DENGUE:

WHO GUIDELINES FOR DIAGNOSIS AND

TREATMENT

Jimmy Mendigo, MD
Infectious Disease
Specialist
Chrysanta D. Viernes, MD
Internal Medicine- ITRMC
 OBJECTIVES

Discuss the epidemiology and burden of

disease of Dengue

Review the transmission

Discuss the new case classification

Discuss algorithms in the diagnosis and

management of Dengue
 EPIDEMIOLOGY

most rapidly spreading mosquito-borne

viral disease in the world

incidence: 30-fold increase

increasing geographic expansion to new
countries, and from urban to rural
settings
50 million dengue infections annually
EPIDEMIOLOGY
 EPIDEMIOLOGY

2001-2008: 1, 020,333 cases in

Cambodia, Malaysia, Philippines and
Vietnam

highest reported deaths in 2008

Cambodia
Philippines
 Burden of Disease

WHO estimates that 2.5 billion

peopleover 40% of the worlds
population-- are at risk for dengue
infection.

Approximately 50-100 million

infections (1 million confirmed)
occur each year resulting in
500,000 hospitalizations and 20,000
 Dengue Virus Profile
Genus Flavivirus
Family Flaviviridae
Single-stranded
RNA
4 serotypes (DEN-1
to 4)

50 nm diameter with
multiple copies of 3
structural proteins
( membrane bilayer and single-
stranded RNA)
 Vector Profile

Aedes
mosquitoes
A. aegypti
A. albopictus
A. polynesiensis
Tropical and
subtropical
species
Urban places
Immature stages
are found in
 The Host

Incubation period: 4-10

days

Primary infection
induce lifelong
immunity to the
infecting serotype

Protection from
different serotype
within 2-3 months
 The Host

Individual risk factors:

Age, ethnicity, chronic diseases

Seroepidemiological studies (Cuba and

Thailand)
Secondary heterotypic infection
Time interval between infections
Antibody-dependent enhancement of
infection
 Replication and Transmission

Blood meal Released in

circulation

Viral
Replication WBC and
Lymphatics
 Replication and Transmission

Replication
in the
salivary
gland

Viral Extrinsic
replication Incubation
in midgut 8--12 days

Female
mosquito
ingests
infected
blood
 Dengue Fever

Wide spectrum of clinical presentation, with

unpredictable clinical evolution and outcome

Three phases
Febrile phase
Critical phase
Recovery phase

Previously classified into

undifferentiated fever, dengue fever and
DHF
Grade 1-IV
 Dengue Fever

Grade 1: fever, non specific constitutional symptoms; (+)

TT- only hgic manifestation

Grade 2: Grade 1 manifestation + spontaneous bleeding

Grade 3: signs of circulatory failure (rapid weak pulse,

narrow pulse pressure, hypotension, cold
clammy skin)

Grade 4: profound shock with undetectable pulse and BP

Dengue Fever
 Febrile Phase

facial flushing
Sudden onset skin erythema
generalized body ache
of high-grade
myalgia and arthralgia
fever headache
Lasts for 2-7 sorethroat, injected
days pharynx, and
conjunctival injection
anorexia, nausea and
vomiting
 Febrile Phase
earliest abnormality:
progressive decrease in total
wbc
(+) TT increases the
probability of dengue

(+) hemorrhagic
manifestations

enlarged and tender

liver
 Critical Phase

temperature drops to 37.5-38 (days 3-

7)

(+) increase in capillary permeability

with increasing hematocrit levels

significant plasma leakage lasts for

24-48 hours

progressive leukopenia followed by

 Critical Phase

if (-) increase in capillary permeability

improve
if (+) increase in capillary permeability
pleural effusion and ascites

degree of increase above the baseline

hematocrit reflects the severity of
plasma leakage
 Critical Phase

shock: critical volume of plasma is lost

temperature may be subnormal
prolonged shock organ hypoperfusion
organ impairment, metabolic acidosis, and
DIC severe hemorrhage
severe hepatitis, encephalitis or myocarditis
 Recovery Phase

gradual reabsorption of extravascular

compartment fluid (48-72 hours)
general well-being improves, appetite
returns, GI symptoms abate, hemodynamic
status stabilizes and diuresis ensues
(+) rash: isles of white in the sea of red
 Recovery Phase

hematocrit stabilizes or may be lower due to

dilutional effect of reabsorbed fluid
wbc starts to rise
recovery of platelet count occurs later
 Approach to the Management

At primary and secondary levels, health

care facilities are responsible for emergency/
ambulatory triage assessment and treatment

Triage is the process of rapidly screening patients

soon after their arrival in the hospital or health
facility in order to identify those
Severe dengue
With warning signs
Non-urgent cases
Approach to the Management
 Approach to the Management

Referral centres receiving severely ill dengue

patients must be able to give prompt attention to
referred cases.

Beds should be made available to those patients who

meet the admission criteria

There should be a designated area to cohort dengue

patients, and a high-dependency unit for closer
monitoring of those with shock.
Staffed by doctors and nurses
 Approach to the Management

Criteria for transfer:

early presentation with shock (on days 2 or 3 of
illness);
severe plasma leakage and/or shock;
undetectable pulse and blood pressure;
severe bleeding;
fluid overload;
organ impairment (such as hepatic damage,
cardiomyopathy, encephalopathy,
encephalitis and other unusual complications).
 Approach to the Management

Disease notification
In dengue-endemic countries, cases of suspected,
probable and confirmed dengue should be
notified
Public health measures
suspected cases
lives in or has travelled to a dengue-endemic area
fever for three days or more
low ordecreasing white cell counts
thrombocytopaenia positive tourniquet test.
 Approach to the Management
Management Decisions

Groups A Groups B Groups C

may be sent referred for require
home in-hospital emergency
tolerate managemen treatment
adequate t and urgent
volumes of with referral
oral fluids severe
warning
and pass dengue (in
urine at
signs, co- critical
least once existing phase)
 Group A Action Plan
Encourage intake of ORS, fruit juice and other fluids
Paracetamol and tepid sponge for fever
Advise to come back if with
no clinical improvement
severe abdominal pain
persistent vomiting
cold and clammy extremities,
lethargy or irritability or restlessness,
bleeding
not passing urine for more than 46 hours.
monitor:
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 (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:
haematocrit 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 6
12 hourly)
blood glucose
organ functions (renal profile, liver profile, coagulation
 Group B (without 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.
 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
judicious intravenous fluid
resuscitation: sole
 Group C Action Plan

Goals of fluid resuscitation:

improving central and peripheral circulation
(decreasing tachycardia, improving BP, warm
and pink
extremities, and capillary refill time <2 seconds)

improving end-organ perfusion

i.e. stable conscious level (more alert or less
restless), urine output 0.5 ml/kg/hour,
decreasing metabolic acidosis.
 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
Treatment of Hemorrhagic Complications

Blood transfusion is life-saving and should be

given as soon as severe bleeding is suspected
or recognized

Do not wait for the haematocrit to drop too

low before deciding on blood transfusion

Risk of fluid overload.

Treatment of Hemorrhagic Complications

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
 Management of Complications

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
 Management of Complications

Clinical Features:

respiratory distress, Other investigations:

difficulty in breathing;
rapid breathing;
CXR
chest wall in-drawing; ECG
wheezing (rather than ABG
crepitations);
large pleural effusions;
tense ascites;
 Management of Complications

Oxygen therapy
Stop IVF
When to discontinue IVF:
stable blood pressure, pulse and peripheral perfusion;
haematocrit decreases in the presence of a good pulse
volume;
afebrile for more than 2448 days (without the use of
antipyretics);
resolving bowel/abdominal symptoms;
improving urine output

If necessary, give oral or intravenous furosemide 0.10.5

mg/kg/dose once or twice daily, or continuous infusion of
furosemide 0.1 mg/kg/hour.
 Management of Complications

If the patient has stable haemodynamic status but is still within

the critical phase, reduce the intravenous fluid accordingly.
Avoid diuretics during the plasma leakage phase

Patients who remain in shock with low or normal haematocrit

levels but show signs of fluid overload may have occult
haemorrhage.
Careful fresh whole blood transfusion
repeated small boluses of a colloid solution
Criteria for Discharge