1. ADENOVIRUS

2. DNA viruses first isolated from adenoidal tissue in 1953

3. ADENOVIRUS Family Adenoviridae Genus Mastadenovirus

4. Transmission electron micrograph of adenovirus Source- PUBLIC Health Image Library, CDC

5. 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

6. ADENOVIRUS – Classification Adapted from Fields Virology SUBGROUPSEROTYPES A12, 18, 31 B3, 7, 11, 14, 34, 35 C1, 2, 5, 6 D8-10, 19, 20, 22-30, 36-39, 42-49 E4 F40, 41

7. ADENOVIRUS - Structure Non-enveloped DNA virus 70-90 nm in size Linear ds DNA genome with core proteins

8. ADENOVIRUS EM APPEARANCE

9. ADENOVIRUS - Ultra structure Icosahedral capsid with 252 capsomeres (12 pentons at vertices and 240 hexons) Each penton has a fibers with terminal knob projecting from it

10. Adenovirus- 3 D structure

11. ADENOVIRUS STRUCTURE

12. Adenovirus - EM appearance

13. ADENOVIRUS-Ultrastructure

14. Structure

15. 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

16. Pathogenesis and Replication (contd.) Fiber protein determines target cell specificity and attachment Viral DNA enters host cell nucleus Virus replicates in cytoplasm

17. Adenovirus- replication

18. Replication (contd.) Early and late phases of replication Error-prone process Inclusion bodies in nucleus

19. ADENOVIRAL INCLUSION BODIES

20. Types of infection Lytic Latent/occult Oncogenic Transformation

21. 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

22. 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

23. 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

24. 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%

25. Timecourse - Respiratory infection Source- Medical Microbiology, 5 th Edition (Murray, Rosenthal, and Pfaller)

26. EPIDEMIOLOGY Endemic, epidemic and sporadic infections Many infections are sub-clinical

27. EPIDEMIOLOGY-contd. ’Tip of the iceberg phenomenon’ Classical disease presentation Mild clinical disease Asymptomatic infection but +infectivity

28. EPIDEMIOLOGY- Outbreaks Military recruits, swimming pool users, hospitals, residential institutions, day care settings

29. EPIDEMIOLOGY-transmission Prolonged infective period (weeks) Intermittent and prolonged rectal shedding Stable in the environment

30. TRANSMISSION Droplets Fecal-oral route Direct and through poorly chlorinated water Fomites

31. CLINICAL SYNDROMES Respiratory Eye Genitourinary Gastrointestinal Others

32. Acute Respiratory Disease (LRI) Fever Tracheobronchitis Pneumonia Children and adults Epidemics in military recruits Types 4 and 7 most frequently

33. Acute Respiratory Disease

34. 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

35. Adenoviral Infections of the eye Epidemic Keratoconjunctivitis (EKC) Acute follicular conjunctivitis Pharyngoconjunctival fever

36. Adenoviral conjunctivitis Early conjunctivitis (top) and Bilateral conjunctivitis (lower)

37. 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

38. 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

39. Gastrointestinal Infections Types 40, 41 Age <4 years Spread via fecal-oral route Year round

40. Gastrointestinal Infections- (contd.) Incubation period 3-10 days Diarrhea lasts for 10-14 days Fever Also, intussusception, mesenteric adenitis, appendicitis

41. INTUSSUSCEPTION

42. 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

43. Other Infections due to Adenovirus Myocarditis Pericarditis Meningitis Rash Arthritis

44. 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

45. Adenovirus infection in the immunocompromised

46. 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

47. Methods for diagnosis Culture in HeLa, HEK cell lines Shell vial cell culture DFA PCR, nucleic acid probes EM and Immune EM

48. Diagnosis- Enteric adenoviruses Isolation requires special media-Graham 293 ELISA for rapid detection is available

49. Prevention Good handwashing Contact precautions Chlorination of water Disinfection or sterilization of ophthalmologic equipment Use of single dose vials Oral vaccine- restricted use

50. 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