REVELAC-i: Progress in measuring influenza vaccine
effectiveness in Latin America and way forward
Red para la Evaluación de Vacunas En Latino América y el Caribe – influenza
SARInet annual meeting, Punta Cana, May 23 2017
Nathalie El Omeiri On behalf of REVELAC-i network, Alba Maria Ropero-Alvarez, PAHO/WHO, Washington D.C. Family, Gender and Life Course, Immunization unit, [email protected]
Why measure influenza vaccine effectiveness in LAC?
40 countries in the Americas with policies in place for influenza vaccination. Over 250 M doses distributed annually.
Despite the substantial increase in influenza vaccines use in LAC, no routine monitoring of influenza VE.
Need for regional evidence to support current policies and guide PH measures
Demonstrate the benefits of current vaccination strategies - sustain
investments in influenza vaccination programs. Information for action Inform program recommendations, their impact, cost-effectiveness Inform vaccine strain selection (GIVE) Assess particular effects: waning, serial vaccination etc.
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Influenza vaccine effectiveness (VE)
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VE varies between seasons and depends on:
Match between vaccine and circulating strains,
Host factors (age, underlying conditions,..),
Prior exposure to influenza virus,
Different products (TIV/LAIV,
adjuvanted/unadjuvanted)
“Field conditions”
Several features of influenza epidemiology and
vaccines create unique challenges for the
evaluation of IVE and the expected benefits of
influenza vaccination programs.
Test-negative design
No ethical limitations (target groups)
Can build on existing influenza surveillance
systems
Provides valid VE estimates Reduces health-care-seeking behaviors biases,
reduces the risk of misclassification of influenza
status
Efficient and timely
Sustainable and cheap
How to monitor VE in LAC?
At least 28 countries across 4 continents
now using the TND for annual influenza VE monitoring
Sullivan et al. Exp Rev. Vaccines 2014
6 The Lancet Resp Med 2017
Evaluation of influenza vaccine effectiveness - A guide to the design and interpretation of observational studies, 2017
Describes challenges and the role of
observational (non-randomized)
influenza VE studies in evaluating
influenza vaccination programs.
Study designs described and their
advantages and limitations reviewed.
For public health scientists, it shows why
VE studies have had a larger role in
policy for influenza vaccines than for
other vaccines.
The guide also addresses the critical
evaluation of influenza VE studies.
7 http://apps.who.int/iris/bitstream/10665/255203/1/9789241512121-eng.pdf
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Countries and networks reporting vaccine effectiveness annually
REVELAC-i network evolution (Red para la Evaluación de Vacunas de Influenza en América Latina y el Caribe)
Multicenter VE case-control study
Members of the network
15 REVELAC-i members
2012 Pilot phase
(4 SH)
2013 Implementation
& network launch (9 SH + 1 NH)
2014 (7 SH + pilot in Ecuador)
2015 (5 SH+ pilot in Peru)
Multicenter case-control study: to estimate VE
against PCR-confirmed influenza-associated
SARI among vaccination target groups during
the influenza season
2016 Uruguay
Costa Rica El Salvador Honduras Panama
+ Argentina
Brazil
Chile Colombia
Paraguay
+ México
REVELAC-i Multicenter Case-control
To estimate VE against PCR-confirmed
influenza-associated SARI per vaccination
target groups during the influenza
season.
Northern hemisphere/southern Hemisphere
VE per Sub-Region?
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Belize
El Salvador Nicaragua
Panama
Costa Rica
Brazil
Paraguay
Uruguay
Argentina
Chile
Peru
Ecuador
Colombia Venezuela
Cuba Bahamas
I. Turcas & Caicos
Jamaica Haiti Dominican
Republic
Anguilla
Trinidad & Tobago
Antigua &
Barbuda
Sta. Lucia
Guatemala Honduras
Source: Country reports to PAHO, MOHs Webpage, PAHO/WHO Surveys
Policy change from NH to SH
vaccine
‒ Colombia (2007) ‒ El Salvador (2011) ‒ Guatemala (2012) ‒ Cuba (2015) ‒ Honduras (2015) ‒ Costa Rica (2015)
Use and formulation of seasonal influenza vaccines in the Americas, 2015
Northern Hemisphere (9)
Southern Hemisphere (31)
Not introduced in the public sector
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Country Vaccination Target groups N SARI hospitals
Children Elderly Individuals with
chronic conditions
Argentina 6–24 months ≥65 years 4
Brazil 6–23 months ≥60 years 29
Chile 6–23 months ≥65 years X 6*
Colombia 6–23 months ≥60 years 7
Costa Rica 6 months–10 years with chronic cond. ≥65 years 6*
Cuba 6–23 months ≥65 years TBD
El Salvador 6–59 months ≥60 years 4*
Ecuador 6–59 months ≥50 years X 3
Honduras 6–35 months with chronic cond. ≥60 years 3*
México 6–59 months;
3–9 years with chronic cond.
≥65 years
X 46
Panamá 6–59 months ≥60 years 10*
Paraguay 6–35 months ≥60 years 2
Peru 6–24 months ≥60 years 3
Uruguay 6–48 months ≥65 years 7*
TOTAL 6–59 months ≥60 years 130
Study population
*All SARI surveillance sentinel hospitals included
Information collected
‒ Age, ‒ sex, ‒ date of symptoms onset, ‒ admission to intensive care, ‒ discharge status following
hospitalization, ‒ dates of hospital admission and
discharge, ‒ preexisting conditions, ‒ antiviral treatment, and date of admin. ‒ influenza vaccination in current and
prior year, ‒ number of doses in children<9 years, ‒ date of vaccination in current year, ‒ date of respiratory specimen
collection, ‒ RT-PCR results for influenza,
type/subtype of influenza and lineage of influenza B,
‒ positivity for other viruses (immunofluorescence).
57%
75%
50%
66% 68% 72%
4% 10%
22%
13%
36%
52%
2%
23%
50% 51%
-20%
0%
20%
40%
60%
80%
Infl
uen
za v
acc
ine
effe
ctiv
enes
s (%
)
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Adjusted VE* among 6 months‒5 years, LAC, 2013-15
*VE adjusted for age, month of symptoms onset and preexisting conditions.
9 countries 7 countries 3 countries
2013 2014 2015
60% 62%
38% 34%
28%
-10%
48% 47%
17%
-20%
0%
20%
40%
60%
80%
Infl
uen
za v
acc
ine
effe
ctiv
en
ess
(%)
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Adjusted VE* among ≥60 years, LAC, 2013-15
9 countries 7 countries 3 countries
2013 2014 2015
*VE adjusted for age, month of symptoms onset and preexisting conditions.
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2015
Northern Hem 2014-2015 ― an A/California/7/2009 (H1N1)pdm09-like virus;
― an A/Texas/50/2012 (H3N2)-like virus;
― a B/Massachusetts/2/2012-like virus. Yamagata
― quadrivalent a B/Brisbane/60/2008-like virus. Victoria Southern Hemisphere 2015
― an A/California/7/2009 (H1N1)pdm09-like virus;
― an A/Switzerland/9715293/2013 (H3N2)-like virusa;
― a B/Phuket/3073/2013-like virus. Yamagata
― quadrivalent a B/Brisbane/60/2008-like virus. Victoria
2016
Northern Hem 2015-2016 ― an A/California/7/2009 (H1N1)pdm09-like virus;
― an A/Switzerland/9715293/2013 (H3N2)-like virus;
― a B/Phuket/3073/2013-like virus. Yamagata
― quadrivalent a B/Brisbane/60/2008-like virus. Victoria Southern Hemisphere 2016 ― an A/California/7/2009 (H1N1)pdm09-like virus;
― an A/Hong Kong/4801/2014 (H3N2)-like virus;
― a B/Brisbane/60/2008-like virus. Victoria
― quadrivalent a B/Phuket/3073/2013-like virus. Yamagata
2017
Northern Hem 2016-2017 ― an A/California/7/2009 (H1N1)pdm09-like virus;
― an A/Hong Kong/4801/2014 (H3N2)-like virus;
― a B/Brisbane/60/2008-like virus. Victoria
― quadrivalent a B/Phuket/3073/2013-like virus. Yamagata Southern Hemisphere 2017 ‒ an A/Michigan/45/2015 (H1N1)pdm09-like virus;
‒ an A/Hong Kong/4801/2014 (H3N2)-like virus; and
‒ a B/Brisbane/60/2008-like virus. Victoria
― quadrivalent a B/Phuket/3073/2013-like virus. Yamagata
Composición recomendada para vacunas de virus de influenza, 2014-2017
REVELAC-i - What We´ve Learned
Feasibility of using SARI platforms + EPI Demographics, clinical, lab data completeness Vaccination status ascertainment Timeliness - active surveillance, information
systems, vaccination registries Sample size
Target groups IVE per type/subtype Subregion
Virological information – antigenic and genetic data
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Influenza cases and controls included in regional VE analysis, REVELAC-i
Argentina Brazil Chile Colombia Costa-Rica Honduras Panama Paraguay El Salvador Total
Influenza 36 277 133 69 71 6 20 75 7 694
(%) 5 40 19 10 10 0.9 3 11 1 100
Controles 54 728 616 165 79 3 49 222 10 1,926
(%) 2.8 37.8 31.98 8.57 4.1 0.16 2.54 11.53 0.52 100
Total 90 1,005 749 234 150 9 69 297 17 2,620
(%) 3 38 29 9 6 0.3 3 11 0.7 100
2013
Argentina Brazil Chile Colombia Honduras Paraguay El Salvador Total
Influenza 16 145 194 24 8 43 4 434
(%) 4 33 45 6 2 10 0.9 100
Controles 54 413 1,027 97 20 128 12 1,751
(%) 3 24 59 6 1 7 0.7 100
Total 70 558 1,221 121 28 171 16 2,185
(%) 3 26 56 6 1 8 0.7 100
2014
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2015
Chile Colombia Paraguay Peru Total
Influenza 394 33 76 17 520
(%) 75.8 6.3 14.6 3.3 100
Controles 1,705 90 222 149 2,166
(%) 79 4 10 7 100
Total 2,099 123 298 166 2,686
(%) 78 5 11 6 100
Argentina Chile Colombia Paraguay Uruguay Total
Influenza 37 226 11 77 67 418
(%) 8.9 54.1 2.6 18.4 16.0 100
Controles 209 1,048 93 224 1,574
(%) 13 67 6 14 0 100
Total 246 1,274 104 301 67 1,992
(%) 12 64 5 15 3 100
2016
Conclusion
Evidence from middle income countries with high vaccination uptake
Moderate protection among yound infants and the elderly, supporting current vaccination strategies
Strengthen REVELAC-i platform and expand VE estimation to new vaccination target groups Increase sample size for select countries and VE data timeliness for GIVE (bi-
annual reports for the WHO influenza vaccine strain selection meeting)
VE interim estimates
2017: Regional VE analysis of pooled seasons (2014-2016) among children and the elderly.
Support countries report national VE results
Data analysis manual and workshop
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The guide covers data handling and analysis including recoding, descriptive analysis, crude analysis, stratified analysis and multivariable regression.
Sample dataset, based on data collected in Chile during the 2016 influenza season as part of the REVELAC-i multicenter VE study in LAC (modified for educational purposes).
Model do-files are included and are referenced in the relevant sections.
The guide includes a supplementary section on analysis with small sample sizes.
The guide also provides proposals how to report VE results
This guide should enable public health professionals to use Stata to analyse data from TND case control studies, to estimate influenza VE
Antigua - Guatemala. 27 February 2013
http://www.paho.org/revelac-i/
GRACIAS! THANK YOU!
1st network meeting La Antigua Guatemala, 2013
3rd network meeting, Santiago de Chile, March 2016
2nd network meeting, Cartagena de Indias, 2014