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Transcript
Dengue Fever
1.
ABOUT DENGUE
Dengue, the most common arboviral illness transmitted
worldwide, is caused by infection with 1 of the 4 serotypes
of dengue virus. Dengue is transmitted by the bite of an
infected female mosquito (more commonly Aedes aegypti),
which are widely distributed in subtropical and tropical areas
of the world.


Dengue virus infections may be asymptomatic, or may lead
to undifferentiated fever, dengue fever (DF) or dengue
hemorrhagic fever (DHF) with plasma leakage that may lead
to hypovolemic shock (dengue shock syndrome, or DSS).
Dengue Fever: Clinical features vary depending on the age
of the patient.

Infants and young children may have an
undifferentiated febrile disease, often with a
maculopapular rash.

Older children and adults may have either a mild
febrile syndrome or the classic incapacitating
disease: high fever of abrupt onset, sometimes with
2 peaks (saddle-backed or biphasic pattern), severe
headache, retro-orbital pain, muscle and bone or
joint pains, nausea and vomiting, and rash.
A small percentage of persons who have previously been
infected by one dengue serotype develop bleeding and
endothelial leak upon infection with another dengue
serotype. This syndrome, termed dengue hemorrhagic fever
(DHF), is a potentially deadly complication.
Dengue Hemorrhagic Fever (DHF) criteria:
WHO criteria for DHF (1997)




History of recent fever
of 2-7 days duration,
usually biphasic
Hemorrhagic tendencies
o (+) tourniquet test
o petechiae,
ecchymoses, purpura
o bleeding from the
GIT, injection sites
o hematemesis or
melena
Low platelet count
(≤100,000/mm3)
Plasma leakage (“leaky
capillaries”) as evidenced
by:
o Rise in hematocrit ≥
20%
With a drop in
hematocrit following
volume replacement
o Decrease in serum
albumin, or
hypoproteinemia
o Pleural or other
effusions
Philippine Pediatric Society (PPS)
criteria for DHF (1998)
 History of recent fever, 2-7
days duration, regardless of
characteristic
 Hemorrhagic manifestations
o (+) tourniquet test,
except in shock
o mucocutaneous
bleeding
o G.I. bleeding
 Evidence of consumptive
coagulopathy
o Fall in Platelet count
o Prolonged bleeding
time
o Prolonged apt
o Prolonged PT
 Increasing hematocrit in spite
of proper hydration
 Serosal effusions
 Edema due to
hypoprotenemia
Grading Severity of DHF: DHF is classified into 4 grades of
severity, where grades III and IV are considered to be DSS.
The presence of thrombocytopenia with concurrent
hemoconcentration differentiates grades I and II DHF from
DF.

Grade I: Fever accompanied by nonspecific
constitutional symptoms; the only hemorrhagic

manifestation is a positive tourniquet test and/or
easy bruising
Grade II: Spontaneous bleeding, in addition to the
manifestations of Grade 1 patients, usually in the
forms of skin or other hemorrhages
Grade III: Circulatory failure manifested by a
rapid, weak pulse, and narrowing of pulse pressure
or hypotension, with the presence of cold clammy
skin and restlessness.
Grade IV: Profound shock with undetectable
blood pressure or pulse.
Dengue Shock Syndrome (DSS): all of the 4 criteria
(WHO 1997), plus signs of circulatory failure:
1) narrow pulse pressure ≤ 20 mmHg
2) cold, clammy skin
3) rapid, weak pulse
4) hypotension
2.
PATHOPHYSIOLOGY
Dengue infection is caused by 1 of 4 related, antigenically
distinct, viral serotypes: dengue virus 1 (DENV-1), dengue
virus 2 (DENV-2), dengue virus 3 (DENV-3), and dengue
virus 4 (DENV-4), which can be distinguished by serological
methods. Albert Sabin speciated these in 1944  Dengue
viruses are small, spherical, single-stranded enveloped RNA
viruses of the family Flaviviridae, genus Flavivirus.
Once inoculated into a human host, dengue has an
incubation period of 3-14 days (average 2 to 7 days). During
this time, viral replication takes place in target dendritic cells,
primarily those of the reticuloendothelial system (dendritic
cells, hepatocytes, endothelial cells) which results in the
production of immune mediators that determine the
quantity, type and duration of cellular and humoral immune
response to both the initial and subsequent virus infections.
The first infection produces life-long immunity to the
infecting serotype, but only temporary and partial protection
against the 3 other serotypes, and secondary or sequential
infections are possible after a short time. Viremia levels
directly predict disease severity. Incubation is followed by an
acute phase of infection (acute febrile illness) lasting 5-7 days.
Recovery is usually complete by 7-10 days.
Dengue hemorrhagic fever (DHF) or dengue shock
syndrome (DSS) usually develops around the 3rd to 7th day
of illness, approximately at the time of defervescence. DSS
occurs with higher frequency in two immunologically defined
groups: 1) children who have experienced a previous dengue
infection, and 2) infants with waning levels of maternal
dengue antibody.
Two main pathophysiological changes occur in DHF/DSS:
1) increased vascular permeability that gives rise to loss of
plasma from the vascular compartment: This results in
hemoconcentration, low pulse pressure, and other signs
of shock, if plasma loss becomes critical.
2) The second change is a disorder in hemostasis involving
vascular changes, thrombocytopenia and coagulopathy.
A constant finding in DHF/DSS is activation of the
complement system, with profound depression of C3 and C5
levels. The mediators that increase vascular permeability and
the precise mechanism(s) of the bleeding phenomena in
dengue infections have not yet been identified; immune
complexes have been described in DHF but their role is not
yet clear.
1
Platelet defects may be both qualitative and quantitative, i.e.
some circulating platelets during the acute phase of DHF
may be exhausted or incapable of normal function.
Therefore, even a patient with platelet count greater than
100,000 per mm3 may still have prolonged bleeding time.
3.
myalgias, headache
UTI or Pyelonephritis
DIFFERENTIALS



Early in the febrile phase, the differential diagnosis
for DHF/DSS includes a wide spectrum of viral,
bacterial and parasitic infections.
By the 3rd or 4th day, laboratory findings may
establish a diagnosis before shock occurs.
Marked thrombocytopenia with concurrent
hemoconcentration differentiates DHF/DSS from
diseases such as endotoxin shock from bacterial
infection, or meningococcemia.
Common differential
diagnoses
Respiratory infections
(e.g. influenza)
Is a differential dx
because:
- acute, nonspecific
clinical picture:
fever, headache,
body malaise,
myalgia
Measles
- appearance of
rash
- severe prostration
or exhaustion
Leptospirosis
- appearance of
maculopapular
eruption
- presents with
myalgia
Typhoid fever
- appearance of
maculopapular rash,
usually on trunk
- presents with:
variable abdominal
pain, headache,
myalgia,
hepatosplenomegaly
Meningococcemia
- appearance of
maculopapular or
petechial eruptions
- presents with:
fever, arthritis,
More likely rule out
dengue with:
- (+) presence of
respiratory symptoms
(cough, sore throat,
nasal discharge)
- bacterial pneumonia
usually presents with
productive cough and
chest pain
- CBC shows elevated
total WBC with
neutrophila; diagnosis
can be made with
CXR
- pre-exanthematic
phase (cough, nasal
discharge,
conjunctivitis) does
not occur in dengue
- rash usually begins in
the face, with cephalocaudal progression
- Koplik’s spots in the
mucous membrane of
mouth/ tongue are
pathognomonic of
measles
- (+) jaundice plus
epidemiologic data
supporting a diagnosis
of leptospirosis
- labs show: increased
ESR, elevated WBC
with neutrophilia,
slightly elevated
transaminase levels,
increased BUN and
creatinine
- (+) history of
ingestion of
contaminated food or
water
- transient, blanchable
erythematous macules
and papules usually
appear on the trunk
(rose spots)
- diarrhea is not a
symptom of dengue
- neurologic
manifestations tend to
be absent in dengue
fever
- evaluation of CSF is
4. DIAGNOSTICS
Test
CBC with
platelet count
and differential
count
- presents with
nonspecific signs
and symptoms: high
grade fever, body
malaise
the basis for diagnosis;
in DF, the CSF is
usually normal
- WBC may show
leukocytosis and
neutrophilia
- diagnosis is based on
urine GS/CS
Laboratory findings in Dengue
WBC count will reveal leukopenia
(presence of leukocytosis excludes
possibility of dengue; bacterial infections
like leptospirosis, meningococcemia,
sepsis, pyelonephritis etc. must be
considered)

Platelet count reveals
thrombocytopenia (≤100,000/mm3)

Hematocrit elevated by >20%
(hemoconcentration)
PT/PTT

May be prolonged in severe cases
Laboratory criteria for the confirmation of the diagnosis
(WHO, 1997)
- at least one must be present

Isolation of the dengue virus from the serum or autopsy
samples

Demonstration of a 4-fold or greater change in the
reciprocal IgG or IgM antibody titers to one or more dengue
virus antigens in paired serum samples

Demonstration of dengue virus antigen in autopsy tissue,
serum, or cerebrospinal fluid samples by immunochemistry,
immunofluorescence or ELISA

Detection of viral genomic sequences in the autopsy tissue,
serum, or cerebrospinal fluid samples by PCR
5.

PLAN
Admitting Orders
Admit to: W___ B ___
Diet: Avoid dark- colored foods (for monitoring of melena) and acidic
foods
VS: Monitor vital signs q1-4 hours and WOF any signs of bleeding;
Monitor temperature q4h, and in between if febrile or with chills
Nursing: I & O qshift
IVF: D5NM x 8 hours; D5NSS or D5LR for shock
Diagnostics:

CBC with PC and DC

PT, PTT

Tourniquet test

SGOT, SGPT

Dengue serology if illness longer than 4 days

U/A

Chest X-ray (check for pneumonia, pleural effusion)

Monitor: Platelet count ± hematocrit levels q12-24 hours
Therapeutics:

Medical treatment
1) Supportive: hydration
2) Optional medications: H2-blockers if with abdominal
pain or GI bleeding
3) WOF complications:

If there is frank, uncontrollable bleeding,
transfuse fresh whole blood if indicated

If PT, PTT are prolonged, and with
thrombocytopenia, FFP transfusion is
indicated

If there is DIC, platelet transfusion is
indicated
Note: in the absence of bleeding, there is no
need to administer platelet transfusion even if
2

platelet count is low
Prevention
1) Environmental: Get rid of mosquito breeding places (ex.
areas with stagnant water)
2) Vaccine: may be available in the near future…
REFERENCES:
 Dengue Hemorrhagic Fever, pp.114-115. Expanded Medicine Blue Book 2nd edition by Willie Ong,
et al. (2007)
 Harrison’s Principles of Internal Medicine 16th and 17th edition
 Dengue Fever article by Price and Wilson, Emedicine (2008)
http://emedicine.medscape.com/article/781961-overview
 Dengue Fever article by Shepherd et al, Emedicine (2007)
http://emedicine.medscape.com/article/215840-overview
 Dengue Hemorrhagic Fever: Diagnosis, treatment, prevention and control. 2nd edition. Geneva:
WHO (1997)
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