DENGUE FEVER

DR M L PATEL MD
ASSOCIATE PROFESSOR
DEPTT OF MEDICINE
KGMU
 INTRODUCTION
EPIDEMIOLOGY
AETIOPATHOGENESIS
DEFINITION AND CLASSIFICATION
CLINICAL SIGNS AND SYMPTOMS
DIAGNOSIS
TREATMENT AND COMPLICATIONS
INTRODUCTION: A neglected tropical disease
Dengue has become a rapidly emerged mosquito-borne viral disease in recent
years and is endemic in all continents.
It is caused by the bite of the female Aedes (Ae.) mosquito with Ae. aegypti
being the most common species.
In India during 2010, a total of 28 292 cases were reported, which increased
to 50 222 in 2012 and 75 808 in 2013.
As per the data from the NVBDCP although the case fatality rate has
declined but incidence is on increasing trend.
Dengue symptoms may range from a mild febrile illness to fatal shock
syndrome and multi-organ failure.
EPIDEMIOLOGY
Of the 36 states/UTs, 35 (all except Lakshadweep) have reported dengue
cases during the last two decades.
Incidence has been increasing due to various reasons construction
activities, lifestyle changes, deficient water management, improper water
storage, stagnation of rain water etc.
The upsurge is seen during the period JulyNovember, a seasonal pattern;
During monsoons the temperatures in the range of 25 C 5 C, relative
humidity around 80% and innumerable small water collections result in
high vector density.
AETIOPATHOGENESIS
VECTOR:
The main vector responsible for dengue transmission in India is the Aedes
aegypti. Other species include Ae. albopictus & Ae. polynesiensis.
VIRUS:
Dengue virus is ssRNA and belongs to genus Flavivirus.
There are seven nonstructural proteins (NS), which are involved in various
functions affecting viral replication and disease pathogenesis.
Four serotypes- DENV-1, DENV-2, DENV-3 and DENV-4. All are found in
India.
All four serotypes are antigenically similar, but are different enough to elicit
crossprotection only for a few months after infection by any one of them.
Infection with any one serotype confers lifelong immunity to the virus serotype.
 Transmission cycle is human-to-mosquito-to-human cycle.
Virus infected Ae. aegypti mosquito bites a person, he/she develops viremia.
4-5 days after the bite, the person develops symptoms of dengue fever.
When aedes mosquito bites a dengue infected person, the virus enters into the
blood stream of the mosquito making it a dengue vector.
Thus it is the human which propagates the infection through the mosquito.
PATHOPHYSIOLOGY
Host immune response to the viral infection plays the most important
role in the pathogenesis of clinical syndrome of dengue.
The ultimate target of the immune cascade is-
Vascular endothelium,
Platelets and
Vital organs.
The end result is vasculopathy and coagulopathy responsible for the
development of haemorrhage and shock.
CLINICAL FEATURES
Dengue viral infected person may be asymptomatic or symptomatic and clinical
manifestations vary from undifferentiated fever to florid hemorrhage and shock.
Classical initial symptoms are common flu like, include-
High grade fever up to 104F.
Severe arthralgia & myalgia.
Headache and retro-orbital pain.
Other important symptoms are-
Maculopapular rash that may or may not be always present.
The rash classically develops on day 2-3 or during defervescence when it is called
as the white islands in the sea of red.
Expanded Dengue Syndrome-(EDS)
Unusual manifestations of DF/DHF are commonly associated with co-
morbidities and with various other co-infections.
Clinical manifestations observed in EDS are as follows:
CLINICAL COURSE OF DENGUE FEVER
CASE DEFINITION
Probable DF/DHF- A case compatible with clinical description of dengue
Fever during outbreak OR Non-ELISA based NS1 antigen/ IgM positive.
Confirmed Dengue Fever- A case compatible with the clinical description
of dengue fever with at least one of the following-
Isolation of the dengue virus from serum, plasma, leucocytes.
Demonstration of IgM antibody titre by ELISA positive in single serum sample.
Demonstration of dengue virus antigen in serum sample by NS1-ELISA.
IgG seroconversion in paired sera after 2 wks with Four fold increase of IgG titre.
Detection of viral nucleic acid by polymerase chain reaction (PCR).
Clinical criteria-
DENGUE FEVER- An acute febrile illness of 2-7 days duration with two or more of
the following manifestations: Headache, retro-orbital pain, myalgia, arthralgia, rash,
haemorrhagic manifestations.
DENGUE HEMORRHAGIC FEVER- a case with clinical criteria of dengue fever
hemorrhagic tendency thrombocytopenia evidence of plasma leakage.

Positive tourniquet test Platelet count < 1 lacs/ A rise in average Hct for age and
Petechiae, ecchymoses or mm3 sex > 20%
purpura A >20% drop in Hct following
Bleeding from mucosa, volume replacement treatment
GI tract, injection sites compared to baseline
etc. Signs of plasma leakage (pleural
effusion, ascites, hypoproteinemia)
DENGUE SHOCK SYNDROME
All the above criteria for DHF with evidence of circulatory failure manifested
by rapid and weak pulse and narrow pulse pressure ( <20 mmHg) or
hypotension for age, cold and clammy skin and restlessness.

Tourniquet test:
The tourniquet test is performed by inflating a blood pressure cuff to a midpoint between
the systolic and diastolic pressure and maintain for five minutes.
The test is considered positive when 10 or more petechiae per one square inch area over
forearm are observed.
In DHF, the test usually gives a definite positive test with 20 petechiae or more.
The test may be negative or only mildly positive during the phase of profound shock
(DSS).
 GRADING OF DENGUE FEVER/DHF

DF: Fever of 2-7 days with two or more of following- Headache, Retro orbital pain,
Myalgia, Arthralgia with or without leukopenia, thrombocytopenia and no evidence of
plasma leakage.
DHFI: DF + positive tourniquet test and evidence of plasma leakage. Thrombocytopenia
with platelet count less than 100000/ cu.mm and Hct rise more than 20% over baseline.
DHFII: DHF + evidence of spontaneous bleeding in skin or other organs (black tarry
stool, epistaxis, gum bleeds) and abdominal pain.
DHFIII (DSS): DHF+ circulatory failure (weak rapid pulse, narrow pulse pressure <
20 mm Hg, Hypotension, cold clammy skin, restlessness).
DHFIV (DSS): Profound shock with undetectable blood pressure or pulse.
 CLASSIFICATION
DENGUE VIRAL INFECTION
SYMPTOMATIC ASYMPTOMATIC

MILD DENGUE MODERATE DENGUE SEVERE DENGUE

DF with high risk & DF with warning signs DF DHF with significant
Undifferentiated DF
comorbid conditions and symptoms Haemorrhage
Fever without
DHF with shock (DHF III & IV- DSS)
complication like Infants 1. DF with warning signs
Severe organ involvement
bleeding, Old age and symptoms
(Expanded Dengue Syndrome)
hypotension and Diabetes Recurrent vomiting
Severe Metabolic Disorder
organ involvement Hypertension Abdominal pain/
Without evidence of Pregnancy tenderness
capillary leakage CAD General weakness/
letharginess/ restless
TERTIARY LEVEL CARE
Hemoglobinopathies
Immunocompromise Mild pleural effusion/
HOME Patient on steroids, ascites
MANAGEMENT anticoagulants or Hepatomegaly
Increased Hct>20%
CLOSE MONITORING &
immunosuppressants.
2. DHF I & II with minor POSSIBLE HOSPITALISATION
bleeds
LABORATORY WORKUP AND DIAGNOSIS
ELISA-based NS1 antigen tests- diagnosis of acute dengue infections, more
specific and shows high sensitivity.
IgM-capture enzyme-linked immunosorbent assay (MAC-ELISA)- The anti-
dengue IgM antibody is usually detectable by day 5 of the illness.
Useful for hospitalized patients, who are generally admitted late in the illness
after detectable IgM is already present in the blood.
Polymerase chain reaction (PCR)- real-time RT-PCR has gradually replaced
the virus isolation method as the new standard for the detection of dengue virus
in acute-phase serum samples.
Isolation of dengue virus- not commonly used now.
IgG-ELISA- used to differentiate primary and secondary dengue Infections, not
considered as a diagnostic test as it indicates past infections only.
MANAGEMENT: KEY POINTS
Approach to clinical management vary depending on severity of illness.
The patients who have simple fever without any danger signs or complications may
be managed with symptomatic approach.
Those with warning signs & symptoms should be closely monitored for progression
of disease.
DHFIII & IV , significant bleeding or involvement of various organs require
aggressive management to reduce morbidity and mortality.
Patient may develop complications during later stage of fever (defervescence) or
afebrile phase, where clinician should be careful to look for danger signs and signs
of fluid overload.
Management of dengue fever(DF) is symptomatic and
supportive-
Bed rest is advisable during the acute phase.
Use cold/tepid sponging to keep temperature below 38.5 C.
Antipyretics may be used to lower the body temperature. Aspirin/NSAIDS
like Ibuprofen, etc should be avoided.
Oral fluid and electrolyte therapy is recommended for patients with excessive
sweating or vomiting.
Patients should be monitored for 24 to 48 hours after they become afebrile
for development of complications.
MANAGEMENT OF DENGUE HEMORRHAGIC FEVER-

Hospitalisation
Early aggressive fluid therapy- (most important aspect)
Close monitoring of vitals and Hct
Transfusion
Vital organ support (ventilator, Hemodialysis)
 Fluid therapy in DHF-
Calculation of fluid- the amount of fluid to be given in 24 hour is
maintenance fluid+ 50ml/kg.
Maintenance fluid is calculated by Holiday Segar formula-
Body weight in kg Maintenance volume for 24 hours
<10 kg 100 ml / kg
10-20 1000+50 ml / kg body weight exceeding 10 kg
>20 kg 1500+20 ml / kg body weight exceeding 20 kg

Choice of fluid-
crystalloids are the initial fluid of choice.
Colloids may be considered in the first step when BP needs to be restored
quickly.
Indication of platelet transfusion-
1. Platelet count less than 10000/cu.mm in absence of bleeding
manifestations (Prophylactic platelet transfusion).
2. Haemorrhage with or without thrombocytopenia.
3. Packed cell transfusion/FFP along with platelets may be required in
cases of severe bleeding with coagulopathy.
4. Platelets are available as RDP(random donor) & SDP(single donor).
Criteria for discharge of the patient-
Afebrile since last 24 hours.
Normal BP
Normal urine output
No respiratory distress
Persistent platelet count >50,000/ mm3
DENGUE VACCINE
Dengvaxia ( Sanofi Pastuer) is the first licensed vaccine for the
prevention of dengue.
A recombinant chimeric live attenuated tetravalent vaccine.
The vaccine induces antibodies to each of the four dengue virus serotypes.
The vaccine is given as three doses over the course of a year.
Currently not approved in India.
DHF
I & II
DHF
III &
IV
DHF
III &
IV
COMPLICATIONS-
Massive bleeding
Circulatory shock
Hepatic failure
Renal failure
Encephalopathy
Myocarditis
Death
TAKE HOME MESSAGE
Prompt recognition of symptoms during the epidemic season.

Not all dengue positive patient require hospitalisation.

Awareness regarding the warning signs.

Identifying the high risk category patients.

Awareness regarding sanitation and use anti mosquito measures.

Prevention is cure.