Saturday, November 11, 2017

DENGUE FEVER



                                                           DENGUE FEVER

Dengue is a mosquito born viral disease
Occurs in tropical areas
Vector- Aedes aegypti mosquito
Cause: dengue virus
4 distinct type of dengue virus- type 1,2,3and 4.

Clinical presentation: 3 broad patterns.
1.       Classical dengue
2.       Dengue hemorrhagic fever
3.       Mild atypical form.

Classic Dengue
Incubation period about 1 week
Prodromal symptoms like mild conjunctivitis,cold
Abrupt onset of fever with splitting headache, retro orbitl pain,back ache,joint pain.
Insomnia,anorexia, loss of taste weakness.

PHYSICAL EXAMINATION
conjunctival congestion,
Tenderness upon pressure on eyeball
Lymph adenopathy,
Skin rash
2-3 days after the onset ,temperature may decrease to  near normal  and other symptoms may disappear.This remission typically lasts 2 days
Following this there is return of fever and symptoms
This is called saddle back fever

Lab findings:
Neutropenia,leuko penia
Virus can be isolated from blood,
Viral antibody titre rises.
TREATMENT: only symptomatic with analgesics and antipyretics.

HEMORRHAGIC FEVER/Dengue shock syndrome
Can be caused by all 4 viral sero types.
WHO clinical classification of Dengue fever
Grade1:                Fever,constitutional symptoms, positive tourniquet test
Grade 2:               Grade1 Plus spontaneous bleeding
Grade3:                  Grade 2 plus circulatory failure plus agitation
Grade4;                    Grade2 plus  profound shock.
All 4 grades are associated with thrombocytopenia and hemoconcentration
TREATMENT
Fluid replacement,
Platelet/blood transfusion
Corticosteroids
Symptomatic treatment.

WHO criteria for diagnosis of Dengue Hemorrhagic fever
Acute onset high continuous fever lasting for 2-7 days
Hemorrhagic manifestations:  petichea/purpura/ecchymoses/epistaxis/bleeding gums
Hemetemisis,melena
Hepatomegaly
Thrombocytopenia ≤ 100000/cubic mm
Hemoconcentration , hematocrit increased by≥ 20%

Dengue Shock syndrome:
Rapid, thready pulse with narrow pulse pressure less than 20mm /hypotension
Cold clammy skin and restlessness.


LAB tests:
Important lab tests  at present available
1.viral culture
2.viral RNA detection by reverse transcriptase(RT-PCR)
3.serological tests-immunoglobulinM
ELISA-enzyme linked immunoabsorbant assay (MAC-ELISA)
All these diagnostic assays have their own snags.
Also  diagnosis at the early stage of illness is very difficult.
Gold standard test is viral culture - disadvantage –time consuming procedure-cannot be used as a routine.
RT-PCR useful in early stage-but trained staff ,cost and sophisticated equipment ‘s need-disadvantage.
MAC-ELISA-commonly used-but sensitivity is low  in first 4 days

 

New approach

ELISA against non structural glycoproteins( NSI antigen)- very useful in early phase
Early diagnosis and treatment reduces mortality
But it may not predict severity of dengue infection early.


Molecular virology- the basis of lab diagnosis

 

The viral poly proteins are classified into 2 types
1.structural polyproteins: 3 in number:- C,PrM and E

2.Non structural poly proteins.:NS proteins: seven in number
Of these NS1 is important.;It  has a role in viral RNA replication

NS1 antigen
This antigen, a glycoprotein, is found in abundance in patient’s serum in early stages
It is useful for the diagnosis in early and acute stage
ELISA based assay of  this antigen- non structural glycoproteins( NSI antigen)- very useful in early phase diagnosis,in the viremic stage

Summarizing,
current therapy is symptomatic consists mainly of fluid  replacement
Selective therapy is not available.
Vaccine
No vaccine is available.
Finding a vaccine agaist all 4 sero types is being problematic.
 A Japenese firm is expected to market a  dengue vaccine soon.


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