Good morning and welcome back to day three of the American College of Preventive Medicine's 33rd Annual Board Review Course. This morning, we'll be starting with Clinical Preventive Medicine Infectious Disease with Dr. Dana Bradshaw. Good morning, colleagues. Yeah, Dana Bradshaw from Eastern Virginia Medical School. And I don't know how much detail you can see in the little inset that has my picture in it, but the background behind me is actually a very empty O'Hare Airport custom section. And the reason it's empty is because of COVID-19, which I know you're all pretty much experts in already. The good news is there's nothing on that from what I'm told from Jill Whalen that's gonna be on the board review questions, but if we have time, we'll quickly go over that as part of this section. But it just emphasizes what the importance of this topic is, Clinical Preventive Medicine Infectious Disease. I've included as a way of preparation for this session, there are a lot of slides. I'm sure you've probably seen the content materials already and maybe even had a chance to review them, but we're going to fly through this, a lot of stuff. Those slides are there mainly for your review and your study and as a reference for you. There are references at the end. I'm mainly gonna go through very quickly and emphasize the things that I think are important on some of these topics. I won't read the slides to you. There's a lot of detail there, but that's there more for your study and review. So we're gonna be going very quickly. And again, I'm just gonna be emphasizing this go through, but we want to try and get through all the material. For that reason, I mean, we do have some polling questions that will help highlight some things as we go through, and that will be a little bit interactive for you. But if you can hold most of your questions to the end, if we get through and we have enough time, we will spend time if he has specific questions on the end, but I'm mainly want to get through all the materials. So with that being said, we'll go ahead and commence at this point. Okay, so this session is, these are learning objectives. We're gonna describe the agents transmission and public health control of WHO's globally significant infectious diseases. As part of that, we review vaccine preventable diseases and immunizations. We'll also talk about the diagnosis, treatment, prevention of infections of clinical and public health importance. And lastly, when we have time, we'll define and describe important examples of emergent infectious diseases like SARS-CoV-2 and COVID-19 or Zika and things like that, as well as biological terrorism agents. But if we don't get to that, that's not gonna be as much of a problem for you. The last thing I wanted to say at the end of that was that for all treatment recommendations, make sure you look up the most current recommendations. Most of these things in these slides are gonna be that way. This slide just reminds you, if you look closely at the leg on this Egyptian steel, the individual has a withered leg and most likely that was due to poliovirus. So obviously these diseases, some of them have been around for thousands of years. The American Board of Preventive says outline on infectious disease, list these topics here. So it's bacteria, viral, parasitic, fungal, spirochetes, atypical bacteria, foodborne illnesses, sexually transmitted diseases, immunizations, and of course, emerging infections. But that's the basic outline of what gets covered. As noted, COVID-19 is probably not gonna be on the board this year, but I'm sure the following year it will be. If you look at Mandel's textbook, he lists all of these infectious disease agents. And it's just a reminder that there are DNA viruses of which smallpox is one of the most well-known ones historically, and then papillomavirus, the Hepatitis A, the different hepatitis, parvovirus, things like that. And then the RNA viruses, which includes the coronaviridae like SARS-CoV-2 and MERS, but Zika and things like yellow fever and dengue that are well-known are also in this group as well. The RNA devices or viruses continue, so you have nasty actors like Ebola and Marburg, but also influenza, which historically has been a big killer of people over time. And then hemorrhagic fevers are in there as well. And then of course, HIV, which has been a scourge for many years and the caliciviridae or caliciviridae, it was just norovirus is the most well-known among that group. And then you have strange things like the prion diseases, chlamydia, mycoplasma, the rickettsiosis and ehrlichiosis like Rocky Mountain spotted fever, and then the bacterial diseases of which we're often in the clinical setting most familiar with or deal with the most, but things like anthrax, Neisseria meningitidis are in there. And then the spirochetes, which includes Lyme disease and syphilis, the anaerobic bacteria or Clostridia are included there, mycobacteria, which includes tuberculosis. And we have the higher bacteria we don't deal with as much, but the mycoses, the fungal diseases like candida, aspergillus and histoplasma are in here. And then we come up on protozoal diseases, amoebiasis, malaria, leishmania, jardi and trichomonas. And they have other things that we include actually as infectious diseases, but it's toxic algae, helminths and ectoparasites like lice, scabies, mites and ticks. So those are all in this category as well. So just a reminder of what the importance again of infectious diseases are, the leading causes mortality in 2016, according to the WHO are often chronic diseases, but you still see in here. And the important thing to note is that HIV AIDS is no longer among the top 10 causes of death. So that's been a recent change since 2015. However, you still see lower respiratory infections, things like diarrheal diseases and tuberculosis there, at least across the globe. But if you look at the developing countries in low-income countries, you still see that five of the 10 top agents, including HIV are still infectious diseases. So at the top of the list are lower respiratory infections, diarrheal diseases, and then again, HIV AIDS is still in there. And then malaria and tuberculosis. So worldwide in developing countries, infectious diseases still predominate and are over half of the total. Looking at deaths in children under age five years and in the neonatal period, again, three of these are pneumonia, diarrhea, and they make up about a third of the total are infectious diseases. So it is still a big killer of infants in the neonatal and infancy period. This brings up our first question. So you can read this. So the first question is an infant formula manufacturer decides to donate formula to a refugee camp. And the question to you is, what would they be effective any on infant mortality in the first six months of life if most mothers did not breastfeed? So take a look at these, use your polling question and bring up what you think might be the issue there for you. So I'm going to see if I can bring my window up and see what you guys have at this point. So I may be having trouble seeing these at this point, but I'm gonna go ahead and bring up the answer here and hopefully most of you got it. The answer for me on this slide is that the infant mortality due to both diarrhea and pneumonia would more than double. And the next slide actually shows that. So if you look at this with a lack of exclusive breastfeeding in the first six months, the partially breastfed infants would have almost four times, almost even up to 10 if partially versus not breastfed at all, it can be up to 10 times as much mortality due to diarrhea and even up to 14 due to pneumonia. So breastfeeding is an important thing to continue and those antibodies that are contained in breast milk are helpful in protecting infants in this circumstance. Doctor, if you look on your side screen, the results are published. You can take a look. Okay, I'll look again just to see. I may just not have the right window up. Let me see if I can bring it up. Yeah, I apologize that I may not see it, but Mark may allow you just to refresh us all when that occurs. So I'm going to go ahead and continue. So the decline in infectious diseases in the 20th century was significant and that just shows a lot of the reasons for that decline over time. And so a lot of it was actually even before we had things, but vaccines have been an important part of that decline. And so vaccine preventable diseases are very important part of clinical preventive medicine infectious disease. So when we look at the annual and current reported illness due to vaccine preventable diseases, at the term of the century, there were about a million cases and of each of these diseases are listed on the left-hand side. With very few adverse events around the turn of the millennium being about 6,000. But by that later date, then that balance came where actually there were more cases of disease or adverse events due to vaccines that were almost double what the illnesses were. But the illnesses remember have been reduced from that 1 million to about 2,000. And the illnesses remember have been reduced from that 1 million to only about 6,000 cases. So very important impact that vaccines have made over time in this situation. And people forget, but I mentioned smallpox earlier, the last case of smallpox was 1977. So the only disease that I know of that's actually been entirely erased from this country and actually the world is been re-erased due to the miracle of immunization and vaccination. And which that actually brings to mind, vaccination was related to vaccinia virus that was part of the original smallpox vaccine. So people forget that this was a horrible killer and a scourge of humanity, but it's now no longer existent except in a lab at CDC and a lab in Moscow anymore. So no longer existent on the earth. There are other disappearing diseases. Measles has been declining, although there's been resurgences due to rotation recently. Polio, we eliminated from the Western hemisphere in Europe and we're getting close to doing it worldwide. But things like this on the far right, you see the thumb sign from epiglottitis that the office ends of B used to do. And so we used to not do any kind of a exam of somebody with a severe sore throat in the department but because we were worried about, inducing laryngism in that situation. But immunization has actually reduced this to significant degree so that we don't worry about a lot of these things anymore the way that we used to. This is a long list now of vaccines, preventable diseases. And you can see, it's a pretty long list and the list is growing. So we have several that are more recent like dengue and Ebola that have been added. And we're hopeful obviously during this timeframe in the next few months or so that we'll have one against SARS-CoV-2 or COVID-19 as well. So just a quick review of the principles of immunization. So immunity, remember, is the ability of the body to tolerate itself by eliminating foreign material. And antibodies are specific binding proteins that remove these foreign substances. Antigens are the foreign substances themselves. And the immune response is the action of the antibodies to help remove these antigens. Active immunity is the immunity produced by a person's own immune response to an antigen stimulus. That lasts for many years, often can be lifelong. Passive immunity is immune protection that's acquired by transfer of antibody produced by another human or animal, usually by an injection. But there are other means to do that. The protection tends to wane over time as antibody degrades, usually within months. There are several different types of passive immunity including homologous pooled antibody. I give you some examples here. There's homologous human hyperimmune antibody, and those exist for hepatitis B rabies, varicella, and vaccinia immune globulin. And there's also a heterologous hyperimmune serum, which would often cause anticoagulant antitoxin. And it's a high titer antibody usually produced in animals, most often horses. Though you may have actually heard llama antibodies being described as a potential for this type of antibody against SARS-CoV-2. So vaccination is this stimulation immune system to produce response similar to natural disease, usually by injection of antigens into the body. And the antigens can be either inactivated, which means killed, or live and attenuated, which means weakened. So for live attenuated vaccines, these are weakened viral or bacterial agents. These replicate to produce an immune response, often effective with only one or two doses if they're live. But circulating antibody can blunt the response and vaccine potency, because they're live, may be unstable, especially if something's affected the way it was stored. Excuse me. And the reversion to wild type, as in the case of polio vaccine, can occur and cause disease. But they can be given at the same time with other live vaccines. But if you don't do that, a live vaccine, you need to wait at least four weeks in between those. So that brings up another question here. This is a little bit long, but you have a patient, a 61-year-old man, who comes to your travel clinic to get a vaccination for a cruise up to Amazon. And he lets you know that two weeks previously, he went to his primary care provider. He got the first dose of hepatitis A, parenteral typhoid, and a routine vaccination. Gets shingles, this time with Zoster vaccine live. If you know that he's otherwise healthy and accepts the aid to save the risk of vaccination, what advice would you recommend at this point? And I think you have a chance to use the polling device. So, doctor, just a reminder, as all the votes are coming in. So when you look on your screen, once I hit publish poll results, there'll be a button that says view results right underneath the chat so that you'll be able to see the results if you click on that button once I publish the results. All right. So I'm gonna go ahead, I'm not, unfortunately I'm not seeing that link as well, but I'm gonna go ahead and give the answer here as we go forward. I published the results right now. Yeah, 16 responses, so if you click view poll results, show results right underneath the chat. Okay, it's much further down on my screen, so I apologize for that. So I'm gonna go ahead and give you what what the answer is here, if I can get toggle between my screens, and it is answer C, so it's defer yellow fever vaccination for at least another two weeks. Remember I said that two live vaccines need to be separated by at least 28 days, so about, you know, four weeks. So you would tell them to defer yellow fever vaccination for at least another couple weeks in this case. So inactivated vaccines are also classified sometimes as wholesale or fractional, and often they require more than three doses for a response. They're not generally as effective as personalized vaccines. The immunity wanes over time, and often boosters are required, but they can be given at the same time or together in combination vaccines, which we often do for some of these vaccines in children, just to reduce the number of shots that they get. So again, wholesale, fractional, there's some examples here of those. Polysaccharide is another subtype. You need to know that these are the least immunogenic. They're T cell independent, so there's no consistent response in children under age two. Booster, no booster response, so we don't tend to use these children. More immunogenic are the conjugate polysaccharide vaccines, and those are T cell dependent, and so we can't use them in younger age children. Other types, recombinant vaccines use genetic engineering to acquire pure antigen for use. Sometimes we attenuate an organism, oral typhoids, a type of that, and adjuvants can be included to help enhance the immune response. Most often we use aluminum compounds, particularly aluminum hydroxide, but we have used oil emulsions, particularly a vaccine used in Europe for that, and there's been some other examples here in the U.S. now, and they can also increase the reactogenicity of the vaccine, so you often get larger local reactions sometimes with that, so you have to be a little careful with those. It's important to know and to use vaccine information sheets that are required, especially by the childhood vaccine regulations, but they inform the patient about the vaccines, what the potential risk and benefits are, and then you can always download the most current versions of these from the CDC website, so remember to use these. There are also vaccine schedules for each age group and also sometimes by risk factors, so this is kind of a parent-oriented vaccine schedule that you can use in your office if you need to. For the health care providers, there's more details here, often with some notes that you can use, but it tells you at what age they're indicated and how many doses and how to do catch-up schedules, so important things to be aware of and know, and you can get all these off the CDC website, so you should know that they're there and know how to use them, and remember that even adult immunizations can be age-indicated, but in addition, there are also risk indications based on chronic diseases, so you see those at the top of the column, and just be aware that you, when you're using immunizations and vaccines, that you need to be aware of these and know when to give them if you're in the clinical setting. Now this is a slide to remind us visually of what the importance of polio has been in the past. Often it would paralyze, you know, patients so much that even their breathing was compromised, so they used iron lungs to help these patients breathe until they got past the weakness induced by the polio, and in fact, many people would not even go to, because it is fecally orally transmitted, they would not even go to the pools in the summertime because they were worried about catching polio itself, and even Franklin Delano Roosevelt was in a wheelchair due to polio himself. So again, first discovered in the late 18th century, and it is an enterovirus, had three serotypes, has that fecal-oral transmission I mentioned, it attacks the motor neurons and produces the classic flaccid paralysis, and even in 1952, just before some of us came on the scene, it was 21,000 cases in the U.S. As I mentioned earlier, it's been eliminated both in the western hemisphere in Europe and most of Asian Africa, but it's still hanging on in a few locations. So the main locations where it's still endemic are in places, areas of conflict, so Afghanistan and Pakistan, although there are some vaccine associated cases elsewhere. You notice that we've lost some ground a little bit in the eradication program, so that in 2020, there were 84 cases of wild polio and 208 cases of vaccine associated poliovirus, whereas the previous year in 2019, there were only 64 cases of wild polio. So we're still working on that. Unfortunately, current events and conflict have made our situation much more difficult than trying to get rid of this. So remember, now in the U.S., we use the inactivated poliovirus, but in places where there's still wild poliovirus, we still use the oral poliovirus. Just remember is it can revert and cause vaccine associated polio in the case of the oral poliovirus, but because it is, you know, shed in the stools, you can sometimes get secondary immunization of, you know, other children when you use this in terms of a polio campaign. Diphtheria is another disease that's been known for hundreds, if not thousands, of years. Hippocrates described this in the 5th century BC. It is caused by an aerobic gram-positive bacillus, and that produces a toxin with gene transfer by viral phage. Incubation is about two to five days. It affects the mucosa, but it produces in the picture there this eggs that sometimes can actually cause respiratory obstruction, and the most complications, however, do the toxin that it elaborates, which in acid cause inflammation of the heart and neuritis, and the early use of the antitoxin reduces these complications, but even as late as the early 1990s in former Russian states, there were 157,000 cases with 5,000 deaths. So tetanus was another disease described by Hippocrates. It's an anaerobic gram-positive spore-forming bacteria clustered in tetany. It's found in spores in the soil dust and animal feces. Usually occurs by wound contamination, so that's why we usually give the immunization related to dirty wounds. The incubation period is about eight days, but the toxins bind to the central nervous system, and they cause unopposed muscle contraction and spasm, and these spasms can persist for several weeks with a very prolonged recovery period, and there was also neonatal tetanus that would occur because of infection of the umbilical stumps if they use a dirty knife or something to cut the cord, and so even that caused over 215,000 deaths in 1998. So we first introduced passive immunity as we described that earlier for you in World War I, and by World War II, we had the tetanus toxoid, and these are just some dramatic, you know, pictures of the spasms that occur, and you might remember that it was often called lockjaw because of the spasms of the masseter muscle. It's a person at increased risk that never got a full primary series of three shots, also the injecting drug users, older adults that are more likely to have not gotten that full primary series, and diabetics are more at risk, and this is tetanus within the United States over time, and it just shows that age-associated increased risk. These are other categories of the types of injuries and conditions that cause tetanus. I'm sure you're pretty familiar with all these. Pertussis is another highly contagious respiratory infection that caused by bordetella pertussis. It also is another toxin-producing kind of bacteria, and it attaches to cilia in the respiratory tract, and these antigens allow evasion of the host defenses. The systemic disease is toxin-mediated, and again, a large number of deaths worldwide in 2001. Even in the U.S., we had almost 17,000 cases in 2009 with 12 infant deaths. There was a big outbreak in California, some of you may remember that, and 10 of the days in the 2010 outbreak, and we still have periodic state outbreaks of this. The Tdap, or tetanus diphtheria acellular pertussis vaccine coverage, this is a 2015 show of the state coverages, which is still very variable, as you notice, as to how well we get coverage in that young adolescent group where this is indicated. Again, the incubation period is five to ten days. It can onset like a cold, a common cold, with a nonspecific cough, with not a lot of fever, but that catural stage, which lasts one to two weeks, can then have a paroxysmal cough that lasts several weeks. So, if you have a cough illness that lasts more than 10 days to two weeks, you need to be thinking pertussis, particularly if it's in a pediatric population, and there's a fairly high secondary attack rate, and adults may also be included in the spread of pertussis. There are a lot more complications by age, so again, the very young and infants less than six months of age are the ones that have the most problem. It can include seizures, encephalopathy, and death. We have had a lot of reduction of disease in the United States with the DTP vaccine, but there was a slight rise, as you noticed, in the late 1990s and early 2000s, which led to the introduction of the Tdap booster because of that rise in adolescence. So, that's why we developed the Tdap vaccines. So, when you do case control measures for a recognized case, then under-immunized contacts should be vaccinated. Any diagnosed symptomatic cases should be excluded from school day care until at least five days are on antibiotics, or if they choose not to take antibiotics, they need to be up for a longer period, for 21 days. The usual treatment is azithromycin, and household or other close contacts should also receive antibiotic chemoprophylaxis. This is just a reminder of the alphabet soup relating to DTaP, Tdap, and all these, and what it means, and you can kind of look at that over your own time, but I know that you are familiar with this. It's just a reminder. There are Tdap vaccine options and recommendations. We had two manufacturers, both first licensed in 2005. They both contain aluminum adjuvant. I have similar antigens contained in there. The initial vaccination is recommended at age 11 or 12. Some states, including my state of Virginia, mandate this, and then at age 13 to 19, there's a catch-up vaccination if not previously vaccinated. If you're 19 or older, you need at least one adult dose, and in certain circumstances, like in children age 7 to 10, if not previously vaccinated, need to be, but the one you should be aware of here is there is a vaccination recommendation for all pregnant women who should receive a dose in pregnancy regardless of their previous Tdap vaccination status, and the optimal timing for the dose in pregnancy is at 27 to 36 weeks, so that brings up this question, which it says there's a 21-year-old woman that's seen for initial prenatal visit. The immunization record shows she had a Tdap vaccine at age 18 but did not get an influenza vaccination in the fall. What's the best recommendation for her in this pregnancy? So I'm going to go ahead and bring this up for you, and the correct answer here is to give an influenza vaccination now and defer the Tdap vaccination until the optimal period of 27 to 36 weeks. Influenza vaccination, we'll get to this in more detail later, but is now at any trimester, you should get that. But it's still never too late to give influenza vaccination. Tetanus wound management, just a reminder, if you ever work in the urgent care or in an emergency room or even maybe within your own clinic, that if they don't have a recent vaccination history, do boost them. And if it's a clean minor wound, may not be needed, but all other wounds, you may want to give it. If it's a really nasty wound and they're not up to date, you might need to give immune globulin as well. So there are some adverse events, rare serious neuropathic events, especially in infancy. But the Tdap vaccines, the acellular ones, are less likely to be ractogenic, and they have similar rises in the antibody titers. There are other bacterial diseases, such as haemophilus influenza, I already mentioned the epithelial titus that occurs with that. It also can cause a preceptal cellulitis, as well as otitis media and less serious. But the meningitis was one of the biggest problems with that. And so that's one of the reasons that this vaccine was very important, because there were some serious diseases that could be caused by it that were life threatening. There are very many vaccine options, and there some cases are conjugate vaccines. They can be interchangeable for primary series or booster, but there's no demonstrated benefit in preventing disease due to the non typable strains. This is just a reminder slide that as people, and we've had some anti-vaccine, and certain communities where vaccinations was not prevalent, but that reduction in measles vaccination, MMR vaccination, and now it's a combined vaccines, measles, mumps, rubella, and varicella, is that we've seen increases in measles cases, and measles is still a very severe disease. And it's certainly still a global problem. 100 million measles cases and 6 million deaths per year in the pre-vaccination era, and even in the last decade or so, WHO listed 266,000 imported cases and 134,000 estimated deaths as of 2015. The imported cases are the ones that occur most often in this country, but then if you don't have a good herd immunity, you can have significant spread. Again, Amish Orthodox Jews have been, but also philosophical exemptions in areas like Washington State. And so we've certainly seen measles outbreaks is still a significant concern. This is kind of global coverage as of 2015, and just a reminder there in the lower right corner is that measles is a leading global cause of mortality among vaccine-preventable diseases. This is the pyramids. A lot of people, because we had pretty much erased it, aren't used to seeing the measles rash, the coplick spots, or this little red punctate rash in the oral pharyngeal mucosa, but it causes a fever, conjunctivitis, cries of cough, and then the characteristic rash. The incubation period is 7 to 18 days, but it can be communicable one day before the proton. Very highly infective. You've probably seen things about the rho status for R0, meaning for the infectious infectivity of the COVID-19 virus, but measles is many, many times higher, and so it's very, very communicable. And aerosolizes and easily transmitted. So you get this red blotchy rash that begins first on the face and then becomes generalized, the coplick spots that I've shown. In developing nations, there's a case fatality rate that rivals the current pandemic, 3 to 5%. It can be as high as 10% in some areas, and that mortality is higher in areas where there's poor nutrition, and vitamin A deficiency particularly creates an increased risk of blindness or death. So in refugee camps, you want to make sure that people have both measles vaccination and vitamin A supplementation. A lot of other complications, everything from pneumonia to acute encephalitis. There is this late complication that's still occasionally seen of subacute scleroselin panencephalitis that occurs many years after the infection. Mumps is also another problematic disease in this category, a paramyxovirus. It can cause architis in males after puberty, and then can get even sterility with testicular atrophy. Aseptic meningitis occurs in about 10%, and actually this is one of my excuses for the impairment in my intelligence, because I actually had mumps back in the day with aseptic meningitis, and I can tell you it wasn't fine. There is airborne and droplet spread. The illness occurs 16 to 18 days after exposure, but again vaccination has markedly reduced it, but we still have occasional outbreaks in the U.S. and the U.K. because of some of the vaccine opposition. The so-called German measles caused by the ruby virus had the problem, the congenital rubella syndrome, that occurred in a lot of women if they were infected in the first trimester. It could cause spontaneous abortion or deafness, cataracts, microcephaly, and retardation. They had an epidemic in the early 1960s with an estimated 12.5 million cases, with 21 cases of this congenital rubella syndrome and 11,000 fetal deaths. So now we get this MMRV combined vaccine with live attenuated virus in all four components. It can have rash, fever, adenopathy. The initial vaccination is given at 12 to 15 months with a booster at 4 to 6 years. If unimmunized contacts of measles case, the vaccine should be given within 72 hours of exposure, but immune globulin can be given if a live vaccine is contraindicated. I've already mentioned how important it is to use measles vaccine in refugee camps if you do any of that kind of work. This just shows the decline in the congenital rubella as we began to make the vaccine more available and more widespread. Especially after those early 1960s problems, we were able to reduce the congenital rubella significantly. Varicella has a high attack rate. Back in the day, it would have 150,000 to 200,000 patients and 10,000 hospitalizations and even 100 deaths annually. Deaths and severe complications were more likely with advancing age. If you didn't get it when you were a small child, it was often more problematic if you were an adult. It's now required by law in many states. It is a live attenuated virus. It's very immunogenic and effective in preventing disease. It causes a persistent immunity and there is a 4 to 5 times lower risk of shingles later in life if you had varicella vaccine when you were a kid. However, because it's live attenuated, it shouldn't be given to anyone who is immune suppressed. Again, this is why it's important to have some herd immunity to protect those that can't take the vaccine. There's now newer versions of the vaccine for prevention of shingles and postherpetic neuralgia in older adults. We'll talk about those as well. As we noted, it's in the combined MMRV vaccine. For shingles vaccines, there's two FDA approved vaccines. The first one out was this live attenuated vaccine and it was given as a single dose. It's actually not as immunogenic as the second recombinant vaccine that became available around 2018. It's more immunogenic so it's been given by age 50 or as the other vaccines given after age 60 or so. It can be given even if you had prior disaster or live vaccine. It's not necessary to screen for history of chickenpox verbally or by serology or either reason. You don't need to do that. We do have vaccines that get strep pneumonia as well, a bacteria that is colonized or the upper respiratory tract. Before vaccine, streptococcus pneumonia was a leading cause of meningitis in kids with 700 cases per year. It could cause sepsis, otitis media, about 200 deaths annually due to invasive pneumococcal disease. The case fatality rates increase in higher risk groups in older folks, those with anatomic or functional asplenia, that have immune suppression such as complement deficiency or those with chronic diseases. Antibiotics have helped to reduce strep disease and fatalities, but the vaccines are, in my mind, the more important protection. The first vaccine available was this 23-valent pneumococcal polysaccharide vaccine. Later, there was a 13-valent conjugate vaccine, which is a capsular polysaccharide and protein complex. That was first 7-valent, now it's 13-valent. It did show that it covered most of the serotypes that were responsible for disease, with the polysaccharide vaccine covering another 13%. The initial 7-valent vaccine, this is the reductions that occurred in the disease in children, invasive disease. So, very important, showing how, again, how vaccinations can make a big difference for us. So, it's indicated in children from age 6 weeks to 71 months. It's a 4-dose series that normally starts at 2 months of age and goes up to 12 to 15 months. Healthy children get a single booster up to almost 5 years of age. In certain medical conditions where there's higher risk, such as the asplenic or functional asplenia with sickle cell disease or diabetes, they can continue to get a booster up to age 6. There was a period, actually, where ACIP was recommending and still recommended it in people that were adults with increased risk factors that are listed here. After age 65, it's shared decision-making now, and if you do happen to give the PCV13 first and over 65, then you would follow the polysaccharide vaccine after 6 to 12 months. However, if your only indication is being over age 65 and you decide not to give PCV13, then just give the pneumococcal polysaccharide vaccine as a current recommendation. The polysaccharide vaccine has 23 serotypes, and it's just the 13 with the conjugate vaccine. The indications are listed here. The one I'd really mention to you is that, at the bottom, is that people that we see often in the clinical setting are smokers, asthmatics, and patients with diabetes mellitus. All these should get the polysaccharide vaccine before age 65 with a booster after age 65. You should be aware of that if you're regularly seeing patients with chronic disease or clinically in adults. Again, I mentioned the boosters, and these are the recommendations for that. Usually, no big problems with this other than local reactions. There is a very excellent vaccine for hepatitis A, this infectious hepatitis. It's an RNA virus that has fecal-oral transmission, so people that travel are at risk, but there was some transmission within the U.S. Initially, we started doing it in certain areas in the western U.S., but military, those that are travels, and those that have high-risk lifestyles, such as drug users and men who have sex with men, needed it. This, again, just shows what the regional prevalence was of hepatitis A, but was reduced significantly after we started vaccination on an almost universal basis. That's the decline that occurred after the initial recommendations and continued use at each of these age groups. Hepatitis B is another very common infection worldwide. About 2 billion infected globally, 350 million that get chronic hepatitis B, more prevalent in Asia and Africa. Many of those that have chronic infection will get cirrhosis, and there is a significant link to hepatic cancer. This is obviously a disease that we want to try and prevent if we can. It's mainly transmitted by blood or body fluids, and in those cases of high endemicity, most of the transmission is actually vertical, meaning perinatal. Those that get it in the perinatal period have a very high probability of getting the chronic infection. If it's intermediate endemicity, the transmission is somewhat mixed between perinatal and horizontal transmission. In low endemicity, it's mostly infections through sexual interactions and things like that. These are the risk factors for hepatitis B in the United States in the early 1990s, and these tend to be somewhat similar still. The important thing that I've already mentioned is to note that if the mother is infected when she delivers, then there's a very high percentage of the infants that become infected, especially if they're HPE antigen positive. But even if there's hepatitis B surface antigen only, there's a significant number of infants that become infected. For this reason, the USPSTF makes an A recommendation to screen for hepatitis B in pregnancy. You may have trouble, as I do from time to time, interpreting HBV serology. This is just a nice little link and also table for you to use to help interpret those that you can always refer to when you're trying to review a panel that may come back on somebody you've done screening for. This brings us up to a good occupational health question. You have a healthcare worker that during pre-employment evaluation is found to have a negative hepatitis B surface antibody after completing an initial three-dose series of hep BV vaccine. What option would you say would be the best compromise to officially afford optimal protective antibody response? The answer to this question is a little bit of a judgment thing that I think still has to be proven out, I think, by a controlled trial. The answer here is the two-dose series of the hep B CPG vaccine, which is a newer vaccine that's actually given in just two doses, and these are reviewed here. The original vaccine was the three-dose series in children or adults. In the adults, it was given on 0, 1, 6 months interval, but this newer vaccine has a novel adjuvant and it was approved in 2018, but it's a two-dose series over one month, and they show data from the studies that suggest they have a 90 to 100% seroconversion with that. Again, I don't know of any head-to-bed study, but I would like to see it that compares this vaccine to the others, and those people say they're getting hep B vaccine as a healthcare provider and haven't shown that they develop a protective antibody response, is whether you could get that. This is just one that's a thought that it might be an educated guess, but I do think we need to see those studies that would do a head-to-head to see if you could increase your seroconversion rate, protect the antibody, and reduce the number of non-responders. Again, those with occupational risk and others in certain risk categories should get this vaccine, but it has decreased by 96% the adolescent cases, particularly with heterosexual transmission in the U.S. The indications, again, should be that you want to do testing four to six weeks after the third vaccine dose to see if people develop a protective antibody response for the occupational purposes, but about 5% don't respond after the sixth doses, so the usual thing is to, if you get the first three, no antibody response, you do the second three, or maybe the two if you use the hep B-CBG vaccine, then you would want to check it again. If it's still negative, then you would check and see if they're actually a carrier and they're antigen positive, and that's often a finding that you find in non-responders. If a non-responder is later exposed, you just treat them with the hep DUSB immune globulin as post-exposure prophylaxis. So that brings us to influenza. So influenza pneumonia among the top 10 causes of death worldwide, the epidemics occur every winter and about 200,000 hospitalizations on average, 36,000 deaths. As you know, we've already eclipsed these number of deaths with the current pandemic, the SARS-CoV-2, but all age groups are susceptible. The rates of infection are highest among children, but those that are elderly also are at increased risk for those with chronic medical conditions. That's sort of what this graph shows, is that the very young and very old are most at risk, but the great transmitters are actually in the school-aged children right in the middle. The viruses, it's an RNA type orthomixovirus. There are three types, A, B, and C, that infect humans. The type A viruses have these surface proteins that aid in their ability to infect people. You have the hemagglutinin, the H, and the neuraminidase N, and each of these combine to produce HN subtypes. The type A influenza is the one that typically causes the pandemics in terms of the influenza virus, and it has to do with both that antigenic grift, which is slight changes that occur from year to year, or the antigenic shift is really more major changes that occur before a pandemic. This kind of reminds us back of the swine flu, the influenza. I don't think it started this way, but it's kind of a graphic reminder that they can go from birds to mammals like pigs to humans that are in close interaction with these species, and that's where some of these changes get incorporated. Back in the day of H1N1, about a decade or so ago, our last influenza pandemic, it's actually the age group that was most effective was the younger age groups, and not so much the older age groups. It's a little bit of a flip side of what's, in terms of morbidity and mortality, is occurring with the current SARS-CoV-2 pandemic. The influenza epidemiology is this cycle of epidemics and pandemics. Usually one strain is pedromena, but sometimes you have both A and B strains circulating. The activity is monitored in the U.S. by inputs like illness surveillance, pediatric hospitalizations, mortality from pneumonia and influenza in 122 cities, and then the global laboratory-based surveillance of strains with regional reports filling in the gaps. This is the late curve that occurred with H1N1 when it was first discovered very late in the year. The major peak and second pandemic wave actually occurred by week 42 or so early in October, and that was that last influenza pandemic. This just shows, again, a type of surveillance that we see. Most times the peak incidence tends to be in the early part of the year in, say, late January, early February, and March that the peaks occur. So, clinical period, the incubation is usually one to four days. There is a period shortly prior to the onset that it can be communicable, and sometimes children can shed this for a longer period of time, including in their stools. The signs are mostly fever, muscle aches, headaches, and dry cough, but the course is usually two to seven days. In children, you want to avoid aspirin use because of Reye's syndrome. It's a complication, and the diagnosis is suspect if in the community, and there are other things that can masquerade as we well know. There are antiviral agents. The main ones that we've used in recent years is the neuraminidase inhibitors, ulcetamivir and zanamivir. There is a newer kit on the block that I don't think is in your notes, but this is the valoxavir that can be given as a single dose of two pills, and it has a similar way of reducing. The illness is reduced by about a day, but you need to give it early if you can within the first 48 hours, and that can help reduce severe illness and death as well as shortening the illness itself. Usually we use inactivated viral vaccines. The current 2019 to 20 strains are listed here. A quadrivalent vaccine adds an additional B virus to the mix, and we now have cell culture-based egg-free vaccines. We have high-dose or oil emulsion vaccines, but note with these, there often are increased reactogenicity and local side effects, and even for those that don't like needles, you can have the intradermal vaccine or actually the live attenuated virus, which is noted here. That's administered by a nasal spray. It's cold adapted, so it doesn't reproduce down in the lungs. There was a period where we didn't have a good match for the H1N1 strain, so there was a period where it wasn't recommended, but it's now again recommended for general use in those aged 2 to 49, but contraindicated because it's attenuated in the immune suppressed in pregnancy or children from 2 to 4 with a history of asthma. The side effects are usually nails, drip, or congestion since it can cause upper respiratory symptoms. Since March of 2010, ACIP has recommended influenza vaccination for all people over age 6 months of age, especially important for high-risk patients, including those in nursing homes or chronic care facilities, those with chronic diseases, including diabetes. Again, I mentioned earlier, pregnant women in any trimester of gestation should get influenza just because they're at increased risk and there's no problem in giving it at any point, and then healthcare workers, of course, both for their own protection as well as patient protection, and it's very important since infants can't get this under age 6 months to make sure the family members surrounding them are immunized. Meningococcal disease, this is a graphic representation of somebody with meningococcal sepsis, but it's a very scary, fulminant disease when it occurs. There's 13 serotypes of five strains, BACY and W135. The most common ones in the U.S. are the B, C, and Y. It has a nasopharyngeal carriage and can be transferred person to person. Disease rates are highest in infancy, and 20% of the cases can occur in adolescents and young adults. Very rapid onset of severe disease with death in less than 24 hours, somebody can come in looking as healthy as a horse, and again, literally within a day be deceased. So up to 40% case fatality rate before antibiotics, college freshmen living dormitories or at higher risk, and then the risk is increased with crowding, so that travel to endemic areas such as sub-Saharan Africa and to Mecca during the Hajj have been associated with these kinds of infections. This shows the annual incidence of severe meningococcal disease, C and Y, and how that has dropped with vaccination over the years. As the different vaccines came out with increased coverage, you had anywhere from 94% decrease to 64% in later years, but again, significant impact of vaccination. The meningococcal conjugate vaccine was licensed in 2005 with age group 11 to 55. Again, it was the main four constituents, but it was harder to produce a B vaccine at that point, but it helps prevent the invasive disease and also reduces the nasal carriage rate and improves herd immunity. It's more likely to get a favorable booster response because it's a conjugate vaccine is given a single IM dose that's boosted at age 16. Again, age 11 to 18 with the booster recommendations, those of anatomic or functional asplenia should also get some doses later and be dosed every five years. The polysaccharide vaccine is not as immunogenic, and so we don't use it as much, but the MCV-4 is the preferred vaccine. However, there is a vaccine now for the B strains, and there's two of those available. They are purified recombinant, and they're recommended in outbreaks or in those who have complement deficiency or functional asplenia. It's estimated to reduce maybe 15 to 20 in cases and two to five deaths yearly, so the cost-effectiveness is reduced because of the rarity of the disease, but it can be given and is effective at reducing disease. Has some adverse events mainly at the injection site and some systemic complaints as well. As recommended, if you have a meningococcal case, adult close contacts, usually household or maybe a girlfriend or something like that, or a spouse, they should get chemoprophylaxis with either ciprofloxacin or ceftriaxone, but this doesn't mean everybody that walked through the emergency department when a meningococcal sepsis case came through. It's just people that were like maybe intubating or did resuscitation. not everybody needs this. But it does eradicate carriage and avoid sepsis complications. And vaccinations that require seven to 10 days to be effective is not really that helpful. It's more the chemoprophylaxis. There is a rotavirus vaccine. Historically, it's caused a lot of vomiting, fever, water, diarrhea, especially in young children, causing several hundred thousand deaths worldwide and even in the U.S. before the vaccine come out. But it's been able to help reduce the hospitalized cases and deaths. The fecal-oral spread only requires a very small inoculum of 10 to 100 virus particles, and the incubation is relatively short. So the first reduced vaccine had a complication that was linked to intussusception. There was a safer vaccine introduced in 2006 and a three-dose series that's very effective. It had a 45% decrease in pediatric gastroenteritis. There is also a monovalent vaccine approved as of 2008 that only has a two-dose series at two and four months. Relatively safe, and actually the relative risk has been reduced so that it looks like that these are a good option, and the initial problem with intussusception is probably more a risk from the vaccine or the disease itself. Just a slide to remind you that reminder recall systems as well as provider assessment feedback and multi-component interventions, including standing orders for vaccination, are important tools to increase vaccination coverage in general. So from there, we move on to other infections of public health interest. Foodborne illness is a very large one of these, almost 10 million episodes and 56,000 hospitalizations on average per year. Some of these include both infections and intoxications. Some toximating agents include Staph aureus, Bacillus serius, Clostridium botulinum, and E. coli. But other infections such as norovirus, Salmonella, Listeria, Campylobacter, and Hepatitis A, which we've already mentioned, are problematic as well. This is just a quick graph of the causes of foodborne outbreaks that you aren't aware of. You notice that a very big chunk are the two biggest slices of the pie here, those that are unknown, but also the norovirus. And the norovirus is particularly problematic many times. It's usually recognized by the occurrence of indulge sharing a meal, often may go unrecognized as an initial event. The general preventive medicines are keeping food surfaces clean, using good hand washing, and separating raw and cooked items, especially during prep, and using surfaces such as glass, stainless steel, and so on that can easily decontaminate it. You cook throughly to correct temperatures, maintain proper food temperatures, and especially starting with safe water and raw materials. I mentioned norovirus is a big problem here. So it is a non-enveloped RNA virus, E. coli virus. It's the most common cause of non-bacterial acute gastroenteritis. Again, very low inoculum to create disease, as few as 10 to 100 virions. Transmission via fecal oral root, but also fomites and aerosols have been suspected. The symptoms of nausea, vomiting, diarrhea can be pretty prolific. Begin relatively soon after exposure, last fortunately just usually a day or two, but very easily spread. You can identify the virus as stools through various means listed here, and that can help verify what's the cause. We do call this sometimes winter vomiting. It does seem to be cyclic and occur during the winter months more often than it can occur theoretically any time of the year. It's very difficult to eradicate. It resists freezing, heating, dilute hypochlorite. It's not very responsive to being eliminated by antiseptic alcohol-based hand gels. You need much longer, larger amounts and longer dwell times. And you've heard, I'm sure, of institutional outbreaks, especially on cruise ships and in some other institutional settings. So it's a very problematic virus to get rid of. The protective measures are to isolate ill personnel, especially if you're a food handler, remove them from handling food products or preparing foods. Use good hand washing with copious soap and water. And the non-porous surfaces should be disinfected with higher concentrations of bleach solution. Carpets, other porous surfaces should have soiling removed, but chemical disinfection, and then steam clean. And you treat rags and trash as biohazards in these cases. Salmonella endercoli is caused by several different strains and serotypes of the bacteria. Often has fever associated with it, along with headache, nausea, and diarrhea, sometimes vomiting. Incubation is relatively short. It can be cultured from stool blood. You can have infection from contaminated food products, such as processed meat. Poultry is a big offender, eggs and dairy products. Again, can be transmitted by fecal oral route from person to person, and carrier states can occur. Rehydration antibiotics in some cases are needed. Staph food poisoning, if you've seen this, is very kind of abrupt with a lot of nausea, vomiting, cramps, and diarrhea. It's a heat-stable enterotoxin, and you can confirm it by finding the organisms of the same phage type in stool or vomitus of two different persons. And you can also find large amount of enterotoxin in the specimen from the same case. The treatment is mainly just symptomatic treatment of the nausea and vomiting. Bacillus cereus also causes similar kind of illness. It's an aerobic spore-firming bacteria. Important to notice that the spores survive in boiling and can germinate later. So you have cooked rice, you leave it out at room temperature, and then reheat it later, then you can get illness from this disease. It has both the heat-stable and heat-label toxins, but again, you want to avoid by promptly refrigerating it after cooked rice if you're going to reuse the cooked rice. There's this sugar toxin producing E. coli. The most common serotype that we're familiar with is O157H7, first detected in U.S. and Canada early 80s, but it is a problem in cattle-producing regions. The disease is contamination of food by the feces of the ruminants, and the infectiousness is relatively low. So poorly cooked hamburger meat, leafy spinach products and lettuce, even apple cider and unpasteurized milk with contaminated water and ice has been noted, and we even had person-to-person transmission in daycare settings. So the diagnosis can be done relatively quickly by ELISA or immunochromatography of stools. There have been some other serotypes of E. coli that produce similar illness, but they're all sugar toxin producing. So the effects of that is this bloody diarrhea. You have renal tissue damage. You can also have hemolytic uremic syndrome. The neurotoxicity can occur with some affecting the central neuro system, including paralysis and deaths. The enterotoxicity is the watery diarrhea, but you also with the hemolytic uremic syndrome can get coagulation abnormalities. So this is the spectrum of that severe STEC infection. The important thing to notice here is that antibiotic therapy, particularly fluoroquinolones, may actually increase the phage and toxin production. So you want to avoid those. And the prediction of the bad, worse outcomes are dehydration, oligo or aneurine, and very high white cell counts or reductions in hematocrit. But again, avoid the fluoroquinolones or antibiotic treatment. There is some suggestion of azithromycin that others may not cause this, but the fluoroquinolones definitely avoid. So to prevent this, we mentioned all we do, they're actually using active immunization of cattle, and then the good hygiene practices and surveillance in the food chain is important. There's other E. coli enteritis. The enterotoxigenic strains are a major cause of traveler's diarrhea. You also have enteroinvasive strains and enteropathogenic strains that have been observed over time, and all of these are part of the spectrum of disease of E. coli. The traveler's diarrhea is defined as a twofold or greater increase in unformed bowel movements in a traveler. It's usually traveled from a developed to an undeveloped region. The highest risk destinations historically have been Latin America, Africa, Middle East, and Asia, with attack rates up to 20 to 50% of travelers for a one to two week period. So it's usually through ingestion of contaminated food or water, and the most common etiology, as I mentioned, is also the enterotoxigenic E. coli, but Shigella, Capitobacter, Jardiaschus, others happen. Capitobacter is a more frequent etiology often in Southeast Asia. Median duration is relatively short-lived, three to four days, but in 10% of cases, it can last more than a week. So again, being careful about what you eat and drink is important. Peptobismol can be an effective prophylactic, but it does turn your stools dark. Usually we don't use prophylactic antibiotics because symptomatic treatment at the first onset of symptoms with Imodium, Quinolones, or Mycin can shorten the three-day illness to one day or less. And Rifaximin is also another systemic antibiotic option. Cholera, with a picture to remind us in the upper right-hand corner, is one of the early causes. In fact, it's linked to the word quarantine that we use anytime someone's in an incubation period, but it has caused different outbreaks in the past. There are toxigenic strains that the classical and L-TOR biotypes endemic in about 50 countries, including more recently in Haiti and the Caribbean. It causes an aferball, watery, voluminous diarrhea with these characteristic rice water stools. It can cause death within hours if you don't get adequate hydration, but even oral solution is enough to counteract that. In very severe cases, you can treat with either doxycycline, or Lucid, or Mycin in a single dose. And there is now also a single-dose live oral vaccine if you're traveling to an area where it's endemic, if you get it at least 10 days prior to travel. Clostridium difficile is one you should be aware of. It's another spore-forming anaerobic bacillus that produces exotocins. It's a common cause of antibiotic-associated diarrhea, and it's a watery diarrhea, fever, nausea, anorexia, and stomach pains. You can get colonization, and it can include complications of pseudomemoris colitis, toxic megacolon, and issues like that, including sepsis and death. Those may require significant risk factors. Again, prior antibiotic treatment, the use of proton pump inhibitors, having had gastrointestinal surgery, chronic disease, and elderly individuals. The stool culture and antigen tests aren't specific, but the PCR assays are used since we're looking for the toxins in those toxin tests on the stool. You need to do it on a relatively fresh stool if you are looking that way. Remember this complication, the toxic megacolon, and be aware of that in somebody that has the risk factors that we described. So this brings up a new question, interactive question here. Let's say you're working as a hospital infection control consultant in a facility that's currently dealing with an outbreak of C. difficile among its patients. Which intervention listed would be least effective in helping stop transmission to other patients in the hospital? So the answer here, I'm going to go ahead and bring that up, is that actually, again, because it's a spore-producing organism, the alcohol-based hand antiseptics are not that good. So hand washing is much more important, or the use of hypochlorite, and these other kind of restriction movement and basic hygiene message are more important in that circumstance. So it's noted that the spores are here, and you can get these shed in the feces. The infection can resolve, but often it requires 10 days or more of metronidazole, vancomycin, or other antibiotics. We've got to be careful with our use of antibiotics that we don't set this up. The precautions are important, again, in those, and I mentioned here that the alcohol-based antiseptic is not as effective at killing spores, so the hand washing is emphasized. And recurrent infections, unusually enough, have been successfully treated with so-called fecal transplants from healthy persons to kind of restore a more normal bacteria in that setting. So the first line here is that actually, C is considered the most common pathogen in the U.S. Early incidence of 230,000 cases per year until more recent blood screening became available. It's a fairly high prevalence in people in the kind of baby boomer population. It's a cause for 30% of liver transplants in the U.S., and again, risk factors are injecting drug users, those on hemodialysis, sex with an injecting drug user, or a history of blood transfusion, and then last on the list were baby boomers. However, you should note, after the initial note to screen all baby boomers, now USPSDF has a B recommendation to screen everyone through age 18 to 79, just because there is an effective treatment for this. And so you do the screening, do the tests, if you see and look for hep C and RNA, and then consider referral for treatment to somebody because the effective, though expensive, can eliminate the virus and prevent the complications of cirrhosis and hopefully also the hepatic cancer. This is the algorithm for ACV screening. I won't go into all of that, but it is what you should refer to if you do the ACV screening and you need to interpret the results of the test. Rabies is an RNA virus that causes a highly fatal acute progressive encephalitis. All mammals are susceptible. The main reservoirs are carnivores and bats, and in the U.S., human cases often usually are caused across the world actually by bites from infected animals because the virus is present in the saliva. It's a neurotrophic virus that moves slowly from the entry site by axonal flow to your brain. The typical incubation period can be one to three months, but if you get bitten on the head or face, then obviously there's less distance for it to travel, so those need to act more kind of temporaneously, much more quickly if you need to bite on the leg or so on. You still need treatment, but you have some time. Disease is marked by several symptoms that are kind of characteristic for this, but it's a very terrible way to die if you get it. So again, prevention is very important. The rabies immunoprophylaxis is a key piece of that. There's no really good treatment for it otherwise. Vaccination of domestic animals, our dogs and cats, help avoid this quite a bit. In some cases, you can do wild animal baiting to help reduce it in the local reservoirs of carnivores and others. Use pre- and post-exposure vaccination and or immune globulin to help in somebody who's been exposed, but there's no really reliable treatment once the symptoms start. In the U.S., raccoons, skunks, bats, foxes, cats, and dogs are kind of the predominant species that transmission is associated with, and this just kind of shows on the east and west coast and the central part of the U.S. where the problems are. East coast tends to be the raccoons and skunks, coyotes and things like that in the plain states and some parts of Arizona and also the west coast. The management, again, is scratched or bitten. Wash the room, the wound very copiously. Observe a healthy domestic animal for 10 days after the illness. If it's a wild animal, you would send them for testing. Inject around the room with a rabies immune globulin, and currently it's at four dose close if the brain exam is positive for the animal once it's been given a necropsy. Group A strep is the classic sore throat pharyngeal tonsillitis. It also causes impetigo, pyoderma, scarlet fever, with the post-streptococcal complication of acute rheumatic fever and glomerulonephritis. These can be prevented by the penicillin treatment and ends the likelihood of transmission to others within 24 hours. In a hospital setting, the outbreaks are usually due to skin or pharyngeal, although I have actually seen and been part of an investigation where it was either anal or vaginal carriage and produced invasive group A strep and endometritis, you know, and was linked to a healthcare provider. There have been foodborne outbreaks described in both milk and eggs materials. The group B strep is recognized as an emerging pathogen in the early 1970s. There's about 10 to 30 percent of mothers that are carriers. 50 percent of infants are colonized at delivery and it progresses to neonatal sepsis in about 2 percent of those, and there's an increased risk of interpartum fever or history of group B strep, prior history of group B strep. Routine screening of mothers by anal and or vaginal and rectal cultures is recommended at 35 to 7 weeks. This is the preferred screening method recommended by both ACOG and American Academy of Pediatrics, and that reduces the risk of the group B strep disease significantly because you can give interpartum penicillin that prevents the disease if you have somebody that's known. I'm just going to briefly mention the common mycoses or fungal infections. Candida, of course, monilia is one of those. Histoplasma, often associated with bat droppings and contaminated soil. Coccidioides is seen and known as valley fever in the southwest U.S. and that aspergillus can increase the severity of asthma or complicate cavitary TB and also cause invasive disease in people that are immune suppressed. You should just be aware that these are some of the fungal diseases that can cause problems. Lyme and other tick-borne diseases are important. Lyme is the one we know most, but anaplasmosis, babesiosis, ehrlichiosis, and Rocky Mountain spotted fever are others. You see the characteristic target rash in the upper right corner here on this slide. First identified in case of Lyme disease in 1975 in Lyme, Connecticut, therefore the name, but it's caused by a spirochete known as Borrelia burgdorferi. Its characteristic transmitted to the black-legged deer tick known as Ixodes scapularis. These ticks are most likely to transmit in the first 36 hours after feeding, again very prominent in the north and upper midwest. There are similar Lyme-like diseases in Europe and Asia that are transmitted there, but this shows the prevalence of Lyme disease, which is again mostly upper midwest and especially the northeast and east coast where it's problematic. The flu-like symptoms occur. The erythema migrans rash, which is this characteristic target rash, just pathognomonic, that only occurs in 70 to 80 percent, so if you see that, you can empirically treat, but just realize that some people may not have that characteristic rash. The rash can begin in 3 to 30 days. It's gradually enlarging a circular red rash with central clearing, and the late symptoms can include neurologic signs including Bell's palsy, also inflammation of the heart or joint inflammation. If you see the tick and it's attached less than 24 hours, it's very low, you know, likelihood of getting Lyme disease, but if you do see it and symptoms of signs of, again, particularly that pathognomonic rash, then you can use antibiotics. There's a number listed here. Doxon cycling is one of those. Use again for two weeks to even up to three weeks, and then chronic Lyme disease is kind of controversial. The guidelines conflict on that, but just be aware that it exists. There are other tick-borne diseases I mentioned there. They're listed here. The babesiosis actually can be confused with malaria smears, blood smears, and you can transmit through blood transfusion, but the prevention, again, of most tick-borne diseases is avoiding tick habitat, dressing in light colors, using permethrin-treated closing, using DEET repellent or similar on exposed skin, and doing tick checks after potential exposures if you've been out in the field to try and help prevent this. That brings us to the sexually transmitted infections, so I'd like to get through these because they are certainly problematic. A lot of millions of cases and worldwide, hundreds of millions, HIVs are a large account still for health loss. This just shows the, you know, case totals in 2018 in the U.S., chlamydia being one of the most prominent ones, but syphilis has been rising in recent years, so that's obviously of concern to us. The risk factors, of course, early onset of sexual activities, increased number of sex partners not practicing safer sex, including use of condoms, poor judgment with alcohol or drug abuse, and then prior history, obviously, of an STI or current STI puts you at increased risk naturally. Again, that risk with number of sex partners just tends to go up both for women and men. There is age-related, and it tends to be in the young adult and adolescent group where it's highest. There also are increased risks due to racial and ethnic factors, so just be aware that those do exist. The chlamydia is, again, the most prominent one. Almost 2 million cases reported in 2018. It's the most common bacterial sexually transmitted infections, four times more common than gonorrhea, but similar clinical syndromes, including urethritis, cervicitis, and tubal infections, even a Fitzcurtis-like syndrome, so these are those problems. Sometimes it can cause, you know, inguinal lymph nodes in terms of the lymphogram, myeloma, venereum, but even can be asymptomatic. Again, that same kind of age-associated risk that you see mostly in the adolescents and young adults who are very sexually active, and then there are the racial and ethnic risk factors as well. Chlamydia, again, cause a urethral discharge, and a mucopurulent cervical discharge. Culture is not very sensitive. Nowadays, we use the nucleic acid amplification test as the best test, both highly sensitive and specific. Can you be used with the first void urine or as a vaginal swab? Just note that dead DNA can produce a positive test, so you don't usually want to repeat these tests within three weeks of treatment, because there may be some of that DNA still residual around, so you wait at least three weeks to do kind of, you know, test of treatment and test of cure if you do it. The LGV is rare in the U.S., but you should be aware that it exists. So the treatment, again, azithromycin one gram once. If for some reason they can't take that, you can use doxycycline for about a week, but it's obviously much easier just as a single dose if they tolerate it. You can treat partners in what's called expedited partner therapy. Usually, if you're treating for reinfection, you test three to six months later. The expedited partner therapy varies by state. You just need to check your current local requirements in terms of that and see what it is for your locality and region. So it's a B recommendation to screen all sexually active women 24 years of age and younger, or if older women are increased risk, and it does reduce the evidence of pelvic inflammatory disease and community prevalence. It's still an I recommendation on screening men, but obviously somebody has a reason to, you should do that. Neisseria gonorrhea, again, is a gram-negative intracellular diplococci. Estimated 820,000 cases annually, plus or minus, and the risk is higher in women probably because of their physiology and anatomy more than anything else from unprotected intercourse. It has these similar clinical syndromes that we mentioned for chlamydia. It does have a disseminated infection of arthritis, which you see a characteristic lesion in the picture here. You can get anorectal infection that can be coexistent, and also you can contain this in glandular infections. The clinical diagnosis is there. We don't usually do Gram-Sanes much anymore. It's usually these nucleic acid amplification tests that we do, but pharyngeal or rectal infection often must be diagnosed by culture. Again, USPSDF screening recommendation is B and the same as that for chlamydia. You do have to worry about penicillin resistance here. That's been increasing as well as chloroquinolone resistance. The first-line treatment, because the resistance problems, is a combination of ceftriaxone plus azithromycin. We recommend both doses. Other things, and quinolones in particular, are no longer recommended, and single treatment is not the best option. You want to use both agents if you can. Syphilis is the classic. It's treponema pallidum caused by spirochete. There are four stages, primary, secondary, latent, and tertiary, that have different extent of their infection, and they also require different treatments based on the stage of infection. Primary, secondary syphilis cases have been increasing and nearly doubled actually in more recent years, especially in the last couple of decades. Most of these are due to men who have sex with men, but they are also increasing in heterosexual populations. The darkfield smear from the chancre is the classic way of doing it. You use serologic tests, including the FDA-ABS or the treponema pallidum particle agglutination test. The RPR or VDRL serologies help us follow the titers during treatment, and the successful treatment should reduce the titer by a factor of four. USPSTF grade A recommendations to screen those at increased risk are pregnant, so you want to do that. The treatments are listed here. You should always again, you know, consult. They do differ by whether you think it's early, late, latent, or neurosyphilis, and usually longer treatments for those things that are at a more chronic or a longer state or more extensive state of spread. So this brings up another question. In this case, a pregnant patient is screened prenatally with a treponema particle antigen test and is found to have a positive result. The reflex RPR titer is one to four. She mentions that she's been treated for syphilis in the past, so at this point, we'd ask what your preferred action would be. So this is with a lot of other board questions. They kind of come based on actual experience, but in this case, you would want to actually do answer C, which is to request records from previous treatment to determine what the previous RPR titer was. So if that was then reduced by that factor of four, then you consider her adequately treated, and you wouldn't need to do anything at this point otherwise. Haemophilus decraei is known as chancroid in the clinical setting. It's gram-negative coxa bacilli and chains on smear. Uncommon in the U.S., but very common in third world countries. The clinical aspects is a soft but painful ulceration, as opposed to the chancre and syphilis, which is, interestingly enough, not painful. So a painful ulceration, you know, in the differential, obviously with herpes, is chancroid. But again, less common here. If the RPR and darkfield are negative, then think about this, and the treatment, again, is ceftriaxone and or azithromycin. Bacterial vaginosis you should be aware of, but I don't necessarily think of it as a sexually transmitted infection, but I included here. It can occur in non-sexually active women. It has several aims criteria that are listed here, including clue swells on wet prep, a fishy odor on a whiff test with the potassium hydroxide, and also using nitrogen paper, you can see that's kind of a alkaline sort of milieu there. But rapid test DNA probes and siolidase rapid tests are available. The treatment is usually with metronidazole for a prolonged period. You can also use clinomycin or tenandeazole, and you see the characteristic clue cells in the top picture in this slide. Frequent recurrences, you want to have a long treatment for several months with the metronidazole gel if need be. Viral infections like herpes exist. There's a first episode primary syndrome, and then you can have recurrent cases because the virus remains in the dorsal root ganglia. This can be either oral, which is the HSV1, or it can be genital, which is HSV2. Diagnosis is usually just by appearance. These painful blisters that occur, they can then rupture and become just a base ulcer. Viral culture often is negative. The PCR DNA is easier. You can do type-specific serologic assays, but to be honest, I mean, they're not that useful, so often we just do this based on the clinical appearance. Treatment doesn't eradicate the virus, but it may help the acute infection resolve or also be used for recurrent infections. For recurrent episodes, you can use this class of drugs here, including acyclovir or valicyclovir, and suppress the treatment. Also, again, reduce partner transmission. Human papillomavirus causes condyloma cuminata or genital warts, but it can also cause cervical dysplasia, cervical cancer, and cancer of penis. Types 16 and 18 are particularly problematic, but women with males that have had more than six sexual partners are at higher risk, and the diagnosis is either by the clinical appearance or in a pap smear, or in some cases by DNA or nucleic acid amplification test. So when you do this, USPSTF recommends cervical cancer screening every three years in women from age 21 to 65. After age 30, if you had a positive HPV or a negative HPV test, then you can go every five years, and it's a D recommendation for continued screening over age 65, and ACOG pretty much is similar, you know, for those recommendations. Treatment may be with podophilux or imiquimod and other things, but no treatment really eradicates the virus. The main thing or approach now is the ACIP recommendations for hepatitis V. We have the nonovalent vaccine, which is the main one that's currently used, recommended to be given at about age 11 to 12, occasionally younger, and it's approved as early as age 9. It's also indicated now as a catch-up vaccine in all persons through age 26, so it's shared decision-making in the older age group from 27 to 45, but if you give it before the 15th birthday, you can only do two doses, but other than that, it's three doses. Very effective in preventing infection who aren't already infected. It is free through the Vaccine for Children program. HIV AIDS, you're very aware of, still large numbers of people affected worldwide, and probably over a million people in the U.S. that are living with it, maybe up to 15 percent unaware of their status, and men who have sex with men are also the biggest percentage they get it. There is some, again, ethnicity and racial risk factors there as well. It's the ninth leading cause of death in 25 to 44-year-olds as of age 2016, though highly active retroviral therapy has helped quite a bit, mainly transmitted by exchange of blood and body fluids. Worldwide transmission actually is mostly heterosexual, as opposed to in the U.S., and it can cause immune deficiency over several years, including opportunistic infections and Kaposi's sarcoma. As I mentioned, the highly active antiretroviral therapy is helpful in helping reduce the complications and the problems with the opportunistic infections, as well as death to the disease, and also transmission vertically. This shows how rates have reduced in various populations over time with the introduction of heart therapy, so it's important to note. The screening recommendation is a recommendation by USPSTF. All ages 15 to 65, younger adolescents, and adults at risk should also be screened, and all pregnant women. There are other recommended recommendations for diagnosis and screening. We now use these P24 antigen tests, no longer use the Western blot, so this is the algorithm for the testing now that you should be aware of, but that P24 antigen test is the important one, and that's what's recommended, and there's a link there you can use to look at that. Prevention, it's the ABCs, the Successful Ugandan Campaign of Adsense-B-Fapal Condoms, but reduction in number of sex partners for high-risk sexual partners. Male circumcision in some developing countries has actually been helpful and shown to be, and there's now also pre- and post-exposure prophylaxis with the interest of being tenofovir combination and raltagravir if you're doing post-exposure prophylaxis, which is for a 28-day period, and it should be begun within 2 to 72 hours after exposure if you do it in an occupational setting. Trichomonas is a protozoal disease that can cause a vaginitis and cervicitis, so you should be aware of that as well. It's this protozoa that's very characteristic when you see it on a smear, and also even the appearance of the discharge is very characteristic, kind of foamy discharge. It's treated also with metronidazole or tenidiazole, and you should treat the partners concurrently in this sort of setting. There are some ectoparasites that cause sexually transmitted infections, including pediculosis pubis, so you can see the nits in the pubic hair. You can treat that with permethrin cream or ivermectin, and the other simple usual things you would treat for lice. Scabies is another type of ectoparasite that can cause infections with a very characteristic rash. It can be transmitted person-to-person by direct or close contact. It usually occurs in family, prison, and nursing home settings. Occasionally, you can see this crested Norwegian scabies in debilitated elderly in a nursing home, and that's very potentially infectious to other people. Again, 5% permethrin cream. Lindane does not affect the insectified. I mentioned oral ivermectin. There are also now some other treatments, but these are the two that we mainly use for this. Scabies is often diagnosed by the characteristic lesions and the characteristic locations that you see in these anatomic views here. Wrists, fingers, web spaces around the waist and in the axilla and places like that. Just remember that a lot of sexually transmitted infections can be neonatally transmitted. These are listed here, so be aware of those and be concerned about those as well. Again, individual STI prevention is important, and just be aware and use those condoms and things like that, and avoid high-risk sexual practices is very important. These are some other, including the expedited partner therapy, that have been shown to be helpful. Tuberculosis is an important worldwide infectious disease problem. It is a slow-growing aerobic bacterium, but it's usually transmitted through droplet nuclei or aerosols. It can affect any organ, but most often it's the lungs that are affected, but just be aware of the extrapulmonary results of tuberculosis infection. The active disease is very destructive due to the caseating necrosis and lung cavitation. This is what it shows like on a MTB acid-fast stain of the sputum, and you see this typical cavitation in the lungs lesions that are on chest x-ray. The epidemiology, again, millions of cases worldwide, U.S. cases peaked in the early 1990s, but have been slowly just declining since, but there's still a lot of prevalent cases in the U.S. of what we call latent TB infection, and 10 percent of those that are initially infected may develop active disease later, and half of that's within the first two years. Ninety percent of those infected, though, have this latent TB infection, which is not infectious to other people. This graph just shows the decline of TB over time, and you notice that the light blue bars are actually the TB cases in the U.S. among foreign-born persons, so they're actually the predominant cases in the U.S. now are in foreign-born. Persistent cough is the most common symptom, but fatigue, anorexia, weight loss, and other things can be also seen. It is a common cause of fever of unknown origin, so you should always remember this if you have a patient that's having a recurrent fever that you can't figure out why. Droplet nuclei is the main suspension because they stay suspended in air for long periods. Certain patients can be more infectious. Certainly, cavitary disease or laryngeal TB is a big problem, and most exposed persons don't get infected. Mostly, it's close contact, less likely others that are not close contacts, and remember, latent TB infection is not contagious, but just be aware that it can progress to active TB later if you're not careful. Infection control has to do with the organism's stability. It is destroyed by direct sunlight and ultraviolet light and disinfectants. The reduction of the airborne droplet nuclei in a hospital session, HEPA filters, and high air exchanges is important, and UV irradiation can help. Covering the mouth and nose is important, and FOMA control is not that big with this particular disease. Prompt identification therapy is important. Most care sees you can't be cured initially. It does require multiple drug therapy because of increasing resistance. It's important to use directly observed therapy in all cases, and you do monthly sputum until negative culture. You monitor for drug toxicity, but also for multi-drug resistant TB, especially in certain foreign countries, which increases the case fatality rate and also the duration of treatment that's required. Treatment for latent tuberculosis is recommended in this country with INH or a true two-drug regimen, and that decreases that lifetime risk of activation that you want to avoid if possible. Contact investigation in public health settings is very important based on concentric circles. You can use the screening tuberculin skin test, also known as the MANTU test, and it's usually positive within two to ten weeks after exposure. Remember that the tuberculin skin test is read based on your risk category, so it's a stratified risk, and the reading of induration more than five millimeters, more than 10 millimeters, or more than 15 millimeters is all based on the risk category that you are in, so just remember that when you are involved in helping reading and interpreting these in each setting. This two-step, you know, PPD or TST testing is required really for adults that will be retested periodically, so that includes, in occupational health, all our healthcare workers. You check for booster reactions, the weakened immune response that might actually allow misinterpretation of the initial test, if the initial test is positive, you consider that person infected. If it's negative, you give a second test one to three weeks later. If the second test is positive, again, you consider the person infected, and that was just a boosted test because they had waned immunity. Interferon gamma release assays are what also known as blood assays for mycobacterium tuberculosis. There's two commercial tests noticed here in this country that use similar antigens to test, and they look at these measures of release of interferon gamma, and the results are often able to be obtained within 24 hours, whereas you have to bring people back in 48 to 72 for the tuberculin skin test. The place where you would want to use these interferon gamma release assays is you can use it in the same place you do TST, including routine screening of immigrants or healthcare workers or in contact investigations. The sensitivity and specificity is comparable to the TST, but there's fewer false positives in BCG vaccinations, and for that reason, it's actually a preferred test in somebody who's been from a country where BCG vaccination is used. It's not adequately evaluated still, I think, for children that are under age five. There's other advantages in terms of not having to return in 48 to 72 hours. There's booster effect in serial testing, but again, remember those limitations in younger children. This brings up another question. In this case, when we're looking at an IGRA test, which one would be preferred to the tuberculin skin test in order to diagnose tuberculosis infection and these persons that are listed? So the answer here is answer B, it's a recent adult immigrant who had BCG vaccination as a child. So remember, this is a very important category and it is the preferred test for somebody that's in this category. Note also that nucleic acid amplification tests are available. CDC recommends those and people to diagnosis being considered, but you get these results back much faster than you get sputum results back. So if they're positive, it can be very helpful. It provides results in much more quickly than the culture test just because the bacterium grows so slowly in the sputum test. It's usually some considerations in using these, but just be aware of those. MDR-TB is less likely if countries are good about using the directly observed therapy. That's just what this slide demonstrates, is that it is more likely to have MDR-TB for not making sure people are taking their adequate treatment in full measure. Be aware that there's molecular line probe assays for epic diagnosis of TB. They use PCR means as well. They're sensitive and specific, especially in areas of endemic TB and high rates of MDR-TB. Again, early results so that you can use that to help and often available through regional protocols in the US and other places. Malaria is still a big killer. We'll go through this quickly, but you should be aware of this if you have people that you treat that are travelers or in the military that you go to these locations. Remember that in areas below that are lower altitudes can be very common. We still have a lot of imported cases in the US of various types of malaria that are problematic. Plasmodium falciparum is the big problem because in terms of deaths, although the plasmodium vivax and the other sorts of plasmodia are problematic in terms of the hepatic stage. But because the plasmodium falciparum affects all of the blood stages, it can cause a lot of anemia and complications. The anopheles mosquito is the problematic transmission. The mosquito can be infected for life. This is the plasmodium life cycle. Just reminding it that you get the sporozoites that go in and then grow in the liver or later released into the blood stage. They can produce the gametocyte that's ingested by another mosquito that can then later create problems for going on. But just be realized, this is actually a CDC slide that has the same basic elements, but it has a lot more detail. Feel free to look at these on your own with more time. Again, malaria cause fever, chills, and sweats that can be a problematic. Remember, it's in the differential for a fever of unknown origin. It can cause icterus, coagulation defects, severe disease including encephalitis and cerebral edema. Fatality in falciparum is greater than 10 percent if you're not treated, and the infection can last for a long period of time. Remember that there are liver stages of P5X, a valley of malaria that's usually not life-threatening like falciparum, but it can be problematic and create long-term infections. Incubation periods are listed for falciparum and VIVAX. Just note that they're the problematic things that are there. Diagnosis characteristic has been with these thick or thin smears, and you do these every 6-12 hour period because the release can be cyclic in order to rule out the malaria. There are other some rapid tests that are now available in places where you have less experienced microscopists to do the thick and thin smears. Just be aware that those are available. But again, the classic is looking at these smears periodically. Prevention is using everything from avoiding being out in the nighttime when the anopheles are out, as well as using bed nets, insect repellents, and permethrin repellent on clothing and bed nets. Chemoprophylaxis is important for travel to these areas. If it's chloroquine resistance, then you need to be aware of that and use the appropriate agent in those cases. These are the available agents in areas of chloroquine resistance. Doxycycline can be used at 100 milligrams a day. Etoboquine progranol once daily is very convenient. Methoquine has been used historically, but because of some CNS and other side effects, it's not used as often. A newer one that's been approved is tefenoglen, which you can use three days before, then once weekly during time in the area, and use it for seven days afterwards. You can also use promicot alfale. We'll just be aware of that. But chloroquine is still useful in areas where there's no resistance to it. Acute treatment, you can use many of these agents for acute treatment, but artemithralumifantrene is approved for three-day treatment, and artesunate has been used or recommended in the US for severe cases. Remember, promiquine removes the liver stages for these VIVAX and other agents, but tefenoquine can also be used in that. Both these agents, tefenoquine and promiquine, you have to screen for G6PD deficiencies, so you don't get hemolysis in somebody that has that. Contrary to the use season pregnancy. Just be aware about the animal or drug resistance and the problems with that. Emerging infectious diseases are our last section along with the bioterrorism. These are diseases that have been increasing in incidence or geographic range. These include things like Zika, Ebola, certainly HIV at one point, West Nile virus. The new one, of course, on the list is the SARS-CoV-2 that we're all very aware of. But Hanta and dengue and things like that are also on this list. The global problem of antimicrobial resistance is also a factor of this. There's some incidents mentioned here that we've already alluded to. High use of antibiotics in cattle and other species that we have been complained of as a contributor to the antibiotic resistance. Methicillin-resistant staph aureus is a problem. These staph infections can cause transmission from contact with skin, cause some serious systemic problems, and there's healthcare-associated infections, but also community-associated infections. The MRSA is a culture in outpatient setting. It helps you decide between community-acquired and otherwise, but there's some risk factors that are shown here for that. The community outbreaks have been described in everything from sports participants to prisoners and military recruits as well as even tattoo recipients. It can look something like this and be thought of as an abscess, pustule, boil, or even misrecognized as spider bites. But just be aware that MRSA can be a problem. The IND is actually 90 percent affected even without antibiotic treatment. But if you're suspecting resistance, you should culture it. Empiric therapy, if you know that it's common in your area or that there's prior infection, just be aware of that. If there's a lot of associated cellulitis, you consider the antibiotic treatment in addition to IND, or there's other problems of maybe immune deficiency that's there. Again, in areas where there's a higher local prevalence of more than 10-15 percent, then you may want to consider septra, trimethopimethoxazole is one of those, or clindamycin. In some cases, you may want to use other antibiotics, but macrolides and fluoroquinolones are usually not useful in this setting. Again, routine colonization screening is not indicated, or decolonization might be selectively useful using nasal immunopuricidine or hexidine wash. But in those cases, you would use these things. Most school settings, just keeping wounds bandaged, not sharing towels, good hand hygiene, and things like that. There's no real need to close the entire school in this way. I'll very just briefly go over SARS-CoV-2, because it's among us. Remember, this is not going to be on probably this year's board review test. But thereafter, obviously, it's certainly going to be potentially at risk. But remember, this is related to SARS and MERS. All three are linked to zoonotic transmission. SARS was civet cats, MERS was camels. All these, our DNA genealogy have been traced to bats at the reservoir, and the Chinese outbreaks, both in 2019 and 2002, were linked to the so-called wet markets that sold live animals for food. Variable human-to-human transmission, the incubation period's 2-14 days. Acute illness diagnosed by PCR and serology can confirm. The case fatality was higher in MERS and SARS than what we're saying with SARS-CoV-2. But the case fatality rate does increase considerably with age. So much supportive treatment, we're still waiting on the vaccine, and hopefully we'll get here. Common symptoms of fever, tiredness, cough, shortness of breath, loss of smell, or anosmia has been described. 80 percent recover with mild to moderate illness. But again, age is a risk factor, and some racial things can also be a factor. The virus targets ACE2 receptors in the lungs and elsewhere, and it has a hypercoagulant inflammatory state, and children can result in a Kawasaki-like syndrome. This just shows that increased risk of case fatality rates by age, which goes up significantly in different age groups. The younger folks are not immune from illness, but less likely to die fortunately for them. This shows you that it also over time, especially if you get the whole denominator, like in a cruise ship, the case fatality rate may actually be lower. Depending on how complete you are at the exposed population, it can go down or vary, but three to four percent has been where it's hoovered. But like in the cruise ship that was infected, it was as low as 0.63 percent. Just a note that during transmissibility, the incubation time and hospitalization, these are comparisons between influenza and SARS-CoV-2 or COVID-19, just to show you a list of the differentials. Remember that flattening the curve is the non-pharmaceutical interventions we've tried to put in place to do these things to using the mask in public, the social distancing more than six feet, the avoiding large gatherings, using hand hygiene, isolation, quarantine, and contact tracing. Then is to try and flatten this curve. The purposes of that are to delay the peak of the outbreak, to decompress the peak burden of hospitals in terms of ventilators, ICU beds, the availability of personal protective equipment, and the impact on healthcare workers, and thereby reducing overall cases and health impact. You allow time for the identification of effective treatments. So far, remdesivir, IV, dexamethasone early have been helpful. We're still looking at other things including convalescent plasma. Multiple vaccines are in development, including an mRNA vaccine as well as others. The second wave of the S has been happening this summer. This just illustrates that, and by region and state in the US, we've had this, unfortunately, a big natural experiment going on based on which government and which community you're in. Other things, remember hantavirus and things like that can be associated with rodent infestations transmitted in the droppings urine and saliva, can cause headache, fever, muscle aches, cough, and dyspnea. But you really want to, if you think you've got a rodent infestation in these areas is use a wet mop instead of sweeping and maybe even wear an N95 mask. Dengue is the most commonly acquired vector-borne viral disease with millions infections and lots of deaths. Limited in the US, but there's been some outbreaks along the Texas-Mexico border and imported cases in Hawaii, even cases in Key West and Puerto Rico. Just be aware that it's the leading cause of acute febrile illness in US travelers returning from the Caribbean, South America, and Asia. It is an RNA virus. It's transmitted by the Aedes aegypti mosquito, which is a data divider. High fever, abrupt headache, it has been known because of the aches as break bone fever, often has retro-orbital pain with it, so pain in the eyes. It can progress to dengue hemorrhagic fever and shock, more likely actually with subsequent infection by other strains. It can be very problematic disease. Supportive treatment, mostly there is a trivalent vaccine that's FDA approved, but mostly in ages 9-6, if you've had prior infection. These are areas with Aedes mosquitoes where potentially there could be transmission and has occurred, as I mentioned, in Key West and in the border in Texas, so that is an emerging infectious disease. Another question here for you to ponder is, one of your patient returns from recent travel to Puerto Rico, and 10 days ago, complained of a low-grade fever and joint pain. Which test is preferred to verify if this patient had Zika? The answer here is actually C, so the urine RT-PCR. Zika, as you know, was first discovered actually in the post-World War II period in the Zika forest in Uganda. But outbreaks have later been noted in the tropical Africa, Southeast Asia, and Pacific Islands. But then PAHUA issued alert in Brazil and declared a public health emergency by WHO in 2016. Again, primarily through the bite of the Aedes species. Many people infected won't have symptoms or only have mild symptoms. But often you'll get a conjunctivitis, you may get a rash like this. Again, they're recommended diagnostic symptoms depending on what time period you're in. Usually, urine tests, but you can do serum tests and others. The problem is that if those are negative, you can do the ELISA, but the ELISA cross-reacts with other flaviviruses such as dengue and West Nile virus and yellow fever. You need that plaque-reducing assay to confirm which one it is. No vaccines or antivirals, but they're still working on those things. Dead produces situation, microcephaly may also cause Guillain-Barre. Again, travel precautions to areas that have it, and remember the Aedes species of the daytime biters. Beware of the viral hemorrhagic fevers that include Ebola, Marburg, and Mechuco. Extensive bleeding, high case fatality rates. Vaccine therapy is underway, including some antivirals. You remember very well the West Africa outbreak with significant case fatality rates. The RSVCV Z-Bob vaccine has been extensively studied now, both in that area as well as in the Congo. And so it is now actually been ACIP approved as of February, 2020 for pre-exposure vaccination if you're going to one of those areas or responding to an outbreak and for healthcare personnel or laboratory and working with these viruses. So it is a fortunate thing to have available. Just be aware we have potential biological agents as well. These are listed. They are the category A agents that have these characteristics that you should be aware of that easily transmission, high case mortality rates that can cause great panic and social disruption. These are the category A agents, which include things like botulism anthrax and the viral hemorrhagic fevers. There are also category B agents that are at a lower level as well as category C agents. So just be aware that those are the case. These are the B agents that are listed. And then the last question that I have for you is the following potential biological warfare agents, which is concerned for person-to-person transmission. And actually the one that's the big problem here is the hemorrhagic fever, the Lassa virus. So that's the one that I have. So in summary, infectious diseases have historically been a significant cause of morbidity and mortality. The introduction of sanitation vaccines and other countermeasures have greatly reduced our disease burden over time. But despite these advances in environmental factors, you know, adaptation by infectious agents and human behavior continue to pose challenges for us in all of these. And then the remainder of your slides are actually the references that might be useful to you to have on hand and links for your study if you wanna read in more depth. So that's it for me. And I'll see if we've been able to actually have any time for questions in the few minutes remaining here, if we can work that out with the chat that I've had problems with, so.

American College of Preventive Medicine

Board Review Course

Clinical Preventive Medicine

Infectious Diseases

Dr. Dana Bradshaw

vaccines

preventive measures

COVID-19

vaccine-preventable diseases

emerging infectious diseases

SARS-CoV-2

Ebola

dengue

Zika

immunization