DENGUE FEVER

Dengue Clinical Case Management Training Workshop

 DENGUE FEVER
A benign syndrome caused by several
arthropod-borne viruses
Member of the family Flaviviridae and has
four distinct antigenic types of dengue virus
Transmitted by mosquitoes
Composed of single-stranded RNA
Has 4 serotypes (DEN-1, 2, 3, 4)
Characterized by biphasic fever, myalgia and
arthralgia, rash, leukopenia and
lymphadenopathy
Dengue Viruses
Each serotype provides specific
lifetime immunity, and short-term
cross-immunity
All serotypes can cause severe and
fatal disease
Genetic variation within serotypes
Some genetic variants within each
serotype appear to be more virulent
or have greater epidemic potential
DENGUE CASES IN ILOILO DECLINE
a total of 274 cases with two deaths was recorded for the
period January 1 to June 6, which is a drop of 19 percent
compared to the 340 cases registered for the same
period last year.
Of the 274 dengue cases, Pavia recorded the highest
number of cases so far this year with 35; followed by
Calinog with 34, Sara and Santa Barbara with 23 each,
Lemery with 13, and Cabatuan and Ajuy with 12 cases
each.

Philippine Information Agency

June 22, 2015
Transmission of Dengue Virus
by Aedes aegypti

Mosquito feeds / Mosquito refeeds /

acquires virus transmits virus

Extrinsic Intrinsic
incubation incubation
period period
Viremia Viremia
0 5 8 12 16 20 24 28
Days
Illness Illness
Human #1 Human #2
 Replication and Transmission
of Dengue Virus (Part 1)

1. Virus transmitted 1
to human in mosquito
saliva

2
2. Virus replicates
in target organs 4

3. Virus infects white 3

blood cells and
lymphatic tissues

4. Virus released and

circulates in blood
 Replication and Transmission
of Dengue Virus (Part 2)

5. Second mosquito 6
ingests virus with blood

6. Virus replicates
in mosquito midgut
and other organs, 7
infects salivary
glands

5
7. Virus replicates
in salivary glands
CLINICAL
MANIFESTATION
S
 CLINICAL DIAGNOSIS OF
DENGUE
Difficult because early s/sx are NONSPECIFIC
Presents like many other acute febrile illness
Clinical manifestations changes throughout
the course of the illness and varies with
disease severity
Early clinical dx important for appropriate
anticipatory guidance and treatment to
prevent morbidity and mortality
 CLINICAL DIAGNOSIS OF
DENGUE
Consider the following:
Exposure history
s/sx consistent with dengue
r/o other diseases that px might be exposed
to at the same time
r/o other acute febrile illnesses
Clinical lab findings consistent with dengue
 CLINICAL DIAGNOSIS OF
DENGUE
CLINICAL ASSESSMENTS
History of present illness
Fever history
Signs and symptoms
Physical examination
Mental status
Hemodynamic status
Hydration status
+/- warning signs
s/sx of plasma leakage
CLINICAL MANIFESTATIONS
In infants and young
children:
Fever for 1-5 days
Pharyngeal inflammation
Rhinitis
Mild cough
In older children and adults:
Sudden onset of fever
Rapidly increasing temp (39.4-
41.1)
Frontal and retro-orbital pain
back-break fever (severe
back pain prior to fever)
 CLINICAL MANIFESTATIONS
Transient, generalized rash that blanches under
pressure seen during the 1st 24-48 hours of fever

Pulse rate slow relative to degree of fever

Myalgia and arthralgia occur soon after the onset and

increase in severity
2nd 6th day of fever:
Nausea and vomiting occur and generalized
lymphadenopathy, cutaneous hyperesthesia,
or hyperalgesia, taste aberrations,
pronounced anorexia
1-2 days after defervescence:
Generalized, morbilliform, maculopapular rash
appears that spares palms and soles
CLINICAL MANIFESTATIONS
Rashes disappear in 1-5 days, desquamation may
occur

Edema of the palms and soles

2nd rash appears, body temp elevated biphasic

temp pattern
 DENGUE SIGNS AND
CLINICAL SYMPTOMS
INCUBATION PERIOD:
3 -14 days; usu 4-7 days (CCMTW)
1-7 days (Nelsons)
Three phases
FEBRILE phase
CRITICAL phase
RECOVERY phase
FEBRILE PHASE
 FEBRILE PHASE
Fever from 0-7 days
biphasic fever pattern possible
Monitor defervescence and warning signs to
recognize START OF CRITICAL PHASE
1-2 days

Symptom
onset Recovery

Mosquito
bite Critical
Phase
0-7 days 3-5 days

Febrile Phase

Incubation ------------------Viremia ------------------ -------------Non Viremia -------------

-7 0 14
 FEBRILE PHASE
CLINICAL MANIFESTATIONS LAB FINDINGS
sudden onset of high fever PLUS CBC with decrease in WBC
any of the ff: Mild to moderate
Severe headache thrombocytopenia
Retro-orbital pain Elevated AST
Myalgia Elevated ALT
Rash transient macular Hyponatremia
maculopapular
Minor hemorrhagic manifestations
eg. petechiae, purpura, epistaxis,
hematuria
Positive tourniquet test
Facial flushing
Anorexia
Injected oropharynx
 Red, pinpoint,
blanching,
Palm and sole sparing

Rashes seen in Febrile Phase

 TOURNIQUET TEST
Part of the new World Health Organization
case definition for dengue
Marker of capillary fragility and it can be
used as a triage tool
Even if a TT was prev done, it should be
repeated if
Prev negative
No bleeding manifestation
TT is
More likely to be (+) NEAR TIME OF
DEFERVESCENCE
Less likely to be (+) in px with SHOCK
 HOW TO DO TOURNIQUET
TEST
Take the px BP and record
Inflate the cuff to a point MIDWAY betwen SBP
and DP and maintain for 5 minutes
Reduce and wait 2 minutes
Count petechiae below antecubital fossa
POSITIVE TEST = 10 or more petechiae per 1
square inch

CDC Dengue Clinical Case Management course (DCCM)

Laboratory Findings
Conditions that Mimic Febrile
Phase
Viral infections Influenza. Measles, rubella
Chikungunya, West Nile Virus
Enterovirus
Other viral hemorrhagic fever
Infectious mononucleosis
Acute HIV seroconversion
Illness
Bacterial infections Leptospirosis
Rickettsia infectios
Typhoid
Parasitic infections Malaria
Febrile illness with Measles. Rubella
rashes Infectious mononucleosis, enterovirus
Chikungunya, West Nile Virus
Scarlet fever, meningococcal infectionsLeptospirosis
Rickettsia infectios, Typhoid, autoimmune diseases
Diarrheal diseases Rotavirus, salmonellosis, other enteric infections
 CLINICAL PROBLEMS IN
FEBRILE PHASE
Dehydration
Hyponatremia
Febrile seizures
Neurologic disturbances
Aseptic disturbances
Encephalitis
CRITICAL PHASE
 CRITICAL PHASE
As early as 3rd day after onset of fever to time of defervescence
May develop severe disease critically ill
Most px may improve during this phase and do not develop
severe disease
Rapid decrease in Platelet count with associated rise in
hematocrit
Presence of warning signs 1-2 days

Symptom
onset Recovery

Mosquito
bite Critical
Phase
0-7 days 3-5 days

Febrile Phase

Incubation ------------------Viremia ------------------ -------------Non Viremia -------------

-7 0 14
 CRITICAL PHASE
CLINICAL MANIFESTATIONS LAB FINDINGS
period of clinically significant plasma inc in HCT
leakage lasts 24-28 hours mod to severe
- ascites, pleural effusion thrombocytopenia
severe abdominal pain
Leukopenia
Liver enlargement > 2 cm
Persistent vomiting (3 or more episodes transient increase in aPTT
within 24 hours)
mucosal bleeding
Lethargy or restlessness
Shock preceded by WS
subnormal temperature
progressive organ impairment
metabolic acidosis and DIC
Laboratory Findings
 CLINICAL PROBLEMS IN
FEBRILE PHASE
Hypovolemic shock due to plasma
leakage
End organ impairment from prolonged
shock
Myocarditis, severe hepatitis, encephalopathy,
encephalopathy
Severe hemorrhage
RECOVERY
PHASE
 RECOVERY PHASE
Follows critical phase
Gradual reabsorption of extravascular
compartment fluid in 48-72 hours

1-2 days

Symptom
onset Recovery

Mosquito
bite Critical
Phase
0-7 days 3-5 days

Febrile Phase

Incubation ------------------Viremia ------------------ -------------Non Viremia -------------

-7 0 14
 RECOVERY PHASE
CLINICAL MANIFESTATIONS LAB FINDINGS
Rash HCT stabilizes of slightly lower
(ISLETS OF WHITE IN A SEA OF RED) due to dilutional effect of
general well being with improving reabsorbed plasma
appetite
WBC starts to rise
GI symptoms start to subside
hemodynamic status stabilizes and Platelet count increases with
diuresis improves WBC recovery
generalized pruritus
bradycardia and ECG changes common
Isles of white in the sea
of red

Rashes seen in Recovery Phase

Laboratory Findings
 CLINICAL PROBLEMS IN
RECOVERY PHASE
Hypervolemia due to excessive fluid
therapy
Acute pulmonary edema
Organ impairment due to prolonged or
refractory shock leading to ischemic
hepatitis and hepatic encephalopathy
Nosocomial infections
LABORATORY
DIAGNOSIS
 DENGUE DIAGNOSTIC
TESTING
Objective of diagnostic testing is to CONFIRM
Obtain a serum specimen as soon after onset of
fever as possible
Request test by timing of specimen collection
Best test include:
ACUTE PHASE SPECIMEN (5 days or less after fever onset)
DENV specific polymerase chain reaction (PCR) to detect
DENV NS1 antigen
CONVALESCENT PHASE (5 days or more after fever onset)
IgM anti-DENV ELISA to detect IgM antibody
Both IgM and PCR or NS1 should be ordered to
maximize chances of confirming dx
 DENGUE DIAGNOSTIC
TESTING
At or shortly before the onset of fever and for about
5 days
DENV is present in the circulation and can be detected
using molecular dx tests such as RT-PCR
NS1 Antigen is detectable in serum and parallels the
detection of DENV by RT-PCR, though it might be
detectable for a few days longer
Later in febrile phase (~ day 3 or 4 after the onset
of fever)
IgM anti-DENV becomes detectable and remains detectable
for several months after DENV infection
During the recovery phase in a patient with their
first (primary) DENV infection
IgG anti-DENV appears for the first time and remains
 DENGUE DIAGNOSTIC
TESTING
Viremia and PCR positivity coincides with fever
An early serum specimen is required fro dx
If the first specimen is obtained at day 5 after onset
of illness, dx might be more difficult since DENV (by
PCR) or IgM anti-DENV by immunoassay might not be
detected.
In this case, a second convalescent specimen mght
be needed if the results are negative
IgM antibodies are detected for up to 3 months after
infection
IgG antibodies are detected for lifetime after infection.
Antibodies to DENV cross-react with antibodies against
other flaviviruses
 DENGUE DIAGNOSTIC
DIAGNOSIS
TESTING
ACUTE PHASE CONVALESCENT PHASE (5
(5 days or less after days or more after symptom
symptom onset) onset)

PCR OR NS1 IgM anti- NS1 IgM anti-

DENV DENV
+ + + +

Dengue + - + -
confirmed
Not tested or -* Not tested or +*
- -

Dengue - + - +
Probable

Dengue - - - -
Negative
* Paired acute and convalescent specimens with seroconversion between 2 time points
NEW DENGUE
CLASSIFICATION
 PROBABLE DENGUE FEVER
Lives in or travels to dengue endemic area with fever PLUS any 2
of the ff:
headache Anorexia
Body malaise Diarrhea
Myalgia Flushed skin
Arthralgia Rash (petechial Hermans sign)
Retro-orbital pain Tourniquet test Positive
Nausea, vomiting
AND
Laboratory test at least CBC (leukopenia with or without thrombocytopenia)
And/or Dengue NS1 antigen test or dengue IgM antibody test (optional test)
CONFIRMED DENGUE FEVER

VIRAL CULTURE ISOLATION

PCR
 Dengue with WARNING
SIGNS
Lives or travels to dengue-endemic area
With fever lasting for 2-7 days, PLUS any of the ff:
Abdominal pain or tenderness
Mucosal Bleeding
Clinical signs of fluid accumulation
Persistent vomiting
Letahrgy, restlessness
Liver enlargement
Decreased or no urine output for 6 hours
Labortaory:
increase in HCT and/or decreasing platelet count
 Severe Dengue
Lives or travels to dengue-endemic area
And any of the above clin manifestations fro dengue
with ir without warning signs,
PLUS any of the ff:
Severe plasma leakage Shock
leading to Fluid accumulation
Severe organ impairment Liver: AST or ALT 1000
CNS: seizuresm impaired
consciousness
Heart: myocarditis
Kidneys: renal failure
Severe bleeding
Revised Dengue Case
Classification
MANAGEMENT
Approach to the
Management
Management Decision
Groups A (DF without Warning Signs)
may be sent home
tolerate adequate volumes of oral fluids and pass urine
at least once every 6 hours
no warning signs

Groups B (DF with Warning Signs)

referred for in-hospital management
with warning signs, co-existing conditions,
with certain social circumstances

Groups C (DF with Severe Warning Signs)

require emergency treatment and urgent referral
severe dengue (in critical phase)
Group A Action Plan
Encourage intake of ORS, fruit juice and other fluids
Paracetamol and tepid sponge for fever
Do not give aspirin, ibuprofen or other NSAIDS aggravate
bleeding
Advise to come back if with
no clinical improvement
severe abdominal pain
persistent vomiting
cold and clammy extremities,
lethargy or irritability or restlessness,
Bleeding
monitor:
not passing urine for more than 46 hours.
temperature pattern, volume of fluid intake and
losses, urine output, warning signs, signs of plasma
leakage and bleeding, haematocrit, and white blood
cell and platelet counts
 Group B (warning signs)
Action Plan
Encourage oral fluids

If not tolerated, start intravenous fluid therapy of 0.9%

saline or Ringers lactate with or without dextrose at
maintenance rate

Patients may be able to take oral fluids after a few hours

of intravenous fluid therapy.

Give the minimum volume required to maintain good

perfusion and urine output.

Intravenous fluids are usually needed only for 2448 hours.

Close monitoring
Group B (with warning signs)
Action Plan
reference hematocrit before fluid therapy
isotonic solutions
57 ml/kg/hour for 12 hours, then reduce to 35 ml/kg/hr for 24
hours, and then reduce to 23 ml/kg/hr or less according to the
clinical response

reassess:
hematocrit remains the same or rises only minimally 23
ml/kg/hr for another 24 hours
worsening vital signs and rising haematocrit rising 510
ml/kg/hour for 12 hours
Group B (with warning signs)
Action Plan
Give minimum intravenous fluid
volume: maintain good perfusion
and urine output of about 0.5
ml/kg/hr
Intravenous fluids are usually needed for only 2448
hours.
Reduce intravenous fluids gradually when the rate of
plasma leakage decreases towards the end of the
critical phase.
monitor:
vital signs and peripheral perfusion (14 hourly until the patient is
out of the critical phase)
urine output (46 hourly)
hematocrit (before and after fluid replacement, then 612 hourly)
blood glucose
organ functions (renal profile, liver profile, coagulation profile)
Group C Action Plan
admit to a hospital with access to
intensive care facilities and blood
transfusion

plasma losses should be replaced

immediately and rapidly with isotonic
crystalloid solution or, in the case of
hypotensive shock, colloid solutions

blood transfusion: with suspected/severe

bleeding
Treatment of Hemorrhagic
Complications
Patients at risk of major bleeding are those who:
prolonged/refractory shock;
hypotensive shock and renal or liver
failure and/or severe and persistent
metabolic acidosis
given non-steroidal anti-inflammatory
agents
pre-existing peptic ulcer disease
anticoagulant therapy
any form of trauma
 blood transfusion if with
bleeding
5-10 ml/kg of PRBC or 10-20 ml/kg FWB
repeat if with further blood loss or no rise in
hematocrit after transfusion

little evidence to support transfusion of

platelet concentrate and FFP
massive bleeding not managed by
FWB/PRBC
may exacerbate fluid overload
 Fluid Overload
Causes:
excessive and/or too rapid intravenous fluids;
incorrect use of hypotonic rather than isotonic
crystalloid solutions;
inappropriate use of large volumes of intravenous
fluids in patients with
unrecognized severe bleeding;
inappropriate transfusion of FFP, platelet
concentrates and cryoprecipitates;
continuation of IVF after plasma leakage has resolved
co-morbid conditions such as congenital or ischaemic
heart disease, chronic lung and renal diseases
Fluid Overload
Clinical Features:
respiratory distress, difficulty in
breathing;
rapid breathing;
chest wall in-drawing;
wheezing (rather than crepitations);
large pleural effusions;
tense ascites;
When to Stop IVF
stable blood pressure, pulse and peripheral
perfusion;
hematocrit decreases in the presence of a
good pulse volume;
afebrile for more than 2448 hours (without
the use of antipyretics);
resolving bowel/abdominal symptoms
improving urine output
Criteria for Discharge
THANK
YOU!
 The results of the
Whats in the NEWS study done over a 25-
month observation
period showed that 3
doses of CYD-TDV
reduced the possibility
of developing dengue
hemorrhagic fever by
88.5%. The risk of
hospitalization due to
dengue was also
reduced by 67%.
II. Vector
Aedes aegypti Mosquito

Close-up of an Aedes mosquito

Aedes aegypti
Dengue transmitted by infected female
mosquito
Primarily a daytime feeder
Lives in and around human habitation
Lays eggs and produces larvae
preferentially in artificial containers
Life span 14 to 21 days
Can lay about 300 eggs
Life cycle of the Aedes
Mosquito

1-2 days

Pupae Larvae Eggs

4-5 days 2-3 days

Stagnant water
Aedes aegypti Breeding Sites