17 - Dengue

Dengue

• Caused by what

• Transmitted by what

• Dengue virus(Single strand RNA)

• Aedes aegypti mosquito

Dengue stages

Febrile(Days 1-7), critical phase(Days 3-7), Recovery

What cells do dengue infect/replicate in, what symptoms does this lead to, and what phase does this correlate to?

Monocytes/macrophages → triggers systemic inflammatory response → fever, myalgia, retro-orbital pain

• Fever phase of dengue

What does defervescence mean, and what does this mean for the patient, and why?

Fever goes down, it means the pt. is about to enter the critical phase. This is because the massive cytokine release has damaged the endothelium and glycocalyx boosts vascular permeability and makes the blood vessels leaky, so plasma begins to leak out

Symptoms of the critical phase

• Symptoms:

  • Elevated Hct: Because plasma leaves the vessels, leaving just the cells(normal: 40-50%)

  • Tachycardia: To maintain CO despite less volume

  • Prolonged capillary refill time: Because vasoconstriction happens to direct flow to crucial organs(normal: <2 seconds)

  • Cold extremities: Due to peripheral vasoconstriction for the same reason

  • Restlessness: Sign of reduced cerebral perfusion

  • Low JVP: Because less blood returns to the RA(normal: 3-4cm)

  • Hypotension: Lower than 90/60 with a narrow pulse pressure(A gap of less than 20-30mmHg)

  • Thrombocytopenia: Platelet activation from the damaged endothelium, bone marrow suppression, presents as petechiae, epistaxis, gingival bleeding

  • Leukopenia with relative lymphocytosis with atypical lymphocytes

Recovery phase of dengue

• Symptoms

• Fluid overload signs(sometimes), improving vitals, regain of appetite, bradycardia, and rashes with small islands of sparing

What antigen do we look for when we do Dengue antigen testing, and how early can we do this?

NS1 antigen, detectable from days 1 to around 5

How long after infection do IgM and IgG dengue antibodies pop up and how long do they last?

IgM: 3-5 days and lasts a few months

IgG: 7-10 and persists for years

What does it mean if a patient has negative NS1 antigen results, negative IgM, but positive IgG?

Signals a past infection has happened

Gold standard of identifying dengue infection

RT-PCR

DF, DHF, DSS

These sit on the same spectrum, but it depends on how much plasma leakage has happened

• Dengue fever: This is the breakbone fever, but there’s no plasma leakage

• Dengue Hemorrhagic Fever: Plasma leakage has began and we might see thrombocytopenia etc

• Dengue Shock Syndrome: Plasma leakage has happened enough to cause shock(Narrow pulse pressure, hypotension, etc), basically high grade DHF

How does the 2009 Dengue classification system work?

DF → Dengue without warning signs

DHF(mild) → Dengue with warning signs

DSS → Severe dengue

Dengue warning signs

• Fever goes down but symptoms haven’t improved

• Abdominal pain/vomiting

• Syncope/dizziness/cold extremities

• Oliguria

• Bleeding

Normal amnt of urine rate and what does it represent?

0.5 mL/kg/hr and this represents normal kidney perfusion

Dengue treatment

No antiviral exists → supportive care via fluid management

1. Dengue w warning signs: Start slow while reassessing if Hct keeps rising/vitals getting worse, if it does, we increase rate

2. Dengue shock syndrome: Start with large bolus then go down until the patient gets better

ADE in Dengue: What is it, and how does it work?

Antibody dependent enhancement

• The body makes antibodies against the dengue serotype(There’s 4) that we get infected with. However, these antibodies are only good at fighting said serotype. If we get infected with a different serotype, those antibodies will try to bind to the dengue, but will suck at it, and will actually allow the virus(now bound to the antibody) to be uptaken into cells like macrophages/monocytes(the very cells they want to infect)

Qdenga vs dengvaxia

Qdenga is made from dengue backbone, while dengvaxia is from yellow fever

• This means that dengvaxia trains the body worse, so it can actually cause ADE in patients who have never been infected w dengue before, so dengvaxia is best just as a booster for people who have been infected before

Dengue causes fluid leakage into ___, but not ___

Into pleural, peritoneal, pericardial spaces, but not generalized edema

What are the 3 things that damage the endothelial cells in dengue, and what component is damaged?

1. DENV(the virus)

2. Cytokines

3. NS1(acts like a toxin and activates immune cells)

The glycocalyx

What type of shock does DSS cause?

• Hypovolemic: Insufficient volume(from the fluid leaking out)

  • Distributive shock(due to loss of vascular muscular tone and dilates too much), also called vasoplegia, and this can happen due to the cytokine storm, and this is superimposed onto the hypovolemic shock

DSS compensatory response

1. Baroreceptor reflex → Symp. NS boosts HR and vasoconstriction → Tachycardia, attempted higher BP

2. Neurohormonal → RAAS, ADH

What is pulse pressure, and what it’s like in DSS, and why?

Pulse pressure: Systolic BP - diastolic BP

• In DSS, it’ll be narrow because the body will try to raise diastolic pressure to keep pressure up to perfuse organs, while the decreased stroke volume leads to a decreased systolic pressure, so it narrows the gap

Decompensated shock simple meaning

The body can no longer boost up it’s MAP to a sufficient level, and vital organs are inadequately perfused

What does delayed capillary refill time and increased lactic acid production indicate in a DSS patient?

• Delayed capillary refill time: The body is doing peripheral vasoconstriction, shunting blood away from peripheral organs to send it to the more vital organs

• Increased lactic acid: Cells aren’t perfused w enough oxygen so they’re doing anaerobic metabolism instead