Dengu Fever by Dr Sarma

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Dengue Fever(Pronounced as Dhen Gey)

• A comprehensive presentation
• by
• Dr.R.V.S.N.Sarma., M.D.,

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Alternative Names

• Onyong- Nyang Fever
• West Nile Fever
• Break Bone Fever
• Dengue like Disease

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Background

• Propagation of viral illnesses
• Transmission of viral illnesses
• Various families of Arbor viruses
• Manifestations of Arborviral illnesses
• Dengue A Flavivirus- EM- Cell culture
• Transmitted by mosquito
• Aedes aegypti

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Viral Illnesses - Propagation
Human
Human
Accidental
Human
Zoonotic
Arthropod
Rodent
Virus
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Transmission of Viral Illnesses

• Droplet infection as in case of
• Measles, Influenza, Coryza etc.
• Blood to blood transmission- HIV, HBV
• Feco-oral Rota, Polio
• Direct contact Herpes simplex etc
• Arthropod borne Dengue, JE, YF
• Tick borne CEE, Colorado TF

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Arthropod borne Viral Diseases

• Flavivirus Mosquito borne YF, DF,JE
• Flavivirus Tick Borne CEE, RSSE, KFD
• Buniyavirus Mosquito- CE
• Plebovirus Sandfly Fever
• Arinavirus LCM virus
• Colivirus Colorado Tick fever
• Vesiculovirus Vesicular stomatitis
• Alphavirus E/W/V equine encephalitides

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Manifestations of Arborviral Illnesses

• Most Arboviral diseases are rural
• Arboviral illnesses cause typical
• manifestations Often overlap
• The following clinical syndromes occur
• FM Fever Myalgia complex
• AR Arthritis Rash complex
• HF Haemorrhagic Fever
• E Encephalitis

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Epidemiology of Dengue

• The Dengue Virus
• The Vector
• Global distribution of Dengue
• Transmission cycle host vector
• Propagation of virus I.P
• Natural History of Dengue
• Dengue Hemorrhagic fever
• Endemicity pattern

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Epidemiological Triangle
The Host
Interaction
The Virus
The Vector
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The Agent

• Dengue Virus

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The Dengue Virus

• Flavivirus
• Positive sense
• Single stranded RNA virus
• 40 to 50 nanometers
• Four sero-sub types
• Type 1 to 4
• Arthropod borne

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Dengue Virus
Electron Micrograms
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Dengue Virus
Cell Culture Of Dengue Virus
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The Vector
Aedes aegypti (Infected Female Mosquito) (rarely
Aedes albapticus)
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Peculiarities of A.aegypti

• It is a day biting mosquito when normally
• coils, repellents, nets etc are not used
• It breads in fresh water around homes
• Lays eggs preferentially in water jars, discar-
  ded containers, coconut shells, old tires etc.
• Can transmit trans-ovarially the infection
• Year round breeding 250 N to 250 S
• Tropics and sub-tropics are its favorite zones.
  It is an urban vector

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Aedes aegypti
Dengue, YF, CGF
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Aedes aegypti
Dengue Yellow Fever Chichungunya Fever
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Dengue on the Globe
Highly endemic
Recently acquired
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Dengue Fever

• Caused by an arthropod borne virus
• It is a zoonotic virus
• Man is accidentally infected
• Other vertebrates are the reservoirs
• Dengue virus has 4 subtypes 1 to 4
• Positive sense, single str RNA- 40nm
• Vector mosquito is Aedes aegypti

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Mechanism of Transmission

• Vector is infected after ingestion of blood meal
  from a viremic vertebrate
• Virus multiplies in the system of vector
• for 2-3 weeks extrinsic incubation pd.
• Natural vertebrate partner has only
• transient viremia and doesnt suffer
• Virus is injected by the A.aegypti into man
• After 2-7 days of IP, man develops FM,HF

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Dengue Transmission Cycle
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Dengue Transmission
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Dengue Illnesses - Propagation
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Natural History of Dengue
In apparent
Human Inf
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Recovery
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DFM
Re infection
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95
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Death
Primary DHF/DSS
Secondary DHF/DSS
5
01
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DHF Endemicity
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Pathogenesis of DHF

• Immuno-pathogenic
• Cascade

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Hypotheses on DHF - DSS

• Neutralizing Ab are type specific nutralize
  the homologous sub type
• Subsequent infection with heterologous sub type
  causes immune complexes
• These Immune Complexes target the mononuclear
  lineage foe enhanced viral replication
• Infected monocytes release vasoactive mediators
  causing vascular damage

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Initial Immunogenecity
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Immune Complexes
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Attack on Host Immune Cells
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Immunopathogenic Cascade of DHF/DSS

• Macrophage monocyte infection
• Previous infection with heterologous
• Dengue serotype results in production
• of non protective antiviral antibodies
• These Ab bind to the virions surface
• Fc receptor and focus the Dengue virus
• on to the target cells macro/monocytes
• T cell - cytokines, interferon, TNF alpha

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The Disease

• Clinical Features

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Dengue Presentations

• Undifferentiated fever
• Dengue Fever (DF) with the Fever- Myalgia (FM)
  presentation (classical)
• Dengue Hemorrhagic Fever (DHF)
• Dengue Shock Syndrome (DSS)

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Hemorrhagic Manifestations

• Skin hemorrhagespetechiae, purpura, ecchymoses
• Gingival bleeding
• Nasal bleeding
• Gastro-intestinal bleeding hematemesis, melena,
  hematochezia
• Haematuria
• Increased menstrual flow

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Clinical Manifestations- DF

• IP of 2 7 days - typical patient develops
• Sudden onset of fever, chills, headache
• Back pain with severe myalgia, arthralgia
• Retro-orbital pain break bone fever
• Macular rash in axillary area
• Adenopathy, palatal vesicles, scleral inj.
• Maculo-papular rash on trunk extremities
• Epistaxis and scattered petechiae

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Other manifestations- DF

• Anorexia. Nausea, vomiting
• In apparent illness-to acute incapacitation
• Illness is about 25 days, biphasic course
• Pain on eye movements
• Pain on palpating abdominal muscles
• Primarily not a respiratory illness
• Rare - aseptic meningitis
• Complete recovery is the rule - asthenia

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Petechiae
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Dengue Haemorrhagic Fever (DHF)

• Vascular instability
• Decreased vascular integrity
• Assault on macro vasculature
• Decreased platelet function
• Increased vascular permeability
• Vascular disruption and local bleeds
• Hypotension, hemoconcentration- shock

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DHF Clinical Criteria
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Criteria for DHF

• Fever, or recent history of acute fever
• Hemorrhagic manifestations
• Low platelet count (100,000/mm 3 or less)
• Objective evidence of leaky capillaries
• Elevated hematocrit -20 or more
• more over baseline or ? 50
• Low albumin, pleural effusion

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Criteria for DSS

• The four criteria of DHF
• Evidence of circulatory failure
• Rapid and weak pulse
• Narrow pulse pressue (less than 20mm)
• Hypotension for the age
• Cold clammy skin
• Altered mental status

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Four Grades of DHF/DSS

• Grade 1
• Fever, Const. Symptoms, ve tourniquet test
• Grade 2
• Grade 1 Spontaneous bleeding
• Grade 3
• Signs of circulatory failure
• Grade 4
• Profound shock - B.P. Pulse not recordable

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Ecchymosis Periorbital Edema
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Large Subcutaneous Bleed
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Capillary Damage
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Tourniquet Test

• Inflate blood pressure cuff to a point
• midway between systolic and diastolic
• pressure for 5 minutes
• Positive test 20 or more petechiae
• per 1 inch² (6.25 cm²)

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Tourniquet Test
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Pleural Effusion
PEI A / B x 100
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Clinical tests for DHF

• Petechiae after tourniquet test
• Overt bleed from previous GI lesions
• Platelet count less than 100,000/ul
• Low pulse pressure, cyanosis, effusions
• Hypotension, Shock

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DHF- Poor Prognostic Signs

• Girl children under 12 with DHF/DSS
• Severe hypotension and shock
• Multifocal bleeding abdominal pain
• CNS encepahlopathy, fits, coma
• Watch for preorbital edema, proteinuria
• postural or otherwise hypotension
• Serotype 2 infection after type 4
• Malnutrition is protective

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Unusual Presentations of Dengue

• Encephalopathy
• Hepatic damage
• Cardiomyopathy
• Severe GI bleeding

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Differential Diagnosis

• FM complex
• Anicteric leptospirosis
• Rickettsial fevers
• Influenza, Measles, Rubella
• DHF / DSS
• Other hemorrhagic fevers
• DIC due to septicemia
• Complicated Malaria
• Meningococcemia

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Laboratory Diagnosis

• Complete Blood Counts
• Hematocrit
• Platelet Count
• Serum GOT, GPT
• Serum Albumin
• Proteinuria, hematuria
• Immunological Tests
• Chest Skiagram

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Laboratory Diagnosis

• Leucopenia. Thrombocytopenia
• Increased SGOT, SGPT
• Rising Ab titre in paired sera
• Antigen detection ELISA
• IgM-capture ELISA within few hours
• Reverse transcription PCR confirmatory
• IgG ELISA significant of past infection

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Immuno Detection Tests
ELISA Plate
IgM-capture ELISA
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Treatment of DF

• Supportive measures - Vector barrier
• Avoid Aspirin and if possible NSAIDs
• Steroids should not be used
• Fluid replacement to avoid hemoconc.
• Children below 12 require careful watch
• for DHF / DSS
• No antiviral agents are of proven value

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DHF / DSS
Intensive Care Oxygen Rehydration Barrier
Nursing Mosquito Screen
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Common Misconceptions- DHF

• Dengue bleeding DHF
• DHF is fatal only due to hemorrhage
• No Majority of deaths are due to shock
• Poorly managed DF turns into DHF
• Positive tourniquet DHF
• it is not specific for DHF,
• it indicates capillary fragility of any origin

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More Common Misconceptions

• DHF is only a pediatric illness
• No, All ages may be involved
• DHF is a problem of poor families
• No, in fact they may not have
• immune complexes to required level
• Tourists will get DHF
• No, in fact they are at low risk

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Management of DHF/DSS

• Close monitoring of hypotension/shock
• Oxygen administration
• IV. Infusion of crystalloids/colloids
• Platelet transfusion
• Clotting factors replacement
• Case fatality is 5 in good centers

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Fluid Balance

• Continue monitoring after defervescence
• Serial hematocrits, BP, Urine output
• Fluid replacement is twice the requirement
• 1500 ml 2 x (weight-20) for 60 kg wt.
• Eg. 1500 2 x (60-20) x 2
• 1500 (2x 40) x 2 (1500 800) x 2
• 2300 x 2 4600 ml 10 pints

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Immunization

• Each serotype produces life long immunity
• There is not efficacious vaccine available
• Vaccine needs to be tetravalent
• Live attenuated vaccines possible
• Several candidate vaccines are on trials
• It may be harmful to vaccinate in view
• of the pathogenesis of DHF/DSS

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Vector Control

• Biological
• Largely experimental
• Use of fish to feed on larvae
• Environmental
• Elimination of larval habitat
• Most likely successful strategy
• Purpose of control
• To reduce female vector density

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Vector Control of Dengue

• Mosquito control is expensive impossible
• Destruction of breeding sites viable
• Spraying insecticides for adult control- ?
• Individual measures to avoid vector contact
• Mosquito screens, repellents (DEET)
• Permithrin impregnated clothing
• Non degradable tires, long life plastics-avoid

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Challenge

• Achieve active community involvement
• Solicit input from the earliest program planning
  stages
• Encourage community ownership
• True community participation is key
•           

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Bibliography

• World Health Organization Reports
• Pan American Health Organization
• Center for Diseases Control, Atlanta
• National Institute of Communicable Diseases, New
  Delhi
• Bangladesh Center for Dengue
• Harrison's Principles of Internal Medicine, 15
  ed.

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Together We Learn Better

• Each Patient is a Book
• Each Day is a Learning Opportunity
• CME has More Relevance
• Now Than Ever

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Reach Yours Sincerely _at_

• Dr.SARMA RVSN
• Voice 91-4116-2309226, 260593
• Mobile [phone]
• E-mail sarma.rvsn_at_gmail.com
• Web site www.drsarma.in
• Snail mail 3, Jayanagar, Tiruvallur
• Tamilnadu, INDIA
• Pin 602 001

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Thank You !