Case Discussion: Dengue

A DEFINITION:
Dengue fever- is a benign syndrome caused by several arthropod-borne
viruses.

- Characterized by biphasic fever, myalgia or arthralgia, rash,

leukopenia and lymphadenopathy.

Dengue hemorrhagic fever (Philippines, Thai or Singapore hemorrhagic fever;

hemorrhagic dengue; acute infectious thrombocytopenic purpura)

- Severe form, often fatal, febrile disease caused by 1 of 4

dengue viruses.
- Characterized by capillary permeability, abnormalities of
hemostasis, in severe cases, a protein-losing shock syndrome
(dengue shock syndrome)

Phases of Dengue:
B ETIOLOGY:
Aedes aegypti- daytime biting mosquito.
- principal vector, it has the 4 antigenic serotype of
dengue viruses (dengue serotype 1, 2, 3 and 4).
DENGUE VIRUS SEROTYPE 2 is the most common
infecting serotype.

C DIAGNOSIS:
A clinical diagnosis of dengue fever derives from a high index of
suspicion and knowledge of the geographic distribution and
environmental cycles of causal viruses.
Serologic Test:

Virologic diagnosis can be established by serologic tests by:

detection of viral proteins or viral RNA
isolation of the virus from blood leukocytes or acute-phase
serum

Following primary and secondary dengue infections, there is a

transient appearance of antidengue (immunoglobulin [Ig] M)
antibodies (disappear after 6-12 wk, a feature that can be used to
time a dengue infection). In secondary dengue infections most
antibody is of the IgG class.
Serologic diagnosis depends on a 4-fold or greater increase in IgG
antibody titer in paired sera by:
hemagglutination inhibition
complement fixation
enzyme immunoassay
neutralization test

IgM and IgG capture enzyme commercial immunoassays

- widely used to identify acute-phase antibodies from
patients with primary or secondary dengue infections in
single-serum samples.

Virus can be recovered from acute-phase serum after inoculating tissue

culture or living mosquitoes. Viral RNA can be detected in blood or
tissues by specific complementary RNA probes or amplified first by
polymerase chain reaction or by real-time polymerase chain reaction.
 A viral nonstructural protein (NS1)
- released by infected cells into the circulation and can be
detected in acute-stage blood samples using
monoclonal or polyclonal antibodies
- detection of NS1 is the basis of commercial tests
including rapid lateral flow tests
- RELIABLE POINT OF CARE DIAGNOSIS OF ACUTE
DENGUE INFECTION
 D PATHOPHYSIOLOGY

Bite of a virus carrying

Precipitating Predisposing
mosquito Factors:
Factors:
Aedes Aegypti Age, Heredity, Sex, Age

Mosquito injects fluid into

patients skin

Virus enters into the hosts blood

Platelet will provide a
stream
shield for the virus from
exposure and binding to
neutralize pre-existing Infects cells and replicate in sufficient
antibody amount

Initiates an immune response

Activation of memory T-cell

Macrophages or monocytes
engulfed the virus having the
platelet (phagocytosis)
response during re-exposure Stimulates release
---
of cytokines
Virus- anti body complex High fever, body
(Binding of ab-virus) weakness, headache and
dizziness

AB- enhance uptake

Cytokines destroy cell

Cytolysis membrane and cell wall (viral
antigens found in
monocytes)

Complement system
activation
Coagulopat Thrombocytopen Vasculopathy
hy ia (plasma Vascular endothelial
(PT/APTT) (< 100x109/L) leakage) activation

Fluid shifting ICF to Management:

ECF Promote bedrest
Medication
Rapid replacement of body
fluids
Blood transfusion
E CLINICAL MANIFESTATION Precautions
Dengue Case Classification and Level of Severity
Dengue without warning
Dengue with Warning signs Severe Dengue
signs/ Probable Dengue
Severe plasma leakage
Live in /travel to dengue leading to:
endemic area. Shock (DSS)
Abdominal pain or
Fever and 2 of the following Fluid accumulation with
tenderness
criteria: respiratory
Persistent vomiting
Nausea, vomiting distress
Clinical fluid accumulation
Rash Severe bleeding
Mucosal bleed
Aches and pains as evaluated by clinician
Lethargy, restlessness
Tourniquet test positive Severe organ involvement
Liver enlargment >2 cm
Leukopenia Liver: AST or ALT >=1000
Any warning sign CNS: Impaired
consciousness
Heart and other organs

For a disease that is complex in its manifestations, management is relatively simple,

inexpensive and very effective in saving lives so long as correct and timely interventions are
instituted. The key is early recognition and understanding of the clinical problems during the
different phases of the disease, leading to a rational approach to case management and a
good clinical outcome.

Febrile phase
Patients typically develop high-grade fever suddenly. This acute febrile phase usually
lasts 27 days and is often accompanied by facial flushing, skin erythema, generalized body
ache, myalgia, arthralgia and headache. Some patients may have sore throat, injected
pharynx and conjunctival injection. Anorexia, nausea and vomiting are common. It can be
difficult to distinguish dengue clinically from non-dengue febrile diseases in the early febrile
phase. A positive tourniquet test in this phase increases the probability of dengue.

Mild haemorrhagic manifestations like petechiae and mucosal membrane bleeding (e.g. nose
and gums) may be seen. Massive vaginal bleeding (in women of childbearing age) and
gastrointestinal bleeding may occur during this phase but is not common. The liver is often
enlarged and tender after a few days of fever. The earliest abnormality in the full blood
count is a progressive decrease in total white cell count, which should alert the physician to
a high probability of dengue.
Critical phase
Around the time of defervescence, when the temperature drops to 37.538oC or less
and remains below this level, usually on days 37 of illness, an increase in capillary
permeability in parallel with increasing haematocrit levels may occur. This marks the
beginning of the critical phase. The period of clinically significant plasma leakage usually
lasts 2448 hours.
Progressive leukopenia followed by a rapid decrease in platelet count usually
precedes plasma leakage. At this point patients without an increase in capillary permeability
will improve, while those with increased capillary permeability may become worse as a
result of lost plasma volume. The degree of plasma leakage varies. Pleural effusion and
ascites may be clinically detectable depending on the degree of plasma leakage and the
volume of fluid therapy.
Shock occurs when a critical volume of plasma is lost through leakage. It is often
preceded by warning signs. The body temperature may be subnormal when shock occurs. In
addition, severe organ impairment such as severe hepatitis, encephalitis or myocarditis
and/or severe bleeding may also develop without obvious plasma leakage or shock.

Recovery Phase
If the patient survives the 2448 hour critical phase, a gradual reabsorption of
extravascular compartment fluid takes place in the following 4872 hours. General well-
being improves, appetite returns, gastrointestinal symptoms abate, haemodynamic status
stabilizes and diuresis ensues. Some patients may have a rash of isles of white in the sea of
red. Some may experience generalized pruritus. Bradycardia and electrocardiographic
changes are common during this stage.

Severe dengue
Severe dengue is defined by one or more of the following: (i) plasma leakage that
may lead to shock (dengue shock) and/or fluid accumulation, with or without respiratory
distress, and/or (ii) severe bleeding, and/or (iii) severe organ impairment.
It usually takes place around defervescence, usually on day 4 or 5 (range days 37)
of illness, preceded by the warning signs.
Severe dengue should be considered if the patient is from an area of dengue risk
presenting with fever of 27 days plus any of the following features:
There is evidence of plasma leakage, such as:
high or progressively rising haematocrit;
pleural effusions or ascites;
 circulatory compromise or shock (tachycardia, cold and clammy extremities,
capillary refill time greater than three seconds, weak or undetectable pulse, narrow pulse
pressure or, in late shock, unrecordable blood pressure).
There is significant bleeding.
There is an altered level of consciousness (lethargy or restlessness, coma,
convulsions).
There is severe gastrointestinal involvement (persistent vomiting, increasing or
intense abdominal pain, jaundice).
There is severe organ impairment (acute liver failure, acute renal failure,
encephalopathy or encephalitis, or other unusual manifestations, cardiomyopathy) or
other unusual manifestations.
 F MANAGEMENT

GROUP A - Patients who may be sent home.

These are patients who are able to tolerate adequate volumes of oral fluids and pass
urine at least once every 6 hours, and do not have any warning signs, particularly when
fever subsides.

Ambulatory patients should be reviewed daily for disease progression: decreasing

WBC, defervescence and warning signs until they are out of the critical period. Those with
stable hematocrit can be sent home with the advice to return immediately to the hospital if
they develop any of the warning signs.

In patients with dengue without warning signs and not admitted Oral Rehydration Solution
should be given as follows based on weight using currently recommended ORS

Calculation of Oral Rehydration Fluids Using Weight (Ludan Method)

Body Weight (kg) ORS to be given

>3 10 100 ml/kg/day
>10 20 75 ml/kg/day
>20 - 30 50 60 ml/kg/day
>30 - 60 40 50 ml/kg/day

Reduce osmolarity of ORS containing sodium 50 to 75 mmol/liter.

Sports drinks should NOT be given due to its high osmolarity which may cause more
danger to the patient.

GROUP B Patients who should be referred for in hospital management

These include patients with any of the following features:

Warning signs
Co-existing conditions that may make dengue or its management more complicated,
such as pregnancy, infancy and old age, obesity, diabetes mellitus, renal failure,
chronic hemolytic diseases, etc.
Social circumstances such as living alone or living far from health facility or without a
reliable means of transport.

Management of Dengue without Warning Signs

Encourage oral fluids.

If not tolerated,
TFR = Maintenance IVF + Fluids as for Mild
start dehydration* intravenous
fluid therapy of 0.9% NaCl (saline) or Ringers Lactate with or without dextrose at
4 mL/kg/h for first 10 kg body weight
maintenance rate;
+ 2 mL/kg/h for next 10 kg body weight

+ 1 mL/kg/h for subsequent kg body weight

Patients may be able to take oral fluids after a few hours of intravenous fluid therapy.

Fluid management for patients who are admitted, without shock (Dengue without
Warning Signs):

Isotonic solutions (D5 LRS, D5 Acetated Ringers D5 NSS/D5 0.9 NaCl) are appropriate for
Dengue patients without warning signs who are admitted without shock.

Maintenance IVF is computed using the caloric expenditure method (Holliday-Segar

Method) or calculation Based on Weight (Ludan Method).

Calculation of Maintenance Fluid (Holiday and Segar Method)

Body weight Total Fluid requirement (ml/day)

(kg)
3 10 (kg) 100ml/kg
>10 20 (kg) 1000ml + 50ml/kg for each kg > 10 kg
>20 (kg) 1500ml + 20ml/kg for each kg > 20kg

If the patient shows signs of mild dehydration but is NOT in shock, the volume
needed for mild dehydration is added to the maintenance fluids to determine the
total fluid requirement (TFR).

The following formula may be used to calculate the required volume of intravenous
fluid to infuse:
*where the volume of fluids for mild dehydration is computed as follows:

Infant 50 mL/kg

Other Child or Adult 30 mL/kg

One-half of the computed TFR is given in 8 hours and the remaining one-half is
given in the next 16 hours

Monitor

Temperature pattern
Volume of fluid intake and losses
Urine output volume and frequency
Warning signs
Hematocrit, white blood cell and platelet counts

MANAGEMENT DENGUE WITH WARNING SIGNS

Obtain a reference CBC and HGT before fluid therapy

Give only isotonic solutions such as 0.9% NaCl (Saline) or Ringers Lactate with or without
glucose.

For infants < 6 months old D5 0.45 NaCl is preferable if available (D5 0.45 NaCl can be
prepared by mixing equal volumes of D5 0.9 NaCl and D5W

May give glucose containing IVF (D5) in the following conditions:

- HGT <80mg/dl
- If HGT is not available and patient is unable to eat and is weak looking

Maintenance IVF is computed using the caloric expenditure method (Holiday and Segar
Method) or Calculation based on weight (Ludan Method).

Calculation of Maintenance Fluid (Holiday and Segar Method)

Body weight Total Fluid requirement (ml/day)

 (kg)
3 10 (kg) 100ml/kg
>10 20 (kg) 1000ml + 50ml/kg for each kg > 10 kg
>20 (kg) 1500ml + 20ml/kg for each kg > 20kg

Rate of infusion is as follows

- Start with 5 -7 ml/kg/hour for 1 2 hours then

- Reduce to 3 5 ml/kg/hour for 2 4 hours and then
- Reduce to 2 3 ml/kg/hour or less according to clinical response

Reassess the clinical status and repeat the complete blood count

If the hematocrit remains the same or rises only minimally, continue with the same rate (2-3
ml/kg/hour) for another 2 4 hours.

If there are worsening of vital signs and rapidly rising hematocrit, increase the rate to 5
10ml/kg/hour for 1 2 hours.

1. Reassess clinical status, repeat hematocrit and review fluid infusion rates accordingly
2. Give the minimum intravenous fluid volume required to maintain good perfusion and
urine output of about 0.5ml/kg/hour. Intravenous fluids are usually needed only for 24
48 hours.
3. Reduce IV fluids gradually when the rate of plasma leakage decreases towards the
end of the critical phase which is indicated by ;
o Urine output and/or oral fluid intake is/are adequate or
o HCT decreases below the baseline value in stable patient

MONITOR

Vital signs and peripheral perfusion (1-4 hourly until the patient is out of
critical phase)
Urine output (4-6 hourly)
Hematocrit (before and after fluid replacement, then 6-12 hourly)
Blood glucose
Other organ functions (such as renal profile, liver profile, coagulation profile,
as indicated)
GROUP C PATIENTS WITH SEVERE DENGUE REQUIRING EMERGENCY
TREATMENT AND URGENT REFERRAL - LMANAGEMENT FOR PATIENTS
ADMITTED TO THE HOSPITAL WITH COMPENSATED SHOCK
FLUID MANAGEMENT FOR PATIENTS ADMITTED TO THE HOSPITAL WITH
HYPOTENSIVE SHOCK
Reference

WHO: DENGUE GUIDELINES FOR DIAGNOSIS, TREATMENT, PREVENTION AND

CONTROL, New Edition 2009

Nelson Text book of Pediatrics 19th Edition

Philippine Pediatric Society Dengue Module: Revised Guidelines on fluid

Management of Dengue Fever and Dengue Hemorrhagic Fever 2012