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Wednesday, October 16, 2019

Dengue fever: Symptoms, treatment, and prevention

Dengue feverr: Symptoms, treatment, and prevention

Dengue fever: Symptoms, treatment, and prevention


Dengue feverr: Symptoms, treatment, and prevention


Dengue fever is a mosquito-borne disease caused by a virus of the same name.It’s a part of the Flaviviridae family, known for its other famous members: YellowFever, West Nile, and Zika.It’s also referred to as breakbone fever, but that should be the least of your concern...whatyou need to worry about is a complete.system.shutdown.Most commonly found in tropical regions, Dengue puts 40-50% of the global population at risk.With symptoms ranging from fever, rashes, painful joint and muscle aches to vomiting,Dengue can resemble the flu, but it can become life-threatening in a much different way.When the pH changes, it changes the configuration of the Dengue virus.Actually, at that point I could grab the model.Great.Okay, thank you.Cool, all right.Dengue prop.Im Shannon Bennett.I work at the California Academy of Sciences.Im curator of microbiology and chief of science, and I study the genetic makeup of Dengue viruses.Ive been working on it since 2000 and I was one of the first people to look at large swathsof the Dengue virus genome to pinpoint where key mutations were occurring to drive itsspread and pathogenicity.

How Dengue spreads


To understand how Dengue spreads, it helps to start with how it gets in.Enter, the mosquito: specifically a species called Aedes aegypti.Its a day-biting mosquito.It actually prefers the crepuscular times of the day, so thats dawn or dusk, and itwill feed on multiple people.It might feed three or four times in its lifetime, and that gives the Dengue virus ample opportunityto be passed between human hosts by a single infected female mosquito.Now, what makes these types of viruses so quick to take off, is their genetic architecture,which allows them to begin producing proteins immediately after they enter the host cell.Dengue virus has been an interesting puzzle for a lot of scientists and clinicians.It is probably infecting almost 400 million people a year as far as we know, but onlya small fraction of people actually get sick, about 90 million a year.So were not really sure why some people get sick and other people dont get sick.Once the Dengue virus gets in through the skin, it can take several days to a week eventuallyfind its way into your lymph nodes and, then, bloodstream.From there, it’s just one big fast-track to Flavivirus-town.So Dengues primary target and the way it sustains itself in your body is in white bloodcells, and these are macrophages and monocytes that are antibody receptor-bearing cells thatthe Dengue virus uses to bind and enter the cell.The cell is naturally taking anything thats bound to its receptors and phagocytizing it,so basically pulling it into an internal cellular capsule, and once that happens, the pH ofthat capsule changes.And when the pH changes and that lock-and-key relationship between the virus protein andthe host cell receptor proteins experience that change in pH, a pore is formed... andthrough that pore, the virus genome enters into the hosts cytoplasm.And from there it’s a pretty sophisticated version of copy and paste.The virus uses the host cell to duplicate itself.Or as Dr. Bennett describes it, budding.In contrast, many people are familiar with other mosquito-borne diseases like malaria.Malaria is a burster.At the sporozoite stage as its replicating in your red blood cells, its copying itselfto a great degree until basically your host cell explodes or bursts open and spreads sporozoitesaround.Dengue virus doesnt do that.Its a budder.Its working with the host cell and taking advantage of host cell energy and metabolismto create new virus particles.Dr. Bennett and her team study the genetic differences between the four serotypes ofDengue.Those differences and similarities are what makes co-circulating stereotypes a dangerouscombination, contributing to more severe episodes of the illness.They are co-circulating today all over the world, but in the old days they didnt overlapso much.When they started to move around...we also saw more hemorrhagic fever and more severeforms of the disease, so one hypothesis is because were being exposed to multiple strainsof Dengue throughout our lifetime and thats creating this risk to develop severe disease.And yes, hemorrhagic fever is just as bad as it sounds.


So what happens in a secondary infection is that those antibodies that youve producedto the first one dont bind as efficiently to the Dengue virus.Instead of being neutralized in the endosome, it can enter the host cell more efficientlyand create more virus.What we think is happening is that its creating more infected cells than you would have inthe case of a primary infection or a re-exposure to that same primary serotype because of theinefficiency and the lack of perfect match between the antibody and the new virus.Typically, once your immune system fights off a disease, it remembers it for futureencounters.Usually that works.But with Dengue, immunity to one serotype doesn’t protect you against a differentserotype, and can in fact enhance the infection, making a second or even third encounter withthe disease much worse...because your immune system’s memory is stimulated but not agreat match.We think that that is whats causing this out of control immune response that acceleratesand eventually leads to the hemorrhagic fever that we see and even in some cases shock syndrome.So Dengue shock syndrome is another severe outcome of this over-reactive proinflammatoryimmune response.


One impact of having an overabundance of proinflammatory cytokines is that membranes become leaky,and when capillary beds become leaky, blood will flow out.And you start to bleed out into your capillary beds and into the tissues, and then fluidsto flow into your bloodstream causing potentially hypovolemic shock and death by Dengue shocksyndrome.And both hypovolemic shock and fever can be deceptive.The most frustrating phenomenon with Dengue virus is that people seem to start to recover.They might have three to four to maybe seven days of fever depending on when they firstexhibit symptoms, and then the fevers starting to go down, we can sort of see the diminishmentof symptoms, and then hemorrhagic fever or shock syndrome can kick in very quickly afterthat.So Dengue is not something to take lightly, but Dr. Bennett says these extreme cases arestill pretty rare.Of the nearly half a billion cases reported annually, only 500,000 are severe, with manycountries reporting less than 1% fatality rate.Still, knowing the symptoms and ways to help prevent initial infection are key.And while there is a vaccine, there’s still a long way to go.The challenge with developing a vaccine for Dengue is that you need to develop a vaccinethats effective against all four serotypes simultaneously, and this is very unusual.There are vaccines that can vaccinate against all four types, but they dont do it to theequivalent level.So you might be mostly immune to one and then a little immune to some of the other stereotypes,and that too is not what we want.So stay tuned.

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