It talk about hemorrhagic fever

1. Viral Hemorrhagic
Fevers
Saeed Mohammed Omar
Associated professor of medicine
Consultant physician of Internal
medicine

2. Viral Hemorrhagic Fevers
 Severe multi-system syndrome (multiple
organs affected).
 Vascular system is damaged and body loses the
ability to regulate itself.
 Accompanied by hemorrhage.
 Many VHF viruses cause life threatening
diseases
 Most have no established treatment or cure.

3. VHF Caused by Viruses
of 4 Families
 Arenaviruses
 Filoviruses (Ebola and Marburg)
 Bunyaviruses
 Flaviviruses

4. Features of these Viruses
RNA Viruses, covered in lipid
coating
Humans are not natural
reservoir, but can transmit virus
Viruses are restricted to areas of
their host species

5.  Family: Flaviviridae
 Genus: Flavivirus
 Virus: Dengue virus
 Also known as ‘break-bone fever’
 Asia, the Caribbean, the Pacific, West Africa,
India
 Morphology
 Similar to yellow fever

6.  The World Health Organization warned that
cases of dengue fever could reach close to
record highs this year, partly due to global
warming benefiting mosquitoes that spread it.
 Dengue rates are rising globally, with reported
cases since 2000 up eight-fold to 4.2 million in
2022, WHO said.

7.  In Januray WHO warned that dengue is the
world's fastest-spreading tropical disease and
represents a "pandemic threat".
 Temperatures over 45 degrees "should kill the
mosquito more than breeding it, but the
mosquito is a very clever insect and it can breed
in water storage containers where the
temperature doesn't rise that high."

8.  Dengue has been called the most important
mosquito-transmitted viral disease in terms of
morbidity and mortality. It is the most prevalent
viral mosquito-borne disease.
 Dengue fever is a benign, acute febrile syndrome
occurring in tropical regions. In a small
proportion of cases, the virus causes increased
vascular permeability that leads to a bleeding
diathesis or DIC known as (DHF)

9.  Secondary infection by a different dengue virus
serotype has been confirmed as an important
risk factor for the development of DHF.
 In 20-30% of DHF cases, the patient develops
shock, known as the dengue shock syndrome
(DSS).

10. Pathophysiology
 Dengue virus is a flavivirus (single-stranded
RNA) transmitted by various mosquitoes.
Person-to-person transmission does not occur.
There are four subtypes of the dengue virus,
named DENV1 through DENV4, which are
antigenically distinct. This characteristic drives
the predominant hypothesis of how clinically
severe dengue infection develops since most
individuals who develop DHF or DSS have had
a prior infection with a nonhomologous dengue

11.  DHF and DSS may evolve based on antibody-
dependent enhancement through a secondary
infection. It is believed that secondary dengue
virus infections greatly increase the risk of
developing elevated levels of cytokines known
to drive the clinical manifestations of DHF and
DSS through endothelial damage, vascular
leakage, and hemorrhage

12.  Dengue infection has three phases: (1) the
febrile phase, (2) the critical phase, and (3) the
recovery phase. The entire course of the illness
is typically 7-10 days with each phase lasting
approximately 48-72 hours. The febrile phase
(the initial phase) coincides with the peak of
viremia during the illness and rapidly resolves
after the first three days. It is associated with
nonspecific signs and symptoms.

13.  The critical phase is marked by vascular
permeability and its resultant complications.
 It is during this time that the clinician must be
vigilant in monitoring for warning signs of
severe dengue.
 The recovery phase includes diuresis and
resolution of the symptoms that mark the
critical phase of the illness.

14. Diagnosis
 Dengue virus infection is largely a clinical
diagnosis.
 The WHO has developed a simplified and
binary system of classification for dengue
infection.
 They classify infection as either (1) dengue
infection with or without warning signs.

15.  2 severe dengue infection.
 Clinicians should suspect dengue infection in
patients with possible exposure (travel or
endemic) and fever and two of the following
characteristics:

16.  Nausea/vomiting
 Rash
 Aches and pains
 Leukopenia
 Any warning sign

17. Warning signs for dengue include the following:
 Abdominal pain or tenderness
 Persistent vomiting
 Clinical fluid accumulation
 Mucosal bleeding
 Lethargy, restlessness

18.  Liver enlargement of more than 2 cm
 Laboratory:
 Increased hematocrit coupled with rapid
decrease in platelet count

19. Severe dengue infection diagnosis criteria include
the following:
 Severe plasma leakage leading to shock and/or
fluid accumulation with respiratory distress
 Severe hemorrhage
 Severe organ impairment

20.  RNA PCR testing is available for DENV1-4
through the CDC for diagnosis during the first 5
days of infection.
 After this period, IgM ELISA testing is
preferred), although this is unlikely to assist
directly in emergency department management.

21.  Complications:
 Complications are rare but may include the
following:
 CNS dysfunction due to prolonged shock or
intracranial hemorrhage
 Myocarditis
 Encephalopathy
 Liver failure

22. Severe Dengue Infection
 Thrombocytopenia and hemoconcentration are
consistent findings in dengue infection.
 When the plasma leakage phase starts to
resolve, the hematocrit level begins to fall,
making identification of significant occult
hemorrhage difficult.

23.  There is no specific pharmacologic treatment for
dengue infection.
 Initiate early supportive care by administering
isotonic NS solution intravenously, as clinically
indicated, to maintain adequate blood pressure
and adequate urine output of 0.5-1
mL/kg/hour.

24.  The plasma leakage period is short (24-48
hours), and intravenous fluids may be reduced
based on clinical response.
 Administer paracetamol for fever control (not
salicylates or ibuprofen, which can further
hinder platelet function and increase bleeding
complications).
 Glucocorticoids are not indicated.

25.  Administer blood transfusion if significant
hemorrhage ensues (GI bleeding may be
profound).
 Administer fresh frozen plasma or platelets if
DIC is extensive and the patient is
hemodynamically unstable.
 Prophylactic platelet transfusions in a stable
thrombocytopenic patient are not needed.

26. Immunization
 Dengue vaccine was approved by the FDA in
2019 for prevention of dengue disease caused by
dengue virus serotypes 1, 2, 3, and 4 in
individuals aged 9-16 years with laboratory-
confirmed previous dengue infection who live in
endemic areas.

27.  It is approved only in individuals previously
infected by any dengue virus serotype or in
whom this information is unknown. Persons not
previously infected are at an increased risk of
severe dengue disease when vaccinated and
subsequently infected with dengue virus.

28.  Admit the patient to the intensive care unit
(ICU) in the setting of severe dengue infection
(DHF or DSS)
 Otherwise, admit to medicine ward for
appropriate hydration, supportive care, and close
reassessment.

29.  Pathogenesis
 4 serotypes; DEN 1, DEN 2, DEN 3, DEN 4
 Vector: Aedes aegypti
 1) Classical dengue fever
 2) Dengue haemorrhagic fever
 3) Dengue shock syndrome

30.  Usually affects older children & adults
 Bite from the infected mosquito enters the
blood stream
 Biphasic fever (saddle back), headache, pain in
muscles & bones
 IP: 5-8 days
 Maculopapular rash appears on 3rd or 4th day
 Febrile illness lasts for about 10 days
 Complete recovery and rarely fatal

31.  More serious form; Hyperimmune response
 Mostly confined among children 5-10 y/o in
area where multiple dengue viruses cause disease
 Seen in patients previously infected with dengue
virus

32.  On reinfection with a different serotype,
antibody formed against the first virus reacts
with the second serotype virus forming immune
complexes (virus-antibody complex)
 Symptoms like those of dengue fever but
 associated with haemorrhagic rash,
 thrombocytopenia & shock

33.  Clinical Manifestation
 Fever of sudden onset
 Headache
 Retrobulbar pain
 Conjunctival infection
 Pain in the back & joints
 Lymphadenopathy
 Maculopapular rash

34.  Microbiological diagnosis
 Serology plays important role
 Detect antibody
 ELISA
 –Ig M (5 days after onset & persist 1-3 months)
 –Ig G (later than Ig M), 4 folds rise titre in
paired

35.  Polymerase Chain Reaction (PCR)
 Viral RNA can be detected in clinical
specimens by
 reverse transcriptase polymerase chain reaction
 (RTPCR)
 Viral genomic can be detected

36.  Prophylaxis
 No effective vaccine available
 Elimination of the mosquitoes (Aedes aegypti)
 To avoid DHF/DSS in immunised persons, a
live
 attenuated vaccine containing all serotypes
 (clinical trials)

37. Prognosis
 Dengue is generally a self-limited viral infection;
however, in patients who develop the potentially
catastrophic complications of DHF and DSS,
survival is directly dependent on the
hemodynamic support of patient through the
disease manifestations.

38.  The 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.

39.  Continued bone pain, bradycardia, and
premature ventricular contractions (PVCs) are
common.
 Pediatric deaths associated with dengue viral
infection most commonly occur in infants
younger than 1 year.