Tis the Season Respiratory that is

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1 Tis the Season Respiratory that is Jason LeBlanc Director Virology, Immunology, Molecular Microbiology, NHSA Central

2 Objectives Understand the etiology and epidemiology of viral respiratory tract infection (RTI)s Influenza virus vs. other respiratory viruses Understand seasonal vs. pandemic influenza Other emerging respiratory pathogens Lab testing: ideal specimens for viral RTI detection Identify therapeutic and preventative options

3 Worldwide ~1 billion cases of influenza/year 3-5 million cases of severe illness 250, ,000 deaths Canada Influenza and pneumonia is ranked among the top 10 leading causes of death ~Avg. 12,200 hospitalizations + 3,500 deaths

4 Economic burden of viral RTIs Significant morbidity and mortality

5 People at high risk of influenza-related complications or hospitalization Children < 5 years of age People 65 years of age Individuals with underlying health conditions Cardiac or pulmonary disorders, diabetes and other metabolic diseases, cancer, immune compromising conditions, renal disease, neurologic conditions, morbid obesity... Residents of chronic care facilities (ex: nursing homes) Pregnant women Indigenous peoples

6 People capable of transmitting viral RTIs Anyone. Community Household contacts / daycares / LTC Health care workers and other care providers

7 Common causes of viral RTIs Influenza virus (FluA and FluB) Respiratory syncytial virus (RSV) Rhinovirus Coronavirus Enterovirus Parainfluenza virus Adenovirus Human metapneumovirus Bocavirus

8 Viral RTIs in immunocompromized hosts Same pathogens as immunocompetent hosts but add other opportunistic viruses HSV, VZV, CMV More severe disease, greater risk of mortality Virus shed for longer periods of time Predisposes for development of antiviral resistance*

9 The ability to detect respiratory viruses depends on many factors Clinical illness Timing of collection* Host factors Type of specimen Collection swab Specimen transport Diagnostic test *Test within 5 days of symptoms onset, preferably within 48h

10 Specimen collection *Nasopharyngeal (NP) swab or aspirates, not nasal or throat Transport media required, but does not support viral growth Flocked swab = better recovery Bronchial alveolar lavages (BAL) or washes for LRTIs Other: lung tissue Viral transport swab Bacterial swab Amies swab

11 VIDEO LINK: Produced by: Dr. Todd Hatchette (NSHA Microbiologist) and Dr. Tim Mailman (IWK Microbiologist) Dr. Todd Hatchette (NSHA) Dr. Tim Mailman (IWK)

12 Respiratory virus Diagnostic methods Electron microscopy (insensitive, slow TAT - not for clinical diagnosis) Culture/direct fluorescent antibody (DFA) = poor sensitivity, slow TAT Rapid antigen testing = rapid, but poor sensitivity (~14% for influenza) Molecular methods = high sensitivity and specificity

13 Ex1: Qualitative real-time multiplex RT-PCR Rapid detection of more severe respiratory viruses (~3h) DNA/RNA extraction RT-PCR amplification and detection FluA (FAM) FluB (MAX) RSV (Cy5)

14 Ex 2: Conventional multiplex RT-PCR Simultaneous detection of 15 respiratory viruses (~6h) Intensive care unit (ICU), outbreaks, immunocompromized DNA/RNA extraction RT-PCR amplification and detection

15 Need for testing algorithms No community testing in NS... We reserve testing for those who need it the most High risk (immunocompromized), intensive care unit (ICU), outbreaks, ER, others (travel?)

16 Influenza and non-influenza respiratory virus testing fall/winter - peak summer - shoulder spring - shoulder No community testing MULTIPLEX TEST USED ON SHOULDER SEASON & REFLEXIVE TESTING ICU, immunocompromised, special requests 1. Influenza A virus 2. Influenza B virus 3. RSV-A 4. RSV-B 5. Parainfluenza virus 1 6. Parainfluenza virus 2 7. Parainfluenza virus 3 8. Parainfluenza virus 4 9. Rhinovirus A/B/C 10. Adenovirus A/B/C/D/E 11. Enterovirus 12. Bocavirus 1/2/3/4 13. Coronavirus 229E / NL Coronavirus OC Human metapneumovirus FLUA/B/ RSV USED WHEN INFLUENZA IS HERE General inpatients / LTCs / outbreaks / ER 1. Influenza A virus 2. Influenza B virus 3. RSV

17 Seasonal trends Forecasting respiratory viruses

18 Monitoring influenza virus activity FluA in red FluB in blue (Last winter)

19 Monitoring influenza virus activity

20 Monitoring influenza virus activity IWK identified first FluA cases in NS this year (Wednesday)

21 Monitoring influenza virus activity

22 Why do we look for respiratory viruses? Influenza - initiation of specific therapy or discontinuation Discontinuation of unnecessary antibiotics Reduce the number of unnecessary investigations Shortened hospital stay

23 Rhinovirus and coronaviruses Most common viral RTIs Common cold Many types Parainfluenza viruses Common cause of upper RTIs usually children ~2% get croup (laryngotracheobronchitis) Inflammation of upper airway Narrowing subglotic region Barking cough

24 Enterovirus >100 serotypes (Coxsackieviruses, Echovirus, enterovisues) Usually mild respiratory illness Affect millions worldwide each year Others: aseptic meningitis*, myocarditis, acute flaccid paralysis >60 types - types 1, 2, 3, 5 and 7 = ~87% disease Spectrum of disease: Adenovirus URTIs or LRTIs, conjunctivitis, hemorrhagic cystitis

25 Respiratory syncytial virus (RSV) Most common cause of bronchiolitis in children Can also affect adults Severe infections may be fatal Vaccine in development!

26 Influenza virus ( Flu ) 3 types (A, B and C, but FluC is extremely rare) FluA and FluB causes seasonal epidemics Flu A is the most important More severe disease (vs. FluB) Pandemic potential FluA subtyping based on: Hemagglutinin (HA)* Neuraminidase (NA)* Ex: H1N1, H3N2

27 Influenza vs. other respiratory viruses Symptoms Other respiratory viruses Influenza Onset Gradual Abrupt Congestion, sneezing Common Rare Sore throat Common Rare Cough Common Common (wet but mild/moderate) (dry but severe) Headache Rare Common Fever Rare Common Malaise Rare Common Fatigue Rare Common Last for weeks Muscle pain Rare Very common, often severe

28 Antiviral treatment Only for influenza 2 classes: Adamantanes (ex: amantidine) = M2 channel inhibitor Neuraminidase inhibitors (ex: oseltamivir or zanamivir)

29 Influenza antivirals

30 Antiviral Resistance Amantidine no longer on option! Mutations in amino acids in the M2 channel All FluA strains are resistant Doesn t work against FluB (no M2 channel) Neuraminidase inhibitors (Tamiflu or Oseltamivir) Mutations in surface proteins (NA or HA) Often linked to immunocompromized individuals Could spread to others!

31 Prevention = vaccine Quadruvalent vaccine Influenza A (ph1n1) Influenza A (H3N2) Influenza B (2 different lineages) Flu vaccines needs to be updated yearly Protection good when matched to circulating viruses Problem: Vaccines take time to manufacture Viruses evolve

32 Strain selection and vaccine production Predictions for vaccine strains made almost a year ahead of circulation.

33 Antigenic drift Viral DNA polymerase makes mistakes (error prone) Mutations over time in surface glycoproteins (HA and NA)

34 Evolution of influenza A HA over time Mutations over time in HA = antibody mismatches to current strains causing disease May lead to loss of vaccine effectiveness

35 Even when mismatched: Some protection = better than none Might ameliorate disease (still protect against severe disease) Might have good protection against other vaccine strains (quadrivalent)

36

37

38 Seasonal vs. pandemic influenza Pandemic arise when there s no pre-existing immunity, and FluA is well adapted to human host replication and spread Can arise from antigenic drift but most likely from antigenic shift Genetic reassortments 18 HA 9 NA

39 ph1n1 was a triple reassortant (avian/swine/human)

40 What will be the next pandemic? Can occur from antigenic drift but most likely form shift

41 What will be the next pandemic?

42 Avian influenza A Transmission: contact with infected birds, or objects contaminated by their feces

43 Avian Influenza A (H7N9) An H7N9 virus was first reported in humans in March 2013, in China >1200 cases to date, 40% mortality To date, no sustained human-to-human transmission

44 Avian influenza A (H5N1)

45 What will be the next pandemic?

46 Avian influenza A (H5N1) Case was linked to travel (China) Human infection with H5N1 virus remains a rare event

47 Overlap between migration of birds

48 Impact on poultry industry

49 Impact on pig farming

50 Emerging or re-emerging pathogens Need to know possible travel history to pick appropriate test

51 Coronavirus Coronaviridae: ssrna(+), enveloped 2 nd most common viral RTI Common cold Rare variants have caused severe disease Severe acute respiratory symptom (SARS) Middle East respiratory syndrome coronavirus (MERS-CoV)

52 Picornaviridae family: ssrna(+) Enterovirus D68 12 species; >100 serotypes Coxsackieviruses, Echovirus, enterovisues Usually mild respiratory illness Affect millions worldwide each year Others: aseptic meningitis*, myocarditis, acute flaccid paralysis EV-D68 = viral RTI linked to acute flaccid paralysis and deaths

53

54

55 Transmission of respiratory viruses Droplet (not aerosol!) Contact Inoculate nose/eyes

56 Protecting yourself and others

57

58 Back to the objectives key points Understand the etiology and epidemiology of viral RTIs Influenza virus vs. other respiratory viruses Understand seasonal vs. pandemic influenza Testing: ideal specimens for viral RTI detection Nasopharyngeal swab*, BAL/BRW, tissue Identify preventative and therapeutic options Vaccine and antivirals IPAC interventions!

59 IPAC plays crucial roles in disease prevention Spatial separation Hand hygiene Precautions and personal protective equipment Visitor restriction Environmental cleaning Laundry/waste management Education Immunization advocacy... and many more

60

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