Transcript Dengue

DENGUE
Dr. Halesh .L.H.
Professor and Head of the department , Microbiology
SIMS,Shimoga
*Virus, Vector and
Transmission
*Causative agent of dengue fever, belongs to family flaviviridae,
genus flavivirus.
*It is a spherical enveloped virus
*Genomic material – single stranded RNA
*There are presently 5 serotypes identified
*
*Fifth serotype, identified in 2013, october follows sylvatic
cycle,and is found only in Sarawak forest, Malaysia
*Each serotype provides specific lifetime immunity, and
short-term cross-immunity
*All serotypes can cause severe and fatal disease
*
*Genetic variation within serotypes
*Some genetic variants within each serotype appear to be more
virulent or have greater epidemic potential
*
oThe first record of dengue fever is in chinese medical
encyclopedia referred as water poison caused by flying insects
oReports of epidemics – 1779-80
oThen until 1940 , epidemics were infrequent
oThen there was marked spread of dengue during and after
second world war
*HISTORY
*The incidence is dramatically increasing
*390 million dengue cases per year
*Infections are acquired in urban
environment
*Rate of dengue has increased 10folds between 1960-2010
*HISTORY
*Replication and
Transmission
of Dengue Virus
1. Virus is transmitted
to human in mosquito
saliva
2. Virus replicates
in target organs
3. Virus infects white
blood cells and
lymphatic tissues
4. Virus released and
circulates in blood
*
5. Second mosquito
ingests virus with blood
6. Virus replicates
in mosquito midgut
and other organs,
infects salivary
glands
7. Virus replicates
in salivary glands
*Aedes aegypti
Mosquito
*Dengue transmitted by infected female mosquito
*Primarily a daytime feeder
*Lives around human habitation
*Lays eggs and produces larvae
preferentially in artificial
containers
*Aedes aegypti
* Clinical Manifestations of Dengue
and DHF
*Undifferentiated fever
*Classic dengue fever
*Dengue hemorrhagic fever
*Dengue shock syndrome
*Dengue Clinical
Syndromes
*Clinical Characteristics
of Dengue Fever
4 Necessary Criteria:
1.Fever, or recent history of acute fever
2.Hemorrhagic manifestations
3.Low platelet count (100,000/mm3 or less)
4.Objective evidence of “leaky capillaries:”
*elevated hematocrit (20% or more over baseline)
*low albumin
*pleural or other effusions
*Clinical Case Definition for
Dengue Hemorrhagic Fever
*Clinical Case Definition for
Dengue Shock Syndrome
criteria for DHF
1.Evidence of circulatory failure manifested indirectly by all
of the following:
*Rapid and weak pulse
*Narrow pulse pressure ( 20 mm Hg) OR hypotension for
age
*Cold, clammy skin and altered mental status
2.Frank shock is direct evidence of circulatory failure
4 Grades of DHF
Grade 1
*Fever and nonspecific constitutional symptoms
*Positive tourniquet test is only hemorrhagic
Manifestation
Grade 2
*Grade 1 manifestations + spontaneous bleeding
Grade 3
*Signs of circulatory failure (rapid/weak pulse, narrow
pulse pressure, hypotension, cold/clammy skin)
Grade 4
*Profound shock (undetectable pulse and BP)
* Abdominal pain - intense and sustained
* Persistent vomiting
* Abrupt change from fever to hypothermia, with sweating and
prostration
* Restlessness or somnolence
DANGER SIGNS OF DHS
Four Criteria for DHF:
• Fever
• Hemorrhagic manifestations
• Excessive capillary permeability
•  100,000/mm3 platelets
Initial Warning Signals:
• Disappearance of fever
• Drop in platelets
• Increase in hematocrit
*
Alarm Signals:
• Severe abdominal pain
• Prolonged vomiting
• Abrupt change from fever
to hypothermia
• Change in level of
consciousness (irritability
or somnolence)
When Patients Develop DSS
• 3 to 6 days after onset of
symptoms
*Encephalopathy
*Hepatic damage
*Cardiomyopathy
*Severe gastrointestinal hemorrhage
*Unusual Presentations
of Severe Dengue Fever
Disease
Pathogenesis
*Higher risk in secondary infections
*Higher risk in locations with two or more serotypes circulating
simultaneously at high levels (hyperendemic transmission)
*Risk Factors for DHF
*Persons who have experienced a dengue infection develop
serum antibodies that can neutralize the dengue virus of
that same (homologous) serotype
*Hypothesis on Pathogenesis
of DHF
Homologous Antibodies
Form Non-infectious
Complexes
Dengue 1 virus
Neutralizing antibody to Dengue 1 virus
Non-neutralizing antibody
Complex formed by neutralizing antibody
and virus
*In a subsequent infection, the pre-existing heterologous
antibodies form complexes with the new infecting virus
serotype, but do not neutralize the new virus
Hypothesis on Pathogenesis
of DHF
Heterologous
Antibodies Form
Infectious Complexes
Dengue 2 virus
Non-neutralizing antibody to Dengue 1 virus
Complex formed by non-neutralizing
antibody and virus
*Antibody-dependent enhancement
is the process in which
certain strains of dengue virus, complexed with nonneutralizing antibodies, can enter a greater proportion of
cells of the mononuclear lineage, thus increasing virus
production
Hypothesis on Pathogenesis of DHF
*
Dengue 2 virus
Non-neutralizing antibody
Complex formed by nonneutralizing antibody and
Dengue 2 virus
*Infected monocytes release vasoactive mediators, resulting in
increased vascular permeability & hemorrhagic manifestations
that characterize DHF and DSS
*Hypothesis on Pathogenesis
of DHF
Virus serotype
*DHF risk is greatest for DEN-2, followed by DEN-3,
DEN-4 & DEN-1
*Viral Risk Factors
for DHF Pathogenesis
*
Diagnosis
Clinical Evaluation in Dengue
Fever
*Blood pressure
*Evidence of bleeding in skin or other sites
*Hydration status
*Evidence of increased vascular permeabilitypleural effusions, ascites
*
Laboratory Tests
in Dengue Fever
*Clinical laboratory tests
*CBC--WBC, platelets, hematocrit
*Albumin
*Liver function tests
*Urine--check for microscopic hematuria
VIRUS SPECIFIC TEST
*Virus isolation
*Serology
*Laboratory Tests
in Dengue Fever
*Virus Isolation:
Cell Culture
Virus Isolation:
Mosquito Inoculation
*Virus Isolation:
Fluorescent Antibody Test
*
Treatment
*No hemorrhagic manifestations and patient is well-hydrated:
home treatment
*Hemorrhagic manifestations or hydration borderline:
outpatient observation center or hospitalization
*Warning signs (even without profound shock) or DSS:
hospitalize
*Outpatient Triage
*Patients treated at home
*Instruction regarding danger signs
*Consider repeat clinical evaluation
*Patients with bleeding manifestations
*Serial hematocrits and platelets at least daily until
temperature normal for 1 to 2 days
*Patient Follow-Up
*All patients
*If blood sample taken in first 5 days after onset, need
convalescent sample between days 6 - 30
*All hospitalized patients need samples on admission and
at discharge or death
*Patient Follow-Up
(cont’d.)
*Treatment of Dengue Fever
*Fluids
*Rest
*Antipyretics (avoid aspirin & NSAIDs)
*Monitor blood pressure, hematocrit, platelet count,
level of consciousness
*Only needed until fever subsides, to prevent Aedes
aegypti mosquitoes from biting patients and acquiring
virus
*Keep patient in screened sick room or under a mosquito
net
*Mosquito Barriers
* Indications for Hospital Discharge
*Absence of fever for 24 hours (without
anti-fever
therapy) and return of appetite
*Visible improvement in clinical picture
*Stable hematocrit
*3 days after recovery from shock
*Platelets  50,000 / mm3
*No respiratory distress from pleural effusions / ascites
*
DHF is a pediatric disease
All age groups are involved
DHF is a problem of low income families
All socioeconomic groups are affected
*No licensed vaccine at present
*Effective vaccine must be tetravalent
*Field testing of an attenuated
tetravalent vaccine currently
underway
*Effective, safe and affordable vaccine is awaited
*Dengue Vaccine?
*Disease Prevention and
Control
*Larvicides may be used to kill immature aquatic stages
*Ultra-low volume fumigation ineffective against adult
mosquitoes
*Mosquitoes may have resistance to commercial aerosol sprays
*Vector Control
Methods:
Chemical Control
Biological control
*Largely experimental
*Option: place fish in
containers to eat larvae
Environmental control
*Elimination of larval habitats
*Most likely method to be effective in the long term
*Vector Control Methods:
Biological & Environmental Control
THANK
YOU