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Title: Dengue


1
DENGUE FEVER
  • By Manar .M. Rashad
  • Student of doctor degree in tropical medicine
  • University of Alexandria

2
History
  • The first record of a case of probable dengue
    fever is in a Chinese medical encyclopedia from
    the Jin Dynasty (265420 AD) which referred to a
    water poison associated with flying insects. 
  • The first recognized Dengue epidemics occurred
    almost simultaneously in Asia, Africa, and North
    America in the 1780s, shortly after the
    identification and naming of the disease in 1779.

3
  • The first confirmed case report
    dates from 1789 and was by Benjamin Rush, who
    coined the term "breakbone fever" because of the
    symptoms of myalgia and arthralgia

4
  • The origins of the word dengue are not clear, but
    one theory is that it is derived from the Swahili
    phrase "Ka-dinga pepo", meaning "cramp-like
    seizure caused by an evil spirit"
  • Dengue fever is the most common arthropod borne
    viral disease.
  • Dengue fever is one of the most important
    emerging disease of the tropical and sub tropical
    regions, affecting urban and pre urban areas

5
Global burden of DENGUE
  • During the 19th century, dengue was considered a
    sporadic disease that caused epidemics at long
    intervals,
  •  Today, dengue ranks as the most important
    mosquito-borne viral disease in the world. In the
    last 50 years, incidence has increased 30-fold.

6
  • An estimated 2.5 billion people live in over 100
    endemic countries and areas where dengue viruses
    can be transmitted
  • Up to 50 million infections occur annually with
    500 000 cases of dengue haemorrhagic fever and
    22,000 deaths mainly among children.

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Dengue virus
  • a mosquito-borne flavivirus.
  • DENV is a positive single stranded RNA virus of
    the family Flaviviridae, genus Flavivirus.

10
  • DENV causes a wide range of diseases in humans,
    from a self limited Dengue Fever (DF) 
  • to a life-threatening syndrome called Dengue
    Hemorrhagic Fever (DHF) or Dengue Shock Syndrome
    (DSS).
  • There are four antigenically different serotypes
    of the virus (although there is report of 2013
    that a fifth serotype has been found)
  • DENV-1 DENV-2 DENV-3 DENV-4

11
  • Infection induces long-life protection against
    the infecting serotype, but it gives only a short
    time protective cross immunity against the other
    types.
  • The first infection cause mostly minor disease,
    but secondary infections has been reported to
    cause severe diseases (DHF or DSS) in both
    children and adults. This fenomenon is
    called Antibody-Dependent Enhancement.

12
Vector Aedes aegypti
Life cycle8-10 days
Adult
Larva
13
  • It can be identified by the white bands or scale
    patterns on its legs and thorax
  • Mosquitoes fly an average of 400 metres.
  • It has daytime activity
  • Lives around human habitation
  • Lays eggs and produces larvae preferentially in
    artificial containers

14
Diseases transmitted by aedes aegypti
15
Geographical distribution of the vector
16
Challenge in controlling vector
  • There is a very important adaptation of dengue
    vectors that makes controlling their populations
    a difficult task. Their eggs can withstand
    desiccation for several months, which means that
    even if all larvae, pupae, and adults were
    eliminated at some point in time, repopulation
    will occur as soon as the eggs in the containers
    are flooded with water. Unfortunately, there is
    no effective way to control the eggs in
    containers..

17
Transmission
  • The viruses are passed on to humans through the
    bites of an infective female Aedes mosquito it
    injects the dengue virus into the skin.
  • The virus infects nearby skin cells called
    keratinocytes, the most common cell type in the
    skin.
  • The dengue virus also infects and replicates
    inside a specialized immune cell located in the
    skin, a type of dendritic cell called a
    Langerhans cell.

18
  • Once the Langerhans cells are infected with the
    dengue virus, they travel from the infection site
    in the skin to the lymph nodes.
  •  The infected Langerhans cells display dengue
    viral antigens on their surface, which activates
    the innate immune response by alerting two types
    of white blood cells, called monocytes and
    macrophages, to fight the virus. 

19
  • . As the infected monocytes and macrophages
    travel through the lymphatic system, the dengue
    virus spreads throughout the body.
  • During its journey, the dengue virus infects more
    cells, including those in the lymph nodes and
    bone marrow, macrophages in both the spleen and
    liver, and monocytes in the blood.
  • The spread and increase of the virus results
    in viremia, a condition in which there is a high
    level of dengue virus in the blood stream.

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Pathogenesis of Dengue
22
  • The microvascular leak occurs at a time when the
    viral load is in steep decline and is associated
    with a more intense immune response.
  • Disruption in the endothelial glycocalyx layer
    has been implicated, through immune-mediated
    mechanisms by the virus or the NS1 antigen
    adhering to the endothelial layer.

23
  • The NS1 antigen is a glycoprotein secreted from
    dengue-infected cells and is required for viral
    replication.
  • Studies have shown that NS1 can selectively bind
    to heparin sulphate in the glycocalyx layer of
    microvascular endothelial cells. Thus
    facilitating immune complex formation and
    antibody-dependent complement activation causing
    the endothelial damage and microvascular leakage.

24
DENGUE fever is a Systemic disease
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Clinical course of Dengue
27
  • In November 2009, World Health Organization (WHO)
    issued a new guideline that classifies
    symptomatic cases as dengue or severe dengue.
  • Dengue is defined by a combination of 2 clinical
    findings in a febrile person who traveled to or
    lives in a dengue-endemic area.
  • Clinical findings include nausea, vomiting,
    rash, aches and pains, a positive tourniquet
    test, leukopenia.
  • the following warning signs abdominal pain or
    tenderness, persistent vomiting, clinical fluid
    accumulation, mucosal bleeding, lethargy,
    restlessness, and liver enlargement. The presence
    of a warning sign may predict severe dengue in a
    patient.

28
  • Severe dengue is classified as dengue with any of
    the following symptoms
  •  
  • severe plasma leakage leading to shock or fluid
    accumulation with respiratory distress
  • severe bleeding
  • severe organ impairment such as elevated
    transaminases 1,000 IU/L, impaired
    consciousness, or cardiovascular compromise.

29
Clinical Case Definition for Dengue Shock
Syndrome(DSS)
  • 4 criteria for DHF
  • Evidence of circulatory failure manifested
    indirectly by all of the following
  • Rapid and weak pulse
  • Narrow pulse pressure (lt 20 mm Hg) ORhypotension
    for age
  • Cold, clammy skin and altered mental status
  • Frank shock is direct evidence of circulatory
    failure

30
Scenario of shock
Hours
Hours
Hours
Minutes
31
Hemorrhagic Manifestations of Dengue
  • Skin hemorrhagespetechiae, purpura, ecchymoses
  • Gingival bleeding
  • Nasal bleeding
  • Gastrointestinal bleeding Hematemesis,
    melena, hematochezia
  • Hematuria
  • Increased menstrual flow

32
Signs and Symptoms of Encephalitis/Encephalopathy
Associated with Acute Dengue Infection
  • Decreased level of consciousness lethargy,
    confusion, coma
  • Seizures
  • Nuchal rigidity
  • Paresis

33
DIAGNOSIS/ LAB WORK
  • ISOLATION OF DENGUE VIRUS
  • INCREASED IgM OR IgG ANTIBODIES TITRES
  • DENQUE ANTIGEN DETECTION (NS1) BY
    IMMUNOHISTOCHEMISTRY,IMMUNOFLUROSCENCE,ELISA
  • PCR(detection of viral RNA)

34
Test Interpretation
DNGV PCR RT- PCR can be detected in the blood (serum) from patients for approximately the first 5 days of symptoms. A positive PCR result is a definite proof of current infection and it usually confirms the infecting serotype as well.
DNG-IgM MAC- ELISA IgM detection is not useful for dengue serotype determination due to cross-reactivity of the antibody .
35
Test Interpretation
DNG-IgG ELISA detection of a past dengue infection Samples with a negative IgG in the acute phase and a positive IgG in the convalescent phase of the infection are primary dengue infections. Samples with a positive IgG in the acute phase and a 4 fold rise in IgG titer in the convalescent phase (with at least a 7 day interval between the two samples) is a secondary dengue infection.
NS1 ELISA Tool for the diagnosis of acute dengue infections  As early as 1 day post onset of symptoms (DPO), and up to 18 DPO.
36
CBC/COAGULATION PROFILE
  • CBC
  • Leukopenia
  • Thrombocytopenia lt100.000 (warning sign)
  • Increased haematocritgt 20 haemoconcentration(
    warning sign), it should be measured every 24
    hours
  • COAGULATION PROFILE
  • Prolonged PT
  • Prolonged PTT
  • Increased FDP
  • Decreased fibrinogen

37
Clinical course of Dengue
38
Primary infection vs Secondary infection
39
Management
  • The initial management of dengue cases involves
    classification into appropriate severity grades
    with early recognition of potential complications
    and warning signs.
  • Early detection of any circulatory compromise
    and judicious fluid resuscitation is the mainstay
    of treatment for severe dengue, with delays being
    associated with worse outcomes.

40
  • Antipyretics may be needed to control the high
    fever.
  • Aspirin and other non-steroidal
    anti-inflammatory agents should not be used, to
    avoid gastric irritation and GI bleeding, and
    because of the link with Reye syndrome.
  • Oral rehydration solution is recommended to
    replace losses from vomiting and high fevers.
  • .

41
  • Fluid therapy
  • The minimum amount of intravenous fluid should be
    given to ensure adequate perfusion, clinicians
    should be guided by vital signs, haematocrit and
    average urine output of 0.5 mL/kg per hour.
  • Isotonic fluids should be given for the duration
    of the critical period only (usually 2448
    hours), as there is a significant risk of fluid
    overload if intravenous fluids are continued into
    the recovery phase.

42
  • Colloids may be given in
  • Hypotensive shock
  • After gt20-30 ml/ kg/ day crystalloids given
  • Haematocrit does not decrease after crystalloids
    administration in shock state

43
Hct Haemodynamic state (vital signs-UOP-cap refill-skin signs) Interpretation Judicious action
High or Rising persistently Unstable Active plasma leakage Further fluid replacement
High or Rising persistently Stable No more extravasated fluid Continue to monitor HCT closely (Expected to decrease 24 hours later)
Decrease Unstable Massive haemorrhage Urgent transfusion
Decrease Stable Haemodilution dt reabsorption of extravasated fluid Reducing IV fluids in stepwise manner or discontinue to prevent pulmonary oedema
44
Dengue in Egypt
  • On 27 October 2015, the National IHR Focal Point
    of Egypt notified WHO of an outbreak of Dengue
    fever in a village in the Dayrout District of
    Assiut Governorate.
  •  
  • Patients developed fever, headache, general body
    aches and abdominal pain with occasional vomiting
    and/or diarrhea but experienced no further
    complications or fatalities.

45
  • Several samples including oropharyngeal swabs,
    blood and serum samples were collected.
  • A total of 28 out of the 118 serum samples were
    positive for Dengue virus type I by ELISA and PCR
    at the Central Public Health Laboratories.

46
  • For further confirmation, samples were sent to
    the Naval Medical Research Unit Three (NAMRU-3)
    laboratory and tested positive for Dengue virus
    type I by ELISA and PCR.
  • They have been responding to the given medical
    care. Some of the cases come from the same
    household.

47
Era of Dengue vaccine(upcoming!)
  • The growing global epidemic of dengue is of
    mounting concern, and a safe and effective
    vaccine is urgently needed.
  • WHO expects vaccines to be an integrated part of
    the Global dengue prevention and control strategy
    (2012-2020).

48
  • The first dengue vaccine, Dengvaxia (CYD-TDV) by
    Sanofi Pasteur, was first registered in Mexico in
    December, 2015.
  • CYD-TDV is a live recombinant tetravalent dengue
    vaccine that has been evaluated as a 3-dose
    series on a 0/6/12 month schedule in Phase III
    clinical studies.
  • It has been registered for use in individuals
    9-45 years of age living in endemic areas

49
Thank you
  • Thank you

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