Dengue Fever

Presenters: Koh Pei Ying

Mak Yi Hong
Chew Jen Pin
Adlina Athirah
 Dengue Virus

● Mosquito-borne flavivirus
● Transmitted by Aedes aegypti & Aedes albopictus
● 4 different serotypes: DENV-1, 2, 3 and 4
● Each episode of infection induces a life-long protective immunity to
the homologous serotype but confers only partial and transient
protection against other serotypes
 Spectrum of Dengue Infection
● Incubation period: 4-7 days (ranging from 3 to 14 days)

Dengue viral illness

Dengue Severe dengue

No warning With warning -Severe shock

signs signs -Respiratory distress
-Severe haemorrhage
-Organ failure (CNS/Liver)
Febrile Phase
● Sudden onset high grade fever (usually last 2-7 days)
● Facial flushing, rash, generalised body ache, vomiting and headache
● Sore throat, injected pharynx and conjunctival injection
● Mild hemorrhagic manifestation=>petechiae and mucosal bleeding
● GI bleeding is not uncommon

*Earliest abnormality in FBC is progressive drop in WCC => platelet reduction

Condition that mimic febrile phase of dengue infection

➔ Flu like symptoms

Eg- influenza, infectious mononucleosis

➔ Illness with a rash

Eg- Rubella, measles, drug reaction, meningococcal infection

➔ Diarrhoeal diseases
Eg- Rotavirus

➔ Illness with neurological manifestation

Eg- meningitis/ encephalitis, febrile seizures
Critical Phase
● Often occurs after 3rd day and lasts for 24-48 hours
● Indicated by a rapid drop of temperature
● Increase in capillary permeability causing plasma leakage to third space

*Rise in HCT correlates with plasma volume loss and disease severity

*Leucopaenia with relative lymphocytosis, clotting abnormalities, elevation of

transaminases (AST > ALT), hypoproteinaemia and hypoalbuminaemia
Pathophysiology of Plasma Leakage in Severe Dengue
Acute increase in vascular permeability
=> plasma leakage into extravascular compartment
=> haemoconcentration and hypovolaemia or shock
=> reflex tachycardia and generalised vasoconstriction due to increased
sympathetic output
=> inadequate perfusion of tissue
=> increased anaerobic glycolysis and lactic acidosis

If hypovolaemia is not corrected promptly, the patient will progress to refractory

shock state.
Common late complications of prolonged shock
=> massive bleeding, DIC and multiorgan failure
Recovery/Reabsorption Phase
● Plasma leakage stops and reabsorption of extravascular fluid
occurs
● General well being improves, appetite returns, GI symptoms
improve, haemodynamic status stabilises and diuresis ensues
● HCT stabilises and drops
● Recovery of platelets is preceded by recovery of WCC
● Organ dysfunction may worsen (hepatitis, encephalitis, and
intracranial bleed) as patient enters reabsorption phase
Classical rash of ‘isles of white in the sea of red’
Classification of Dengue Viral Infection
WHO classification 1997 vs 2009
The term DHF used in previous The new classification encompass
classification put too much emphasis various categories of dengue since
on hemorrhage; dengue exists in continuum.

The hallmark of severe dengue (and the manifestation that should be

addressed early) IS NOT HEMORRHAGE but increased vascular
permeability that lead to shock.
Criteria for dengue with or without warning signs

Probable Dengue

*Live in and travel to dengue endemic area

*Fever and any 2 of the following:
1. Nausea, vomiting
2. Rash
3. Aches and pain
4. Positive Tourniquet test
5. Leukopenia

*Any warning signs

Laboratory confimed dengue
NS1, IgM, IgG
(important when no sign of plasma leakage)
Criteria for dengue with or without warning signs

Warning Signs

Clinical:
• Intense abdominal pain or tenderness
• Persistent vomiting
• Clinical fluid accumulation
• Mucosal bleed
• Lethargy, restlessness
• Liver enlargement > 2cm

Laboratory:
Increased in haematocrit with concurrent
rapid decrease in platelet count
Criteria for severe dengue

1. Severe plasma leakage leading to:

• Shock (Dengue Shock Syndrome)
• Fluid accumulation (pleural effusion, ascites)
with respiratory distress

2. Severe bleeding
As evaluated by paediatrician

3. Severe organ involvement:

• Liver: elevated transaminases (AST or ALT ≥ 1000)
• CNS: impaired consciousness, seizures
• Heart and other organ involvement
Importance of early recognition
• Dengue is a complex and unpredictable disease but success can be achieved
with mortality rates of 1% when care is given in simple and inexpensive ways
provided they are given appropriately at the right time.

• The timing of intervention starts at frontline healthcare personnel whether they

are in A&E or OPD or even health clinics.

• Early recognition of disease and careful monitoring of IV fluid is important right

from beginning.
Role of healthcare personnel
• The healthcare personnel involved in managing dengue cases day to day

need to familiarize themselves with the THREE main well demarcated

phases of dengue: febrile, critical; and recovery.

• To recognize dengue when child presents with fever;all we need is TO GO

through the PROBABLE CASE DEFINITION OF DENGUE.

You do not NEED rapid test always to diagnose dengue.

Role of healthcare personnel

● In early phase of disease, it is difficult to differentate dengue with other

 

childhood illness; therefore performing a tourniquet test with FBC at first

encounter would be useful to differentate dengue from other illness.

● Temporal relationship of fever cessation (defervescence) is important as in

DENGUE (unlike other viral illness) manifest its severity (leakage/shock)
when temperature seems to have declined.
Investigations
In early phase of disease, it is difficult to differentiate dengue with
other childhood illness; therefore performing a tourniquet test with
FBC at first encounter would be useful to differentiate dengue from
other illness.
Rapid test
Non structural protein-1 (NS1 antigen)
•Present in high concentrations during early phase of the disease
•Detection drops from day 4-5 of illness
During viraemic phase (febrile phase) of dengue, NS1 Ag test will
be positive.
HCT or PCV
HCT
May be Increased
-A hematocrit level increase greater than 20% is a sign of
hemoconcentration and precedes shock.

May be decreased
-Suspect occult bleeding when HCT is inappropriately low for
clinical condition of pt
-Most common site of major bleeding is the GIT
WCC:Leukopenia near the end of the febrile phase of illness.

PLT
Low due to immune mediated platelet destruction
(The half-life of platelets are decreased)
BUSE
Hyponatremia is the most common electrolyte abnormality in
patients with dengue hemorrhagic fever or dengue shock
syndrome.

Liver function test

Mildly elevated AST and ALT in patients with dengue hemorrhagic
fever who have acute hepatitis.
PT/APTT
Worse in the critical phase
Due to loss of essential coagulation proteins due to plasma
leakage.

ABG
To assess pH, oxygenation, and ventilation.
Metabolic acidosis is observed in those with shock due to tissue
hypoperfusion.
Dengue Serology
Serodiagnosis is made based on a rise in antibody titer in paired
specimens obtained during the acute stage and during
convalescence.

•ELISA method : Ig M and Ig G

•Ig M only positive after 5 days – 30 to 90 days
•Ig G appear later, can be higher in secondary infection
Others

Cultures of blood, urine, CSF: to exclude or confirm other potential

causes of the patient's condition.

GSH: Typing and crossmatching of blood should be performed in

cases of severe dengue hemorrhagic fever or dengue shock
syndrome.
Imaging
CXR: to look for pleural effusions and bronchopneumonia.

CT brain: may be indicated in patients with altered level of

consciousness, to detect intracranial bleeding or cerebral
edema from dengue hemorrhagic fever.
 Management Of Patients With Dengue
• Complex & unpredictable disease

• Timing of intervention starts at frontline healthcare personnel (A&E/ OPD/ health clinics)

• Early recognition of disease & careful monitoring of IV fluid is important right from beginning.

• Familiarize with the THREE main well demarcated phases of dengue: febrile, critical; & recovery

• Recognize dengue when child presents with fever; all we need is TO GO through the PROBABLE CASE DEFINITION OF
DENGUE. You DO NOT NEED rapid test always to diagnose dengue.

• In early phase of disease, difficult to differentiate dengue with other childhood illness; therefore performing a tourniquet
test with FBC at first encounter would be useful to differentiate dengue from other illness.

• Temporal relationship of fever cessation (defervescence) is important as in DENGUE (unlike other viral illness) manifest its
severity (leakage/ shock) when temperature seems to have declined.

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian hospitals(4th ed.). Kuala Lumpur: Ministry Of Health Malaysia.
First Encounter
Priorities during first encounter:

1 - Establish whether patient has dengue

2 - Determine phase of illness

3 - Recognise warning signs and/or the presence of severe dengue if present.

Most patients with Dengue Fever without warning signs can be managed without hospitalization provided they are

● alert,

● there are no warning signs

● or evidence of abnormal bleeding,

● their oral intake and urine output are satisfactory,

● and the caregiver is educated regarding fever control and avoiding non-steroidal anti-inflammatory agents
and is familiar with the course of illness.

• A dengue information/home care card that emphasizes danger/warning signs is important. This should be given to
parents/guardian if child is not admitted.

• These patients need daily clinical and/or laboratory assessment by trained doctors or nurses until the danger period has
passed
Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian hospitals(4th ed.). Kuala Lumpur: Ministry Of
Health Malaysia.
Hospitalisation
● If dengue is suspected or confirmed, disease notification is mandatory.

● Indication for Hospitalisation

• Warning signs.

• Infants.

• Co-morbid factors (diabetes, renal failure, immune-compromised state, hemoglobinopathies

and obesity).

• Social factors - living far from health facilities, transport issues.

● The THREE major priorities of managing hospitalized patient with dengue in the critical phase
are:

A - Replacement of plasma losses.

B - Early recognition and treatment of hemorrhage.

C - Prevention of fluid overload. Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian
hospitals(4th ed.). Kuala Lumpur: Ministry Of Health Malaysia.
 Fluid Therapy

• In dengue shock has two parts:

● initial, rapid fluid boluses to reverse shock

● followed by titrated fluid volumes to match ongoing losses.

• However, for a patient who has warning signs of plasma leakage but is not yet in shock, the initial fluid
boluses may not be necessary.

• Fluids in dengue MUST be managed in way that it is given ONLY when it’s needed and off when patient
enter convalescent/recovery phase.

• Haemodynamic state should be used as MAIN driver of IVF therapy. HCT as guide. Not the other way
around.

• Limit fluid in febrile phase. If IVF is needed to correct hydration USE only isotonic solutions (example
NS).

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian hospitals(4th ed.). Kuala Lumpur: Ministry Of Health
Malaysia.
Severe Dengue And
Compensated Shock

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for
Malaysian hospitals(4th ed.). Kuala Lumpur: Ministry Of Health Malaysia.
Severe Dengue And
Hypotension

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian hospitals(4th
ed.). Kuala Lumpur: Ministry Of Health Malaysia.
Severe Dengue And Refractory Shock
(Late Presenters)

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian
hospitals(4th ed.). Kuala Lumpur: Ministry Of Health Malaysia.
Dengue With
Warning Signs

Ismail, H. I. H. M., Ng, H. P., &

Thomas, T. (2019). Paediatric
protocols for Malaysian hospitals(4th
ed.). Kuala Lumpur: Ministry Of
Health Malaysia.
Refractory Dengue
Shock

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019).

Paediatric protocols for Malaysian hospitals(4th
ed.). Kuala Lumpur: Ministry Of Health Malaysia.
Guidelines For Reversing Dengue Shock While Minimizing
Fluid Overload
Severe dengue with compensated shock:
● Stabilize airway and breathing,
● obtain baseline Hct level
● initiate fluid resuscitation with NS/RL at 10-20 mL/kg over 1 hr, and insert urine catheter early.

Severe dengue with hypotension:

● Stabilize airway and breathing,
● Obtain baseline Hct level,
● Initiate fluid resuscitation with 1-2 boluses of 20 mL/kg NS/RL or synthetic colloid over 15-30 mins until pulse is palpable,
● Slow down fluid rates when hemodynamics improve, and repeat second bolus of 10 mL/kg colloid if shock persists and Hct level
is still high.
● Synthetic colloids may limit the severity of fluid overload in severe shock.

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian hospitals(4th ed.). Kuala Lumpur: Ministry Of Health Malaysia.
Guidelines For
Reversing Dengue
Shock While
Minimizing Fluid
Overload

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric

protocols for Malaysian hospitals(4th ed.). Kuala Lumpur:
Ministry Of Health Malaysia.
Goals For Rapid Fluid Boluses:

● Improvement in systolic BP, widening of pulse pressure,

● Extremity perfusion and the appearance of urine,
● Normalization of elevated Hct level.
● If baseline Hct level is low or “normal” in presence of shock, hemorrhage likely to have worsened shock, transfuse
fresh WB or fresh PRBCs early.
● After rapid fluid boluses, continue isotonic fluid titration to match ongoing plasma leakage for 24–48 hrs;
● if patient not vomiting and is alert after shock, correction with oral rehydration fluids may suffice to match ongoing
losses.
● Check Hct level 2-4 hourly for first 6 hrs and decrease frequency as patient improves.

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian hospitals(4th ed.). Kuala Lumpur: Ministry Of Health Malaysia.
Goals For Ongoing Fluid Titration:
● Stable vital signs,
● Serial Hct measurement showing gradual normalization
● Low normal hourly urine output are the most objective goals indicating adequate circulating volume; adjust fluid rate
downward when this is achieved.
● Plasma leakage is intermittent even during the first 24 hrs after the onset of shock; hence, fluid requirements are
dynamic.
● Targeting a minimally acceptable hourly urine output (0.5-1 mL/kg/hr) is an effective and inexpensive monitoring
modality that can signal shock correction and minimize fluid overload.
● A urine output of 1.5–2 mL/kg/hr should prompt reduction in fluid infusion rates, provided hyperglycemia has been
ruled out.
● Separate maintenance fluids are not usually required; glucose and potassium may be administered separately only if
low.
● Hypotonic fluids can cause fluid overload; also, avoid glucose-containing fluids, such as 1/2Glucose Normal Saline
(GNS or I/2 GNS): the resultant hyperglycemia can cause osmotic diuresis and delay correction of hypovolemia.
Tight glucose monitoring is recommended to avoid hyper/hypoglycemia.
Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian hospitals(4th ed.). Kuala Lumpur: Ministry Of Health Malaysia.
Discharge of Children with Dengue
Patients who are resuscitated from shock rapidly recover. Patients with dengue hemorrhagic fever or dengue shock
syndrome may be discharged from the hospital when they meet the following criteria:

■ Afebrile for 24 hours without antipyretics.

■ Good appetite, clinically improved condition.

■ Adequate urine output.

■ Stable hematocrit level.

■ At least 48 hours since recovery from shock.

■ No respiratory distress.

■ Platelet count greater than 50,000 cells/μL.

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric
protocols for Malaysian hospitals(4th ed.). Kuala Lumpur:
Ministry Of Health Malaysia.
Home Care Card For Dengue Patients
(Please Take This Card To Your Health Facility For Each Visit)

What should be done?

● Adequate bed rest.

● Adequate fluid intake: >5 glasses for average-sized adults or accordingly in children.
● Milk, fruit juice (caution with diabetes patient) and
● Isotonic electrolyte solution (ORS) and barley/rice water.
● Plain water alone may cause electrolyte imbalance.
● Take Paracetamol (not more than 4 grams per day for adults and 15mg/kg/dose 4-6 hourly in children).
● Tepid sponging.
● Look for mosquito breeding places in and around the home and eliminate them.

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian hospitals(4th ed.). Kuala Lumpur: Ministry Of Health Malaysia.
What should be avoided?
● Do not take acetylsalicylic acid (Aspirin), mefenamic acid (Ponstan), ibuprofen or other non-steroidal anti-inflammatory agents
(NSAIDs), or steroids. If you are already taking these medications please consult your doctor.
● Antibiotics are not necessary.
● If any of following is observed, take the patient immediately to the nearest hospital. These are warning signs for danger:
○ Bleeding:
● Red spots or patches on the skin
● Bleeding from nose or gum,
● vomiting blood
● black-colored stools;
● heavy menstruation/vaginal bleeding.
○ Frequent vomiting
○ Severe abdominal pain.
○ Drowsiness, mental confusion or seizures.
○ Pale, cold or clammy hands and feet.
○ Difficulty in breathing.

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian hospitals(4th ed.). Kuala Lumpur: Ministry Of Health Malaysia.
Home Care Card

Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian
hospitals(4th ed.). Kuala Lumpur: Ministry Of Health Malaysia.
References
1. Ismail, H. I. H. M., Ng, H. P., & Thomas, T. (2019). Paediatric protocols for Malaysian hospitals(4th ed.). Kuala
Lumpur: Ministry Of Health Malaysia.
2. A1.mayomedicallaboratories.com. (2019). Complete Blood Count Normal Pediatric Values. [online]
Availableat:http://a1.mayomedicallaboratories.com/webjc/attachments/110/30a2131-complete-blood-count-normal-p
ediatric-values.pdf
3. Bronze, M. and Smith, D. (2019). Dengue Workup: Approach Considerations, Complete Blood Cell Count, Metabolic
Panel and Liver Enzymes. [online] Emedicine.medscape.com. Available at:
https://emedicine.medscape.com/article/215840-workup
4. Cdc.gov. (2019). Bleeding Manifestations in Patients with Dengue. [online] Available at:
https://www.cdc.gov/dengue/training/cme/ccm/Bleeding%20Manifestations_F.pdf
5. Cdc.gov. (2019). Differentiating dengue from other febrile acute illnesses [online] Available at:
file:///C:/Users/User/Desktop/Differentiating%20Dengue%20AFI.pdf