Dengu Fever By Dr Mahipal

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Dengu Fever By Dr Mahipal

  1. 2. Dengue Fever (Pronounced as Dhen Gey) A comprehensive presentation by Dr.P MAHIPAL REDDY
  2. 3. Alternative Names <ul><li>Onyong- Nyang Fever </li></ul><ul><li>West Nile Fever </li></ul><ul><li>Break Bone Fever </li></ul><ul><li>Dengue like Disease </li></ul>
  3. 4. Background <ul><li>Propagation of viral illnesses </li></ul><ul><li>Transmission of viral illnesses </li></ul><ul><li>Various families of Arbor viruses </li></ul><ul><li>Manifestations of Arborviral illnesses </li></ul><ul><li>Dengue – A Flavivirus- EM- Cell culture </li></ul><ul><li>Transmitted by mosquito </li></ul><ul><li>Aedes aegypti </li></ul>
  4. 5. Viral Illnesses - Propagation Human Human Human Zoonotic Accidental Virus Arthropod Rodent
  5. 6. Transmission of Viral Illnesses <ul><li>Droplet infection as in case of </li></ul><ul><li>Measles, Influenza, Coryza etc. </li></ul><ul><li>Blood to blood transmission- HIV, HBV </li></ul><ul><li>Feco-oral – Rota, Polio </li></ul><ul><li>Direct contact – Herpes simplex etc </li></ul><ul><li>Arthropod borne –Dengue, JE, YF </li></ul><ul><li>Tick borne – CEE, Colorado TF </li></ul>
  6. 7. Arthropod borne Viral Diseases <ul><li>Flavivirus – Mosquito borne – YF, DF,JE </li></ul><ul><li>Flavivirus – Tick Borne –CEE, RSSE, KFD </li></ul><ul><li>Buniyavirus – Mosquito- CE </li></ul><ul><li>Plebovirus – Sandfly Fever </li></ul><ul><li>Arinavirus – LCM virus </li></ul><ul><li>Colivirus – Colorado Tick fever </li></ul><ul><li>Vesiculovirus – Vesicular stomatitis </li></ul><ul><li>Alphavirus – E/W/V equine encephalitides </li></ul>
  7. 8. Manifestations of Arborviral Illnesses <ul><li>Most Arboviral diseases are rural </li></ul><ul><li>Arboviral illnesses cause typical </li></ul><ul><li>manifestations – Often overlap </li></ul><ul><li>The following clinical syndromes occur </li></ul><ul><ul><li>FM – Fever – Myalgia complex </li></ul></ul><ul><ul><li>AR – Arthritis – Rash complex </li></ul></ul><ul><ul><li>HF – Haemorrhagic Fever </li></ul></ul><ul><ul><li>E – Encephalitis </li></ul></ul>
  8. 9. Epidemiology of Dengue <ul><li>The Dengue Virus </li></ul><ul><li>The Vector </li></ul><ul><li>Global distribution of Dengue </li></ul><ul><li>Transmission cycle – host – vector </li></ul><ul><li>Propagation of virus – I.P </li></ul><ul><li>Natural History of Dengue </li></ul><ul><li>Dengue Hemorrhagic fever – </li></ul><ul><li>Endemicity pattern </li></ul>
  9. 10. Epidemiological Triangle The Host The Virus The Vector Interaction
  10. 11. The Agent <ul><li>Dengue Virus </li></ul>
  11. 12. The Dengue Virus <ul><li>Flavivirus </li></ul><ul><li>Positive sense </li></ul><ul><li>Single stranded RNA virus </li></ul><ul><li>40 to 50 nanometers </li></ul><ul><li>Four sero-sub types </li></ul><ul><li>Type 1 to 4 </li></ul><ul><li>Arthropod borne </li></ul>
  12. 13. Dengue Virus Electron Micrograms
  13. 14. Dengue Virus Cell Culture Of Dengue Virus
  14. 15. The Vector Aedes aegypti (Infected Female Mosquito) (rarely Aedes albapticus)
  15. 16. Peculiarities of A.aegypti <ul><li>It is a day biting mosquito when normally </li></ul><ul><li>coils, repellents, nets etc are not used </li></ul><ul><li>It breads in fresh water around homes </li></ul><ul><li>Lays eggs preferentially in water jars, discar- ded containers , coconut shells, old tires etc. </li></ul><ul><li>Can transmit trans-ovarially the infection </li></ul><ul><li>Year round breeding 25 0 N to 25 0 S </li></ul><ul><li>Tropics and sub-tropics are its favorite zones. It is an urban vector </li></ul>
  16. 17. Aedes aegypti Dengue, YF, CGF
  17. 18. Aedes aegypti Dengue Yellow Fever Chichungunya Fever
  18. 19. Dengue on the Globe Highly endemic Recently acquired
  19. 20. Dengue Fever <ul><li>Caused by an arthropod borne virus </li></ul><ul><li>It is a zoonotic virus </li></ul><ul><li>Man is accidentally infected </li></ul><ul><li>Other vertebrates are the reservoirs </li></ul><ul><li>Dengue virus has 4 subtypes 1 to 4 </li></ul><ul><li>Positive sense, single str RNA- 40nm </li></ul><ul><li>Vector mosquito is Aedes aegypti </li></ul>
  20. 21. Mechanism of Transmission <ul><li>Vector is infected after ingestion of blood meal from a viremic vertebrate </li></ul><ul><li>Virus multiplies in the system of vector </li></ul><ul><li>for 2-3 weeks – extrinsic incubation pd. </li></ul><ul><li>Natural vertebrate partner has only </li></ul><ul><li>transient viremia and doesn’t suffer </li></ul><ul><li>Virus is injected by the A.aegypti into man </li></ul><ul><li>After 2-7 days of IP, man develops FM,HF </li></ul>
  21. 22. Dengue Transmission Cycle
  22. 23. Dengue Transmission
  23. 24. Dengue Illnesses - Propagation
  24. 25. Natural History of Dengue Human Inf In apparent DFM Primary DHF/DSS 30% 69% 01% Re infection Secondary DHF/DSS 10% Recovery 100% Death 5% 95%
  25. 26. DHF Endemicity
  26. 27. Pathogenesis of DHF <ul><li>Immuno-pathogenic </li></ul><ul><li>Cascade </li></ul>
  27. 28. Hypotheses on DHF - DSS <ul><li>Neutralizing Ab are type specific nutralize the homologous sub type </li></ul><ul><li>Subsequent infection with heterologous sub type causes immune complexes </li></ul><ul><li>These Immune Complexes target the mononuclear lineage foe enhanced viral replication </li></ul><ul><li>Infected monocytes release vasoactive mediators causing vascular damage </li></ul>
  28. 29. Initial Immunogenecity
  29. 30. Immune Complexes
  30. 31. Attack on Host Immune Cells
  31. 32. Immunopathogenic Cascade of DHF/DSS <ul><li>Macrophage – monocyte infection </li></ul><ul><li>Previous infection with heterologous </li></ul><ul><li>Dengue serotype results in production </li></ul><ul><li>of non protective antiviral antibodies </li></ul><ul><li>These Ab bind to the virion’s surface </li></ul><ul><li>Fc receptor and focus the Dengue virus </li></ul><ul><li>on to the target cells – macro/monocytes </li></ul><ul><li>T cell - cytokines, interferon, TNF alpha </li></ul>
  32. 33. The Disease <ul><li>Clinical Features </li></ul>
  33. 34. Dengue Presentations <ul><li>Undifferentiated fever </li></ul><ul><li>Dengue Fever (DF) with the Fever- Myalgia (FM) presentation (classical) </li></ul><ul><li>Dengue Hemorrhagic Fever (DHF) </li></ul><ul><li>Dengue Shock Syndrome (DSS) </li></ul>
  34. 35. Hemorrhagic Manifestations <ul><li>Skin hemorrhages: petechiae, purpura, ecchymoses </li></ul><ul><li>Gingival bleeding </li></ul><ul><li>Nasal bleeding </li></ul><ul><li>Gastro-intestinal bleeding: hematemesis, melena, hematochezia </li></ul><ul><li>Haematuria </li></ul><ul><li>Increased menstrual flow </li></ul>
  35. 36. Clinical Manifestations- DF <ul><li>IP of 2 – 7 days - typical patient develops </li></ul><ul><li>Sudden onset of fever, chills, headache </li></ul><ul><li>Back pain with severe myalgia, arthralgia </li></ul><ul><li>Retro-orbital pain – break bone fever </li></ul><ul><li>Macular rash – in axillary area </li></ul><ul><li>Adenopathy, palatal vesicles, scleral inj. </li></ul><ul><li>Maculo-papular rash on trunk – extremities </li></ul><ul><li>Epistaxis and scattered petechiae </li></ul>
  36. 37. Other manifestations- DF <ul><li>Anorexia. Nausea, vomiting </li></ul><ul><li>In apparent illness-to acute incapacitation </li></ul><ul><li>Illness is about 2–5 days, biphasic course </li></ul><ul><li>Pain on eye movements </li></ul><ul><li>Pain on palpating abdominal muscles </li></ul><ul><li>Primarily not a respiratory illness </li></ul><ul><li>Rare - aseptic meningitis </li></ul><ul><li>Complete recovery is the rule - asthenia </li></ul>
  37. 38. Petechiae
  38. 39. Dengue Haemorrhagic Fever (DHF) <ul><li>Vascular instability </li></ul><ul><li>Decreased vascular integrity </li></ul><ul><li>Assault on macro vasculature </li></ul><ul><li>Decreased platelet function </li></ul><ul><li>Increased vascular permeability </li></ul><ul><li>Vascular disruption and local bleeds </li></ul><ul><li>Hypotension, hemoconcentration- shock </li></ul>
  39. 40. DHF – Clinical Criteria
  40. 41. Criteria for DHF <ul><li>Fever, or recent history of acute fever </li></ul><ul><li>Hemorrhagic manifestations </li></ul><ul><li>Low platelet count (100,000/mm 3 or less) </li></ul><ul><li>Objective evidence of “leaky capillaries:” </li></ul><ul><ul><li>Elevated hematocrit -20% or more </li></ul></ul><ul><ul><li>more over baseline or  </li></ul></ul><ul><ul><li> Low albumin, pleural effusion </li></ul></ul>
  41. 42. Criteria for DSS <ul><li>The four criteria of DHF </li></ul><ul><li>Evidence of circulatory failure </li></ul><ul><ul><li>Rapid and weak pulse </li></ul></ul><ul><ul><li>Narrow pulse pressue (less than 20mm) </li></ul></ul><ul><ul><li>Hypotension for the age </li></ul></ul><ul><ul><li>Cold clammy skin </li></ul></ul><ul><ul><li>Altered mental status </li></ul></ul>
  42. 43. Four Grades of DHF/DSS <ul><li>Grade 1 </li></ul><ul><li>Fever, Const. Symptoms, +ve tourniquet test </li></ul><ul><li>Grade 2 </li></ul><ul><li>Grade 1 + Spontaneous bleeding </li></ul><ul><li>Grade 3 </li></ul><ul><li>Signs of circulatory failure </li></ul><ul><li>Grade 4 </li></ul><ul><li>Profound shock - B.P. Pulse not recordable </li></ul>
  43. 44. Ecchymosis – Periorbital Edema
  44. 45. Large Subcutaneous Bleed
  45. 46. Capillary Damage
  46. 47. Tourniquet Test <ul><ul><ul><li>Inflate blood pressure cuff to a point </li></ul></ul></ul><ul><ul><ul><li>midway between systolic and diastolic </li></ul></ul></ul><ul><ul><ul><li>pressure for 5 minutes </li></ul></ul></ul><ul><ul><ul><li>Positive test: 20 or more petechiae </li></ul></ul></ul><ul><ul><ul><li>per 1 inch² (6.25 cm²) </li></ul></ul></ul>
  47. 48. Tourniquet Test
  48. 49. Pleural Effusion PEI = A / B x 100
  49. 50. Clinical tests for DHF <ul><li>Petechiae after tourniquet test </li></ul><ul><li>Overt bleed from previous GI lesions </li></ul><ul><li>Platelet count less than 100,000/ul </li></ul><ul><li>Low pulse pressure, cyanosis, effusions </li></ul><ul><li>Hypotension, Shock </li></ul>
  50. 51. DHF- Poor Prognostic Signs <ul><li>Girl children under 12 with DHF/DSS </li></ul><ul><li>Severe hypotension and shock </li></ul><ul><li>Multifocal bleeding – abdominal pain </li></ul><ul><li>CNS encepahlopathy, fits, coma </li></ul><ul><li>Watch for preorbital edema, proteinuria </li></ul><ul><li>postural or otherwise hypotension </li></ul><ul><li>Serotype 2 infection after type 4 </li></ul><ul><li>Malnutrition is protective </li></ul>
  51. 52. Unusual Presentations of Dengue <ul><li>Encephalopathy </li></ul><ul><li>Hepatic damage </li></ul><ul><li>Cardiomyopathy </li></ul><ul><li>Severe GI bleeding </li></ul>
  52. 53. Differential Diagnosis <ul><li>FM complex </li></ul><ul><ul><li>Anicteric leptospirosis </li></ul></ul><ul><ul><li>Rickettsial fevers </li></ul></ul><ul><ul><li>Influenza, Measles, Rubella </li></ul></ul><ul><li>DHF / DSS </li></ul><ul><ul><li>Other hemorrhagic fevers </li></ul></ul><ul><ul><li>DIC due to septicemia </li></ul></ul><ul><ul><li>Complicated Malaria </li></ul></ul><ul><ul><li>Meningococcemia </li></ul></ul>
  53. 54. Laboratory Diagnosis <ul><li>Complete Blood Counts </li></ul><ul><li>Hematocrit </li></ul><ul><li>Platelet Count </li></ul><ul><li>Serum GOT, GPT </li></ul><ul><li>Serum Albumin </li></ul><ul><li>Proteinuria, hematuria </li></ul><ul><li>Immunological Tests </li></ul><ul><li>Chest Skiagram </li></ul>
  54. 55. Laboratory Diagnosis <ul><li>Leucopenia. Thrombocytopenia </li></ul><ul><li>Increased SGOT, SGPT </li></ul><ul><li>Rising Ab titre in paired sera </li></ul><ul><li>Antigen detection ELISA </li></ul><ul><li>IgM-capture ELISA within few hours </li></ul><ul><li>Reverse transcription PCR confirmatory </li></ul><ul><li>IgG ELISA significant of past infection </li></ul>
  55. 56. Immuno Detection Tests ELISA Plate IgM-capture ELISA
  56. 57. Treatment of DF <ul><li>Supportive measures - Vector barrier </li></ul><ul><li>Avoid Aspirin and if possible NSAIDs </li></ul><ul><li>Steroids should not be used </li></ul><ul><li>Fluid replacement to avoid hemoconc. </li></ul><ul><li>Children below 12 require careful watch </li></ul><ul><li>for DHF / DSS </li></ul><ul><li>No antiviral agents are of proven value </li></ul>
  57. 58. DHF / DSS Intensive Care Oxygen Rehydration Barrier Nursing Mosquito Screen
  58. 59. Common Misconceptions- DHF <ul><li>Dengue + bleeding = DHF </li></ul><ul><li>DHF is fatal only due to hemorrhage </li></ul><ul><li>No Majority of deaths are due to shock </li></ul><ul><li>Poorly managed DF turns into DHF </li></ul><ul><li>Positive tourniquet = DHF </li></ul><ul><li>it is not specific for DHF, </li></ul><ul><li>it indicates capillary fragility of any origin </li></ul>
  59. 60. More Common Misconceptions <ul><li>DHF is only a pediatric illness – </li></ul><ul><li>No, All ages may be involved </li></ul><ul><li>DHF is a problem of poor families – </li></ul><ul><li>No, in fact they may not have </li></ul><ul><li>immune complexes to required level </li></ul><ul><li>Tourists will get DHF – </li></ul><ul><li>No, in fact they are at low risk </li></ul>
  60. 61. Management of DHF/DSS <ul><li>Close monitoring of hypotension/shock </li></ul><ul><li>Oxygen administration </li></ul><ul><li>IV. Infusion of crystalloids/colloids </li></ul><ul><li>Platelet transfusion </li></ul><ul><li>Clotting factors replacement </li></ul><ul><li>Case fatality is 5% in good centers </li></ul>
  61. 62. Fluid Balance <ul><li>Continue monitoring after defervescence </li></ul><ul><li>Serial hematocrits, BP, Urine output </li></ul><ul><li>Fluid replacement is twice the requirement </li></ul><ul><li>1500 ml + 2 x (weight-20) – for 60 kg wt. </li></ul><ul><li>Eg. {1500 + 2 x (60-20)} x 2 </li></ul><ul><li>= {1500 + (2x 40)} x 2 = (1500 + 800) x 2 </li></ul><ul><li>= 2300 x 2 = 4600 ml = 10 pints </li></ul>
  62. 63. Immunization <ul><li>Each serotype produces life long immunity </li></ul><ul><li>There is not efficacious vaccine available </li></ul><ul><li>Vaccine needs to be tetravalent </li></ul><ul><li>Live attenuated vaccines possible </li></ul><ul><li>Several candidate vaccines are on trials </li></ul><ul><li>It may be harmful to vaccinate in view </li></ul><ul><li>of the pathogenesis of DHF/DSS </li></ul>
  63. 64. Vector Control <ul><li>Biological </li></ul><ul><ul><li>Largely experimental </li></ul></ul><ul><ul><li>Use of fish to feed on larvae </li></ul></ul><ul><li>Environmental </li></ul><ul><ul><li>Elimination of larval habitat </li></ul></ul><ul><ul><li>Most likely successful strategy </li></ul></ul><ul><li>Purpose of control </li></ul><ul><ul><li>To reduce female vector density </li></ul></ul>
  64. 65. Vector Control of Dengue <ul><li>Mosquito control is expensive –impossible </li></ul><ul><li>Destruction of breeding sites – viable </li></ul><ul><li>Spraying insecticides for adult control- ? </li></ul><ul><li>Individual measures to avoid vector contact </li></ul><ul><ul><li>Mosquito screens, repellents (DEET) </li></ul></ul><ul><ul><li>Permithrin impregnated clothing </li></ul></ul><ul><li>Non degradable tires, long life plastics-avoid </li></ul>
  65. 66. Challenge <ul><li>Achieve active community involvement </li></ul><ul><li>Solicit input from the earliest program planning stages </li></ul><ul><li>Encourage community ownership </li></ul><ul><li>True community participation is key </li></ul><ul><li>           </li></ul>
  66. 67. Bibliography <ul><li>World Health Organization Reports </li></ul><ul><li>Pan American Health Organization </li></ul><ul><li>Center for Diseases Control, Atlanta </li></ul><ul><li>National Institute of Communicable Diseases, New Delhi </li></ul><ul><li>Bangladesh Center for Dengue </li></ul><ul><li>Harrison's Principles of Internal Medicine, 15 ed. </li></ul>
  67. 68. <ul><li>Each Patient is a Book </li></ul><ul><li>Each Day is a Learning Opportunity </li></ul><ul><li>CME has More Relevance </li></ul><ul><li>Now Than Ever </li></ul>Together We Learn Better
  68. 69. Thank You !

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