AKA “breakbone fever”
>300 million cases/yr; 96 million with manifestations
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
Fever, arthralgia, rash...
Febrile phase (days 1-3)
Characterised by fever, viraemia, NS1 positive
Normal platelets, haematocrit
Critical phase (days 4-6)
Low platelets, raised haematocrit
Shock, bleeding, organ impairment
Recovery phase (days 6+)
Fluid resorption (fluid/electrolytes back into the plasma)
Factors associated with severe infection:
2nd infection: antibody dependant enhancement (ADE)
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.
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)
Retro-orbital pain; LN, photophobia
Rash in 50%; maculopapular
Positive tourniquet test in 30%
Dengue haemorrhagic fever (DHF)
Increased vascular permeability on day 3-7
Restless ? ARF, hepatomegaly
1: positive tourniquet test
2: Spontaneous bleeding
4: BP unrecordable
Classification (after 2009)
Rash (not all patients will have… macular, petechial..)
Aches and pains
Tourniquet test +
Any warning sign
Clinical fluid accumulation
Lab: increased HCT with decreased platelets (do daily FBC)
Severe plasma leakage leading to shock or fluid accumulation with resp. distress
Severe organ involvement e.g liver (raised LFTs), CNS (acute encephalitis syndrome), cardiac (acute myocarditis, arrhythmias)
Issue with the vaccine:
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
Arbovirus.. viruses transmitted by insects
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
Non-specific febrile illness
2nd infection can be the worst.. 3rd & 4th less so
What are the clinical features of dengue?
Illness course…see WHO 2009 guidelines…
- 48 hours, shock etc.
- reabsorption . fluid overload.. IgM/IgG
How is dengue managed?
Assess for shock
Fluids: risk of fluid overload (base on haematocrit)… flow chart
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
Dengvaxia efficacy 56%.. 65% LA, works if have dengue Abs, poor against DENV2
****story of Sanofi vaccine and Philippines..***
Introduce Wolbachia to mosquitoes so can’t transmit dengue.
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.