A.Y. 2021-2022 (1ST Semester)
Dengue
Dr. Endymion Tan and Dr. Mary Carmelle Coronel
LECTURE OUTLINE
I.
Overview of Dengue
A. Epidemiology
B. Etiology & Transmission
C. Pathophysiology
II. Differential Diagnoses
III. Dengue Case Classification
IV. Clinical Course & Presentation of Dengue
V. Laboratory Diagnosis
VI. Clinical Management of Patients with Dengue
A. Out-Patient Management
B. In-Patient Management
C. Treatment of Hemorrhagic Complications
D. Discharge Criteria
VII. Prevention and Vaccination
VIII. References
LEGEND
PPT
LECTURE
BOOK
OTHER TRANS
REMEMBER
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OVERVIEW OF DENGUE
I.
EPIDEMIOLOGY
III. PATHOPHYSIOLOGY
 Most important arbovirus among humans
 DENV imposes a substantial burden to communities and health
systems in most tropical and subtropical countries
 Dengue is a major public health problem in the Philippines and is
endemic in all regions of the country
 Most episodes occurring during the wet season (June–February)
II.
ETIOLOGY AND TRANSMISSION
 Dengue is caused by a virus of the Flaviviridae family
 Primary and secondary vectors in the Philippines:
o Aedes aegypti (lifespan: 15-65 days; average of 21 days)
o Aedes albopictus
 Four distinct but closely related serotypes: DENV 1, DENV-2.
DENV-3, DENV-4
o Infection with one dengue serotype confers lifelong
homotypic immunity and a brief period of partial heterotypic
immunity (2 years)
o But each individual can eventually be infected by all 4 serotypes.
 Transmitted by the bite of an infected female mosquito
o Both males and females require nectar for energy
o Females require a blood meal as a source of appropriate protein
for egg development (daytime feeders)
o Mosquitoes acquire the virus when they feed on a carrier of
the virus and can transmit dengue if it immediately bites
another host
o The virus does not adversely affect the mosquito and remains
infected for the remainder of its life.
 Humans serve as the primary reservoir for dengue
o Persons with DENV in their blood can transmit the viruses to
the mosquito 1 day before the onset of the febrile period.
o The patient usually remains infectious for the subsequent 4-5
days (up to 12 days)
 Transmission occurs after 8-12 days of viral replication in the
mosquito's salivary glands (extrinsic incubation period). ‘
 Dengue has an incubation period of 3-14 days (average 4-7 days)
while viral replication takes place in target dendritic cells
 Vertical transmission is common among mothers who are viraemic at
delivery and breastfeeding
Viral Structural Proteins:
Proteins
Functions
Capsid (C)
o Encapsidates the genome that is then
surrounded by a lipid bilayer membrane
o Binds cellular receptors to enable virus entry into
Envelope (E)
susceptible cells
o Contains the epitopes crucial for neutralisation
by antibodies that develop following infection
Non-Structural
o Form the replication complex that amplifies the
(NS1-5)
viral genome
o Necessary for successful virus replication.
 Infected monocytes induce the production of interferon-a (IFN-a) and IFN-b
Proposed Dengue Immunopathogenesis:
A. ANTIBODY-DEPENDENT ENHANCEMENT
 DENV serotypes 1–4 share a sizeable proportion of their structural antigens
that, following infection with one DENV, induce antibodies that are typespecific, as well as cross-reactive with other DENVs.
 Upon infection with any DENV, the adaptive immune response that develops
provides long-term immunity to the homologous virus, but protection against
heterologous DENVs is short-lived
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 Cross-reactive antibodies or sub-neutralising concentrations of
antibodies bind heterologous DENV to facilitate virus entry through Fc
receptors expressed on target cells, such as monocytes,
macrophages, and dendritic cells.
 Virus-host interaction during ADE also enables the virus to evade host
antiviral and immune responses that would otherwise limit infection
 ADE thus results in a greater burden of infection that induces
imbalanced pro-inflammatory and anti-inflammatory responses, which
are thought to induce capillary endothelial pathology and vascular
leakage, potentially leading to dengue shock syndrome
DIFFERENTIAL DIAGNOSES
1.
Influenza-like syndromes: influenza, adenovirus, SARS, measles,
chikungunya, infectious mononucleosis, and HIV
a. Mimics febrile phase of dengue
b. Influenza: cough, rhinitis and nasal congestion is always present
c. Adenovirus: rhinitis, pharyngitis, cough and other respiratory
symptoms are present
d. Chikungunya: symmetric arthritis of small joints; less frequent
bleeding and thrombocytopenia
2. Malaria and typhoid: splenomegaly and prolonged fever
3. Infectious hepatitis: hepatomegaly and elevated LFTs
4. Exanthems: measles and rubella, erythema infectiosum
(Parvovirus B19). herpes virus 6, enteroviruses, infectious
mononucleosis, scarlet fever, and Kawasaki disease
5. Sepsis and meningococcal disease
6. Leptospirosis: jaundice and pulmonary hemorrhage
7. Systemic autoimmune diseases: SLE, HSP, TTP
8. Acute leukemia
9. Acute appendicitis: acute abdominal pain w/ right illiac fossa
tenderness and rebound tenderness
10. Other medical emergencies mimicking abdominal pain of
dengue: acute cholecystitis, diabetic ketoacidosis, renal failure and
lactic acidosis
11. Other arboviral diseases: yellow fever, Hantavirus pulmonary
syndrome, Lassa fever, Ebola fever and Marburg fever
Case Definition for Dengue with Warning Signs
o Lives in or travels to dengue-endemic area, with fever lasting for 2-7 days,
plus any of the following:
- Abdominal pain or tenderness
- Persistent vomiting
- Clinical signs of fluid accumulation
- Mucosal bleeding
- Lethargy, restlessness
- Liver enlargement
- Laboratory: increase in Hct and/or decreasing platelet count
o Confirmed dengue:
- Viral culture isolation
- PCR
Case Definition for Severe Dengue
o Lives in or travels to a dengue-endemic area with fever of 2-7 days and
any of the above clinical manifestations for dengue with or without
warning signs, plus any of the following:
- Severe plasma leakage, leading to:
a. Shock
b. Fluid accumulation with respiratory distress
o Severe bleeding
o Severe organ impairment
- Liver: AST or ALT >1000
- CNS: e.g., seizures, impaired consciousness
- Heart: e.g., myocarditis
- Kidneys e.g., renal failure
Note: Above manifestations and/or laboratory parameters require strict
observation, monitoring, and appropriate medical intervention.
CLINICAL COURSE AND PRESENTATION
I.
CLINICAL COURSE
 Dengue infection is a systemic and dynamic disease. It has a wide clinical
spectrum that includes severe and non-severe forms of clinical
manifestations
 After the incubation period, the illness begins abruptly and will be followed
by 3 phases: febrile, critical and recovery phase.
“A differentiating feature of an acute surgical abdomen and the severe
"abdominal pain of dengue shock is that the abdomen in dengue shock
is soft and the pain subsides with fluid resuscitation.”
NEW DENGUE CASE CLASSIFICATION
A. FEBRILE PHASE
Revised Dengue Clinical Case Management Guidelines 2011
Case Definition for Dengue without Warning Signs
o Probable dengue:
Lives in or travels to dengue-endemic area, with fever, plus any two of
the following:
- Headache
- Body malaise
- Myalgia
- Arthralgia
- Retro-orbital pain
- Anorexia
- Nausea
- Vomiting
- Diarrhea
- Flushed skin
- Rash (petechial, Hermann’s sign) AND
- Laboratory test, at least CBC (leucopenia with or without
thrombocytopenia) and/or dengue NS1 antigen test or dengue IgM
antibody test (optional)
o Confirmed dengue:
- Viral culture isolation
- PCR
 The acute febrile phase usually lasts 2-7 days
 Monitoring for warning signs is crucial to recognize its progression to the
critical phase.
 Mild hemorrhagic manifestations like petechiae and mucosal membrane
bleeding (e.g., nose and gums) may be seen.
 The earliest abnormality in the full blood count is a progressive leukopenia
which should alert the physician to a high probability of dengue
 Clinical Signs and Symptoms:
1. Fever
7. Anorexia
2. Headache
8. Vomiting
3. Body malaise
9. Diarrhea
4. Myalgia
10. Flushed skin
5. Arthralgia
11. Rash (petechial, Hermann’s sign)
6. Retro-orbital pain
 Laboratory test, at least CBC (leucopenia with or without thrombocytopenia)
and/or dengue NS1 antigen test or dengue IgM antibody test (optional)
 With the onset of fever patients may suffer an acute and progressive loss in
their ability to perform their daily functions such as schooling, work and
interpersonal relations
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II.
DENGUE SHOCK SYNDROME
 Dengue shock syndrome (DSS) is a form of hypovolaemic shock and results
from continued vascular permeability and plasma leakage
 This usually takes place around defervescence, i.e. on days 4−5 of illness
(range of days 3−8), and is often preceded by warning signs
 Patient is considered to have compensated shock if:
o Systolic pressure is maintained at the normal or slightly above normal
range but the pulse pressure is ≤ 20 mmHg (e.g. 100/85 mmHg)
o Signs of poor capillary perfusion (cold extremities, delayed capillary refill,
or tachycardia)
 Compensated metabolic acidosis is observed when the pH is normal with low
carbon dioxide tension and a low bicarbonate level.
LABORATORY DIAGNOSIS
B. CRITICAL PHASE
 During the transition from the febrile to afebrile phase, patients without
an increase in capillary permeability will improve without going through
the critical phase.
 Defervescence occurs on day 3-7 of illness, when the temperature drops
to 37.5-38°C or less and remains below this level.
 Around the time of defervescence, patients can either improve or
deteriorate
o Those who improve after defervescence have Dengue without
Warning Signs.
o Those who deteriorate will manifest warning signs have Dengue
with Warning Signs.
 Warning signs are the result of a significant increase in capillary fragility.
(marks the beginning of the critical phase)
 Some of these patients may further deteriorate to severe dengue with
severe plasma leakage leading to shock (dengue shock) ± respiratory
distress, severe bleeding and/or severe organ impairment
 Period of clinically significant plasma leakage usually lasts 24-48 hours.
o
o
o
o
o
o
o
 Objectives of dengue laboratory diagnosis:
o To confirm the clinical diagnosis and
o To provide information for epidemiological surveillance
 Laboratory diagnosis is not necessary for clinical management except in
atypical cases or when carrying out differential diagnosis with other
infectious diseases.
 Laboratory diagnosis of dengue is made by:
o Detecting the virus and/or any of its components (infective virus, virus
genome, dengue antigen)
o Investigating the serological responses present after infection
(specifically IgM and IgG levels)
 The four dengue viruses (DEN-[1–4]) are serologically related but antigenically
and genetically distinctive
3 Main aspects should be considered for an adequate dengue diagnosis:
1. Virological and serological markers in relation to the time of dengue
infection
2. Type of diagnostic method in relation to clinical illness
3. Characteristics of the clinical samples.
I. VIROLOGICAL AND SEROLOGICAL MARKERS IN RELATION TO
TIME OF DENGUE INFECTION
 During incubation period (4-10 days), virus replicates and an antibody
response is developed.
o Viraemia is detectable in most dengue cases at the same time that
symptoms appear, and is no longer detectable at the time of
defervescence
o Development of IgM antibody is coincident with the disappearance of
fever and viraemia
Warning Signs
Abdominal pain or tenderness
Persistent vomiting
Clinical signs of fluid accumulation
Mucosal bleeding or bleeding of venepuncture sites
Lethargy; restlessness
Liver enlargement and tenderness
Laboratory: Increase in hematocrit and/or leukopenia (≤ 5000
cells/mm3 ); progressive thrombocytopenia (100 000 cells/mm3)
 Some patients may deteriorate to Severe Dengue, defined by one
or more of the following:
a. plasma leakage that may lead to shock (dengue shock) and/or
fluid accumulation, with or without respiratory distress, and/or
b. severe bleeding (decrease in Hct and increase total white cell
count) and/or
c. severe organ impairment (hepatitis, encephalitis or myocarditis
and/or severe bleeding)
 Shock occurs when a critical volume of plasma is lost through leakage
 The body temperature may be subnormal when shock occurs
 Consequent organ hypoperfusion due to shock results in progressive
organ impairment, metabolic acidosis and DIC
C. RECOVERY PHASE
 A gradual re-absorption of extravasated fluid from the intravascular to
the extravascular space (e.g., pleural effusion, ascites) by way of the
lymphatics will take place in the next 48-72 hours.
 Patients’ general wellbeing improves, hemodynamic status stabilizes
and diuresis ensues.
 Classical rash of “isles of white in the sea of red.”
 The hematocrit stabilizes or may be lower due to the dilution effect of
reabsorbed fluid.
 White Blood Count usually starts to rise soon after defervesence but
the normalization of the platelet count is typically later than that of
WBC count.
Clinical Problems Encountered During the Different Phases of Dengue:
Phases
Complications
Febrile
o Dehydration; high fever may cause febrile seizures
in young children; neurological disturbances
Critical
o Shock from the plasma leakage; severe hemorrhage;
organ impairment
Recovery
o Hypervolemia (only if intravenous fluid therapy has
been excessive and/or extended into this period)
 Primary infection: anti-dengue IgM specific antibodies can be detected 3−6
days after fever onset.
o IgM is detected in 50% of cases by days 3–5 after the onset of illness
(this figure increasing to 95–98% for days 6−10)
o Low levels of IgM are still detectable around 1-3 months after fever
o Also characterized by slowly increasing but low levels of dengue-specific
IgG, becoming elevated at days 9−10.
o Low IgG levels persist for decades (indication of a past dengue infection)
 Secondary infection: rapid and higher increase of anti-dengue specific IgG
antibodies and slower and lower levels of IgM
o High IgG levels remain for 30–40 days
o A short-lasting but higher viraemia level characterizes the secondary
infection compared to the primary infection
II.
TYPE OF DENGUE DIAGNOSTIC METHOD IN RELATION TO TIME
OF CLINICAL ILLNESS
 The diagnostic method to confirm an acute infection depends on the time of
clinical illness
o Febrile phase is coincident with the presence of viraemia, some viral
components and replication products in blood
o Critical and convalescent phases coincide with the development of
antibodies
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CLINICAL MANAGEMENT OF DENGUE
Stepwise Approach to the Management of Dengue:
Phase
Febrile
(Day 1-5 of fever)
Critical &
Convalescent
(After 4-5 days of
illness)
Diagnostics
o Isolation by tissue culture mosquitoes 
identifies viral serotype
o RT-PCR and real time RT-PCR confirms
acute dengue infection and allows
serotype identification and quantification of
genome copies
o NS1 Ag- marker of acute dengue infection
detected by ELISA and rapid test kits
o Specific IgM- best marker of recent infection
detected by MAC-ELISA and rapid tests
- Single serum sample collected after day 6
of fever (most useful)
o High levels of specific IgG can also be detected
by ELISA and HIA
o IgM/IgG optical density ratio
- >1.2 (px sera at 1/100 serum dilution) or
1.4 (serum dilution 1/20): primary infection
- >1/1280: secondary infection
 The study of paired sera (acute and convalescent serum samples with
the second sample being collected 15–21 days after the first sample),
allows for serological confirmation of dengue infection.
 The diagnosis depends upon the demonstration of rising titres of dengue
antibodies between acute and convalescent sera
 Broad cross-reactivity with other flaviviruses has been observed.
Step 1: Overall Assessment
o History:
- Date of onset of fever/illness
- Quantity of oral intake
- Assess for warning signs
- Diarrhea
- Seizures, impaired consciousness, behavioral changes
- Urine output (frequency, volume and time of last voiding)
- Other important relevant histories:
a. Family members or neighbors with dengue, or travel to dengueendemic areas
b. Co-existing conditions such as infancy, pregnancy, obesity, diabetes
mellitus, hypertension, etc.
c. Jungle trekking and swimming in waterfall (consider leptospirosis,
typhus malaria)
d. Recent unprotected sexual or drug use behavior (consider acute
HIV seroconversion illness)
o Physical Examination:
- Assess mental state and Glasglow Coma scale (GCS) score
- Assess hydration status
- Assess hemodynamic status
- Look out for tachypnea/acidotic breathing/pleural effusion
- Check for abdominal tenderness/hepatomegaly/ascites
- Examine for rash and bleeding manifestations
- Tourniquet test (repeat if previously negative or if there is no bleeding
manifestation)
o Investigation:
- Full blood count (FBC) should be done at the first visit
- Dengue diagnostic tests
Laboratory tests should be performed to confirm the diagnosis
a. Viral culture isolation or PCR
b. However, it is not necessary for the acute management of patients
except in cases with unusual manifestations
Step 2: Diagnosis, Assessment of Disease Phase and Severity
o Determine:
- Is it dengue?
- Which phase of dengue? (febrile/critical/recovery)
- Are there warning signs?
- What is the hydration and hemodynamic status?
- Does the patient require admission?
Step 3: Management
o Disease notification
o Management decisions – depending on the clinical manifestations and
other circumstances, patients may
- Be sent home (GROUP A); or may
- Be referred for in-hospital management (GROUP B); or may
- Require emergency treatment and urgent referral (GROUP C)
III. LABORATORY CONFIRMATION OF DENGUE
 A diagnosis of dengue infection is confirmed by the:
o Detection of the virus, the viral genome or NS1 Ag, or
o Seroconversion of IgM or IgG (from negative to positive IgM/IgG
or four-fold increase in the specific antibody titre) in paired sera
 A positive IgM serology or a haemagglutinin inhibition test (HIA) antibody
titre of 1280 or higher (or comparable figures by ELISA in a single
specimen), are all diagnostic criteria of a probable dengue infection
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 Watch for warning signs as temperature declines 3 to 8 days after
symptoms began. Return IMMEDIATELY to clinic or emergency
department if any of the following warning signs appear:
o Severe abdominal pain or persistent vomiting
o Red spots/patches on skin
o Bleeding from nose or gums
o Vomiting blood
o Black, tarry stools
o Drowsiness or irritability
o Pale, cold, or clammy skin
o Difficulty breathing
II.
IN-PATIENT MANAGEMENT
A. DENGUE PATIENTS WITH WARNING SIGNS (GROUP B)
Dengue Management DO’s and DON’Ts:
Do’s
o DO tell outpatients when to return. Teach them about warning signs
and their timing, and the critical period that follows defervescence.
o DO recognize the critical period. The critical period begins with
defervescence and lasts for 24–48 hours. During this period, some
patients may rapidly deteriorate.
o DO closely monitor fluid intake and output, vital signs, and
hematocrit levels. Ins and outs should be measured at least every shift
and vitals at least every 4 hours. Hematocrits should be measured every
6–12 hours at minimum during the critical period.
o DO recognize and treat early shock. Early shock (also known as
compensated or normotensive shock) is characterized by narrowing pulse
pressure (systolic minus diastolic BP approaching 20 mmHg), increasing
heart rate, and delayed capillary refill or cool extremities.
o DO administer colloids (such as albumin) for refractory shock.
Patients who do not respond to 2–3 boluses of isotonic saline should be
given colloids instead of more saline.
o DO give PRBCs or whole blood for clinically significant bleeding. If
hematocrit is dropping with unstable vital signs or significant bleeding is
apparent, immediately transfuse blood
Don’ts
o DON’T use corticosteroids. They are not indicated and can increase
the risk of GI bleeding, hyperglycemia, and immunosuppression.
o DON’T give platelet transfusions for a low platelet count. Platelet
transfusions do not decrease the risk of severe bleeding and may
instead lead to fluid overload and prolonged hospitalization.
o DON’T give half normal (0.45%) saline. Half normal saline should not
be given, even as a maintenance fluid, because it leaks into third spaces
and may lead to worsening of ascites and pleural effusions.
o DON’T assume that IV fluids are necessary. First check if the patient
can take fluids orally. Use only the minimum amount of IV fluid to keep
the patient well-perfused. Decrease IV fluid rate as hemodynamic status
improves or urine output increases.
I.
OUT-PATIENT MANAGEMENT (GROUP A)
 GROUP A – Patients who may be sent home
o 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.
Home Care for Dengue
o Adequate bed rest
o Adequate fluid intake (>5 glasses for average-sized adult 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
o Take paracetamol (not more than 4 grams per day for adults and
accordingly in children)
o Tepid sponging
o Look for mosquito breeding in places in and around the home and
eliminate them
o Do not take NSAIDS, e.g. acetylsalicyclic acid (aspirin)/ mefenamic acid
or steroids. If you are already taking these medications, please consult
your doctor.
o Antibiotics are not necessary
 Action Plan: Oral rehydration solution (ORS) should be given 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
o 100 mL/kg/day
>10-20
o 75 mL/kg/day
>20-30
o 50-60 mL/kg/day
>30-60
o 40-50 mL/kg/day
Source: Ludan A. Chapter 41: Pediatric fluid and Electrolyte Therapy. Textbook of Pediatrics and Child Health.
del Mundo F, Estrada FA, Santos-Pcampo PD, Navarro XR, editors. Manila: JMC Press. Fourth Edition. 2000:
1485-1499
 GROUP B – Patients who should be referred for inhospital management
 These include patients with any of the following features:
o Warning signs
o 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.
o Social circumstances such as living alone or living far from health facility or
without a reliable means of transport.
 Action Plan:
o Dengue without Warning Signs
- Encourage oral fluids. If not tolerated, start IV fluid therapy of 0.9%
NaCl (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 fluid therapy.
- Fluid management for patients who are admitted, without shock
(Dengue without Warning Signs):
a. 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.
b. Maintenance IVF is computed using the caloric expenditure
method (Holliday-Segar Method) or calculation Based on Weight
(Ludan Method).
c. Clinical parameters should be monitored closely and correlated
with the hematocrit. This will ensure adequate rehydration,
avoiding under and over hydration.
d. The IVF rate may be decreased anytime as necessary based on
clinical assessment.
e. If the patient shows signs of deterioration see Management for
Compensated or Hypotensive Shock, whichever is applicable.
- Monitoring by health care providers:
a. Temperature pattern
b. Volume of fluid intake and losses
c. Urine output – volume and frequency
d. Warning signs
e. Hematocrit, white blood cell and platelet counts
o Dengue with Warning Signs:
- Obtain a reference hematocrit before fluid therapy
- Give only isotonic solutions such as 0.9% NaCl (saline), Ringer’s
Lactate, Hartmann’s solution. Start with 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 clinical response
- Reassess the clinical status and repeat the hematocrit
- If the hematocrit remains the same or rises only minimally, continue
with the same rate (2-3 mL/kg/hr) for another 2-4 hours.
- If there are worsening of vital signs and rapidly rising hematocrit,
increase the rate to 5-10 mL/kg/hour for 1-2 hours
- Reassess the clinical status, repeat hematocrit and review fluid
infusion rates accordingly
- Give the minimum intravenous fluid volume required to maintain
good perfusion and urine output of about 0.5 mL/kg/hr. Intravenous
fluids are usually needed for only 24 to 48 hours.
- Reduce intravenous fluids gradually when the rate of plasma
leakage decreases towards the end of the critical phase. This is
indicated by:
a. Urine output and/or oral fluid intake is/are adequate, or
b. Hematocrit decreases below the baseline value in a
stable patient
- Patients with warning signs should be monitored until the
“at-risk” period is over. A detailed fluid balance should be
maintained. Parameters that should be monitored include:
a. Vital signs and peripheral perfusion (1-4 hourly until
the patient is out of critical phase)
b. Urine output (4-6 hourly)
c. Hematocrit (before and after fluid replacement, then
6-12 hourly)
d. Blood glucose
e. Other organ functions (such as renal profile, liver
profile, coagulation profile, as indicated)
 Reduce osmolarity of ORS containing sodium 45 to 60 mmol/liter.
 Sports drinks should NOT be given due to its high osmolarity which may
cause more danger to the patient
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 If vital signs are still unstable (shock persists), check the hematocrit
after the first bolus:
o If hematocrit increases or is still high (>50%), repeat a second bolus of
crystalloid solution at 10- 20 mL/kg/hr for 1 hour. After this second bolus,
if there is improvement, then reduce the rate to 7-10 mL/kg/hr for 1-2
hours, and then continue to reduce as above
o If hematocrit decreases compared to the initial reference hematocrit
(<40% in children and adult females, <45% in adult males), this
indicates bleeding and the need to cross-match and transfuse blood as
soon as possible
 Further boluses of crystalloid or colloidal solutions may need to be given
during the next 24 to 48 hours
Calculation of Maintenance Intravenous Fluid Infusions (Holliday
and Segar Method):
Body Weight (kg)
0-10
>10-20
>20
Total Fluid Requirement (mL/day)
o 100 mL/kg
o 1,000 mL + 50 mL/kg for each kg >10 kg
o 1,500 + 20 mL/kg for each kg >20 kg
Source: Holliday MA, Segar WE. Maintenance need for water in parenteral fluid therapy. Pediatrics 1957;19:823.
 GROUP C – Patients with Severe Dengue Requiring Emergency
Treatment and Urgent Referral
B. EMERGENCY MANAGEMENT FOR COMPENSATED SHOCK
(GROUP C)
C. EMERGENCY MANAGEMENT FOR HYPOTENSIVE SHOCK (GROUP C)
 Start IV fluid resuscitation with isotonic crystalloid solutions at 5-10
mL/kg/hr over 1 hour, then reassess the patients condition (vital signs,
capillary refill time, hematocrit, urine output) and decide depending on
the situation:
 If the patients condition improves, intravenous fluids should be
gradually reduced to:
o 5-7 mL/kg/hr for 1-2 hours, then
o To 3-5 mL/kg/hr for 2-4 hours, then
o To 2-3 mL/kg/hr and then
o To reduce further depending on hemodynamic status, which can be
maintained for up to 24 to 48 hours
 Patients with hypotensive shock should be managed more vigorously 1
 Initiate intravenous fluid resuscitation with crystalloid or colloid solution (if
available) at 20 mL/kg as a bolus given over 15 minutes to bring the patient
out of shock as quickly as possible.
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Hemodynamic Assessment:
 How to recognize severe bleeding
o Persistent and/or severe overt bleeding in the presence of unstable
hemodynamic status, regardless of the hematocrit level
o A decrease in hematocrit after fluid resuscitation together with unstable
hemodynamic status
o Refractory shock that fail to respond to consecutive fluid resuscitation of
40-60 mL/kg.
o Hypotensive shock with low/normal hematocrit before fluid resuscitation
o Persistent or worsening metabolic acidosis ± a well-maintained systolic
blood pressure, especially in those with severe abdominal tenderness
and distension
 If the patient’s condition improves, give a crystalloid/ colloid
infusion of 10 mL/kg/hr for 1 hour, then continue with crystalloid
infusion and gradually reduce:
o To 5-7 mL/kg/hr for 1-2 hours, then
o To 3-5 mL/kg/hr for 2-4 hours and then
o To 2-3 mL/kg/hr or less, which can be maintained for up to 24 to
48 hours
 If vital signs are still unstable (shock persists), check hematocrit
after the first bolus:
o If hematocrit increases compared to the previous value or remains
very high (>50%), change intravenous fluids to colloid solutions at
10-20 mL/kg as a second bolus over ½ to 1 hour. After this dose,
reduce the rate to 7-10 mL/kg/hr for 1-2 hours, then change back to
crystalloid solution and reduce rate of infusion as mentioned above
when the patient’s condition improves
o If hematocrit decreases compared to the previous value (<40% in
children and adult females, <45% in adult males), this indicates
bleeding and the need to cross-match and transfuse blood as soon
as possible (see treatment for hemorrhagic complications)
 Further boluses of fluid may need to be given during the next 24 hours.
The rate and volume of each bolus infusion should be titrated to the
clinical response. Patients with severe dengue should be admitted to the
high dependency or intensive care areas.
III. TREATMENT OF HEMORRHAGIC COMPLICATIONS
“Mucosal bleeding may occur in any patient with dengue but if the
patient remains stable with fluid resuscitation/ replacement, it should
be considered as minor. This usually improves rapidly during the
recovery phase”
 In patients with profound thrombocytopenia, ensure strict bed rest and
protection from trauma to reduce the risk of bleeding
 Do not give intramuscular injections to avoid hematoma.
“Note: Prophylactic platelet transfusions for severe thrombocytopenia
in otherwise hemodynamically stable patients are not necessary.”
 If major bleeding occurs, it is usually from the gastrointestinal tract
and/or per vagina in adult females. Internal bleeding may not become
apparent for many hours until the first black stool is passed
 Who are at risk of major bleeding?
o Patients with prolonged/refractory shock
o Patients with hypotensive shock and renal or liver failure and/or
severe and persistent metabolic acidosis
o Patients given non-steroidal anti-inflammatory agents (NSAIDs)
o Patients with pre-existing peptic ulcer disease
o Patients on anticoagulant therapy
o Patients with any form of trauma, including intramuscular injection
“Note: Patients with hemolytic conditions will be at-risk for acute
hemolysis with hemoglobinuria and will require blood transfusion”
Action Plan
o Give 5-10 mL/kg of fresh packed red blood cells or 10-20 mL/kg of fresh
whole blood at an appropriate rate and observe the clinical response
o A good clinical response includes improving hemodynamic status and acidbase balance.
o Consider repeating the blood transfusion if there is further blood loss or no
appropriate rise in hematocrit after blood transfusion
o Although there is little evidence to support the practice of platelet
concentrates and/or fresh frozen plasma transfusion for severe bleeding, they
may be given judiciously.
IV. DISCHARGE CRITERIA
ALL of the following conditions must be present:
1. No fever for 48 hours
2. Improvement in clinical status (general well-being, appetite,
hemodynamic status, urine output, no respiratory distress)
3. Increasing trend of platelet count
4. Stable hematocrit without intravenous fluids
PREVENTION
I.

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PREVENTION
Prevention of mosquito breeding
Personal protection from mosquito bites
Community engagement
Reactive vector control
Active mosquito and virus surveillance
II.
VACCINATION
 Dengvaxia® CYD-TDV
o CYD-TDV is the first dengue vaccine to be licensed
o It was first licensed in Mexico in December 2015 for use in individuals 945 years of age and is now licensed in 20 countries
o The WHO recommends that the vaccine only be given to persons with
confirmed previous dengue virus infection.
o The vaccine manufacturer, Sanofi Pasteur, announced in 2017 that
people who receive the vaccine and have not been previously infected
with a dengue virus may be at risk of developing severe dengue if they
get dengue after being vaccinated.
o CYD-TDV is a live recombinant tetravalent dengue vaccine
- Three doses of vaccine are required
- Each shot is spaced 6 months apart.
o In February 2019, the Philippines Food and Drug Administration
permanently withdrew the vaccine’s licence.
REFERENCES
1. 3D Powerpoint
2. WHO Dengue Guidelines for Diagnosis, Treatment, Prevention and Control 2009:
https://www.who.int/tdr/publications/documents/dengue-diagnosis.pdf
3. Handbook Clinical Management of Dengue 2012:
https://pcp.org.ph/images/Web_Posting/others/PSBIM/handbook_for_clinical_management_of_dengue.pdf
4. DOH Revised Dengue Clinical Case Management Guidelines 2011:
https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue%20Clinical%20Case%20M
anagement%20Guidelines%202011-DOH.pdf
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