Dengue: Clinical Features,

Investigations, Differential Diagnosis

Manifestations of Dengue Infection
 Dengue Fever
• Symptomatic dengue infection is a systemic and dynamic disease having
wide clinical spectrum that includes both severe and non-severe clinical
manifestations.
• The incubation period lasts for 5 to 7 days and the onset of the
illness is abrupt.
• Common presenting symptoms include high-grade fever, headache,
retro-orbital pain, myalgia, arthralgia, nausea, vomiting and rash.
The symptoms usually last for 2-7 days.
• Three phases: febrile, critical and recovery.
• The severity of the disease becomes apparent during defervescence
(transition from the febrile to the afebrile phase).
• Increased capillary permeability, that lasts approximately for 24 to 48
hours, is more common in secondary dengue infections.
 Clinical Criteria of DF

Dengue fever: Acute febrile illness of 2-7 days duration with two or more
of the manifestations: eg. Headache, retro-orbital pain, myalgia, arthralgia,
rash, haemorrhagic manifestations, thrombocytopenia / leucopenia,
warning signs and symptoms
 Clinical Criteria of DHF
a) A case with clinical criteria of dengue fever plus
b) Haemorrhagic tendencies, evidenced by one or more of the following:
• Positive tourniquet test
• Petechiae, ecchymoses or purpura
• Bleeding from mucosa gastrointestinal tract, injection sites or other site plus
c) Thrombocytopenia (<100000 cells per cumm) plus
d) Evidence of plasma leakage manifested by one or more of the following:
• A rise in average haematocrit for age and sex >= 20%
• A more than 20% drop in haematocrit following volume replacement
• Signs of plasma leakage (pleural effusion, ascites, hypoproteinemia )
 Grading of DHF
• DHF-I
• DHF-II: some evidence of spontaneous bleeding in skin or other organs (black tarry
stool, epistaxis, gum bleeds) and abdominal pain.
• DHF-III (DSS): Circulatory failure (weak rapid pulse, narrow pulse pressure < 20 mm
Hg, Hypotension, cold clammy skin, restlessness).
• DHF-IV (DSS): Profound shock with undetectable BP or pulse.
Various risk factors associated with severe disease of dengue

Infant young children pregnant women elderly person

Immuno-
obese patient hypertension diabetes mellitus compromised
persons

CLD and CKD ;

Hb-pathies e.g.
haemolytic
sickle - cell disease,
conditions
and autoimmune
diseases
Course of Dengue illness
 Course of Dengue illness
Febrile or Viraemic Phase Critical Phase Recovery Phase
• Lasts for 2 to 7 days. • Warning signs • Gradual re-absorption of
between days 3 extra-vascular compartment
• Symptoms: Headache, fluid takes place in following
Myalgia, Arthralgia, Retro- and 7 of illness. 48 to 72 hours.
orbital pain • Increased capillary
permeability • General well-being
• Children: anorexia, N/V improves
causing plasma
• Progressive decrease in WBC leakage. • Isles of white in the sea of
(TC<5000/ cu mm) & mild
Thrombocytopenia +/- mild • A Rising Hematocrit red
hemorrhage is the earliest sign • Fluid Overload may
of plasma leakage. happen
• Positive Tourniquet Test
Dehydration, High fever Shock from plasma Hypervolemia and acute
leakage: severe pulmonary oedema
neurological disturbances
hemorrhage and
& febrile seizure organ impairment
 Phase Complication

Dehydration: High fever may cause neurological

Febrile phase
disturbances and febrile seizures in young children

Shock from plasma leakage; severe hemorrhage and

Critical phase
organ impairment

Hypervolemia (only if intravenous fluid therapy has

Recovery phase been excessive and/or has extended into this period)
and acute pulmonary oedema
 Dengue patient
with
Maculopapular
rash

Finger impression
on skin isles of white in the sea of red
of a dengue patient

Rounded Stetho
impression on
skin of a dengue
patient
 Clinical Evaluation

• History taking

• Clinical examination

• Investigations

• Diagnosis and assessment of disease phase & severity

 Step 1: A patient’s history to be asked
1. Date of onset of fever (date is
6. Shortness of breath/ inability to
preferable to the number of days of
walk or sit
fever)
2. A history of dengue fever among
households and neighbor, living in or 7. Bleeding from any orifice, any
recent travel to a dengue endemic bleeding spot on skin/mucosa
region
3. History of chills, rash and facial 8. Reduced urine output, cold
flush peripheries
4. Retro-orbital headache, arthralgia, 9. Profuse sweating, postural
malaise dizziness, blurring of vision.

5. Persistent vomiting/diarrhea, pain 10. Yellowish discoloration of skin

abdomen and mucosa, altered sensorium
 Ask 3 golden questions
1. Oral fluid intake-quantity and types of fluids
Assess hydration
2. Urine output-quantify in terms of frequency and
status from estimated volume and time of most recent voiding
history
3. Types of activities performed during this illness (e.g.,
can the patient go to school, work, market, etc.)

These questions, though not

• Other fluid losses, such as vomiting or
specific to dengue, give a good
diarrhea
indication of patient’s hydration
• Presence of warning signs, particularly
status and how well the patient
after the first 72 hours of fever
copes with his illness.
• Medications (including non-
prescription or traditional medicine) in
Other Relevant History
use and the time they were last taken
• Risk factors
 Step 2: Clinical examination: Assess

Peripheral Perfusion: Hold the patient’s hand

and assess peripheral perfusion by the Color,
Temperature Capillary refill time, Temperature of the
extremities, Pulse Volume and Pulse Rate
(CCTVR)
Tachypnea/ Acidotic breathing/Pleural
Blood pressure
effusion
Abdominal tenderness/Hepatomegaly/
Mental state
Ascites
Maculopapular or macular
Tourniquet test
confluent Rash; Conjunctiva
Hydration status Examine Top Sheet
 Warning and danger signs of dengue fever
Warning signs in dengue fever
 Bleeding: epistaxis, scanty haemoptysis, hematemesis, gum bleeding,
black coloured stools, excessive menstrual bleeding, dark-coloured urine
or haematuria.
 Lethargy and/or restlessness; sudden behavioural changes
 Convulsions.
 Difficulty in breathing or palpitation or breathlessness.
 Persistent vomiting >3 times a day.
 Severe abdominal pain
 Postural hypotension - dizziness.
 Pale, cold clammy extremities.
 Not able to drink and no urine output for 4-6 h or urine output less than
0.5 ml/kg/h.
 Warning and danger signs of dengue fever
 Additional danger signs for clinicians
 Enlarged and/or tender liver
 Rising haematocrit together with rapid fall in platelet count.
 Metabolic acidosis.
 Derangement of liver/ kidney function tests.
 Pleural effusion/ ascites/ gall bladder oedema clinically or by
imaging.

Key points:
 Warning signs between days 3 and 7 of illness.
 Increased capillary permeability causing plasma leakage is the
main pathophysiology.
 A rising haematocrit is the earliest sign of plasma leakage
 Shock in Dengue
Compensated shock:
• Systolic BP normal but there are tachycardia & tachypnoea without
increased effort.
• Extremities cold and capillary refill time delayed (> 2 seconds).
• Pulse pressure < 20 mm Hg in children.
• PCV increased due to plasma leakage.

Normal SBP and/or Narrowed Pulse Pressure alongside Delayed CRT

& Increased Hematocrit: Prompt action warranted
Prevention or Correction of Dehydration at the compensated shock
stage avoids many of the dengue complications
 Shock in Dengue......contd.
Hypotensive shock:
Results from worsening of compensated shock.
• Increasing tachycardia and peripheral vasoconstriction.
• Limbs become mottled, cold and clammy.
• Breathing becomes more rapid and deep (a compensation for the
metabolic acidosis - Kussmaul’s breathing).
• Change in mental state as brain perfusion declines. However, children
and young adults may have a clear mental status.
• Finally, decompensation, when both systolic and diastolic BPs decrease
suddenly.
• Prolonged hypotensive shock and hypoxia lead to severe metabolic
acidosis and multiple organ failure and also DIC.
 Hypotensive shock.......contd.
• Hypotension is a late finding and it signals an imminent total cardio-
respiratory collapse and hence requires urgent intervention to
prevent mortality.
• Prolonged hypotensive shock and hypoxia lead to severe metabolic
acidosis and multiple organ failure. When major bleeding occurs, it
is almost always associated with profound shock and can lead to
multiple organ failure and advanced disseminated intravascular
coagulation.
 Hypotensive shock.......contd.
• Massive bleeding may occur without prolonged shock in instances
when NSAID or corticosteroids have been taken.
• Acute liver and renal failure, encephalopathy and cardiomyopathy
may be present in severe shock; or even in the absence of shock.
However, most deaths from dengue occur in patients with
profound and prolonged shock resulting from plasma leakage
and complicated by bleeding and/or fluid imbalance.
 Case study

• A 19 years old girl is brought to the emergency at night with history of

profound weakness and dizziness. On examination the patient is
conscious and alert.
• Blood pressure - 88/66 mmHg
• Pulse – 116/min
• Respiration - 28/ min
• Temperature – 97o F
• The relatives gave a history that she was running a temperature for the
last three days. She was treated by a local doctor who had prescribed
paracetamol and antibiotics. No blood investigations were advised.
• What will be your approach to this patient?
 Laboratory Investigations

Complete Blood Count (CBC) (including WBC count, platelets, Haematocrit/ PCV):
- Should be done at the first visit to establish the baseline hematocrit
- HCT in the early febrile phase can be used as the patient’s own baseline.
Should be repeated after the 3rd day of illness or with warning signs and
with risk factors for severe disease
- In the absence of baseline haematocrit, age-specific population haematocrit
levels can be used as a surrogate during the critical phase
- HCT value of >40% in female adults and children aged <12 years and >45%
in male adults should raise the suspicion of plasma leakage
- Leucopenia usually precedes the onset of the critical phase
 Other haematological features
• Leukopenia with Relative Lymphocytosis
• Thrombocytopenia (< 100,000 per mm3)
(A decreasing WBC and platelet count makes the diagnosis of
dengue very likely and rapid decrease in platelet count with
concomitant rising haematocrit is suggestive of plasma
leakage/critical phase )
 Baseline tests other than CBC in dengue
Additional baseline tests should be done in the following conditions:
a. Patient having comorbidity
b. Patient having warning sign(s)
c. Preferably in all admitted dengue cases.
d. These tests should be done during first consultation to get the
baseline characteristics like Haematocrit and Complete blood count if
the patient presented within 5days of fever. Follow up testing may be
done on 1st afebrile day, but should be done daily once if DHF is
suspected or warning signs are present.
e. A regular haematocrit is more important for management than the
thrombocytopenia. Even in severe dengue especially with shock hourly
haematocrit is crucial for management.
 Baseline tests other than CBC in dengue…….contd.

The additional baseline tests include:

• FBS
• Liver function test –AST levels are higher as compared to ALT in dengue
• Kidney function test – serum urea & creatinine
• Coagulation profile (Prothrombin Time, INR etc.)– around Day 5 of
illness (if facility exists).
Other Required Investigations: As per Clinical Judgement
- Complete Blood Count - CXR (PA & Lateral Decubitus)
- Blood Sugar - USG abdomen including IVC diam.
- LFT & RFT - Serum Amylase/Lipase
- Serum Electrolytes - Bicarbonate or lactate
- ABG - Cardiac enzymes
- ECG

Features helpful for differentiation from other viral aetiologies:

1. Positive Tourniquet Test
2. Leucopenia with Relative lymphocytosis
3. Thrombocytopaenia
4. Aspartate Aminotransferase (AST) elevation higher than ALT elevation
 Differential Diagnosis
Disease Classical s/s Differentiating feature of Dengue

Upper respiratory symptoms like rhinitis and cough

may be present in both. Patients with dengue
Fever, headache,
Influenza usually have gastrointestinal symptoms (i.e.
myalgia, malaise, RTI
abdominal discomfort, vomiting and sometimes
diarrhea) during the febrile phase.

High fever with chill and Splenomegaly and prolonged fever should prompt
rigor, Hepatosplenomegaly, the consideration of malaria. Thrombocytopenia
Malaria
features of complication may be present in both, further diagnostic studies
sometimes are needed.

Fever, headache, malaise, Splenomegaly and prolonged fever should prompt

anorexia, abdominal pain, the consideration of typhoid. Severe break bone
Typhoid
rose spots, feature usually absent .Very difficult to differentiate
fever
hepatosplenomegaly, complicated typhoid fever from DSS; diagnostic
altered mental status studies are needed.
 Initial phase-fever
Jaundice more often associated with leptospirosis, but
Headache
ocular pain, arthralgia and diarrhea could be present as
Chill
well, whereas dengue may be associated with elevated
Myalgia
liver enzymes and mild jaundice. Pulmonary
transient rash & non-
hemorrhage is a particular form of leptospirosis without
Leptospirosis purulent conjunctival
jaundice that may confuse with severe dengue though
discharge
uncommon in dengue. Evidence of plasma leakage
Second phase-
would suggest the diagnosis of dengue. Fever,
Meningitis,
thrombocytopenia, raised liver enzyme, renal
Renal disease,
involvement are common features in both.
Liver failure
Eschar, if present, is a characteristic feature. History of
Fever, chill, myalgia, living at a high endemic place can provide a clue. Some
headache
degree of thrombocytopaenia may occur in scrub
lymphadenopathy,
typhus. However, leucocytosis is common (unlike
rash - usually
leucopaenia in dengue). Spleen & liver may enlarge.
maculopopular.
Scrub Typhus
Vital organ involvement Dry cough & pneumonitis may develop. Encephalitis is
in complicated stage. more common, as compared to dengue. IgM ELISA is
confirmatory after 5 days of illness.
 While fever, arthralgia, rash, malaise and
Fever
leucopenia are common in both Chikungunya and
Rash
dengue, symmetric arthritis of small joints is
Chikungunya Arthralgia
pathognomonic of the former and bleeding
Arthritis
tendency and pronounced thrombocytopenia are
Headache
more frequent in dengue.

The rash associated with rubella has a particular

Fever, Rash, Posterior
distribution from the head to the trunk and
auricular or sub-occipital
Rubella extremities, but in dengue the rash usually first
lymphadenopathy, Headache,
appears on the trunk and later extends to the
Conjunctivitis, Polyarthritis
face and extremities

The rash associated with measles has a particular

Fever distribution from the head to the trunk and
Maculopapular rash extremities, but in dengue the rash usually first
Measles
Sore throat appears on the trunk and later extends to the
RTI face and extremities. Severe thrombocytopenia is
uncommon.
 Attending a fever case in the OPD or ER
Mild URTI or mild Fever > mild, or fever with other
fever without any significant symptoms. Or, a mild case but
significant symptom; with h/o of close contact or travel to high
no h/o close contact incidence State or health care worker
with covid-19 (+)ve
case or travel to high
incidence State; not a
health care worker CBC Not required if Test for Tests for dengue, covid-
(Complete fever obviously malaria i.e. 19, scrub typhus etc.
Blood Count) attributable to RDT or Malaria
diseases like Microscopy
If case fits into If fever exceeds 5
Give necessary UTI, clinical case days and features
treatment. pneumonia etc. definition of meet the clinical
Advise domiciliary dengue, especially criteria
management. in absence of
If positive, treat
for malaria as respiratory
per protocol symptoms / in Test by scrub
presence of vital typhus IgM ELISA
organ involvement

Test by
Dengue NS-1
**Please note: ELISA/ IgM
ELISA
• Until covid-19 test report is available, keep the patient
in isolation bed of your hospital or in a Pre-Covid Hospital.
• Please utilize the covid-19 diagnostic facility available in your If features point
hospital for prompt report i.e. CBNAAT or TrueNat or Rapid towards the possibility
Antigen Test; otherwise try fast-tracking with the tie-up RT- of covid-19 and if
PCR Lab. hospitalization is
required, get test
done for covid-19**

If report is negative, treat in general ward thereafter and do

not refer out unless essential. If hospitalization
If report is positive, send to a suitable Covid Hospital not required,
advise test and
isolation in home
or Safe Home
 Expanded Dengue Syndrome (EDS)
•“Unusual manifestations of patients with severe organ involvement such as liver, kidneys, brain or
heart associated with dengue infection” (WHO 2011)
• EDS is commoner in dengue with co-morbidities.

System Manifestations System Manifestations

Encephalopathy
Myocarditis
Encephalitis ⁄ aseptic meningitis
Neuro- Conduction
Intracranial haemorrhages⁄ thrombosis Cardiac
logical abnormalities
Mononeuropathies⁄ polyneuropathies,
Pericarditis
Guillain-Barré syndrome, Myelitis
Hepatitis ⁄ fulminant hepatic failure ARDS
Respiratory
Acalculous cholecystitis Pulmonary hemorrhage
GI ⁄
Acute pancreatitis
Hepatic Musculo- Myositis
Febrile diarrhea
skeletal Rhabdomyolysis
Acute parotitis
Hemolytic uremic
Lympho- Spontaneous splenic rupture,
Renal syndrome
reticular Lymph node infarction
Renal failure
 Laboratory Diagnosis of Dengue
 NS1 Antigen Detection
 Serology: The study of the diagnosis of disease by measuring antibody levels in
serum is referred to as serology.
 IgM-captured enzyme-linked immunosorbent assay
(MAC ELISA)
 Haemagglutination-inhibition
 Neutralization
 Indirect IgG ELISA
 Rapid test
 RT-PCR and Real time RT PCR
 Virus Isolation and Culture
 Step 3 : Investigation for Diagnosis
From onset of Illness to 5 days of From 6th Day onwards
fever
Antibody Detection
Virus detected in serum, Plasma, First antibody to appear– IgM
circulating blood cells and tissues Secondary Antibody– IgG

Virus isolation
Nucleic Acid Detection
NS1 Antigen Detection
For practical purposes any one of the NS1Ag and IgM assays is
confirmatory for diagnosis of Dengue if done through ELISA method
 Collection, storage and transportation of samples

• 3-5 ml clotted blood to be collected in screw capped vials or vacutainers.

• Samples to be transported in cold chain (2-80 C e.g. vaccine carrier)
• Appropriate labeling is most important
• Serum must be separated before transportation
• No Frozen whole blood
• Storage, if necessary, also in 2-8℃ (not more than 1 week)
Thank You
Severe Dengue
 Case definition…..

• Laboratory confirmed Dengue Virus infection with clinical features

of Severe manifestation
• Severe manifestation like,
a. Severe plasma leakage
b. Severe Bleeding
c. Shock +/- Organ involvement
Severe plasma leakage

Severe plasma leakage that may

lead to,

o Shock(Dengue Shock)(DSS)
o +/- fluid accumulation in third
space
o +/- Respiratory distress
 Dengue shock syndrome…(1/2)
1. Increase vascular permeability ----hypovolemia ----shock
2. Usually on Day 4-5 illness
3. Initial stage : Normal SBP, Tachycardia, peripheral
vasoconstriction, reduce skin perfusion, cold extremities,
delayed capillary refill time
4. Diastoloic BP raises
5. Pulse pressure narrows(<= 20mmhg)
 Dengue shock syndrome…(2/2)
6. Hypotension (Systolic BP: 90-80mm Hg for adult/older children &
<80mm hg for children <5 yrs age)
7. Patient may conscious and lucid
8. Hypotension and hypoperfusion may lead to MOF
9. Rising HCT (>20% of baseline)indicate plasma leakage like Pleural
effusion, ascities, hypoproteinemia /hypoalbuminemia
 Severe Bleeding
-----as evaluated by clinician
1. Acute onset of fever with 2-7 days duration
2. Haemorrhagic manifestation –
a. +ve Tourniquet Test
b. petechia/ecchymoses/purpura
c. Bleeding from mucosa/GI tract or other location
3. Platelet count <1,00,000/cmm of blood
4. Hypoxia and acidosis
5. MOF and advanced DIC
6. If patient is on Aspirin, NSAIDS ,Corticosteroid massive severe bleeding
without shock
 Grading of DF and DHF…(1/3)

• DF: Fever 2-7 days + Headache, Retro-orbital pain, Myalgia, Arthralgia,

+/- Leukopenia, Thrombocytopenia & no evidence of plasma leakage
• DHF-I: DF + a. Positive T-Test, b. evidence of plasma leakage, c. Platelet
count <1,00,000/cmm, d. HCT>20% of baseline, e. HCT <20% of
baseline
 Grading of DF and DHF…(2/3)
• DHF-II: DHF-I+ evidence of bleeding and abdominal pain
• DHF-III (DSS): DHF-II + circulatory failure (weak rapid pulse, narrow Pulse
pressure, hypotension,cold clammy skin, restlessness
• DHF-IV (DSS) Profound shock + undetectable BP/pulse
 Grading of DF and DHF …(3/3)

• DHF-I: considered as compensated shock and should be managed with

IVF
• DHF-I & II: may be severe when they present with significant bleeding or
with metabolic & electrolyte abnormalities
• DHF-III & IV: considered as Severe Dengue with or without significant
bleeding
 DF with Organ involvement
• DF with sepsis or severe Respiratory distress (ARDS/Pulmonary
hemorrhage)
• Vital Organ involvement
i) Elevated Liver enzyme: AST/ALT>1000IU, Hepatitis, Acute Pancreatitis,
Acute acalculous chelecystitis, Acute dirrhoea
ii) CNS: impaired consciousness, encephalopathy, meningitis
iii) Dysfunction of Heart (Myocarditis, conduction abnormalities,
pericarditis/ Kidney (Renal Failure/ Hemolytic uremic syndrome) or
other organ/ system (Musculo-skeletal/ Lympho-reticular)
 Risk factors associated with Severe Dengue
• Infant
• Young children
• Pregnant women
• Older person
• Obese patients
• Hypertension
• Diabetes Mellitus
• Immunocompromised persons
• Chronic Liver Diseases
• Chronic Kidney Diseases
• Hemolytic condition
 Clinical management

• Follow Clinical management of DHF(I &II) and DSS(DHF III &IV),choice of

IVF for resuscitation, management of severe bleeding and Intensive care
management of Severe cases as per MO manual of Dengue/Malaria/AES-
JE

(last version 2024)

Indication of Red cell transfusion

• Loss of blood (overt blood)-10% or more of

total blood volume (preferably given PRBC/
components)
• Refractory shock despite adequate fluid
administration and declining HCT
• Replacement volume should be 10ml/kg
body wt. at a time and coagulogram should
be done
• If fluid overload is present, PCV transfusion
to be given @5ml/kg body wt.
 Indication of Platelet transfusion

• Prophylactic platelet transfusion: may be given

<10,000/cmm. of blood in absence of bleeding
manifestation
• Platelet transfusion may be given with higher
platelet count with bleeding manifestation
• Prophylactic platelet transfusion in surgical
cases
• Therapeutic transfusion
o Haemorrhage +/- Thrombocytopenia
o Prolonged shock+ coagulopathy +abnormal
coagulogram
o Systemic bleeding : with Red cell transfusion
o Whole fresh blood transfusion does not have
any role in managing Thrombocytopenia
 Guideline of Platelet transfusion

• Follow the guideline of Platelet transfusion as per Memo no. HFW-

28013(17)/16/2023-BS SEC –Dept. of H&FW/57, dated 07.05.2024 of
the Department of H&FW, WBSAPCS, Swasthya Bhavan, Kol-91
 Operational aspect..(1/2)
• Severe Dengue is properly classified by clinicians and the correct count
to be reflected in DKPI portal(www.wbhealth.gov.in) daily
• Vitals records and other Biochemical parameters of Severe Dengue
cases admitted at IPD to be entered in DKPI portal(www.wbhealth.gov.in)
daily till the outcome is achieved
• Identify the cases of compensated shock which need a specific fluid
therapy
• Re-assessment and repeated f/u are necessary to take decision for
further fluid management
• Correct dehydration of cases where there is no obvious shock but dry
tongue/low urine output /repeated vomiting occurred
 Operational aspect..(2/2)

• Dengue with Organ involvement require additional investigation viz

1. In case of pain abdomen: USG, Serum amylase, lipase
2. In case of SOB: Chest X-Ray, ECG, Echocardiography
3. In case of oliguria: RFT
4. In case of repeated vomiting: LFT
---advise the same
Thank You