Seasonal Influenza: Vaccines & Prevention Kristin Nichol, MD, MPH, MBA Professor of Medicine...
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Transcript of Seasonal Influenza: Vaccines & Prevention Kristin Nichol, MD, MPH, MBA Professor of Medicine...
Seasonal Influenza:Vaccines & Prevention
Kristin Nichol, MD, MPH, MBAProfessor of Medicine
University of MinnesotaChief of Medicine and Director
Primary Care Service LineMinneapolis VA Medical Center
Minneapolis, MN
Overview
• Trivalent inactivated (TIV) and live attenuated influenza virus (LAIV) vaccines
• Efficacy & effectiveness in children, adults, elderly
• Cost effectiveness of vaccination
• Vaccination rates
• Remaining issues
Epidemic Influenza Continuesto Have a Huge Annual Impact
+ Avg respiratory & circulatory = 294,000 1979-80 thru 2000-01.* Avg all cause, 1976-77 thru 1998-99. **Avg all cause 1990-91 thru 1998-99.
MMWR. 2005;54 (RR-8). Thompson et al. JAMA. 2003;289:79.Thompson et al. JAMA. 2004;292:1333.Adams PF et al. Vital Health Stat. 1999;10(200).
Estimates for the US• Cases: 25 – 50+ million
• Days of illness: 100 – 200 million
• Work & school loss: Tens of millions
• Hospitalizations: 85,000 – 550,000+
• Deaths: 34,000* – 51,000**
• Costs: Billions of dollars
Options for Preventingand Controlling Influenza
• Hand hygiene
• Respiratory hygiene/cough etiquette
• Contact avoidance
• Antivirals
• Immunization
CDC. Preventing the Flu. www.cdc.gov/flu/protect/stopgerms.htm
Influenza Vaccines: A Trivalent Defense
CDC. MMWR Morb Mortal Wkly Rep. 2005;54(RR-8).
Type AH3N2
Type AH1N1
Influenza
Protection
Type B
Trivalent Inactivated (TIV) and Live Attenuated Influenza Virus (LAIV) Vaccines
Category TIV LAIV
Administration &immune response
IM Serum antibodies
Intranasal Mucosal immunity
Formulation Inactivated Live attenuated
Safety (side effects) Sore arm Runny nose
Growth medium Chick embryos Chick cells
Storage Refrigerated Frozen
Indication >6 mo (healthy & HR) 5–49 yrs (healthy)
MMWR. 2005;54 (RR-8).
Outcome / case definition & RRR vs ARR
• Typical kinds of outcomes assessed in VE studies– Cause specific (specific outcomes)
• Infection• Lab confirmed illness (LC ILI)• LC Influenza + otitis media
– “All cause” (sensitive outcomes)• Clinical illness (ILI) without lab confirmation• Complications
– Otitis media– Pneumonia hospitalization– Death
• Cause specific outcomes provide highest RRR because there is less “noise”
• But this does not mean that the lower RRR seen with all cause outcomes means that the vaccine is less effective (ie the ARR would be the same or greater if it could be measured)
Influenza Vaccine Efficacy in Children
Study & Vaccine Efficacy (lab / cx confirmed)
Effectiveness (clinical illness)
Cochrane [1]
Live attenuated
Inactivated
79% (48% - 92%)
65% (47% - 76%)
38% (33% - 43%)
28% (22% - 33%)
Negri et al [2]
Live attenuated
Inactivated
80% (53% - 91%)
65% (45% - 77%)
34% (31% - 38%)
33% (22% - 42%)
1. Jefferson TJ, et al. Lancet. 2005;365:773-80.2. Negri E, et al. Vaccine. 2005;23: 2851-61.
Influenza Vaccine Efficacy in Healthy Adults
Serologically Confirmed Influenza
Illness
Clinical ILI
RRR ARR RRR ARR
Figure 01.01 69% (54%-79%) 6.1/100 22% (9%-33%) 13.5/100
Figure 01.02 70% (56%-80%) 6.8/100 25% (13%-35%) 12.1/100
Demicheli V, et al. Cochrane Library 2004; issue 3.
Effectiveness of Influenza Vaccination in High Risk Persons < 65 Years of Age
Age Group & Outcome Vaccine Effectiveness (95% CI)
< 18 yrs, high-risk
GP visits for ARD/CVD
43% (10% - 64%)
18 – 64 yrs, high-risk
GP visits for ARD/CVD
Hospitalizations for ARD/CVD
Death (any cause)
26% (7% - 47%)
87% (39% - 97%)
78% (39% - 92%)
65 yrs & older
GP visits for ARD/CVD
Hospitalizations for ARD/CVD
Death (any cause)
7% (-11% - 23%)
48% (7% - 71%)
50% (23% - 68%)
Hak E, et al. Arch Intern Med 2005; 165: 274.
Influenza VE in Community Dwelling Elderly (Results of 2 Meta Analyses)
Outcomes Vu, et al. Jefferson, et al.
Lab confirmed influenza -- 81% (-101% - 98%)
Clinical ILI 35% (19% - 47%) -5% (-89% - 42%)
Hospitalizations for
Pneumonia & Influenza 33% (27% - 38%) 27% (21% - 33%)
Respiratory Conditions 30% (25% - 35%) 22% (15% - 28%)
Cardiovascular Disease -- 24% (18% - 30%)
All Cause Mortality 50% (45% - 56%) 47% (39% - 54%)
Vu T, et al. Vaccine. 2002;20:1831.Jefferson T, et al. Lancet. 2005;366:1165-74.
Influenza VE in LTCF Elderly(results of 2 meta analyses)
Outcome Gross, et al. Jefferson, et al.
Respiratory Illness/ILI 56% (39% to 68%) 23% (6% - 36%)
Pneumonia 53% (35% to 66%) 46% (30% - 58%)
Hospitalization 48% (28% to 65%) 45% (16% - 64%)
Death 68% (56% to 76%) 60% (23% - 79%)
Gross PA, et al. Ann Intern Med. 1995;123: 518 – 27.Jefferson TJ, et al. Lancet. 2005;366:1165-74.
Influenza Vaccination Has Downstream Benefits
• Vaccination of school children– Lower illness rates in the community
• Tecumseh, MI study [1]• Texas study [2]
– Lower death rates in the elderly• Japanese experience [3]
• Vaccination of children in households [4]– Lower illness rates in school-aged siblings– Fewer work loss days among parents
• Vaccination of healthcare workers– Lower death rates in residents of LTCFs [5]
1. Monto AS et al. J Infect Dis. 1970;122:16. 2. Piedra PA et al. Vaccine. 2005;23:1540. 3. Reichert T, et al. NEJM. 2001;344:889. 4. Hurwitz ES. JAMA. 2000;284:1677. 5. Carman WF, et al. Lancet. 2000;355:93.
Sensitivity of Symptoms
68
93
64 59 56
0
10
20
30
40
50
60
70
80
90
100
Fever Cough Fever & Cough Fever & Cough& Nasal
Congestion
Fever & Cough& Sore Throat
Sen
sitiv
ity (
%)
....
.
Adapted from Monto AS, et al. Arch Intern Med 2000; 160: 3243-7.
Sensitivity of Laboratory Diagnostic Tests
56 6171
0
10
20
30
40
50
60
70
80
90
100
Culture Serology RT-PCR
Sen
sitiv
ity (
%)
....
.
Based on data from 533 US subjects included in neuraminidase trials.Zambon M et al. Arch Intern Med 2001; 161: 2116-22.
42.4
79
16.5
186.4
271.5
44.8
0
50
100
150
200
250
300
Work loss days Impairedproductivity
days
Health careprovider visits
No. P
reve
nte
d b
y Vac
cinat
ion
(per
100
0)
Febrile URI / Peak Outcome Period
Any Symptom / Total Outcome Period
Impact of More Sensitive Outcomes on ARRMore sensitive outcomes will have a higher ARR – ie they are more inclusive
Nichol KL. Virus Res 2004; 103: 3 – 8.
CEA Studies of Influenza Vaccination of Children
Country ResultsCost
SavingCost
EffectiveNot Cost Saving– Cost Effective ?
USA multiple studies [1] √ √
Hong Kong [1] √
Argentina (high risk children 6 mos to 15 yrs) [1]
√
US High risk children [2] √
US non-high risk children [2] √ (break-even ~$30/dose)
√(not cost saving if vacc
costs > break-even threshold)
1. Nichol KL. Vaccine. 2003;21. 2. Meltzer MI. Vaccine. 2005;23:1004.
CEA Studies of Influenza Vaccinationof Working Adults Around the Globe
Country ResultsCost
SavingCost
EffectiveNot Cost Saving – Cost Effective ??
USA multiple studies [1,2] √ √ √
Canada (HCW’s) [1] √
UK [1] √ √(for British Army)
France [1] √
Finland [1] √(inefficient delivery)
Hong Kong [1] √
Brazil [1] √
UK (HTA 2003) [3] √£10,184/QALY
South Africa [4] √(BCR 5:1)
1. Nichol KL. Vaccine. 2003;21:1769.2. Rothberg MB. Am J Med. 2005;118:68.3. Turner D et al. HTA. 2003;7(35). 4. Martin DJ. Occup Health SA. 1997;3:23.
CEA Studies of Influenza Vaccinationof the Elderly Around the Globe
Country Results
CostSaving
Cost Effective
Not Cost Saving– Cost Effective ??
USA – multiple studies √ √
Canada √
England, France, Germany, the Netherlands
√ √
New Zealand √
Taiwan √
Hong Kong √
Nichol KL. Vaccine. 2003;21:1769.
Expansion of Goals for Influenza Vaccination – Everyone Can Benefit
ACIP Recommendations 2005-06
• High Priority – High risk for serious complications
• Age 65+• Chronic medical conditions• Conditions that compromise respiratory function or ability
to handle secretions • Residents of LTCFs• Pregnant women• Children/adolescents on chronic ASA Rx• Children 6 to 23 months of age
– Likely to be high risk (ages 50–64)– Persons who can transmit to high risk groups
• Special emphasis on HCWs
• OthersCDC. MMWR. 2005;54 (RR-8).
Influenza and Pneumococcal Vaccination Rates Are Still Too Low
MMWR 2001;50(25):532-537. NHIS (‘01, ’03, Jan – Jun ‘04).
2010 Goal
Disparities by Age: Influenza & Pneumococcal Vaccination of High Risk Persons, 2003
69.964.2
4937.1 34
0
20
40
60
80
100
Elderly Diabetes < 65 Asthma < 65
Influenza Pneumococcal
MMWR. 2004;53:1007.
Disparities by Race: Influenza & Pneumococcal Vaccination of Elderly Persons, 2004
59.3
72.9
4834.8
61.6
34.5
0
20
40
60
80
100
Influenza Pneumococcal
Hispanic White Black
NHIS early release estimates, Jan – Jun 2004.
Influenza Vaccination Coverage2004-05
2003(NHIS)
2004-05 (BRFSS)
Adults Elderly 65.5% 62.7%
HR Adults 18 – 64 34.2% 25.5%
HCWs 40.1% 35.7%
Non-priority Adults 19.6% 8.8%
Children Children 6 – 23 mos 7.7% 48.4%
HR Children 2 – 17 -- 34.8%
Non-priority children -- 12.3%
CDC; MMWR. 2005; 54:304-7.
Summary
• Influenza is a bad disease (for everyone) and current vaccines provide many benefits (for everyone)
• Current vaccines are underused
• Current vaccines are imperfect
• Roles for– More effective vaccine delivery
• To expanded target groups (?)
– More timely availability and adequate quantities of vaccine
– Better vaccines