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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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Presentation on theme: "Dengue Fever (Pronounced as Dhen Gey) A comprehensive presentation by Dr.R.V.S.N.Sarma., M.D.,"— Presentation transcript:

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2 Dengue Fever (Pronounced as Dhen Gey) A comprehensive presentation by Dr.R.V.S.N.Sarma., M.D.,

3 Alternative Names l Onyong- Nyang Fever l West Nile Fever l Break Bone Fever l Dengue like Disease

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

5 Viral Illnesses - Propagation Human Zoonotic Accidental Virus Arthropod Rodent

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

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

8 Manifestations of Arborviral Illnesses l Most Arboviral diseases are rural l Arboviral illnesses cause typical manifestations – Often overlap l The following clinical syndromes occur 1. FM – Fever – Myalgia complex 2. AR – Arthritis – Rash complex 3. HF – Haemorrhagic Fever 4. E – Encephalitis

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

10 Epidemiological Triangle The Host The Virus The Vector Interaction

11 The Agent Dengue Virus

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

13 Dengue Virus Electron Micrograms

14 Dengue Virus Cell Culture Of Dengue Virus

15 The Vector Aedes aegypti (Infected Female Mosquito) (rarely Aedes albapticus)

16 Peculiarities of A.aegypti l It is a day biting mosquito when normally coils, repellents, nets etc are not used l It breads in fresh water around homes l Lays eggs preferentially in water jars, discar- ded containers, coconut shells, old tires etc. l Can transmit trans-ovarially the infection l Year round breeding 25 0 N to 25 0 S l Tropics and sub-tropics are its favorite zones. It is an urban vector

17 Aedes aegypti Dengue, YF, CGF

18 Aedes aegypti Dengue Yellow Fever Chichungunya Fever

19 Dengue on the Globe Highly endemicRecently acquired

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

21 Mechanism of Transmission l Vector is infected after ingestion of blood meal from a viremic vertebrate l Virus multiplies in the system of vector for 2-3 weeks – extrinsic incubation pd. l Natural vertebrate partner has only transient viremia and doesn’t suffer l Virus is injected by the A.aegypti into man l After 2-7 days of IP, man develops FM,HF

22 Dengue Transmission Cycle

23 Dengue Transmission

24 Dengue Illnesses - Propagation

25 Natural History of Dengue Human Inf In apparent DFM Primary DHF/DSS 30% 69% 01% Re infection Secondary DHF/DSS 10% Recovery100% Death 5% 95%

26 DHF Endemicity

27 Pathogenesis of DHF Immuno-pathogenic Cascade

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

29 Initial Immunogenecity

30 Immune Complexes

31 Attack on Host Immune Cells

32 Immunopathogenic Cascade of DHF/DSS l Macrophage – monocyte infection l Previous infection with heterologous Dengue serotype results in production of non protective antiviral antibodies l These Ab bind to the virion’s surface Fc receptor and focus the Dengue virus on to the target cells – macro/monocytes l T cell - cytokines, interferon, TNF alpha

33 The Disease Clinical Features

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

35 Hemorrhagic Manifestations l Skin hemorrhages: petechiae, purpura, ecchymoses l Gingival bleeding l Nasal bleeding l Gastro-intestinal bleeding: hematemesis, melena, hematochezia l Haematuria l Increased menstrual flow

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

37 Other manifestations- DF l Anorexia. Nausea, vomiting l In apparent illness-to acute incapacitation l Illness is about 2–5 days, biphasic course l Pain on eye movements l Pain on palpating abdominal muscles l Primarily not a respiratory illness l Rare - aseptic meningitis l Complete recovery is the rule - asthenia

38 Petechiae

39 Dengue Haemorrhagic Fever (DHF) l Vascular instability l Decreased vascular integrity l Assault on macro vasculature l Decreased platelet function l Increased vascular permeability l Vascular disruption and local bleeds l Hypotension, hemoconcentration- shock

40 DHF – Clinical Criteria

41 Criteria for DHF l Fever, or recent history of acute fever l Hemorrhagic manifestations l Low platelet count (100,000/mm 3 or less) l Objective evidence of “leaky capillaries:” Elevated hematocrit -20% or more more over baseline or  Low albumin, pleural effusion

42 Criteria for DSS l The four criteria of DHF l 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

43 Four Grades of DHF/DSS l Grade 1 Fever, Const. Symptoms, +ve tourniquet test l Grade 2 Grade 1 + Spontaneous bleeding l Grade 3 Signs of circulatory failure l Grade 4 Profound shock - B.P. Pulse not recordable

44 Ecchymosis – Periorbital Edema

45 Large Subcutaneous Bleed

46 Capillary Damage

47 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)

48 Tourniquet Test

49 PEI = A / B x 100 Pleural Effusion

50 Clinical tests for DHF l Petechiae after tourniquet test l Overt bleed from previous GI lesions l Platelet count less than 100,000/ul l Low pulse pressure, cyanosis, effusions l Hypotension, Shock

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

52 Unusual Presentations of Dengue l Encephalopathy l Hepatic damage l Cardiomyopathy l Severe GI bleeding

53 Differential Diagnosis l FM complex 1. Anicteric leptospirosis 2. Rickettsial fevers 3. Influenza, Measles, Rubella l DHF / DSS 1. Other hemorrhagic fevers 2. DIC due to septicemia 3. Complicated Malaria 4. Meningococcemia

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

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

56 Immuno Detection Tests ELISA PlateIgM-capture ELISA

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

58 DHF / DSS Intensive Care Oxygen Rehydration Barrier Nursing Mosquito Screen

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

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

61 Management of DHF/DSS l Close monitoring of hypotension/shock l Oxygen administration l IV. Infusion of crystalloids/colloids l Platelet transfusion l Clotting factors replacement l Case fatality is 5% in good centers

62 Fluid Balance l Continue monitoring after defervescence l Serial hematocrits, BP, Urine output l Fluid replacement is twice the requirement l 1500 ml + 2 x (weight-20) – for 60 kg wt. Eg. { x (60-20)} x 2 = { (2x 40)} x 2 = ( ) x 2 = 2300 x 2 = 4600 ml = 10 pints

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

64 Vector Control l Biological 1. Largely experimental 2. Use of fish to feed on larvae l Environmental 1. Elimination of larval habitat 2. Most likely successful strategy l Purpose of control l To reduce female vector density

65 Vector Control of Dengue l Mosquito control is expensive –impossible l Destruction of breeding sites – viable l Spraying insecticides for adult control- ? l Individual measures to avoid vector contact 1. Mosquito screens, repellents (DEET) 2. Permithrin impregnated clothing l Non degradable tires, long life plastics-avoid

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

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

68 l Each Patient is a Book l Each Day is a Learning Opportunity l CME has More Relevance Now Than Ever Together We Learn Better

69 Reach Yours l Dr.SARMA RVSN l Voice : , l Mobile : l l Web site : l Snail mail :3, Jayanagar, Tiruvallur Tamilnadu, INDIA Pin :

70 Thank You !


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