Dengue Fever,Pathophysiology, Symptoms, Diagnosis & Treatment

 

Hi everyone welcome to another lesson

this lesson is on dengue fever so we're

gonna talk about how we become infected

with dengue fever what are some of the

signs and symptoms are also going to

talk about how we diagnose it and how we

can treat it so dengue fever is an

illness due to an infection with a virus

of the family flaaaav e'r'day and there

are a subset of five of e'r'day viruses

known as the dengue viruses so there are

actually four dengue viruses and we name

them the env1 to be envied for so then

v1 that then v4 they are all enveloped

viruses we're going to talk about why

this is important a little later and

they're all positive single-stranded RNA

viruses now dengue fever is an important

cause of what we call a fever or in a

returned traveler so what that means is

that if there is a traveler to a perhaps

exotic locale and they come back to

their home country and they have a fever

dengue fever actually accounts for about

5% of those cases so where are some of

those exotic locales so most of them are

in tropical and subtropical climates and

a couple in particular that I want you

to think about are the Caribbean and

Southeast Asia

so how do we get infected with this

virus we actually get it from our lovely

friends the mosquitoes once again and

the mosquitoes in particular are the

species 80s Egypt I which is actually

the same mosquito that can infect us

with yellow fever and the related

species 80s el Bob pictus so what is the

pathogenesis of dengue fever once we

actually become infected once a mosquito

bites us in our skin the viruses can

actually fuse with a host cell now there

are some theories as to what some of the

host cells might be some theories are

that they are the Langerhans cells in

our skin which is an immune cell

whatever that host cell might be the

dengue virus fuses with that cell and

enters the cell so how does it fuse with

the cell it's actually mediated by the

viral envelope a glycoprotein which is

important for infectivity so that is

actually how the dengue virus can attach

to a host cell and enter that host cell

what are some of the viral receptors

that it attaches to well some of these

receptors include heparin sulfate that

is located on the host cell there's some

other ones as well but we won't talk

about them here once the virus enters

the cell it gets packaged into an

endosome and acidified vacuole and it

eventually becomes disassembled into its

viral RNA once that viral RNA has been

exposed it can become replicated inside

the cell and once we have enough of

viral replication the virus actually

assembles and we can think about it

assembling in the ER or the endoplasmic

reticulum once the virus has assemble

that can mature into a variety into

plasmic reticulum and Golgi apparatus

and can get packaged again and it can be

released to be able to infect other

cells so that is actually the basic

process as to how the dengue virus and

many other viruses infect host cells

once that virus leaves that host cell it

can

move on to infecting local lymph nodes

and in lead to very Mia or virus in the

blood so what are some of the signs and

symptoms of dengue fever so thingy fever

actually leads to a variable clinical

presentation can anywhere from

asymptomatic to life-threatening what we

find is that

bengi fever is more likely to be a

somatic in children now when we do

become infected with the virus the

incubation period for that virus is on

average anywhere from 3 to 14 days and

there are actually three phases of

infection I'm going to talk about here

in the next few slides the first phase

is the febrile phase the second is the

critical phase the critical phase

doesn't necessarily have to occur in

every infection but we'll talk about

what are some of the risk factors for

getting this critical phase and then the

third phase is the recovery phase so

each of these phases has different signs

and symptoms and different clinical

outcomes so we'll start with the febrile

phase the febrile phase is where this

infection begins to become symptomatic

and the symptoms usually begin at a four

today seven and when we do begin to have

symptoms of the febrile face the febrile

phase lasts for three to seven days and

as its name suggests it has a fever and

the fever is a fever of sudden onset it

rapidly and suddenly occurs and it is a

high grade fever greater than 38 point

five degrees Celsius again it is a very

important cause of fever in the return

traveler other common symptoms include

headache and we can also get retro

orbital eye pain so pain in behind the

eyes and this is something that will be

almost like a key phrase for you if you

hear fever headache return traveler and

retro orbital pain you are thinking

dengue fever so retro orbital pain Clues

you into this being dengue fever

patients can also have myalgias or

muscle pain and arthralgias or joint

pain and some other symptoms that might

not necessarily occur

include some gastrointestinal symptoms

like nausea and vomiting diarrhea and

abdominal pain if a patient is having

persistent vomiting and abdominal pain

we consider this a worrisome find which

means it could be a more severe

presentation some other signs and

symptoms of the febrile phase include

lymph adenopathy so swollen tender lymph

nodes

how paddle megali so an enlarged liver

and this is actually another warning

sign that may indicate a severe

presentation of NJ fever we can also see

a maculopapular rash so maculopapular

rash like here in this image so we can

see this reddened flat or perhaps

slightly raised rash and it occurs in

approximately 50% of cases and it's more

common in the first dengue infection so

if someone gets dengue fever for the

first time they're more likely to have

the maculopapular rash compared to if

they were to be infected with dengue

fever a second or a third time and the

maculopapular rash generally erupts

about two to five days after fever has

started and dengue fever can have some

other symptoms that are less common

including respiratory symptoms like

cough nasal congestion and sore throat

and some of the more worrisome things

that can happen in the febrile phase in

dengue fever are the findings of

leukopenia or low white blood cell count

thrombocytopenia or low platelet count

and Trans Am and itis or elevated liver

enzymes like alt and ast

so these only happen in a small subset

of febrile faced patients but if they do

they are again well worrisome sign that

this is a severe dengue fever so what is

the critical phase so the critical phase

occurs again in a small subset of

patients most patients have the febrile

phase and they recover fine but some get

this more severe presentation and the

critical phase of dengue fever is more

likely to occur in the following cases

having a secondary infection of dengue

fever and when I mean by secondary

infection is that they've had a previous

dengue fever infection before they

recovered they were fine and then they

get it again

and a lot of times it's with another and

gay serotype remember we said there are

four different named gay viruses if they

were to be infected with one of those

and then they're infected again with a

second different dengue serotype then

they are more at risk for having the

critical phase in particular if they've

had that first infection within 18

months of the second infection so again

if they had a primary infection and

within 18 months they get another

infection with a different dengue virus

they're more likely to enter the

critical phase of dengue fever infection

in critical phase of infection is also

more common or occurs more often in

patients with other medical

comorbidities if the critical phase does

occur it occurs about 3 to 7 days into

the infection after d4 vessels which

means that it's after the fever has

resolved and the critical phase lasts

for about 24 to 48 hours and what we see

in the critical phase is

thrombocytopenia so low platelet count

and can be very severe even less than a

count of 20 and because of the low

platelet count we see increased risk of

bleeding so we can see hematochezia so

red blood in the stool

melina or black tarry stool hematemesis

so vomiting up of blood epistaxis so

nosebleeds and even menorrhagia or heavy

menstrual periods so all of these can

occur due to that very low platelet

count and these symptoms are often what

we call dengue hemorrhagic fever now

this term is not often used anymore we

can still hear it but a lot of times now

we describe dengue fever as mild or

severe so we may still hear dengue

hemorrhagic fever this is essentially

what this means you get very severe

thrombocytopenia and increased risk of

bleeding so again we may see the

beginning of the thrombocytopenia in the

febrile phase not always but we can but

if it does occur in the febrile phase

it's not as severe as it would be in the

critical phase and in the critical phase

we may also see vascular leakage so

there's so much inflammatory cytokines

that it can lead to leakage out of the

intravascular space we can lose

intravascular volume leading to

hypotension or shock and this can lead

to a variety of organizations leverage

and central nervous system involvement

so these signs and symptoms are what we

call in gay

shock syndrome but like dengue

hemorrhagic fever the term engage shock

syndrome is not being used as often we

actually prefer to use newer criteria

that describes dengue fever without

warning symptoms with warning symptoms

or severe dengue fever so these would be

considered part of severe dengue fever

but you may still hear the term dengue

hemorrhagic fever so think about

thrombocytopenia in the bleeding or

dengue shock syndrome where we can think

of vascular leakage leading to

hypertension and shock and organ

impairment so again older terms that are

still being used but we may use other

types of terminology nowadays and the

third phase is the recovery phase so

recovery phase as its name suggests is

essentially a resolution of all those

problems we talked about resolution of

vascular permeability and the

hemorrhagic risk the vital signs also

stabilize but you may also see an

eruption of a new rash similar to the

first rash so again it looks exactly the

same it's a maculopapular rash and it

may be pure attic so maybe itchy and it

usually lasts about 1 to 5 days and what

often happens is that even though these

patients may recover they may experience

chronic fatigue which can be

debilitating for them and this can last

for weeks to months so how do we make

the diagnosis and how do we treat engei

fever so the diagnosis is through

generally serology we can look for anti

dengue IgM so immunoglobulin M

antibodies against dengue virus and

these can be detected by about day four

of infection before that we may have to

use PCR to detect viral genomes or viral

genetics and the treatment of dengue

fever is often supportive a lot of times

patients recover on their own and there

is spontaneous resolution we can use

acetaminophen for symptom relief but we

want to avoid using ie Pro fin or Advil

due to its anti coagulation properties

because we've talked about before we

have decreased thrombocytes or decreased

platelet count so we don't want to

decrease platelet functioning by using

ibuprofen or Advil so we avoid using

this and we can try to prevent getting

dengue fever in the first place and we

can use a dengue vaccination but

unfortunately even if you get the dengue

vaccine you may not be fully protected

against dengue

infections but the good news is that

having a dengue vaccination reduces the

symptoms and the length of infection so

again diagnosis of dengue fever is by

looking for anti dengue IgM antibody

that is usually present by day four of

infection treatment is often supportive

this is a viral infection so we don't

have the right tools to fight this

infection we can use acetaminophen for

symptom relief for helping with

headaches and retro orbital pain but we

want to avoid Advil due to the bleeding

risk and we can try to prevent the

dengue fever in the first place by using

a dengue vaccination so if you want to

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