Dengue

By Prof. Datin Dr. G. Duraisamy   Clinical Consultant (Haematology) 

Dengue and dengue hemorrhagic fever (DHF) are caused by one of four closely related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus. Infection with one of these serotypes does not provide cross-protective immunity, so persons living in a dengue-endemic area can have four dengue infections during their lifetime. The viruses that cause it are maintained in a cycle that involves humans and Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans.

Dengue is a notifiable disease. The incidence of clinically diagnosed DHF has increased this past year. The case fatality rate for DHF has been increasing this year (2005). Dengue Haemorrhagic Fever (DHF) has

• High continuous fever for 2 to 7 days
• Haemorrhagic manifestations include petichiae, epistaxis, GIT bleeds and a positive tourniquet test (Hess's test)
  Tourniquet Test inflate blood pressure cuff to a point midway between systolic and diastolic pressure for 5 minutes
  Positive test: 20 or more petichiae per/inch² (6.25 cm²)
  The tourniquet test assesses capillary fragility.
• Hepatomegaly may occur on day 3 to 4 of the fever, more in children (>90%) than in adults (60%)
• Circulatory disturbances (shock in severe cases) = Dengue Shock Syndrome (DSS) - on day 2 to 7 of fever.Period of shock is short but life threatening.

Plasma Leakage causing haemoconcentration with a rising haematocrit or packed cell volume (PCV) andthrombocytopenia hallmarks the plasma leakage and abnormal haemostasis. This usually occurs before fever subsides and before the shock syndrome. Positive Tourniquet test and petichiae are observed early in the febrile phase. Mild gum bleeding, epistaxis, bruising at the site of venepuncture are early signs of abnormal haemostasis.


Lab Findings:

• Full blood count - WBC, platelets, hematocrit or PCV
  In patients with dengue, do serial hematocrits / PCV for hemoconcentration. Leukocyte counts are often low, and the patient may even be neutropenic.
  
  Atypical Lymphocytes with basophilic cytoplasm is seen.
  
  Platelet levels should also be checked, may fall to usually below 100 x 10⁹/dl, remains low for 3-5 days in most cases. It increases to normal rapidly during convalescence. Reduction of platelets follows that of leucopenia. Giant platelets may be seen, suggests increased platelet turn over.
  
  In shock platelet count may fall below 50 x 10⁹/dl. Risk of bleeding occurs if there is prolonged shock. This may be due to increased peripheral consumption & destruction of platelets. Impaired platelet function has been shown (shortened platelet survival time).
  
  Patients with bleeding manifestations should have serial hematocrit and platelet levels checked at least daily until their temperature is normal for 1-2 days.
  
  If a bone marrow is done, (in the febrile phase), there is hypocellularity with arrest of the maturity of all cell lines, especially megakaryocytes. During convalescence there is a rapid recovery of all the cell lines.
• Liver function tests - check albumin levels
• Urine - check for microscopic hematuria
• Coagulation Defects - Prolonged aPTT (activated Partial Thromboplastin Time) and PT (Prothrombin Time) may be seen with bleeding. There may be DIC (Disseminated Intravascular Coagulation).
• Dengue-specific tests
• Serology
  IgM ELISA test for Dengue antibodies

A convalescent-phase sample may also be drawn to test for IgM antibody. This sample should be drawn between 6 and 21 days after symptom onset.

If the blood sample was taken the first five days after the onset of symptoms, a convalescent-phase sample to measure IgM antibody is needed between 6-30 days after the onset of symptoms.

Gribbles performs the PanBio Rapid Strip Dengue Test for IgM and IgG and picks up primary, (increased IgM antibodies) and secondary (increased IgG) dengue infection. The test only takes 25-30 minutes to perform and uses a drop of sera.


Risk Factors Reported for DHF

• Virus strain
• Pre-existing anti-dengue antibody
• Previous infection
• Maternal antibodies in infants
• Host genetics
• Age
• Higher risk in secondary dengue infection
• Higher risk in locations with two or more serotypes circulating, hyperendemic at high levels (hyperendemic transmission).

In a subsequent infection, the pre-existing heterologous antibodies form complexes with the new infecting virus serotype, but do not neutralize the new virus.

Antibody-dependent enhancement is the process in which certain strains of dengue virus, complexed with non-neutralizing antibodies, can enter a greater proportion of cells of the mononuclear lineage, thus increasing g virus production.

Infected monocytes probably release vasoactive mediators, resulting in increased vascular permeability and hemorrhagic manifestations that characterize DHF and DSS.