adenovirus infections
DESCRIPTION
Adenovirus InfectionsTRANSCRIPT
ADENOVIRUSES Basics
Dr.T.V.Rao MD
Dr.T.V.Rao MD 1
Human Adenoviruses
Adenoviruses were first isolated in 1935 from human adenoid tissues.
Since then, at least 52 distinct antigenic types have been isolated from humans and many other types from animals.
All human serotypes are included in a single genus within the family Adenoviridae.
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Basis of Adenovirus typing
52 human serotypes, 7 distinct species A-G
based on hemagglutination properties, DNA homology
and oncogenic potential in rodents
Different serotypes may cause infection or
distinct diseases in different age groups or
patient populations
Neutralizing antibodies are serotype-specific
Cellular immune response cross-reactive across
various serotypes
What are Adenoviruses
Adenoviruses are a
group of medium
sized, nonenvelopedd,
double stranded DNA
viruses that share a
common complement
fixing antigen
They infect humans
and animals
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Chaterstics of Adenovirus
Adenoviruses are medium-sized (90–100
nm, nonenveloped (naked) icosahedral
viruses composed of a nucleocapsid and a
double-stranded linear DNA genome.
There are over 52 different serotypes in
humans, which are responsible for 5–10%
of upper respiratory infections in children,
and many infections in adults as well.
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Adenovirus Genome
The adenovirus genome is linear, non-segmented double stranded (ds) DNA which is around 30–38 Kbp. This allows the virus to theoretically carry 30 to 40 genes. Although this is significantly larger than other viruses in its Baltimore group it is still a very simple virus and is heavily reliant on the host cell for survival and replication. An interesting feature of this viral genome is that it has a terminal 55 kDa protein associated with each of the 5' ends of the linear dsDNA, these are used as primers in viral replication and ensure that the ends of the virus' linear genome are adequately replicated Dr.T.V.Rao MD 6
Morphology of Adenovirus
Adenovirus are 70-75 nm
in size
The capsid contains 252
capsomers arranged as
icosahedrons with 20
triangular facets and 12
vertices
240 are called as hexons
12 are called as pentons
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Appear as space vehicle
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Adenoviruses are prevalent all over
the world Over 50 serotypes
are isolated
Most of the recent
isolates are from
AIDS patients
Infections are
common in children
and world wide
prevalence.
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Morphological configuration
Each penton unit
consists of penton
base anchored in the
capsid and projection
or fibre consists of a
rode like portion with a
knob attached at the
distal end
The virus appears like
a space vehicle.
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Classification
Contain two genera
Mast adenovirus.
Infects the mammals
Aviaadenovirus
Infects birds
They infect only the homologues species with the
exception of oncogenic human adenovirus
Type 12, 18,and 31 cause sarcoma when injected
into new born hamsters.
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Diseases caused by Adenoviruses Group Affected Syndromes Serotypes
Neonates Fatal disseminated infection 3, 7, 21, 30
Infants Coryza, pharyngitis 1, 2, 5 (C)
Children Upper respiratory disease
Pharyngoconjunctival fever
Hemorrhagic cystitis
Diarrhea
Intussussception
Meningoencephalitis
1, 2, 4-6
3, 7 (B)
7, 11, 21 (B)
2, 3, 5, 40, 41 (F)
1, 2, 4, 5
2, 6, 7, 12
Young adults Acute respiratory disease and PNA 3, 4, 7
Adults Epidemic keratoconjunctivitis 8, 19, 37 (D)
Immunocompromised
patients
PNA with dissemination
Liver infection
Urinary Tract Infection
Intestinal Infection
CNS disease including encephalitis
5, 31, 34
1, 2, 5 (C)
35, 39
42-51 (D)
7, 12, 32
Pathogenesis:
Adenoviruses infect and replicate in the
epithelial cells of the:
pharynx,
conjunctiva,
urinary bladder
small intestine.
They usually do not spread beyond the regional lymph nodes EXCEPT IN THE IMMUNE COMPROMIZED HOST.
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Pathogenesis
Adenovirus cause
infections in
Respiratory tract
Eye, Urinary bladder,
and Intestines
More than one type of
virus may cause
clinically different
diseases
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CLINICAL SYNDROMES
A. Respiratory diseases:
B. Eye infections:
C. Gastrointestinal disease
D. Other diseases:
E. Adenoviral infections of the immune compromised host
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Clinical Features
Clinical features: Adenoviruses most commonly cause respiratory illness; however, depending on the infecting serotype, they may also cause various other illnesses, such as gastroenteritis, conjunctivitis, cystitis, and rash illness. Symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia, croup, and bronchitis.
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A. Respiratory diseases:
Four different syndromes of respiratory infection have been linked to Adenoviruses.
Acute febrile pharyngitis: most commonly seen in infants and young children,
symptoms include cough, stuffy nose, fever and sore throat.
Pharyngo conjunctival fever: symptoms are similar to those of acute febrile pharyngitis but
conjunctivitis is also present.
It tends to occur in outbreaks such as at children's summer camps (swimming pool conjunctivitis).
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A. Respiratory diseases:
Acute respiratory disease: is characterized by pharyngitis,
fever, cough and malaise.
It occurs in an epidemic form among young recruits under conditions of fatigue and overcrowding
Pneumonia: a complication of acute respiratory disease in both children and adults.
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Adenovirus infections are important
in Military Medicine
Adenoviruses are responsible for 3-5% of
acute respiratory infections in children and
2% of respiratory illnesses in civilian adults.
They are more apt to cause infection among
military recruits and other young people who
live in institutional environments. Outbreaks
among children are frequently reported at
boarding schools and summer camps.
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Adenovirus - Pharyngitis
Major cause of
infections
associated with
nonbacterial
pharyngitis and
tonsillitis
Causes febrile
common cold
Types 1 – 7 are
common types
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Adenovirus Common cause of
Respiratory infections
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Pneumonia - Adenovirus
Adenovirus types 3
and 7 are associated
with pneumonia
resembles like atypical
pneumonia in adults.
Type 7 causes serious
and even fatal
pneumonia in infants
and young children
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ARD – Acute respiratory disease
with Adenovirus
Occurs usually
in military
recruits
Serotypes
4,7,and 21 are
agents
commonly
associated.
Doctorrao'sslideshare
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Pharyngocongunctival fever
Occurs in civilian
population manifest
with syndrome of
febrile Pharyngitis
and conjunctivitis
Serotypes 3, 7, and
14 are associated.
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B. Eye infections:
Mild conjunctivitis:
can occur as a part of respiratory pharyngeal syndromes.
Complete recovery with no lasting sequellae is the
common outcome.
Can occur sporadically or in outbreaks.
Epidemic keratoconjunctivitis: a highly contagious and a more serious disease occurring mainly
in adults.
Corneal involvement may be followed by
various degrees of visual disability.
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Epidemic keratoconjunctivitis
Occurs with
serious
epidemic
Caused by
serotypes 8,
and less
frequently with
19, and 37. Dr.T.V.Rao MD 26
A severe Adenoviral Infection
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C. Gastrointestinal disease:
1. No disease association
1. Many Adenoviruses replicate in intestinal
cells and are present in the stools without
being associated with GIT disease.
2. Infantile gastroenteritis 1. Two serotypes (40, 41) have been
etiologically associated with infantile
gastroenteritis.
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D. Other diseases:
Acute
hemorrhagic
cystitis:
types 11, 21 may
cause acute
hemorrhagic
cystitis in children
especially boys.
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Other manifestations
Acute follicular conjunctivitis, types 3,4 and 11
are responsible
Adenoviral and chlamydial conjunctivitis are
clinically similar
Diarrhoea – not conclusively established
Acute hemorrhagic cystitis in children and
types 11 and 21 are responsible
Mesenteric adenitis and intussusceptions in
children.
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E. Adenoviral infections of the
immune compromised host
The most common clinical manifestations are:
pneumonia,
hepatitis
gastroenteritis.
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Adenovirus in
immunocompromised Patients with compromised immune
systems are especially susceptible to
severe complications of adenovirus
infection. Acute respiratory disease
(ARD), first recognized among
military recruits during World War II,
can be caused by adenovirus
infections during conditions of
crowding and stress. Dr.T.V.Rao MD 32
Immunity in Children
Most children have
been infected by at
least one adenovirus
by the time they reach
school age. Most
adults have acquired
immunity to multiple
adenovirus types due
to infections they had
as children.
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Diagnosis of Adenoviral Infections
Diagnosis: Antigen detection, polymerase
chain reaction assay, virus isolation, and
serology can be used to identify
adenovirus infections. Adenovirus typing is
usually accomplished by
haemagglutination-inhibition and/or
neutralization with type-specific antiserum.
Since adenovirus can be excreted for
prolonged periods, the presence
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Laboratory Diagnosis
Direct
detection:
Isolation
Serology
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Laboratory Diagnosis
Direct detection:
Virus particle by EM can be detected by direct examination of fecal extracts
Detection of adenoviral antigens by ELISA.
Enteric Adenoviruses
Detection of adenoviral NA by Polymerase chain reaction: can be used for diagnosis of Adenovirus infections in tissue samples or body fluids.
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Laboratory Diagnosis
Isolation Isolation depending on the
clinical disease, the virus may be recovered from throat, or conjunctival swabs or and urine.
Isolation is much more difficult from the stool or rectal swabs
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Laboratory Diagnosis
Serology
Haemagglutination
inhibition
Neutralization tests
can be used to
detect specific
antibodies
following
Adenovirus
infection.
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Adenovirus Treatment
Antivirals against AdV:
Potential targets: AdV DNA polymerase
AdV cysteine protease
receptors for binding host cells
Antivirals in use: Ribavirin
Cidofovir
Ganciclovir
(Vidarabine)
Prevention and control
Careful hand washing is the easiest way to prevent infection.
Disinfection of Environmental surfaces with hypochlorite's.
The risk of water borne outbreaks of conjunctivitis can be minimized by chlorination of swimming pools.
Epidemic keratoconjunctivitis can be controlled by strict asepsis during eye examination.
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Prevention of Adenoviral Infections
Prevention: Vaccines were developed for adenovirus serotypes 4 and 7, but were available only for preventing ARD among military recruits. Strict attention to good infection-control practices is effective for stopping nosocomial outbreaks of adenovirus-associated disease, such as epidemic keratoconjunctivitis. Maintaining adequate levels of chlorination is necessary for preventing swimming pool-associated outbreaks of adenovirus conjunctivitis.
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Adenovirus asVectors On trails
Vaccine
production
HIV
Malaria
Ebola
Hepatitis C
TB
Hand Washing still can reduce
Adenoviral Infections
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