Dengue Fever

WHAT IS DENGUE FEVER?

 

n   An acute ,self-limited, febrile disease .

 

n   Dengue virus are maintained in a cycle that involves humans and Aedes aegypti

 

n   primarily a disease of the tropics

 

n   OCCURS IN two forms:

        Dengue fever(DF)

        Dengue haemorrhagic fever(DHF)

 

 Clinical manifestations

n   DF: fever, headache, myalgias, bone pain.Lymphadenopathy,  skin rash.

       Leukopenia

n   DHF:  high fever, haemorrhage,

            hepatomegaly

           evidences of “leaky capillaries”

        signs of circulatory failure(dengue shock syndrome,DSS.)

Why should we learn it ?

n   2500 million at risk from dengue per year.

 

n   Epidemic in more than 100 countries in Africa, America, Eastern Mediterranean,

      South –east Asia and the Western pacific.

 

n   The global prevalence of DHF grown dramatically in recent decades:   1970/1995:4 fold increase.

 

n   The most important mosquito-transmitted viral disease in term of mortality and morbidity.

 

 

Etiology

n     Dengue virus: enveloped RNA virus

n     Classified :   family of Flaviviridae.

n     Serum type:1-4

n    causes closely related illness, severe and fatal disease

n    but antigenically distinct

       homotypic immunity: lifelong

      heterotypic immunity :short period

               but cross-response may worsen the second infection by a another serum type.

 

How DF transmitted?

n   Sources of infection: patients and 

        anyone who with Covert infection

 

 

n   Transmitted vectors:

    Aedes aegypti is the most common vectors

 

           other Aedes mosquitos are less effiecitent :

               Ae.albopictus,Ae.polynesiesis

     Primarily a daytime feeder

     Lives around human habitation

                    (Women and children  summer time or rainny season)

 

n   The host:  all susceptible if never came across dengue fever.

 

 

How dengue virus cause the disease?

  (pathogenesis and clinical presentations)

 

risk factors for DHF

Important risk factors for DHF include

n   Virus factors:

n  the serotype :2 is the predominating

n  the strain: virulent strain

n   Host factors:

n  genetic predisposition

n  the age

n  Children : experienced a precious dengue infection     

n     Infants with waning levels of maternal dengue antibody.

n  immune status: if there are enhancing Ab.

 

 

 

Enchancing antibody

 

n  heterotypic antibodies

                

n  enhancement of virus replication in macrophages

n   worsen the condition

A mechanism of DHF/DSS

 

Heterologous (异型的)Complexes Enter More Monocytes, Where Virus Replicates

 

pathophysiological changes occur in DHF/DSS:

n     Increased vascular permeability

          haemoconcentration(Hct>20%)

          low pulse pressure

          other signs of shock.

n     Disorder in haemostaisis :

         vascular changes

          thrombocytopenia

          coagulopathy.

    CLINICAL PRESENTATIONS

n        Incubation:      5-8 days

n      Clinical features depend on the age of the patient:

Infants and young children 

           undifferentiated febrile disease,

            with maculapapular rash.

Older children and adults either

          a mild febrile syndrome

         or the classic disease.

 

 

       Undifferentiated Fever

n   the most common manifestation of dengue

 

n   87% of students infected were either asymptomatic or mildly symptomatic

 

n   studies including all age- groups also demonstrate silent transmission

      

Dengue fever (DF)

        1. fever

n   Abrupt onset, rising to 39.5-41.4 C

n   Accompanied by

         frontal or retro-orbital headache

         Pain behind the eyes

         chillness

n   Last 1-7 days

n   Biphasic:

        defervesce for 1-2 days

        recurring with second rash

        but :T not as high

    2. Bone pains

break bone fever is the another name of DF

 

n   After onset of fever

n   May last several weeks

n   Increase in severity

n   Most common in legs, joints, and lumbar spine;

n   With muscular and joint pains.

 

        3. Rash

n     first rash: first 1-2 days of fever, transient, generalized, macular and blanching;

n     Second rash

n    3-6 days.

n     morbilliforms , maculopapular , rubella type

n    Involving the trunk first, spreading to the face and extremities,

                 sparing palms and soles.

n     other rash:   petechiae

 

      4.  Hemorrhage

n  Skin hemorrhages:                          petechiae, purpura

n  Gingival bleeding

n  Nasal bleeding

n  GI bleeding:                                    hematemesis, melena, hematochezia

n  Hematuria

n  Increased menstrual flow

Physical exams(1)

n   Fever

 

n   Conjunctival injection, pharyngeal erythema

 

n   Rash: Measles-like rash over chest and upper limbs

 

n   Generalized lymphadenopathy

 

Physical exams(2) :
Tourniquet Test

n  Method:

n   Inflate blood pressure cuff

n   to a point:  midway between systolic and diastolic pressure

n   for 5 minutes

n  Positive test:

        20 or more petechiae per 1 inch² 

                                                                  (6.25 cm²)

Clinical forms of DF(china)

n  Mild type

 

n  Typical type

 

n  Severe type:

           Unusual bleedings

           meningoencephalitis

 

Presentations of
DHF/DSS(1)

n   high fever: remains >39  for 2-7days

n   hepatomegaly : varies in size

n    common haemorrhage       

n      bleeding at venepuncture sites (coagulopathy)

n      GI bleeding

n   Evidence of plasma leakage:

n  a rise in hematocrit (Hct):=>20%

n   pleural effusion ,ascites , hypoproteinemia

n   a distinctive laboratory finding :

           Moderate to marked thrombocytopenia with

        concurrent haemoconcentration  

DSS(2)=DHF+SHOCK

n   at the end of the febrile phase

n     signs  of circulatory disturbance

n    sweat,         cool extremities      restless

n  rapid ,weak pulse                       hypotension

n   varying severity

n  less severe: transient   recover spontaneously

n  more severe: uncorrected Shock ensues:

       metabolic acidosis,   severe bleeding

n   Patient may dies or recovers within 12-24hours

 

 finding               DF        DHF

(+1-25%,++26-50%,+++51-75%,++++76-100%)

 

Fever                             ++++           ++++

Petechiae                        ++                ++

Lymphadenopathy            ++               ++

GI bleeding                       +                  +

 

 

finding                DF        DHF

Maculopapular rash            ++                    +

Myalgia/arthralgia              +++                 +

Leukopenia                      ++++               ++

 

Thrombocytopenia            ++              ++++

Positive tourniquet test      ++             ++++

Hepatomegaly                   0                ++++

Shock                               0                 ++

 

 

Lab tests(1)

n  Clinical laboratory tests

n   CBC-- Leukopenia is typical; 

              thrombocytopenia , hematocrit

n  Liver function tests :  Albumin

 

n  Urine--check for microscopic hematuria

 

 

Lab tests(2) :Dengue-specific tests

n     serologic tests:    Antibody assay

         useful for documenting:

          IgM and complement fixing (CF)Ab : short –lived

          Fourfold increase in titer between acute and convalescent sera

 

n   Viral antigen  or viral RNA by PCR :  

               prove the diagnosis

 

n   Virus isolation:

       grown in vertebrate and mosquito cell lines

       Virus is best isolated from serum:   febrile patients.

         but  are difficult

 

 

ELISA Test for
Serologic Diagnosis

Virus Isolation:
Cell Culture

 

Virus Isolation:
Fluorescent Antibody Test

Diagnosis of DF

n  Epidemiological evidences

n  Clinical presentations

n  Lab tests:

n  Routine test: for monitoring the severity

n  serologic tests: for clinical diagnosis

n  Virus isolate: to distinguish the serum types.

 

four criteria for DHF

n  Fever , last for 2-7days

n  at least one of Hemorrhage evidences

ⁿ     Thrombocytopenia :PLT<100,000/mm³

n  Evidence of plasma leakage:

n  a rise in Hct:>=20%

n   pleural effusion ,ascites and      

                         hypoprotinemia

 

Diagnosis  criteria for DSS

n   four criteria for DHF

n  Evidence of shock

n  sweat, restless, cool extremities

n   rapid ,weak pulse

n   narrowing of pulse pressure<2.7kpa

n   hypotension

 

 

Differencial diagnosis

Include a wide spectrum of

n  viral

 

n  bacterial 

 

n  Parasitic infections

prognosis

n  Self-limit disease

n  Convalescence may be prolonged

n  with weakness and mental depression

n  Continued bone pains, bradycardia

n  Survival is related to

n  early hospitalization

n  aggressive supportive care

 

Treatment of DF

      complicated, no specific trx

n  Fluid replacement: adequate hydration

n  Bed Rest

n  Antipyretics

n   acetaminophen (if no liver dysfunction)

n   No aspirin(association with Reye syndrome ),

n  steroids, avoid NSAIDS(anticoagulant properties).

   Continuous Monitoring of

n  VS

n  Diuresis,mental status

n  Evidence of bleeding

n  Hydration status

n  Evidence of increased vascular permeability

n  hematocrit, platelet count(manual)

Management for DHF

 

n   Prevent and Treatment of shock:

        mild to moderate isotonic dehydration (5%-8% deficit)

n  Iv crystalloids ; colloids; central line

n   Correct electrolyte abnormalities and acidemia

n    Monitor the vital signs:    avoid hypovolemia or fluid overload.

n   therapy for DIC:     if indicated

n    Unknown  effective    =  steroid      ,immune globulin

                                   platelet transfusions

                  

                     

 

 

 

prevention

 Three operations

               must be conducted

 

n   isolation of patients.

 

n   emergency mosquito control simultaneously

n   Personal protection

vaccine

n  no vaccine currently available

n   research is underway for the development of a vaccine.

n  vaccine  will not  available for 5 to 10 years.

     as

§   it must provide immunity to all 4 serotypes

§   Lack of dengue animal model

 

Personal protection

 

n  remain in well-screened or completely enclosed, air-conditioned areas;

n  wear light-colored clothing with full-length pant legs and sleeves;

n  use insect repellent on exposed skin.

n  Use netting when sleeping

 

 

Discharge criteria

n  afebrile for 24 h               appetite

n  clinical improvement     3 days post shock

 

n  Stable Hct                   Platelets 50,000/mm³

n  Eupnea: No respiratory distress from pleural effusions/ascites

Common Misconceptions about DHF

v Dengue + bleeding = DHF

v Need 4 WHO criteria, capillary permeability

v DHF kills only by hemorrhage

v Patient dies as a result of shock

v Poor management turns dengue into DHF

v Poorly managed dengue can be more severe, but DHF is a  distinct condition, which even well-treated patients may develop

v Positive tourniquet test = DHF

v Tourniquet test is a nonspecific indicator of capillary         fragility

Rehydrating Patients Over 40 kg

n  Volume required: twice the recommended maintenance volume

n  Formula for calculating maintenance volume:   1500 + 20 x (weight in kg - 20)

n  For example

n   55 kg patient: maintenance volume :  

                  1500 + 20 x (55-20) = 2200 ml

n  For this patient, the rehydration volume would be 2 x 2200, or 4400 ml