So, good morning, everyone. My name is Michael Sowery, and it is indeed an honor for me to be invited to speak to my peers at this annual ACOM meeting. Short introduction, I started my love affair with parasites at the University of Texas as a double major in microbiology and chemistry. And during the Vietnam War, I received an Air Force scholarship to pay my way through medical school in Chicago. In the Air Force, in addition to being a flight surgeon, I was an epidemiologist and EIS officer representative for CDC. I eventually became the director of the General Preventive Medicine Residency Program in the Air Force and course director for the Global Medicine course. After about six years, I switched over to the Army for another six and entered an internal medicine residency program at Brooke, Army Medical Center, and an infectious disease fellowship at the National Naval Hospital. I separated from the service and entered private practice in infectious disease, consultant in the Washington metropolitan area, primarily caring for AIDS patients, and for 20 years have served as a chief of infection control in one of the local hospitals. As luck would have it, the biomedical industry was exploding in the Washington areas in the 90s, and research companies were desperately in need of occupational medicine physicians who were comfortable treating HIV and various emerging diseases that they were having their workers exposed to in the lab. As my practice began to, occupational side began to eclipse my ID side, I decided to go ahead and grandfather and get my occupational medicine boards and joined ACOM in the 90s, the mid-90s. As a clinical professor at Johns Hopkins and also at the Uniformed Services University of Health Sciences in Bethesda, I've had the privilege to train some of the future leaders in occupational health. It was actually the residents who asked me to formally talk about this topic since they were realizing that they were going to be expected in the future to deal with these, to manage these wide variety of biohazardous exposures in the workplace. I would be remiss if I didn't mention the work of Dr. Warner Hudson when he was president of ACOM and when he was chief of occupational medicine at UCLA in his efforts to try to standardize biomedical occupational medical surveillance. At the same time, I'd have to say that I have a lot of respect for Dr. Melanie Swift, who has led the, for quite a while, the Medical Center Occupational Health Section, both in Vanderbilt and now in Mayo Clinic, and has done a lot to help in bringing some type of standardization to occupational health and has been a real asset during this COVID pandemic. So here we are. I'm talking about my experiences with post-exposure prophylaxis and PrEP. I would appreciate if you'd leave your questions to the end. I do have a microphone that you can use. So definitions usually are how I start things off, and oftentimes it's important because I've seen it misused so many times. What is prophylaxis? Is it different than treatment? What is, you know, is supportive care, is that a form of preventive therapy or medicine? And during, frankly, during my pre-AIDS experience as a physician, post-exposure prophylaxis usually referred to 1% silver nitrate and eye drops to prevent gonococcal neonatorum minocycline or rifampin for meningococcal disease, chloroquine and fansadar for malaria, pepto-bismol for teresta's disease. But when we really get down to looking at the how we fit in post-exposure prophylaxis, we need to kind of put it into the context of why we're doing it. And so we get back into primary, secondary, tertiary, and quaternary care. So primary prevention, obviously, is intervening before health effects occur through measures such as altering risk behaviors. It can be environmental monitoring, chlorination to prevent Legionnaires' disease outbreaks in hospitals, banning substances known to be associated with disease and health conditions like the FDA does, promoting heat, altitude, acclimatization. Vaccinations is what people think of right away, but there's other forms of it. And certainly helping HIV-infected patients or adopt safer sex to prevent their discordant couple from getting infected, things like that. Secondary prevention, screening to identify disease at its earliest stage is the definition before the onset, usually, of symptoms. And we're really talking here about periodic mammograms, regular blood pressure testing, probiotic use before we start to use antibiotic therapy in hospitals to prevent C. difficile, HIV, post-exposure prophylaxis, COVID, post-exposure prophylaxis, and that's, you know, what you're seeing with the monoclonal therapies and the new antivirals. Secondary prevention, managing the disease after the diagnosis to slow or stop the disease progression. And here we're really talking about therapies that we've known to work for altitude sickness, chemotherapy for cancer, rehabilitation after stroke, screening for complications, and trying to identify diseases and treat them and some of them. And really, all we can do is do supportive care, like for prion disease and for certain emerging diseases. Quaternary prevention is really focusing on preventing medical intervention that is likely more to cause harm than good, incorporates a need for this evidence-based clinical practice we've all embraced, and trying to just protect people from iatrogenic harm. And these would include alternative therapies that are non-FDA approved for cancer, chronic Lyme's disease, chronic fatigue syndrome, COVID-19, I listed a few of the ones that are controversial. I'm not here to argue the values of these therapies, but certainly these are ones that come to my mind. The reality is quaternary prevention really applies to all levels of prevention. We're trying to do no harm. So just to put it in... Now trying to put examples, and I tried to figure out, okay, let me give you some examples of post-exposure prophylaxis, PrEP, things like that, and base it on the level of prevention. So in primary preventions, we obviously think of vaccines and certainly we in the biomedical industry use things like vaccinia to prophylax workers who are working with non-highly attenuated vaccinia strains. We have HIV PrEP, which I'll talk about a little later. We have rifamixin for Theresa's disease, Diflucan, to prevent esophageal candidovaginitis as well as, well, esophageal and vaginal candidonitis, and monoclonal therapies that you're aware of for COVID. Secondary preventions, things that come to mind to me is things like SB prophylaxis and antibiotic therapies, antiviral therapies, the things you're used to, the standard immunoglobulins that we used, IgG, HIPIG, Hyperrig, RhoD, varicella, zoster, and variola immunoglobulin. HIV, post-exposure prophylaxis is what we certainly have gotten used to doing in secondary prevention, primarily using combinations of nukes, non-nukes, PIs, and intergray strand transfer inhibitors. We also, in the research area, when we're working with emerging diseases like avian flu, we'll use things like Tamiflu in order to, or other products at higher doses, sometimes two, three times the normal, in order to try to prevent disease in workers. Obviously, COVID-19 has had certain monoclonals that have been effective. The new sub-variants have flipped those to different monoclonals that are now front-line agents. And now we have the advent of the dual PIs and the nukes. So I'm beginning to feel like I'm back in the old 80s, or 90s actually, with HIV therapy, giving my patients nukes and PIs, and having to worry about, are they taking a statin? Are they going to develop rhabdo, you know? So there's those types of issues. Tertiary prevention examples would be certainly the use or using monoclonals in COVID in order to try to minimize the amount of disease. And primarily the goal with antivirals is to reduce the disease intensity so that we can reduce this upcoming surge of long haulers that we're going to be, that we're seeing and we're going to be seeing. So this is kind of one of the reasons to give these agents, despite some of their hazards. And then we do supportive care in the tertiary level for certain diseases that we really don't have good treatments for. And that can be HUS, Yaqub-Kreutzfeld disease, and frankly, most of the emerging diseases. Once you have the disease, there's really not much you can do. You've seen the stories with Ebola and other emerging diseases, dengue hemorrhagic shock syndrome. Tertiary prevention examples to me are really falling outside of what I would normally do. And it's usually management of gestational diabetes and health antenatal women, intensive glycemic control, and looking at the pros and cons of that, and obviously the controversy of extended use of hormonal therapy in postmenopausal women. Most of the examples are non-FDA approved treatments that have gotten, that I can use as examples of how do we try to prevent harm, and that would be anything from the use of laetrile for cancer, prolonged IV antibiotics for chronic Lyme disease, CoQ10 for AIDS, chelating for chronic fatigue syndrome, and again, a variety of drugs that have been used for COVID. I could talk about infection control, and it would take another lecture or two, but the reality is that the primary function is to focus on vaccine-preventable diseases and a hierarchy of control to prevent the spread of nosocomial infections, and they do this through arranging prompt diagnosis and management of job-related illnesses and provide adequate post-exposure prophylaxis. But they use the standard hierarchy of control in order to accomplish this, and obviously that arena has some special cases that give us all kinds of headaches, pregnant healthcare workers, the immunosuppressed, emergency response employees, and personnel linked to outbreaks, and you certainly have seen some presentations on those. Modern pathogen exposure, again, started in the early 90s with the OSHA exposure plan, and it went from universal precautions to standard precautions, and that's what we—and use of blunted needles, safety-engineered devices, a lot of education, education, education, use of double gloves, eliminating recapping needles. And frankly, in 20 years of infection control, I can tell you the most unnatural act is to wash your hands, and it has to be constantly reinforced. However, the most natural human act is to touch your face about 20 times, you know, in an hour. Okay, so I could go into that. So obviously, our standard precautions, and if we look at it from the standpoint of PrEP, are the standard vaccinations that we all give, primarily to healthcare providers, but we also have other indications for using it that aren't PrEP, and it can be post-exposure, it can be in outbreaks, and so these are just examples of how some of these vaccinations have been used. We have special-use vaccines that we use in our clinic almost all the time because we're protecting researchers who are working with these select agents. We also, unfortunately, have to deal with exposures to agents that have no treatment, and all we can do is essentially support them, sort of reserve an ICU room and watch and see how they do. There are some agents that are suitable for post-exposure prophylaxis, and then there are some that are not. The ones that are usually suitable for post-exposure prophylaxis are listed here for HIV, SIV, SHIV, influenza, COVID-19, these are just examples, and then we've seen recently, well, the Marburg and Ebola agents that were developed, but haven't yet been fully tried because of the fact that the epidemic ended before they could be tested in the field. There's pre-exposure vaccinations that we do all the time as part of our pre-employment physicals, and that's hepatitis A and B, and we do a lot of, in hospitals, we'll do a lot of measles, mumps, rubella, titering, and varicella titering in order to get people up to speed, giving them Tdap if there's a neonatal unit or pediatric unit in the hospital. We also give, there's a lot of field teams, research teams that are going into the field, and so we're providing these individuals with vaccines that are present in the areas that they're going to be studying, whether it's JE or dengue, yellow fever, and so forth. So from the bacteria, that was the virals, from the bacterial sides, we have obviously the vaccine preventable disease, vaccines that are commonly used. RSV prophylaxis is essentially a way to try to prevent infection, and again, we use, sometimes abuse or probably oftentimes abuse it for terestis disease, ehrlichiosis, we use the short course one-day therapy, at least in the east coast a lot for exposures less than 36 hours. Other examples where it's suitable are broken down by a class of pathogens, so fungal diseases, rickettsial diseases, spirochetal diseases, mycobacterial, and obviously the noninfectious therapies. Then we get into groups that are not so suitable for post-exposure prophylaxis, and the main reason for that is that they don't really have any symptoms, and they can spread the disease asymptomatically. So we really don't get them in a window that necessarily where they would benefit from any type of post-exposure prophylaxis, even if it existed. So examples of the viruses would be hepatitis C, and then obviously we have a lot of non-preventable viral diseases that are listed here, and we have some of the vector-borne diseases that if they're not vaccinated, we're not going to be able to give them likely effective post-exposure prophylaxis. So there's spirochetal diseases, and really, to me, HIV was just syphilis. And if you think historically back, 20% of the world population in the turn of the century had syphilis, that means my great-grandmother, grandfather May, had a 20% chance of having it. Well, if we lose our current heart therapies, highly active antiretroviral therapies for HIV by abusing PrEP and other things, we may end up with that same prevalence. Relapsing disease, another example. Bacterial examples that are not suitable are these particular enteric pathogens that we deal with, tularemia, legionella. By the time they present with therapy, there's no prophylaxis that we can give them. We have to just start with treatment. Acute fever, especially in pregnant women, is literally a disaster. And listeriosis and bordetellar pertussis. Obviously, nosocomial infections aren't really amenable to post-exposure prophylaxis. We have to look at it from an institutional standpoint and from using other methods like antibiotic stewardship and things like that. Mycobacterial diseases, rickettsial diseases, fungal diseases, these agents are examples of ones that really don't have anything to offer from a post-exposure prophylaxis. By the time you see them, you've got to give them full therapy. Novel agents, prions, nanoparticles, emerging diseases, no antidotes, and frankly, they're the headaches that we have in biomedical industry where we're doing surveillance because even nanoparticles with our current respiratory protection, which only is good to 0.3 microns, will not protect the worker against these agents. And when they get down to the nanoparticle level, they actually become biologically active. And so silver, if you bring it to the nanoparticle level as an antibacterial, they put it in clothes that you cut down on the amount of perspiration, damage to the clothes, things like that. But they use it for chemotherapy and tagging it with other active agents. So what is PrEP? So examples of PrEP obviously are vaccine-preventable agents, as we were talking about before, and being proactive about giving influenza to our immunosuppressed and at-risk patients with multiple medical conditions, COVID, using monoclonal in those high-risk patients in order to sort of prevent severe disease. Bacterial, again, plenty of vaccines that you can think of. Those are the ones I'm thinking of, and Teresita's disease prophylaxis. To me, those are what PrEP is. Protozoal, we give Bacrim to immunosuppressed individuals, whether it's cancer patients receiving chemotherapy or AIDS patients with CD4 counts less than 200, malaria prophylaxis, mycobacterial therapies, and we'll talk a little bit about latent TB and fungal diseases that also are quite opportunistic in the immunosuppressed. Noninfectious agents that are beneficial in PrEP, oftentimes these are sort of limited to travel medicine, and so we have a travel clinic, and we deal with advice and giving medications to our travelers that are coming in. Air sickness is an example of PrEP where, as a flight surgeon, you want to give to trainees who tend to get air sick something to help prevent the air sickness, so you give them, like, five capsules for five flights, and hopefully they won't wash out. Usually that's sufficient to get them over the nerves and the jitters of flying. So I'll move into HIV PrEP because you've heard a lot about that, but that's not HIV post-exposure prophylaxis, and it has its own particular peculiarities. It is designed to prevent, to reduce the spread of nonoccupational HIV infection, and actually the idea originated back when we had in the 90s when we were trying to treat discordant couples. How do we protect the other spouse from getting infected? It was initially promoted in high-risk populations, and it seemed to be fairly effective, but we didn't really have user-friendly drugs until we got out of the ACT drug regimens, and that didn't happen until, you know, probably six or seven years ago. It's highly effective if you take it as prescribed. It reduces the risk of contracting HIV. It reduces the risk of that in IV drug abusers. It has to be prescribed to people who are asymptomatic, I mean, who are asymptomatic and who are also confirmed to be HIV negative. So you're going to waste this drug if you don't do that test and you give it to somebody who's HIV positive. They're going to develop Truvada resistance, and then you've pretty much... This is going to be, I think, unfortunately, the way we're going to lose this very powerful workhorse in HIV treatment. So confirming it and then repeating it every three months. And then we're still telling them that there's 18 other venereal diseases out there that you can get, so, you know, use a condom and stuff like that. Well, the problem that we've seen is that there's a significant disparity in even how this is being utilized. And so a lot of the CME efforts, like in Washington, D.C., and Baltimore, where they have the highest rates of HIV transmission, are really focusing on trying to get the prescriptions to the right people. And right now there's a discordance, a disparity in how this medicine is being available and presented to people. In response to this disparity, on March 19th, the Biden administration earmarked $9.8 billion in funding to be allocated over 10 years in an effort to end the HIV epidemic in the U.S. by providing broader access to PrEP. So PrEP is essentially Truvada or one of another brand name, but it's essentially the same particular medication, and it's used for exposures within 72 hours. Now, that's totally different than occupational HIV exposure, which from the very beginning in the 90s, CDC said you had to get that medicine into them within 2 hours. Well, ever since CDC said that or the U.S. Public Health Service said that, there was no way that I've ever seen anybody get it within 2 hours after an exposure. I mean, you don't even get to see an emergency room doctor in 2 hours. You know, you don't even get it down from the pharmacy in 2 hours. So what we do is we actually keep it in our office and give it to people who come in, or we keep it in lockboxes in their institutions if it occurs after hours so it can be released and given to them so that we try to get a 4-hour window to it. HIV PrEP has a different philosophy. You're not going to be able to tell which day in Las Vegas did you get infected with HIV, you know. And so the idea is they're giving it a wider range of time before you can go ahead and start PrEP. And that's a major change because we were beaten in OCMED about giving it as soon as possible, and now PrEP, it's okay to wait 72 hours. We'll talk about that a little bit later. There are some warnings about DSCOVI that have come out. There's some significant renal issues and hepatic issues that have to be closely monitored. So it's not like you can just give it to them and say, I've done my job, and write 5 refills. You really have to follow them and monitor them for side effects of the drug. Like I mentioned, HIV Occupational Post-Exposure Prophylaxis started back in around 85, and we, Gebhardine, who ended up being the director of CDC, was at the time an ID doc in San Francisco General Hospital, and she did a study of about 2,400 exposures, and she found that single therapies, AZT, prevented the disease from taking hold on these individuals who were exposed. And from then on, we started to use post-exposure prophylaxis, AZT, and then when we got the better drugs, especially the protease inhibitors, we started to use it. So it all started back as soon as even AZT was discovered, or developed back in 85. Now remember, the disease came in in 81. So since then, we have had cases where health care workers have gotten HIV, but currently CDC does not believe that HIV is an occupational hazard for health care workers, and the reason is because of the availability of HIV post-exposure prophylaxis. So there are some exposures that we consider high-risk, and these are examples of high-risk exposures. The fluids that are considered to be higher risk, these are the ones that should be treated. There are some that are considered low-risk exposures, and these are the fluids, body fluids, that are considered to be low-risk. And I think that it's important to always, when you're dealing with these exposures, to first verify that there was an exposure, because sometimes they feel something, but when they put water in their glove, there's no leaking of the glove. There wasn't really an exposure, and so you don't need to necessarily start on 28 days of post-exposure prophylaxis. So the Public Health Service no longer recommends using severity of the exposure to determine the number of drugs that you use. A lot of that has to do with the fact that we have better drugs, and we have better drugs that are less toxic to the individual. When we had AZT-containing regimens for post-exposure prophylaxis, in my experience, only 75% of the people could actually take it, even if they had a severe exposure. Otherwise, they were throwing their guts out, they were having headaches, they were pretty much bedridden, couldn't work. And finally, the New York State Health Department revolted against CDC in around 2014 and said, we're not doing this anymore. We're not going to use AZT-containing regimens. We're going to use newer agents like the integrase strand transfer inhibitors like Reltigravir. We're also going to take advantage of the fact that we have now fourth-generation ELISAs, that we don't have to be taking people out six months in order to monitor them for exposure. They can cut it down to four months. And so by using this particular approach, they found it was a lot more user-friendly and just as effective. It took about a year for CDC to finally agree and say, okay, we agree, and it became the established regimen. And so what you'll see is Reltigravir, which is the integrase transfer inhibitor, it actually is attacking the virus at an earlier stage in its infection process. And you have Truvada, the workhorse, the same agent that is being used in PrEP. So I think that a lot of what I say about four hours and what I say about taking it for four weeks have been well-established and it's well-referenced, and I have it all referenced in this presentation that hopefully you'll have full access to. So this is pretty much how we deal with it. And I think that I've never seen it really fail. I have seen people who didn't need it, but they couldn't sleep at night if they didn't get it. So I gave it to them. I've had others that I've had to be on my knees begging them to take it because it was such a bad exposure and they didn't want to take it. So I think that there's a little bit of you have to understand where they're coming from, but you have to clearly document if they decline the therapy and what were your efforts to counsel them about it. I don't have any problems giving someone who is going off the deep end emotionally from an exposure, especially if it's a young nurse who has two small children and she's had an exposure and it doesn't look like it's a significant exposure from the subsequent investigation, but she wants to have treatment. I'll treat her. So I don't think you have to be necessarily so dogmatic in the approach. So there are some situations, let me go back, the harder ones to deal with are the ones where there was an exposure to someone who was already HIV positive. What you need to do at that stage is ask the doctor who's caring for that individual, what is his heart regimen or her heart regimen and what is her viral load or his viral load? And if they're in a successful heart therapy, that's the heart therapy you want to give them, not necessarily Truvada and Kaletra, but Truvada and Encentrase. Remember, these are people that are experienced HIV positive victims. They have gone through a bunch of regimens and developed resistance to all of them so you really have to find the right regimen that's appropriate for that type of exposure. It's different when you just don't know what the exposure was, who you could tie the exposure to, in which case give Truvadin and Centris. So the regimens are below. There are some alternative regimens. I won't get into this so much, but just to let you know that there are others that are recommended. Most of the recommendations are usually the ones that you'll find in the U.S. public health recommendations for treating naive HIV positive individuals. So these are combinations that would be used to treat somebody who just comes off the street and now they're positive and you want to start them on therapy. So they have a set of regimens. There isn't just one regimen that you can use. Truvadin and Centris is the frontrunner, but there are other options. There are some that you probably shouldn't use. They're too toxic and you shouldn't use without consultation with ID. And there are some that are contraindicated in pregnancy. So understand that if you have any questions, I'll give you one telephone number that you can call and you'll get the answer to your question about what to do in that particular case. We also have obviously other bloodborne pathogens in that blood. The post-exposure hepatitis B protocol is pretty straightforward and it's been present for many years. This is essentially the table that I think all residents should know before the boards, but at the same time this is a summary of what to do when the source is positive and the source is negative or you just don't know what the source is and what is the status of the victim. Do they have detectable titers? Are they immune or non-immune? And remember that HBIG should be administered preferably within 24 hours. It's tremendously expensive. You're probably going to have to send them to either the health department or the ER because no one's going to carry that because of the cost. Hepatitis C, unfortunately we have nothing to offer them to date. And we've been waiting 40 years for them to develop a vaccine for it. All we can do is follow them out to six months and give them a notification that they've been infected and get them to a GI doctor. That being said, there are phenomenal treatments for hepatitis C that are 100% cure. The problem is that they're $120,000 for 12 weeks. Tremendously expensive. And so they are currently doing a clinical trial in phase four with one of these regimens for 14 days. And that hasn't yet been released. So there may actually in the near future be a treatment that we can use for hepatitis C. In the past, I can tell you back in the 70s and 80s, we would tell people, well, you know, you can't, they stopped, they started screening for hepatitis C antibodies in the blood banks for pooled sera. So there wasn't any antibodies for C in the U.S. But if you go to Mexico and you get their gamma globulin, they don't screen for C. And so go there and get triple gamma globulin. Bring back three doses for triple gamma globulin and we'll give it to you in a month. It was that type of desperation that we were doing in order to try to help these people who had serious exposures to hepatitis C. Also interferon was used a lot and it never was shown to really work and never approved. So the, let me just let me go to the next slide. This is the number that I really want you to know. What you're going to do if you call this number is you're going to get an overworked, tired I.D. fellow at San Francisco General Hospital who will be able to tell you what you should do given the information you gave them. Now, in some cases, that may not be the right answer or the best answer, but I view it as cover because I'm calling them because I don't know and he may not know and if it goes south and they get infected at least I tried to call somebody. So this is the person that you should be calling. Not necessarily just for HIV, but for hepatitis B, hepatitis C. So I would certainly recommend that you keep that somewhere to call in case you have a case and I had clients who only studied multi-drug resistant HIV and they would get infected. Now that's a quandary of how to post-exposure prophylax those people. The key thing that I want to emphasize about post-exposure prophylaxis for HIV is you're not doing it in ten days or two, you know, a month. You're following these people out for four to six months and you need to have a system where you can make sure that these records don't fall through the cracks. Because a lot of these people, they're not going to keep their appointments. They're going to forget about the exposure and they may seroconvert and then you find it out after the fact. So we usually use checklists in order to monitor them, getting all the pertinent demographic information that's necessary and also making sure that they have been counseled as to what this prophylaxis can do and cannot do. We get information from the exposed healthcare worker. We give them information about how we're going to treat them. We also let me go back. We also sort of tell them that nowadays the current guidelines are you don't have to avoid sex and those types of exposures after hepatitis B exposure. They've loosened up some of the restrictions that were previously present. When you're dealing with research and medical surveillance our biggest headaches are lab animal workers because they are the ones that are more likely going to be exposed to those emerging diseases that are being studied for vaccine development or antiviral therapies. So we do our typical examinations and these are the things that we do that you're all familiar with. We do serological testing and titers, rabies titers. And TB is obviously a big problem especially in primate research because the veterinarians are very protective about their non-human primates. They're very expensive animal models and they want to and TB can pretty much kill the entire colony, sweep right through it. So they do a lot of effort to supersede even CDC's guidelines of just asking, giving a questionnaire every year or so of symptoms. They'll actually require people to be treated for a start prophylaxis treatment for latent TB as a requirement for the job and they will not use age or chest x-ray results. Normal chest x-ray result is a reason not to require that. So just to let you know that you can always supersede CDC requirements but you have to apply it across the board. You can't be discriminatory about it. One interesting thing, a little bit of history, is that in 95 OSHA had to rescind one of their acts. It's the first time they ever rescinded any act that they had published and that was the TB Control Act. And the reason that they rescinded it is because somebody finally realized that the number one reason for TB in the workplace was reactivation of latent TB. And there was no way to really control that. So they had to revamp their approach to that whole process. So like I say, we certainly are very concerned about TB in certain high-risk populations, the immunosuppressed, those that are using targeted biologics. And obviously a lot of companies still are using PPDs. They're not using Quantum Interferon or T-Spot because it's too expensive. I mean, it has to do with the institution and what kind of deal you can make on the test. But I even have institutions that are only studying TB and they won't use Quantum Interferon or T-Spot unless I ask them in a specific case to use it to sort of figure out a question. There's a controversy about TB but we certainly know that there's risk that increase with certain factors. And so this is sort of showing you how TB, what the risk is. Usually it's .1% per year. But if someone was negative and two years later they convert, they're a TB skin test converter, their risk is pretty much four-fold. If they have a CD4 count less than 200, they're going to go active with their disease in about six weeks. And this is based on a lot of prison studies back in the 80s with HIV. So looking at your population, the standard has always been INH but obviously over the past decade and more there's been this push to accelerate therapy in order to improve compliance and they've always had to deal with increased toxicities associated with doubling up therapies or using different therapies. And there's been Cochrane reviews and there's been findings that have shown that there's probably some combinations that shouldn't be used. And all of this is addressed here and available to you in the presentation. Again, these are our standard vaccinations we give to care workers, tetanus, rabies, measles, mumps, rubella for primate work, and then obviously for clinical research for these workers working with these emerging diseases. B virus has always been a hot topic and I think that it's something to mention. It's endemic to macaques. It's essentially herpes in macaques. They get these blisters around their mouth. But if they infect humans, it is essentially rabies. It presents and kills the human just as rabies would. But the difference between rabies and B virus is that we can prevent it with a very simple medication, Valtrex that we use for but it has to be at a much higher dose. The routes are obviously what we see, bites, scratches, secretions in the eyes, open wounds. The incubation period for humans depends on where their exposure occurred because it's following a neuropathic manner for pathogenesis. It can present as a flu-like illness and then progresses to encephalitis. There's been a number of cases. The last one actually was in CDC. One of the veterinarians didn't report a splash in her eye and she died of this disease. That wasn't too long ago. The protocol is essentially well described in CDC for how do you manage B virus. One of the peculiar aspects is that you clean the wound, you cut down to the bottom of the bite, you clean it out, then you culture it and send it out. You do titers at zero and at three weeks and you put them on high dose Valtrex. This is the highest dose you'll see in any setting. It's a gram three times a day for 14 days. It usually is pretty well tolerated though even at that high dose. Sometimes we'll actually test people later if they're having some funky neurological symptoms but generally it's just the one in three weeks. We will also test, we'll pair the sera with the primate if there's a primate that we know was involved. We also deal with SIV. Now SIV is essentially HIV in monkeys. It will cause a wasting disease in monkeys and some monkeys, we call them the hot monkeys, have this and if an individual gets exposed to this, this monkey will actually give them post exposure prophylaxis just like we would for HIV exposure. You might have heard about lentiviruses. These are essentially retroviruses similar to HIV but they're not highly attenuated. What I mean by highly attenuated is that they use them primarily for chimeric vaccine research where they will gut a certain amount of genomic material out of the lentivirus and insert whatever they want to insert in there to see if they can get an immune response and very similar to what you see with the AstraZeneca type of product for COVID. Essentially you're using it as a vector. The problem is there's a theoretical chance if you didn't take enough of the genomic material out that it could recombine in the host and go back to its wild state and actually cause disease. Because of that potential especially in the first generation lentiviruses, we will prophylax people as we would with HIV. These are all the references about everything I said. Hopefully that will be able to give you a reference that you can use when you're having to deal with post exposure prophylaxis. Any questions? Why don't I give you this microphone and you can pass it on to the others. Thank you. So after you did that post exposure prophylaxis on that nurse that was interested in getting it even though you didn't think it was clinically indicated, what's your follow up testing? There's no difference in how we would approach. If we're going to start the therapy we're going to give them the full follow up treatment. There are some people that often times will choose not to be treated but want the follow up just to make sure they dodge the bullet. To me it's documenting what they want and documenting what you're recommending which may not be in concordance with their desires because they can come back to you and say well nobody ever told me. If you don't have it documented you didn't do it. I think it's important to listen to what they're saying. Back in the days of AIDS where there was no treatment before even AZT I had exposures of doctors and nurses and we had to follow them out for a year at that point. They were so depressed. They were totally different people until that year came. When they had that test and they were negative they were back to themselves. You can't imagine what the trauma, the emotional trauma is because back then that was a lethal disease. That was a two year death sentence back then. People have different concerns. It could be their children. They don't want to give it to their children or they want to be there for their children or whatever the reason. You have to listen to what they're saying. that's why I'm saying you don't necessarily have to follow the guidelines. You know what the guidelines are. You make sure that you have documented, that you've counseled them on the guidelines. But if they still want therapy and they weren't exposed, you know, you may have to tell them, well, your company may not pay for it or, you know, whatever. But if you want it, I'll give it to you. But that's how I look at it. I mean, I treat the patient. And I don't treat the guidelines. Great talk. Mike, thanks. Appreciate it a lot. So Mel and I are sitting here, Gavin. And we both have treated a handful of people with blood borne path exposure to syphilis patients, like secondary syphilis, with pen post-exposure style. And I've also treated a handful of people that are clinical laboratorians who open up the plate in the lab and discover after they've sniffed it that that's coccytoidetes. And it's at the arthroconidia stage. And we put them on the antifungal oral agents for a long time. And they've all done well. So just a comment about those two post-exposure. Those are, I've seen those also. And I actually will do a syphilis test on all blood borne pathogens. I mean, people look at me and wonder, you know, really? But rarely you'll see an exposure. But no. We see it when people are sniffing all kinds of plates, you know. And you're thinking, what were you thinking, you know? But you have to prophylax them. And some don't necessarily need prophylaxis if they're immunocompetent. So you have to decide what the risk is. But nevertheless, no, I didn't include all the examples. I could have included the use of the prescribing of naloxone to someone who has more than 50 milligrams of morphine equivalent as a tertiary prevention. I didn't include all those things. So you can make your own list. I'm just giving you my list of things I was thinking about when I'm thinking of post-exposure prophylaxis. Thank you for this really comprehensive overview, despite those points. So one quick question, and then maybe a bit more of a discussion topic. I'm curious about if you're able to get JYNNEOS for vaccinia researchers, because we've not been successful in getting that from CDC. We're still just getting ACAM2000, which, of course, a lot of people have contraindications to or just choose not to take. Quick answer on that one, and I'll do my other comment. We have several companies that are using vaccinia as a vector, and it all depends on whether or not they're highly or non-highly attenuated. That means just how much genomic material has been removed and how likely is it that this thing can actually go back to its wild form by recombinating somewhere in the host. So generally for the highly attenuated, we don't prescribe any vaccinia for the workers prior to their working with that project. However, CDC is very adamant about it. They believe that workers should be protected if they're working with non-highly attenuated vaccinia, and there are plenty of examples in the literature. There's more in Europe because they're a little more liberal about doing it, but I can tell you there's reported of eight people going blind by having the aerosolized exposure of vaccinia. So it's cutting edge. It's what we're dealing with in biomedical research. It's an excellent vector. Hopefully it will be a way we can develop a herpes vaccine. Maybe it's going to be our way of developing an effective HIV vaccine. So believe me, we're going to have to deal with that issue of vaccinia and which ones do we prophylax and which ones do we not. Have you been able to obtain, so the FDA has approved the inactivated vaccine, JYNNEOS, but CDC has it all sequestered and they are, quote, evaluating it for about five years now. Right. I haven't been able, well, I don't know any company that's been able to get it. I haven't been given it. We give, we've probably given 3,000 smallpox vaccinations in about the past 15, 20 years. But part of the problem is that some of these highly attenuated vaccines, vaccinia vaccines, aren't very effective in immunizing the host against the agent that they want to have them develop an immune response to. So that's why they're still using some of these agents. But from the standpoint of how do you protect them, no. I don't have access. They're still giving us the same agent. So I just wanted to circle back and comment about the employer mandate for treatment of latent TB for workers working in a primate colony. Just to put a few caveats on that, I think that an employer can require that employees be counseled, offered latent TB treatment. Once that clinic door closes, an employer cannot require that the doctor override any of their concerns about the person's hepatitis and their individual risk, which may outweigh their individual benefit, and require that they prescribe it. So it may be not indicated for some people. And you've got to weigh that against the risk, depending upon how recently they converted, they might be in that 0.1% per year, and they're source controlled in the facility. So you sort of have to do that risk assessment. But secondarily, even if it's prescribed, unless you're doing directly observed therapy for a longitudinal oral medication like this, all you really know is the person filled a prescription. You don't know if it went in their mouth or in their toilet. And that's obviously the advantage of observed therapy. But two things about that. First, the companies that supersede OSHA will not hire someone who can't receive INH therapy. So if there is a contraindication to receiving therapy, they won't work there. They won't be hired. It's a requirement of the job. Now the same thing applies to working with vaccinia. There are companies that across the board have a policy, we will not hire anybody who cannot receive vaccinia. And the reason is because their legal beagles feel that they cannot take that type of liability exposure because it's not going to look good in court. Well, sir, why did you not give them this vaccine preventable vaccine, a disease vaccine for this disease when you could have? They don't want to be in that position. So they are across the board will not hire someone who cannot, they won't let the person work in that project if they can't receive vaccinia. The same thing is true about INH with primates. They won't take that risk to their monkeys, to their primates, and at the same time it's across the board. So they're not discriminating against anybody. That's their policy. It's a requirement of the job. You know, I've dealt with over 900 AIDS patients and I've always been very advocate of making sure they don't have a problem with getting a job or whatever because they're HIV positive. But that is one situation where they won't get the job because remember, right now CDC controls vaccinia. And at this point, one of the requirements is they can't be HIV positive. So if they can't receive the vaccine, which is a requirement of the job, you know, they don't get the job. That's a direct threat under ADA. That's the direct threat provision they can do that. Any last questions? Hello. Thank you. That was a great talk. I was just curious if you have any recommendations on resources for just a synopsis or summary of treating the workup and treating these in healthcare workers, firefighters, et cetera. I feel like the times, I don't do it frequently enough that I have it all memorized and the times I have to look it up, I feel like I don't have a concise reference. Well, I think certainly I have the guidelines in the references that you can use and they are broken up into HIV, hepatitis B, hepatitis C. So you can see the current guidelines and you can just go to that web link and you'll find it. But what I will say is that there's plenty of places that you can, like that 800 number, you can go to get somebody to help you advise what to do in that situation. The same thing is true with if you're trying to find somebody who offers PrEP. Somebody comes to you and says, I'd like to receive PrEP. Well, you know, there's web links and CDC and others that can give you based on your geographic location, the doctors that are offering PrEP. So at one point the CDC had like a one page PDF summary that I thought was pretty convenient, but I can't find that anymore and the link says that. It's not one page anymore. But nevertheless, it's in the link in the references and it is available. But at the same time, you're going to run across some unusual exposures. You're not quite sure how to approach it. So you always know that there's that resource to call that, that number to call. Thank you. All right. So I think that. I was just going to add that when you call that PEP line at UCSF, they're great for a lot of things, but they don't do research exposures and neither does CDC. So for research exposures, you really need to look elsewhere. For leniviral vector exposures, a group of us had a symposium a few years ago and JOM published the Leniviral Vector Post-Exposure Prophy Plan, which is a shorter course of one or two drugs than the full HIV exposure plan. So the other comment I'll make is that Phil Harbour and Amy Berman and Mark Roussey are the editors of a book that you can see or pick up and buy today at the OEM press station in the little trade center down the hall on biologic exposures, research exposures in research institutions and actually it's occupational health for research institutions and institutions of higher education. And it's just out and it covers a lot of these areas in some detail as well as the great talk that Michael just gave. That's an excellent reference. And I think that, you know, there's going to be more and more requirements of occupational medicine doctors to give advice to their clients, to their employer about what to do about this exposure. I mean, we've dealt with business continuity issues with these emerging diseases. All right, there's somebody who's on top of it, has the book to show. But I do think that it's a challenge and it's one of our, the cutting edge of occupational medicine for many of the doctors. I can tell you back in the, during the period of AIDS, you wouldn't find an occupational medicine doctor nor even a surgeon who would take care of your HIV patient. That kind of fear exists. You see it with Ebola. You see it with COVID. I mean, so the idea is the disease changes, but people don't change. And so you have to understand the fear that, and what lack of data and what lack of information does to people, and we've certainly seen it here with COVID. So it's a challenge. I think that it's exciting. So hopefully some of you will embrace it and become Achmed docs in university systems that do a lot of research and things like that. Well, thank you very much for your time. Sorry, one more question. Oh, sure, no. I think we've got. I just had a question about like alpha-syn fibrils, or alpha-synuclein commercially available ones that behave like prions. I know some of your comments there. Have you seen any research, depending on bleach versus hypochloric, or hypochlorous acid for post-exposure, whether immersion or irrigation or what's, what options exist for that kind of research? I'd have to say that it's not something that I'm familiar with. And though I'd be hesitant to recommend it to anyone only because of its destructive nature to tissue, when you think of things like hydrogen peroxide, the last thing you want to do is continue to put hydrogen peroxide on a wound. You know, you use it once to clean the blood. You don't put it on every day because the wound will never heal. So, when you're using caustic agents, what I always worry about is going back to the early days of AIDS, we had all kinds of spermicides that were being used, offered, recommended to women that had certain types of agents that might prevent or be neutralizing to HIV, but what they found was that it was actually causing so much irritation that it was a portal of entry for HIV, so it made them even more susceptible to it. So, I always think about, you know, host-parasite relationships and, you know, are we doing good or not? The standard answer to that would be more research is required. But, you know, I worry, those are the things that come to my mind because there's always, there's desperate people looking for salvation and there's a lot of people out there that are willing to sell them a lot of snake oil, you know. So, you have to be really careful and make sure that you're able to justify why you went outside of FDA-approved standard therapies because if things go wrong, it's going to be very difficult for you to defend that, I think. So, that's just looking at it from the medical legal aspect, not from the patient care perspective. Yes? So, the question was, is there any guidelines for healthcare workers who have blood-borne pathogen diseases? And in the past, we used to restrict surgeons who were HIV-positive, hepatitis C-positive from surgery. And currently, I think the policy is to allow them to work in that setting. MRSA is sort of a similar history. What happens when you're seeing multiple MRSA cases in an orthopedist and they end up having MRSA when you do an investigation, pretty much what you do is you restrict them, you treat them, clear their infection, and they can go back to work. But I think Jennifer, I mean, I'm sorry, Melanie can probably answer some of that. So, the guidelines have evolved. Shea just issued some updates within the last year. And if you're coming to the Medical Center Occupational Health course, which is on Thursday, I'm doing a session on that topic. If you're not able to come see me and I'll share my slides with you. But the answer is it has evolved. There are new thresholds for viral load that allow people to acceptably continue to practice exposure-prone procedures for each different disease. That's the perfect answer. Okay. Thank you, Melanie. I appreciate it. All right. Any other questions? Well, thank you very much for your patience and attention. Thank you. Thank you.

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occupational health practices

HIV

blood-borne pathogens

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