Dengue

  • AKA “breakbone fever”

  • >300 million cases/yr; 96 million with manifestations

  • Flavivirus: RNA virus with 4 distinct serotypes: DENV 1-4 (consider actually as 4 separate viruses, as similar to zika)

  • Transmitted by Aedes aegypti (mainly) and aedes albopictus mosquito (car tyres, overcrowding, travel, fresh water around, daytime feeding)

  • Human to human with no significant virus amplification in animals

Clinical features

  • Fever, arthralgia, rash...

Febrile phase (days 1-3)

  • Characterised by fever, viraemia, NS1 positive

  • Normal platelets, haematocrit

Critical phase (days 4-6)

  • Normal temperature

  • Low platelets, raised haematocrit

  • Shock, bleeding, organ impairment

Recovery phase (days 6+)

  • Fluid resorption


Factors associated with severe infection:

2nd infection: antibody dependant enhancement (ADE)

Diagnosis

  • Non-specific: leucopenia, thrombocytopenia, raised haematocrit

  • Antigen detection: Non-structural protein 1 (NS1)

  • Nucleic acid detection: PCR: can distinguish different serotype?

  • Antibody detection: IgM / IgG: ELISA, after fever subsides.

Specific tests

  • PCR or ELISA (NS1) using rapid test in the first week

  • Clinics use rapid tests but not good for all serotypes e.g. DENV 2 (worst type)

  • Dengue Duo: combined Ag/Ab test:

  • Sensitivity: 92.4% (Dengue NS1 Ag), 94.2% (Dengue IgG/IgM)

  • Specificity: 98.4%(Dengue NS1 Ag), 96.4% (Dengue IgG/IgM)

Classification (before 2009)

Dengue Fever

  • FAR

  • Retro-orbital pain; LN, photophobia

  • Rash in 50%; maculopapular

  • Petechiae

  • Positive tourniquet test in 30%

Dengue haemorrhagic fever (DHF)

  • Increased vascular permeability on day 3-7

  • Thrombocytopenia, haematocrit

  • Restless ? ARF, hepatomegaly

Grading (previous)

1: positive tourniquet test

2: Spontaneous bleeding

3: shock

4: BP unrecordable

Classification (after 2009)

Probable dengue

  • Nausea/vomiting

  • Rash (not all patients will have… macular, petechial..)

  • Aches and pains

  • Tourniquet test +

  • Leucopenia

  • Any warning sign

  • Lab confirmed

Warning signs

  • Abdo pain/tenderness

  • Persistent vomiting

  • Clinical fluid accumulation

  • Mucosal bleed

  • Lethargy/restlessness

  • Hepatomegaly

  • Lab: increased HCT with decreased platelets (do daily FBC)

Severe dengue

  1. Severe plasma leakage leading to shock or fluid accumulation with resp. distress

  2. Severe bleeding

  3. Severe organ involvement e.g liver (raised LFTs), CNS (acute encephalitis syndrome), cardiac (acute myocarditis, arrhythmias)

Management

Supportive

Vaccine

Issue with the vaccine:

History

  • 1950's "Manila" haemorrhagic fever, later Bangkok, 1980's-1990's severe haemorrhagic fever recognised throughout Asia. 1980-1997 increasing spread of dengue haemorrhagic fever in the America's

  • Previously big outbreaks every four years, however more frequent now due to all four serotypes circulating with different serotypes dominating

  • Outbreaks in Japan in WW2 and Tokyo in 2014 (DENV1), Cambodia in 1995 in refugee camps

References

Virus> arbovirus>FAR/VHF

Arbovirus.. viruses transmitted by insects

Flavivirus


What is dengue?

  • AKA “breakbone” fever

  • >100 million cases/yr; global pandemic

  • 4 distinct serotypes; (DENV 1-4)

  • Aedes mosquitoes; poor control leads to epidemics

  • transport of car tyres; overcrowding; travel

  • peri-domestic; fresh water around house

  • Daytime feeding

Non-specific febrile illness

Pathophysiology

  • 2nd infection can be the worst.. 3rd & 4th less so

What are the clinical features of dengue?

Illness course…see WHO 2009 guidelines…

Febrile phase

Critical phase

- 48 hours, shock etc.

Recovery phase

- reabsorption . fluid overload.. IgM/IgG


How is dengue managed?

Symptomatic treatment

  • Assess for shock

  • Fluids: risk of fluid overload (base on haematocrit)… flow chart

No benefit

  • Trials to reduce viraemia: Chloroquine, Balapiravir, steroids, Lovastatin … no effect

  • ? too late as virus starts to fall early


How is dengue prevented?

  • Vector control: Aedes mosquitoes

  • Larvicides stored water

  • Vaccines- tetravalent


  • Dengvaxia efficacy 56%.. 65% LA, works if have dengue Abs, poor against DENV2

****story of Sanofi vaccine and Philippines..***


Future ?

Introduce Wolbachia to mosquitoes so can’t transmit dengue.


MCQs

Dengue fever

a. is spread by the vector Aedes aegypti

b. has an incubation period of 2-3 weeks

c. is caused by a flavivirus

d. characteristically causes severe myalgia

e. is more likely to cause haemorrhage in patients previously infected by a Dengue virus


Dengue fever is at present the second most common cause of imported fever. Only malaria is more common as a cause of fever in travellers returning to the UK from the tropics. Enteric fever and hepatitis A are also common.


Dengue fever is particularly common in travellers to South East Asia but is widely distributed throughout the tropics.


The dengue virus is a single-stranded RNA virus, a flavivirus related to yellow fever virus. There are four serotypes.


The incubation period is short: about 4 days. Indeed viral infections should always be considered in those who develop fever within a week of arriving in a tropical area. The fever lasts about 4 days and may be biphasic ("saddleback").


The clinical presentation may be :

1. non-specific fever

2. Dengue fever syndrome characterised by severe myalgia

3. Dengue haemorrhagic fever / Dengue septic shock. This life-threathening form is more common in those previously infected. There is increased antibody production and DIC.

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