Dengue overview, clinical features and management.

1. DENGUE
Dr. NAVIN ADHIKARI
Internal Medicine Resident

2. PROBLEM STATEMENT
Worldwide, annually in over 100 countries
 99 million symptomatic dengue infections
 404 million asymptomatic infections
 500,000 cases of severe dengue
 20,000 deaths.
 The global burden of dengue has increased at
least fourfold over the last three decades.
 There are now 2.5 billion people at risk of the
disease.

4. Status In Nepal
 The earliest cases were detected as early as
2005
 Initially most of the reported cases had travel
history to neighbouring country (India).
 Studies carried out in close collaboration of
WARUN/AFRIMS in the year 2006 by
EDCD/NPHL showed all 4 sub-types (DEN-1,
DEN-2, DEN-3 and DEN-4) of Dengue virus
circulation in Nepal.
 Upto 2019, a total of 3425 confirmed dengue
cases were reported.

6. AGENT FACTOR
 Virus group: Flavivirus
 Is a single-stranded enveloped RNA virus.
 Four serotypes are known: DEN1, DEN2,
DEN3, DEN4
 Principal Reservoir Host: Non human
primates

7. VECTOR
 Different species of Aedes mosquitoes.
 Aedes aegypti, Ae. albopictus, Ae.
Polynesiensis, Ae. scutellariscomplex.
 Also known as Tiger Mosquito because of
stripped and branded nature of their leg.
 Areas that are favourable for mosquito
breeding are household water storage like
bottles, buckets , pots, trees holes.

8. AEDES MOSQUITO

9. TRANSMISSION
 The female mosquito bites humans during the
day.
 After feeding the female Ae. aegypti can
transmit dengue immediately by a change of
host.
 After an extrinsic incubation period of 8–10
days, during which time, the virus multiplies in
the salivary glands and which mosquito
becomes infective.
 The mosquito host remains infective for life (30–
45 days).

10. ENVIRONMENTAL FACTORS
 Survives around 16 to 30 degree celsius and
humidity of around 60-80 percent.
 Outbreaks occurs around rainy season
because of pooling of household water.

11. PATHOPHYSIOLOGY
 Major pathophysiologic changes that
determine the severity of disease in severe
dengue are plasma leakage and abnormal
hemostasis leading to rising hematocrit
values, moderate to marked
thrombocytopenia.
 Sequential infection with any two of the four
serotypes of dengue virus results in severe
dengue infections in an endemic area.

12. PATHOPHYSIOLOGY ……
 The residual antibodies produced during the
first infection are able to neutralize a second
viral infection with the same serotype.
 However, when no neutralizing antibodies
are present (i.e. infection due to another
serotype of dengue virus), the second
infection is under the influence of enhancing
antibodies i.e increase their uptake by
cells, which express Fc. receptors on their
surfaces, like tissue dendritic cells, monocytes
and macrophages.

14. CLINICAL COURSE
 INTO 3 PHASES:
1. FEBRILE PHASE
2. CRITICAL PHASE
3. CRITICAL PHASE

15. FEBRILE PHASE
 Incubation period is around 2–7 days.
 There is acute onset of fever with severe
headache, chills, pain behind the eyes,
particularly on eye movement, backache and
pain in the muscles, bones and joints( break
bone fever).
 During the febrile period the temperature can be
as high as 40°C.
 Fever is Continuous or ‘saddle-back’, with
break on 4th or 5th day and then
recrudescence; usually lasts 7–8 days.

16. Rashes
 Initial flushing faint macular rash in first 1–2
days.
 Maculopapular, scarlet morbilliform
blanching rash from days 3–5 on trunk,
spreading centrifugally and sparing palms
and soles; onset often with fever
defervescence.
 May desquamate on resolution or give rise to
petechiae on extensor surfaces.

18. MACULOPAPULAR
RASH

19. CRITICAL PHASE
 The critical phase, which occurs at fever
defervescence usually around day 5.
 This is peroid where an increase in capillary
permeability and plasma leakage can occur.
 This may present clinically as pleural
effusions and ascites depending on the
degree of plasma leakage.
 Once a critical volume is lost, shock ensues.

20.  The pulse pressure becomes narrow (20
mmHg) with elevation of diastolic pressure to
meet the systolic pressure.
 The platelet count drops shortly before or
simultaneously with the haematocrit rise
(20%) and both changes occur before the
subsidence of fever and before onset of shock.
 Usually last for 24-48 hrs.

21. RECOVERY PHASE
 The extravascular fluid begins to be resorbed
over the next 48–72 hours.
 If intravenous fluids are continued into this
period there is significant risk of fluid overload,
manifesting as respiratory distress from pleural
effusions and/or ascites.
 General symptomatic improvement is seen, with
return of appetite, haemodynamic stability and
diuresis. During this period, the white cell count
begins to rise followed by the platelets, the
haematocrit may drop.

23. CLINICAL FEATURES

24. WHO CLASSIFICATION
 Dengue was previously classified (1997) into
dengue fever and dengue haemorrhagic fever
(DHF) of which there were four grades, with DHF
III and IV compiling dengue shock syndrome
(DSS).
 In 2009, the WHO reclassified dengue due to
difficulty applying the old classification system in
clinical situations and increasing reports of severe
cases not fitting the criteria for DHF.
 The new classification emphasizes levels of
severity with patients being classified as
dengue without warning signs
dengue with warning signs
and severe dengue.

30. Tourniquet test
 It is a clinical diagnostic method to determine
patients hemorrhagic tendency.
 It assesses fragility of capillary walls and is
used to identify thrombocytopenia.
 Used for diagnosis of dengue fever.

31.  A blood pressure cuff is applied and inflated to
the midpoint between the systolic and
diastolic blood pressure for 5 minutes.
 Test is positive if there are more than 10 to
20 petechiae per square inch.

32. Positive torniquet test

33. Investigation
 CBC reveals Leukopenia, thrombocytopenia
and raised hematocrit.
 LFT may show elevations of serum
aminotransferase concentrations.
 CXR and ultrasound shows pleural effusion (
common on rt side ) and ascitis respectively.
 Stool occult blood test
 Urine routine examination may show
hematuria.

34. LABAROTORY DIAGNOSTIC
TESTS
 Virus Isolation
 Genome Detection
 NS1 Detection
 IGM antibody
 IGG antibody detection

36. NS1 antigen
 The NS1 glycoprotein is produced by all
flaviviruses and is secreted from mammalian
cells.
 NS1 is used to make an early diagnosis of
dengue virus infection.
 Commercial kits for the detection of NS1
antigen are available, though they do not
differentiate between dengue serotypes.
 ELISA based antigen detection test.

39. Differential Diagnosis
 Hemorrhagic fevers
 Influenza
 Malaria
 Enteric fever
 Leptospirosis
 Meningococcemia
 Rickettsial infections.
 Malaria, leptospirosis, flu and enteric fever
may also be coinfected with dengue.

40. Management
Dengue infection without warning signs.
 May be treated symptomatically.
 Fever and bodyaches are best treated with
paracetamol.
 Salicylates and other nonsteroidal
antiinflammatory drugs should be avoided .
 Plenty of fluids. There is no specific therapy.
 Monitor the patient for warning signs along
with hematocrit and platelet counts.

41. Management
Dengue with warning signs
 Require admission to the hospital
 Need intravenous fluids, preferably
crystalloids
 Frequent monitoring of hematocrit and vital
parameters.

43. Severe dengue
 hospitalized preferably in Intensive Care Unit
 Treated with normal saline or lactated Ringer
solution.
 10-20 ml/kg is infused over one hr or given as
a bolus if blood pressure is unrecordable.

45. MANAGEMENT OF BLEEDING
 Avoid IM injections.
 There is no role of prophylactic platelet rich
plasma (PRP) infusions even with severe
thrombocytopenia. Avoid any procedures
predisposing .
 Should be treated with blood transfusion if
required.
 When bleeding cannot be managed with fresh
whole blood and there is possibility of DIC, fresh-
frozen plasma and platelet rich plasma may be
considered.

46. MANAGEMENT OF FLUID
OVERLOAD
 Stop intravenous fluids but continue close
monitoring.
 If necessary, give oral or intravenous
furosemide 0.1-0.5 mg/kg/dose once or twice
daily.
 If patient is in critical phase, reduce the
intravenous fluid accordingly. Avoid
diuretics during the plasma leakagep hase
because they may lead to intravascular
volume depletion.

47. CONTROL MEASURES
 Environmental control by source reduction
should be no opportunity for stagnation of
water in the bathroom, kitchen, terrace, lawn
and other open places. The stored water
should be kept covered.
 Larval control by use of larvicides e.g paris
green, Mineral oils, chlorpyriphos.
 Mesocyclops, the shellfish are credited to eat
and effectively eliminate larvae of Aedes
aegypti.

48.  Anti adult measures like residual spray (e.g
DDT), space spray (e.g pyrethum).
 Protection against the mosquito bite by using
mosquito nets, screening the building and
use of repellents.

51.  Nine studies involving 34 248 participants were
included. The overall efficacy of CYD-TDV was 60%
(RR 0.40 (0.30 to 0.54)). Serotype-specific efficacy of
the vaccine was 51% for dengue virus type-1 (DENV-
1) (RR 0.49 (0.39 to 0.63)); 34% for DENV-2 (RR 0.66
(0.50 to 0.86)); 75% for DENV-3 (RR 0.25 (0.18 to
0.35)) and 77% for DENV-4 (RR 0.23 (0.15 to 0.34)).
Overall immunogenicity (MD) of CYD-TDV was
225.13 (190.34 to 259.93). Serotype-specific
immunogenicity was: DENV-1: 176.59 (123.36 to
229.83); DENV-2: 294.21 (181.98 to 406.45); DENV-3:
258.78 (146.72 to 370.84) and DENV-4: 189.35
(141.11 to 237.59). The most common adverse events
were headache and pain at the injection site.

52. TAKE HOME MESSAGES.
 Potiential outbreak in Nepal in rainy season.
 Secondary infection by another serotype can
result in severe Dengue.
 Patient dies of shock not of bleeding.
 Management is the FLUID, FLUID & FLUID.
 No role of prophylactic platelet rich plasma
(PRP)
 Always watch for the warning signs.
 Source control best method for disease
outbreak control.

53. REFERENCES
 HARRISONS PRINCIPLE OF INTERNAL
MEDICINE 20 EDITION
 DAVIDSON’S PRINCIPLE AND PRACTICE
OF MEDICINE 23 EDITION
 UPTODATE
 WHO DENGUE GUIDELINE 2009

54. THANK
YOU