Arboviruses – Flaviviruses

by Sean Elliott, MD

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    00:01 Now, let's turn to the arboviruses.

    00:03 And keeping in mind, again, these are exposed through the bite or the saliva of an insect vector, which in this case, in the arbovirus' case, is almost always mosquitoes.

    00:14 The mosquitoes participate in a sylvatic cycle, which is where the mosquito and a primate host, not the human, cycle back and forth a viremia.

    00:26 With the arbovirus, mosquito takes a blood meal, processes it in the salivary gland, and then gives it back to the mammalian host.

    00:35 Humans are accidental hosts as occurs in all vector transmission.

    00:40 In this case, once the human is bitten by an infected mosquito, then the saliva and the arbovirus transfer into the bloodstream creating a primary viremia.

    00:52 Primary infection is then acquired with delivery into the monocytes, their macrophages, where initial viral replication can occur.

    01:01 Then, there's a secondary viremia, so monocytes -- macrophages first, and then, as those cells are lysed and release brand new virions, then secondary viremia occurs.

    01:13 And then, the arbovirus goes to whatever its site of action is, whether that's brain, liver, blood vessels, skin, etc.

    01:24 So, the transmission of the viruses and all the arboviruses, is due to pretty much 1 of 2 mosquito types.

    01:33 The Aedes mosquito, and that's usually the Aedes aegypti or the Aedes albopictus mosquitoes, these are known as flood plain mosquitoes, meaning that they exist close to bodies of water, and mosquito eggs which have been laid during drought season can regenerate and create a new mosquito larvae as soon as that dried floodplain again becomes wet.

    01:56 o, as you see here, Aedes mosquitoes, anywhere near water, and they carry the viruses for dengue and yellow fever infections.

    02:05 The Culex mosquito is the larger mosquito, and it typically loves forested or grassy or, sort of, cool, moist environments.

    02:14 And many of the encephalitis viruses' site, for example, the St. Louis encephalitis virus, come from the Culex mosquito.

    02:23 Let's look down at the specific diseases caused by some of these arboviruses.

    02:28 And we'll start with dengue as it is of quite significant human concern.

    02:32 Dengue syndrome or dengue infection is caused by the dengue virus, makes sense.

    02:38 And as just mentioned, it is carried by the Aedes mosquito.

    02:41 The tropism or the target of the dengue virus is primarily vascular endothelium, and secondarily, macrophages and liver.

    02:50 Because the target is vascular in nature, then the severe manifestations of dengue are almost always hemorrhagic in nature.

    02:57 However, the very first part of dengue syndrome, the first infection one gets, has high fever, headache, and especially, postseptal pain, so pain behind the eyes, as a prominent manifestation.

    03:12 In addition, there is a nonspecific erythematous rash, and then bone pain for at least 7 days of the total dengue syndrome.

    03:21 The bone pain is so severe that in many parts of the world where dengue is common, it is referred to as Break Bone Fever because the bone pain is so -- people swear that their bones are breaking during the episode of dengue.

    03:35 Now, there are 4 serotypes of dengue and infection with 1 of those will cause the first dengue syndrome, the Break Bone Fever.

    03:44 However, reinfection with a 2nd or a 3rd or a 4th of the serotypes causes a new process, which always has some degree of hemorrhage, hemorrhagic shock, multi-organ failure, etc.

    03:57 So, to be infected with 1 is bad enough.

    04:00 A 2nd or 3rd infections, many times, can be fatal.

    04:04 Yellow fever.

    04:05 This is caused by the yellow fever virus, also carried by the Aedes mosquito.

    04:10 Its primary focus of infection, its tissue tropism, is the liver.

    04:15 And of course, because of that, patients become jaundiced, hence, yellow.

    04:19 Primary infection with high fever, rapid onset of jaundice, black vomit due to gastrointestinal hemorrhage.

    04:27 So, even though there isn't a primary vascular focus for this, yet still, due to backup congestion, there can be bleeding into the stomach bleeding into the gut, and one can have black vomit and indeed, black stools.

    04:42 The prevention for this is actually accomplished with a live attenuated vaccine, which currently is required, not upon entry to, but on departure from a country which is afflicted or endemic with yellow fever prior to returning to a country which has no yellow fever.

    05:01 Encephalitis virus.

    05:02 And now there are several here and will include St. Louis encephalitis virus and West Nile virus.

    05:08 These are carried by the Culex, that larger mosquito that we talked about, and their focus, their tissue tropism, is the central nervous system.

    05:16 So, of course, patients with these viruses will have your typical viral syndrome: fever, headache, but they'll progress to neck stiffness -- nuchal rigidity -- followed by loss of consciousness or altered consciousness.

    05:30 So, stupor, disorientation, they may enter coma, they may develop seizures, certainly, potentially a spastic paralysis.

    05:38 West Nile virus, especially, seems to mimic, in some ways, Guillain-Barre syndrome, so an ascending paralysis.

    05:46 And some patients will present with both confusion hallucinations and urinary retention because they've had, sort of, a paralysis of the motor control allowing for urinary let down.

    05:58 And then Zika virus.

    06:00 We're probably all currently familiar with Zika virus at the time of this filming, primarily because of a fairly recent outbreak in the Rio de Janeiro region of Brazil.

    06:10 But, of course, Zika virus is historic and has caused outbreaks in other parts of the world.

    06:15 It is carried by the Aedes aegypti or a Aedes albopictus mosquitoes, And there are several areas of tissue tropism which you see listed there.

    06:24 Indeed, the brain, the eye, the body fluids, sexual organs, placenta, basically, the whole body can be affected, and especially, infants born to mothers who have been Zika infected can have prominent findings and demonstration by PCR a viral presence in every tissue system present.

    06:44 However, primary Zika virus in the non- infants, a non-congenitally infected baby, is a relatively mild process.

    06:54 Patients will have conjunctivitis which does not have any discharge.

    06:58 They'll have low grade fevers.

    07:00 They'll have a rash, and they may also have some arthralgias, all of which starts in the periphery, so hands and feet and move to the central region.

    07:10 Adult patients with Zika virus frequently do not seek medical attention because most are a very low level of severity.

    07:20 However, mothers, because they are transiently immuno- suppressed may have a more severe collection of disease symptoms, and certainly, they can transfer disease to their infants.

    07:31 The classic finding in congenital Zika virus is microcephaly, and not just a little, but severe microcephaly, more than 3 SDs below the normal mean for head circumference for the baby.

    07:45 And there also have been many evidences of miscarriage and birth.

    07:49 So, these viruses, a full range, again, from hepatitis -- one of the classic parenteral or sexually acquired hepatitis viruses, all the way to mosquito or vector-associated viruses, which have a wide variety of tissue targets.

    08:04 It again goes to show that even the same family of virus could have multiple different targets.

    08:10 Very much the unintentional dinner guest.

    About the Lecture

    The lecture Arboviruses – Flaviviruses by Sean Elliott, MD is from the course Viruses.

    Included Quiz Questions

    1. Monocytes
    2. Neutrophils
    3. Eosinophils
    4. Basophils
    5. Lymphocytes
    1. Aedes aegypti
    2. Culex pipiens
    3. Anopheles quadrimaculatus
    4. Ochlerotatus triseriatus
    5. Culiseta melanura
    1. Dengue virus
    2. Yellow fever virus
    3. Chikungunya virus
    4. Rift Valley fever virus
    5. Zika virus
    1. 4
    2. 3
    3. 5
    4. 6
    5. 7

    Author of lecture Arboviruses – Flaviviruses

     Sean Elliott, MD

    Sean Elliott, MD

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