Dengue Fever

Alternative Names

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

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

Viral Illnesses - Propagation

Human Human

HumanZoonotic Accidental

Virus

Arthropod

Rodent

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

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

Manifestations of Arborviral Illnesses

Most Arboviral diseases are rural Arboviral illnesses cause typical

manifestations – Often overlap The following clinical syndromes occur

1. FM – Fever – Myalgia complex

2. AR – Arthritis – Rash complex

3. HF – Haemorrhagic Fever

4. E – Encephalitis

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

Epidemiological Triangle

The Host

The Virus The Vector

Interaction

The Agent

Dengue Virus

The Dengue Virus

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

Dengue Virus

Electron Micrograms

Dengue Virus

Cell Culture

Of Dengue

Virus

The Vector

Aedes aegypti(Infected Female Mosquito)

(rarely Aedes albapticus)

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

Aedes aegypti

Dengue, YF, CGF

Aedes aegypti

Dengue

Yellow Fever

Chichungunya

Fever

Dengue on the Globe

Highly endemic Recently acquired

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

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 doesn’t suffer Virus is injected by the A.aegypti into man After 2-7 days of IP, man develops FM,HF

Dengue Transmission Cycle

Dengue Transmission

Dengue Illnesses - Propagation

Natural History of Dengue

Human Inf In apparent

DFM

Primary

DHF/DSS

30%

69%

01%

Re infection

Secondary

DHF/DSS

10%

Recovery100%

Death5%

95%

DHF Endemicity

Pathogenesis of DHF

Immuno-pathogenic

Cascade

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

Initial Immunogenecity

Immune Complexes

Attack on Host Immune Cells

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 virion’s surface

Fc receptor and focus the Dengue virus

on to the target cells – macro/monocytes T cell - cytokines, interferon, TNF alpha

The Disease

Clinical Features

Dengue Presentations

Undifferentiated fever Dengue Fever (DF) with the Fever-

Myalgia (FM) presentation (classical) Dengue Hemorrhagic Fever (DHF) Dengue Shock Syndrome (DSS)

Hemorrhagic Manifestations

Skin hemorrhages:petechiae, purpura, ecchymoses

Gingival bleeding Nasal bleeding Gastro-intestinal bleeding:

hematemesis, melena, hematochezia Haematuria Increased menstrual flow

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

Other manifestations- DF

Anorexia. Nausea, vomiting In apparent illness-to acute incapacitation Illness is about 2–5 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

Petechiae

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

DHF – Clinical Criteria

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 moremore over baseline or

Low albumin, pleural effusion

Criteria for DSS

The four criteria of DHF Evidence of circulatory failure

1. Rapid and weak pulse

2. Narrow pulse pressue (less than 20mm)

3. Hypotension for the age

4. Cold clammy skin

5. Altered mental status

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

Ecchymosis – Periorbital Edema

Large Subcutaneous Bleed

Capillary Damage

Tourniquet Test

Inflate blood pressure cuff to a pointmidway between systolic and diastolicpressure for 5 minutes

Positive test: 20 or more petechiaeper 1 inch² (6.25 cm²)

Tourniquet Test

PEI = A / B x 100

Pleural Effusion

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

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

Unusual Presentations of Dengue

Encephalopathy Hepatic damage Cardiomyopathy Severe GI bleeding

Differential Diagnosis

FM complex1. Anicteric leptospirosis

2. Rickettsial fevers

3. Influenza, Measles, Rubella DHF / DSS

1. Other hemorrhagic fevers

2. DIC due to septicemia

3. Complicated Malaria

4. Meningococcemia

Laboratory Diagnosis

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

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

Immuno Detection Tests

ELISA Plate IgM-capture ELISA

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

DHF / DSS

Intensive Care

Oxygen

Rehydration

Barrier Nursing

Mosquito Screen

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

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

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

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

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

Vector Control

Biological1. Largely experimental

2. Use of fish to feed on larvae Environmental

1. Elimination of larval habitat

2. Most likely successful strategy Purpose of control

To reduce female vector density

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

1. Mosquito screens, repellents (DEET)

2. Permithrin impregnated clothing Non degradable tires, long life plastics-avoid

Challenge

Achieve active community involvement Solicit input from the earliest program

planning stages Encourage community ownership True community participation is key          

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.

Thank You !