Influenza Testing Today: Keeping Up with a Moving Target

Transcription

1 Influenza Testing Today: Keeping Up with a Moving Target Webcast Clinical Lab Products November 19, 2015

2 Moderator Steve Halasey Chief Editor Clinical Lab Products

3 Sponsor

4 Speaker Wallace Greene, PhD, D(ABMM) Medical Director, Diagnostic Virology Laboratory Associate Professor of Pathology Penn State Hershey Medical Center

5 Influenza Testing Today: Keeping Up with a Moving Target Wallace Greene, PhD, D(ABMM) Penn State Hershey Medical Center November 19, 2015

6 Disclosures I have received research support from BD Diagnostics, Focus Diagnostics, GenMark Diagnostics, Meridian Bioscience, Quidel Corp, Roche, and TechLab Inc. I have received honoraria from Abbott Diagnostics, BD Diagnostics, Meridian Bioscience, Quidel Corp, and Sekisui Diagnostics. I will not discuss any off-label use of the tests discussed in this webcast.

7 Objectives Provide an overview of genetic changes and the transmission of influenza strains Describe the impact of diagnostic testing on patient and community health Review projections for the flu season, including available vaccines Discuss current diagnostic testing options for influenza

8 Respiratory Viruses Cause more than half of hospitalizations for acute respiratory infection (ARI) in children <5 years of age A major cause of disability in the elderly Viruses most commonly associated with ARI: Influenza A & B Respiratory syncytial virus (RSV) Parainfluenza viruses 1 3 Adenovirus Rhinovirus Coronavirus (SARS) and others Human metapneumovirus (hmpv) Bocavirus

9 An unimpeded sneeze sends 2000 to 5000 droplets into the air. Image copyright Andrew Davidhazy, Rochester Institute of Technology.

10 Audience Poll Does your facility mandate influenza immunization or is it voluntary? o Voluntary o Mandated

11 Audience Poll Does your facility mandate influenza immunization or is it voluntary? Voluntary 42% Mandated 58% 0% 10% 20% 30% 40% 50% 60% 70% Respondents (%) N = 52

12 Influenza

13 Subtyped based on surface glycoproteins: 16 hemagglutinins (HA) and 9 neuraminidases (NA) Current human subtypes: H1N1 H1N2 H3N2 Influenza A Viruses

14 Influenza Virus

15 Influenza Virus Life Cycle

16 Viral evolution cannot be predicted Reassortment: Rapid development of a new variant Explosive spread H1N Adaptive mutations: Viral Evolution More gradual development Limited transmission in the beginning H7N9

17 Antigenic Drift Infographic courtesy National Institute of Allergy and Infectious Disease

18 Antigenic Shift Infographic courtesy National Institute of Allergy and Infectious Disease

19 Influenza A H1N1 2009

20 Influenza A H3N2v H3N2v is a variant of H3N2 influenza virus that infected 321 people in the United States in 2011 and 2012 In 2013, 18 cases of H3N2v were reported in the United States, including 14 in Indiana, 2 in Michigan, 1 in Illinois, and 1 in Ohio Among those patients, there was one hospitalization and no deaths No human-to-human spread was identified When this virus occurs in pigs, it is called swine influenza. The virus does not usually infect people or spread among people. It is very different from human seasonal H3N2 viruses 307 of the cases occurred from July to November 2012 Symptoms of H3N2v are similar to seasonal flu symptoms There has been limited person-to-person transmission and one death

21 #1 Recommendation for Avoiding Swine Flu DO NOT DO THIS!!!

22 Transmission Typical incubation 2 days Range 1 4 days Viral shedding Seasonal Influenza Can begin one day before onset of symptoms Peak shedding first 3 days of illness Subsides by days 5 7 in adults, >10 days in children

23 Audience Poll Does your institution offer different influenza assays for outpatient clinics and the emergency department than it offers for inpatients? o No o Yes

24 Audience Poll Does your institution offer different influenza assays for outpatient clinics and the emergency department than it offers for inpatients? N = 39

25 Public Health Importance of Influenza Approximately 40,000 deaths yearly Over 85% mortality among persons 65 and older Normal flu attack rates of 5% 20% in general populations Nursing home attack rates of 60%

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29 United States, influenza season

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34 Influenza Vaccines, All of the influenza vaccines are made to protect against the following three viruses: A/California/7/2009 (H1N1)pdm09-like virus A/Switzerland/ /2013 (H3N2)-like virus B/Phuket/3073/2013-like virus (a B/Yamagata lineage virus) Some of the flu vaccine is quadrivalent vaccine and also protects against an additional B virus B/Brisbane/60/2008-like virus (a B/Victoria lineage virus)

35 Fluzone High-Dose Containing three flu strains, a high-dose flu vaccine is a flu shot aimed at defending against illness for a specific flu season Containing four times the amount of antigen in regular flu shots, high-dose flu shots, along with the additional antigen produced, are intended to create a stronger immune response With age also comes decreased ability to have a good immune response to a flu vaccine, thus creating a greater risk for older people of severe illness from influenza. But with a higher dose of antigen, older people gain a heightened immune response Fluzone High-Dose is approved for use in people age 65 and older, but those who have suffered from a severe reaction in the past and people with a severe allergy to chicken or eggs should refrain from using the Fluzone High-Dose vaccine

36 Influenza Vaccine Manufactured Using Animal Cell Culture In November 2012, FDA approved Flucelvax, the first seasonal influenza vaccine produced using cultured animal cells to be licensed in the United States. Flucelvax is approved to prevent seasonal influenza in people aged 18 years and older Flucelvax virus strains are grown in animal cells of mammalian origin instead of in fertilized chicken eggs Advantages of cell culture include the ability to maintain an adequate supply of previously tested and characterized cells, speeding vaccine production start-up in the event of a pandemic Flucelvax was evaluated in a US and European randomized controlled clinical study involving about 7,700 people aged 18 to 49. The study showed that Flucelvax was 83.8% effective in preventing influenza when compared to placebo.

37 Quadrivalent Intradermal Influenza Vaccine 2,3 Vaccine is injected into the skin rather than the muscle Uses much smaller needle (90% smaller) than the regular vaccine Uses 40% less antigen to be as effective as the regular vaccine Approved for people18 through 64 years of age Preservative free (no thimerosal) Prefilled syringe

38 Influenza A H5N Cases = 32 Egypt = 11 cases Indonesia = 9 cases Deaths = (as of November) Cases = 143 Egypt = 136 cases China = 5 cases Indonesia = 2 cases Deaths = 42 Cumulative data as of November 2015 Cases = 844 Deaths = 449

39 Influenza A H7N9 As of February 2015, a total of 571 laboratory-confirmed cases of human infection with avian influenza A(H7N9) virus, including 212 deaths, had been reported to the World Health Organization

40 Audience Poll Do you offer rapid antigen testing for influenza yearround, or limit it to when influenza is in your community? o Limited o Year-round

41 Audience Poll Do you offer rapid antigen testing for influenza yearround, or limit it to when influenza is in your community? N = 41

42 Clinical Laboratory Diagnosis of Infectious Respiratory Diseases A dog sitting in First Class is still a dog.

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44 Specimen and Collection Device Alters Test Sensitivity 4 6 Flocked swabs are equal to or better than nasal wash/ aspirates, and are less invasive and less messy

45 Assay Methods Cell culture Direct fluorescent antibody (DFA) staining Molecular-based assays Rapid enzyme immunoassays Serology

46 Influenza A DFA

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48 Direct Detection Immunoassays Many different assays have been developed over the years, with varying sensitivities from year to year Due to the reduced sensitivities of these assays compared to more sensitive detection methods such as culture or molecular detection, CDC and other organizations have made recommendations for their use

49 POC Tests for Influenza and RSV Rapid point-of-care (POC) assays should be used when influenza or RSV have been confirmed to be present in the population being tested The positive predictive value for these assays in periods of low prevalence is very low Positive results should be interpreted with caution and confirmed by another method During the peak of an outbreak, not every single patient with flu symptoms needs to be tested, unless a positive result will result in the withholding of antibiotics

50 Suggested Algorithm for Test Interpretation Positive rapid influenza test result: Is there culture-confirmed influenza in your state? Is your test s positive predictive value (PPV) likely to be acceptable? u If the answer to both questions is yes: report result u If either answer is no: qualify result and submit specimen for confirmation assay Negative rapid influenza test result: Are you at peak influenza season? Is your test s negative predictive value (NPV) likely to be less than acceptable? u If the answer to both questions is yes: qualify result and submit specimen for confirmation assay u If the answers to the above questions are no: report result

51 When Are You Going to Start Testing for Flu?

52 Cell Culture

53 Cell Culture

54 Hemadsorption

55 Shell Vial

56 Molecular Amplification Numerous FDA-cleared molecular amplification detection assays are available for detection of respiratory viruses, several of them highly multiplexed Some are technically complex requiring highly skilled technologists; others are relatively simple Multiplex assays are available that detect all major respiratory viruses and bacteria responsible for communityacquired pneumonia This year, FDA has approved two rapid molecular assays that provide results in minutes and are simple enough to qualify as waived tests

57 Audience Poll What type of assay(s) do you use to test for influenza? o Cell culture o Direct fluorescent antibody (DFA) o Molecular assay flu only o Molecular assay multiplex assay o Rapid enzyme immunoassay

58 Audience Poll What type of assay(s) do you use to test for influenza? N = 43

59 Rapid Influenza Diagnostic Tests (RIDTs) FDA Microbiology Advisory Committee recommendations for regulating RIDTs

60 RIDTs: Proposed Changes FDA will identify the minimum acceptable performance criteria FDA will identify the appropriate comparator test or method for establishing performance FDA will require that annual tests be performed by all manufacturers of cleared RIDTs to demonstrate that they detect newly circulating and/or emerging influenza viruses CDC will provide the panel of viruses annually The results will be made public annually

61 RIDTs: Sensitivity and Specificity If comparing to viral culture: For influenza A, sensitivity of 90% with lower bound of 95% CI at 80% For influenza B, sensitivity of 80% with lower bound of 95% CI at 70% Specificity for A and B, 95% with a lower bound of 95% CI at 90%

62 RIDTs: Sensitivity and Specificity If comparing to a molecular assay: For influenza A and B, positive percent agreement of 80% with lower bound of 95% CI 80% For influenza A and B, negative percent agreement of 95% with lower bound of 95% CI 90% Specificity for A and B, 95% with a lower bound of 95% CI at 90%

63 RIDTs: New Labeling Requirements On July 31 each year, the product s package insert must be updated to show the results of annual testing against CDC s panels for the previous 3 years The manufacturer s website must ensure easy and ready access to each year s panel test results If the FDA commissioner declares a public health emergency, each test manufacturer must test the emergent influenza strain within 30 days of receipt of the virus from CDC Within 60 days, these results must be presented in the package insert and/or on the manufacturer s website

64 Q&A To type in a question, navigate to the Q&A section of the event panel.

65 Sponsor

66 Contacts Wallace Greene, PhD, D(ABMM) 717/ Steve Halasey 626/

67 View This Webcast On Demand To revisit this webcast, log in via the CLP website at or access the registration page with the shortlink at

68 Thanks for attending!

69 References 1. Weekly US influenza surveillance report [online]. Atlanta: US Centers for Disease Control and Prevention, Available at: Accessed November 17, Intradermal influenza (flu) vaccination [online]. US Centers for Disease Control and Prevention, Available at: Accessed November 17, Fluzone influenza vaccine [online]. Swiftwater, Pa: Sanofi Pasteur, Available at: Accessed November 17, Walsh P, Overmyer CL, Pham K, et al. Comparison of respiratory virus detection rates for infants and toddlers by use of flocked swabs, saline aspirates, and saline aspirates mixed in universal transport medium for room temperature storage and shipping. J Clin Microbiol. 2008;46(7): ; doi: /jcm

70 References 5. Abu-Diab A, Azzeh M, Ghneim R, et al. Comparison between pernasal flocked swabs and nasopharyngeal aspirates for detection of common respiratory viruses in samples from children. J Clin Microbiol. 2008;46(7): ; doi: /jcm Faden H. Comparison of midturbinate flocked-swab specimens with nasopharyngeal aspirates for detection of respiratory viruses in children by the direct fluorescent antibody technique. J Clin Microbiol. 2010;48(10): ; doi: /jcm