60 Arboviruses

James Whitehorn 04/10/18

Arboviruses are arthropod borne viruses

60.1 Dengue

NS1 antigen test

Can be self limiting with febrile illness. Can be severe with DIC, acidosis, death.

Transmitted by aedes

21,000 deaths. 2 million severe cases. Up to 500 million infections. (Globally yearly). This makes it the most abundant arboviral infection globally.

Can either be endemic/epidemic. It can overwhelm health systems during epidemic period (the rainy season)

60.1.1 Definitions

Reclassified in 2009 into:

  1. Dengue
  2. Dengue With Warning Signs
  3. Severe Dengue

We don’t talk about Dengue Haemorrhagic Fever any more

Warning Signs:

  • Abdo pain
  • Vomiting
  • Fluid
  • Mucosal bleed
  • Lethargy
  • Hepatomegaly
  • Increase in HCT

Severe Dengue:

  • Shock
  • Resp Distress from Pulm Oedema
  • Severe Bleeding
  • Severe Organ (liver, brain, heart) Involvement

60.1.2 Virus

Dengue Virus (Flavivirus - 4 serotypes). Basically 4 totally seperate viruses

Single stranded RNA virus

Simple virus genome. We use one of the non structural proteins in the genome for the diagnostic test.

60.1.3 Illness

  • Febrile Phase
  • Critical Phase - when you get plasma leak and properly sick
  • Recovery Phase

When monitoring the disease progression, we use the platelet count as a measure of severity, at it’s lowest is usually the sickest point. So when platelets are improving, patient is likely to improve

Incubation is between 4-14 days.

Most cases self limiting but fairly debilitating fevrile illness. With fever, headache, rashes

Rash: Petechial

Then in recovery you get a weird islands of white in a see of rash, like a sunburn

60.1.4 Platelets

Low in all patients w/ dengue

Normal platelets = no dengue

60.1.5 Severe

  • Vascular Depletion (increased vascular permeability)
  • Haemorrhage
  • Organ Impairment

Liver - LFTS almost always raised. Can get severe hepatitis

Brain - Acute encephalitis. more common in kids

Heart - Myocarditis, arrhythmias (bradycardia, others), myocardial depression

60.1.5.1 RF for severe disease

Why are secondary infections more likely to be severe?

Probs due to antibody dependent enhancement

This is where preexisting antibodies to old infection bind to a virus, but dont knock it out properly, the antibodies pull it into a monocyte (who have FC gamma receptor cells), and the virus then replicates in the cell, increasing viral load rather than lowering it!

Infants are probably the most vulnerable groups to severe disease, due to having maternal antibodies causing this response

60.1.5.2 Other RF’s

  • Older Ages
  • Under 5’s
  • Pregnant Women
  • Comorbidities (DM/HTN)
  • Obesity/Malnutrition

60.1.6 Capillary Leakage

Very transient but very severe.

There’s no lasting damage to the endothelial layer. This is prob caused by the NS1 antigen.

If we block this antigen, we can maybe stop the leakage

60.1.7 Diagnosis

  • NS1 Rapid Test

A really good rapid dest for most serotypes of dengue

A week later you can use serology

60.1.8 Treatment

Supportive, fluids, antipyretics.

Most patients could be managed as outpatients, but admit if warning signs.

Need careful fluid resuscitation in dengue. Recommend reserving colloids for refractory shock.

Really gentle fluids. CHECK ALGORITHM FROM SLIDES

60.1.8.1 Therapeutics for dengue?

We’re talking about therapeautics to prevent vascular leakage phase.

No viable drugs for it.

60.1.9 Vaccine?

Dengvaxia was the candidate

Live attenuated. All 4 serotypes. Uses a yellow fever back bone.

There are major safety concerns. Give it to people who haven’t had dengue before, you’ll increase their risk of severe disease

So now it’s withdrawn in many places

60.1.10 Vector Control

Thinking about introducing artifical wolbachia to aedes aegypti. May prevent it transmitting dengue.

60.2 Chikungunya

Chikungunya - “that which bends up” - refers to the bone pain caused

Alphavirus (another arbovirus)

Only one serotype, so once you’ve had it, you’re immune

Clinically similar to dengue, but you don’t get shock, and you only get minor bleeding

Aedes albopictus (asian tiger mosquito)

Most infections are symptomatic (loads of dengue aren’t)

Loads of polyarthralgia and skin manifestations

You can get some severe organ involvement, but that is really rare.

20-80% of patients get persistant joint symptoms (up to three months). And half of those will get a secondary inflammatory arthritis (needed treated w things like methotrexate)

Diagnose w/ serology or PCR

All symptomatic management.

60.3 Zika

Another flavivirus, v close to dengue.

First seen in africa in the 1940’s. 6% seroprevalence back in the 1950’s in Uganda. We think there’s been a really recent mutation making it more severe.

Aedes africanas in african lineage.

Aedes aegypti in asian lineage (maybe also aedes albopictus). This is the one that’s big and important in the world now.

Only 1/5 of patients are symptomatic.

Fever/arthralgia/skin rashes. V mild disease itself. It’s the complications that are scary. An explosive outbreak in brazil in 2015, showed a load of microcephaly, and neurological stuff.

We think there’s zika perinatal transmission in early pregnancy.

60.3.1 Diagnosis

  • Serology
  • PCR

DOn’t test asymptomatic not pregnant patients. Early illness, PCR on blod. Later illness (1 week) PCR on urine/serology. Later still (after 2 weeks) serology

60.3.2 WHO

WHO guidelines suggest if you leave an endemic area wait 6/12 months before unprotected sex.

CDC say if asymptomatic wait 8 weeks.

60.4 Yellow Fever

Yellow fever is the namesake for the flavivirus family

Vaccine preventable

Aedes mosquitoes

600 million in at risk areas. Africa and Latin America. No one really knows why it hasn’t spread to asia, the mosquitoes live there.

In Latin America - sylvatic cycle In Africa - more urban human to human.

You have a:

  • Infection Phase
  • Remission Phase after (can also have subconjunctival haemorrhage and relative bradycardia)
  • But some people get Intoxication with severe illness after

Diagnose:

  • AST more than ALT (cardiac disease)
  • Virus isolation

Severe yellow fever needs supportive treatment in ICU. Need isolated from mosquitoes.

Vaccine is live attenuated (17D vaccine), been around since 1930’s - but risks of viscerotropic disease in older age groups.