Dengue fever recent advances

A comprehensive presentationby

DR MANDAR HAVALDR SANDIP KADE

Alternative Names

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

Dengue fever • Etiology • Epidemiology • Pathogenesis• Clinical presentation • Classification of disease spectrum • Diagnosis • Management

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 VirusElectron Micrograms

Dengue Virus

Cell Culture

Of Dengue

Virus

The Vector

Aedes aegypti(Infected Female Mosquito)

(rarely Aedes albapticus)

Aedes aegypti

Dengue, YF, CGF

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

Pathogenesis

Increased vascular permeability

Bone marrow suppression

Decreased levels of anticoagulants

Pathogenesis

Dengue InfectionInfected monocytes

Vasoactive mediators

Increased vascular permeability

Plasma leaking & hemoconcentration

Pathogenesis

Bone marrow supression

Leucopenia Thrombocytopenia

Neutropenia

Pathogenesis

• Decreased levels of fibrinogen , prothrombin factor II , VII ,IX, X ,XII, Antithrombin III

• Disseminated intravascular coagulation

• PT ,PTTK,TT may be normal or increased .• C3 & C5 levels decreased and C3a & C5a elevated

Causes of THROMBOCYTOPENIA

• Depression of bone marrow leading to impaired production of megakaryocyres

• Increased platelet destrucion :

virus itself

circulating immune complexes

and antiplatelet antibodies

• Periferal sequesrtation and consumption :

as in DIC

Causes of hemorrhagic manifestation

• Vascular instability• Decreased vascular integrity• Assault on macro vasculature• Decreased platelet function• Increased vascular permeability• Vascular disruption and local bleeds

Spectrum of clinical Presentations

• Undifferentiated fever• Dengue Fever (DF) with the Fever- Myalgia

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

Undifferentiated fever

• First infection with dengue virus presents with undifferentiated viral illness.

• Maculopapular rash during the fever or during defervescence

• Nausea vomiting and myalgia

Dengue fever • IP of 2 – 7 days • Sudden onset of fever, chills, headache• Anorexia. Nausea, vomiting• Back pain with severe myalgia, arthralgia• Retro-orbital pain – break bone fever• Macular rash – in axillary area• Maculo - papular rash on trunk – extremities• Leucopenia

Dengue Hemorrhagic fever

1. Fever or history of acute fever lasting 2-7 day occasionally biphasic

2. Hemorrhagic tendencies evidenced by at least one of the following :

~Positive torniquet test ~Petichiae ,ecchymosis, purpura ~Bleeding from mucosa and GIT ~Hematemesis maleana ~Thrombocytopenia

Dengue Hemorrhagic fever

3 . Thrombocytopenia < 100000/mm3 4 . Plasma leakage evidenced by atleast one ~Rise in hematocrit > 20 % ~ Fall in hematocrit > 20% after IV fluids ~Plural effusion,acites,hypoalbunemia

Dengue shock syndrome

• All four DHF Criteria plus • Signs of circulatory failure as: > Rapid and weak pulse > Narrow pulse pressure { < 20 mmHg } > Hypotension > Cold clammy skin , restlessness

Earlier WHO classification

Four Grades of DHF/DSS

• Grade 1Fever, Const. Symptoms, +ve tourniquet test

• Grade 2Grade 1 + Spontaneous bleeding

• Grade 3Signs of circulatory failure

• Grade 4Profound shock - B.P. Pulse not recordable

Petechiae

Ecchymosis – Periorbital Edema

Large Subcutaneous Bleed

Capillary Damage

Unusual Presentations of Dengue

• Encephalopathy• Hepatic damage• Cardiomyopathy• Severe GI bleeding

DHF- Poor Prognostic Signs

• Girl children under 12 with DHF/DSS• Severe hypotension and shock• Multifocal bleeding – abdominal pain• CNS encephalopathy ,fits ,coma• Watch for preorbital edema, proteinuria

postural or otherwise hypotension• Serotype 2 infection after type 4• Malnutrition is PROTECTIVE

Laboratory Diagnosis• Complete Blood Counts• Hematocrit• Platelet Count• SGOT, SGPT• Serum Albumin• Urine for Protein , hematuria• Immunological Tests• Chest X ray

Laboratory Diagnosis• Leucopenia. Thrombocytopenia• Increased SGOT, SGPT• Rising Ab titre in paired sera• NS1 detection ELISA(<3days)• IgM -capture ELISA within(3-5 days)• IgG ELISA significant of past infection• Reverse transcription PCR confirmatory

Management

• Group A – patient who may be sent home.

• Group B – patient who needs in hospital management.

• Group C – Patients who need emergency treatment and Intensive care.

Group A• Ambulatory patients - Able to tolerate fluids• Adequate urine output • No warning signs • Rx • Reviewed daily for disease progression { warning signs

hct and leucopenia }• Plenty of oral fluids • Antipyretics {aspirin, ibuprofen NSAIDS should be

avoided – gastritis and bleeding}• Immediate consultation for severe abdominal pain

vomitings cold clamy limbs black stools and oligourea

Group B

• Patients with warning signs or those with co-existing that may make dengue or its management more complicated (infancy, dual infection, or congenital anomalies)

Group B

• Rx• Obtain baseline hematocrit before IV fluids• Start with 5-7 ml/kg for 1-2 hours • Reduce to 3-5 ml/kg for 2-4 hours • Reduce to 2-3 ml/kg/hr as per clinical

response and urine output .• Isotonic solutions should be preferred.

Group C

• Pt who require emergency treatment and urgent referral

• Severe Plasma leakage, severe HEMORRHAGES, severe organ impairment.

Treatment Of Compensated Shock

Treatment of hypotensive shock

Monitoring during T/t of shock

• Vitals { pulse oxymetry }• ECG • Arterial blood gas • Sr. lactate• Blood glucose level • LFTs and KFT • Coagulation profile

Risk of bleeding

• Patient at risk of major bleeding • Renal & Hepatic failure & persistent metabolic

acidosis • NSAID Therapy • Pre existing peptic disease • On anticoagulant therapy • Any trauma including IM Injection

Treatment of hemorrhagic complication

• No IM injections • Strict bed rest • Blood transfusion is life saving but should be

used cautiously • Platelet in case of profound thrombocytopenia

and active bleeding • Maintainace of perfusion of vital organs with

judicious use of crystalloid and colloids

Management of fluid overload

• Causes :• Excessive and too rapid IV fluids • Incorrect use of hypotonic fluids rather than

isotonic crystalloids • Inappropriate use of FFP & platelet conc. And

cryoprecipitate • Continued IV fluids after plasma leakage has

restored • Co morbidities{CHD chronic lung or renal disease}

How to deal

• Depends on phase of disease and according to hemodynamic status of patient

• HD stable and out of critical phase > STOP IV fluids instantly and continue close monitoring.

• If necessary IV or ORAL furoseamide along with monitoring of eletrolytes

• Fresh Blood Transfusion advise in low or normal Hct. But shows s/o volume overload

Cont….

• Small boluses of collides are preffered in pt with shock with elevated Hct.

Adjuvant Therapy

• Vasopressor and inotrops ( fluid refrac..)

• Renal replacement therapy in ARF

• Treatment of complication like LIVER FAILURE and ENCEPHALOPATHY

Is there any role of Platelets ????

• NO….

• Indicated only in Pt with active BLEED or PROFOUND THROMBOCYTOPENIA (<10,000)

Is there role of STEROID??????

• NO….

Choice Of Iv Fluids • Crystalloids – NORMAL SALINE(300), RINGER

LACTATE(273) • NS – is ideal for initial ressucitation but if

continued there is a risk of hyperchloremic acidosis

• RL – its may be not sutaible for initial ressuci.. But is continued as a maintainance fluid. Contraindicated in liver failure..

Colloids

• Indicated in Narrow pulse pressure shock, if Blood pressure has to be restore urgently.

• It improves cardiac index and Hct in intractable shock

RCT on CRYSTALOID V/S COLLOIDS

• No CLEAR ADVANTAGE of colloids over crystalloid

Vector Control of Dengue

• Mosquito control is expensive –impossible• Destruction of breeding sites – viable• Individual measures to avoid vector contact

1. Mosquito screens, repellents (DEET)2. Permithrin impregnated clothing

• Non degradable tires, long life plastics-avoid

Immunization

• Each serotype produces life long immunity

• Vaccine needs to be tetravalent

• A live-attenuated tetravalent vaccine based on chimeric yellow fever-dengue virus (CYD-TDV), has progressed to phase III efficacy studies.

• It may be harmful to vaccinate in viewof the pathogenesis of DHF/DSS

(Sanofi Pasteur)

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

Now Than Ever

Together We Learn Better