This document provides information on dengue fever, a mosquito-borne viral infection. It discusses the clinical presentation and pathophysiology of dengue fever and the more severe forms of dengue hemorrhagic fever and dengue shock syndrome. Key points include that dengue fever presents as an acute febrile illness and is caused by one of four related viruses. In rare cases it can progress to dengue hemorrhagic fever or dengue shock syndrome, characterized by bleeding and shock. Treatment involves supportive care and fluid replacement for dehydration.

5. Dr. Saleem Akhtar Rana
Dr. Mahboob Ashraf
Dr. Arshad Javaid Sh

6. KEY FACTS
 A mosquito-borne infection : No mosquito = no infection
 A severe flu-like illness
 Rarely a potentially lethal complication called dengue hemorrhagic
fever (DHF) or Dengue Shock Syndrome (DSS).
 Global incidence of dengue has grown dramatically in recent decades.
 About two fifths of the world's population are now at risk.
 Dengue is found in tropical and sub-tropical climates worldwide,
mostly in urban and semi-urban areas.
 Dengue hemorrhagic fever is a leading cause of serious illness and
death among children in some Asian countries.
 No specific treatment; appropriate medical care saves the lives.

7. Virology &Transmission
 Aedes aegypti (albopictus) mosquitoes.
 After virus incubation for eight to 10 days, an infected mosquito is capable, during
probing and blood feeding, of transmitting the virus for the rest of its life. (15-60 days)
 Infected female mosquitoes may also transmit the virus to their offspring by
transovarial (via the eggs) transmission, but the role of this in sustaining transmission
of the virus to humans has not yet been defined.
 Infected humans are the only hosts.
 The virus circulates in the blood of infected humans for two to seven days, at
approximately the same time that they have a fever;
 Some studies have shown that monkeys in some parts of the world play a similar role in
transmission.

8. Virology & Transmission
 Dengue infection is caused by anyone of 4 related,
 But antigenically distinct, viral serotypes:
 Dengue virus 1 (denv-1), dengue virus 2 (denv-2), dengue virus 3 (denv-3), and dengue virus 4 (denv-4);
serotypes of dengue virus,
 RNA virus family flaviviridae, genus flavivirus. : Yellow fever, Hep C
 Recovery from infection by one provides
 lifelong immunity against that virus serotype
 But confers only partial and transient protection against subsequent infection by the other three viruses.
 There is good evidence that sequential infection increases the risk of developing DHF.

9. Immunization
 There is no vaccine to protect against dengue.
 With four closely related viruses that can cause the disease,
the vaccine must immunize against all four types to be
effective.
 Two vaccine candidates have advanced to evaluation in
human subjects in countries with endemic disease, and several
potential vaccines are in earlier stages of development.

10. Epidemiology
 An estimated 2.5-3 billion people in approximately 110 tropical and
subtropical countries.
 Approximately 50-100 million people are infected with dengue.
 Less than 1 % , 250,000 individuals develop dengue hemorrhagic fever.
 Annually, approximately 500,000 individuals are hospitalized with the
infection, and 24,000 deaths are attributed to dengue worldwide.
 Although initial epidemics were located in urban areas, increased dengue
spread has involved suburban and rural locales in Asia and Latin
America.

11. Factors For Increased Spread
1. Explosive population growth,
2. Unplanned urban overpopulation with inadequate public
health systems(most Important)
3. Poor standing water and vector control,
4. Viral evolution,
5. Increased international recreational, business, and military
travel to endemic areas.

12. PATHOPHYSIOLOGY
During INCUBATION PERIOD (4-7 days, 3-14)
 Viral replication takes place in target dendritic cells.
 Infection of target cells, primarily those of the reticuloendothelial system, such as
dendritic cells, hepatocytes, and endothelial cells,
 Result in the production of immune mediators that serve to shape the quantity, type,
and duration of cellular and humoral immune response to both the initial and
subsequent virus infections.
FOLLOWING INCUBATION
 Due to chemical mediators ; A 5- to 7-day acute febrile illness ensues. Recovery is
usually complete by 7-10 days.
 Dengue hemorrhagic fever or dengue shock syndrome usually develops around the third
to seventh day of illness, approximately at the time of de-effervescence.

13. Patho-physiology Of DHG & DSS
Most patients who develop dengue hemorrhagic fever or dengue shock syndrome have had prior
infection with one or more dengue serotypes. These patients have two types of antibodies in their
bodies. Neutralizing antibodies are present but not enough to eliminate the virus. Non-neutralizing
antibodies result in antibody-antigen complexes which initiate damaging immune mechanisms.
 Circulating dengue antigen-antibody complexes,
 Activation of complement,
 Release of vasoactive amines.
 In the process of immune elimination of infected cells, proteases and lymphokines may be
released and activate complement coagulation cascades and vascular permeability factors.
 Increased capillary permeability
 Increased capillary fragility
 Thrombocytopenia
 Increased coagulation parameters; PT, PTT.
 DAMAGE TO THE LIVER: Liver damage manifests as increases in levels of alanine
aminotransferase and aspartate aminotransferase, low albumin level, resulting in severe fluid
losses and bleeding.

14. Two Main End Results
THE RAPID ONSET OF PLASMA LEAKAGE
Plasma leakage is caused by increased capillary permeability and may
manifest as hemoconcentration, as well as pleural
effusion and ascites. USG can pick up thickening of GB wall due to
edema in early stages and serial USG can be helpful to monitor the
progress of plasma leakage.
BLEEDING
It can ranges from petechial skin hemorrhages ,
mild bleeding from gums or nose to life-
threatening gastrointestinal bleeding.

15. Clinical Features: Two Types of populations;
Two types of responses.
Virgin Communities: Dengue Fever
 No previous exposure of the whole population.
 Mosquitoes are present; An infected person arrives and starts infection.
 Transmission appears to begin in urban centers and then spreads to the rest of a country.
 Infection rates may go up to 25-50 % of the population.
 Infection may be asymptomatic or symptomatic.
 This will be only flue like febrile illness with no DHF or DSS. This illness can be called
Dengue Fever
 This is known as epidemic Dengue.
 This community will now harbour antibodies and be ready for second round of infection
with possibility of DHF & DSS, if mosquitoes are not eliminated.
Epidemic Transmission of Dengue Infection

16. Clinical features in already exposed communities;
Hyper endemic Transmissions
 Breeding seasons of mosquitoes create seasonal variations.
 Infection and immunity is present in community.
 To be completely safe from infection, immunity against all four sero-
types of virus is required; which is not present in all persons, especially
children.
 Infection in non-immune persons, against all four types, will present as
Dengue fever only. No danger of DHF & DSS.
 Infection in persons immune only against other than the infecting
sero-type, may lead to life threatening DHF or DSS.
 So typical presentation of Dengue fever may lead to DHF & DSS.
Hyper endemic Dengue Transmissions

17. Dengue infections In Pakistan
(Majority = Asymptomatic)
Asymptomatic
50-90 %
Leaves behind Immunity only
Dengue Fever
Febrile illness of < 10 days.
No consequence
DHF &
DSS <1%
3rd-7th day
90 % = children
Bleeding
diathesis leading
to shock
20-30 % of DHF go
into shock

18. Classical Dengue Fever
(Both epidemic and hyper-endemic transmissions)
 Symptoms begin after a 5- to 10-day incubation period.
 Illness begins abruptly with a minor stage of 2-4 days' duration followed by rapid
deterioration.
 High grade fever lasting for few days; usually < 7 days. Fever does not persist for 24
hours. Severity varies within 24 hours.
Fever that lasts longer than 10 days are probably not due to dengue.
 Fever is often preceded by
 Chills,
 Erythematous mottling of the skin
 Facial flushing (a sensitive and specific indicator of dengue fever).
 The fever typically begins on the third day and lasts 5-7 days, abating with the cessation of viremia.
 Fever in persons with symptomatic dengue fever may be as high as 41°C.
 Occasionally, and more commonly in children, the fever abates for a day and then returns, a pattern
that has been called saddleback fever.

19.  Severe aches pains; myalgias; lower back, arms, and legs,
 Joint pains; especially of the knees and shoulders.
 Flushing of face
 Severe Headache with Retro bulbar pain
 Rash on the body.
 Fatigue & malaise
 Conjunctival injection in 1/3rd ; pharyngeal injection = 97 % of DHF
 Sore throat and cough
 Nausea, vomiting and abdominal pain
 Restlessness, change in mental status
 Hypothermia
 Cardiomyopathy is reported, with tachycardia during the febrile period and
bradycardia and conduction defect. Myocarditis and congestive heart failure
are rare
Fever is accompanied by:
Dengue infection can affect many organs and thus may present unusually
as liver dysfunction, renal impairment, meningo-encephalitis or
gastroenteritis.

20. Rash
Patients typically describe a maculopapular or macular confluent rash over the face, thorax,
and flexor surfaces, with islands of skin sparing. The rash typically begins on day 3 and
persists 2-3 days.

22. The diagnosis of dengue
is usually made clinically with CBC.
High fever with no localising source of
infection,
Rash
Thrombocytopenia
High Hematocrit
 Relative Leukopenia

23. Progress of Dengue Fever to DHF & DSS
Warning Symptoms/Signs
 Scare is much more than warranted. Only 0.25-0.5 % patients of Dengue infections progress to DHF &
DSS.
 Out of these mortality is only 5 %, if treated properly and promptly.
 Most dangerous period is towards the end of febrile period, especially within 2-3 days of disappearance of
fever.
 There are warning signs and symptoms but any patient can abruptly go into DHF & DSS.
 Warning symptoms:
 Rising pulse pressure; < 20; Difference between Systolic & Diastolic
 Decreasing platelet counts
 Rising hematocrit
 Minor bleeding from gums etc; Petechiae & bleeding at venipuncture sites.
Positive tourniquet test
This is performed by inflating a blood pressure cuff on the upper arm to
midway between diastolic and systolic blood pressures for 5 minutes. The
results are considered positive if more than 20 petechiae per square inch
are observed on the skin of the arm.

24. Full Blown DHF
Vomiting
Restlessness
Bleeding episodes
Shock
Hemorrhagic manifestations may range from
 Small amounts of bleeding from the nose or gums
 Melena
 Menorrhagia,
 Hematemesis.

25. Grading the Severity Of Dengue Infection
The decision about where to treat depends upon the severity of infection.
It is important to grade the severity of Dengue infection. Following
table grades the severity of infection
DHF/DSS Grades Symptoms Laboratory
DF Fever with two of the four following symptoms.
 Headache
 Retro-bulbar pain
 Myalgias
 Arthralgias
 Leucopenia occasionally
 Thrombocytopenia may
be present
 No evidence of plasma
loss
DHF I Above signs with positive tourniquet test  Platelet count =
< 100,000
 HCT = > 20 % riseDHF II Above signs with spontaneous bleeding
DHF III Above signs and circulatory failure
 Hypotension
 Weak pulse
 Restlessness
DHF(DSS) IV Profound shock with undetectable blood pressure
and pulse.

26. Laboratory Diagnosis: CBC
•Leukopenia, Lymphopenia, Abnormally shaped lymphocytes
• Near the end of febrile period and onset of DHG & DSS
• Hematocrit: A rise of > 20 % is dangerous.
• *Sign of hemoconcentration
• *Monitor every 24 hours in DF
• *3-4 hourly in DHF & DSS
• Thrombocytopenia: Most important parameter to watch.
• Count < 100,000 should ring the warning bells.
• Monitor 24 hourly .
• Should not get lower than 50,000.
• Give platelets if count is less than 50,000.

27. Confirmatory
Test
Ig M
antibody to
Dengue Virus;
CAM Eliza
Method
From Most
Reliable lab

28. 1. PT Prothrombin
time is prolonged.
2. APTT; Activated
partial thromboplastin
time is prolonged.
3. Low fibrinogen:
4. For DIC: FDP
Elevated fibrin
degradation product
levels are signs
of disseminated
Intravascular coagulation
•Coagulation
Studies
1. Hyponatremia:
2. Metabolic
acidosis:
3. Elevated BUN;
due to shock, no
renal injury
1. Transaminase
levels may be mildly
elevated or into the
several thousands in
patients with dengue
hemorrhagic fever who
have acute hepatitis.
2. Low albumin
levels.
Signs of early
coagulopathy may be as
subtle as a guaiac test
positive for occult blood
in the stool. This test
should be performed on
all patients in whom
dengue virus infection is
suspected.

29. Imaging Studies
 Chest radiography: Right-sided pleural effusion is typical. Bilateral pleural
effusions are common in patients with dengue shock syndrome.
 Serial ultrasonography:
 Head CT scan without contrast
1. For altered level of consciousness
2. Intracranial bleeding
3. Cerebral edema
 Electrocardiography
1. Nonspecific changes may be effects of fever, electrolyte disturbances,
tachycardia, or medications.
2. Usefulness of these changes as a marker of cardiac involvement is
unclear

30. DSS
Loss of blood & plasma leads to Rapid, weak pulse, Narrow pulse pressure (<20 mm
Hg), with increased peripheral vascular resistance (PVR) and elevated diastolic
pressure, Hypotension, Cool, clammy skin, Altered mental status, although the
patient may initially remain alert.
DIC
A: Patient is not responding to I/V fluids and blood.
B: Disseminated intravascular coagulation.
C: Whole circulation is at standstill.
Patient is at grave risk. Mortality is very high; reaching 80-90 %.
Patient must be in tertiary care ICU. Do not take risk.

31. Treatment: General Considerations
 Dengue fever is usually a self-limited illness, and only supportive care is required.
 Paracetamol may be used to treat patients with symptomatic fever.
 Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids should be
avoided.
 Patients with known or suspected dengue fever should have their platelet count and
hematocrit measured daily from the third day of illness until 1-2 days after defervescence.
 Patients with a rising hematocrit level or falling platelet count should have intravascular
volume deficits replaced.
 Patients who improve can continue to be monitored in an outpatient setting. Patients
who do not improve should be admitted to the hospital for continued hydration.
 Patients who develop signs of dengue hemorrhagic fever warrant closer observation.
Patients who develop signs of dehydration need immediate referral.
 Intravascular volume deficits should be corrected with isotonic fluids such as Ringers
lactate solution. Boluses of 10-20 mL/kg should be given over 20 minutes and may be
repeated. Starch, dextran 40, or albumin 5% at a dose of 10-20 mL/kg may be used. If the
patient does not improve after this, blood loss should be considered.

32. Treatment: General Measures
 Diet
1. No specific diet is necessary for patients with dengue fever.
2. Patients may become dehydrated from fever, lack of oral intake, or vomiting. Patients who are
able to tolerate oral fluids should be encouraged to drink oral rehydration solution, fruit juice, or
water to prevent dehydration.
3. Return of appetite after dengue hemorrhagic fever or dengue shock syndrome is a sign of
recovery.
 Activity
1. Bed rest is recommended for patients with symptomatic dengue fever, dengue hemorrhagic
fever, or dengue shock syndrome.
Risk Of Overload
•After patients with dehydration are stabilized, they usually require intravenous fluids for no more than 24-48 hours.
•Intravenous fluids should be stopped when the hematocrit level falls below 40% and adequate intravascular volume is
present.
•At this time, patients reabsorb extravasated fluid and are at risk for volume overload if intravenous fluids are
continued.
•Do not interpret a falling hematocrit value in a clinically improving patient as a sign of internal bleeding

33. Treatment: Policies to save lives
Emergency Care
 Initiate supportive therapy
 Intravenous (IV) crystalloids, as needed to keep systolic blood pressure above
90 mm Hg
 O2, empirically
Emergency Department Care
 Supportive therapy
 IV access, O2, and monitoring are helpful.
 IV crystalloids may be necessary for hypotension; central line may be needed.
 Correct electrolyte abnormalities and academia.
 Implement therapy for DIC if indicated.
 Corticosteroids are not helpful.
 No antiviral therapy is available.

34. Manage
1-Platelets
2-Hematocrit
3-BP
By Platelets
FFP
I/V fluids
Avoid Blood
Dengue Shock
Syndrome
Shock is a grave
emergency
Only ICU care in
Terciary care level
facility
Management Of DHF
& DSS
A recent case report demonstrated good improvement following intravenous
anti-D globulin administration in two patients.

35. Prognosis
 Rapid clinical response to aggressive fluids and electrolytes in even
moribund children with DHF/DSS "is among the most dramatic events in
clinical medicine."
 Treated promptly, children in shock and coma can wake up and return to
near normalcy within hours.
 Convalescence may be prolonged, with weakness and mental depression.
 Continued bone pain, bradycardia, and premature ventricular contractions
(PVCs) are common.
 Survival is related directly to early hospitalization and aggressive
supportive care.
.

36. What not to do?
 Don't give Aspirin or Brufen for treatment of fever.
 Avoid giving intravenous therapy before there is evidence of
hemorrhage and bleeding.
 Avoid giving blood transfusion unless indicated, reduction in
hematocrit or severe bleeding.
 Avoid giving steroids. They do not show any benefit.
 Do not use antibiotics.
 Do not change the speed of fluid rapidly, i.e. rapid increase and
decrease in speed of fluids.
 Insertion of nasogastric tube to determine concealed bleeding or to
stop bleeding (by cold lavage) is not recommended since it is
hazardous.

37. Signs of Recovery:
 Patients who are resuscitated from shock rapidly recover.
 Patients with dengue hemorrhagic fever or dengue shock syndrome may be
discharged from the hospital when they meet the following criteria:
 Afebrile for 24 hours without antipyretics
 Good appetite, clinically improved condition
 Adequate urine output
 Stable hematocrit level
 At least 48 hours since recovery from shock
 Absence of respiratory distress
 Platelet count greater than 50,000 cells/μL

38. Prevention and control
 At present, the only method of controlling or preventing dengue virus
transmission is to combat the vector mosquitoes.
 In Asia and the Americas, Aedes aegypti breeds primarily in man-made
containers like earthenware jars, metal drums and concrete cisterns used
for domestic water storage, as well as discarded plastic food containers,
used automobile tires and other items that collect rainwater.
 WHO/TDR/Crump
Vector control is implemented using environmental management and
chemical methods. Proper solid waste disposal and improved water storage
practices, including covering containers to prevent access by egg-laying
female mosquitoes are among methods that are encouraged through
community-based programs.
 The application of appropriate insecticides to larval habitats, particularly
those that are useful in households, e.g. water storage vessels, prevents
mosquito breeding for several weeks but must be re-applied periodically.
Small, mosquito-eating fish and copepods (tiny crustaceans) have also
been used with some success.