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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Programme created by Dr.T.V.Rao MD

for Medical and Paramedical students

in the developing world

Email

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