Well, thank you, and thank you for that introduction. I don't have any relevant disclosures. And so, I was asked to cover non-influenza and non-SARS viruses that were not preventable by routine vaccination. So, you know, I had a huge number of options. And in the Americas alone, I could have chosen from these viruses. But I decided that I wanted to focus on something that we are seeing with increasing frequency and that causes critical illness, and especially is impacted by climate change, that people really need to be aware of these that haven't seen them before. So on the mosquito-borne viruses, I decided to focus on dengue, and then I'm also going to focus on the hantaviruses. So first, hantavirus is carried by rodents, and transmission is rodent-to-human, very, very rarely human-to-human. And this is a picture of a deer mouse, and it is in Central and Western U.S. and Canada, the Sin Nombre virus, and has caused intermittent outbreaks of hantavirus pulmonary syndrome. And the transmission is airborne, and it's from stirring up fresh rodent urine, rodent droppings, or nesting materials, usually when people are cleaning out old cabins, camping, or certain areas of the U.S. And most people don't even know they are exposed. So taking a history, it's hard to figure out what is going on and to identify these cases. In America's New World, it causes hantavirus pulmonary syndrome, and these quote-unquote old-world hantaviruses in Europe and Asia may cause hemorrhagic fever with renal syndrome. So the hantavirus pulmonary syndrome, there's this asymptomatic period, so the critical illness can emerge up to eight weeks after exposure, but it's highly fatal. There really is no treatment except for supportive care. It starts off with sort of a flu-like illness, fever, headaches, muscle aches, and then five to seven days later, late symptoms, pulmonary edema, capillary leak, basically ARDS. And there's a differential of other community-acquired pneumonias, influenza, as well as other rarer things. But unfortunately, despite high supportive care, this can have a very high fatality. And the hemorrhagic fever with renal syndrome, which is mainly seen in Europe and Asia, is different hantaviruses, like this sole virus, which it can even be the domestic rat. The mortality is much lower, but it can cause long-term renal injury. And these are also growing in number, these renal injury viruses, although we don't see as much of them in the Americas. So the differences are the hemorrhagic fever with renal syndrome is really the target organs, the kidney, and the hantavirus pulmonary syndrome is really the lung. Both of them cause shock, and as I mentioned, the mortality is very high with hantavirus pulmonary syndrome, so it's fortunate that it's not human-to-human transmission, or it would be very hard to care for these patients in the ICU. Yet anyways, it's not human-to-human. Now I'm going to switch over to dengue, where 40% of the world's population is at risk for dengue. And it's spread to people through the bite of this infected Aedes species mosquito, and there's four serotypes. And you can get infected four times, because there's not cross-immunity that's durable protection for these four strains. And the subsequent infections with dengue increase the risk of severe dengue. And all of this that I'm showing is from CDC and WHO websites. So this is from the CDC website, dengue cases. I'm just showing the U.S. I know this is an international meeting, and many of the international members are very aware of dengue, because they've cared for patients with severe dengue in their ICUs, but it's less common in the U.S. Florida has the most locally transmitted cases. Most of the cases we see in the U.S. are from travel. But the WHO has noted that it's increased eightfold over the last two decades to over 2.4 million in 2010 and 5.2 million in 2019 cases of dengue, with deaths markedly increasing. And these are mostly young, healthy people. So this is a really great updated algorithm that's 2020 for clinical management of dengue. So there's a lot of resources online for people who haven't cared for them, these patients. And this is the two classifications. It's either dengue or severe dengue. And the dengue is high fever accompanied by two of these following symptoms in the febrile phase. So this is when they're febrile. Pain behind the eyes and this rash, which I'll show you something about that in a minute, is characteristic of dengue that are sort of unique. Severe dengue has to have the fevers now dropping, but they're in this critical phase. And now they're emerging with these other symptoms. And there's two ways in the first five days that you can test this with this rapid antigen blood test for this NS1 protein, or you can do PCR testing. So we used to call dengue dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. But that's not the name since 2009. It's either dengue without warning signs or with warning signs, and then severe dengue. The without warning signs is outpatient ambulatory management. And you can do this petechiae or tourniquet test, which I'll show in a minute. This is all in this handout that is available online from the World Health Organization, Pan American Health Organization. And then if it progresses to dengue with warning signs, that's when there's intense abdominal pain, persistent vomiting, fluid accumulation. There's a progressive increase in hematocrit. And these patients need to be admitted and monitored because they could progress to severe dengue, which has a case that then has either shock or respiratory distress due to this plasma leak, severe bleeding, or severe organ involvement with liver impairment myocarditis. And these are ICU patients. So this is the tourniquet test. There's this great CME-eligible training that you can do at the CDC where they have all these tips about dengue and patient cases. And you put the tourniquet on for two minutes, then measure this square, how many petechiae you see. There's also these algorithms for management. I don't expect you to see this small font here, but basically this is the dengue with warning signs. You start off with 10 cc's per kilo of crystalloid solution of normal saline or Hartman's, and you give it over an hour. And then you keep titrating, reevaluating for improvement. If they're not improving, you keep giving 10 per kilo. If they're improving, you go down the next hour. You give five to seven, the next hour three to five, the next hour two to four. And then they have the criteria for improvement, your hematocrit's falling to less than your baseline. And this is the critically ill patients with dengue, the severe dengue. And there's a separate algorithm if patients have comorbid conditions or are pregnant. But this you start with 20 per kilo and titrate down to 10, to five, to three over the next each hour while you're monitoring and you're doing these drips for different periods of hours. It's all about titration and monitoring and seeing whether there's remission of shock, stable vital signs, the hematocrit's falling, that's signs of improvement. If they're not improving, you keep giving 20 per kilo and continually monitoring. You might need to give colloid and other things. So there's a paucity of evidence supporting what we should do despite the fact that dengue is pretty common. Hantavirus is very rare. There's really only two RCTs I could find on PubMed with my searching. Both of them were negative but underpowered and it was hard to recruit. For severe dengue disease though, there was only six RCTs of treatment. And paracetamol actually didn't even improve the fever and increase the liver enzymes. Prophylactic platelet transfusion or IVIG for patients with platelet under 20,000 who weren't bleeding, wasn't effective. And then there was this New England Journal pilot and then larger pediatric study of fluid resuscitation but that was in 2005. So those algorithms that I showed you really don't have much evidence base despite the fact that dengue is pretty common. For hantavirus, there is some funding looking at antibody therapy for hantavirus disease and it's a category A which is a high priority virus with the biggest risk to national security is its categorization. For dengue, they really focused on the dengue vaccine and the problem with it was that when they first gave it for prevention, it actually made patients worse when they got infected. So it's only given to patients who have laboratory confirmed prior dengue and live in areas where it's endemic. And then it improves outcomes in the U.S. it's only for 9 to 16 years children, 9 to 16, they get three doses. For other parts of the world, it goes up to age 45. And that's all that I have on those two viruses and there's a lot of other things I could talk about but it's important that we're prepared to take care of these patients as climate change we might see these in our ICU more commonly. Thank you.

hantaviruses

dengue

climate change

transmission

mosquitoes