Dengue fever Zhao zhixin The 3rd affiliated hospital of Sun Yat-Sen University [email_address]
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 haemorrhagic fever(DHF)
DF: fever, headache, myalgias, bone pain.Lymphadenopathy, skin rash.
DHF: high fever, haemorrhage,
evidences of “leaky capillaries”
signs of circulatory failure(dengue shock syndrome,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.
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 second infection by a another serum type.
How DF transmitted?
Sources of infection: patients and
anyone who with Covert infection
Aedes aegypti is the most common vectors
other Aedes mosquitos are less effiecitent :
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
the serotype :2 is the predominating
the strain: virulent strain
Children : experienced a precious dengue infection
Infants with waning levels of maternal dengue antibody.
immune status: if there are enhancing Ab.
enhancement of virus replication in macrophages
worsen the condition
A mechanism of DHF/DSS
Neutralizing antibody to Dengue 1 virus Dengue 1 virus Homologous Antibodies( 同型抗体 ) Form Non-infectious Complexes Non-neutralizing antibody Complex formed by neutralizing antibody and virus 1 1 1 1 1
Heterologous ( 异型的 )Complexes Enter More Monocytes, Where Virus Replicates Non-neutralizing antibody Dengue 2 virus Complex formed by non-neutralizing antibody and Dengue 2 virus 2 2 2 2 2 2 2 2 2 2 2 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
low pulse pressure
other signs of shock.
Disorder in haemostaisis :
Incubation: 5-8 days
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 .
Manifestation Of Dengue Virus Infections ASYMPTOMATIC DSS SYMPTOMATIC Without haemorrhage With unusual haemorrhage No shock Undifferentiated Fever Dengue Fever Dengue Haemorrhagic 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)
Abrupt onset, rising to 39.5-41.4 C
frontal or retro-orbital headache
Pain behind the eyes
Last 1-7 days
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.
first rash: first 1-2 days of fever, transient, generalized, macular and blanching;
morbilliforms , maculopapular , rubella type
Involving the trunk first, spreading to the face and extremities,
sparing palms and soles.
other rash: petechiae
Skin he morrhages: petechiae, purpura
Gin gi val bleeding
Na sal bleeding
GI bleeding: hema te mesis, me le na, hemato che zia
Hemat u ria
Increased menstrual flow
Conjunct i val injection, pharyngeal eryth e ma
Rash: Measles-like rash over chest and upper limbs
Generalized lymphade no pathy
Physical exams(2) : Tourniquet Test
Inflate blood pressure cuff
to a point: midway between systolic and diastolic pressure
for 5 minutes
20 or more petechiae per 1 inch 2
(6.25 cm 2 )
Clinical forms of DF(china)
Presentations of DHF/DSS(1)
high fever : remains >39 for 2-7days
hepatomegaly : varies in size
bleeding at venepuncture sites ( coagulopathy)
Evidence of plasma leakage:
a rise in he matocrit (Hct):=>20%
pleural effusion ,ascites , hypoproteinemia
a distinctive laboratory finding :
Moderate to marked thrombocytopenia with
at the end of the febrile phase
signs of circulatory disturbance
sweat, cool extremities restless
rapid ,weak pulse hypotension
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
Fever ++++ ++++
Petechiae ++ ++
Lymphadenopathy ++ ++
GI bleeding + +
finding DF DHF
Maculopapular rash ++ +
Myalgia/arthralgia +++ +
Leukopenia ++++ ++
Thrombocytopenia ++ ++++
Positive tourniquet test ++ ++++
Hepatomegaly 0 ++++
Shock 0 ++
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
grown in vertebrate and mosquito cell lines
Virus is best isolated from serum: febrile patients .
mild to moderate isotonic dehydration (5%-8% deficit)
Iv cr y stalloids ; 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
must be conducted
isolation of patients.
emergency mosquito control simultaneously
no vaccine currently available
research is underway for the development of a vaccine.
vaccine will not available for 5 to 10 years.
it must provide immunity to all 4 serotypes
Lack of dengue animal model
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
afebrile for 24 h appetite
clinical improvement 3 days post shock
Stable Hct Platelets 50,000/ mm 3
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
For mula for calculating maintenance volume: 1500 + 20 x (weight in kg - 20)
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 effusion coapulopathy hypovolaemia shock DIC Severe bleeding death
Antiinflamatory agents Monitor vital sings q2h Provide 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