CDC/James Gathany

2. CDC/James Gathany

3. COMMON COLD MOST COMMON CAUSES RHINOVIRUSES (MEMBERS OF THE PICORNAVIRIDAE) CORONAVIRUSES - many other viruses as well CDC/James Gathany

4. Paramyxovidae (paramyovirus family) HPIV 1-4 human parainfluenza virus RSV respiratory syncytial virus hMPV human metapneumovirus Adenoviridae (adenovirus family) adenoviruses Respiratory viruses

5. PARAMYXOVIRUSES HN/H/G glycoprotein SPIKES pleomorphic F glycoprotein SPIKES helical nucleocapsid (RNA plus NP protein) lipid bilayer membrane polymerase complex M protein

6. PARAMYXOVIRUS FAMILYSURFACE GLYCOPROTEINS GENUS GLYCOPROTEINS TYPICAL MEMBERS PARAMYXOVIRUS SUBFAMILY Paramyxovirus HN, F HPIV1, HPIV3 Rubulavirus HN, F HPIV2, HPIV4, mumps virus Morbillivirus H, F measles virus PNEUMOVIRUS SUBFAMILY Pneumovirus G, F respiratory syncytial virus Metapneumovirus G, F human metapneumovirus

7. Human parainfluenza virusesHPIV 1, 2, 3 and 4 • FOUR SEROTYPES • HPIV 1, 2, 3 and 4 • INFECTION • aerosol, person to person and fomites • unstable, but can survive on surfaces for a few hrs • highly contagious • susceptible to soap and water, alcohol based disinfectants, etc. • incubation 1-7 days

8. EPIDEMIOLOGY”Iceberg phenomenon” Classical disease presentation Mild clinical disease Asymptomatic infection but infectivity (+)

9. Human parainfluenza viruses DISEASE • usually see as upper respiratory tract infections • one of causes ‘common cold’ • coryza - inflammation nasal mucous membranes • ->congestion, headache, runny nose • fever • pharyngitis • however can be more serious as spreads down respiratory tract • croup, bronchitis, bronchiolitis, pneumonia • highest % of serious disease due to HPIV is seen in young children • second to respiratory syncytial virus in importance for lower respiratory tract disease in very young • can cause disease in adults (reinfections occur) – usually mild • reinfections in adults can sometimes be severe • especially elderly and immunocompromised – bronchiolitis, pneumonia • viremia is rare for HPIV • very rarely parotitis, meningitis, encephalitis

10. AIRWAY NARROWING IN CROUP

11. Human parainfluenza virusesCROUP • laryngotracheitis or laryngotracheobronchitis • primarily in young • usually <6 yrs • HPIV is most common cause of croup • other viruses also cause croup • fever, cough, hoarseness, stridor • outbreaks most often associated with HPIV1 and HPIV2 • HPIV3 – sporadic cases • humidification, racemic epinephrine, steroids (some cases)

12. Human parainfluenza viruses • DIAGNOSIS • viral culture (shell vial cultures) http://www.lhsc.on.ca/lab/MICRO/virology/vir_cult.htm

13. Human parainfluenza viruses DIAGNOSIS • viral culture (shell vial assays) • detect with fluorescent antibodies, hemadsorption • direct detection virus in respiratory secretions (first week of symptoms) • immunoassays or PCR • serology • rise of IgG in paired specimens or high levels IgM

14. Human parainfluenza viruses TREATMENT • no antiviral therapy • supportive • usually self-limited • various treatments for croup

15. Human parainfluenza viruses EPIDEMIOLOGY • restricted to humans, important and ubiquitous • most people have had all types of HPIV by 5yrs of age • reinfections throughout life • usually less severe, may be symptomatic or asymptomatic • asymptomatic infections can be infectious • usually shed for ~1 week • immunocompromised individuals with lower respiratory tract disease may shed for weeks • antigenically stable • HPIV 1 and 2 tend to be in fall • HPIV2 tends to be biennial • HPIV 3 throughout year, but especially spring and summer • HPIV 4 • less often recognized, usually milder infections • less common cause of croup, bronchiolitis

16. Human parainfluenza viruses PREVENTION • no vaccine • passive maternal antibodies may help in first few months • hand, nose and surface hygiene

17. Respiratory syncytial virus PARAMYXOVIRUS FAMILYSURFACE GLYCOPROTEINS GENUS GLYCOPROTEINS TYPICAL MEMBERS PARAMYXOVIRUS SUBFAMILY Paramyxovirus HN, F HPIV1, HPIV3 Rubulavirus HN, F HPIV2, HPIV4, mumps virus Morbillivirus H, F measles virus PNEUMOVIRUS SUBFAMILY Pneumovirus G, F respiratory syncytial virus Metapneumovirus G, F human metapneumovirus

18. Respiratory syncytial virus (RSV) • 2 major strains • group A and group B (G protein differences) • multiple genotypes of each strain • currently not clear how these affect the clinical picture

19. Respiratory syncytial virus (RSV)INFECTION • infections • aerosol, person-to-person and fomites • virus unstable, but can survive for an hour or so on hands, and on inanimate surfaces for a few hrs • easily spread (infants may have 10 million pfu/ml in nasal secretion) • virtually all children have been infected by 2yrs of age • primary infections are usually symptomatic • reinfections are common – may be symptomatic or asymptomatic • incubation period • a few days to a week • recovery takes a week or two • virus shedding • a few days to a week • 3-4 weeks in infants or immune suppressed individuals

20. Respiratory syncytial virus (RSV) • virus confined to respiratory tract • infects respiratory epithelial cells • mucosal edema • increased mucin production • cell necrosis • obstruction by mucin/cell debris • host immune response contributes to pathology • cell mediated immunity important for recovery

21. Respiratory syncytial virusDISEASE • common cause upper respiratory tract infections • runny nose, cough, sore throat, headache, fever, malaise, loss appetite • co-infection with bacteria usually not a problem except otitis media common • 25% of primary infections result in lower respiratory tract infections – bronchiolitis, viral pneumonia • commonest cause of bronchiolitis • if previously healthy, only a few individuals with bronchiolitis need hospitalization • re-infections usually not associated with LRT disease • but...reinfections can be associated with LRT disease • risk factors include immunosuppression, cardiopulmonary disease

22. Respiratory syncytial virusSEVERE LRT DISEASE • risk factors for severe disease • age (especially if less than 6 months) • preterm birth • heart disease • pulmonary hypertension • lung disease of prematurity • immunodeficiency

23. Respiratory syncytial virusTREATMENT • no specific antivirals • supportive care • hydration • assessment and management of respiratory status • ribavirin • not used routinely, may be considered in life threatening situations

24. Respiratory syncytial virusDIAGNOSIS • rapid antigen assay • isolation (shell vial culture) • PCR • especially useful in older children and adults when viral load is usually lower and so antigen detection or viral isolation less reliable • not widely available yet • serology • usually used for epidemiology rather than diagnosis

25. Respiratory syncytial virusEPIDEMIOLOGY • worldwide distribution • restricted to humans • US ~3000 deaths per yr • In USA usually late winter, early spring • earlier in Florida • timing helps to determine when to give prophylaxis to high-risk children • timing varies from year to year • surveillance system in US http://www.cdc.gov/Features/dsRSV/

26. Respiratory syncytial virusPREVENTION • No vaccine • passive immunization is available for high-risk children • Hand, nose and surface hygiene • Nosocomial infections common • need to be especially rigorous when high risk patients involved • pediatric wards, neonatal units, transplantation units, etc. • gloves, gowns, masks, goggles; isolation and cohort nursing

27. Respiratory syncytial virusPREVENTION • palivizumab (Synagis®) • humanized monoclonal antibody • for high-risk children • monthly IM injections during the RSV season • not effective in treatment of infection

28. PARAMYXOVIRUS FAMILYSURFACE GLYCOPROTEINS GENUS GLYCOPROTEINS TYPICAL MEMBERS PARAMYXOVIRUS SUBFAMILY Paramyxovirus HN, F HPIV1, HPIV3 Rubulavirus HN, F HPIV2, HPIV4, mumps virus Morbillivirus H, F measles virus PNEUMOVIRUS SUBFAMILY Pneumovirus G, F respiratory syncytial virus Metapneumovirus G, F human metapneumovirus Human metapneumovirus (hMPV)

29. Human metapneumovirus (hPMV) • only recently (2001) recognized • common – probably 15% of childhood colds • commercial tests only recently available • serogroup A and group B, each group has 2 subgroups based on genotype • all 4 circulate Note: can get co-infections with more than one respiratory virus

30. Human metapneumovirus (hPMV)DISEASE • pathophysiology very similar to RSV • most children infected by age 5 • reinfections common • upper respiratory tract • common cold, croup • often complicated by otitis media • lower respiratory tract • bronchiolitis (may be involved in 10-15% cases in infants) • pneumonia • possible fatal pneumonia in bone marrow and lung transplants?

31. Human metapneumovirus (hPMV)EPIDEMIOLOGY • worldwide • humans only source of infection • hPMV season has similar timing to RSV season • incubation period: few days to a week

32. Human metapneumovirus (hPMV)DIAGNOSIS • antigen detection • commercially available • PCR, culture • not yet commercially available

33. Human metapneumovirus (hPMV)TREATMENT • supportive • hydration • respiratory monitoring and management

34. Human metapneumovirus (hPMV)PREVENTION • hand, nose and surface hygiene • similar hospital infection control practices as for RSV

35. Adenoviruses • linear, double stranded DNA • non-enveloped • stable in environment • icosahedral • first isolated from adenoidal tissue http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/em_adeno.gif

36. Adenovirus- Properties • Stable in the environment • Relatively resistant to various disinfectants • Alcohol, detergents, chlorhexidine • Stable in GI tract- can withstand low pH, bile acids and proteolytic enzymes

37. Adenoviruses • Fiber protein – virus attachment protein • determines host cell specificiy • Virus -> nucleus • replicates DNA in nucleus • assembles nucleocapsid in nucleus • nuclear inclusion bodies • Released by cell lysis

38. Adenoviruses • Infect mucoepithelial cells • respiratory, GI and GU tracts • Enter via epithelium, replicate and spread to lymphoid tissue • Viremia occurs • Secondary involvement of viscera

39. Adenovirusestypes of infection • lytic • mucoepithelial cells • latent/occult • virus remains in cell – seen in lymphoid tissue • oncogenic transformation (animals only)

40. Human Adenoviruses • Approx 51 human serotypes (1-51) • Classified into six subgroups (A-F) based on hemagglutination patterns, hexon antigenicity and sequence • members of a subgroup often cause similar spectrum of disease • enteric adenoviruses are in subgroup F (40,41)

41. Human Adenoviruses Remaining serotypes are infrequently isolated or not clearly associated with disease. * Association with gastroenteritis not as firmly established as with types 40 and 41.

42. Human adenoviruses TRANSMISSION • person-to-person, aerosols, fomites • respiratory secretions, tears, fecal/oral • stable in environment • not very susceptible to many disinfectants • underchlorinated swimming pools, shared towels • under sterilized medical equipment (eye exam equipment, etc)

43. Human adenoviruses infection and shedding • incubation period few days to a couple of weeks • virus shedding usually highest during acute phase • may continue to shed at lower levels for a long time (months) • high rate of transmission to other family members (up to 50%)

44. Human adenoviruses Timecourse - Respiratory infectionSource- Medical Microbiology- Murray, Rosenthal, Kobayshi and Pfaller

45. Human adenovirusesDISEASE • common cold (coryza, fever, headache, malaise) • pharyngitis • bronchitis • pneumonia • diarrhea • conjunctivitis • pharyngoconjunctival fever • cystitis • rash • neurologic disease

46. 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, DIC, CNS involvement

47. Human adenoviruses EPIDEMIOLOGY • human • asymptomatic infections common • reinfections common • crowding and stress can be risk factor • military basic trainees – may see in up to 10% in first week • daycare centers

48. Human adenoviruses DIAGNOSIS • antigen testing in some body fluids • can be very rapid • cell culture (shell vial) • prolonged shedding (especially in feces) so may mean that not cause of current disease • virus isolated from URT from site associated with disease may be more relevant to current disease • not applicable for enteric types 40, 42 • PCR

49. Human adenoviruses TREATMENT • supportive care • most infections mild • for life threatening infections (immunocompromised patient) • cidofovir

50. Human adenoviruses PREVENTION • good hygiene • take into account that virus fairly stable • take care to thoroughly decontaminate medical equipment • adequate chlorination of swimming pools • to reduce risk pharynoconjunctival fever • use disposable or adequately sterilized items in ophthalmic practice • to reduce risk epidemic keratoconjunctivitis • no vaccine • one for military recruits no longer made