NATIONAL GUIDELINES FOR CLINICAL MANAGEMENT Of DENGUE SYNDROME FOR BANGLADESH

1. Dr Shahjada Selim
Registrar (Medicine)
Shaheed Suhrawardy Medical College Hospital, Dhaka

2. Dengue
 The word dengue is derived from African
word denga: meaning fever with hemorrhage .
Is caused by virus transmitted of bites of
mosquito aedes.

3. Definition of Dengue Syndrome
Dengue Fever, a benign syndrome caused
by several arthropod–borne viruses, is
characterized by biphasic fever, Myalgia, or
Arthralgia, rash, Leukopenia and
lymphadenopathy.

4. History
Over the last two hundred years dengue
was known to the physician as a self
limiting benign febrile condition.
The first outbreak that resembles a
disease now recognized as dengue fever
was that described by Benjamn Rush in
Philadelphia, Pennsylvania in 1780.

5. History
Epidemics probably due to dengue were
common from the eighteenth to the
twentieth centuries among the inhabitants
of the Atlantic coast of the United States.

6. History
Dengue viruses almost certainly were the
cause of the 5 and 7 day fevers that
occurred among European Colonists in
Tropical Asia.
In 1905 Aedes Aeggpti was identified as a
dengue vector by Bancroft Ashburn and C
raig.

7. History
In 1956 Philippine hemorrhage fever was associated
with dengue when types 3 and 4 were recovered.
It now has become endemic through out tropical Asia
since 1967 the term dengue hemorrhagic fever and
DSS have come in to general use.

8. The Dengue Virus
Flavivirus
Positive sense
Single stranded RNA virus
40 to 50 nanometers
Four sero-sub types
Type 1 to 4
Arthropod borne

9. ETIOLOGY of VIRUS
Dengue virion are spherical particles approximately
50 nm in diameter.
 contains a single plus strand of RNA. Surrounded by
a lipid bilayer.
Mature virions are composed of 6% RNA, 9%
carbohydrate, and 17% lipid.
Because of the lipid envelope, flavviviruses are readily
inactivated by organic solvents and detergents.

10. ETIOLOGY
VIRUS

11. ETIOLOGY
VIRUS
Three viral proteins are associated with virions.
The E (envelop), M (membrane) and C (capsid)
proteins.

12. VIRUS
The E protein is the major surface protein of the viral
particle probably interacts with viral receptors, and
mediates virus-cell membrane fusion.
Antibodies that neutralize virus infectivity usually
recognize this protein and mutations in E can affect
virulence.

13. VIRUS
M protein is a small proteolytic fragment which is
important for maturation of the virus into an
infectious form.
C protein is a component nucleocapsid.

14. Etiology
Types
Four distinct antigenically related serotypes ( 1to 4) of
dengue virus of the family flaviviridae are
etiologically responsible.
Infection in human by one serotypes produces life
long immunity against re-infection by the same
serotype.
subsequent infection with other serotypes may result
in a severe illness ie., DHF or DSS

15. Etiology
Dengue like fever
Three other arthropod born viruses cause similar
febrile diseases with rash.
Chikungunya, Onyong-nyong and West Nile Fever

16. Etiology
Dengue like fever
Dengue like diseases may also occur in epidemics.
Epidemiological features depends on the vector and
their geographic distribution.

17. EPIDOMIOLOGY
Dengue outbreaks in urban areas infested with
A.aegypti may be explosive upto 70-80% of
population may be involved.
 During epidemic most disease occur in older
children and adults because A.aegypti has a
limited range spread, epidemic occurs mainly
through viremic human beings and follows the
main lines of transportation .
Where dengue is endemic children and
susceptible foreigners may be the only persons to
acquire overt disease adults having become
immune.

18. EPIDOMIOLOGY
Vector
Dengue viruses are transmitted by mosquitoes of the
stegomyia family.
 Acdes aegypti a day time biting mosquito is the
principal vector and all 4 types of virus have been
recovered from it.

19. Vector
Aedes mosquitoes (Tiger mosquito): distinguished by
white stripes on black body.
 Important members aedes family:A. aegypty,
A.vittatus and A. albopictus.
 They are most abundent during rainy season.

20. Vector
Lays egg singly, and eggs are cigar shaped.
Female mosquito acts as vector.
 They do not fly over long distance-
<100mts(110yards), this factor facilitates its
eradication.

21. Transmission
In most tropical areas A-aegypti is highly urbanized.
They breed in fresh water like water stored for
drinking or bathing and in rain water collected in any
container.
Dengue viruses have also been recovered from Aedes-
Albopictus.

22. Transmission
Outbreaks in the Pacific area have been attributed to
several other Aedes species.
These species breed in water trapped in vegetation.

23. The pathogenesis of severe disease is not well
understood
Various mechanisms of severe disease have been
suggested , including
1. Antibody –dependent enhancements
2.Complement activation by virus- antibody
complex
3. T-cell mediated immuno pathology
4.Cytokine abundance

24. Pathogenesis
In experimental studies of dengue virus infection in
rhesus monkeys, after subcutaneous inoculation,
virus was disseminated rapidly to regional lymph
nodes and then to lymphatic tissue through out the
body.

25. Pathogenesis
Early in the viremic period virus could be recovered
only from lymphonodes.
2-3 days later there will be evidence of dissemination
of skin and other tissues
Virus was recovred from skin, lymphonodes and
several leukocyte –rich tissues for up to 3 days after
termination of Viremia.

26. Pathogenesis
The number of sites of virus recovery greater as the
infection progresses. Intra cellular infection is
terminated abruptly 2-3 days after viremia ceases.
Animals infected with dengue virus type, 1,3 & 4 and
then infected with dengue virus type 2 circulated
virus at higher titer than when the strain was
inoculated on to susceptible animals.

27. Pathogenesis
Epidemiological , Clinical and virologic studies of
DHF / DSS in humans have shown a significant
association between severe illness and infection in
presence of circulating dengue antibody.
If tissue culture or suckling mice are used for virus
recovery, dengue virus almost invariably is absent in
tissues at the time of death. Tissue suspension
contain large qualities of dengue neutralizing
substances.

28. Pathogenesis
DHF / DSS occurred in children who were circulating
enhancing antibodies from a previous single dengue
virus infection. But did not occur in children whose
first infection left them with low levels of cross
reactive Dengue virus type-2 neutralizing antibodies
at the time of second dengue virus infections.

29. Pathogenesis
In vitro studies of dengue virus type-2 demonstrated
enhanced growth in cultures of human mononuclear
phagocytes that were supplemented with very small
qualities of dengue antibodies.
It has been proposed that the number of infected
mono nuclear phagocytes in individuals with
naturally or passively acquired antibody may exceed
that in non immune individuals.

30. Pathogenesis
Increase production of infected cells may contribute
to shock, possibly through the release of cytokines,
themselves the products of the immune elimination
of virus infected, mononuclear phagocytes through
cell mediated mechanisms.

31. Pathogenesis
It is thought that the reduced risk to DHF / DSS of
protein – calorie malnourished children is consistent
with hypothesis that a competent immune
elimination system generates the cytokines that
produce DHF / DSS.

32. Pathogenesis
Early in the acute stage of secondary dengue virus
infection, there is rapid activation of the complement
system.
During shock :
Blood levels of C1q, C3, C4, C5, C6, C7, C8 and C3
proactivator are depressed.
C3 catabolic rates elevated.
The blood clotting and fibrinolytic system are
activated.

33. Pathogenesis
Recent studies suggest a role for tumor
necrosis factor and interferon gamma.
As yet neither the mediator of vascular
permiability nor complete mechanism of bleeding has
been identified.

34. Pathogenesis
Capillary damage allows fluid electrolytes, protein,
and in some instances red blood cell to leak in to intra
vascular spaces. This internal redistribution of fluid
together with deficit due to fasting, thirsting and
vomiting results in hemo concentration, hypovolemia,
increased cardiac work, tissue hypoxia, metabolic
acidosis and hyponatremia.

35. Pathogenesis
A mild degree of DIC plus liver damage and
thrombocytopenia Could contribute additively to
produce haemorrhage.

36. Pathology
Pathologic examination there usually are no gross or
microscopic lesions found that might account for death.
 In rare instances death may be due to gastro intestinal or
intra cranial hemorrhages.
 Haemorrhages are seen in: Upper GI tract intra
ventricular septum of heart, on the pericardium. And on the
subserosal surfaces of major viscera.


37. Pathology
Focal hemorrhages occasionally seen in the lungs,
liver, adrenals, sub arachniod space.
The liver is usually is enlarged often with fatty
changes.
 Yellow watery at times blood tinged effusions are
present in serous cavities in about ¾ of patient and
retro peritoneal tissues are markedly edematous.

38. Pathology
Microscopy
Perivascular edema in the soft tissues and wide
spread of diapedesis of RBC.
There may be maturational arrest of megakaryocytes
in the bone marrow and increased numbers of them
are seen in capillaries of lungs, in renal grlomeruli and
in sinusoids of the liver and spleen.

39. Pathology
Microscopy
Proliferation of lymphoid and plasma cytoid cells,
lymphocytolysis and lymphophagocytosis occurs in
the spleen and lymphonodes.
In the spleen malpighian corpuscle germinal centres
are necrotic there is a depletion of lymphocytes in
the thymus.

40. Pathology
Microscopy
 Liver: there are varying degrees of
Falty metamorphosis,
Focal midzonal necrosis
Hyperplasia of the Kupffer Cells.
Non nucleated cells with vacuolated
acidophilic cytoplasm resembling councilmanbodies
are seen in the sinusoids.

41. Pathology
Microscopy
Kidney:There is a mild proliferative glamerulo
nephritis .
Skin: Biopsies of the rash reveal swelling and minimal
necrosis of endothelial cells. Subcutaneous deposits of
fibrinogen and in a few cases dengue antigen in extra
vascular mononuclear cells and on blood vessel walls.

42. Dengue
Classification
 Dengue fever
Dengue haemorrhagic fever
Dengue shock syndrome
Expanded dengue syndrome

44. Classification
Dengue fever
 Dengue fever is an acute febrile viral illness
presenting with Headache, bone (break bone fever),
or joint (chikungunya or o-nyony-nyong) and
muscular pains, rash and leucopenia caused by
arthropod borne viruses.

45. Age & sex distribution
1
7
9
3
2
4
8
4
0
2
4
6
8
10
<1 yr 1-5 yrs 5-10 yrs >10 yrs
Male
Female

46. Population distribution
11
6
22
0
5
10
15
20
25
Rural
Urban
slum
Urban

47. Manifestations
16
9
20
0
10
20
30
Dengue fever
DHF
DSS

48. Fever
14
15
7 7
0
5
10
15
20
<5 days
5-10 days
>10 days
Biphasic

49. Symptoms - Typical
11
12
10.5
11
11.5
12
12.5
Flushing
Rashes

50. Natural course of illness
2.1. Undifferentiated fever
Those who have been infected with dengue
virus,especially for the first time (i.e. primary dengue
infection), may develop a simple fever
indistinguishable from other viral infections.
2.2. Dengue fever (DF)
It is generally an acute febrile illness, with severe
headache, myalgia,

51. arthralgia and rashes. Leucopenia and
thrombocytopenia may also be
observed. Although DF may be benign, it could be
an incapacitating
disease with severe headache, muscle and joint and
bone pains (breakbone
Fever). Occasionally unusual haemorrhage such as
gastrointestinal
bleeding, hypermenorrhea and massive epistaxis
may occur.

52. Dengue haemorrhagic fever (DHF)
DHF is characterized by the acute onset of high
fever and is associated
with signs and symptoms similar to DF in the early
febrile phase. Plasma
leakage is the hallmark of DHF which occurs soon
after the end of the
febrile phase. There is a tendency to develop
hypovolemic shock (dengue
shock syndrome) due to plasma leakage.

53. High-risk patients
Infant and the elderly
Obesity
 pregnant women
PUD
 Women who have menstruation or abnormal vaginal
bleeding
Hemolytic disease
Congenital heart disease
Chronic disease such as DM, HTN,CRF,IHD,
Asthama, Liver cirrhosis
Patient on steroid or NSAID treatment

54. Warning signs
No clinical improvement or worsening of the
situation just before or during the transition to
afebrile phase or the disease progresses .
Persistent vomiting .
Severe abdominal pain .
Lethargy and / or restlessness ,sudden behavioral
change .
Bleeding : Epistaxis, black stool, haematemesis,
excessive menstrual bleeding , dark coloured urine
(haemoglobinuria)or haematuria.

55. Giddiness
Pale, cold and clammy hands and feet .
Less /no urine output for 4-6 hours .
Liver enlargement >2cm.
Haematocrit>20%.

57. Tourniquet Test
Inflate blood pressure cuff to a point
midway between systolic and diastolic
pressure for 5 minutes
Positive test: 20 or more petechiae
per 1 inch² (6.25 cm²)

58. Tourniquet Test

60. Atypical manifestation
Neurolgical:
•Febrile seizures in young children
•Encephalopathy
•Encephalitis/aseptic meningitis
•Subdural effusions
•Mononeuropathies/polyneuropathies/guilane-barre syndrome
•Transverse myelities

61. Gastrointestinal/hepatic:
Hepatitis/fulminant hepatic failure
Acalculous cholecystitis
Acute pancreatitis
Hyperplasia of peyer’s patches
Acuteparotitis

62. Renal:
Acute renal failure
Hemolytic uremic syndrome
Cardiac:
Conduction abnormalities
myocarditis
pericarditis

63. Respiratory
Acute respiratory syndrome
Pulmonary haemorrhage
Musculoskeletal
Myositis with raised creative phosphokinase
Rhabdomyolysis

64. Lymphoreticular/ bonemarrow :
Infection associated haemophagocytic syndrome
ITP
Spontaneous splenic rupture
Lymph node infarction

65. Eye
Macular haemorrhage
Impaired visual acuity
Optic neuritis
Others
Post-infectious fatigue syndrome,
depression, hallucinations, psychosis,
alopecia

66. Expanded dengue syndrome / Isolated
organopathy ( unusual manifestation )
patients with dengue illness can sometimes develop
unusual manifestations such as involvement of liver
,kidneys ,brain or heart with or without evidence of
fluid leakage and therefore do not necessarily fall into
the category of DHF. These conditions are very rare
and management is symptomatic . Such unusual
manifestations may be associated with coinfections
and comorbidities. However , these manifestations if
seen in DHF patients are mostly a result of prolonged
shock leading to organ failure .

68. Lab investigations for diagnosis
management
Dengue virus infection creates a broad spectrum of
symptoms , several of which are non – specific .
Thus ,a clinical diagnosis based on only symptoms is
untrustworthy .Early laboratory confirmation of
clinical diagnosis may be important because some
patients progress within a short period from mild to
severe disease and sometimes to death . Early
intervention may be life –saving. The management of
DS is based on clinical judgment rather than
laboratory evaluations alone . However , few indirect
tests may be suggestive of DS from the outset . The
following tests may be done .

69. Lab tests for diagnosis and
monitoring :
CBC: including Total Leucocyte Count, Total Platelet
Count and Hct should be done on first consultation
of the patient to have the baseline :
Recommendations:
 All febrile patients at the first visit .
 All patients with warning signs .
 All patients with fever >3 days .
Leucopenia is common in both adults and children
with DF and has an important diagnostic implication
in early period . The change in total white cell count
(<_5ooo cells /mm3) and ratio of neutrophils to
lymphocyte (neutrophils< lymphocytes ) is useful to

70. predict the critical period of plasma leakage . This
finding precedes thrombocytopenia or rising
haematocrit. This changes seen in DF and DHF
both .
Thrombocytopenia is observed in some patients
with DF Mild thrombocytopenia (100,000-150,000
cells /mm3)is common and about half of all DF
patients have platelet count below 100,000 cells
/mm3; A sudden drop In platelet count to below
100,000 occurs before the onset of shock or
subsidence of fever . The level of platelet count is
correlated with severity of DHF. Severe
thrombocytopenia (<100,000/mm3) usually
precedes / accompanies overt plasma leakage .

71. Hct : A slight increase may be due to high fever ,
anorexia and vomiting (10%). A sudden rise in
haematocrit is observed simultaneously or shortly
after the drop in platelet
count.Haemoconcentration or rising haematocrit
by 20% from the baseline , e.g. from haematocrit of
35% to >_42% is objective evidence of leakage of
plasma .1 of haematocrit may be affected by early
volume replacement and by bleeding .
 Serum AST(SGOT) and ALT(SGPT):
AST and ALT levels are frequently elevated in both
adults and children with DF and DHF; -- Levels are
significantly higher (5-15 times the upper limit of
normal )in patients with DHF.

72. Other findings are hypoproteinemia/
albuminaemia (as a consequence of plasma leakage
), hyponatremia, Albuminuria.
Occult blood is often found in the stool .
In DSS cases , assays of coagulation and
fibrinolytic factors show reduction . Partial
thromboplastin time and prothrombin time are
prolonged in about half and one third of DHF cases
respectively . Thrombin time is also prolonged in
severe cas.

73. Dengue Diagnostic Test
Detection of antigen: NS1 antigen (non-
structural protein 1):
NS1 antigen rapid test –positive within minutes of
starting symptoms .
The ELISA NS1 antigen will be positive on first day of
illness .
This test becomes negative from day 4-5 of illness .
Commercial kits for the detection of NS1 antigen are
now available in ELISA or rapid test format .

74. Detection of Antibody(Anti dengue
antibody test )
Dengue lgM/lgG test (MAC ELISA or Rapid ICT)
 Anti –dengue lgM specific antibodies can be detected
3-5 days after the onset of fever .
 lgM is detected and which increase to 95-98%, by day
6-10.
 It can be detected in low level up to 1-3 months after
fever .
 In primary dengue infection –IgM will be more than
lg G early period and increased lg G at 9 or 10th
day of
fever . Level of this lgG may persist at low levels for
decades , indicating past dengue infection .

75. Detection of antibody(cont..)
In secondary dengue infection – higher elevation of
anti- dengue specific lgG antibodies and lower levels
of lgM. The higher lgG levels remain for 30-40 days .
Rapid ICT test provides result within 15-20 minutes .

76. Dengue virus isolation
Dengue virus isolation from serum ,plasma and leukocytes
is the most definitive test for dengue infection ,which can
be accomplished in majority of cases if the sample is taken
in the few days of illness .
Isolation of dengue virus from serum ,CSF or autopsy
sample
Detection of dengue virus or antigen in tissue ,serum or
cerebrospinal fluid by immunohistochemistry
,immunofluorescence or enzyme –linked immunosorbent
assay.
Detection of dengue virus genomic sequence by reverse
transcription –polymerase chain reaction.

77. Nucleic Acid Detection
The reverse transcriptase ploymerase chain reaction
(RT-PCR)-confirm diagnosis (<5 days of illness ).
The amplified DNA viral RNAs can be detected by
tradition or real time PCR.
The test is expensive and available only in referral
centers.

78. Case definitions
Purpose
Case definitions are developed as aid tools for Early
Diagnosis and Promote Treatment ,Epidemiological
surveillance and Reporting .But this should not
supersede the good clinical judgment in
individualized situation .The purpose is as follows :
1. For uniformity in clinical case management at both
outpatient and inpatient setups .
2. For uniform reporting of the cases to designed
appropriate health authority .

79. Dengue fever
Suspected Dengue
Actual febrile illness with two or more of following :
Headache
Retro-orbital pain
Myalgia
Rash
Haemorrhagic manifestations
Leucopenia (wbc<_5000 cells mm3)
Thrombocytopenia(platelet count<150000 cells/mm3)
Rising haematocrit(5-10%)
And
High index of suspicion based on period ,population &
place .
And
Absence of convincing evidence of any other febrile illness .

80. Probable dengue
Suspected dengue and at least one of following :
Supportive serology on single serum sample : titre
>_1280 with haemagglutination inhabition test
,comparable IgG titre with enzyme –linked
immunosorbent assay, or testing positive in IgM
antibody test .

81. Confirmed dengue
Probable dengue and at least one of the following :
Isolation of dengue virus from serum ,CSF or
autopsy samples .
Fourfold or greater increase in serum lgG (by
haemagglutination inhalation test ) or increase in
lgM antibody specific to dengue virus .
Detection of dengue virus or antigen in tissue
,serum or cerebrospinal fluid by
immunohistochemistry ,immunofluorescence or
enzyme –linked immunosorbent assay.
Detection of dengue virus genomic sequence by
reverse transcription –polymerase chain reaction .

82. Therefore suspected DF and DHF patients should
be closely monitored to identify patients with
DHF.For efficient management of DHF it is
important to understand its natural history and its
dynamic nature. Clinical course of DHF is
stereotypic and consists of three stages
Febrile phase
Critical phase (leakage phase)
Convalescent phase

83. Febrile phase
Febrile phase is characterized by continuing high fever lasting for
2-7
days. Other features seen in the febrile phase include facial
flushing/diffuse blanching erythema of the skin, myalgia,
arthralgia,
headache, nausea and vomiting. Some patients may have sore
throat,
injected pharynx, conjunctival injection and diarrhoea. Mild
haemorrhagic
manifestations can occur. Leucopenia (WBC<5000 mm3) and mild
thrombocytopenia (<150,000 /mm3) are common in the late
febrile phase.
Above features are usually indistinguishable between DF and DHF
during
the febrile phase. However, the presence of tender hepatomegaly
favours
the diagnosis of DHF.

84. Critical phase (leakage phase)
The critical phase is heralded by the onset of
plasma leakage. This
usually occurs towards the late febrile phase, often
after the 3rd day of
fever, usually around the 5th or 6th day of illness
with defervescence
(settling of fever). However some patients may
enter the critical phase
while having high fever.

85. Plasma leakage is due to increased capillary permeability.
Plasma leakage
in DHF is selective and transient and usually lasts f o
r 24-48 hours.
Increased capillary permeability is the result of immune
mediators and is
not a result of destruction of capillaries. Though the
disease is systemic,
plasma leakage occurs selectively into the peritoneal and
pleural spaces.
Pericardial effusion, if there is any, is rather minimal.
Generalized or facial
oedema, if seen, is more likely to be due to fluid overload
rather than due to
plasma leakage.

86. With the leakage of plasma there will be haemo-
concentration which will
manifest as an increase in HCT. A 20% rise of HCT from
the baseline is
indicative of significant plasma leakage. (A smaller rise in
HCT which may
be seen in the early phase of the disease is usually due to
dehydration). A
rise in HCT less than 20% can be found in patients who
received excess
oral/I.V. fluids or in patients with bleeding.
Other evidence of plasma leakage are a decrease in serum
albumin
(<3.5g/dl) and non-fasting serum cholesterol (<100
mg/dl).

87. Convalescent phase (recovery phase)
This starts after the end of the critical phase and usually lasts 2-5 days.
There will be reabsorption of extravasated fluid during this period.
Features which would suggest that the patient has reached the
convalescent phase are:
 Improved general wellbeing and improved appetite
 Appearance of convalescent rash
 Generalized itching (more intense in palms and soles)
 Haemodynamic stability
 Bradycardia (seen in some patients)
 Diuresis
 Stabilization of Haematocrit (HCT) may even be lower than baseline
due to reabsorption of extravasated fluid)
 Rise in white cell count followed by a rise in the platelet count

88. Dengue haemorrhagic fever

89. Suspected DHF

90. Probable DHF
Suspected DHF and at least one of following :
Supportive serology on single serum sample : titre
>_1280 with haemagglutination inhabition test
,comparable IgG titre with enzyme –linked
immunosorbent assay, or testing positive in IgM
antibody test .

91. Confirmed DHF
Probable case with at least one of the following :
Isolation of dengue virus from serum ,CSF or
autopsy samples .
Fourfold or greater increase in serum lgG (by
haemagglutination inhalation test ) or increase in
lgM antibody specific to dengue virus .
Detection of dengue virus or antigen in tissue
,serum or cerebrospinal fluid by
immunohistochemistry ,immunofluorescence or
enzyme –linked immunosorbent assay.
Detection of dengue virus genomic sequence by
reverse transcription –polymerase chain reaction .

92. DHF
Approximately 20-30% of cases of dengue H.F. are
complicated by shock (DSS)
Fewer than 10% of patients have gross echymosis or
gastro intestinal bleeding usually after a period of
corrected shock.

93. DHF
After a 24 to 36 hrs period of crisis, convalescence is
fairly rapid in children who recover.
The temperature may return to normal before or
during the stage of shock.
Bradycardia and ventricular extrasystoles are
common during convalescence.

94. Dengue shock syndrome
Dengue shock syndrome is a presentation of Dengue
syndromes when a case of DHF manifests circulatory
failure with one or more of the following features :
Criteria for dengue haemorrhagic fever as above with
signs of shock including :
o Tachycardia ,cool extremities ,delayed capillary
refill ,weak pulse ,lethargy or restlessness ,which may
be a sign of reduced brain perfusion .
o Pulse pressure _< 20mmHg with increased diastolic
pressure ,e.g. 100/80mmHg.
o Hypotension by age ,defined as systolic pressure .

95. Severity grading of dengue
syndrome
DF /DHF Grad
e
Symptoms Laboratory
DF Fever with two or more of the
following signs; headache, retro-
orbital pain, Myalgia, arthralgia.
Luecopenia occasionally
Thromocytopenia may
be present, no evidence
of plasma leakage.
DHF I Above signs plus positive tourniquet
test.
Thrombocytopenia
<100,000 HCt
rise>20%
DHF II Above signs plus spontaneous
bleeding
Thrombocytopenia
<100,000, HCt
rise>20%.
DHF III Above signs plus circulatory failure
(rapid weak pulse, pressure, cold
clammy skin, restlessness and capillary
refill time >3sec)
Thrombocytopenia
<100,000, Het rise
>20%
DHF IV Profound shock with undectable blood
pressure and pulse
Thrombocytopenia
<100,000, rise >20%.


96. Diagnosis
D.F
Clinical diagnosis (High suspicion)
Knowledge of the geographic distribution.
Environmental cycles of causal viruses.
The term dengue like disease should be used until a
specific diagnosis is established.

97. Diagnosis
D.H.F
WHO Criteria For DHF :
Fever, Minor or Major Hemorrhagic manifestations.
Thrombocytopenia ( < 100000 / mn3)
Objective evidence of increased capillary permeability
(hematocrit increased > 20%) X-ray pleural effusion
Hypoalbuminemia.
DSS : Above mentioned criteria plus hypo tension and
narrow pulse pressure ( < 20 mm of Hg)

98. Diagnosis
D.H.F
Virologic diagnosis can be established by serologic tests
or by isolation of the virus from blood leukocytes or
serum.
Both in primary and second dengue infections, there is
relatively transient appearance of anti dengue
immunoglobulin IgM antibodies. These antibodies
disappear after 6-12 weeks which can be used to time a
dengue infection.

99. Diagnosis
D.H.F
In secondary infection most antibody is of the IgG
class.
Serological diagnosis depends on a four fold or
greater increase in IgG antibody titer in paired
sera
By:
Hemaglutination inhibition.
Complement fixation
Enzyme immunoassay
Neutralization tests

100. Diagnosis
D.H.F
Carefully standardized immunoglobulin IgM, and IgG
capture enzyme immuno assays are now to identify the
acute phase antibodies from patients with primary or
secondary dengue infections in single serum samples.
(IgG antibody concentrations are abundant in secondary
but minimum in primary) usually such samples should
be collected not earlier than 5 days nor later than 6
weeks after onset.

102. D/D
D.F
The DDS of DF includes viral respiratory and
influenza like diseases. Early stages of Malaria , mild
yellow fever, scrub typhus, viral hepatitis and
leptospirosis.
Four arboviral diseases have dengue like courses but
without rash – Colorado Tick fever, sand fly fever, Rift
valley fever and Ross river

103. D/D
D.H.F
Meningo Cocccemia , Yellow Fever other viral
hemorrhagic fevers, many in rickettsial diseases and
other severe illneses caused by a variety of agents may
produce clinical picture similar to DHF.

104. Management of those who do
not need Admission
Following treatment measures are recommended:
 Ensure adequate oral fluid intake of around 2500 ml for
24 hours
(if the body weight is less than 50kg give fluids as 50ml/kg
for 24
hours). This should consist of oral rehydration fluid, coconut
water, other fruit juices, kanji or soup rather than plain
water.
Exclude red and brown drinks which could cause confusion
with
haematemesis or coffee ground vomitus.commercial
carbonated drinks that exceed the isotonic level should be

105.  Adequate physical rest
 Tepid sponging for fever
 Paracetamol not exceeding 2 tablets six hourly (reduce
dose for
patients with lower body weights). Warn the patient that
the fever
may not fully settle with paracetamol and advice not to
take
excess.
 A nti-emetics and H2 receptor blockers if necessary
 Avoid all NSAIDS and steroids
 Withhold Aspirin, Clopidogrel & Dipyridamole in
patients who take
these on long term basis

106. Advise immediate return for review if any of
the following occur:
 Clinical deterioration with settling of fever
 Inability to tolerate oral fluids
 Severe abdominal pain
 Cold and clammy extremities
 Lethargy or irritability/restlessness
 Bleeding tendency including inter-menstrual
bleeding or
menorrhagia
 Not passing urine for more than 6 hours

107. Management
Indications of hospitalizations
 Restlessness or lethargy frequent vomiting one or two days of
febrile illness.
 Cold extremities or circumoral cyanosis.
 Bleeding in any form.
 Rapid and weak pulse.
 Capillary refill time > 3 seconds.
 Narrowing of pulse pressure (<20 mm Hg) or Hypo tension.
 Hematocrit of 40 or rising hematocrit.
 Platelet count of < 1,00000/ mm3
 Acute abdominal pain
 Evidence of Plasma leakage. Eg. Pleural effusion /Ascities

108. Management
Dengue fever
 There is no specific anti viral treatment and
 The management is essentially supportive and
symptomatic (Bedrest)
 The key to success is frequent monitoring and
changing strategies depending on clinical and
laboratory evaluations.

109. Management
Dengue fever
 The management of dengue fever is symptomatic
and supportive.
 Bed rest is advisable during the acute febrile phase.
 Antipyretics or cold sponging should be used to
keep the body temperature < 400C.
 Analgesics and mild sedation may be required to
control pain

110. Management
Dengue fever
 Fluids and electrolyte replacement therapy is
required when there are deficits due to sweating/
fasting / thirsting / vomiting or diarrhea.
 Because of the dengue hemorrhageic diathesis
aspirin should not be given to reduce fever or
control pain.

111. Management
DHF
Electrolyte and dextrose Solution ( as used in
diarrhea disease) or Fruit Juice or both are preferable
to plain water.
With high fever there is a risk of convulsion and
antipyretic drugs may be indicated.

112. Management
DHF
Acetaminophen is preferable at the following
doses younger than year of age 60mg / dose, 1-3
years 60-120mg/dose, 3-6 years – 120 mg/dose, 6-
12 years 240mg /dose children should be observed
closely for early signs of shock. The critical period
is the transition from febrile to afebrile phase.
A rise in hematocrit value indicates significant
plasma loss and a need for parenteral fluid
therapy.

113. Management
DHF
In grade I and II volume replacement can be given in
a period of 12-24 hours.
Patients with any signs of bleeding and persistently
high hematocrit values dispite being given volume
replacement should be admitted to hospital.

114. Management
DHF
The volume and type of fluid should be similar to that
used in the treatment of diarrhea with moderate
isotonic dehydration but the rate should be carefully
titrated. The required volume should be charted on a
2 – 3 hours basis and the rate of administration
adjusted throughout the 24 – 48 hours period of
leakage.

115. 6.5.3 When the patient is in the critical phase
(leakage phase)
The fluid requirement, both oral and intravenous,
in critical phase (48
hours) is calculated as M+5% (maintenance + 5%
deficit). Maintenance
(M) is calculated as follows:
 For the 1st 10 kg -100 ml/kg
 For the 2nd 10 kg - 50 ml/kg
 From 20 kg and above up to 50 kg - 20 ml/kg
 5% deficit is calculated as 50 ml/kg up to 50kg

116. Management
DHF
Serial haemetocrit determination every 4 – 6 hours
and frequent recording of vital signs are recorded for
adjusting the fluid replacement. In order to assume
adequate volume replacement and avoid over
transfusion.

117. DHF
Fluid Management

118. DHF
Fluid Management
Formula
ml / hr = (drop / min) x 3
The fluid replacement should be the minimum
volume i.e. sufficient to maintain effective
circulation during the period of leakage.
Excessive replacement will cause respiratory
distress (from massive pleural effusion and
ascites). Pulmonary congestion and edema

119. D H F
Fluid management
The type of fluid used are 1) Crystalloid and 2)
Colloidal
I. Crystalloid
1/3 to ½ of the total fluid as physiologic saline
solution (NS)
½ to 2/3 of the remainder as 5% glucose in water.
For acidosis ¼ of the total fluid should be 1/6
molar sodium bicarbonate.

120. D H F
Fluid management
 5% dextrose in ringer lactate solution
 5% dextrose in ringer acetate solution
 5% dextrose in half strength NS.
 5% dextrose in NS solution.

121. Fluid management
Colloids
 Dextran 40 and plasma
Management of Shock :
DSS is a medical emergency that requires prompt
and vigorous volume replacement therapy.
There are also electrolytes (sodium) and acid base
disturbances it must be consider that there is a
high potential for developing DIC. And stagnant
acidemia. Blood will promote and or enhance
DIC which may lead to sever hemorrhage and or
irreversible shock.

122. The replacement of plasma loss
 Immediate replacement of plasma loss with isotonic
salt solution (5% dextrose in ringer acetate solution or
5% dextrose in NS) at the rate of 10-20ml / kg body
weight are in case of profound shock (grade-4) as a
bolus of 10ml/kg body weight (1-2 times) should take
place.

123. ABCS
If the patient is not responding to two boluses of
crystalloid, contributory
causes for shock other than plasma leakage should
be considered. These
are,
Acidosis check venous blood gas (if present,
check liver and renal profiles)
Bleeding check HCT
Calcium and other electrolytes (sodium and
potassium) - check serum
Sugar check random capillary blood sugar

124. It is important to correct these conditions as quickly as possible. If
the
patient is clinically acidotic one dose of 50 ml of 8.4% sodium
bicarbonate
may be given empirically if blood gas cannot be assessed.
Empirical treatment with 10% calcium gluconate 10 ml over 10
minutes is
justifiable if a patient is in shock and is not responding to
adequate fluid
replacement, this may be continued six hourly. IV calcium
gluconate may
be used in patients who show evidence of myocardial involvement
as well,
as hypocalcaemia is common in DHF patients and calcium may
improve
the myocardial contractility in such patients

125. If the blood g l u c o s e l e v e l i s less than 7 0
mg/dl correct it by giving
15 – 20g glucose orally or intravenously. At the time
of shock, use
30–40 ml of 50% Dextrose (15-20g) intravenously.
Re-check capillary
blood sugar in 15 minutes and if it is less than 7 0
mg/dl repeat 30-
40ml of 50% Dextrose intravenously.

126. The replacement of plasma loss
In case of continued or propound shock (with high
haematocrit values) colloidal fluid (dextran or
medium molecular weight in NSS or plasma) should
be given the following initial fluid at a rate of 10-
20ml/kg body weight / hour.
Blood transfusion is indicated in cases with profound
and persistent shock dispite declining hematocrit
values after initial fluid replacement

127. The replacement of plasma loss
When improvement is apparent the rate of I/V fluid
replacement should be reduced and adjusted 1-2
hourly throughout the 24 hours period.
Colloidal fluid is indicated in cases with massive
leakage and to whom a large volume of crystalloid
fluid as been given.

128. The replacement of plasma loss
In small children 5% dextrose in a half strength
normal saline solution (5% dextrose / ½ NSS ) initial
resuscitation and 5% dextrose in ½ NSS may be used
in infants under 1 year age. If the serum sodium is
normal.

129. D H F
Discontinuation of IV fluids
WHEN:
The hematocrit reading drops to around 40%
Vital signs are stable.
A good urine out flow indicates sufficient circulate
renal volume.
A return of appetite and diuresis are signs of recovery

130. D H F
Discontinuation of IV fluids
It is extremely important to emphasize that a drop in
heamatocrit reading at this stage should not be
interpreted as a sign of internal hemorrhage.
Strong pulse, BP with wide pulse pressure and
diuresis are good vital signs during this re-absorption
phase.

131. D H F
Management (contd)
 Sedations are needed in some cases because of
marked agitation.
 Hepatotoxic drugs should be avoided.
 Chloral hydrate orally or rectally recommended in a
dose of 30 – 50 mg/kg as a single hypotonic dose
(maximum dose 1gram).

132. D H F
Management (contd)
 In cases without pulmonary complications
paraldehyde 0.1ml/kg I.M. (maximum dose 10ml)
also be use.
 Oxygen therapy should be given to all patients in
shock. The oxygen mask or tent may increase
apprehension.

133. Management of fluid overload
Review the total intravenous fluid therapy and
clinical course and check and correct for abcs.
All hypotonic solution should be stopped .
Switch from crystalloid to colloid solutions as bolus
fluid .
Dextran 40 is effective as 10 ml/kg bolus infusion , but
the dose is restricted to 30ml/kg/day because of its
renal effects .

134. Management
Blood transfusion
Transfusion with fresh whole blood is preferable and
the amount to given should be such that normal RBC
concentration is not exceeded.
Fresh Frozen Plasma (FFP) may be indicated in cases
where consumptive coagulopathy causes massive
bleeding. DIC is usual in sever shock and may play an
important part in the development of massive
bleeding or lethal shock.

135. Management
Platelet transfusion
Platelet transfusion in cases of DHF / DSS is also
surrounded with controversies. Mild reductions in
platelet counts are usually not associated with
significant bleeding.
Secondly thrombocytopenia in DHF / DSS is a short
lived phenomenon with platelets returning to normal
by 7 to 9 days.

136. Management
Platelet transfusion
Platelet transfusions are recommended only for
children with platelet count of 50,000 / mm3 and
having significant bleeding manifestations.
Prophylactic platelet concentrate is indicated when
platelet count is less than 10000-20000 / mm3 (10 to
20ml / kg of platelet).

137. Polyserosities
Need the insertion of intercostal tube or ascitic drainage
respectively.
Caution must be taken before drainage as the chances of
sever hemorrhages are high.
Patients should be haematologically stabilized first with use
of fresh whole blood, FFP or platelet concentrates and
drainage of these fluids should be done slowly to prevent
sudden circulatory collapse.

138. Polyserosities
Large pleural effusions during the recovery phase
after 48 hours may need small doses of frusemide
(0.25 to 0.5 mg / kg B/w 6th hourly) with these
method it may possible to avoid insertion of
intercostal drains.
Generally steroids do not shorten the duration of
disease or improve the prognosis in children
receiving careful supportive therapy.

139. Management of Hepatic
Encephalopathy in DHF
 Maintain adequate airway and oxygenation
 Infuse minimal intravenous fluids sufficient to maintain
intravascular volume (80% of maintenance)
 Use hyper-oncotic colloid solution early if HCT is increased
 Infuse Mannitol to reduce intracranial pressure if renal
functions are normal
 Take measures to maintain serum sodium in-between 145-155
meq/L. (3% hypertonic saline may be of use if Mannitol cannot
be used, and if serum sodium is very low)

140. Maintain blood sugar above 60 mg/dl
 Give a single dose of Vitamin K 10 mg IV
 Give Lactulose to maintain 3-4 bowel motions per day. However,
lactulose commonly causes gaseous abdominal distension and this
may interfere with respiration in these patients and may even
cause aspiration
 Treat with broad spectrum antibiotics, which are not excreted
through liver, if secondary bacterial infection is suspected
(Cefotaxime is preferred)
 Oral Metronidazole may be used (supportive evidence is
limited)
 Ventilate (IPPV) early, if the features of encephalopathy are
getting worse

141. Fresh Frozen Plasma (FFP) should not be used
routinely, but may be
used if there is active bleeding or prior to invasive
procedures.
(However, be aware of possible fluid overload with
FFP)
Bowel washes and enemas should be avoided
There is no evidence to support the use of L-
Arginine L-Ornithine (LOLA)
or N-Acetyl Cysteine (NAC) in these patients and
therefore, use of which is
not recommended

142. Dengue in Co-morbid
Conditions
Liver Disease:
Baseline liver function tests (LFT) including prothrombin time
(PT) is of
value when dengue is suspected in patients with chronic liver
disease. If
AST/ALT is very high the patient is likely to develop neurological
involvement (Hepatic Encephalopathy) especially in those with
gastrointestinal
(GI) bleeding. In such patients liver failure regime should be
used early . If baseline albumin level is low these patients
may have more plasma leakage.

143. Managing these patients with the
minimum amount of IV fluids to maintain intravascular
volume in order to
prevent respiratory distress (acute pulmonary oedema)
and/or heart
failure is crucial. Prolonged PT or INR (>1.3) indicates
that these patients
have a tendency for more bleeding and therefore Vitamin
K1 IV is
recommended. In addition, assessment of the degree of
bleeding and
transfusing adequate amount of blood and blood
components are
important considerations.

144. Heart Disease:
The key consideration in patients with heart diseases would be
to identify
the underlying heart disease and the current medication.
These patients
should be observed carefully with close and continuous
monitoring
preferably echocardiography especially during the critical
phase. Careful
adjustment of IV fluid is the key to success and to prevent
complications.
Those who are on anti-platelet or anti-coagulation therapy are
recommended to stop the medication for a few days especially
during the
critical phase.

145. Myocardial Involvement in Dengue
Global dysfunction of myocardial contractility may be seen
in DHF patients
who are in prolonged shock and the most likely reason is
metabolic
acidosis. However hypocalcaemia (which is a common
finding in DHF
patients with moderate to large pleural effusion / ascites)
should be
considered as well.
Hence, if there is evidence of cardiac dysfunction,
acidosis and
hypocalcaemia should be corrected quickly

146. Empirical treatment with calcium is justifiable if
clinically indicated.
Myocarditis is an uncommon finding in Dengue and
is very unlikely to
cause death in a patient with DHF. However, such a
patient could easily
develop pulmonary oedema with fluid overload.
Therefore, if myocardial Involvement is
suspected fluid should be
given very carefully
Treatment of myocardial Involvement is
symptomatic.

147. Diabetes Mellitus:
Frequent monitoring of blood sugar is important from
the time the patients
are admitted to hospital. All anti-diabetic drugs have to
be switched to
insulin in order to keep blood sugar level preferably
below 150-200mg/dl.
Closely monitor the patient and look for the possible
development of
Diabetic Ketoacidosis where patient will need more IV
fluid, IV insulin as
an infusion and monitoring of central venous pressure if
possible. Manage
the commonly associated conditions with DM, e.g.
hypertension

148. Renal Disease:
The baseline renal function tests (Blood Urea, Creatinine), electrolytes,
acid-base balance, GFR, urine output per day and urine analysis should
be performed during the early febrile phase and regularly tested during
the
course of the illness. Close monitoring of fluid intake and urine output
is
very important. Fluid overload during convalescent phase is the most
important cause of death among these patients. Early consultation
with a
Nephrologist and early planning of any renal replacement therapy in
those
patients who are oliguric with signs and symptoms of fluid overload is
important.

149. Management of Pregnant patients
with DF/DHF close to delivery
Risk of bleeding is at its highest during the period of
plasma leakage therefore ,
Unless to save mothers life, avoid Lower segment
caesarean section during the critical ( plasma
leakage ) phase.
Obstetric procedure should be avoided .
If obstetric procedure are to be undertaken ,
Maintain the platelet count above 50,000/mm3.
 Single donor platelet transfusion is preferred , if
available , if platelet transfusion is necessary .

150. If patient goes into spontaneous labor during
critical phase take steps to prevent vaginal tears by
performing an episiotomy.
Increase of fetal compromise priority should be
given to the mothers life .

151. Monitoring
Patients should be monitored constantly until there is
a reasonable certainly that the danger as passed in
practice.
Pulse, BP, RR & Temp. be taken every 15 to 30
minutes are more often until the shock resolves.

152. Monitoring
 Hematocrit or Hb studies should be performed
every two hours for the first six hours then every
four hours thereafter until the patient is stable.
 Accurate record of intake and output including the
type of fluid given should be made.

153. Management of Epidemic Dengue
Hemorrhagic Fever
 During epidemics, outpatient and inpatient facilities
may be overwhelmed.
 It is essential that only children requiring hospital
care be admitted.
A recently elevated body temperature and positive
tourniquet test are sufficient to suggest DHF

154. Management of Epidemic Dengue
Hemorrhagic Fever
When possible, a microhematocrit and platelet count
should be done in the outpatient department.
Patients with thrombocytopenia and elevated
hematocrit counts should be sent to a rehydration
ward or, if hematocrit does not fall or rises in the face
of fluid therapy, admitted to hospital.

155. Management of Epidemic Dengue
Hemorrhagic Fever
. If a patient lives a long distance from the hospital
and nearby accommodations are not available,
admission for observation may be necessary.

156. Regulatory Measures
Dengue diseases are not subject to international
surveillance regulations. An intensive and effective
voluntary reporting system has been devised by the
regional offices of the World Health Organization.

157. Prognosis
 Children who develop profound shock rapidly with
no detectable diastolic pressure or with
unobtainable blood pressure.
 Children in shock with delayed admission to
hospital.
 Children in shock with gastrointestinal hemorrhage
have a poor prognosis.
 Mortality rates may exceed 50 per cent in these
groups.

158. Discharge criteria

159. PREVENTION
 Tissue culture-based vaccines for dengue virus
types 1, 2, 3 and 4 are immunogenic but not
available for general use.
 Prophylaxis depends on use of insecticides,
repellents, body protective clothing, and screening
of houses to avoid the bite of the mosquito.
 Destruction of A. aegypti breeding sites also is
effective.

160. PREVENTION
 If water storage is mandatory, a light-fitting lid or a
thin layer of oil may prevent egg deposits or
hatching.
 A larvicide, such as Abate, available as a 1% sand
granule formulation and effective at a
concentration of 1 part per million, may be added
safely to drinking water.

161. EPIDEMIC MEASURES
World Health Organization recommendations are as
follow :
On the basis of epidemiologic and entomologic information,
the size of the area that requires adult mosquito abatement
should be determined.
With technical malathion or fenitrothion at 438 ml/ha, two
adulticidal treatments at a 10-day interval should be made
by use of a vehicle-mounted or portable ultra-low-volume
aerosol generator or mist blower.

162. EPIDEMIC MEASURES
Cities of moderate size should stockpile at least one
vehicle-mounted aerosol generator, five mist blowers,
10 swing fog machines, and 1000 liters of ultra-low-
volume insecticides to be prepared to carry out
adulticidal operations over a 20-km2 area rapidly.

163. EPIDEMIC MEASURES
 With limited funds, such equipment and
insecticides can be stockpiled centrally for rapid
transportation where required. Priority areas for
launching ground applications are those having a
concentration of cases.

164. EPIDEMIC MEASURES
 Special attention should be focused on areas where
people congregate during daylight hours, for example,
hospitals and schools. If necessary, ultra-low-volume
insecticides may be applied from aircraft. C47 or
similar aircraft, smaller agricultural spray planes, and
helicopters have been used to make aerial
applications.
 During the early stages of epidemics, ultra-low-
volume spray of 4 % malathion in diesel oil or
kerosene may be used to spray all houses within a
100-m radius of the residence of DHF patients.

165. Eradication and Control
A. aegypti was eradicated from countries and whole
continents with use of the techniques pioneered by
the Rockefeller Foundation.
With time, the species successfully reestablished
itself in much of its former range.

166. Eradication and Control
An eradication campaign in the United States was
abandoned and was replaced by a program of disease
surveillance and containment of introduced virus.

167. Eradication and Control
 Mosquito control or eradication programs require
the simultaneous use of two approaches:
Reduction in breeding sites
Application of larvicides
Alternatively, a significant reduction in population
may be effected by closely spaced application of
adulticides.

168. Reduction in breeding sites
Source reduction campaigns should be well
organized, supervised, and evaluated.
 Includes proper disposal of discarded cans, bottles,
tires, and other potential breeding sites not used for
storage of drinking or bathing water.
 Drinking and bathing water storage containers and
flower vases should be emptied completely once
weekly.

169. Reduction in breeding sites
Water containers that can not be emptied should be
treated with Abate 1% sand granules at dosage of 1
ppm (e.g., 10 g of sand to 100 L of water).
Treatments should be repeated at intervals of 2 to 3
months.

170. Application of larvicides
Vehicles-mounted or portable ultra-low-volume
aerosol generators or mist blowers can be used to
apply technical grade malathion or fenitrothion at 438
mL/ha.
Three applications made at 1-week intervals can
suppress. A aegypti populations for about 2 months.

171. Health Education
 A. aegypti control has been maintained effectively
in some tropical areas through the simple
expedient of emptying water containers once a
week.
 During the yellow fever campaigns, strong sanitary
laws made the breeding of mosquitoes on premises
a crime punishable by fine or jail

172. Health Education
 In the modern era, Singapore and Cuba have
adopted these measures successfully.
 Health education through mass media or through
the schools has been attempted in Burma,
Thailand, Malaysia, and Indonesia without
spectacular success.