Dengue Fever (Pronounced as Dhen Gey)

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

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

4. 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

5. Viral Illnesses - Propagation Human Human Accidental Human Zoonotic Arthropod Rodent Virus

6. 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

7. 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

8. 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

9. 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

10. Epidemiological Triangle The Host Interaction The Virus The Vector

11. The Agent Dengue Virus

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

17. Aedes aegypti Dengue, YF, CGF

18. Aedes aegypti Dengue Yellow Fever Chichungunya Fever

19. Dengue on the Globe Highly endemic Recently acquired

20. 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

21. 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

22. Dengue Transmission Cycle

23. Dengue Transmission

24. Dengue Illnesses - Propagation

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

26. DHF Endemicity

27. Pathogenesis of DHF Immuno-pathogenic Cascade

28. 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

29. Initial Immunogenecity

30. Immune Complexes

31. Attack on Host Immune Cells

32. 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

33. The Disease Clinical Features

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

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

36. 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

37. 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

38. Petechiae

39. 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

40. DHF – Clinical Criteria

41. 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

42. 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

43. 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

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. Pleural Effusion PEI = A / B x 100

50. 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