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 people

over 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
deaths.
 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 water-filled
habitats
 The Host

Incubation period: 4-10 days

Primary infection induce

lifelong immunity to the
infecting serotype

Protection from different

serotype within 2-3
months of primary
infection
No long-term cross-
protective immunity
 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 replication Extrinsic 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

Critical Phase

Recovery Phase
 Febrile Phase

facial flushing
skin erythema
Sudden onset of generalized body ache
myalgia and arthralgia
high-grade fever
headache
Lasts for 2-7 days sorethroat, injected
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 rapid

decrease in platelet precedes plasma leakage
 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 B
Groups A referred for in- Groups C
may be sent hospital require
home management emergency
tolerate with warning treatment and
adequate
signs, co- urgent referral
volumes of oral
existing severe
fluids and pass
conditions, dengue (in
urine at least
with certain critical phase)
once every 6
hours social
circumstances
 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 1
2 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 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.
Close monitoring
 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 intervention required
 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, difficulty

Other investigations:
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