Dengue Clinical features and management

A self limiting fever - Dengue
Practice guidelines
management of dengue

1. HAPPY TEACHER ‘S DAY

2. DENGUE
A Self Limiting Fever
Dr A P Naveen Kumar DNB FICP
Chief Specialist ( Gen. Med. )
Visakha Steel General Hospital

3. • Dengue is the most rapidly emerging vector borne
viral infection world wide.
• 30 fold increase in incidence
• 19% of SEAR cases in 2013
• Three phases – febrile ,critical and recovery
•390 million positive cases world wide detected in 2017
•In India, 18700 cases detected, 46 people died in 2017.
EPIDEMIOLOGY

4. Caused by Flavi virus
Four types of Dengue infection :
1.DEN 1
2.DEN 2
3.DEN 3
4.DEN 4.
Recently in 2013 in Malaysia Dengue type 5(DEN 5) has been
detected in 7 positive patients.
ETIOLOGY

5. •First time infected with Dengue virus.
•Mild release of cytokines(TNF Alfa, IL2 etc..).
•Patient develops with Fever, body pains and head
ache etc..
Primary Dengue Pathophysiology

6. Secondary Dengue Pathophysiology
•It always develop in a patient (who already had a prior
dengue infection in past) get re infected with a different
dengue serotype other then primary serotype

•Secondary dengue almost always lead to severe plasma
leakage, severe thrombocytopenia, vasculopathy. (DSS/
DHF)
•Very high level of Cytokines (TNF Alfa, IL2, IL8 etc.)and
Viral Multiplication observed, which lead to disruption of
glycalyx , main component vascular endothelium.

7. Aedes Aeygpti

8. CASE
•Patient presents with 3 days fever -moderate
•Headache
•Bodyaches
•Cough cold and sore throat
•Expectoration present -yellow

9. CLINICAL FEATURES

10. CLINICAL FEATURES

11. Mild Dengue Infection
•Mild dengue infections are characterized by
undifferentiated DF, fever without complications like
bleeding, hypotension, organ involvement or any
evidence of capillary leakage.
•These patients usually do not have warning signs and
symptoms; hence, can be managed at home with
proper counseling.

12. Moderate dengue infection
•Moderate dengue infections were characterized
into two groups
Dengue infection with warning signs and
symptoms, DHF-I and II
Dengue infection with high-risk and
comorbid conditions.

13. DF with warning signs and symptoms
•„Recurrent vomiting
•„Abdominal pain/tenderness
•„General weakness/lethargy/restlessness
•„Minor bleeding
•„Pleural effusion/ascites
•„Hepatomegaly
•„Increased hematocrit (Hct).

14. Moderate dengue with high-risk and
comorbid conditions
•Infants
•„Old age
•„Diabetes
•„Hypertension
•„Pregnancy
•„Coronary artery disease (CAD)
•„Hemoglobinopathies
•„Immunocompromised patient
•„Patient on steroids, anticoagulants or
immunosuppressants.

15. Severe Dengue Infection
Severe dengue patients are recognized by the
presence of shock, capillary leakage,
significant bleeding, severe organ
involvement and severe metabolic
abnormalities.

18. 1.Patient developed Primary dengue(DEN-I) Infection.
2.Develops Haplotypic and Heterotypic antibodies.
3.Haplotypic antibodies provides life long protection against DEN-I.
4.Heterotypic antibodies provides protection against other dengue
serotypes (DEN-2, DEN-3) for 10 to 15 years.
5.After 10 to 15 years this heterotypic antibodies becomes non
neutralizing and attached with the virus and help its entry into a
target monocyte (like a Trojan Horse )
Antibody Dependent Mechanism (ADE)/Trojan
Horse Theory

19. •Direct viral induced platelets destruction
•Viral induced Bone marrow suppression
•Increase Platelet consumption (most important) cause due
to trapping of platelets via increased VWF and low
ADAMTS-13 in a sticky and damaged endothelium.
THROMBOCYTOPENIA IN SEVERE DENGUE
(PATHOPHYSIOLOGY )

20. •Metalloprotease which cleaves VWF.
•Low ADMTS-13 leads to unusually big large VWF
multimers .
•This VWF entrap platelets in damaged endothelium.
•In severe dengue there is unusually very low
ADAMTS-13 in blood.
ROLE OF ADAMTS-13/VWF

21. DSS

22. LAB DIAGNOSIS
•National Vector Borne Disease Control Program
(NVBDCP), Govt. of India recommends

• use of enzymelinked immunosorbent assay (ELISA)-
based antigen detection test (NS1) for diagnosing the
cases from 1st day onwards
• antibody detection test immunoglobulin M (IgM)
capture ELISA (MAC-ELISA) for diagnosing the cases
after 5th day of onset of disease to confirm dengue
infection

23. •A number of rapid diagnostic test (RDT) kits for NS1 antigen
and anti-dengue IgM/IgG antibodies are commercially
available at present, which produces the results within 15-25
minutes.
• However, the accuracy of most of these tests is not known
since they have not yet been properly validated. Some of
the RDTs have been independently evaluated.
•The sensitivity and specificity of some RDTs are also found
to vary from lot to lot.
• Hence, currently, use of RDT is not recommended under
the program.

24. CASE
•Fever 4 days
•Severe bodyaches
•Severe headache
•Vomitings
•Weakness and prostration
•Abdominal pain
•No significant cold / cough

25. What investigations
•CBC
•HCT
•PLATELETS
•LFT
•RFT
•CRP
•ELECTROLYTES

26. DATEHB TC PLTS.HCT SGOTSGPTAK.PHBIL CREA.
24-814.235009000043 50 38 92 0.5 0.9
27-815.8105001000050 76 51 148 0.7 0.8
28-814.8131003000052 248 160 81 0.6 0.8
30-814.5134001.5 44 72 114 86 0.6 0.7

27. DATEHB TC PLTS.SGOTSGPTAL.PH.BIL CREAHCT
24-815.260002.3429 57 98 2.4 1.0
27-4 330042000118 65 66 1.4 52
29-816 370016000 54
30-414.8440030000 44
31-814.465001.0 43

29. 1.Dengue Day 1 to Day 3
Finding: NS1AG (+ve/-ve), IgM(-ve), IgG(-ve / +ve)
2.Dengue Day 3 onword
Finding : NS1AG (+ve), IgM(-ve), IgG(+ve/-ve)
3.Dengue: Day 5 onward
Finding : NS1 +ve, IgM (strongally +ve), IgG (+ve/-ve)
4.Dengue: Day 3 onward
Finding : NS1+ve, IgM(+ve/-ve), IgG (Strongly Positive)
Common Clinical Situations

30. •Febrile phase
•High grade fever
•IV paracetamol
•Oral fluids
•Fruit juices
•Control fever
•Nausea

31. •Recovery phase
•Hypotension
•Bradycardia
•Platelets decrease
•Postural hypotension
•Capillary leak
•Coagulopathy
•Good monitoring

33. Indications of platelet transfusion
•No need of prophylactic – even below 20000
•May be given at < 10000
•Prolonged shock with coagulopathy
•Severe massive bleeding in addition to
packed cells
•5-6 units of random donor platelets
•1 unit SDP
•FFP /CRYO in coagulopathy

35. Tourniquet test

36. DD
•Malaria
•Chickengunya
•Viral
•Leptospirosis
•Enteric
•Gastroenteritis
•UTI
•Scrub

37. MANAGEMENT
•Management of DF is symptomatic and supportive.
•Antipyretics may be used to lower the body temperature.
•Aspirin/NSAIDs (nonsteroidal anti-inflammatory drugs) like
ibuprofen, etc. should be avoided since it may cause gastritis,
vomiting, acidosis, platelet dysfunction and severe bleeding
complication.
•Oral fluid and electrolyte therapy is recommended for patients with
excessive sweating, vomiting or hypotension.

38. Fall in SBP more then 20 mm hg from base line.
Rise in Pulse more then 20 per minute from base line
Rise in Hematocrit from base line more then 20%
Fall in pulse pressure more then 20 mm hg more
the base line.
Torniquit test more then 20 petchia.
Dr.KK Formula of 20 to Identify High Risk
individual

39. •Remember it is fluid resuscitation and not just
simple fluids.
•Patient may be in compensated shock
(tachycardia, tachypenia,SBP normal) or
decompensate shock (SBP below 90,organ
perfusion compromised).
•Compensated shock is extremely labile stage so
can be missed by physician if the patient is not
touched by the physician.
•Monitor the Vitals (BP and Pulse) every 6 hourly.
TREATMENT FOR SEVERE DENGUE

41. FLUID RESUSCITATION FOR SEVERE
DENGUE

42. FLUIDS IN DECOMPENSATED SHOCK

43. If HCT is low, but hemodynamically patient is stable, do
not give Blood transfusion
If HCT is high, but hemodynamically patient is stable, do
not give fluids
Best fluid to start is 0.9% normal saline, but change to
Ringer lactate once hyperchloremia develops
In diabetics on metformin or CKD Patients always try to
avoid Ringer lactate as a first fluid - acidosis
KEY POINTS (FLUID TREATMENT)

44. •Crystalloids : Normal Saline , Ringer Lactate
•Colloids : Dextran 40 /Degraded gelatine
polymer ( polygeline )

45. INDICATIONS FOR PLATELET TRANSFUSION:
•Low platelets in dengue has minimum co-relation with disease
severity, but raising platelets has strong positive co-relation with
improvement of disease(IPF more than 10%).
•As per WHO recommendations, there is no need of platelet
transfusion upto platelet count 10,000 with no bleeding.
•Below 10,000, platelet transfusion maybe given in absence of
bleeding.
•Its alway better to give whole blood or FFP instead of platelets(as
whole blood/FFP contains ADAMTS-13).

46. COMPLICATIONS OF PLATELET TRANSFUSION IN SEVERE
DENGUE
•Risk of fluid over load.
•High risk of platelet transfusion related bacterial infections.
•Transfusion related Allergic reactions.
•Prolong hospitalization(due to supression of thrombpoitin).

47. DENGUE - HEPATITIS
•AST/ALT –high and PT prolonged
•Viral hepatitis , cirrhosis and fatty liver
•Hepatic encephalopathy and liver failure
•Low albumin – increased leak
•GI bleeding –severe DSS
•Managed carefully - fluids , vitamin K

48. DENGUE - MYOCARDITIS
•CAD , HTN , Valvular heart disease ,T2DM
•Shock management is difficult
•Pulmonary edema and arrythmias

49. DENGUE -RENAL
•ATN
•Hematuria
•Acidosis
•Nephropathy in presence of co-morbid
conditions

50. DENGUE -PREGNANCY
•Risk of more bleeding , fetal complications , low birth weight
and premature birth
•Vertical transmission increased
•Pleural effusion, ascites and hypotension more common
•Lung and liver involvement more
•Fluid replacement difficult as it is a hyperdynamic circulation
•Frequent counts and coagulation profile
•Fulminant hepatic failure , ARF and ARDS
•Management should be taken seriously

51. •The WHO guidelines for management of dengue do not
recommend the use of corticosteroids
•Nonetheless, some clinicians use steroids in
treatment,though there is currently no clear evidence to
justify the use of corticosteroids in the treatment of severe
dengue.
•There is a clear need for adequately powered, randomized,
double-blind, placebo-controlled clinical trials in both children
and adults to evaluate fully the possible benefit or lack of
benefit of corticosteroids in dengue infection.

52. PATIENT INCLUSION CRITERIA
• POSITIVE NS1 ANTIGEN
• IgG OR IgM ANTIBODIES.
•PLATELET COUNT < 20,000 / cu mm.
•RASH WITH HIGH FEVER
EXCLUSION CRITERIA
• EVIDENCE OF MIXED INFECTIONS
•EVIDENCE OF HAEMATOLOGICAL DISORDERS
•DENGUE SHOCK SYNDROME

53. MATERIALS AND METHODS
•TWO GROUPS WERE TAKEN INTO THIS STUDY.
•IN EACH GROUP 25 PATIENTS WERE SELECTED
•TO ONE GROUP , PLATELETS WERE TRANSFUSED .
•TO THE OTHER GROUP , HYDROCORTISONE 100mg WAS GIVEN BID FOR 2 DAYS
AND THEN TAPERED OFF FOR ANOTHER 2 -3 DAYS.

54. 25
18
24
21
12
20 20
25
18
14
0
5
10
15
20
25
30
Rash Fever ErythemaAbdominal
pain
Polyserositis
HC group
Platelet group
No of Patients
CLINICAL FEATURES

55. INVESTIGATIONS
25
23
8
24
16
121212
24
25
22
6
25
18
1010
14
23
0
5
10
15
20
25
30
HC Group
Platelet Group
No of
Patients

56. RECOVERY
4
3
2 2 2
6
5
4 4
5
0
1
2
3
4
5
6
7 HC Group
Platelet Group
No of Days

57. •AVERAGE DURATION OF STAY IN HOSPITAL.
HC GROUP - 4 DAYS
PLATELET GROUP 6 DAYS

SYMPTOM REGRESSION
POLYSEROSITIS REGRESSED FASTER.
ABDOMINAL PAIN RELIEVED QUICKER.
LEUCOPENIA RECOVERED IN 2 DAYS AVERAGE .

58. REVIEW
Study Drug Effect
Kularatne et al
2004
Dexamethasone Not effective
Srichaicul et al
2008 - 2010
Dexamethasone Decreased duration
of illness and
hospital stay
Panpanich R et al
2006
Corticosteroid Insufficient data to
support steroids
Present study –
VSGH
2012-2013
Hydrocortisone Decreased duration
of illness and stay

59. CRITERIA FOR DISCHARGE:
•Afebrile >48 hours.
•Clinical improvement.
•Platelet count increasing more than 50000
.
•No respiratory distress.
•Stable haematocrit without intravenous
fluids.
•No postural hypotension.

60. VACCINATION
CYD-TDV DENGUE VACCINE (DENGVAXIA by Sanofi )
•Developed by recombinant DNA technology
•It is Live attenuated chimeric dengue vaccine.
•Dose 0.5ml subcutaneous in more than 9 years of
age at 0, 6 & 12 months .
•2015: WHO recommended for DENGUE vaccination.
•2015: Mass vaccination done in Latin America, Brazil
and Philippines.
•2015: In India, phase II safety trial done in 5 cities in
age group of 18-45 years.

61. DENGVAXIA –RECENT CONTROVERSES:
•29
th
NOV-2017: Sanofi Revealed that Dengue Vaccinated
Individuals Who had not any prior dengue infection are at risk of
very severe Dengue Disease in future on subsequent Dengue
Infection.
•Dec-2017: Brazil and Philippines Govt has immediately suspended
ongoing vaccination programe.
•Jan-2018: 14 children died in Philippines of viral fever who are
previously vaccinated with dengue vaccine. Post mortem analysis
indicated severe bleeding in vital organs(lungs and kidneys etc..)
suggestive of severe dengue.
•Jan-2018 : FDA Has advised Sanofi to stop marketing.

62. Vector (A.Aegypti mosquito) control:
•Larvicide and Insecticide over mosquito
breeding area.
•Insecticide treated nets(ITN),against mosquito
biting particularly early morning and day time
biting.
VECTOR PREVENTION
THANK YOU