Introduction Adenoviruses is a group of medium sized, nonenveloped, double stranded DNA viruses that replicate and produce disease in the eye and in the respiratory, gastrointestinal and urinary tracts. They infect humans and animals. At least 47 serotypes associated with human diseases. • Most infections asymptomatic; • Infections are common in children;
Morphology 1. They are non-enveloped, 70-90 nm in size, possess 252 capsomeres. 2. Icosahedral symmetry with fibre proteins projecting from each vertex ( unique property): This gives a typical space vehicle shaped appearance . 3. They contain a linear dsDNA
Pathogenesis Adenoviruses infect and replicate in the epithelial cells of the respiratory tract, eye, gastrointestinal tract, urinary bladder and liver. Though one-third of the serotypes can cause human diseases, types 1-7 are most common worldwide. Single serotype may cause different manifestations and conversely, more than one type may cause the same clinical illness.
Clinical Manifestations Respiratory diseases • Upper respiratory tract infection in children-mainly caused by serotypes 1, 2, 3 and 5 • Pneumonia: Adenoviruses particularly types 3, 7, and 21 are responsible for about 10-20% of pneumonia in childhood. • Acute respiratory disease syndrome outbreaks among military recruit-are commonly associated with type 4, 7 and occasionally type 3.
Ocular infections: • Pharyngoconjunctival fever: It tends to occur in outbreaks, at children's summer camps (also called swimming pool conjunctivitis), and is associated with types 3 and 7. • Epidemic keratoconjunctivitis or shipyard eye: It occurs mainly in adults and is highly contagious, caused by types 8, 19 and 37.
Epidemic keratoconjunctivitis
Infantile gastroenteritis: Serotype 40 and 41 may account for 5-15% of cases of viral gastroenteritis in young children. Acute haemorrhagic cystitis in children, especially in boys-caused by serotypes 11 and 21. Immunocompromised patients are at higher risk of developing serious pneumonia. Transplant recipients may develop pneumonia, hepatitis, nephritis, colitis, encephalitis and haemorrhagic cystitis. Types 34 and 35 are isolated commonly from transplant recipients.
Laboratory Diagnosis Specimen collection: Depending on the manifestations, various specimens such as throat swab, conjunctival swab, stool or urine may be collected. Virus isolation: Primary human embryonic kidney cell line and A549 cell line are the most susceptible cell lines. Others such as HEp-2, HeLa, and KB cell lines can also be used Viral growth can be detected by: • Characteristic cytopathic effect: Rounding and grape-like clustering of swollen cells • Antigen detection by direct-IF test.
This digitally-colorized transmission electron microscopic (TEM) image revealed some of the ultrastructural details exhibited by a small cluster of adenovirus virions.
• Reporting: Reporting should be done cautiously when adenovirus is recovered from throat or stool as they can persist for long duration in the gut and in adenoids and shed intermittently in the setting of other infections. • Shell vial technique can be performed prior to cell culture to enhance viral replication so that detection time can be reduced • Explant culture: Adenoviruses (especially group-C) can grow on adenoid explants, however, it is no longer in use now. Serotyping: Type specific antigens ( viral capsid proteins) can be identified by hemagglutination test ( targeting HA antigens) and neutralization test (targeting capsid proteins)
Direct-IF test: It can be employed to detect adenoviral antigens from clinical samples such as throat or conjunctival secretions by using fluorescent tagged antihexon Antibody. Fastidious enteric serotypes such as type 40 and 41 from stool: They can be detected by electron microscopy or by antigen detection by ELISA.
Molecular methods: PCR has been available targeting group -specific conserved hexon or fibre genes. Multiplex PCR followed by sequencing is done for detection of adenovirus types. PCR is rapid and more sensitive than conventional culture. Real-time PCR is used to monitor viral load, which is useful for immunocompromised and transplant recipients. Serum antibody detection: It can be done by various tests such as CFT, neutralization test, ELISA, or rarely hemagglutination inhibition test (HAI) for few hemagglutinating serotypes.
This transmission electron microscopic (TEM) image reveals some of the ultrastructural morphology exhibited by two adenovirus-2 virions.
Treatment and Control There is no specific antiviral drug available. Only symptomatic treatment is given. General Preventive Measures 1. Effective hand washing: Use of paper towels is better than cloth towels for hand drying 2. Sodium hypochlorite to disinfect environmental surfaces 3. Chlorination of swimming pools and waste water should be followed to prevent waterborne conjunctivitis or gastroenteritis. 4. Strict asepsis during eye examinations
Live Adenovirus Vaccine Live adenovirus vaccine containing types 4 and 7 has been used in military recruits. It was available as gelatin coated capsules and given orally It was highly effective, but not in use since 1999 due to manufacturer issues. There are plans to develop this vaccine again. Adenoviruses used for Gene Therapy Replication defective adenoviruses can also be used as live virus vectors for the delivery of vaccine antigens and for gene therapy; e.g. trials on adenovirus vectored M. tuberculosis (using SSA antigen) and HIV vaccines.