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DR ANJANA NAIR A
 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 structural protein genes: C, M, E
 Non structural protein genes:
NS1,2A, 2B,3,4A,4B,5
 NS1- diagnostic value
 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
 Rain - Temp, humidity
 16- 30 C
 60-80 % humidity
 Altitude
 Cool shady places
 Humans, lower primates
 Infants
 Travel, migration
 Extrinsic incubation period : 8-10 days
 Intrinsic incubation period : 4-7 days (3-14)
 Blood transfusion, organ transplantation
 Congenital
CYTOKINE TSUNAMI!!
Mononuclear
cells
 “A double edged sword”
 non neutralising cross reacting antibodies
 Ab-Ag(virus) complex ----- enhanced uptake by Ig receptor containing cells
Widen gap
junctions(transien
t endothelial
dysfunction)
DENGUE FEVER WITHOUT WARNING
SIGNS
DENGUE FEVER WITH WARNING SIGNS
SEVERE DENGUE FEVER
DENGUE FEVER (DF)
DENGUE HEMORRHAGIC FEVER(DHF)
DENGUE SHOCK SYNDROME (DSS)
 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
 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)
 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
 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
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
 Severe plasma leakage – shock or fluid accumulation + resp distress
 Severe bleeding
 Severe organ involvement ( AST/ALT >/= 1000 u/l, impaired consciousness, organ
failure)
 Unusual presentations
 Comorbidities/coinfections
 A case compatible with clinical criteria during outbreak or
 Non ELISA based NS1 antigen/IgM positive(RDT)
 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
Febrile
Critical
Convalescent
 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)
 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
 Leaked ECF returns to circulation
 After D6-D7
 For days-weeks
 Rash- white islands in red sea( pruritic)-5 days
 Complication: Pulmonary oedema
 Viral Hgic fevers- Ebola, Marburg, Lassa, YF, CCHF, Hanta
 Chikungunya
 Zika Virus
 Malaria
 Enteric fever
 Leptospirosis
 Viral hepatitis
 Rickettsial infection
 Influenza
 COVID
 Meningococcal infection
 1st 5 days- Nucleic acid by RTPCR
 Antigen – NS1 – 1st 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
 No comorbidities/ high risk factors
 Near normal blood counts (Plt > 1,00,000)
 Tolerating oral fluids
 Adequate urine output
 No Warning signs
 Bed Rest
 Tepid sponging
 Antipyretics- Paracetamol ( No NSAIDSs)
 ORS
 Warning signs during critical phase
 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
Chart 1. volume replacement algorithm for patients with moderate Dengue Fever (DHF grades I & II)
41
 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
Chart 2. Volume replacement algorithm for patients with Severe Dengue Fever (DHF grades III)
43
 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
Chart 3. Volume replacement algorithm for patients with Severe Dengue Fever (DHF IV (DSS))
45
 VS every 15 mins till stable and hourly thereafter
 HCT every 1-2 hours
 Reassess clinical status every 1-2 hours
 NO bleeding- plt <10,000
 Bleeding +/- thrombocytopenia
 Severe bleed + coagulopathy- PRBC/FFP
 No role for Whole blood in managing thrombocytopenia
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
1)PERSONAL PROTECTION-
 Mosquito repellants(DEET)
 Insecticides
 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
2)MOSQUITO CONTROL
 Reduce breeding sites
 Larva control- Copepods feed on larva
 Endosymbiotic control- Mosquitos infected with Wolbachia less vulnerable to
DENV
 Which is the cardinal feature that distinguishes DHF from DF??
a) Thrombocytopenia (<1,00,000)
b) Bleeding manifestations (Positive tourniquet test)
c) Evidence of plasma leakage
d) Both b and c
e) All of the above
DENGUE FEVER.pathogenesis, clinical features and management.pptx

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DENGUE FEVER.pathogenesis, clinical features and management.pptx

  • 2.
  • 3.  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
  • 4.  3 structural protein genes: C, M, E  Non structural protein genes: NS1,2A, 2B,3,4A,4B,5  NS1- diagnostic value
  • 5.  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
  • 6.
  • 7.  Rain - Temp, humidity  16- 30 C  60-80 % humidity  Altitude  Cool shady places
  • 8.  Humans, lower primates  Infants  Travel, migration
  • 9.
  • 10.
  • 11.  Extrinsic incubation period : 8-10 days  Intrinsic incubation period : 4-7 days (3-14)  Blood transfusion, organ transplantation  Congenital
  • 12.
  • 14.  “A double edged sword”  non neutralising cross reacting antibodies  Ab-Ag(virus) complex ----- enhanced uptake by Ig receptor containing cells
  • 16.
  • 17.
  • 18. DENGUE FEVER WITHOUT WARNING SIGNS DENGUE FEVER WITH WARNING SIGNS SEVERE DENGUE FEVER DENGUE FEVER (DF) DENGUE HEMORRHAGIC FEVER(DHF) DENGUE SHOCK SYNDROME (DSS)
  • 19.
  • 20.  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
  • 21.  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)
  • 22.  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
  • 23.  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
  • 24. 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
  • 25.  Severe plasma leakage – shock or fluid accumulation + resp distress  Severe bleeding  Severe organ involvement ( AST/ALT >/= 1000 u/l, impaired consciousness, organ failure)
  • 26.  Unusual presentations  Comorbidities/coinfections
  • 27.  A case compatible with clinical criteria during outbreak or  Non ELISA based NS1 antigen/IgM positive(RDT)
  • 28.  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
  • 30.  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)
  • 31.  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
  • 32.  Leaked ECF returns to circulation  After D6-D7  For days-weeks  Rash- white islands in red sea( pruritic)-5 days  Complication: Pulmonary oedema
  • 33.  Viral Hgic fevers- Ebola, Marburg, Lassa, YF, CCHF, Hanta  Chikungunya  Zika Virus  Malaria  Enteric fever  Leptospirosis  Viral hepatitis  Rickettsial infection  Influenza  COVID  Meningococcal infection
  • 34.
  • 35.  1st 5 days- Nucleic acid by RTPCR  Antigen – NS1 – 1st 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
  • 36.
  • 37.
  • 38.  No comorbidities/ high risk factors  Near normal blood counts (Plt > 1,00,000)  Tolerating oral fluids  Adequate urine output  No Warning signs
  • 39.  Bed Rest  Tepid sponging  Antipyretics- Paracetamol ( No NSAIDSs)  ORS  Warning signs during critical phase
  • 40.  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
  • 41. Chart 1. volume replacement algorithm for patients with moderate Dengue Fever (DHF grades I & II) 41
  • 42.  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
  • 43. Chart 2. Volume replacement algorithm for patients with Severe Dengue Fever (DHF grades III) 43
  • 44.  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
  • 45. Chart 3. Volume replacement algorithm for patients with Severe Dengue Fever (DHF IV (DSS)) 45
  • 46.  VS every 15 mins till stable and hourly thereafter  HCT every 1-2 hours  Reassess clinical status every 1-2 hours
  • 47.  NO bleeding- plt <10,000  Bleeding +/- thrombocytopenia  Severe bleed + coagulopathy- PRBC/FFP  No role for Whole blood in managing thrombocytopenia
  • 48. 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
  • 49. 1)PERSONAL PROTECTION-  Mosquito repellants(DEET)  Insecticides  Vaccines
  • 50.  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
  • 51. 2)MOSQUITO CONTROL  Reduce breeding sites  Larva control- Copepods feed on larva  Endosymbiotic control- Mosquitos infected with Wolbachia less vulnerable to DENV
  • 52.  Which is the cardinal feature that distinguishes DHF from DF?? a) Thrombocytopenia (<1,00,000) b) Bleeding manifestations (Positive tourniquet test) c) Evidence of plasma leakage d) Both b and c e) All of the above