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DENGUE:

Denggoy, Dengvaxia, Dengue ba sya?


OBJECTIVES

• Discuss the epidemiology and burden of disease of


Dengue

• Review the transmission

• Discuss the new case classification

• Discuss algorithms in the diagnosis and management of


Dengue
EPIDEMIOLOGY

• most rapidly spreading mosquito-borne viral disease


in the world

• incidence: 30-fold increase


• increasing geographic expansion to new countries,
and from urban to rural settings
• 50 million dengue infections annually
Burden of Disease

•  WHO estimates that 2.5 billion people—over


40% of the world’s population-- are at risk for
dengue infection.

• Approximately 50-100 million infections (1


million confirmed) occur each year resulting
in 500,000 hospitalizations and 20,000
deaths.
Dengue Virus Profile

• Genus Flavivirus
• Family Flaviviridae
• Single-stranded RNA
• 4 serotypes (DEN-1 to 4)

• 50 nm diameter with multiple copies


of 3 structural proteins ( membrane
bilayer and single-stranded RNA)
Vector Profile

• Aedes mosquitoes
• A. aegypti
• A. albopictus
• A. polynesiensis
• Tropical and
subtropical species
• Urban places
• Immature stages are
found in water-filled
habitats
The Host

• Incubation period: 4-10 days

• Primary infection induce lifelong


immunity to the infecting serotype

• Protection from different serotype


within 2-3 months of primary
infection
• No long-term cross-protective
immunity
The Host

• Individual risk factors:


• Age, ethnicity, chronic diseases

• Seroepidemiological studies (Cuba and Thailand)


• Secondary heterotypic infection
• Time interval between infections
• Antibody-dependent enhancement of infection
Replication and Transmission

Blood meal Released in


circulation

Viral Replication
WBC and
Lymphatics
Replication and Transmission

Replication in
the salivary
gland

Viral replication Extrinsic Incubation


in midgut • 8--12 days

Female mosquito
ingests infected
blood
Dengue Fever

• Wide spectrum of clinical presentation, with unpredictable


clinical evolution and outcome

• Three phases
• Febrile phase
• Critical phase
• Recovery phase

• Previously classified into


• undifferentiated fever, dengue fever and DHF
• Grade 1-IV
Dengue Fever

Grade 1: fever, non specific constitutional symptoms; (+) TT- only hgic manifestation

Grade 2: Grade 1 manifestation + spontaneous bleeding

Grade 3: signs of circulatory failure (rapid weak pulse, narrow pulse pressure, hypotension, cold
clammy skin)

Grade 4: profound shock with undetectable pulse and BP


CLINICAL
MANAGEMENT
Dengue Fever
Febrile Phase

◼ facial flushing
◼ skin erythema
◼ generalized body ache
• Sudden onset of
◼ myalgia and arthralgia
high-grade fever ◼ headache
• Lasts for 2-7 days ◼ sorethroat, injected pharynx,
and conjunctival injection
◼ anorexia, nausea and
vomiting
Febrile Phase

• (+) TT increases the


probability of dengue

• (+) hemorrhagic
manifestations
earliest abnormality: progressive decrease
in total• wbc
enlarged and tender liver
Critical Phase

• temperature drops to 37.5-38 (days 3-7)

• (+) increase in capillary permeability with


increasing hematocrit levels

• significant plasma leakage lasts for 24-48 hours

• progressive leukopenia followed by rapid


decrease in platelet precedes plasma leakage
Critical Phase

• if (-) increase in capillary permeability 


improve
• if (+) increase in capillary permeability  pleural
effusion and ascites

• degree of increase above the baseline


hematocrit reflects the severity of plasma
leakage
Critical Phase

• shock: critical volume of plasma is lost


• temperature may be subnormal
• prolonged shock  organ hypoperfusion  organ
impairment, metabolic acidosis, and DIC  severe
hemorrhage
• severe hepatitis, encephalitis or myocarditis
Recovery Phase

• gradual reabsorption of extravascular compartment


fluid (48-72 hours)
• general well-being improves, appetite returns, GI
symptoms abate, hemodynamic status stabilizes and
diuresis ensues
• (+) rash: “isles of white in the sea of red”
Recovery Phase

• hematocrit stabilizes or may be lower due to dilutional


effect of reabsorbed fluid
• wbc starts to rise
• recovery of platelet count occurs later
Approach to the Management

• At primary and secondary levels, health care


facilities are responsible for emergency/ ambulatory
triage assessment and treatment

• Triage is the process of rapidly screening patients soon


after their arrival in the hospital or health facility in order to
identify those
– Severe dengue
– With warning signs
– Non-urgent cases
Approach to the Management
Approach to the Management

• Referral centres receiving severely ill dengue patients must


be able to give prompt attention to referred cases.

• Beds should be made available to those patients who meet the


admission criteria

• There should be a designated area to cohort dengue patients,


and a high-dependency unit for closer monitoring of those with
shock.
• Staffed by doctors and nurses
Approach to the Management

Criteria for transfer:


• early presentation with shock (on days 2 or 3 of illness);
• severe plasma leakage and/or shock;
• undetectable pulse and blood pressure;
• severe bleeding;
• fluid overload;
• organ impairment (such as hepatic damage,
cardiomyopathy, encephalopathy,
• encephalitis and other unusual complications).
Approach to the Management

Disease notification
• In dengue-endemic countries, cases of suspected, probable
and confirmed dengue should be notified
• Public health measures
– suspected cases
• lives in or has travelled to a dengue-endemic area
• fever for three days or more
• low ordecreasing white cell counts
• thrombocytopaenia ± positive tourniquet test.
Approach to the Management
Management Decisions

Groups A Groups B
• may be sent • referred for in- Groups C
home hospital • require
• tolerate management emergency
adequate • with warning treatment and
volumes of oral signs, co- urgent referral
fluids and pass existing • severe dengue
urine at least conditions, (in critical
once every 6 • with certain phase)
hours social
Group A Action Plan

• Encourage intake of ORS, fruit juice and other fluids


• Paracetamol and tepid sponge for fever
• Advise to come back if with
no clinical improvement
severe abdominal pain
persistent vomiting
cold and clammy extremities,
lethargy or irritability or restlessness,
bleeding
not passing urine for more than 4–6 hours.

monitor:
temperature pattern, volume of fluid intake and losses, urine output, warning signs, signs of plasma
leakage and bleeding, haematocrit, and white blood cell and platelet counts
Group B (with warning signs)
Action Plan

• reference hematocrit before fluid therapy


• isotonic solutions
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 the clinical response

reassess:
• haematocrit remains the same or rises only minimally  2–3 ml/kg/hr for
another 2–4 hours
• worsening vital signs and rising haematocrit rising  5–10 ml/kg/hour for 1–2
hours
Group B (with warning signs)
Action Plan

Give minimum intravenous fluid volume: maintain


good perfusion and urine output of about 0.5
ml/kg/hr
• Intravenous fluids are usually needed for only 24–48 hours.
• Reduce intravenous fluids gradually when the rate of plasma leakage decreases
towards the end of the critical phase.

monitor:
• vital signs and peripheral perfusion (1–4 hourly until the patient is out
of the critical phase)
• urine output (4–6 hourly)
• hematocrit (before and after fluid replacement, then 6–12 hourly)
• blood glucose
• organ functions (renal profile, liver profile, coagulation profile)
Group B (without warning signs)
Action Plan

• Encourage oral fluids


• If not tolerated, start intravenous fluid therapy of 0.9%
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
intravenous fluid therapy.
• Give the minimum volume required to maintain
good perfusion and urine output.
• Intravenous fluids are usually needed only for 24–
48 hours.
• Close monitoring
Group C Action Plan

• admit to a hospital with access to intensive care


facilities and blood transfusion
• plasma losses should be replaced immediately and
rapidly with isotonic crystalloid solution or, in the case
of hypotensive shock, colloid solutions

• blood transfusion: with suspected/severe bleeding

• judicious intravenous fluid resuscitation:


sole intervention required
Group C Action Plan

Goals of fluid resuscitation:


• improving central and peripheral circulation
(decreasing tachycardia, improving BP, warm and pink
extremities, and capillary refill time <2 seconds)

•improving end-organ perfusion


– i.e. stable conscious level (more alert or less restless), urine
output ≥ 0.5 ml/kg/hour,
decreasing metabolic acidosis.
Treatment of Hemorrhagic Complications

Patients at risk of major bleeding are those who:


• prolonged/refractory shock;
• hypotensive shock and renal or liver failure and/or severe
and persistent metabolic acidosis
•given non-steroidal anti-inflammatory agents
• pre-existing peptic ulcer disease
• anticoagulant therapy
• any form of trauma
Treatment of Hemorrhagic Complications

• Blood transfusion is life-saving and should be given as soon


as severe bleeding is suspected or recognized

• Do not wait for the haematocrit to drop too low before


deciding on blood transfusion

• Risk of fluid overload.


Treatment of Hemorrhagic Complications

• blood transfusion if with bleeding


• 5-10 ml/kg of PRBC or 10-20 ml/kg FWB
• repeat if with further blood loss or no rise in
hematocrit after transfusion

• little evidence to support transfusion of platelet


concentrate and FFP
• massive bleeding not managed by FWB/PRBC
• may exacerbate fluid overload
Management of Complications

• Fluid Overload
Causes:
– excessive and/or too rapid intravenous fluids;
– incorrect use of hypotonic rather than isotonic crystalloid solutions;
– inappropriate use of large volumes of intravenous fluids in patients with
unrecognized severe bleeding;
– inappropriate transfusion of FFP, platelet concentrates and
cryoprecipitates;
– continuation of IVF after plasma leakage has resolved
– co-morbid conditions such as congenital or ischaemic heart disease, chronic
lung and renal diseases
Management of Complications

Clinical Features:
Other investigations:
– respiratory distress, difficulty in
breathing; • CXR
– rapid breathing;
– chest wall in-drawing; •ECG
– wheezing (rather than crepitations);
– large pleural effusions;
•ABG
– tense ascites;
Management of Complications

• Oxygen therapy
• Stop IVF
• When to discontinue IVF:
– stable blood pressure, pulse and peripheral perfusion;
– haematocrit decreases in the presence of a good pulse volume;
– afebrile for more than 24–48 days (without the use of antipyretics);
– resolving bowel/abdominal symptoms;
– improving urine output

•If necessary, give oral or intravenous furosemide 0.1–0.5 mg/kg/dose


once or twice daily, or continuous infusion of furosemide 0.1 mg/kg/hour.
Management of Complications

• If the patient has stable haemodynamic status but is still within the critical phase,
reduce the intravenous fluid accordingly. Avoid diuretics during the plasma
leakage phase

• Patients who remain in shock with low or normal haematocrit levels but show
signs of fluid overload may have occult haemorrhage.
• Careful fresh whole blood transfusion
• repeated small boluses of a colloid solution
Criteria for Discharge
Dengue Vaccine

» Vaccination is an important component of a


comprehensive dengue prevention and control
strategy in highly endemic areas.
» Philippines is has high endemicity for Dengue
» Limited study on seroprevalence (Cebu)
» Seroprevalence for all ages >80%
Recommended Vaccine
» Recombenant live attenuated tetravalent
dengue vaccine
» approved for ages 9-45 years old
» Schedule: 0,6,12 months at 0.5 ml
subcutaneously
Efficacy
» 65.6% reduction in symptomatic dengue
» 80.8% reduction in hospitalised dengue
» 93.2% reduction in sever dengue
» Serologic testing is recommended since its
effectivity in preventing mortality and
morbidity is higher among among seropositive
(81.9% vs 52.5%)
There is no ethics and morals in
Philippine Politics
Never trust a Politician with your
health…..
Or with anything

J. Ancheta, MD

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