cafeterias, contaminate office spaces. So when people are working with prions, they're usually working at a BSL 3 level, mainly to kind of contain an agent that is very difficult to decontaminate. These are just examples of the type of practices. When you get up to the BSL 4 level, there is a protocol for everything, literally. And if you think of a BSL facility, it's really a biosafety cabinet inside a biosafety cabinet. And the outside facility is essentially isolated from the environment, and everybody's working in level 4 protective equipment. So obviously, types of controls that we deal with are the ones that we also deal with in hospitals. And for 20 years, I've been Chief of Infection Control at one of the local hospitals, and we utilize these particular things. One of the hardest things to convince people to do is to wash their hands. It is not a natural human act. What is a natural human act is to touch your face several times an hour. So breaking habits, reminding them continually to do these things is the challenge of most infection control services. Air exchange, we often talk a lot about, well, we need to have better air exchange. And if you look at the slide here, what a standard hospital room has, six air changes an hour, ICUs have 12. If you go up to an airplane, an airline, it's 20. But it's only 20 when the power is full. So if it's idling on a tarmac, you don't have any protection, so to speak, or any significant circulation. So it's only when you're doing it at full power. But all of these were based on a formula, and this is how they calculate air changes per hour. And it goes on these assumptions that were based on the prototypical aerosol. I think this is automatically progressing. Progressing was based on the fact that you have TB, and somebody coughs. And they'll cough essentially 1,000 particles in a cough, and they've defined that you're only going to be coughing once a minute, and they have a set room dimension and everything. But when you get down to reality, people are coughing more than just one time a minute. And oftentimes, they have significant shedding of TB. So you need to understand that sometimes where the guidelines were developed when you're talking about air changes. Common routes of exposure, this is what we deal with all the time. If you looked at the methods by which people got their infection in the 30s, 40s, 50s, 60s, it's no different now. And we see these same. The only thing we don't see is mouth pipetting. That has changed. They have automatic pipetters. That was a major problem back 30 years ago until they automated pipettes. But for the most part, direct contact, ingestion, percutaneous, inhalation, standard methods. Most of the failures in individual control are using defective equipment, continuing to use defective equipment, knowing it's defective, performing procedures without appropriate supervision. The accidents usually occur when someone is new, working too fast, distracted. Most of the bad accidents I've seen occur at about 5 o'clock on a Friday or just before a three-day weekend. People just aren't focused. And certainly disregarding established safety protocols. And that's really just fighting human nature and complacency. They know for the most part what they need to do and they do shortcuts. So I think that these are just examples of what I see on a regular basis as the reasons for why people get infections. So obviously risk assessment is the key and identifying the hazard, going through the process of evaluation and implementation and then following up on the effectiveness of what you do is the key. And certainly carefully, you are tasked usually in biological safety meetings to review procedures and review the agents that are being used and determine whether or not everything has been thought of that needs to be thought of. And that the proper safety engineering equipment is being used. I have references to all of this. Every one of these is referenced. And going through the entire literature. So I just wanted you to know that it's available for you to have as a handout to use as you feel necessary. I'm sorry about all the noise. And I was going a little faster but I didn't know when I figured it's time for you to go. But anyway. Any questions? I'd be happy to try to answer. This is my life. This is what I do for 20 years. Yes. Can you tell the rest of the story from your intro? It should be a BSL-3 agent and it sounds like something else happened. What happened? Why did that occur? Actually he was manipulating the agent without gloves. But sometimes you can actually get away with that because it's considered low risk. So they suspect that really what put him at risk was his diabetes. But inside a BSL-3 facility and inside is whatever it is. Yeah it doesn't sound good. Fancy biosafety cabinets? Yeah. No. He wasn't doing it in a biosafety cabinet. But again he had no lesions. But the way the lymphadenopathy tracked it suggested that it was probably due to some cut microscopic cut or something. But really what puts this individual I think at the highest risk is his comorbidity with diabetes that put him at much more risk. But you know frankly this happens. This is an example of a case where you know to me it could have been he could have died had he not been diagnosed. And a lot of it is he wasn't forthcoming. I'm a consultant for Plum Island right now. I was now that they moved it. But when you take two ferries to get to the island and you have two ferries back one's going to Connecticut one's going to Long Island. And if these people get infected with a zoonotic infection they're going to go to their primary physician and say they have a fever. And you know when you think of you know Hoof Beach you think of horses not camels. So we would give them a card to carry in their wallet that they had to present to the emergency room and to their primary care provider telling them oh yes and by the way I work with these agents so that they would at least be thinking about those particular unusual outliers. I don't know if that's helpful. That helps. That helps quite a bit. We did that when I was overseeing the support for a non-human primate facility did the same thing. They had a card said this person works with weird things then call me at my cell phone number. Absolutely. And I think that's a very that has worked out. I just read this guy was working with it like at his desk while he was eating lunch or something. No but he did break a few protocols. But there were no other sources that they could identify where he could have gotten it. All right. Well any other questions. Well I'm sorry a little disorganized but thank you very much for your time. Have a safe trip.

laboratory-associated infections

axilla

Burkholderia mallei

biosafety cabinets

biosafety levels

laboratory safety