ADENOVIRUS DISEASES

8/3/2019 ADENOVIRUS DISEASES

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ADENOVIRUSES

BasicsDr.T.V.Rao MD

Dr.T.V.Rao MD 1



Human Adenoviruses

Adenoviruses were first isolated in1935 from human adenoid tissues.

Since then, at least 52 distinct antigenic types have been isolatedfrom humans and many other typesfrom animals.

All human serotypes are included ina single genus within the familyAdenoviridae.

Dr.T.V.Rao MD 2



Basis of Adenovirus typing

52 human serotypes, 7 distinct species A-G

based on hemagglutination properties, DNA homologyand oncogenic potential in rodents

Different serotypes may cause infection ordistinct diseases in different age groups orpatient populations

Neutralizing antibodies are serotype-specific

Cellular immune response cross-reactive acrossvarious serotypes



What are Adenoviruses

Adenoviruses are agroup of mediumsized, nonenvelopedd,

double stranded DNAviruses that share acommon complementfixing antigen

They infect humansand animals

Dr.T.V.Rao MD 4



Chaterstics of Adenovirus

Adenoviruses are medium-sized (90 –100nm, nonenveloped (naked) icosahedralviruses composed of a nucleocapsid and a

double-stranded linear DNA genome.There are over 52 different serotypes inhumans, which are responsible for 5 –10%

of upper respiratory infections in children,and many infections in adults as well.

Dr.T.V.Rao MD 5



Adenovirus Genome

The adenovirus genome is linear, non-segmented double stranded (ds) DNA which isaround 30 –38 Kbp. This allows the virus totheoretically carry 30 to 40 genes. Although thisis significantly larger than other viruses in itsBaltimore group it is still a very simple virus andis heavily reliant on the host cell for survival andreplication. An interesting feature of this viral

genome is that it has a terminal 55 kDa proteinassociated with each of the 5' ends of the lineardsDNA, these are used as primers in viralreplication and ensure that the ends of the virus'

linear genome are adequately replicatedDr.T.V.Rao MD 6



Morphology of Adenovirus

Adenovirus are 70-75 nmin size

The capsid contains 252capsomers arranged as

icosahedrons with 20triangular facets and 12vertices

240 are called as hexons

12 are called as pentons

Dr.T.V.Rao MD 7



Appear as space vehicle

Dr.T.V.Rao MD 8



Adenoviruses are prevalent all over

the world Over 50 serotypes

are isolated

Most of the recent

isolates are fromAIDS patients

Infections are

common in childrenand world wideprevalence.

Dr.T.V.Rao MD 9



Morphological configuration

Each penton unitconsists of pentonbase anchored in the

capsid and projectionor fibre consists of arode like portion with aknob attached at the

distal end The virus appears like

a space vehicle.

Dr.T.V.Rao MD 10



Classification Contain two genera

Mast adenovirus.

Infects the mammals

Aviaadenovirus

Infects birds

They infect only the homologues species with theexception of oncogenic human adenovirus

Type 12, 18,and 31 cause sarcoma when injectedinto new born hamsters.

Dr.T.V.Rao MD 11



Diseases caused by AdenovirusesGroup Affected Syndromes Serotypes

Neonates Fatal disseminated infection 3, 7, 21, 30Infants Coryza, pharyngitis 1, 2, 5 (C)

Children Upper respiratory disease

Pharyngoconjunctival fever

Hemorrhagic cystitis

DiarrheaIntussussception

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)

Immunocompromisedpatients

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 theepithelial cells of the: pharynx,

conjunctiva, urinary bladder

small intestine.

They usually do not spread beyond theregional lymph nodes EXCEPT IN THEIMMUNE COMPROMIZED HOST.

Dr.T.V.Rao MD 13



Pathogenesis

Adenovirus causeinfections in

Respiratory tract

Eye, Urinary bladder,and Intestines

More than one type of

virus may causeclinically differentdiseases

Dr.T.V.Rao MD 14



CLINICAL SYNDROMES

A. Respiratory diseases:

B. Eye infections:

C. Gastrointestinal disease

D. Other diseases:

E. Adenoviral infections of the immunecompromised host

Dr.T.V.Rao MD 15



Clinical Features

Clinical features: Adenoviruses mostcommonly cause respiratory illness;however, depending on the infecting

serotype, they may also cause variousother illnesses, such as gastroenteritis,conjunctivitis, cystitis, and rash illness.Symptoms of respiratory illness caused by

adenovirus infection range from thecommon cold syndrome to pneumonia,croup, and bronchitis.

Dr.T.V.Rao MD 16




Four different syndromes of respiratory infectionhave 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).

Dr.T.V.Rao MD 17




Acute respiratory disease: is characterized by pharyngitis,

fever, cough and malaise.

It occurs in an epidemic formamong young recruits underconditions of fatigue andovercrowding

Pneumonia: a complication ofacute respiratory disease in bothchildren and adults.

Dr.T.V.Rao MD 18



Adenovirus infections are important

in Military Medicine

Adenoviruses are responsible for 3-5% ofacute respiratory infections in children and

2% of respiratory illnesses in civilian adults.

They are more apt to cause infection amongmilitary recruits and other young people wholive in institutional environments. Outbreaks

among children are frequently reported atboarding schools and summer camps.

Dr.T.V.Rao MD 19



Adenovirus - Pharyngitis

Major cause of

infectionsassociated with

nonbacterialpharyngitis andtonsillitis

Causes febrilecommon cold

Types 1 – 7 are

common types Dr.T.V.Rao MD 20



Adenovirus Common cause of

Respiratory infections

Dr.T.V.Rao MD 21



Pneumonia - Adenovirus

Adenovirus types 3and 7 are associatedwith pneumonia

resembles like atypicalpneumonia in adults.

Type 7 causes seriousand even fatal

pneumonia in infantsand young children

Dr.T.V.Rao MD 22



ARD – Acute respiratory disease

with Adenovirus

Occurs usually

in military

recruitsSerotypes

4,7,and 21 areagents

commonly

associated. Dr.T.V.Rao MD 23



Pharyngocongunctival fever

Occurs in civilianpopulation manifest

with syndrome offebrile Pharyngitisand conjunctivitis

Serotypes 3, 7, and14 are associated.

Dr.T.V.Rao MD 24



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 byvarious degrees of visual disability.

Dr.T.V.Rao MD 25



Epidemic keratoconjunctivitis

Occurs with

serious

epidemicCaused by

serotypes 8,and less

frequently with

19, and 37.Dr.T.V.Rao MD 26



A severe Adenoviral Infection

Dr.T.V.Rao MD 27



C. Gastrointestinal disease:

1. No disease association

1. Many Adenoviruses replicate in intestinal

cells and are present in the stools withoutbeing associated with GIT disease.

2. Infantile gastroenteritis1. Two serotypes (40, 41) have been

etiologically associated with infantilegastroenteritis.

Dr.T.V.Rao MD 28



D. Other diseases:

Acutehemorrhagiccystitis:

types 11, 21 maycause acutehemorrhagiccystitis in children

especially boys.Dr.T.V.Rao MD 29



Other manifestations

Acute follicular conjunctivitis, types 3,4 and 11are 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.

Dr.T.V.Rao MD 30



E. Adenoviral infections of the

immune compromised host

The mostcommon clinical

manifestationsare: pneumonia,

hepatitis

gastroenteritis.

Dr.T.V.Rao MD 31



Adenovirus inimmunocompromised

Patients with compromised immune

systems are especially susceptible to

severe complications of adenovirusinfection. 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 havebeen infected by atleast one adenovirus

by the time they reachschool age. Mostadults have acquiredimmunity to multiple

adenovirus types dueto infections they hadas children.

Dr.T.V.Rao MD 33



Diagnosis of Adenoviral Infections

Diagnosis: Antigen detection, polymerasechain reaction assay, virus isolation, and

serology can be used to identify

adenovirus infections. Adenovirus typing isusually accomplished byhaemagglutination-inhibition and/or

neutralization with type-specific antiserum.Since adenovirus can be excreted forprolonged periods, the presence

Dr.T.V.Rao MD 34



Laboratory Diagnosis

Direct

detection: Isolation

Serology

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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 Polymerasechain reaction: can be used for diagnosis ofAdenovirus infections in tissue samples or bodyfluids.

Dr.T.V.Rao MD 36




Isolation Isolation depending on the

clinical disease, the virusmay be recovered fromthroat, or conjunctivalswabs or and urine.

Isolation is much moredifficult from the stool orrectal swabs

Dr.T.V.Rao MD 37




Serology

Haemagglutinationinhibition

Neutralization testscan be used todetect specificantibodies

followingAdenovirusinfection.

Dr.T.V.Rao MD 38



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 easiestway to prevent infection.

Disinfection of Environmental surfaces

with hypochlorite's. The risk of water borne outbreaks of

conjunctivitis can be minimized bychlorination of swimming pools.

Epidemic keratoconjunctivitis can becontrolled by strict asepsis during eyeexamination.

Dr.T.V.Rao MD 40



Prevention of Adenoviral Infections

Prevention: Vaccines were developed foradenovirus serotypes 4 and 7, but wereavailable only for preventing ARD among militaryrecruits. Strict attention to good infection-control

practices is effective for stopping nosocomialoutbreaks of adenovirus-associated disease,such as epidemic keratoconjunctivitis.Maintaining adequate levels of chlorination is

necessary for preventing swimming pool-associated outbreaks of adenovirusconjunctivitis.

Dr.T.V.Rao MD 41



Adenovirus asVectors On trails

Vaccine

production

HIVMalaria

Ebola

Hepatitis C

TB



Hand Washing still can reduce

Adenoviral Infections

Dr.T.V.Rao MD 43



Programme created by Dr.T.V.Rao MDfor Medical and Paramedical students

in the developing world

Email

[email protected]

ADENOVIRUS DISEASES

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