Dengue fever

Zhao zhixinThe 3rd affiliated hospital of

Sun Yat-Sen Universityzxzhao@21cn.com

WHAT IS DENGUE FEVER?

An acute ,self-limited, febrile disease .

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

primarily a disease of the tropics

OCCURS IN two forms: Dengue fever(DF) Dengue haemorrhagic fever(DHF)

Clinical manifestations DF: fever, headache, myalgias, bone pain.

Lymphadenopathy, skin rash. Leukopenia DHF: high fever, haemorrhage, hepatomegaly evidences of “leaky capillaries” signs of circulatory failure(dengue shock s

yndrome,DSS.)

Why should we learn it ?

2500 million at risk from dengue per year.

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

South –east Asia and the Western pacific.

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

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

Etiology

Dengue virus: enveloped RNA virus Classified : family of Flaviviridae. Serum type:1-4

causes closely related illness, severe and fatal disease

but antigenically distinct homotypic immunity: lifelong heterotypic immunity :short period but cross-response may worsen the se

cond infection by a another serum type.

How DF transmitted?

Sources of infection: patients and

anyone who with Covert infection

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)

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

How dengue virus cause the disease?

(pathogenesis and clinical presentations)

Dengue virus

Blood stream

Mononuclear-phagocyte system

second viremia Antigen antibody complexes

complement

system

incubation

Lymphadenopathy,hepatomegly

Bone marrow depress

Vascular permeability↑

Rash, haemarrhagic

fever

Bone pains,etc

Imfllamatory materials

risk factors for DHF

Important risk factors for DHF include Virus factors:

the serotype :2 is the predominating the strain: virulent strain

Host factors: genetic predisposition the age

Children : experienced a precious dengue infection Infants with waning levels of maternal dengue antibod

y. immune status: if there are enhancing Ab.

Enchancing antibody

heterotypic antibodies

enhancement of virus replication in macrophages

worsen the condition

A mechanism of DHF/DSS

Neutralizing antibody to Dengue 1 virus

1

1

Dengue 1 virus 1

Homologous Antibodies( 同型抗体 ) Form Non-infectious Complexes

Non-neutralizing antibody

1

1 Complex formed by neutralizing antibody and virus

2

2

2

2

22

2

22

2

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

Non-neutralizing antibody

Dengue 2 virus 2

Complex formed by non-neutralizing antibody and Dengue 2 virus

2

First infection

heterotypic antibodies

fail to neutralize virus of the other serum type infection

the number of infected monocytes

activation of cytotoxic lymphocytes

rapid release of cytokines

plasma leakage

viral uptake and the replication in the mononuclear phagocytes.

haemorrhage Haemoconcentrationor shock

pathophysiological changes occur in DHF/DSS:

Increased vascular permeability haemoconcentration(Hct>20%) low pulse pressure other signs of shock. Disorder in haemostaisis : vascular changes thrombocytopenia coagulopathy.

CLINICAL PRESENTATIONS Incubation: 5-8 days Clinical features depend on the age of t

he patient:Infants and young children undifferentiated febrile disease, with maculapapular rash.Older children and adults either a mild febrile syndrome or the classic disease.

Manifestation Of Dengue Virus Infections

ASYMPTOMATICASYMPTOMATIC

DSS

SYMPTOMATICSYMPTOMATIC

Without haemorrhage

With unusual haemorrhage

No shock

Undifferentiated Fever

Dengue Fever

DengueHaemorrhagicFever

Undifferentiated Fever

the most common manifestation of dengue

87% of students infected were either

asymptomatic or mildly symptomatic

studies including all age- groups also

demonstrate silent transmission

Dengue fever (DF)

1. fever Abrupt onset, rising to 39.5-41.4 C Accompanied by frontal or retro-orbital headache Pain behind the eyes chillness Last 1-7 days 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

After onset of fever May last several weeks Increase in severity Most common in legs, joints, and lumbar

spine; With muscular and joint pains.

3. Rash first rash: first 1-2 days of fever, transient,

generalized, macular and blanching; Second rash

3-6 days. morbilliforms , maculopapular , rubella type Involving the trunk first, spreading to the face

and extremities, sparing palms and soles. other rash: petechiae

4. Hemorrhage

Skin hemorrhages: petechiae, purpura

Gingival bleeding Nasal bleeding GI bleeding: hematemesis,

melena, hematochezia Hematuria Increased menstrual flow

Physical exams(1) Fever

Conjunctival injection, pharyngeal erythema

Rash: Measles-like rash over chest and upper limbs

Generalized lymphadenopathy

Physical exams(2) :

Tourniquet Test

Method: Inflate blood pressure cuff to a point: midway between systolic and di

astolic pressure for 5 minutes

Positive test: 20 or more petechiae per 1 inch2

(6.25 cm2)

Clinical forms of DF(china) Mild type

Typical type

Severe type: Unusual bleedings meningoencephalitis

Presentations ofDHF/DSS(1)

high fever: remains >39 for 2-7days hepatomegaly : varies in size common haemorrhage

bleeding at venepuncture sites (coagulopathy) GI bleeding

Evidence of plasma leakage: a rise in hematocrit (Hct):=>20% pleural effusion ,ascites , hypoproteinemia

a distinctive laboratory finding : Moderate to marked thrombocytopenia with concurrent haemoconcentration

DSS(2)=DHF+SHOCK at the end of the febrile phase signs of circulatory disturbance

sweat, cool extremities restless rapid ,weak pulse hypotension

varying severity less severe: transient recover spontaneously more severe: uncorrected Shock ensues: metabolic acidosis, severe bleeding

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)

Clinical laboratory tests CBC-- Leukopenia is typical; thrombocytopenia , hematocrit Liver function tests : Albumin

Urine--check for microscopic hematuria

Lab tests(2) :Dengue-specific tests

serologic tests: Antibody assay useful for documenting: IgM and complement fixing (CF)Ab : short –lived Fourfold increase in titer between acute and convalescent sera

Viral antigen or viral RNA by PCR : prove the diagnosis

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:Mosquito Inoculation

Virus Isolation:Fluorescent Antibody Test

Diagnosis of DF

Epidemiological evidences Clinical presentations Lab tests:

Routine test: for monitoring the severity serologic tests: for clinical diagnosis Virus isolate: to distinguish the serum types.

four criteria for DHF

Fever , last for 2-7days at least one of Hemorrhage evidences Thrombocytopenia :PLT<100,000/mm3

Evidence of plasma leakage: a rise in Hct:>=20% pleural effusion ,ascites and

hypoprotinemia

Diagnosis criteria for DSS

four criteria for DHF Evidence of shock

sweat, restless, cool extremities rapid ,weak pulse narrowing of pulse

pressure<2.7kpa hypotension

Differencial diagnosisInclude a wide spectrum of viral

bacterial

Parasitic infections

prognosis

Self-limit disease Convalescence may be prolonged

with weakness and mental depression Continued bone pains, bradycardia

Survival is related to early hospitalization aggressive supportive care

Treatment of DF

complicated, no specific trx Fluid replacement: adequate hydration Bed Rest Antipyretics

acetaminophen (if no liver dysfunction) No aspirin(association with Reye syndrome ), steroids, avoid NSAIDS(anticoagulant

properties).

Continuous Monitoring of

VS Diuresis,mental status Evidence of bleeding Hydration status Evidence of increased vascular permeabilit

y hematocrit, platelet count(manual)

Management for DHF

Prevent and Treatment of shock: mild to moderate isotonic dehydration (5%-8% deficit)

Iv crystalloids ; colloids; central line Correct electrolyte abnormalities and acidemia Monitor the vital signs: avoid hypovolemia or fluid overload.

therapy for DIC: if indicated Unknown effective = steroid ,immune globulin

platelet transfusions

prevention

Three operations must be conducted

isolation of patients.

emergency mosquito control simultaneously

Personal protection

vaccine

no vaccine currently available research is underway for the

development of a vaccine. 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

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

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

use insect repellent on exposed skin. Use netting when sleeping

Discharge criteria

afebrile for 24 h appetite clinical improvement 3 days post sho

ck

Stable Hct Platelets 50,000/mm3

Eupnea: No respiratory distress from pleural effusions/ascites

Common Misconceptions about DHF

Dengue + bleeding = DHF Need 4 WHO criteria, capillary permeability

DHF kills only by hemorrhage Patient dies as a result of shock

Poor management turns dengue into DHF Poorly managed dengue can be more severe,

but DHF is a distinct condition, which even well-treated patients may develop

Positive tourniquet test = DHF Tourniquet test is a nonspecific indicator of

capillary fragility

Rehydrating Patients Over 40 kg

Volume required: twice the recommended maintenance volume

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

For example 55 kg patient: maintenance volume : 1500 + 20 x (55-20) = 2200 ml For this patient, the rehydration volume

would be 2 x 2200, or 4400 ml

Dengue virus infection

Asymptomatic

symptomatic

Undifferentiated fever (viral syndrome)

dengue hemorrhagic fever (plasma leakage)

dengue fever syndrome

no shock

DSS

Without hemorrhage

with unusual hemorrhage

DF DHF

Fever

tournigeut test(+) Increased vascular permeability

heptomegaly

thrombocytopenia

Dengue infection

Other haemorrhagic manifestations Leakage

of plasma

Rising haematocrit

Hypoproteinaemia

Serous effusioncoapulopathy

hypovolaemia

shock

DIC

Severe bleeding

death

Antiinflamatory agentsMonitor vital sings q2hProvide oral hydration

Same as above +type and cross match

Determine PT AND PTT

Same as above+ iv isotonic fluids,monitor q30mins,

follow urine output

Same as above+Iv colloids or plasma

Provide critical care support

1.Four Criteria for DHF

1+spontaneaous bleeding

1+Sings of shock:hypotention

1+undetectalbe pulse

and blood pressure

Grade 1

Grade 2

Grade 3

Grade 4