This document discusses dengue virus, which is transmitted by mosquitoes and causes dengue fever and dengue hemorrhagic fever. It describes the four serotypes of the dengue virus and their modes of transmission. It outlines the signs and symptoms of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. It also discusses laboratory tests for diagnosis and clinical management, including fluid resuscitation protocols. The goal of treatment is to manage fluid levels and output during the critical phase of potential plasma leakage while avoiding fluid overload.

1. Dr.Sanaullah khan
(29th August, 2016)
Department of General Medicine
PIMS Islamabad

2.  The most rapidly spreading mosquito born viral disease in
the world.
 Dengue virus:
 Single stranded RNA Virus
 Family Flaviviridae
 Genus Flavivirus
 04 Serotypes: DEN1,DEN2,DEN3 and DEN4.
 In Asia DEN2 and DEN3 are dominating serotypes and these
are frequently associated with sever disease.

3. Mode Of Transmission
 Infection is transmitted by the bite of an infected female
mosquito- Ades aegypti. It usually bite at day time.
 Mosquito breeds on stagnant water. It becomes infected by
biting a patient with dengue infection. Once the mosquito
becomes infected it remains so for life.(Survival of mosquito
under normal circumstances is up to 3 weeks). It takes 8-11
days by an infected mosquito to propagate the virus to levels
sufficient to transmit.

5.  Incubation period of dengue virus is 4-10 days.
 Primary infection induce lifelong protective immunity to the
infecting serotype.
 Individuals suffering an infection are protected from clinical
illness with a different serotype within 2--3 months of the
primary infection but with no long-term cross-protective
immunity.

7. Undifferentiated fever :
Primary dengue infection, Fever indistinguishable
from other viral infection.
Maculopapular rashes may accompany the fever.

8. Dengue Fever:
Dengue fever (DF) is generally an acute febrile illness.
Fever with severe headache,
Retro-orbital pain.
Myalgias,
Arthralgia/Bone Pains,
Rashes,
Hemorrhagic manifestations: Skin hemorrhages may
be present as a positive tourniquet test.
Leucopenia (<5000 cells)
Thrombocytopenia (<150,000).

10. Dengue hemorrhagic fever:
(DHF) is more common in children less than 15 years of age
and is associated with repeated dengue infections.
 High Grade fever sudden onset like in DF.
 Hemorrhagic Manifestations: Petechiae, purpura (at
venipuncture sites), ecchymosis, epistaxis, gum bleeding, and
hematemesis and/or melena, with (+ve Tourniquet Test).
 Low platelet count (Thrombocytopenia <100 000 cells/mm3).
 Evidence of plasma leakage:
Elevated Haematocrit (10-20% or more over baseline).
Pleural effusion or Ascites etc.

11. Dengue hemorrhagic fever:
 The presence of preceding warning signs such as persistent
vomiting, abdominal pain, lethargy or restlessness, or
irritability and oliguria are important for intervention to
prevent shock.
 Plasma leakage and hemostasis are the main
pathophysiological hallmarks of DHF.

12. Dengue shock syndrome:
 Four (4) criteria for DHF
High grade fever
Hemorrhagic manifestations
Low platelet count
Evidence of plasma leakage
Plus
 Evidence of circulatory failure manifested indirectly
by:
Rapid and weak pulse, Delayed perfusion.
Narrow pulse pressure (<20mmHg)
Cold, clammy skin and altered mental status.

13.  Expanded dengue syndrome
 Unusual manifestations of patients with severe organ
involvement such as liver, kidneys, brain or heart associated
with dengue infection have been increasingly reported in DHF
and also in dengue patients who do not have evidence of
plasma leakage. These unusual manifestations may be
associated with coinfections, comorbidities or complications
of prolonged shock. Exhaustive investigations should be done
in these cases.

17.  High-grade fever sudden onset lasts for 2-7days.
 Facial flushing, skin erythema, generalized body ache,
myalgia, arthralgia and headache.
 Indistinguishable between dengue and non-dengue febrile
diseases in the early febrile phase.
 Positive tourniquet test.
 Monitoring for warning signs to recognizing progression to
the critical phase.

18.  Mild hemorrhagic manifestations like Petechiae and mucosal
bleed.
 Tender Hepatomegaly.
 Earliest abnormality in the full blood count is a progressive
decrease in total white cell count.

19.  Days 3–7 of illness.
 Increase in capillary permeability in parallel with increasing
hematocrit levels are hallmarks for beginning of the critical
phase.
 Significant plasma leakage usually lasts 24–48 hours.
 The degree of increase above the baseline hematocrit often
reflects the severity of plasma leakage.
 Critical volume loss of plasma leads to shock. Prolonged shock
results in progressive organ impairment, metabolic acidosis and
disseminated intravascular coagulation.
 Non-severe dengue and sever dengue.

20.  If the patient survives the 24–48 hour critical phase, a
gradual reabsorption of extravascular compartment fluid
takes place in the following 48–72 hours. General well-being
improves, appetite returns, gastrointestinal symptoms abate,
hemodynamic status stabilizes and diuresis ensues.
 The hematocrit stabilizes or may be lower due to the dilution
effect of reabsorbed fluid.
 During the critical and/or recovery phases, excessive fluid
therapy is associated with pulmonary edema or congestive
heart failure.

21. Antibody Detection Tests:
 Rapid Diagnostic Test : (RDT) kits for anti-dengue IgM and
IgG antibodies are commercially available, which produces
the results within 15 to 20 minutes. However, the
sensitivity/specificity of most of these tests is not known.
According to WHO guidelines, these kits should not be used
in the clinical settings to guide management of DF/DHF
cases because many serum samples taken in the first five
days after the onset of illness will not have detectable IgM
antibodies.

22. Antibody Detection Tests:
 ELISA (IgG/IgM).
IgM Antibodies are detectable from Day 5 of infection, peak
levels reach in 2 weeks. Undetectable 2-3 months after
infection.
Low levels of IgG are detected in early phase.
 HEAMAGLUTINATION TEST
It is sensitive, and detect HI antibodies titer.
The HI antibody usually begins to appear at detectable levels
(titer of 10) by day five or six of illness, and antibody titers in
convalescent-phase serum specimens are generally at or
below 1:640 in primary infections, although there are
exceptions.

23. Heamaglutination Test
 By contrast, there is an immediate response in secondary
and tertiary dengue infections, and antibody titers increase
rapidly during the first few days of illness, often reaching
1:5,120 to 1:10,240 or more. Thus, a titer of 1:1,280 or
greater in an acute-phase serum is considered a presumptive
diagnosis of current dengue infection
 The major disadvantage of the HI test is lack of specificity,
which makes the test unreliable for identifying the infecting
virus serotype.

24. Antigen Detection Test:
 NS1 Antigen (Non structural protein 1):
It allows rapid detection on the first day of fever, before
antibodies appear some 5 or more days later.
NS1 is present in the serum of infected persons directly at the
onset of clinical symptoms in primary dengue infection.
 RNA Detection:
By PCR.

25. Additional laboratory investigations
• Complete blood count (CBC).
• Blood glucose.
• Blood gas analysis, lactate.
• Serum electrolytes and BUN, creatinine.
• Serum calcium.
• Liver function tests.
• Coagulation profile.
• CXR.
• Group and match for fresh whole blood or fresh packed red cells.
• Cardiac enzymes or ECG if indicated, especially in adults.
• Serum amylase and ultrasound if abdominal pain does not
resolve with fluid therapy.
• Any other test, if indicated.

26. Clinical Management
of
Dengue Fever
&
Dengue Hemorrhagic Fever

27.  The clinical spectrum of dengue infection includes
asymptomatic infection, DF and DHF.
 Triage is the process of rapidly screening patients soon after
their arrival in hospital in order to identify patients with
sever dengue
warning signs
Non urgent cases.
 Triage is done by trained staff.

28. Patients who do not have warning signs and tolerate adequate
vol. of oral fluid with passage of urine at least once every 6hrs
are treated as below:
 Bed rest is advisable during the acute phase.
 Antipyretics (Avoid Aspirin& NSAIDs)
 Fluids Oral fluid and electrolyte therapy are recommended
for patients with excessive sweating or vomiting.
 Monitoring with BP, Hematocrit, platelet count, Abdominal
pain, persistent vomiting and level of consciousness in DHF
endemic area until they become afebrile and platelet and
hematocrit determinations are stable. (Platelet count >
50,000).

29. Critical period of DHF starts around the time of transition from
febrile to afebrile phase.
Thrombocytopenia and Hematocrit--- Early indicator for plasma
leakage.
Patient is monitored for:
Vital Signs
Peripheral Perfusion
Serial Hematocrit
Urine Output
Intravenous fluid therapy should be started in patients with
increase in hematocrit above the baseline and those with
warning signs

30. Intravenous fluid therapy:
General Principles:
 Isotonic crystalloid solutions should be used throughout the
critical period.
 Hyper-oncotic colloid solutions such as dextran 40 or starch
solutions may be used in patients with massive plasma
leakage.
 The duration of intravenous fluid therapy should not exceed
24 to 48 hours for those with shock. However, for those
patients who do not have shock, the duration of intravenous
fluid therapy may have to be longer but not more than 60 to
72 hours.
 A maintenance +5% dehydration volume for adequate”
intravascular volume and circulation

32.  Fluid of Maintenance (for one day) + 5% deficit (oral and IV
fluid together), to be administered over 48 hours. This fluid
is required to maintain effective circulation during the period
of plasma leakage.
 For example, in a child weighing 20 kg, the deficit of 5% is
50 ml/kg x 20 = 1000 ml. The maintenance is 1500 ml for
one day. Hence, the total of M + 5% is 2500 ml.
 The rate of IV replacement should be adjusted according to
the rate of plasma loss, guided by the clinical condition, vital
signs, urine output and haematocrit levels.

33.  Obtain Reference Hematocrit before initiation of fluid
therapy.
Start isotonic sol. 0.9% saline or Ringers Lactate @ of
5-7ml/kg/hour for 1-2 hour, then reduce to
3-5ml/kg/hour for 2-4 hour, then
2-3ml/kg/hour or less according to clinical resps.
Reassess patient clinically and repeat HCT:
 If HCT remains same or minimally rises continue fluid @ 2-
3ml/kg/hour for 2-4 hours.
 If worsening Vital signs and rising HCT then Increase fluid to
5-10ml/kg/hour for 1-2 hours.

34. Reduce I/V fluids gradually when the rate of plasma leakage
decreases towards the end of critical phase, this is indicated by
Adequate urine output/Fluid intake
HCT decrease below the baseline.

35. Group Criteria:
Sever plasma leakage with shock
sever bleeding
Sever organ impairment
Start I/V Fluids with isotonic crystalloids @ 5-10ml/kg/hour
over 1 hour or bolus.
If patient improves then reduce fluids gradually as,
5-7ml/kg/hour for 1-2 hours
3-5ml/kg/hour for 2-4 hours
2-3ml/kg/hour for 2-4 hours
Reduce IV fluid as peripheral perfusion improves; but it must be
continued for a minimum duration of 24 hours and
discontinued by 36 to 48 hours. Excessive fluids will cause
massive effusions due to the increased capillary permeability.

37. Fluid resuscitation in Grade 4 DHF is more vigorous.
Ten to twenty ml/kg of bolus fluid should be given as fast
as possible, ideally within 10 to 15 minutes. When the
blood pressure is restored, further intravenous fluid may
be given as in Grade 3. If shock is not reversible after the
first 10 ml/kg, a repeat bolus of 10 ml/kg and review HCT.
Low HCT indicates bleeding: Urgent blood transfusion should be
considered as the next step.
Restoring the blood pressure is critical for survival otherwise
prognosis is extremely grave.

39. FLUID Overload
The most common complication is fluid overload
Early signs and symptoms include puffy eyelids, distended
abdomen (ascites), tachypnoea, mild dyspnoea.
Late signs and symptoms include all of the above, along with
moderate to severe respiratory distress, shortness of breath
and wheezing (not due to asthma) which are also an early sign
of interstitial pulmonary edema and crepitations.
Restlessness/agitation and confusion are signs of hypoxia and
impending respiratory failure.

40. Treatment:
 Start Oxygen therapy.
 In the early stage, switch from crystalloid to colloid solutions
as bolus fluids. Dextran 40 is effective as 10 ml/kg bolus
infusions.
 In the late stage of fluid overload or those with frank
pulmonary edema, furosemide may be administered if the
patient has stable vital signs.
 If they are in shock, together with fluid overload 10 ml/kg/h
of colloid (dextran) should be given. When the blood pressure
is stable, usually within 10 to 30 minutes of infusion,
administer IV 1 mg/kg/dose of furosemide and continue with
dextran infusion until completion. Intravenous fluid should
be reduced to as low as 1 ml/kg/h until discontinuation
when hematocrit decreases to baseline or below (with clinical
improvement)

41. Crystalloids:
0.9% Normal saline is suitable choice for initial resuscitation, but large
volume of 0.9% saline lead to Hyperchloremic acidosis. Monitor chloride
and lactate levels.
Ringers Lactate: may not be suitable in patient with hyponatremia but can
be given after 0.9% saline.
Colloids: Types of colloid are gelatin based, dextran based and starched
based solutions. Biggest issue– Impact on coagulation (bind with willebrand
factor/factor VII).
Dextran is suitable option for colloids.
Gelatin has least impact on coagulation but has adverse allergic reaction.