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 world’s 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 crossprotective 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
Viral
Replication
Released in
circulation
WBC and
Lymphatics
Replication and Transmission
Replication in
the salivary
gland
Viral replication
in midgut
Female mosquito
ingests infected
blood
Extrinsic Incubation
• 8--12 days
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
• Sudden onset of
high-grade fever
• Lasts for 2-7 days
facial flushing
skin erythema
generalized body ache
myalgia and arthralgia
headache
sorethroat, injected
pharynx, and conjunctival
injection
 anorexia, nausea and
vomiting






Febrile Phase
•
(+) TT increases the
probability of dengue
•
(+) hemorrhagic
earliest abnormality: progressive
decrease
manifestations
in total wbc
•
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:
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•
•
•
•
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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
• may be sent
home
• tolerate
adequate
volumes of oral
fluids and pass
urine at least
once every 6
hours
Groups B
• referred for in-
hospital
management
• with warning
signs, coexisting
conditions,
• with certain
social
circumstances
Groups C
• 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
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 4–6 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
5–7 ml/kg/hour for 1–2 hours, then reduce to
3–5 ml/kg/hr for 2–4 hours, and then reduce to
2–3 ml/kg/hr or less according to the clinical
response
reassess:
•
•
haematocrit remains the same or rises only minimally  2–3 ml/kg/hr for
another 2–4 hours
worsening vital signs and rising haematocrit rising  5–10 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 24–48 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 (1–4 hourly until the patient is
out of the critical phase)
• urine output (4–6 hourly)
• hematocrit (before and after fluid replacement, then 6–12 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 Ringer’s 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 24–48
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
in breathing;
– rapid breathing;
– chest wall in-drawing;
– wheezing (rather than
crepitations);
– large pleural effusions;
– tense ascites;
Other investigations:
• CXR
• ECG
• ABG
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 24–48 days (without the use of antipyretics);
– resolving bowel/abdominal symptoms;
– improving urine output
•
If necessary, give oral or intravenous furosemide 0.1–0.5 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