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ADENOVIRUS. ADENOVIRUS. DNA viruses first isolated from adenoidal tissue in 1953. ADENOVIRUS. Family Adenoviridae Genus Mastadenovirus. Transmission electron micrograph of adenovirus Source- PUBLIC Health Image Library, CDC. ADENOVIRUS - Classification.
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ADENOVIRUS DNA viruses first isolated from adenoidal tissue in 1953
ADENOVIRUS FamilyAdenoviridae GenusMastadenovirus
Transmission electron micrograph of adenovirusSource- PUBLIC Health Image Library, CDC
ADENOVIRUS - Classification Subgroups- 6 subgroups (A-F), based on hemagglutination Serotypes- 1-49 (human) Common serotypes:- 1-8, 11, 21, 35, 37, 40 Enteric Adenoviruses belong to subgroup F
ADENOVIRUS - Structure Non-enveloped DNA virus 70-90 nm in size Linear ds DNA genome with core proteins
ADENOVIRUS - Ultra structure Icosahedralcapsid with 252 capsomeres (12 pentons at vertices and 240 hexons) Each penton has a fibers with terminal knob projecting from it
Pathogenesis and Replication Infects mucoepithelial cells of respiratory, GI and GU tracts Enter via epithelium, replicate and spread to lymphoid tissue Viremia occurs Secondary involvement of viscera
Pathogenesis and Replication (contd.) Fiber protein determines target cell specificity and attachment Viral DNA enters host cell nucleus Virus replicates in cytoplasm
Replication (contd.) Early and late phases of replication Error-prone process Inclusion bodies in nucleus
Types of infection Lytic Latent/occult Oncogenic Transformation
Types of infection • Lytic • Results in cell death; seen in mucoepithelical cells • Latent/occult • Virus remains in host cell; seen in lymphoid tissue, Groups B and C • Oncogenic Transformation • Uncontrolled cell growth and replication occur; seen with Group A viruses in hamsters
Adenovirus Used as VECTORS to transfer desired genetic material into cells Viral genome is relatively easily manipulated in vitro Efficient expression of inserted DNA in recipient cell
Adenovirus- Properties • Stable in the environment • Relatively resistant to disinfection • (Alcohol, chlorhexidine, detergents) • Stable in GI tract- can withstand low pH, bile acids and proteolytic enzymes
Time-course of infection Incubation period- 2-14 days Infective period continues for weeks Intermittent and prolonged rectal shedding Secondary attack rate within families up to 50%
Timecourse - Respiratory infectionSource- Medical Microbiology, 5th Edition (Murray, Rosenthal, and Pfaller)
EPIDEMIOLOGY Endemic, epidemic and sporadic infections Many infections are sub-clinical
EPIDEMIOLOGY-contd.’Tip of the iceberg phenomenon’ Classical disease presentation Mild clinical disease Asymptomatic infection but +infectivity
EPIDEMIOLOGY- Outbreaks Military recruits, swimming pool users, hospitals, residential institutions, day care settings
EPIDEMIOLOGY-transmission Prolonged infective period (weeks) Intermittent and prolonged rectal shedding Stable in the environment
TRANSMISSION Droplets Fecal-oral route Direct and through poorly chlorinated water Fomites
CLINICAL SYNDROMES Respiratory Eye Genitourinary Gastrointestinal Others
Acute Respiratory Disease(LRI) Fever Tracheobronchitis Pneumonia Children and adults Epidemics in military recruits Types 4 and 7 most frequently
Pharyngoconjunctival fever Headache, fever, malaise Conjunctivitis and Pharyngitis Cervical adenopathy, rash and diarrhea also Main adenovirus types: 3, 4, 7, 14 Epidemics in summer months Contaminated water in swimming pools, fomites
Adenoviral Infections of the eye Epidemic Keratoconjunctivitis (EKC) Acute follicular conjunctivitis Pharyngoconjunctival fever
Adenoviral conjunctivitis Early conjunctivitis (top) and Bilateral conjunctivitis (lower)
Epidemic Keratoconjunctivitis Incidence in summer Types 8, 19, 37 Outbreaks- in situations of close contact (e.g., schools, hospitals, camps, nursing homes, workplaces) Spread via droplets and contaminated water (ophthalmologic solutions and equipment, swimming pools), fomites, hands
EKC-Clinical features SYMPTOMS • Pink/red eye • Irritation, tearing, foreign-body sensation • Ocular pain • Photophobia • Fever, malaise • Respiratory symptoms SIGNS • Conjunctival injection, ecchymosis • Corneal injection (limbus) • Diffuse→focal epithelial keratitis • ↓Visual acuity (subepithelial corneal opacities) • Ipsilateral pre-auricular lymphadenopathy
Gastrointestinal Infections Types 40, 41 Age <4 years Spread via fecal-oral route Year round
Gastrointestinal Infections- (contd.) • Incubation period 3-10 days • Diarrhea lasts for 10-14 days • Fever • Also, intussusception, mesenteric adenitis, appendicitis
ADENOVIRAL INFECTIONS- Genitourinary system Acute hemorrhagic cystitis • fever, dysuria, hematuria • Types 11, 7, 4, 21, 1 • More common in boys Others • Orchitis, nephritis, cervicitis with ulcerated vesicular lesions, urethritis • Types 2, 8, 19, 37
Other Infections due to Adenovirus Myocarditis Pericarditis Meningitis Rash Arthritis
Adenovirus infections in Immunocompromised hosts Disseminated, severe and often fatal infections Due to new infection or reactivation of latent virus Prolonged infections with prolonged viremia and viral shedding Necrotizing pneumonia, hepatitis, rash, disseminated intravascular coagulation (DIC), CNS involvement
DIAGNOSIS OF ADENOVIRAL INFECTIONS • Variety of clinical specimens depending on clinical syndrome-NP, conjunctival, stool, urine, • tissue, etc. • Transport in viral transport media • Isolation from pharyngeal site correlates better with current clinical infection
Methods for diagnosis Culture in HeLa, HEK cell lines Shell vial cell culture DFA PCR, nucleic acid probes EM and Immune EM
Diagnosis-Enteric adenoviruses Isolation requires special media-Graham 293 ELISA for rapid detection is available
Prevention Good handwashing Contact precautions Chlorination of water Disinfection or sterilization of ophthalmologic equipment Use of single dose vials Oral vaccine- restricted use
ADENOVIRUS VACCINE • Oral live attenuated vaccine • Strains 4, 7 • Used in military recruits • Manufacture of vaccine was halted in 1996 • Lapse in immunization was associated with outbreaks in military recruits