The Current Season: A Review of the 2003-04 Influenza Season Nancy J. Cox, Ph.D. Chief, Influenza...
-
Upload
frederick-holmes -
Category
Documents
-
view
226 -
download
0
Transcript of The Current Season: A Review of the 2003-04 Influenza Season Nancy J. Cox, Ph.D. Chief, Influenza...
The Current Season: A Review of the 2003-04 Influenza Season
Nancy J. Cox, Ph.D.Chief, Influenza Branch
National Center for Infectious DiseasesCenters for Disease Control and
Prevention
Timeline of Emergence of Timeline of Emergence of Influenza Viruses in HumansInfluenza Viruses in Humans
1918 1957 1968 1977 1997
1998/9
2003
H1
H1
B
H2
H7H5H5
H9
SpanishInfluenza
AsianInfluenza
RussianInfluenza
AvianInfluenza
Hong KongInfluenza
H3
Pan
dem
icvaccin
es
Reg
ula
r vaccin
es
Influenza Virus Types & Subtypes in Humans (Trivalent Vaccine)
• Type A– Seasonal epidemics caused by H3N2, H1N1, and
H1N2 subtypes– Pandemics (caused by new subtypes)
• Type B– No subtypes– Seasonal epidemics only
Influenza VirusInfluenza Virus
Antigenic Change
• Antigenic ‘drift” occurs in HA and NA– Continual development of new strains secondary to
genetic mutations/seasonal epidemics– A viruses >> B viruses
• Antigenic “shift” occurs in HA and NA– Associated with pandemics – Appearance of novel influenza A viruses bearing new
HA or HA & NA
135
135135
145
145
145
262
A
B
C
D
E
Model of the influenza A H3 HA structure
Top view Side view
N. HemisphereTemperate
(Japan & US. West Coast)
Rel
ativ
e In
fluen
za A
ctiv
ity
Tropical(Singapore & S. China)
S. HemisphereTemperate(Australia)
0
1
0.4
0.6
0.8
0.2
JAN FEB MAR APR MAY JUN JUL AUG SEP OCT NOV DEC
Seasonal Occurrence of Influenza(Reichelderfer PS, et al. Current Topics in Medical Virology, 1988)
Influenza Disease
• National morbidity and mortality data
• Comparison with other influenza seasons
• Mortality in children
• The circulating viruses
What Was Different About the 2003-04 Influenza Season?
• Sustained increases in influenza activity were reported unusually early
• Reports of influenza-related pediatric deaths were prominently reported by national media
• Vaccine manufacturers had sold almost all vaccine by mid-December, a time when demand continued
• There was a less than optimal match between the predominant circulating viruses (A/Fujian/411/02-like) and the corresponding vaccine component, A/Panama/2007/99
Virologic Surveillance
• Virologic data are the foundation of influenza surveillance– Specific for influenza– Detect changes in circulating strains– Detect novel influenza viruses– Used for vaccine strain selection– Monitor vaccine match
WHO/NREVSS Collaborating LaboratoriesNational Summary, 2003-04
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
2600
2800
3000
40 42 44 46 48 50 52 1 3 5 7 9 11 13 15 17 19
Week
Nu
mb
er
of Is
ola
tes
0
5
10
15
20
25
30
35
40
45
50
Pe
rce
nt P
ositiv
e
A(H3N2)
A(H1N1) and A(H1N2)
A(Unsubtyped)
B
Percent Positive
Percentage of Specimens Testing Positive for Influenza National Summary, 2003-04
0
10
20
30
40
50
40 42 44 46 48 50 52 1 3 5 7 9 11 13 15 17 19
Week
% o
f Vis
its fo
r IL
I
%pos. 2003-04 %pos. 1999-2000* %pos 2002-03
Percentage of Visits for Influenza-like IllnessReported by Sentinel Providers
National Summary, 2003-04
0
1
2
3
4
5
6
7
8
9
10
11
12
40 42 44 46 48 50 52 1 3 5 7 9 11 13 15 17 19
Week
% o
f V
isits
fo
r IL
I
% ILI 2003-04 %ILI 1999-2000* %ILI 2002-03 national baseline
Weekly Influenza Activity Estimates Reportedby State & Territorial Epidemiologists
Week ending December 20, 2003 - Week 51
No Report Sporadic Regional Widespread No Activity Local Activity
Weekly Influenza Activity Estimates Reportedby State & Territorial Epidemiologists
Week ending January 24, 2004 - Week 3
4
6
8
10
12
Weeks
% o
f A
ll D
eath
s D
ue
to P
&I
Pneumonia and Influenza Mortality for 122 U.S. Cities
Week Ending 01/24/04
2000 2001 2002 2003
Epidemic Threshold
Seasonal Baseline
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
Summary of 2003-04 Influenza Activity in the U.S. as of Week 3
• Influenza activity has declined in all regions• For week 51 of 2003, widespread influenza activity
was reported by more states than during any week during the past 10 years
• Influenza-related deaths rose above the “epidemic threshold” for the first time during week 51 and has stayed above the baseline for 5 consecutive weeks
• Reports suggest that highest ILI attack rates were among children and young adults
Influenza-Associated Deaths Among Children < 18 Years of Age
• 121 influenza-associated deaths (lab confirmed) reported to CDC
• Median age, 3.8 years (2 weeks to 17 years)• 72 (60%) < 5 years of age• 33 (27%) 6-23 months of age• 26 (21%) had underlying medical conditions• Available vaccination histories indicate 57
unvax and 2 vax according to recs
Is 2003-04 Different in Impact Among Children?
• Influenza-associated deaths not reportable conditions in the U.S. and annual average number of influenza deaths unknown.
• During 1990-1999, and estimated annual average of 92 respiratory and circulatory deaths occurred among children < 5 years; estimate based on mathematical modeling, not on counting lab confirmed fatalities.
• Studies to determine if hospitalization increased in children are ongoing.
The Viruses: 2003-04 Influenza Season
• 573 influenza viruses from U.S. characterized antigenically by CDC’s WHO Collaborating Center
• 565 were H3N2 viruses (2 H1s and 6 Bs)– 106 (18.8%) were well inhibited by antiserum to
the A/Panama vaccine strain– 459 (81.2%) were similar to the
A/Fujian/411/2002 drift variant and not well inhibited by antiserum to A/Panama
Why Wasn’t an A/Fujian-like Virus Included in the 2003-04 Influenza Vaccine?
• The A/Fujian/411/02 (H3N2) antigenic variant was identified at CDC on January 31, 2003.
• European and U.S. regulatory authorities have required that influenza viruses used to produce vaccine be isolated and passaged only in eggs or cells such as primary chick kidney cells for safety reasons.
• An A/Fujian-like (H3N2) egg-derived vaccine candidate was first available in April and its use required further characterization and preparation of reagents, steps that would have delayed vaccine availability.
• Time constraints and uncertainty about antigenic differences among circulating strains led to a decision retain A/Panama/2007/99 (H3N2) in the 2003-04 vaccine.
Considerations for Recommendations
• Are there new antigenic variants?
• Are new variants spreading?
• Are current vaccines able to induce antibodies to the new variants?
• Are any new variants useful for vaccine production?
Influenza Vaccine
• Vaccine uptake
• Vaccine production and distribution
• Vaccine effectiveness– What we know from past studies– What we know about this year
Influenza Vaccination Coverage Estimated per Influenza Season
1988 – 2001, U.S.
0
10
20
30
40
50
60
70
80
90
1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
Influenza Season
Per
cent
Vac
cina
ted >64 Yrs.
50-64 High Risk
50-64 All
18-49 High Risk
18-49 All
Source: National Health Interview Survey, Jan.-June interviews, 2002 data preliminary
Influenza Vaccine Production and Distribution, 1999-2003
Year Doses Produced Doses Distributed Number and Proportion of Doses
Produced Not Distributed
1999 77.2 M 76.8 M 0.4 M (0.5%)
2000 77.9 M 70.4 M 7.5 M (9.6%)
2001 87.7 M 77.7 M 10 M (11.4%)
2002 95.0 M 83.0 M 12 M (12.6%)
2003 (projected) 87.1 M 83.2 M 3.9 M (4.5%)
Influenza Vaccine Effectiveness
• Determinants–age and immune status–vaccine match
• Effectiveness by age and status–< 65 years, healthy 70-90% influenza– 65 years, community 30-70% influenza– 65 years, nursing home 30-40% influenza
50-60% hospital.
80% death
Estimates of Vaccine Effectiveness for the 2003-04 Influenza Season
• Study conducted by NIP/CDC among HCW at a hospital in Denver
• Endpoint was effectiveness against influenza like illness (not vs. lab-confirmed influenza more specific endpoint or vs.more serious outcomes, such as hospitalization or death)
• This study was unable to demonstrate vaccine effectiveness vs. influenza-like illness
• Other studies ongoing in the U.S.• One study in France has reported approx. 60%
effectiveness against lab-confirmed influenza
Improvements Underway or Being Discussed
• Enhancing global influenza surveillance (early warning system)- Asia, Central and South America
• Establishing confirmatory tests for hemagglutination inhibition test (virus neutralization)
• Using reverse genetics for making vaccine reference viruses if egg derived virus unavailable
• Conducting annual vaccine effectiveness studies• Requiring reporting of laboratory confirmed deaths
in children
Acknowledgements
• Members of the Influenza Branch
• The WHO National Influenza Centers
• The WHO Collaborating Centers in London, Tokyo and Melbourne
• The WHO Regional Offices
• WHO Headquarters in Geneva
The 2003-04 Influenza Season: The 2003-04 Influenza Season: We’re on a RollWe’re on a Roll