ADENOVIRUSES

Basics
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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 (90100 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 510% of upper respiratory infections in children, and many infections in adults as well.
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Adenovirus Genome

The adenovirus genome is linear, nonsegmented double stranded (ds) DNA which is around 3038 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 6 Dr.T.V.Rao MD

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
Neonates Infants Children

Syndromes
Fatal disseminated infection Coryza, pharyngitis Upper respiratory disease Pharyngoconjunctival fever Hemorrhagic cystitis Diarrhea Intussussception Meningoencephalitis Acute respiratory disease and PNA Epidemic keratoconjunctivitis PNA with dissemination Liver infection Urinary Tract Infection Intestinal Infection CNS disease including encephalitis

Serotypes
3, 7, 21, 30 1, 2, 5 (C) 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 3, 4, 7 8, 19, 37 (D) 5, 31, 34 1, 2, 5 (C) 35, 39 42-51 (D) 7, 12, 32

Young adults Adults Immunocompromised patients

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.

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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

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serious epidemic Caused by serotypes 8, and less frequently with 19, and 37.

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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. Two serotypes (40, 41) have been etiologically associated with infantile gastroenteritis.
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2.

Infantile gastroenteritis
1.

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.
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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 poolassociated 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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