PUBLIC ENEMY NO.

Dengue Haemorrhagic Fever

Dr. SOMESH MEHROTRA

Critical care Specialist

Siddhi Vinayak Hospital

Bareilly , UP, india
9837000048
To fight- you should know the enemy inside out
 Four lives of Dengue virus
• Family flaviviridae .
• has four serovars.den1-den2,den3and den4
• Infection with one serotype confers long term immunity to
that serotpt only
• Efficient vector susceptible to Dengue virus.
• Bites many human for a single meal in day time.
• Urban dweller
 Global problem
• Recognized in the Philippines in 1953.
Transmission of Dengue Viruses
• Viruses are transmitted from humans to
mosquitoes to humans
• Next generation of mosquitoes
• Human are the main amplifying hosts
• Monkeys can also be reservoirs
• The virus circulates in the blood approx.
at the time of fever
 OUT BREAK-PART I
(Two important epidemiological patterns)
DHF/DSS in where multiple dengue
serotypes are endemic.
Sporadic cases or small outbreaks in urban
areas that steadily.increase in size
Pattern of epidemic activity every 2-5 years.
 OUT BREAK PART - II
A second pattern
Low endemicity
Multiple Dengue serotypes
Relatively low rates of infections
 Pathology
……At autopsy Frequency of Hemorrhage
• Skin and subcutaneous tissue<Mucosa of the GIT< Heart <
Liver.<Subarachnoid or cerebral hemorrhage is rarely seen.
• Serous effusion with a high protein content is seen in pleural and
abdominal cavities but not in pericardial.
• Light microscopy of blood vessels shows no significant changes in
vascular walls.
• Lymphocyte tissue shows an increased activity of B-lymphocyte
system with Plasma cells and lymphoblastoid cells
 Liver
• There is focal necrosis of hepatic cells,
swelling.
 Kidney
• Immune-complex type of
glomerulonephritis which resolves
completely in 3 weeks
• Perivascular Oedema
• Sderum complement, immunoglobulin and
fibrinogen.
 Bone marrow
• Depression of all haematopoietic cells was
observed, which would rapidly improve as
fever subsided.
 Pathogenesis of DHF/DSS
• Vascular permeability. Disorder in haemostasis
(Haemoconcentration, ( Vascular changes,
low pulse pressure. Thrombocytopenia and
Sign of shock.) coagulopathy.)

• of the complement system of C3 and C5 levels.

• Platelet defects both qualitative and quantitative.

 Secondary Infections
• Enhancement of virus replication in
macrophages by heterotypic antibodies.
• Cross-reactive but not neutralizing
antibodies.
• Cross-reactive CD4+ and CD8 + cytotoxic
lymphocytes.
• Cross Reaction
 Classic Features
Breakbone fever, sudden onset ,severe headache, retro-
orbital pain, and fatigue, severe myalgia and arthralgia .
lasts five to seven days.
• Rash, typically macular or maculopapular and confluent
with the sparing of small islands of normal skin , near the
time of defervescence, lasts for two to four days, and may
have scaling and pruritus.
• Flushed facies ( the first 24 to 48 hours),
lymphadenopathy, injected conjunctivae, an inflamed
pharynx, and mild respiratory and gastrointestinal
symptoms.
 Case Definitions
• Probable Dengue Fever

• An acute febrile illness with two or more of the following :

• — headache
• — retro-orbital pain
• —myalgia
• —rash
• —heamorrhagic manifestations
• —leukopenia
and
• supportive serology : antibody titre >1280, a comparable IgG ELISA titre, or a positive
IgM antibody test
Or
• —occurrence at the same location and time as other confirmed cases of dengue
fever.
 Case Difination
Confirmed dengue fever
• Isolation of the dengue virus from serum or autopsy; or

• A fourfold or greater change in rciprocal IgG or IgM antibody titres

to one or more dengue virus antigens in paried serum samples; or

• Dengue virus antigen in autopsy tissue, serum or C.S.F. samples by

immunohistochemistry, immunofluorescence or ELISA; or

• Dengue virus genomic sequences in autopsy tissue serum or C.S.F.

samples by PCR.
 Case definition
Dengue haemorrhagic fever
All of the following must be present
• Fever, or history of acute fever, lasting 2-7 days occasionally biphasic.
• Haemorrhagic tendencies(at least one of--)
Tourniquest test
1. Petechiae, ecchymoses,purpura
2. Bleeding-mucosa,git,injection site
3. Haemetemesis, malena
• Thrombocytopenia (100000 cells per mm3 or less).
• Evidence of plasma leakage due to increased vascular permeability,
manifested by at least one of the following.
1. A rise in PCV equal to or greater then.
2. A drop in the haematocrit following volume-replacement treatment
equal to or greater than 20% of baseline;
3. Signs of plasma leakage such as pleural effusion, ascities and
hypoproteinaemia.
 Case Definition for Dengue
Shock Syndrome
All four points of DHF and ;
• Rapid and weak pulse.
• Narrow pulse pressure(< 20mm Hg
(2.7KPa))
or manifested by :
• Hypotension for age.
• Cold, clammy skin and restlessness.
Drugs for dengue
 Tourniquet test

Blood pressure cuff on the upper arm to a point between the

systolic and diastolic pressure for 5 minutes. Positive when
20 or more petechiae per 2.5cm. (1 inch) square are
observed.
 Grading severity of DHF
Grade I : Fever + non-specific cc + tourniquet test and/or easy
bruising.

Grade II : Spontaneous bleeding.

………………..DSS………………..

Grade III : Circulatory failure i.e. a rapid, week pulse and narrowing
of pulse pressure or hypotension, + cold, clammy skin and
restlessness.

Grade IV : Profound shock with undetectable blood pressure or pulse.

 Indications for hospitalization
for bolus intravenous fluid therapy may be
necessary where significant dehydration
(>10% of normal body weight) has
occurred and rapid volume expansion is
needed. Signs of significant dehydration
include :
• Tachychardia
• Ivreased capillary refill time (>2s)
• Cool, mottled or pale skin
• Diminished peripheral pulses
• Changes in metal status
• Oliguria
• Sudden rise in haematocrit or continuously elevated
haematocrit despite administration of fluids
• Narrowing of pulse pressure (<20mmHg (2.7KPa))
• Hypotension (a late finding representing uncorrected
shock).
 DHF-treatment
# ORS
• Hyperpyrexia
• Day of judgment;is the day of
defervescence
 DSS-treatment
rapid replacement of fluid
• RL ,ringer acetate, DNS, in< 20 minutes
,10-20ml/kg
• Another bolus to total 20-30ml/kg
….Still shock-
• PCV rising—plasma, plasma substitute or
albumin
• If PCV falling—fresh blood
 DSS- continued replacement
• Plasma loss may continue for 24-48 hrs
• CVP measurement
• Reabsorption of extravasated plasma=pcv
falls
• Blood transfusion
 Essential lab tests
Hb%, Haematocrit, GBP
• Serum electrolytes and blood gas studies
• Platelet count, prothrombin time, partial
thromboplastin time and thrombin time.
• LFT,SGPT,SGOT, and serum protrins.
• CXR
 Unusual manifestations of
dengue haemorrhagic fever
• Acute hepatic failure
• Maintainance of consciousness even in
presence of severe shock
Criteria for discharging inpatients
• Absence of fever for at least 24 hours.
• Return of appetite.
• Visible clinical improvement.
• Good urine out put.
• Stable haematocrit.
• Passing of at least 2 days after recovery from
shock.
• No respiratory distress from pleural effusion or
ascites.
• Platelet count of more then 1 lakh per mm3.
 Chikungunya; that which bends up
• Is the little sister clinically
• Joint pains are the major feature of both acute and
chronic phase
• Ankle & wrist
• Intense pain caused by the pressure on wrist is
diagnostic
• Lymphopenia, thrombocytopenia,hepatitis
• High viremia causes direct man to man
transmission
• World wide 2 million cases
Perils of Platelet transfusion

platelet concentrate
-has contaminating wbcs ,plasma-from centrifuging fresh
blood-Has 7x1010
Apherisis ;taken from a single donor
5x10 11

Storage;at rom temperature under agitation

Room temperatue causes bacterial growth
 Perils of platelet transfusion
• Compatibility; destroyed by HLA1 protein
on membranes –less commonly by ABO or
specific antibodis

• Indication for transfusion -prophylactic

role to forestall bleeding is controversial
• Threshold -by gados et all-remains at
20,000.per cc
 Refractoriness

. Perils of platelet transfusion

• Nu. & condition of pl.extract.
• Fever, spelnomeghaly,drugs,DIC,
• Alloimmunization-from wbc,rbcs in
pl.extract—irradation by ultraviolet B helps
• TRAP study-apherisis ???
#
 Future possibilities
• Thrombopoietin-
• #lyophilization
• #cold storage#
• infusible platelet membranes or other
platelet substitutes
 Drugs for Dengue

• Corticosteroids’
• Carbazochrome –decreases capilary
permeability
• Ribavirin,-also for lassa fever
• Interferon alpha
• 6-azauridine
• Last three drugs have some invitro antiviral
activity
 steroids
1: Southeast Asian J Trop Med Public Health. 1975 Dec;6(4):573-9. Links
Hydrocortisone in the management of dengue shock syndrome.
Min M, U T, Aye M, Shwe TN, Swe T.
A total of 98 patients with dengue shock syndrome admitted into Children's Hospital from February
1973 to February 1974 were randomly selected into 2 groups. A double blind controlled trial of the
efficacy of pharmacologic doses of hydrocortisone hemisucinate was carried out. The 2 groups were
confirmed to be completely matched by age, sex and severity of the disease. Nine deaths occurred
out of 48 cases in the steroid group (Case Fatality Rate 18.75%) and 22 deaths out of 50 cases in
the non-steroid group (Case Fatality Rate 44%), the difference being statistically significant. No
significant difference was detected in fluid requirements and other morbidity pattern.

1: Pediatrics. 1993 Jul;92(1):111-5. Links

Failure of high-dose methylprednisolone in established dengue shock
syndrome: a placebo-controlled, double-blind study.
Tassniyom S, Vasanawathana S, Chirawatkul A, Rojanasuphot S.
Department of Pediatrics, Faculty of Medicine
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