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Dengue in Children

Case of B.S.

A case of B.S., 2 years old,


born last January 17, 2019 at
MRXUH, CDOC, female,
Filipino, Christian, currently
residing at Gusa, CDOC. No
history of prior hospital
admissions.

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History of Present Illness

❏ 3 days PTC, fever at 38.1°C


❏ No associated symptoms
❏ No other members had fever
❏ Paracetamol 100mg/mL, 1.2mL (12 mk dose)
per drops every 4 hours.
❏ Fever persisted,
❏ (+) Vomited (-) Abdominal Pain
❏ No measures done for vomiting
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History of Present Illness

❏ Two days PTC, fever (38-39°C)


❏ (-) vomiting, (-) associated symptoms
❏ same dose of Paracetamol -> fever persisted

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History of Present Illness

❏ One day PTC, highest temperature, 39.6 °C


❏ Every less than 4 hours
❏ Same dose of Paracetamol
❏ Loss of appetite and decrease in play
❏ Preferred drinking milk

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History of Present Illness

❏ On the day of consult, fever


❏ despite taking Paracetamol
❏ irritable and clingy to her mother
❏ fever, loss of appetite, irritability, and with a
recent history of fever and dengue in the
neighborhood -> seek consult

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Patient’s Profile
▫ Born to a ▫ Term, delivered ▫ exclusively
38-year-old via NSVD breastfed
mother with an attended at ▫ still
OB score of G1P1 MRXUH breastfeeding at
(1001) ▫ BW 3 kgs 2 yrs of life
▫ (-) Obstetric ▫ (-) Cyanosis ▫ Complementary
complications ▫ (-) Resuscitation at 6 months
▫ Duration of ▫ (+) Good cry ▫ non-picky eater
pregnancy was ▫ (+) Good suck ▫ (-) supplements
nine months ▫ (+) Jaundice ▫ (-) allergies
▫ Complete ▫ Normal Newborn
prenatal visits Screening Test

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Patient’s Profile
▫ no gross and fine ▫ never been ▫ completed her
motor red flags hospitalized vaccination at
▫ no receptive and ▫ (-) viral MRXUH
expressive red exanthems Pediatrician
flags ▫ (-) contagious ▫ childhood
▫ Sleep: 10 hours diseases immunization
▫ Screen time: 1h ▫ (-) asthma, schedule
AM, 1hr PM diarrhea ▫ fever after MMR
▫ Teeth erupted at ▫ (-) medical vaccination
7 months illnesses ▫ immunization
▫ (-) fall and fire record not
injuries available for
review
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Patient’s Profile
❏ Mother 40 yrs old, ▫ Subdivision in Gusa
housewife ▫ 4 family members living
❏ Father 40 yrs old, IT, in the house
breadwinner ▫ (-) pets
❏ (-) familial illness and ▫ Cleaning regularly
abnormalities ▫ Cases of Dengue
❏ younger brother (M.S.) ▫ Plays regularly outside
10 months old the house but within
the vicinity.

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Physical Examination
awake, alert, irritable but Height: 87 cm
consolable, weak looking Weight: 12kg
with flushed skin and not in
BMI: 15.8 kg/m2
respiratory distress
febrile at 39.6 °C,
normotensive at 90/60 WHO Z scores within
mmHg, tachycardic at 120 normal ranges
bpm, eupneic at 24 cpm

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Primary Working Impression:

Dengue with Mild Dehydration

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1 Introduction
Dengue pathophysio & classifications
Dengue
▫ belongs to the family Flaviviridae and is
transmitted to humans by Aedes
mosquitoes, mainly Aedes aegypti
▫ four serotypes (DENV-1, DENV-2, DENV-3,
and DENV-4)

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Dengue w/o Warning Signs
▫ Probable dengue
▫ Lives in or travels to dengue-endemic area,
with fever, plus any 2 of the ff:
▫ headache, body malaise, myalgia, arthralgia,
retro-orbital pain, anorexia, nausea, vomiting,
diarrhea, flushed skin, rash, laboratory test
▫ Confirmed dengue
▫ viral culture isolation; PCR

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Dengue with Warning Signs
▫ Lives in or travels to dengue-endemic area, with
fever lasting for 2-7 days, plus any of the ff:
▫ abdominal pain or tenderness, persistent vomiting,
clinical signs of fluid accumulation, mucosal
bleeding, lethargy, restlessness, liver enlargement,
increase in Hct and/or decreasing platelet count
▫ Confirmed dengue
▫ viral culture isolation; PCR

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Severe Dengue
▫ Lives in or travels to a dengue-endemic area with
fever of 2-7 days and any of the above clinical
manifestations, plus any of the ff:
▫ Severe plasma leakage
▫ Severe bleeding
▫ Severe organ impairment (liver, CNS, kidneys,
heart)

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Pathophysiology
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Clinical & Laboratory
Features of Dengue
Comparing severe and non-severe forms
Clinical & Laboratory Features of Dengue
Dengue patients are classified as severe dengue or non-severe
dengue

● with the group of patients with non-severe dengue subdivided


into those
○ with warning signs and those without warning signs
● After an incubation period of 3 to 14 days, the illness begins
abruptly and is followed by the three phases:
○ Febrile
○ Critical
○ recovery

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Clinical & Laboratory Features of Dengue
Acute febrile phase of dengue

● usually lasts 2–7 days


● generalized body ache, muscle and joint pains, headache,
retro-orbital pain, facial flushing, sore throat, hyperemic
pharynx, macular or maculopapular rash, petechiae and mild
mucosal membrane bleeding
● A positive tourniquet test and progressive decrease in
total white cell count are early findings which could
differentiate dengue from other acute febrile illnesses

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Clinical & Laboratory Features of Dengue
Critical Phase

● During fever defervescence, usually on days 3–7 of illness, an


increase in capillary permeability in parallel with increasing
hematocrit levels
● The period of clinically significant plasma leakage usually
lasts 24–48 hours, followed by a convalescent phase with
gradual improvement and stabilization of the hemodynamic
status

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Clinical & Laboratory Features of Dengue
Warning signs of progression to severe dengue

● occur in the late febrile phase


● persistent vomiting, severe abdominal pain, mucosal
bleeding, difficulty breathing, and early signs of shock
○ Progressive leukopenia followed by a rapid decrease in
platelet count usually precedes plasma leakage
● people with clinically significant plasma leakage attributable
to increased vascular permeability become worse and
develop severe dengue disease with pleural effusion and/or
ascites, hypovolemic shock, severe hemorrhage, or organ
impairment

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Clinical & Laboratory Features of Dengue
Plasma leakage → Shock → organ hypoperfusion →
progressive organ impairment, metabolic acidosis and
disseminated intravascular coagulation → severe
hemorrhage → ↓hematocrit in severe shock

Severe organ impairment such as severe hepatitis,


encephalitis or myocarditis and/or severe bleeding may also
develop without obvious plasma leakage or shock

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Clinical & Laboratory Features of Dengue
Recovery Phase

● Gradual reabsorption of extravascular compartment fluid


● May have bradycardia, stabilization of hematocrit
● Improvement of well-being & return of appetite
● Hemodynamic status stabilized & diuresis ensues
● WBC count usually starts to rise soon after
defervescence, but the recovery of platelet count is
typically later than that of WBC
● Hermann’s rash
● Excessive fluid therapy is associated with pulmonary edema
or congestive heart failure

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Clinical Signs and Symptoms that Warrant
Admission
patients with the following signs and symptoms should be
admitted in a healthcare facility for closer monitoring and
observation:

● Shortness of breath
● Irritability or drowsiness
● Pleural effusion
● Abdominal pain
● Melena
● Elevated hematocrit
● Decreased or decreasing platelet count
● vomiting*

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Risk Factors associated with Mortality
any of the ff:

● Hypotension on admission
● Narrow pulse pressure on admission
● DHF stage 3 and 4 (severe dengue)
● History of previous dengue
● Prolonged shock
● Respiratory failure
● Liver failure (AST elevation > 200 u and INR > 1.3)
● Renal failure (BUN >20 mg% and serum Creatinine >1.0mg %)
● Significant bleeding including gastrointestinal bleeding
● Severe plasma leakage in multiple sites (pleural effusion,
pericardial effusion and ascites)
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Risk Factors associated with Mortality
two or more of the ff:

● severe abdominal pain


● arterial hypotension
● neurologic manifestation
● painful hepatomegaly
● hypovolemic shock
● liver failure
● myocarditis

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Risk Factors associated with Mortality
one or more of the ff: warrants admission and close monitoring

● Decline in Hgb by ≥20%


● Thrombocytopenia, with APC < 50,000
● Hemoconcentration, with Hct > 40 % or 20% increase in
lowest and highest
● hematocrit
● Creatinine > 1 mg %
● AST>1000u
● Acidosis

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Fluid Therapy for
Dengue
Maintenance fluids commonly used
Fluid Therapy for Dengue
● WHO 2009 Guidelines
○ Ambulatory patients
■ ORS, fruit juices and other fluids containing electrolytes and
sugar
○ Ideal physiologic fluid
■ Resembles the ECF and ICF closely
○ Patient develops warning signs without shock
■ Isotonic solutions (0.9% Saline or Ringer’s Lactate)
○ Patients with shock
■ Start IVF resuscitation with isotonic crystalloid solutions
■ Colloids may be the preferred choice over crystalloids if the
blood pressure needs to be restored urgently

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Fluid Therapy for Dengue
● Isotonic
○ Approximates the effective osmolality of plasma (275-295
mosm/kg)
● Hypotonic
○ Osmolality is lower than the effective plasma osmolality
● Balanced isotonic electrolyte solutions
○ Sterofundin ISO, Plasmalyte 148
○ Contain sodium, electrolytes and osmolality with values closer to
plasma
● 0.9% NaCl and Ringer’s lactate
○ The most readily available and cheapest
○ Recommended by WHO

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Among patients without shock, how effective
are isotonic IVFs compared to hypotonic IVFs
in reducing mortality?

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● There is insufficient evidence that the
tonicity of the intravenous fluid has an
effect on mortality in dengue patients
without shock
● Isotonic fluids can be used as
maintenance for dengue patients
without shock
● The use of hypotonic IVF is associated
with hyponatremia among hospitalized
pediatric patients

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Among dengue patients with shock, how
effective are colloidal IVFs compared to
crystalloid IVFs in reducing mortality?

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● In dengue patients with shock, either
crystalloids or colloids may be used for
fluid resuscitation.
● There is insufficient evidence to say that
the use of colloid IVF compared to
crystalloids will have an effect on
mortality.
● The use of colloids may be associated
with more adverse reactions (e.g.
bleeding, allergic reactions) compared to
crystalloids.

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Role of Blood Product
Transfusion in Dengue
Blood products
Use of Blood Products
▫ Blood products not routine
▫ Profuse bleeding
▫ Clinical deterioration refractory fluid resuscitation
▫ Components of choice: Fresh Whole Blood &
Packed RBCs
▫ Controversial: Platelet concentrate/Plasma
transfusion
▫ Persistent or DIC suspected: Fresh frozen plasma
or cryoprecipitate
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Components of Choice

Blood Product Dose Indication

Persistent and/or severe overt


Fresh whole bleeding in the presence of
10-20 ml/kg
Blood “FWB” unstable hemodynamic status;

Unstable hemodynamic status


or refractory shock with
Packed RBC decreasing Hct despite
5-10cc/kg adequate fluid administration
“PRBC”

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Other Blood Products
Blood Product Dose Indication

Fresh frozen Massive bleeding not responsive to transfusion


10 -20 cc/kg
plasma “FFP” of FWB or fresh packed cells;

Cryoprecipitate 1 u/ 5kg coagulopathy with bleeding


Suspected or confirmed DIC

platelet count ≤ 10,000/mm3


associated with systemic massive bleeding or
Platelet
1 unit/10 kg prolonged shock with bleeding not responsive
concentrate
to red cell products (FWB or PRBC) or plasma
products (FFP or cryoprecipitate)

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Among patients with thrombocytopenia
because of dengue, how effective is prophylactic
platelet transfusion in improving platelet count,
preventing hemorrhage, and reducing mortality?

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Prophylactic Platelet Transfusion

There is insufficient evidence


to say that prophylactic
platelet transfusion in patients
with minimal or no active
bleeding will improve platelet
counts, prevent hemorrhage
and reduce mortality.

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Prophylactic Platelet Transfusion

Children with dengue who have


platelet count <50,000/mm3 with
minimal or no active bleeding
should NOT be given prophylactic
platelet transfusion.

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Among Dengue patients with significant bleeding,
how effective is plasma transfusion in controlling
bleeding and reducing mortality?

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Plasma Transfusion

Among dengue patients with significant


bleeding, there is insufficient evidence
that plasma transfusion has an effect on
controlling bleeding and reducing
mortality.

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Plasma Transfusion

The potential adverse effects of FFP


were also higher in those given FFP
compared to those given isotonic saline,
such as increased risk for allergic
reaction and volume overload.

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Plasma Transfusion

In children exhibiting signs of


disseminated intravascular
coagulopathy (DIC), plasma transfusion
may be considered. (strongly
recommended based on low quality
evidence)

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Insect Repellents
in Dengue
(Brief Intro to chapter)
Repellants
● Repellants play a very important role in prevention of mosquito-borne
infections

● Pesticides
○ Substances intended for preventing, destroying, repelling, or
reducing any pests
○ Do not necessarily kill the insects but may also just make the user
less attractive to the mother

● All products need to be approved before release for use among


consumers due to effectiveness & safety issues 54
FDA-approved Repellents
N,N-diethyl-m-toluamide - Chemically Disadvantages:
(DEET) synthesized
- Effective in dispelling - Development of
Dimethyl phthalate (DMP) blood-sucking insects tolerance in
- Highly effective mosquitoes
- Toxic reactions
- Ill effects in the
environment
- Effect on other
non-target organisms
- Damaging effects on
plastrics & synthetic
fabrics

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Chemical Repellents
Nitrogen Terpenoids Phenolics Proteinase Growth
compounds Inhibitors Regulators
(primary - Suggested: - Affects
alkaloids) competitive insect - Neurotoxins - Mimic
inhibition of physiology that act on hormones in
- Toxicity the enzyme ion young
effect acetylcholin - Dec. larval channels on insects
sterase weight axonal
membranes, - Disrupt how
- Inc. disrupting insects grow
oxidative impulse and
stress transmissio reproduce
n and cause
- Reduce paralysis
lactate
dehydrogen
ase activity

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Green Leaf “Volatiles”
Geranyl Acetate Citronella

- Deterrent or repellant due to high vapor toxicity in preventing insect bites


- No studies directly show how much these repellents really lower incidence rates of
actual infections

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CDC Recommendations
● CDC recommends that only EPA-approved products are used

● Market products with no EPA approval


○ main ingredients appear to pose minimal risk for human health
○ Citronella oil
○ Cedar oil
○ Geranium oil
○ Peppermint oil
○ Soybean oil

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References
▫ Martina B, Koraka P, & Osterhaus A. 2009. Dengue
Virus Pathogenesis: an Integrated View. Clinical
Microbiology Reviews, 22:4, pp. 564-581

▫ PPS-PIDSP 2017. Clinical Practice Guidelines on


Dengue in Children. Retrieved from
http://www.pidsphil.org/home/wp-content/uploads/2
017/06/2017_Dengue_CPG_Final.pdf last November 17,
2021
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