DENGUE HEMORRHAGIC FEVER

1. DENGUE HEMORRHAGIC FEVER PROF S SHIVAKUMAR’S UNIT D RAVI SHANKAR MD PG

2. Komala • 20yrs/ female • Admitted on 11/ 04/ 06 • C/o • Fever with rigor - 3 days • Running nose • Dry cough - 3 days • Severe headache • Body ache - 3 days • Redness of eyes • Maculopapular rash- 1 day

3. No H/o • Dysuria • Jaundice • Vomiting • Diarrhea • Bleeding symptoms • Abdominal pain • Vaginal discharge • Past / Personal/ Family/ Drug H/o • Nothing relevant

4. GENERAL EXAMINATION • Conscious • Oriented • Febrile • No pallor/ icterus/ cyanosis/ clubbing/ • Lt posterior cervical LN + • Maculo papular rash over the face and neck + • Conjuntival suffusion + + • PR – 110/ mt, BP 110/ 70mmHg • Temp- 102 F, RR – 18/ mt

5. CVS • RS NAD • ABD • CNS DIAGNOSIS VIRAL EXANTHEMATOUS FEVER

6. ON 12/ 04/ 06 • Morning • Conscious • Highly febrile • Rash spread all over the body • Conjunctival suffusion increased • Little breathless • PR – 100/mt , BP – 100/ 70 • ECG & CXR – normal • Treated with IV fluids and antibiotics

7. ON 12/ 04/ 06 • Evening • Conscious, Disoriented • Febrile with severe rigors • Restless • Excessive sweating • Breathless • C/o • Black vomitus • Vaginal bleeding • Epistaxis • Sub conjunctival heamorrhage

8. Contd…… • Suddenly patient • Unconscious • Peripheries became cold • Sweating++ • Urinary and fecal incontinence • Pulse – feeble 130/ mt • BP - 50/ ? • Hemogram done in the morning was normal

9. Contd…… • Patient was treated with • 3- 4 liters of Normal saline • Fresh blood • Platlet transfusion • Dopamine infusion • BP picked up and patient became conscious • Patient shifted to IMCW • PLATLET count done outside at 11pm • 68,000/ cu mm

10. DIAGNOSIS • VIRAL HEMORRHAGIC FEVER • ? DENGUE SHOCK SYNDROME

11. ON 13/ 04/ 06 in IMCW • Conscious, oriented • Afebrile • No rash • Severe conjunctival hage • Loose stools • Vaginal bleeding + • Blood stained vomiting • BP stable • Treated with IV fluids, platlets(12 units), blood transfusion ( 2 units ), antibiotics.

12. INVESTIGATIONS • HEMOGRAM 12/04 17/04 20/04 • Hb 10.2 9.8 8.1 • TLC 54OO 4000 3600 • DLC P58 L42 P65L35 P63 L37 • ESR 12/ 20 8/ 20 10/ 22 • RBC 3.6 million 3.12 2.9 • PCV 3O% 30% 29% • PLATLET 68,000 50,000 1.45Lac

13. SERIAL PLATLET COUNT • 12/ 04 / 06 - 68,000 • 18/ 04 / 06 - 50,000 • 21/ 04 / 06 - 1.45 Lacs • 20/ 04 / 06 - 1.84 Lacs • 24/ 04 / 06 - 2.1 Lacs

14. OTHER INVESTIGATIONS • RFT • UREA - 38 mg/ dl • Creatinine- 1.0 mg/ dl • Blood sugar - 138mg /dl • LFT • TB - 1.0 mg/ dl • SGOT - 126 IU/ L • SGPT - 83 IU / L • SAP - 63 IU / L • T. protein- 7.8 g/ dl • Sr. Alb - 3.8 g/ dl

15. QBC MP - -VE • MSAT - -VE • WIDAL - -VE • DENDUE Ig M - +VE Ig G - +VE • PS STUDY - Microcytic Hypochromic anemia and thrombocytopenia. • USG ABD - N study

16. DIAGNOSIS DENGUE HEMORRHAGIC FEVER WITH DENGUE SHOCK SYNDROME

18. VIRAL HEMORRHAGIC FEVER • DENGUE • YELLOW FEVER • EBOLA • LASSA • HANTA • MARBURG • RIFT VALLEY FEVER • CRIMEAN CONGO

19. SIMILARITIES IN VHF • All are membrane bound viruses • All are RNA viruses • Most have Zoonotic life cycles except DENGUE • Acute fever and myalgia • Capillary leak syndrome • Host immune response decides severity of disease • All infections are immunosuppressive • All are mosquito or tick born

20. COMMON PATHOGENESIS • Affinity to capillary endothelium • Immune complex mediated endothelial injury • Complement mediated increased capillary permeability Increased capillary permeability Capillary Leak – ascites, pl effusion, edema Hypovolemia, hypotension, shock, Hypoxia , Acidosis and Hyperkalemia DIC

21. DENGUE • RNA virus, Flavi viridae • Four serotypes ( 1 – 4 ) • Transmitted by Aeidis aegypti and albopictus • Artificial containers • Day biter • Mosquitoes infective life long • Trans ovarian transmission • Preferentially in urban areas • Common in children and is mild than in adults

22. DENGUE - EPIDEMIOLOGY • All continents are endemic except Europe • 50- 100 million cases • 5 lac DHF • All 4 types reported in INDIA(1&2 common) • Epidemics in INDIA • 1970 – DEN 3 • 1996 - DEN 2 ( Delhi ) • 2003 status • 12,750 cases • 217 deaths • 1600 cases and 8 deaths in TN

23. ASYMPTOMATIC DENGUE INFECTION SYMPTOMATIC DENGUE FEVER DENGUE HEMORRHAGIC FEVER BREAK BONE FEVER VIRAL SYNDROME WITHOUT SHOCK WITH OR WITHOUT HEMORRHAGE WITH SHOCK ( DSS )

24. CLINICAL FEATURES • Undifferentiated fever with myalgia • Typical dengue fever • Older children and adults • Biphasic fever ( 5 – 7 days ) • Head ache, Myalgia, arthralgia • Upper Resp. symptoms • Flushed face, retro orbital pain, photophobia • RASH • Diffuse flushing or fleeting pin point eruptions fece, neck & chest during 1-3 days of fever • Maculopapular or scarlantiform – 4th day • After defevescence – petichiae and +ve Tourniquet test • Epistaxis, gum bleeding and GI bleeding may occur • Lecopenia with left shift

25. DHF AND DSS • High fever • Hemorrhagic phenomena • Peticheal rash • Epistaxis • GI bleed • Vaginal bleeding • Bleeding at IV cannula sites • +ve tourniquet test • Thrombocytopenia • Hemoconcentration • Circulatory failure( Febrile to afebrile) • Narrow pulse pressure • Hypotension • Cold clammy skin • Cyanosis • Profound shock • ICH, convulsions and encephalopathy

26. DHF - GRADES • Grade I - Fever Non sp symptoms Torniquet test +ve • Grade II - Spontaneous bleeding with above symptoms • Grade III - Rapid, weak pulse Narrow pulse pressure Hypotension • Grade IV - Profound Shock Platelet < 1 lac, PCV > 20 % in all grades

27. IMMUNOLOGY DENGUE INFECTION HETEROLOGOUS ANTIBODIES to other 3 serotypes HOMOLOGOUS ANTIBODIES CMI NEUTRALISING LEVEL 2-12 MONTHS (partial protection ) LIFE LONG PROTECTION AGAINST SAME SEROTYPE REDUCED TO NON NEUTRALISING LEVEL AFTER 12 MONTHS

28. IMMUNE ENHANCEMENT PRIMARY DENGUE INFECTION Secondary Dengue Infection – diff serotype NON NEUTRALISING LEVEL- Heterotypic Antibodies ( 1 – 5 yrs) MACROPHAGE VIRUS Highly infected Macrophage

29. DSS - PATHOGENESIS Uncontrolled multiplication Of virus in Macrophage Macrophage activation Excessive release Of cytokines (TNF & IL) VASODILATATION INCREASED PEMEABILITY HYPOTENSION CAPILLARY LEAK SHOCK HEMATOCRIT ( INTERNAL HEMORRHAGE)

30. DSS - PATHOGENESIS CD 8 mediated destruction of infected Macrophage Release of proteolytic Enzymes Immune complex Viral endothelial damage Complement activation Coagulation activation Thrombocytopenia C 3a C 5a anphylotoxins DIC( rare) Potent vasodilatation/ Leak

31. DSS – PRE REQUISITE • Primary dengue infection • Secondary & sequential infection with other serotypes with in 1-5 yrs of primary infection • DSS can occur in primary infection in infants who has maternal antibodies in non neutralizing level

32. LAB PROFILE • Hemogram • Leucopenia with relative Lymphocytosis • Thrombocytopenia < 1 lac • PCV increased > 20 % • Prolonged PT & aPTT • Reduced complement levels • Hypoproteinemia , mild SGOT & SGPT elevations • Virus isolation < 5 days • Serology - Ig M & Ig G ELISA

33. Treatment of DF/ DHF • Febrile phase • Bed rest • Paracetamol – 4times/day • Avoid Aspirin & Brufen • Avoid antibiotics • Oral Rehydration therapy – fluid loss due to vomiting / high temp. (2.5-4 litres /day) • Afebrile phase- observe

34. DHF CRYSTALLOIDS (RL/DNS) Improvement 6ml/kg/hr 3ml/kg/hr Discontinue after 6-12 hrs No Improvement CRYSTALLOIDS 6ml/kg/hr 10ml/kg/hr No improvement Hct Hct Blood transfusion Colloids discontinue Crystalloids 10-6-3ml improvement improvement

35. DSS Improvement CRYSTALLOIDS (10-20 ml/kg/hr) Reduce 10-6-3ml/kg/hr No Improvement CRYSTALLOIDS (10-20 ml/kg/hr) Hct  Hct  Blood transfusion ( 10ml/ kg/ hr ) COLLOID 10-6-3ml Discontinue Crystalloids Improvement 10-6-3ml

36. Points to be remembered • Hct  - IV Crystalloids or colloids (Dextran 40) or plasma (10 ml/kg/hr) • Hct  - Blood Transfusion (10ml/kg/hr) • Platelets < 5000cu.mm - platelet transfusion

37. thank u