DENGUE FEVER.pathogenesis, clinical features and management.pptx

All about dengue

1. DENGUE FEVER DR ANJANA NAIR A

2. THE CULPRIT!!! Genus: Flavi virus 4 serotypes: DENV -1,2,3,4 Cross protection only for few months Life long protection Genotypes (Subtypes) DENV1-3 DENV 2-2 DENV 3-4 DENV 4-4

3. Structure 3 structural protein genes: C, M, E Non structural protein genes: NS1,2A, 2B,3,4A,4B,5 NS1- diagnostic value

4. VECTOR Female Aedes mosquito(Aegypti, Albopictus) Aedes- day time feeder (&twilight), 400 m Eggs in damp places---------  7days- adult emerges Dry------ 1year Rain---- survival of vectors longer

5. environment Rain - Temp, humidity 16- 30 C 60-80 % humidity Altitude Cool shady places

6. Host Humans, lower primates Infants Travel, migration

7. Transmission cycle

8. BANGALORE CALICUT

9. Extrinsic incubation period : 8-10 days Intrinsic incubation period : 4-7 days (3-14) Blood transfusion, organ transplantation Congenital

10. PATHOGENESIS IMMUNOPATHOGENESIS Capillary leakage and shock Coagulopathy

11. immunopathogenesis CYTOKINE TSUNAMI!! Mononuclear cells

12. ANTIBODY DEPENDENT ENHANCEMENT “A double edged sword” non neutralising cross reacting antibodies Ab-Ag(virus) complex -----  enhanced uptake by Ig receptor containing cells

13. CAPILLARY LEAKAGE AND SHOCK Widen gap junctions(transient endothelial dysfunction)

14. COAGULOPATHY

15. CLASSIFICATION(WHO) 1997 2009 DENGUE FEVER WITHOUT WARNING SIGNS DENGUE FEVER WITH WARNING SIGNS SEVERE DENGUE FEVER DENGUE FEVER (DF) DENGUE HEMORRHAGIC FEVER(DHF) DENGUE SHOCK SYNDROME (DSS)

16. High risk group

17. CLINICAL CRITERIA- DF Clinical features: An acute febrile illness of 2-7 days duration + 2/more of following: - Headache -Retro orbital pain -Myalgia/bone pain -Arthralgia -Rash - Hemorrhagic manifestations

18. CLINICAL CRITERIA- DHF DF + + Hemorrhagic manif evidenced by 1 /more of foll : - Positive tourniquet test - Petechiae, ecchymoses or purpura -Bleeding from mucosa , GIT, injn sites or other sites + Thrombocytopenia ( < 1 lkh /mm3) + evidence of plasma leakage manifested by 1 /more of foll : - rise in avg HCT for age and sex >/= 20 % - > 20 % drop in HCT following vol replacement compared to baseline - signs of plasma leakage (pleural effusion, ascites, hypoproteinemia )

19. TOURNIQUET TEST/ HESS’S TEST Test to assess Capillary fragility BP cuff to mid point b/w SBP & DBP (120/80  100) 5 MINS >/= 10 petechiae in 1 square inch over forearm DHF: 20 Neg / mild positive in profound shock

20. CLINICAL CRITERIA- DSS All the previous criteria + circulatory failure : - Restlessness - Cold clammy skin - rapid,thready pulse - Narrow pulse pressure( </= 20 mmHg) - Hypotension for age (SBP < 90 mmHg) - reduced urine o/p

21. WARNING SIGNS AND SYMPTOMS Persistent vomiting Abdominal pain/tenderness Clinical fluid accumulation-(Pleural effusion/ Ascites) Mucosal Bleeding Lethargy, Restlessness hepatomegaly > 2 cm Increase in HCT with rapid fall in Platelet count

22. SEVERE DENGUE Severe plasma leakage – shock or fluid accumulation + resp distress Severe bleeding Severe organ involvement ( AST/ALT >/= 1000 u/l, impaired consciousness, organ failure)

23. Expanded dengue syndrome Unusual presentations Comorbidities/coinfections

24. Case definition-PROBABLE A case compatible with clinical criteria during outbreak or Non ELISA based NS1 antigen/IgM positive (RDT)

25. Case definition-CONFIRMED A case compatible with clinical criteria + 1 or more of: Isolation of virus ( culture) from serum, plasma or leucocytes IgM Ab by ELISA positive in single serum sample Antigen by NS1 ELISA IgG sero conversion in paired sera after 2 weeks with 4 fold rise in titre Viral nucleic acid detection by PCR

26. NATURAL COURSE Febrile Critical Convalescent

27. FEBRILE High grade - 2-7 days , Biphasic (5 %) Head ache, eye pain ( 60-70 %) Rash (50 % )- 1st > 2 nd – D2- D5- macular/maculopapular- face,trunk , extremities, pruritus +/- Breakbone fever O/E: Conj redness, pharyngeal erythema, lymphadenopathy, hepatomegaly, bleeds Leucopenia , thrombocytopenia, raised AST (2-5 times), synthetic liver function ( aPTT normal)

28. Critical D3-D7 36- 48 hrs Plasma leakage, Bleeding , Shock( early- narrow PP) Mod- Severe thrombocytopenia Rising HCT aPTT inc , fibrinogen low( transient) Imaging- CXR, USG Abdomen, chest

29. CONVALESCENce /RECOVERY Leaked ECF returns to circulation After D6-D7 For days-weeks Rash- white islands in red sea ( pruritic)-5 days Complication: Pulmonary oedema

30. DIFFERENTIAL DIAGNOSES Viral Hgic fevers- Ebola, Marburg, Lassa, YF, CCHF, Hanta Chikungunya Zika Virus Malaria Enteric fever Leptospirosis Viral hepatitis Rickettsial infection Influenza COVID Meningococcal infection

31. LAB DIAGNOSIS

32. INVESTIGATIONS 1 st 5 days- Nucleic acid by RTPCR Antigen – NS1 – 1 st week (1-5) IgM – after 4 days(ELISA) (2-3 months) IgM seroconversion b/w paired acute and recovery phase(10-14 days after acute phase) 4fold / greater rise in Ab titre. Serology unreliable in : Vaccinated( recent months),recent infection/ vaccination with an antigenically related flavi virus- yellow fever , Japanese encephalitis, zika virus. Virus culture

33. MANAGEMENT

34. MANAGEMENT

35. Home management No comorbidities/ high risk factors Near normal blood counts ( Plt > 1,00,000) Tolerating oral fluids Adequate urine output No Warning signs

36. HOME MANAGEMENT( Mild DF) Bed Rest Tepid sponging Antipyretics- Paracetamol ( No NSAIDSs) ORS Warning signs during critical phase

37. IP management (MODERATE & SEVERE) Fluid management guided by PR,BP,PP ,RR,GCS, Temp,Urine o/ p, HCT Improvement in VS and HCT : Taper fluids VS worsening + HCT falling : Internal bleeding- Blood transfusion

38. Chart 1. volume replacement algorithm for patients with moderate Dengue Fever (DHF grades I & II) 41

39. DHF –I, II Vitals every 2-3 hours HCT every 4-6 hours Urine o/p every 4-8 hours Goal: Urine o/p: 0.5-1 ml/kg/hr

40. Chart 2. Volume replacement algorithm for patients with Severe Dengue Fever (DHF grades III) 43

41. DHF-III VS every 1-2 hours HCT every 4-6 hours( Bleeding- every 1-2 hours) Reassess clinical status at completion of crystalloid infusion Colloid: 10% Dextran 40 in NS preferred

42. Chart 3. Volume replacement algorithm for patients with Severe Dengue Fever (DHF IV (DSS)) 45

43. DHF-IV VS every 15 mins till stable and hourly thereafter HCT every 1-2 hours Reassess clinical status every 1-2 hours

44. CRITERIA FOR PLATELET TRANSFUSION NO bleeding- plt <10,000 Bleeding +/- thrombocytopenia Severe bleed + coagulopathy- PRBC/FFP No role for Whole blood in managing thrombocytopenia

45. 48 Criteria for discharge of patients Absence of fever for at least 24 hours without the use of anti-fever therapy No respiratory distress from pleural effusion or ascites Platelet count > 50 000/ cumm Return of appetite Good urine output Minimum of 2 to 3 days after recovery from shock Visible clinical improvement

46. PREVENTION 1)PERSONAL PROTECTION- Mosquito repellants (DEET) Insecticides Vaccines

47. VACCINES CYD-TDV( Dengvaxia )- Live attenuated - 4 Chimeric yellow fever- 17D dengue vaccine viruses ( preM , E proteins replace the same in YF 17D backbone virus) - WHO- 9-45 years with confirmed previous dengue infection who live in endemic areas. (Not for seronegative individuals) -0,6,12 months -Not for travellers visiting enedemic areas TAK-003- Tetravalent vaccine Attenuated lab derived DENV2 virus- genetic back bone for all 4 viral strains, other 3 are chimeras generated by replacing preM and E genes of TDV-2 with those from DENV1,3 and 4 -Both in seronegative and seropositive individuals

48. 2)MOSQUITO CONTROL Reduce breeding sites Larva control- Copepods feed on larva Endosymbiotic control- Mosquitos infected with Wolbachia less vulnerable to DENV

49. Q & A Which is the cardinal feature that distinguishes DHF from DF?? Thrombocytopenia (<1,00,000) Bleeding manifestations (Positive tourniquet test) Evidence of plasma leakage Both b and c All of the above

50. THANK YOU!!!!