1. Dengue virus is transmitted to humans through the bites of infected Aedes aegypti mosquitoes. It causes a range of illnesses from dengue fever to the potentially lethal dengue hemorrhagic fever/dengue shock syndrome. 2. There are four distinct types of dengue virus. Infection produces both neutralizing and non-neutralizing antibodies. Non-neutralizing antibodies can enhance viral entry and increase severity of infection through antibody-dependent enhancement. 3. Clinical manifestations are caused by a combination of mechanisms including antibody-dependent enhancement, cytokine storm, vasculopathy, and coagulopathy. Treatment involves fluid management and monitoring for warning signs that may require hospitalization.

1. Dengue (DF)
Dengue Hemorrhagic Fever (DHF)
Dengue Shock Syndrome (DSS)
n.shruthi

2. ETIOLOGY
1. Small single-stranded RNA virus
2. Genus : Flavivirus
3. Four distinct antigenic types: DENV 1, DENV 2, DENV 3, DENV 4
4. Vector: Aedes aegypti (Stegomyia family) a daytime biting mosquito &
Aedes albopictus. Breeds in water stored for drinking or bathing and in
rainwater collected in any container.
5. Other possible transmissions:
1. Organ transplants
2. Blood transfusions
3. Mother to her fetus.

3. Aedes aegypti

4. Dengue Virus
• Serotypes and subtypes
• Serotype : Subtype/Genotype
• DENV-1: Three
• DENV-2: Six
• DENV-3: Four
• DENV-4: Four

5. Viral antigens:
1. The dengue virus is composed of three structural proteins
1. The nucleocapsid of core protein (C),
2. A membrane-associated protein (M),
3. An envelope protein(E) and
2. Seven non-structural (NS) proteins - NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5.
3. In dengue virus infection, patients have measurable levels of NS1 protein in the blood,
which are utilized as a diagnostic marker of the infection. (NS1 test)

6. Antibodies
1. As a result of infection, there are two types of antibodies being produced,
neutralizing and non neutralizing.
2. The neutralizing antibodies can protect against a specific serotype of the
virus.
3. The non-neutralizing antibodies bind to but do not neutralize an infecting
virus. Thses antibodies enhance viral entry and increase the severity of
infection. They are called infection enhancing antibodies and the
phenomenon is known as Antibody-Dependent Enhancement (ADE) of
infection.

7. Pathophysiology
Various mechanisms are proposed to explain the signs and symptoms observed in a
patient, and most have the following central themes:
i. Antibody-dependent enhancement (ADE)
ii. Cytokine Storm
iii. Vasculopathy
iv. Coagulopathy

8. Inflammatory response
1. Dengue virus-specific CD4+ and CD8+ T cells lyse dengue virus-infected cells and
produce cytokines such as IFN-gamma, tumour necrosis factor (TNF)-alpha, and
lymphotoxin, all of which results in a "Cytokine storm" and ultimately leads to more
severe disease.
2. IFN-gamma also enhances the expression of immunoglobulin receptors, which
augments the antibody-dependent enhancement of infection.

9. Vasculopathy
1. Vasculopathy is characterized by plasma leakage and a haemorrhagic diathesis.
2. Plasma leakage may be profound, sometimes resulting in life-threatening illness.
3. Hypotension is caused by plasma leakage, which may progress to profound shock with
an undetectable pulse and blood pressure.
4. A transient increase in capillary permeability and plasma leakage into interstitial,
pleural, pericardial spaces (third spaces) occur.
5. All these manifest as a combination of haemoconcentration, pleural, pericardial
effusion or ascites and various organ involvements like CNS depression, myocardial
dysfunction, hepatomegaly etc.

10. Coagulopathy
1. An increase in activated Partial Thromboplastin Time (aPTT) and reduction
in fibrinogen concentrations are relatively consistent findings in most
cases.
2. Thrombocytopenia increases the severity of haemorrhage.
3. Release of heparan sulphate or chondroitin sulphate (molecules similar in
structure to heparin that can mimic its function of anticoagulation) from
the glycocalyx also contributes to coagulopathy.

11. Clinical features of dengue
1. Probable Dengue fever:
a. A case compatible with the clinical description of dengue fever during the outbreak
b. NS1/IgM positive test
2. Confirmed Dengue Fever: any one of the following.
a. Demonstration of dengue virus antigen in a serum sample by NS1-ELISA
b. Demonstration of IgM antibody titer by ELISA in the single serum sample
c. IgG seroconversion in paired sera after 2 weeks with a fourfold increase of IgG titer
d. Detection of viral nucleic acid by PCR
e. Isolation of the virus (virus culture positive) from serum, plasma or leucocytes).

12. Dengue Warning Signs
1. Abdominal pain or tenderness
2. Persistent vomiting
3. Clinical fluid accumulation
4. Mucosal bleed
5. Lethargy; restlessness
6. Liver enlargement >2cm
7. Laboratory: Increase in HCT with rapid decrease in platelet count

13. The clinical course
1.Febrile phase
2.Critical phase
3.Convalescent phase

14. Febrile phase
1. The onset of dengue fever is usually with a sudden rise in temperature
which may be biphasic
2. It may be lasting for 2-7 days and is commonly associated with headache,
flushing, retro-orbital pain and/or rash, myalgia.
3. Maculopapular or rubelliform rash usually appear after 3rd or 4th day of
fever and is commonly seen on the face, neck and another part of the
body, it generally fades away in the latter half of febrile phase.

15. Critical phase (Leakage phase)
1. Dengue patients usually enter the critical phase after 3 to 4 days of onset of
the fever. During this phase plasma leakage and haemoconcentration occurs
in most cases and patients may develop hypotension.
2. Abnormal haemostasis and plasma leakage lead to bleeding, hypotension
and fluid accumulation in pleural, pericardial or abdominal cavities.
3. High morbidity and mortality are usually seen in cases with multiple organ
involvement or severe metabolic derangements.
4. The period of plasma leakage usually lasts for 36-48 hrs.

16. Convalescent phase (recovery phase)
1. During this phase, the extracellular fluid, which was lost due to capillary
leakage, returns to the circulatory system and signs and symptoms of the
patient improve.
2. This phase usually starts after 6-7 days of fever and lasts for 2-3 days.
3. The patient may develop pulmonary oedema due to fluid overload during
this phase, especially if the fluid replacement rate is not reviewed and
revised periodically.

17. LABORATORY FINDINGS
1. Hall mark: hemoconcentration and thrombocytopenia
2. white blood cell counts of <2,000/mm3.
3. Platelets rarely fall below 100,000/mm3.
4. The tourniquet test result may be positive.
a. Inflating a blood pressure cuff between the systolic and diastolic blood
pressures for approximately 5 minutes.
b. After release, the number of petechiae in a 2.5 x 2.5 cm patch is counted.
c. Greater than 20 petechiae indicates a positive test.

18. Treatment
Mild Dengue
1. Dengue infection without warning signs.
a. Patients with fever, body aches, rashes or minor bleeding may be treated
symptomatically. Fever and body aches are best treated with paracetamol.
b. Salicylates and other non-steroidal anti-inflammatory drugs (NSAIDs) should be
avoided as these may predispose to mucosal bleeds.
c. The patient should be encouraged to drink plenty of fluids.
2. Physician should monitor the patient for warning signs, along with haematocrit and platelet
counts. Any patient who develops warning signs as listed below should be admitted to a
hospital.

19. Moderate Dengue (Dengue with warning signs)
1. Patients with suspected dengue infection who have any of the following features
should be admitted to the hospital:
2. Abdominal pain or persistent tenderness vomiting
3. Fluid accumulation in pleural cavity, abdomen or subcutaneous tissues
4. Mucosal bleeds
5. Lethargy, restlessness or irritability Liver enlargement >2 cm.
6. Progressive increase in haematocrit (PCV normal is 45%) with a concurrent decrease in
platelet count (normal is 2L)

20. Severe dengue
1. Patients presenting or developing any of the following complications are diagnosed to
have severe dengue infection.
2. Severe plasma leakage leading to
a. Shock, delayed capillary refill or oliguria
b. Fluid accumulation in serosal cavities with respiratory distress
c. Severe bleeding manifestations
d. Severe organ involvement of Liver: Hepatomegaly, liver failure, AST or ALT >1000
units
e. CNS: Impaired consciousness
f. Heart: Myocardial dysfunction

21. Fluid management
1. Dengue infection without warning signs.
Child should be encouraged to drink plenty of fluids & ORS
2. Dengue with warning signs:
a. In the hospital, all children without hypotension should be given Ringer lactate or
normal saline infusion at a rate of 7 mL/kg over one hour.
b. After one hour, if PCV has decreased and vital parameters are improving; fluid infusion
rate should be decreased to 5 mL/ kg over next hour and to 3 mL/ kg/ hour for 24-48
hours with frequent monitoring of PCV and vital parameters.
c. When the patient is stable as indicated by normal blood pressure, good oral intake and
urine output, the child can be discharged.

22. Fluid management
Severe dengue
1. They should be treated with normal saline or Ringer lactate; 10-20 ml/kg is infused over
1 hour or as bolus, if blood pressure is unrecordable (earlier known as dengue shock
syndrome, DSS IV).
2. In critically sick children, it is preferable to establish two IV lines, one for administration
of normal saline and other for infusing 5% dextrose and potassium.
3. If there is no improvement in vital parameters and PCV is rising, colloids 10 ml/kg are
given rapidly. If PCV is falling without improvement in vital parameters, blood
transfusion is recommended.
4. Once improvement begins, fluid infusion rate is gradually decreased.

23. Management of bleeding manifestations
1. Platelet counts are unreliable to predict bleeding. In a small study in which
children with severe thrombocytopenia were included, platelet infusion did
not alter the outcome of patients.
2. In a recent RCT in adults with confirmed dengue infection and
thrombocytopenia (≤20 000 platelets per μL), without persistent mild
bleeding or any severe bleeding, prophylactic platelet transfusion was not
superior to supportive care

24. COMPLICATIONS
1. Dehydration
2. Hyperpyrexia
3. Febrile convulsions
4. Clinically significant bleeding
5. Mental depression
6. Bradycardia
7. Ventricular extrasystoles

25. PROGNOSIS
1. Passively acquired antibody or by prior infection with a closely related
virus predisposes to DHF
2. Death has occurred in 40–50% of patients with shock, but with
adequate intensive care deaths should occur in <1% of cases.
3. Residual brain damage caused by prolonged shock

26. PREVENTION
1. Avoiding mosquito bites by use of insecticides, repellents, body covering with
clothing, screening of houses, and destruction of A. aegypti breeding sites.
2. If water storage is mandatory, a tight-fitting lid or a thin layer of oil may prevent egg
laying or hatching.
3. The possibility exists that dengue vaccination may sensitize a recipient so that ensuing
dengue infection could result in hemorrhagic fever
4. Newr