Different Viral Fevers
Presenter :
Dr. Nabila Nawar
Lecturer,
Dept. of Microbiology
At the end of the session students
will be able to
• Mention the structure of the virus
• Explain the mode of transmission of the disease
• Explain the etiopathogenesis of the disease
• Mention the organ involved in this disease
• Explain the mechanism of organ involvement
Dengue virus
• It is named after the swahili word “dinga” meaning fastidious
or careful, which would describe the gait of a person
suffering from the bone pain of dengue fever.
Properties of Dengue virus
• It is a single-stranded RNA virus that belong to the family
Flaviviridae and genus Flavivirus.
• It has four serotypes (DEN-1 to DEN-4). Recently, the fifth
serotype (DEN-5) was discovered in 2013 from Bangkok.
Dengue virus structure
• The virus is roughly spherical in shape.
• It has nucleocapsid, which is made of the
viral genome and C proteins.
• The nucleocapsid is surrounded by a
membrane called the viral envelope, a lipid
bilayer that is taken from the host.
• The viral envelope is embeded with E and
M proteins that span through the lipid
bilayer. These proteins form a protective
outer layer that controls the entry of the
virus into human cells.
Vector
Aedes aegypti is the principal vector followed by
Aedes Albopictus.
A. aegypti is a nervous feeder (so it bites repeatedly
to more than one person to complete a blood meal)
and resides in domestic places, hence is the most
efficient vector.
Transmission
Aedes aegypti mosquito becomes infective only
when it feeds on viremic patients (generally from a
day before to the end of the febrile period, i.e. 5 days)
After an extrinsic incubation period of 8 to 10 days,
the mosquito becomes infective, and is able to
transmit the infection. However, once infected, it
remains infective for life.
Primary and secondary dengue
infection
• When the patient become infected first time with any of the
four strain, it is called ‘primary infection’.
• When an individual becomes infected 2nd time with any of
the rest 3 strains, it is called ‘secondary infection’.
• One strain can’t infect more than one time. Because strain
specific immunity is developed against specific strain.
Pathogenesis of
dengue fever
Classical dengue fever (First exposure of dengue virus)
Dengue infection by one of the four serotypes
↓
Antibody is formed
↓
Formation of immune-complex & activation of complement
↓
By the products of classical complement pathway it
increases vascular permeability & thrombocytopenia.
Pathogenesis of dengue haemorrhagic fever
The patient recovers from classical dengue caused by one of
the four serotypes, and antibody against that serotype is
produced
↓
Patient infected with another serotype of dengue virus
↓
An anamnestic, heterotypic response occurs
↓
Large amount of cross-reacting antibody to the first serotype
are produced.
Pathogenesis of dengue haemorrhagic
fever Contd…
There are several hypothesis for the production of dengue
haemorrhagic fever:
When 2nd serotype infect the same person
↓
Stimulate the preexisting memory cell, which produces
IgG (anamnestic reaction). But these IgG can’t neutralize
the 2nd serotype (Because it is heterologous to it)
↓
These IgG enhance the entry of virus into monocyte &
macrophage
↓
Pathogenesis of dengue
haemorrhagic fever Contd…
As a consequence, infected monocytes & macrophage
release large amount of cytokines (TNFα; INFγ; IL-2,6,8);
vasoactive mediators & procoagulants
↓
Increase vascular permeability & extravasation of fluid
↓
Disseminated intravascular coagulation (DIC)
Pathogenesis of dengue haemorrhagic
fever
Contd…
Immune complexes composed of virus & antibody are formed
↓
Stimulate classical pathway of complement
↓
Complement component C3a, 4a, 5a are produced
↓
C3a,4a,5a acts as anaphylatoxin
↓
Degranulate the mast cell
↓
Release of mediators (histamin, serotonin)
↓
↑ vascular permeability & resulting extravasation of fluid
↓
■ Hypotension
■ ↑ Hematocrit
Pathogenesis of dengue
haemorrhagic fever Contd…
C5a is a chemotactic agent
↓
Attracts neutrophil
↓
Neutrophil release proteolytic enzymes causing tissue damage
↓
Platelet aggregation on the damaged site
↓
Decrease platelet in the periphery
↓
● Thrombocytopenia
● Bleeding manifestation.
Chikungunya virus
Chikungunya virus
The name Chikungunya is derived from the word “kungunyala”
meaning “that which bends up or gets folded” in reference to
the stooped posture which develops as a result of the severe
joint pain that occurs during the course of illness.
Important properties of
Chikungunya virus
• It is a single stranded RNA virus.
• It belongs to family Togaviridae, of genus Alphavirus.
• It is an Enveloped virus.
• Vector: Aedes mosquitoes, both Aedes aegypti and Aedes
albopictus.
• Mode of transmission: By bite of infected female Aedes
mosquito during day time.
Structure of chikungunya virus
• It is a spherical, Single Stranded enveloped
RNA virus.
• At the center of the virion is the
nucleocapsid (NC) core which is composed
of the C protein in complex with the viral
genome .
• The E1 and E2 glycoproteins form
heterodimers and assemble into spikes on
the surface.
• It encods four nonstructural proteins (nsP1–
4), which are required for virus replication,
and five structural proteins (capsid protein
C, glycoproteins E1, E2, E3, and 6K)
Pathogenesis of Chikungunya
fever
Chikungunya virus infection begins when an infected mosquito bites a
human and the virus is introduced into the skin and blood stream
↓
The virus replicates in the fibroblasts of the dermis and disseminate
through the blood stream to several tissues
↓
Viral replication occurs in target tissues- mainly muscles, joints and skin
as well as the liver, spleen and meninges
↓
Pathogenesis of Chikungunya
fever contd…
Inflammatory cells are recruited to the infected tissues.
↓
Joints (including in the fingers, wrists, elbows, ankles and toes) become
inflamed in response to viral replication and inflammatory infiltrates.
Coronavirus disease
2019 (COVID-19)
Coronavirus disease 2019 (COVID-19)
Coronavirus disease 2019 (COVID-19) is an acute respiratory
disease caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2).
It has caused an explosive catastrophic pandemic that
affected almost all part of the world and produced significant
loss of lives and the worst crisis recorded ever, since World
War II.
SARS-CoV-2
SARS-CoV-2 was first identified in December 2019 in Wuhan,
China, which produced a large cluster of pneumonia cases-
hence, the virus was initially called as the “Wuhan virus”.
Subsequently it was named as the 2019-novel coronavirus
(2019-nCoV).
On 11th February 2020, WHO announced the official name
‘COVID-19’ for this new coronavirus disease and also renamed
the virus as SARS-CoV-2 because its genome closely related to
SARS-CoV.
On 11th March 2020, WHO declared it as a global pandemic.
Structure of SARS-CoV-2
• SARS-CoV-2 is a ssRNA virus.
• Nucleocapsid is surrounded by an envelope.
• It possess 4 structural proteins which includes spike protein
(S), envelope protein (E), membrane glycoprotein (M) and
nucleocapsid protein (N) and 16 non-structural proteins.
Structure of SARS-CoV-2
Mode of Transmission
SARS-CoV-2 is primarily transmitted via respiratory droplets
and contact routes.
Droplet transmission: Droplet transmission occurs when a
person is in close contact (within 1 meter) with an infected
person.
Contact transmission: Transmission can occur directly by
contact with infected people or indirectly with objects used
on or by the infected person.
Pathogenesis of COVID-19
Host cell entry:
SARS-CoV-2 enters into the target cells by binding of its spike
glycoprotein (S) antigen with the host cell receptor, i.e.
angiotensin converting enzyme-2 (ACE-2).
ACE-2 receptors are highly expressed on type-II alveolar cells
in lungs and on the epithelial cells of oral mucosa; also found
on cells of heart, kidney, endothelium, and intestine. Therefore,
the patients develop extrapulmonary manifestations in addition
to respiratory symptoms.
Pathogenesis of COVID-19
contd…
Development of influenza-like illness (ILI):
ACE-2 receptors are highly expressed on the epithelial cells of
oral mucosa. Therefore, at the initial stage, SARS-CoV-2 infects
the pharyngeal epithelium, induces inflammation. This
accounts for the influenza-like illness (ILI) which occurs at the
beginning stage of most of the symptomatic cases.
Pathogenesis of COVID-19
contd…
Development of ARDS: The leading cause of mortality in
patients with COVID-19 is hypoxemic respiratory failure which
can result in acute respiratory distress syndrome (ARDS).
Reduced surfactants: In lungs, ACE-2 receptors are highly
expressed on type-II alveolar cells. These cells normally produce
pulmonary surfactants which lower the alveolar surface tension.
In COVID-19 patients, damage to the alveolar cells leads to
reduced production of pulmonary surfactants; as a result of
which alveoli tend to collapse. The air-liquid-interphase is
perturbed which leads to fluid retention in the interstitial space.
Pathogenesis of COVID-19 contd…
Cytokine storm: The presence of SARS-CoV-2 in lung induces
an uncontrolled generalized immune response. Several
immune cells like neutrophils, T-lymphocytes, macrophages are
recruited to the lungs.
These immune cells release pro-inflammatory cytokines (IL-2,
IL-6, IL-8, IFN-ү, TNF-α etc). The elevated cytokines leads to
various consequences such as:
- causes tissue damage and necrosis
- Impaired gas exchange, which leads to reduced blood
oxygenation and tissue hypoxia
Pathogenesis of COVID-19
- Endothelial damage of pulmonary vasculature, leading to
vasodilation, microvascular thrombosis and hypercoagulability.
- Dilatation of blood vessels underlying the alveoli; which allows
passage of fluid from the blood vessels to lungs leads to
pulmonary edema. These infiltrates in the lungs appear as
‘ground-glass’ in chest imaging.
- In the later stage, there occurs recruitment of fibroblast, which
causes lung fibrosis and ultimately, leads to respiratory failure.
- Cytokines can also induce damage to other organs of the body
such as heart, kidney, liver etc. leads to multiorgan failure.
