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Dengue Fever

Dengue Fever

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Dengue Fever

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  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 Human Zoonotic Arthropod Rodent Virus

  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. The Vector Aedes aegypti (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 HumanInf 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