B1M3L1 - The Philippines has the highest number of

DENGUE FEVER 101: DX, TX, and cases (135,355) and deaths (793) in 2010
PREVENTION - The Philippines case fatality rate actually
July 23, 2019 drop from 1.02% to 0.59% from 2006 to
Dr. Ronald Limchiu 2010 respectively
(Team Notes) - The overall cost of a dengue case is $828

Disclosure Local Epidemiology

- Curriculum based workshops on dengue
clinical management by the Malaya Medical
Center supported by the World Health
Organization Western Pacific Region and
CDC USA.
- Reading materials for the dengue vaccine
was provided by Sanofi Pasteur through the
Medical Affairs Division
- The Who September 2018 position paper on
CYD-TDV
Outline
- Diagnosis
o Clinical presentation
o Laboratory features
o WHO case definition
- Treatment
o Dengue without warning signs
o Dengue with warning signs
o Severe dengue
- Prevention
o Vector control
o Dengue vaccine
Dengue Worldwide: WHO 2018
- 3.9 billion people in 125 countries are at risk
of dengue infection
- 390 million dengue infection occurs annually
- 500,000 requires hospitalization
- 20,000 deaths due to severe dengue are
recorded every year
Dengue in the Western Pacific Region (WPR)
- Dengue is the most important public health
problem in the WPR
- All four serotypes (DENV 1,2,3,4) are
present
- Occurs throughout the year but rates increase
1-2 months after the start of the rainy season
in June
- Cambodia, Malaysia, Philippines, and
Vietnam are the four countries in the WPR
with the highest number of cases and deaths
reported in 2000-2010
Transition from Febrile Phase to Critical Phase
- Cases in the Philippines were over 200,000
for both 2015 and 2016
- Regions with the highest number of cases :
VII (12.9%), VI (12.4%), IV (10.4%), III
(9.6%)
- The total number of cases reported
nationwide from Jan. 1 to Dec. 31, 2016 was
211,108 this was 1.3% lower compared to
the same period the previous year (213,930)
- Deaths in 2016 have increased by 36.6%
compared to 2015
Diagnosis
- Clinical course of the disease
o Incubation period
o Febrile phase
o Critical phase
o Recovery phase
Incubation Period
- Extrinsic incubation period (Virus within the
mosquito) is 8 to 12 days
- Intrinsic incubation period (Virus within a
person) is 3 to 14 days
- Vertical transmission - DENV can be
transmitted from the mother to fetus in utero
or to the neonate in parturition
- Average time between mom to newborn is 7
days (range: 5-13 days) similar to intrinsic
incubation
Febrile Phase
- Heralds the onset of symptoms
- Usually lasts for 2-7 days
- High temperature; may be modified by
antipyretics
- Common symptoms: myalgia, headache,
retro-orbital pain, aches and rashes
- Difficult to differentiate dengue from other
viral febrile illnesses
- Normal CBC in the first 1 to 2 days
- In children nausea and vomiting may be
prominent

- Clinical warning signs
o Severe abdominal pain
▪ Severe enough to be Px
chief complaint
▪ Could be mistaken as
surgical condition
▪ Signifies vascular
permeability, could be a
prelude to shock
▪ Tense abdomen due to
ascites and liver
congestion can cause
severe abdominal pain
o Persistent vomiting
▪ Three or more times per
day
▪ Px not able to tolerate oral
fluid
▪ Important sign of plasma
leakage
o Mucosal bleeding
▪ Warning of more severe
manifestation (occult
internal bleeding)
o Lethargy or restlessness
▪ Px confined to bed most of
the day
▪ Px sleeps most of the time
▪ Px in uninterested in food
or television
▪ Px too weal to walk to the
toilet
▪ Restlessness could be a
sign to severe shock with
cerebral hypo perfusion
o Liver enlargement > 2cm
o Clinical fluid accumulation
▪ Ascites, pleural effusion,
puffy eyelids
▪ Mild fluid accumulation
may be undetectable
▪ Significant fluid
accumulation usually
signifies severity of
vascular permeability plus
fluid therapy
- Laboratory warning signs
o Leukopenia
▪ Occura 24 hours prior to
rapid decrease in platelet
count
▪ Not predictive of plasma
leakage
o Rapid decrease platelet count
▪ Occurs shortly before or at
defervescence
Diagnosis: Dengue Classification by Severity
▪ May precede changes in
blood pressure and pulse
pressure
▪ Indicate an increase in
vascular permeability
o Rising hematocrit
Critical Phase
- What happens during the critical phase
o Increase vascular permeability
o Significant plasma leakage usually
not lasting for more than 24 to 48
hours
o Development of warning signs
o Deterioration of Px condition
o Not all patients will experience the
critical phase
- Characteristics of shock in severe dengue
o Shock occurs when critical volume
of plasma is lost through capillary
leakage or hemorrhage
o Shock is often preceded by warning
signs
o Body temperature is often
subnormal when shock occurs
o The Toal WBC may increases in
patients with severe bleeding
Recovery Phase
- What happens during the recovery phase
o Vascular permeability reverts to
normal
o Gradual reabsorption of
extravascular fluid in next 48 to 72
hours
o Clinical clues
▪ Improvement in general
well being
▪ Stable hemodynamic status
▪ Diuresis
▪ Biphasic fever
▪ May have bradycardia
▪ Isles of white in a sea of
red
o Laboratory clues
▪ Hct stabilizes, may lower
due to dilution effect of
reabsorbed fluid
( hemodilution)
▪ WBC will start to rise soon
after defervescence
▪ Thrombocytopenia persists
longer than leucopenia
- WHO WPR proposed a dengue case o History taking
definition system in 2009 o Clinical Examination
o Aims to show clear-cut differences o Investigations
between patients with non-severe o Diagnosis, phase, and severity
with/out warning
dengue versus severe dengue signs, or severe dengue
o Classification levels helps clinicians History Taking
in decision making about intensity
of treatment and monitoring - Three golden questions
- Dengue o How much oral fluid intake
o Without warning signs o How much urine output
o With warning signs o What activities could the patient do
- Severe Dengue during the febrile illness
o Severe plasma leakage - Ask for presence of warning signs
o Severe hemorrhage - Medications given
o Severe organ impairment - Risk factor or co-existing conditions
- Criteria for dengue without warning signs

o Probable dengue Clinical Examination
▪ Live in or travel to
endemic area
- Hemodynamic assessment
▪ Fever plus 2 of the
o Stable patient - all hemmedynamic
following:
parameters are within normal limits
• Nausea, vomiting
o Compensated shock - blood
• Rash
pressure is either normal or high but
• Tourniquet test
there are signs of hemodynamic
(+)
compromise, e.g. rising diastolic
• Leucopenia 10,000 or below
pressure, narrow pulse pressure,
• Laboratory
prolonged CRT, weak, thready, and
confirmed dengue
rapid pulse. Quiet tachypnea
- Criteria for dengue with warning signs
however sensorium may still be
o Abdominal pain or tenderness
clear and lucid
o Persistent vomiting
o Hypotensive shock- decrease to
o Mucosal bleeding
absent blood pressure, restlessness/
o Lethargy/restlessness
combative or lethargic, cold
o Clinical fluid accumulation
clammy mottled skin, narrow pulse
o Liver enlargement of > 2cm
pressure (<20 mmHg), Kausmaul
o Increase in Hct with steep decline in
breathing
the platelet count
- The 5-in-1 maneuver magic touch - CCTVR
o Requires strict observation and
o Color - pale or mottle
medical intervention
o CRT - prolonged (> 2 secs)
- Criteria for
severe dengue secondary to:
o Temperature - cold and clammy
o Severe plasma leakage leading to:
o Volume of pulse - weak and thready
▪ Shock (DSS)
o Rate of pulse - rapid
▪ Fluid accumulation with
respiratory distress
o Severe bleeding Laboratory Investigations
▪ Bleeding that causes
hemodynamic instability - CBC with hematocrit and platelet count are
and may require blood usually all that is necessary
transfusion - Look for a steep drop in platelet count with a
o Severe organ involvement rising Hct which suggest progression in
▪ Liver: AST or ALT > 1000 plasma leakage/critical stage of dengue
▪ CNS: impaired - Dengue specific diagnostic test e.g. NS1 or
consciousness dengue IgM or IgG are not necessary for the
▪ Impaired cardiac function acute management of patients but are
valuable in unusual presentations, suspected
Patient Assessment and Evaluation deaths or patients who rapidly progress from
mild to severe dengue
- Four important steps
 Diagnosis, Phase of Disease and Severity • 38.8 C
Paracetamol if fever >38C
• Avoid ibuprofen or aspirin
- Does the patient have dengue?
- Which phase of dengue? ▪ Return to hospital immediately if warning
- What is the state of hydration? signs appear
- Are dengue warning signs present?
- What is the hemodynamic state?
- What is the best medical plan for the patient? Group B: Dengue without warning signs but with
the ff:
TREATMENT
▪ Co-existing conditions
Management decision • Diabetes mellitus
▪ Group A • Renal failure
o Send home
• Pregnancy
▪ Group B • Infant
o Refer for hospital management • Elderly
▪ Group C
▪ Social conditions
o Require emergency treatment and urgent • Living alone
referral • Living far away without reliable means
of transport
Group A: Dengue without warning signs
Management decision: Refer for hospital
▪ Getting adequate oral fluids and passing management
urine at least once every 4 to 6 hours
▪ Patients are able to “drink enough to pee Group B: Dengue with warning signs
enough”
▪ Admit to in-patient care
▪ Has stable Hct and hemodynamic status
▪ Monitor hemodynamic status frequently
▪ Does not have co-existing conditions
▪ Use Hct to guide interventions
▪ Send home if patient meets all the criteria
▪ Use isotonic IV fluids judiciously
Management decision: Send home
▪ Correct metabolic acidosis, electrolytes as
1. Give anticipatory guidance before sending
needed
home (patient handouts)
2. Follow-up daily Group C – Severe dengue
3. Do serial CBCs
▪ Severe plasma leakage with shock and/or
4. Identify warning signs early
fluid accumulation with respiratory distress
Keys to good home care
▪ Severe bleeding
▪ Bed rest
▪ Severe organ impairment
▪ Encourage oral fluids
• ALT >1000
• 6 to 8 glasses /day
• Impaired consciousness
• Milk, coconut water, fruit juices, ORS,
Don’t advise mangagaw rice water or clear soup
because of parent’s
Treatment: Fluid Management
false sense of hope that • Water alone may cause electrolyte
its treating the patient
imbalance ▪ Group B

▪ Manage fever
 • Dengue with warning signs (not in
shock)
o Obtain Hct before starting IV
o Start isotonic crystalloid 5-7 ml/kg/
hr for
1 to 2 hours
o Reassess: if improving decrease IVF
rate by
1-2 cc/kg every 2 to 4 hours
o Stop IVF therapy within 24-48 hours
If no improvement after first bolus,
o Obtain Hct before starting IV
o Start isotonic crystalloid 5-7 ml/kg/
hr for 1 to 2 hours
o Reassess: Not improving: recheck
Hct
• Hct increasing: Increase IV rate
to
5 to 10ml/kg/hr for 1to 2 hours
• Hct increasing with beginning
signs of shock go to severe
dengue algorithm or Group C
protocol
▪ Group C- Emergency Treatment
• Severe dengue
o Compensated shock- Systolic BP
maintained but with signs of reduced
perfusion
• Obtain baseline Hct
• Start IV fluid therapy with
isotonic crystalloids, 5-10 ml/
kg/hr (adults) or 10-20 ml/kg/hr
(children)
• Reassess: improved-decrease
IVF rate to 5–7 ml/kg/hr
• Reassess: if improvement
continues, decrease IVF rate by
1-2 cc/kg/hr every 2 to 4 hours
• Stop IV fluids at 24 – 48 hours
If no improvement after first bolus,
• Obtain baseline Hct
• Start IV fluid therapy with
isotonic crystalloids, 5-10 ml/
kg/hr (adults) or 10-20 ml/kg/hr
(children)
• Reassess: Not improved,
recheck Hct.
Hct increasing.
• Give 2nd bolus colloid at
10-20ml/kg for 1 hour
• Reassess: improved, reduce
IV crystalloid to 7 to 10 ml/
kg/hr for
1 to 2 hours
• Continue stepwise
reduction of IVF
• Discontinue IVF in 24 to 48
hours
o Hypotensive shock
• Obtain baseline Hct
• Start IVF resuscitation with
crystalloid or colloid as a bolus
given at 10- 20 ml/kg (adults) or
20ml/kg (children) over 15 to
30 mins
• Reassess: if improved- give
crystalloid or colloid at 10 ml/
kg for 1 hour
• If patient continues to improve,
continue with crystalloid and
reduce IVF in stepwise manner
• Stop IVF at 24 to 48 hours
If no improvement after first
bolus,
• Obtain baseline Hct
• Start IVF resuscitation with
crystalloid or colloid as a bolus
given at 10- 20 ml/kg (adults) or
20ml/kg (children) over 15 to
30 mins
 • Reassess: Not improved.
Recheck Hct. DISCHARGE CRITERIA

If increasing or high give 2nd ▪ No fever for 24 – 48 hours

bolus of ▪ Improvement in clinical status
10-20 ml/kg of colloid over • General well being, good appetite,
30-60 mins stable hemodynamic status
• Reassess: if improved, reduce • Increasing trend of platelet count
IVF rate to 7-10 ml/kg for 1 to 2 • Stable Hct with oral intake, off IV
hours. Continue stepwise • Follow patient with organ impairment
reduction of with crystalloid.
• Discontinue IVF with 24 to 48 PREVENTION: VECTOR CONTROL
hours
▪ WHO Global Strategy of Dengue
o Hypotensive shock: Bleeding?
Prevention and Control 2012
• Obtain baseline Hct
• Vector control in most endemic
• Start IVF resuscitation with
countries is frequently insufficient or
crystalloid or colloid as a bolus
ineffective
given at 10- 20 ml/kg (adults) or
• Dengue outbreaks still occur annually in
20ml/kg (children) over 15 to
endemic countries
30 mins • An integrated strategy of both sustained
TRANSFUSE! Do not wait for Hct • Reassess: Not improved, Hct
to go down. 10% drop in Hct + vector control and vaccination is
patient not improving = patient decreasing, consider bleed,
required to reduce the burden of dengue
bleeding urgent blood transfusion
in endemic countries.
o Pearls: Group C monitoring and
action PREVENTION: DENGUE VACCINE
• Estimate the start of significant
▪ Summary of the key points for WHO
plasma leakage, project 24 to 48
position paper on dengue vaccine. July 29,
hours from time of plasma
2016
leakage. This would be the
• Dengue vaccination should be a part of
estimated time by which IVF
a comprehensive dengue control
should be discontinued
strategy, which includes well executed
• Before this time, plasma
and sustained vector control, evidence-
leakage is still active. Further
base best practices for clinical care and
boluses of fluids may be
strong dengue surveillance
required during the first 24 to
• WHO objectives are to reduce mortality
36 hours of admission
by 50% by 2020 and reduce morbidity
• Volume and rate of infusion
by 25% by 2020
should be titrated to the
• Vaccination is a critical pillar of the
hemodynamic response with
WHO strategy towards effectively
stepwise reduction of IVF if the
fighting dengue
patient improves
▪ A live attenuated tetravalent vaccine has
been approved for use by the DOH in the
Philippines
▪ It is freeze-dried product to be reconstituted
before injection
▪ Administered subcutaneous route
▪ Schedule: 3 doses six months interval
▪ Indication : for the prevention of dengue
illness in individuals 9-45 years of age,
living in endemic areas
▪ Contraindications
• Individuals with a history of severe
reaction to any component of the
dengue vaccine
• Individuals with congenital or acquired
immune deficiency
• Individuals with symptomatic or
asymptomatic HIV
• Pregnant or breastfeeding women
• Vaccination should be postpone in
individuals with moderate or severe
febrile or acute disease
▪ Consistent efficacy results
• 65.6% reduction in symptomatic dengue
• For each serotype
• DENV 1 – 58.4%
• DENV 2 – 47.1%
• DENV 3 – 73.6%
• DENV 4 – 83.2%
• 80.8% reduction in hospitalized dengue
• 93.2% reduction in severe dengue
▪ Philippine medical societies that endorsed or
recommended the use of the vaccine include
the following
• PIDSP
• PSMID
• PPS
• Phil. Foundation For Vaccination
▪ WHO position paper on Dengvaxia
September 2018
• Dengvaxia vaccine has been shown in
clinical trials to be safe and effective
vaccine in persons who have had a prior
dengue infection.
• For baseline seronegative individuals,
there is an increase risk for
hospitalization and severe dengue for
those who experience their first natural
dengue after vaccination.
• Policy options
1. Screen and vaccinate – screen with
RDT to determine sero-status,
vaccinate only those seropositive
2. Mass-vaccination with
seroprevalence threshold –
vaccinate populations in areas
where transmission intensity
exceeds >80% seroprevalence in 9
year old children
▪ Zeng W. et al. Cost-effectiveness of dengue
vaccination in ten endemic countries.
Vaccines 2018 Jan. 8, 36(3):413-420
▪ Using a health system perspective, the
incremental cost effectiveness ratio
(disability adjusted life-year or DALY)
averted is US. $5,101 (P270.353) in the
Philippines
▪ Highly cost-effective vaccine