DENGUE

Manuel S. Vidal, Jr., MD, PhD

Department of Family and Community Medicine
Sta. Ana Hospital
DENGUE

DENGUE
PATHOPHYSIOLOGY, CLINICAL MANIFESTATIONS
DENGUE

DENGUE infections are caused by four

closely related viruses named
DEN-1, DEN-2, DEN-3, and
DEN-4

positive-sense RNA because it can

be directly translated into proteins

Aedes aegyptii
Vector of the dengue virus

Three are structural proteins: the

capsid (C), envelope (E), and
membrane (M) proteins. Seven are
nonstructural proteins: NS1, NS2A
NS2B, NS3, NS4A, NS4B, and
NS5.

https://www.nature.com/scitable/topicpage/dengue-viruses-22400925
DENGUE

• clinical course of dengue is divided into three

distinct phases:
• a febrile phase, lasting 3–7 days
• a critical phase, lasting 2–3 days
• a recovery phase, lasting 2–5 days
• increase in capillary permeability that occurs
in some patients, and can cause intravascular
hypovolaemia and shock, is the best known
cardiovascular complication

https://www.nature.com/articles/nrcardio.2014.40
DENGUE

• Febrile phase
• sudden high-grade fever (≥38.5°C)
• accompanied by headache (retroorbital),
vomiting, myalgia and arthralgia
(breakbone fever)
(60-70%)
• a transient macular rash that may be
pruritic – if present, occurs 2-5 days after
fever
• tourniquet test – positive if with >10
petechiae in one square inch

https://www.uptodate.com/contents/dengue-virus-
infection-clinical-manifestations-and-diagnosis
DENGUE

• Febrile phase
• Leukopenia, thrombocytopenia
• AST usually 2-5x UL

• Remitting fever (5%)

https://www.uptodate.com/contents/dengue-virus-
infection-clinical-manifestations-and-diagnosis
DENGUE

• Critical phase
• vascular leakage reduces intravascular
volume and decreases organ perfusion
• persistent vomiting
• increasingly severe abdominal pain
• tender hepatomegaly
• development of pleural effusions
and/or ascites
• mucosal bleeding
• lethargy or restlessness
• high or increasing hematocrit level (≥20
percent from baseline) concurrent with a
rapid decrease in the platelet count

https://www.uptodate.com/contents/dengue-virus-
infection-clinical-manifestations-and-diagnosis
DENGUE

https://www.nejm.org/doi/full/10.1056/
nejmra1110265
DENGUE

• Recovery phase
• plasma leakage and hemorrhage resolve,
vital signs stabilize, and accumulated
fluids are resorbed
• a confluent, erythematous eruption with
small islands of unaffected skin that is
often pruritic) may appear during the
recovery phase (within one to two days of
defervescence and lasting one to five days

https://www.uptodate.com/contents/dengue-virus-
infection-clinical-manifestations-and-diagnosis
DENGUE

DENGUE
DIAGNOSIS
DENGUE

Immune responses
• first week of illness
• detection of IgM
(first 4 days)
• detection of viral nucleic acid in
serum by means of RT-PCR
(first 5 days)
• detection of viral antigen NS1
(first 7 days)
• seroconversion in second
week of illness
• IgG is detectable at low titer
beginning seven days after
onset and increases slowly
Peeling RW, Artsob H, Pelegrino JL, et al. Evaluation of diagnostic tests: Dengue.
Nat Rev Microbiol 2010; 8:S30
DENGUE

DENGUE
MANAGEMENT
DENGUE

DENGUE
CLASSIFICATIONS
WHO 2009, DOH 2011

https://www.cardi-oh.org/best-practices/5Rs-of-Accurate-Blood-Pressure-Measurement
DENGUE

MANAGEMENT

https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue
%20Clinical%20Case%20Management%20Guidelines%202011-DOH.pdf
DENGUE

MANAGEMENT

https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue
%20Clinical%20Case%20Management%20Guidelines%202011-DOH.pdf
DENGUE

MANAGEMENT
Admissible patient

https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue
%20Clinical%20Case%20Management%20Guidelines%202011-DOH.pdf
DENGUE

MANAGEMENT
Admissible patient
(+) mild dehydration, (-) shock

https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue
%20Clinical%20Case%20Management%20Guidelines%202011-DOH.pdf
DENGUE

MANAGEMENT
Admissible patient

https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue
%20Clinical%20Case%20Management%20Guidelines%202011-DOH.pdf
DENGUE

MANAGEMENT
Admissible patient

https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue
%20Clinical%20Case%20Management%20Guidelines%202011-DOH.pdf
DENGUE

MANAGEMENT
Admissible patient

WHO and Special Programme for Research and Training in Tropical Diseases. Dengue
Guidelines for Diagnosis, Treatment, Prevention and Control 2009
DENGUE

MANAGEMENT
Compensated
shock

https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue
%20Clinical%20Case%20Management%20Guidelines%202011-DOH.pdf
DENGUE

MANAGEMENT
Compensated
shock

https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue
%20Clinical%20Case%20Management%20Guidelines%202011-DOH.pdf
DENGUE

MANAGEMENT
Hypotensive
shock

https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue
%20Clinical%20Case%20Management%20Guidelines%202011-DOH.pdf
DENGUE

MANAGEMENT
Hypotensive
shock

https://pcp.org.ph/images/PSBIM/PSBIM_Local_Guidelines_2019/Revised%20Dengue
%20Clinical%20Case%20Management%20Guidelines%202011-DOH.pdf
DENGUE

MANAGEMENT
OF BLEEDING Mucosal bleeding may be
minor, if px is stable clinically
• In patients with
profound Do not give IM injections
to avoid hematoma.
thrombocytopenia,
CBR and protection
from trauma
• GI bleeding may not Major bleeding = either
be immediately from GI or vagina
apparent until first
black stool is passed
DENGUE

MANAGEMENT
OF BLEEDING RISK FACTORS
• Recognize severe bleeding
• Persistent and/or severe overt
Prolonged/refractory shock
Hypotensive shock + renal/liver failure ± severe metabolic acidosis 1
bleeding
• ↓Hct after fluid resuscitation + If on NSAIDs or anticoagulant therapy 2
unstable hemodynamic status
• Refractory shock that fail to
respond to consecutive fluid Comorbid: peptic ulcer disease 3
resuscitation of 40-60 mL/kg
• Hypotensive shock + Any form of trauma 4
low/normal hematocrit before
fluid resuscitation
• Persistent or worsening
metabolic acidosis especially in
those with abdominal
tenderness and distension
DENGUE
MANAGEMENT
OF BLEEDING
• Recognize severe bleeding
• Persistent and/or severe overt
bleeding
• ↓Hct after fluid resuscitation +
unstable hemodynamic status
• Refractory shock that fail to
respond to consecutive fluid
resuscitation of 40-60 mL/kg
• Hypotensive shock +
low/normal hematocrit before
fluid resuscitation
• Persistent or worsening
metabolic acidosis especially in
those with abdominal
tenderness and distension
• ACTION PLAN
• Give 5-10 mL/kg of fresh
packed red blood cells or
10-20 mL/kg of fresh whole
blood at an appropriate rate
• A good clinical response
includes improving
hemodynamic status and
acid-base balance.
• Consider repeating the blood
transfusion if there is
• further blood loss or no
appropriate rise in Hct after
blood transfusion
• Give PPCs/ FFPs judiciously
DENGUE

DISCHARGE CRITERIA
• ALL of the following conditions must be present
• 1. No fever for 48 hours
• 2. Improvement in clinical status (general wellbeing,
appetite, hemodynamic status, urine output,
no respiratory distress)
• 3. Increasing trend of platelet count
• 4. Stable hematocrit without intravenous fluids
DENGUE

VACCINATION
• ALL of the following conditions must be present
• 1. No fever for 48 hours
• 2. Improvement in clinical status (general wellbeing,
appetite, hemodynamic status, urine output,
no respiratory distress)
• 3. Increasing trend of platelet count
• 4. Stable hematocrit without intravenous fluids
DENGUE

DENGUE
PREVENTION
DENGUE

PRACTICE 5S
• Search and destroy
• Self-protect
• Seek consultation
• Support fogging in outbreak areas
• Sustain hydration

DOH, 2014
DENGUE

VACCINATION
DENGVAXIA TAK-003
four chimeric yellow tetravalent vaccine
fever 17D-dengue based on an
vaccine viruses attenuated laboratory-
derived DENV-2 virus
superior efficacy and
clinical benefit in may be used in
seropositive versus seropositive or
seronegative vaccine seronegative
recipients individuals

trend of superior high efficacy against

efficacy and beneficial hospitalized dengue
vaccine effect in older
children

DOH, 2014
 DENGUE
DENGVAXIA CONTROVERSY
Mendoza et al. Int J Health Plann Manage.
2021 Nov; 36(6): 2048–2055.
• 2016 recommendation - use among 9 – 45 year‐olds in endemic countries
• 2017 – Sanofi publicly announced that Dengvaxia increased the risk of
severe dengue for seronegative individuals
• 2017 – reconvention and strategy making
to screen prior to vaccination and
to vaccinate populations with high
vaccinate only seropositive
seroprevalence rates (above 80%)
individuals in endemic areas
• 2017-2019 – heavy mainstream sensationalization, leading to banning of
the vaccine in 2019 in the Philippines
Given the vaccine's proven efficacy, withholding it would be inflicting harm by omission
to seropositive individuals.
• 2019 – WHO endorsed Dengvaxia in their List of Essential Medicines
DENGUE
Manuel S. Vidal, Jr., MD, PhD
Department of Family and Community Medicine
Sta. Ana Hospital