Flu Vaccination. John Hann, MD UC Irvine Health

Transcription

1 Flu Vaccination John Hann, MD UC Irvine Health

2 So you got the flu. What to do about.

3 Influenza spread in US

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5 Influenza spread world wide

6 What is going on? Influenza A H3N2, which usually causes more severe disease than influenza A H1N1 and influenza B viruses, predominated, with 55 percent of virus isolates tested representing an H3N2 strain. The overall adjusted vaccine effectiveness in Australia was estimated to be 33 percent, but only 10 percent for H3N2. Since the vaccine for the 2017 to 2018 influenza season in the Northern Hemisphere has the same composition as the vaccine used in the Southern Hemisphere during the 2017 season, there is concern that regions in the Northern Hemisphere could experience a severe influenza season, particularly if influenza A H3N2 virus circulates widely.

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8 Why is flu vaccine typically less effective against influenza A(H3N2) viruses? While all influenza viruses undergo frequent genetic changes, the changes that have occurred in influenza A(H3N2) viruses have more frequently resulted in differences between the virus components of the flu vaccine and circulating influenza viruses (i.e., antigenic change) compared with influenza A(H1N1) and influenza B viruses. That means that between the time when the composition of the flu vaccine is recommended and the flu vaccine is delivered, H3N2 viruses are more likely than H1N1 or influenza B viruses to have changed in ways that could impact how well the flu vaccine works. Growth in eggs is part of the production process for most seasonal flu vaccines. While all influenza viruses undergo changes when they are grown in eggs, changes in influenza A(H3N2) viruses tend to be more likely to result in antigenic changes compared with changes in other influenza viruses. These so-called egg-adapted changes are present in vaccine viruses recommended for use in vaccine production and may reduce their potential effectiveness against circulating influenza viruses. Other vaccine production technologies, e.g., cell-based vaccine production or recombinant flu vaccines, could circumvent this shortcoming associated with the use of egg-based candidate vaccine viruses in egg-based production technology, but CDC also is using advanced molecular techniques to try to get around this short-coming.

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10 Table. Adjusted vaccine effectiveness estimates for influenza seasons from

11 How the studies are done Difficult to perform RCT for every year of the flu vaccine They use test-negative case-control studies in order to assess efficacy Compared the odds of vaccination among those with a respiratory illness who tested negative by reverse transcription polymerase chain reaction for influenza to those who tested positive. Effectiveness was calculated as: 100 (1 odds ratio).

12 Cohort study

13 Test negative study

14 data

15 data

16 data Live attenuated

17 What does this mean in the real world?

18 Influenza pubmed start page

19 Cochrane review Collected data ending in 2013 Compared RCT, quasi-rct comparing vaccine against placebo, 90 reports, 116 data sets, 70,000 people Collected data on pregnant women and healthy individuals aged 16 to 65 years. Conclusion that the NNV (number needed to vaccinate) to prevent influenza like illness was 40, and to prevent confirmed infection was 71 Regarding pregnancy: No RCTs assessing vaccination in pregnant women were found. The only evidence available comes from observational studies with modest methodological quality. Insufficient evidence was gathered during the studies to assess harm of the vaccine. A limited impact on hospitalization was found (NNV 94, 95% CI 70 to 1022). This review includes 90 studies, 24 of which (26.7%) were funded totally or partially by industry. Out of the 48 RCTs, 17 were industry-funded (35.4%).

20 Deaths averted by influenza vaccination in the U.S. during the seasons 2005/06 through 2013/14 Using the data collected by the CDC over 9 years, US health and human services performed statistical modeling to calculate number of deaths averted by influenza vaccination

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22 Deaths attributed to influenza

23 Over the nine seasons included in this study, we estimated that over forty thousand deaths were averted by the US influenza vaccination program (Table 4).

24 Deaths averted by influenza vaccination in the U.S. during the seasons 2005/06 through 2013/14 Using the data collected by the CDC over 9 years, US health and human services performed statistical modeling to calculate number of deaths averted by influenza vaccination Almost 90% of the averted deaths would have occurred among persons aged 65 yrs Clinical trial data for that age group (>65) are scarce and suggest an efficacy below 50%

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26 Side effects GB has been associated with inactivated influenza vaccine Immediate immunoglobulin (Ig)E-mediated hypersensitivity reactions have been reported (anaphylaxis). Mild-moderate Local skin reaction, esp with higher dose vaccine

27 Vaccine in Ca patients Observational data suggests a lower mortality with influenza vaccination. The strength of evidence is limited by the small number of studies and by the fact that only one was a RCT. Influenza vaccination evidence, although weak, is in favour of vaccinating adults with cancer receiving chemotherapy. Vaccine in COPD patients It appears, from the limited number of studies performed, that inactivated vaccine reduces exacerbations in COPD patients Vaccine in health workers Offering influenza vaccination to healthcare workers who care for those aged 60 or over in LTCIs may have little or no effect on laboratory proven influenza (low quality evidence). Vaccine in SNF residents Overall, influenza vaccination is estimated to prevent 1 death for every 302 vaccinees at a vaccination coverage that varied between 64% and 74%.

28 Efficacy of Neuraminidase inhibitors outpatient Published in 2016 from the NHS specifically evaluating the efficacy of 2009 swine flu by reviewing all clinical study reports. Conclusion that Oseltamivir reduced time of first alleviation in adults by 16.8 hours (CI ) Zanamivir reduced time of first alleviation by 0.6 days Oseltamivir Reduced unverified PNA by 1% (CI %) PPX reduced risk of symptomatic influenza in individuals by 3% (CI ) and in household by 13.6% ( 9.52%-15.47%) Increased the risk of emesis in kids 5.34% (CI %) and adults 1.56% (2.39 to 7.58%) After adjusting for time-dependent bias and potential confounding variables, competing risks analysis of the IPD showed insufficient evidence that oseltamivir reduced the risk of mortality (hazard ratio 1.03, 95% CI 0.64 to 1.65)

29 Regarding hospitalized patients, from the CDC No randomized, placebo-controlled clinical trials have been conducted of neuraminidase inhibitors for treatment of influenza in hospitalized patients. Numerous observational studies, some positive Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0.48; 95% CI ; p<0 0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0 50; 95% CI ; p<0 0001) These associations with reduced mortality risk were less pronounced and not significant in children. 107 of 183 untreated case patients (58%) survived, compared with 1260 of 1676 treated case patients (75%; P.0001). There was a trend toward improved survival for those treated earliest (P <.0001). Treatment initiated within 5 days after symptom onset was associated with improved survival compared to those never treated (P <.05) Some negative, We did not find a reduction in mortality associated with early NAI therapy in adult patients hospitalized for influenza. the in-hospital mortality of the former ( without early NAI) (2.9%, 8/273) did not differ from that of the latter ( with NAI) (3.4%, 8/233) (p = 0.75).

30 This has lead the CDC to make such strong recommendations as Antiviral treatment might be effective in reducing morbidity and mortality in hospitalized influenza patients, especially adults, even if treatment is started more than 48 hours after onset of illness The optimal duration and dosing of antiviral treatment are uncertain for severe or complicated influenza Clinical judgment and virologic testing of lower respiratory tract specimens by real-time reverse transcription-polymerase chain reaction (RT-PCR) should guide decisions to consider treatment regimens longer than 5 days for hospitalized influenza patients with severe and prolonged illness. A higher dose of oral or enterically-administered oseltamivir has been recommended by some experts (e.g., 150 mg twice daily in adults with normal renal function) for treatment of influenza in immunocompromised patients and in severely ill hospitalized patients.

31 Current recommendations sent by our staff Please review risk factors for all patients exposed and consider prophylactic treatment with Tamiflu as clinically appropriate. The following patients are considered high risk for flu-related complications: Age >65 years Chronic health conditions (asthma, COPD, metabolic disorders, certain neurologic conditions, heart disease) Immunosuppression (HIV, malignancy, on medications such as steroids, chemotherapy, immunomodulators) Note: immunocompromised patients are considered at risk for influenza regardless of vaccination status.

32 What to do with staff? Please provide us a list of exposed coworkers on your team. We will need to them directly with instructions on monitoring for symptoms and possible prophylaxis as needed tonight. General guidelines are as follows and we appreciate your help in disseminating this information to your team: All staff/coworkers should monitor themselves actively for symptoms, regardless of vaccination status If symptomatic, healthcare workers should call their supervisor/attending at the first sign of illness and see their primary care physician immediately for testing and treatment with Tamiflu. Healthcare workers who were exposed and did not get vaccinated may need to start Tamiflu prophylaxis this should be coordinated by their primary care physician or UCIMC Occupational Health (available only during business hours).

33 Please also provide us with the workroom(s) that the infected healthcare worker used yesterday and today so that we can have EVS come and clean all surfaces. We also appreciate your team taking an active role in cleaning all surfaces with the disinfecting wipes (CaviWipes) provided in those workrooms, concentrating on high touch surfaces such as keyboards, phones/keypads, and counter surfaces. This is recommended for tonight but should be continued regularly, especially throughout the influenza season.

34 CDC flu recommendations Order PCR and not DFA, the lab will do the order that is written, even if it is the worse test. Always collect nasopharyngeal swab from the Cephied kit (red top with Cepheid specimen collection tube). No longer do nasal rinse, otherwise DFA will be performed