2. • Epidemiology
• Dengue virus & serotype trends in Malaysia
• Course of dengue illness
• Clinical evaluation
• Plan of management in primary care
OBJECTIVES
3. EPIDEMIOLOGY
Latest updated on August:
• From January to Aug 6, 2021, a total of 16,565 dengue
cases were reported compared to 63,988 in the same
period in 2020, which is a reduction of 47,423 cases or
74.1 per cent.
• "The average weekly dengue cases reported so far is 534
cases a week, compared to 1,700 a week in 2020 and
2,500 a week in 2019.
4. VIROLOGY
Dengue infection dengue virus (mosquito-borne flavivirus)
Transmitted by Aedes aegypti & Aedes albopictus
Serotypes : DENV-1,2,3 and 4
Each episode of infection induces a life-long protective
immunity to the homologous serotype but only partial and
transient protection against other serotypes
5. COURSE
• Incubation period is 4-7 days (range 3-14)
• It may be asymptomatic or may result in a spectrum of illness ranging from
undifferentiated mild febrile illness to severe disease, with or without plasma
leakage & organ impairment
• Symptomatic dengue infection is a systemic and dynamic disease with clinical,
hematological and serological profile changing from day to day
• After the incubation period, the illness begins & followed by :
Febrile, critical and recovery phase
6. FEBRILE
Last 2-7 days
• facial flushing , rash
• generalised body ache
• vomiting, headache
• petechiae, mucosal
membrane bleeding , PV
bleeding, GI bleeding
• tender liver
FBC bicytopenia : WCC <7,
PLT <150
Tender liver
*tourniquet test
Time
Characteristic
Blood
investigations
Warning signs
CRITICAL
Last 24-48H (occurs 3rd day of
fever, may occur earlier)
• Rapid drop in temperature
(defervensce)
1. Increase in capillary
permeability Plasma
leakage compensated/
decompensated shock
2. Decrease plasma volume
PLT <150 & increase HCT
• Altered GCS
• Restlessness
• Mucosal bleed
• Fluid accumulation
• Tender liver
• Abdominal pain
• Persistent GI loss
RECOVERY
After 24-48H of critical phase
• Plasma leakage stops
followed by reabsorption
• Well being improves
• Appetite returns
• Haemodynamically stbale
• Isles of white in the sea of
red
WCC & HCT levels stabilize
In some instances, organ
dysfunctions may worsen
• Hepatitis
• Encephalitis
• ICB
7.
8.
9. Tourniquet Test
The sensitivity of
the test: 0% to
57%, depending
on the phase of
illness and how
often the test
was repeated, if
negative.
5-21% of patients
with dengue like
illness had
positive
tourniquet test
but subsequently
have negative
dengue serology
A recent study demonstrated that
there was 95.3% positive
predictive value if fever, positive
tourniquet test, leucopenia/
thrombocytopaenia/
haemoconcentration were used as
screening criteria.
10. Acute increase in vascular permeability leakage of plasma into
extravascular compartment haemoconcentration
hypovolaemia / shock tachycardia & generalised vasoconstriction
due to increased sympathetic output
Clinical manifestations of vasoconstriction :
• Skin - coolness, pallor, delayed CRT
• CVS - raised DBP
, narrowing of PP
• Renal system - reducing UO
• GI system - persistent vomiting & diarrhoea, abdominal pain
• CNS – lethargy, restlessness, reduced consciousness level
• Respiratory – tachypnoeic ( RR > 20 )
Plasma leakage
11.
12. • Inadequate perfusion of the tissue increased
anaerobic glycolysis & lactic acidosis
• Late complications of prolonged shock :
• massive bleeding
• disseminated intravascular coagulopathy (DIC)
• multi-organ failure
13.
14.
15. Medical complications seen in dengue phases
1. Febrile : dehydration. High fever cause neurological
disturbancs and febrile seizures in young children
2. Critical : shock from plasma leakage : severe
haemorrhage and organ impairment
3. Recovery : hypervolaemia (only in IV Fluid therapy
has been excessive and/or has extended into this
period) and APO.
16. Clinical evaluation of the patients involves 4 STEPS
1. History taking
2.Clinical examination
3.Investigations
4.Diagnosis and assessment of disease phase and
severity.
Clinical evaluation
17. A patient’s history should include:
• Date of onset of fever
• Oral intake
• Assess of warning signs
• Change in mental state/ seizure/ dizziness
• Other important relevant histories :
1. Family or neighbourhood history if dengue
2. Jungle trekking or swimming in waterfall : Consider
leptospirosis, typhus and malaria
3. Travelling (consider covid 19)
4. Recent unprotected sexual or drug use behavior : Consider
acute HIV seroconversion illness
5. Co-morbidities (consider sepsis particularly in patients with
DM)
STEP 1 : HISTORY
19. STEP 3 : INVESTIGATIONS
1. Full blood count (FBC)
• Should done at the first visit to establish the baseline haematocrit. However, a normal FBC during the first 72 hours of
illness does not exclude dengue infection
• Should be repeated daily from the 3rd day onwards until the critical phase is over.
• A decreasing white blood cell and platelet count makes the diagnosis of dengue very likely.
2. Haematocrit (HCT) : A rising HCT is a marker of plasma leakage in dengue infection. The median values of normal
HCT level among Malaysian populations are
• male < 60 years – 46%
• male > 60 years – 42%
• female (all age groups) – 40%
• Other important blood tests in disease monitoring are Liver Function Test (LFT), Renal profile (RP), coagulation profile,
lactate and blood gases.
• Special tests such as Troponin and Creatine Kinase (CK) should be discussed with the Specialists/Registrars before
performing
3. Point of care test for dengue (Rapid combo Test ; RCT & NS1 Antigen / Dengue IgM and IgG test )
20. 1. Rapid Combo Test
• detect the presence of virus as well as antibodies simultaneously. Generally RCT tests can be
read within 15-20 minutes.
• Interpretation : presence or absence of bands for dengue NS1 antigen and dengue IgM and
IgG antibodies. These tests have a longer detection window as they can detect both the virus
and antibodies, thus reducing the possibility of false negative results.
• Useful during the early phase of onset when there is viraemia as well as at a later stage when
antibodies against dengue begin to rise. The sensitivity is 93.9% and specificity is 92%.
2. Dengue Antigen And Serology Tests By ELISA
• Non-Structural Protein-1 (NS1 Antigen)
• Dengue IgM & Dengue IgG test
3. Dengue Viral RNA Detection (Real time RT-PCR)
4. Virus Isolation : for research, surveillance and genotyping purposes.
Diagnostic tests
21. • NS1 antigen is a highly conserved glycoprotein that seems to be
essential for virus viability. Secretion of the NS1 protein is a hallmark of
flavivirus infecting mammalian cells and can be found in dengue
infection as well as in yellow fever and West Nile virus infection.
• False positive results have been reported in chronic diseases and
haematological malignancies.
• The detection rate is much better in acute sera of primary infection
(75%-97%) when compared to the acute sera of secondary infection
(60%-70%). The sensitivity of NS1 antigen detection drops from day 4-5
of illness onwards and usually becomes undetectable in the
convalescence phase.
• The presence of NS1 detection after day five may predict severe dengue
Non-Structural Protein-1 (NS1 Antigen)
22. • The IgM capture enzyme-linked immunosorbent assay (ELISA) is
the most widely used serological test. The antibody titre is
significantly higher in primary infections compared to secondary
infections. Once the IgM is detectable, it rises quickly and peaks at
about two weeks after the onset of symptoms, and it wanes to
undetectable levels by 90 days.
• In primary dengue infection, anti-dengue IgM can be detected
after five days of illness in approximately 80% of the cases. Almost
93%-99% of cases will have detectable IgM from day 6 through
day 10. In the event of a negative IgM result, a repeat serum
should be collected after five days.
Dengue IG M test
23. • However, in secondary dengue infections, IgM was detected in among
78% of patients after day seven. IgM appears earlier or at the same time
frame but usually at lower titres compared to primary dengue. This is
possibly due to appearance of high levels of anti-dengue IgG before or
sometimes simultaneously with the IgM response. Thus, 28% of all
secondary dengue infections were undiagnosed when only IgM was the
only assay performed
• In primary and secondary dengue infection, dengue IgG was detected
in 100% of patients after day seven of onset of fever. Therefore, a repeat
dengue IgG is recommended if dengue IgM is still negative after day
seven with the negative IgG in the initial test sample
Dengue IG G test
24. • The method is useful only during the viraemic stage of the disease
and can detect the viral RNA target up to five days after onset of
the symptoms.
• The test is useful for determination of circulating dengue
serotypes in the country.
• Limitations of RT-PCR are: This test is only available in a few
centres with facilities and trained personnel. The test is expensive.
The specimen requires special storage temperatures and short
transportation time between collection and extraction.
Dengue Viral RNA Detection (Real time RT-PCR)
25. • Dengue rapid combo test or NS1-Ag should be taken as soon as
dengue infection is suspected
• If dengue IgM is negative <7 days, a repeat sample must be taken
at recovery phase
• If dengue IgM is still negative >7 days, dengue IgG should be
done for diagnostic confirmation of secondary dengue infection
26. • Serological tests for dengue have been shown to cross-react with:
• other flavivirus – Japanese Encephalitis
• non-flavivirus – malaria, leptospirosis, toxoplasmosis, syphilis
• connective tissue diseases – rheumatoid arthritis
False Positive Dengue Serology
27.
28.
29. STEP 4 : DIAGNOSIS, DISEASE
STAGING & SEVERITY ASSESSMENT
• Based on the evaluations of history, physical
examination and/or FBC and haematocrit, the
clinicians should be able to determine:
• Likelihood of dengue infection
• The phase of dengue infection
(febrile/critical/recovery)
• Severity of the illness
30. PLAN OF
MANAGEMENT
1. Dengue assessment checklist must be filled by the
attending doctor
2. Notify the district health office followed by disease
notification form
3. If admission is indicated
• Stabilise the patient at primary care before transfer
• Communicate with the receiving hospital/emergency
department before transfer
4. If admission is not indicated
• Daily follow up is necessary especially from day 3 of illness
onwards until the patient is afebrile for at least 24-48H
without antipyretics
• Provide the patient with Outpatient Dengue Monitoring
Record & Home Care Advice leaflet for Dengue Patients
31. CLINICAL &
LABORATORY
CRITERIA FOR
PATIENTS WHO
CAN BE
TREATED AT
HOME
• Able to tolerate orally well, good urine
output and no history of bleeding
• Absence of warning signs
• Physical examination
1. Haemodynamically stable
2. No tachypnoea or acidotic breathing
3. No tender liver or abdominal tenderness
4. No bleeding manifestations
5. No signs of third space fluid accumulation
6. No alterations in mental status
• Investigations : stable serial HCT
• No other criteria for admission (co-
morbidities, pregnancy, social factors)
32. • Any abdominal pain/tenderness
• Persistent vomiting (>3X/24H)
• Persistent diarrhea (>3X/24H)
• 3rd space fluid accumulation (eg : ascites, pleural and pericardial effusion)
• Spontaneous bleeding tendency
• Lethargy/restlessness/confusion
• Tender liver
• Raised HCT with rapid drop in PLT
HCT male <60 years – 46%
HCT male >60 years – 42%
HCT female (all age groups) – 40%
Warning Signs
33. ADMISSION CRITERIA
• Symptoms
• Warning signs
• Bleeding manifestations
• Inability to tolerate oral fluids
• Reduced urine output
• Seizure
• Signs
• Dehydration
• Shock
• Bleeding
• Any organ failure
• Special situations
• Patient with co-morbidities (DM,
Hypertension, IHD, Coagulopathy,
morbid obesity, renal failure, CLD,
COPD)
• Elderly >65 years old
• Patients who are on anti-platelet
and/or anticoagulants
• Pregnancy
• Social factors that limit follow up
(living far from healthy facility, no
transport, patient living alone)
• Laboratory criteria : rising HCT
accompanied by reducing PLT
count
34.
35. • Severe plasma leakage leading to dengue
shock
• Severe haemorrhages
• Severe organ impairment (hepatic damage,
renal impairment, cardiomyopathy,
encephalopathy or encephalitis
- During this period, plasma loss should be replaced
immediately ; IV Fuid therapy of 5 to 10 mL/kg of 0.9% saline over 1
hour may be life-saving
Emergency Treatment and Urgent Referral