Welcome

Clinical management of dengue

syndrome
Presenter

Prof. Dr M A Quddus
Head ,
Department of Medicine,
Parkview Medical College, Sylhet.
 Dengue Fever

 Dengue infection is caused by dengue virus which is a

mosquito-borne flavivirus.
 There are four distinct serotypes, DENV-1,2,3 and 4.
 Each episode of infection induces a life-long protective immunity
to the homologous serotype but confers only partial and
transient protection against other serotypes.
 Secondary infection is a major risk factor for severe dengue due
to antibody-dependent enhancement.
 Epidemiology

 Dengue is one of the most important arthropod-borne viral diseases

in terms of public health problem with high morbidity and mortality. It
affects tropical and subtropical regions around the world.
 Today,the disease is endemic in more than 100 countries.
 WHO estimate indicates that 390 million dengue infections occur
every year, of which 96 million manifest clinically.
A.Aegypty distribution with history of epidemic dengue
A.Aegypty distribution without history of epidemic dengue
Dengue Case Burden in Bangladesh
 Current Dengue Situation in
Bangladesh………

 A record 66,000 dengue patients were admitted to hospitals

across the country till yesterday, according to the Directorate
General of Health Services (DGHS) among them 94 were doctors
and 330 health workers.
 Over the last week, on average 1650 dengue patients were
admitted in hospitals which slightly drop down to 1255 in
yesterday
Current Dengue Situation in
Bangladesh………
Vector

 Dengue virus is transmitted by Aedes aegypti and Aedes

albopictus.
 The egg of the aedes mosquito can remain in a viable dry
condition for more than a year and emerge within 24 hours
once it comes in contact with water. So this is a major hurdle
in prevention and control of dengue.
 But they do not fly over log distance (<110 yards). So this
factor can facilitates its eradication.
SPECTRUM OF DENGUE INFECTION
Dengue Syndrome

 The symptomatic manifestations for all practical purpose are

overlapping in nature and not differentiable at the beginning.
 So they are grouped into 'Dengue Syndrome'. Dengue
syndrome will encompass the following:
1. Dengue Fever (DF)
2.Dengue Hemorrhagic Fever (DHF)
3. Dengue Shock Syndrome (DSS)
 Symptomatic dengue infection is a systemic and dynamic disease
with clinical, haematological and serological profiles changing from
day to day.
 These changes accelerate within hours or even minutes during the
critical phase, particularly in those with plasma leakage.
 Understanding the systemic and dynamic nature of dengue disease
as well as its pathophysiological changes during each phase of the
disease will produce a rational approach in the management of
dengue infection.
CLINICAL COURSE OF DENGUE
INFECTION
 After the incubation period, the illness begins abruptly and will
be followed by three phases:
1. Febrile Phase
2. Critical Phase and
3. Recovery Phase
Febrile Phase

 Patients develop high grade fever suddenly and usually last

2-7 days. It is often accompanied by facial flushing, rash,
generalised body ache, vomiting and headache
 Mild haemorrhagic manifestations like petechiae and mucosal
membrane bleeding may be occur during this phase but the
findings of tender liver are warning sign.
 The earliest abnormality in the full blood count is a
progressive decrease in total white cell count followed by
platelet reduction.
Critical Phase

 The critical phase often occurs after third day of fever (may
occur earlier) or around defervescence indicated by a rapid
drop in temperature.
 The critical phase lasts about 24-48 hours.
 Clinical deterioration often occurs during the critical phase
with plasma leakage or organ dysfunction.
Recovery/Reabsorption Phase

 After 24-48 hours of critical phase, usually plasma leakage

stops followed by reabsorption of extravascular fluid.
 It is important to note that during this phase, HCT level
stabilises and drops further due to haemodilution following
reabsorption of extravascular fluid.
 The recovery of platelet count is typically preceded by
recovery of white cell count (WCC).
 In some instances, organ dysfunctions may worsen
(hepatitis, encephalitis and intracranial bleed) as the patient
enters reabsorption phase.
 Clinical Course of dengue
haemorragic fever
11-13
Figure 5 : Clinical Course of DHF
PATHOPHYSIOLOGY OF PLASMA LEAKAGE
IN SEVERE DENGUE INFECTION

 The primary pathophysiological abnormality seen in dengue

infection is an acute increase in vascular permeability that
leads to leakage of plasma into the extravascular
compartment, resulting in haemoconcentration and
hypovolaemia or shock
 Inadequate perfusion of the tissue leads to increased
anaerobic glycolysis and lactic acidosis.
 If the hypovolaemia is not corrected promptly, the patient will
progress to a refractory shock state. By then, the tissue
perfusion would not respond to vasopressor drugs, even if the
blood pressure and intravascular volume were to be restored
and cardiac output would remain depressed.
 The resultant lactic acidosis further depresses the
myocardium and worsens the hypotension.
 A continuum of pathophysiological changes from normal circulation to
compensated and decompensated/hypotensive shock
Normal Circulation Compensated Shock Decompensated /
Hypotensive Shock
• Clear consciousness • Clear consciousness - shock can be • Change of mental
missed if you do not touch the patient state - restless, combative or lethargy
• Brisk capillary refill time (<2 sec)
• Prolonged capillary • Mottled skin, very prolonged capillary
• Warm and pink refill time
refill time (>2 sec)
peripheries
• Cool extremities • Cold, clammy
• Good volume extremities
peripheral pulses • Weak & thready
peripheral pulses • Feeble or absent peripheral pulses
• Normal heart rate for age
• Severe tachycardia with bradycardia in
• Tachycardia
• Normal blood late shock
pressure for age • Normal systlic pressure with raised • Hypotension / unrecordable BP
diastolic pressure
• Normal pulse pressure for age • Narrowed pulse pressure (<20 mmHg)
• Postural hypotension
• Normal respiratory rate for age • Metabolic acidosis/ hyperpnoea /
• Narrowing pulse pressure Kussmaul’s breathing
• Normal urine output
• Tachypnoea • Oliguria or anuria
• Reduced urine output

• Intense thirst
 Case Definitions for Clinical Management

Dengue Fever
1. Sudden onset continuous fever
And
2. Two or more
of the following features:
a. Severe headache b. Retro-orbital pain c. Severe myalgia / arthralgia
/ back pain d. Hemorrhagic manifestations e.
Nausea/vomiting/abdominal pain f. Leucopenia
And
3. High index of suspicion based on Period, Population & Place And
4. Absence of convincing evidence of any other febrile illness
CASE DEFINITION FOR DENGUE
HAEMORRHAGIC FEVER
1. Features of dengue fever at initial stage
And
2. Hemorrhagic manifestations evidenced through one or more
of the following:
a. Positive tourniquet test
b. b. Petechiae / ecchymosis / purpura
c. c. Mucosal bleeding: Epistaxis, gum bleeding
d. Bleeding from injection or other site
e. Hematemesis, melena, hematuria, PV bleeding
f. Thrombocytopenia with platelets 100,000 / m3 or less
And
3. Any evidence of plasma leakage
 Evidence of plasma leakage

 Evidence of plasma leakage due to increased capillary

permeability manifested by one or more of the following:
a. A ≥ 20% rise in hematocrit for age or sex
b. A ≥ 20% drop in hematocrit following treatment with fluids
as compared to base line c. Pleural effusion / ascitis /
hypoproteinemia

 Therefore, early detection of critical period ( onset of plasm

leakage) and appropriate fluid management is of paramount
importance.
CASE DEFINITION FOR DENGUE SHOCK
SYNDROME

Dengue Shock Syndrome is a presentation of Dengue

Syndrome when a case of DHF manifests circulatory failure with
one or more of the following features:
1. Hypotension for age
2. Cold clammy skin, restlessness, rapid weak pulse
3. Narrow pulse pressure (≤ 20 mm of Hg)
4. Profound shock
Expanded dengue syndrome

 unusual manifestations such as involvement of liver, brain or

heart with or without evidence of fluid leakage
 However, these manifestations if seen in DHF patients are
mostly a result of prolong shock leading to organ failure
 Investigations for confirmation

 Dengue Antigen and Serology Tests by ELISA

 Dengue Viral RNA Detection (Real time RT-PCR).
 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.
 DISEASE MONITORING TESTS
White cell count (WCC) and Platelet count:
 In the early febrile phase WCC and platelet count are usually
normal but will decrease rapidly as the disease progresses.
 The There is no correlation between disease severity and platelet
count. In recovery phase, the WCC normalises followed by platelet.
Haematocrit (HCT): A rising HCT is a marker of plasma leakage in
dengue infection.
Other important blood tests in disease monitoring are Liver
Function Test (LFT), Renal profile (RP), coagulation profile,
lactate and blood gases, CK
 Dengue IgM test
 In primary dengue infection, anti-dengue IgM can be detected
after five days of illness in approximately 80% of the cases.
 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 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..
 Thus, 28% of all secondary dengue infections were
undiagnosed when only IgM was the only assay performed.
Dengue IgG test

 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
Differentiation between primary and
secondary dengue infection
 Detection of significant elevation of IgG antibodies to dengue
virus by ELISA is very useful for identification of secondary
dengue infections.
 MANAGEMENT OF DENGUE INFECTION

 The management of dengue infection is symptomatic and

supportive
 Management issues vary according to the three phases of the
clinical course.
 It is crucial to recognise plasma leakage, early shock and
severe organ dysfunction.
 This can be achieved by frequent clinical and laboratory
monitoring during the early febrile phase of dengue infection.
Classifiacation of dengue cases

 Group A-these are patients who are dengue patients without

warning sign and they may be sent home.
 Group B-These include patients with warning signs who
should be admitted for in-hospital management for close
observation as they approach the critical phase.
 Group C-Patients who have severe plasma leakage leading to
shock and/or fluid accumulation with respiratory distress or
severe organ impairment. These patient need urgent
hospitalization,
Warning Signs

 Any abdominal pain/tenderness

 Persistent vomiting ( >3 times over 24 hours)
 Persistent diarrhoea ( >3 times over 24 hours)
 Third space fluid accumulation (such as ascites, pleural and
pericardial effusion)
 Pale, cold, clammy hands and feets
 Spontaneous bleeding tendency
 Lethargy/restlessness/confusion
 Tender liver
 Raised HCT with rapid drop in platelet
 Less or no urineoutput for 4-6 hours
 Clinical and Laboratory Criteria for
 Patients Who Can Be Treated at home
:

1. Able to tolerate orally well, good urine output and no history of

bleeding
2. Absence of warning signs
3. Physical examination:
• Haemodynamically stable
• No tachypnoea or acidotic breathing
• No tender liver or abdominal tenderness
• No bleeding manifestation
• No sign of third space fluid accumulation
• No alterations in mental state
4. Investigation: Stable serial HCT
5. No other criteria for admission (i.e. co-morbidities, pregnancy,
social factors)
HOME CARE ADVICE FOR DENGUE PATIENTS
 WHAT SHOULD BE DONE?
 Adequate bed rest
 Adequate fluid intake (more than 8 glasses or 2 litres for an
average person).
 Milk, fruit juice (caution with diabetes patient) and isotonic
electrolyte solution (ORS) and barley water.
 Plain water alone is not sufficient and may cause
electrolyte imbalance.
 Take paracetamol (not more than 4 gram per day).
 Tepid sponging.
 If possible, use mosquito repellent or rest under a mosquito
net even during day time to prevent mosquito bites.
 Look for mosquito breeding places in and around the home
and eliminate them.
WHAT SHOULD BE AVOIDED?
Do not take non steroidal anti-inflammatory (NSAIDS) eg. aspirin /
mefenamic acid (ponstan) or steroids. If you are already taking these
medications, please consult your doctor.
Antibiotics are not required
Do not take injection
Do not do massage / cupping / quasa
Inpatient Disease Monitoring
Fluid management of Non-Shock
Patients
 In dengue patients without co-morbidities who can tolerate
orally, adequate oral fluid intake of two to three litres daily
should be encouraged. These patients may not require
intravenous (IV) fluid therapy.
Indication of IV fluid administration in non-
shock patient
 vomiting, unable to tolerate oral fluids or severe diarrhoea
 increasing haematocrit (with other signs of ongoing plasma
leakage) despite increased oral intake
 In patients with persistent warning signs with increasing or
persistently high HCT
 The maintainance dose of IV fluid in this case is 1.2 -1.5
ml/kg/hour.
 the graded fluid bolus may be initiated with caution.
Crystalloids solution should be the fluid of choice for non-
shock dengue
 HAEMATOCRIT REMAIN UNCHANGED AFTER
FIRST FLUID RESUSCITATION

Consider other causes of shock

Bleeding and leaking at Severe metabolic

same time acidosis with
hyperlactataemia (liver
Look for source of bleeding + multiorgan failure)
(eg. OGDS )
Vasopressor
Evidence of leaking (USG, +
chest X-ray)
Supportive care
Check for coagulopathy +
Transfuse packed red cells Continuous renal replacement
and blood components therapy (CRRT)

Cardiac dysfunction
Vasodilated state Noradrenaline
and fluids
Noradrenaline
titrated to MAP Check for disease
65 mmHg markers of
haemophagocytic
syndrome
Low CO : High CO :
Inotrope Vasodilated shock with
(eg. dobutamine/ myocardial dysfunction
adrenaline)
Inotropes + vasopressor
(eg. noradrenaline +
 DISCHARGE CRITERIA

 The following should be taken into consideration before

discharging a
improved general well-being
afebrile for 24-48 hours
rising white cell count followed by platelet count
stable haematocrit
resolution/recovery of organ dysfunction
 It is important to note that the main problem that needs to be
dealt with in dengue infection is the plasma leakage and/or
immune activation issues, not only about the low platelet
count.
 Manipulation of platelet count alone does not alter the clinical
course of the disease as it is just a surrogate marker of
disease progression or evolution.
 Plasma leakage and organ dysfunction should be the main
focus of management.
THANK YOU