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Dengue Fever.

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Presentation on theme: "Dengue Fever."— Presentation transcript:

1 Dengue Fever

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

3 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

4 Viral Illnesses - Propagation
Human Human Accidental Zoonotic Human Arthropod Virus Rodent

5 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

6 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

7 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

8 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

9 Epidemiological Triangle
The Host Interaction The Virus The Vector

10 The Agent Dengue Virus

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

12 Dengue Virus Electron Micrograms

13 Dengue Virus Cell Culture Of Dengue Virus

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

15 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

16 Aedes aegypti Dengue, YF, CGF

17 Aedes aegypti Dengue Yellow Fever Chichungunya Fever

18 Dengue on the Globe Highly endemic Recently acquired

19 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

20 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

21 Dengue Transmission Cycle

22 Dengue Transmission

23 Dengue Illnesses - Propagation

24 Natural History of Dengue
In apparent Human Inf 30% 100% Recovery DFM Re infection 69% 95% 10% Death Primary DHF/DSS Secondary DHF/DSS 5% 01%

25 DHF Endemicity

26 Pathogenesis of DHF Immuno-pathogenic Cascade

27 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

28 Initial Immunogenecity

29 Immune Complexes

30 Attack on Host Immune Cells

31 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

32 The Disease Clinical Features

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

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

35 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

36 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

37 Petechiae

38 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

39 DHF – Clinical Criteria

40 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

41 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

42 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

43 Ecchymosis – Periorbital Edema

44 Large Subcutaneous Bleed

45 Capillary Damage

46 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)

47 Tourniquet Test

48 Pleural Effusion PEI = A / B x 100

49 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

50 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

51 Unusual Presentations of Dengue
Encephalopathy Hepatic damage Cardiomyopathy Severe GI bleeding

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

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

54 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

55 Immuno Detection Tests
ELISA Plate IgM-capture ELISA

56 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

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

58 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

59 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

60 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

61 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. { x (60-20)} x 2 = { (2x 40)} x 2 = ( ) x 2 = 2300 x 2 = 4600 ml = 10 pints

62 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

63 Vector Control Biological Environmental Purpose of control
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

64 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

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

66 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.

67 Thank You !

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