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, elomeirin@paho.org

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.

2

Influenza vaccine effectiveness (VE)

3

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

8

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?

11

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

12

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 (%

)

16

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

(%)

17

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.

18

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

20

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

21

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

22

23

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