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Research Project
Initiative for the MObility and deVElopment of researchers’careers
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The European I-MOVE Multicentre 2013-2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2)
Publication . Valenciano, Marta; Kissling, Esther; Reuss, Annicka; Jiménez-Jorge, Silvia; Horváth, Judit K.; Donnell, Joan M.O.; Pitigoi, Daniela; Machado, Ausenda; Pozo, Francisco; I-MOVE Multicentre Case Control Study Team
BACKGROUND:
In the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013-2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013-2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season.
METHODS:
Practitioners systematically selected ILI patients to swab within eight days of symptom onset. We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I(2) index and Cochrane's Q test. If the I(2) was <50%, we estimated pooled VE as (1 minus the OR)×100 using a one-stage model with study site as a fixed effect. If the I(2) was >49% we used a two-stage random effects model.
RESULTS:
We included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p=0.695) and the I(2) index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4-67.0). For A(H3N2), the I(2) was 51.5% (p=0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: -34.4-63.2).
CONCLUSIONS:
The results suggest a moderate 2013-2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses.
Virological data integration on influenza vaccine effectiveness, Portugal 2015/16
Publication . Rodrigues, Ana Paula; Pechirra, Pedro; Guiomar, Raquel; Conde, Patrícia; Gomez, Verónica; Nunes, Baltazar; Machado, Ausenda
Regarding the wide genetic and antigenic variability of influenza viruses, overall or subtype influenza vaccine effectiveness (IVE) estimates may not be sufficient to assess vaccine protection against circulating strains. This is particularly important when low VE against a specific clade is suspicious or a new drifted virus is emerging.
Viral genetic characterization is routinely performed in influenza surveillance but viruses are selected according patient age, severity and vaccine status. For instance, last season genetic characterized cases were more vaccinated than those not selected.
A protocol for virological data integration on IVE studies within I-MOVE network was performed. It intended to solve the following issues:
1. Selection of the clade of interest to provide IVE;
2. Determination of the number of cases needed for genetic characterization;
3. Selection of cases for genetic characterization independently of patient features.
During the 2015/16 season, a closely contact between epidemiological and laboratorial teams allows to perform a random selection of influenza cases for genetic characterization independently of cases features. Influenza A(H1N1)pdm09 was the selected subtype given its predominance and the emergence of new subclades (6B.1 and 6B.2). 52.2% of A(H1)pdm09 cases were successfully characterized. No differences regarding age, sex and vaccine status were found between selected and unselected cases for genetic characterization.
The large sample size needed to estimate IVE against a specific clade requires an important effort on genetic characterization behind virological surveillance. However, random selection of cases for genetic characterization along season seems to be feasible without interfering with virological surveillance and obtains a representative sample of cases of the clade of interest.
Virological data from randomly selected cases will permit to estimate IVE against a specific clade during influenza season.
An extra effort on influenza genetic characterization is needed to achieve the needed sample size.
Sequenciação de nova geração e efetividade da vacina antigripal: um estudo sobre o vírus da gripe A(H3), em doentes com síndroma gripal, épocas 2016/2017 e 2017/2018
Publication . Pechirra, Pedro; Borges, Vítor; Cristóvão, Paula; Costa, Inês; Conde, Patrícia; Machado, Ausenda; Rodrigues, Ana Paula; Gomez, Verónica; Kislaya, Irina; Mendonça, Joana; Nunes, Baltazar; Gomes, João Paulo; Guiomar, Raquel
A tecnologia de sequenciação de nova geração (NGS) permite uma análise
genética do vírus da gripe muito mais profunda, quando comparada com
a sequenciação pelo método de Sanger, pois permite a análise do genoma
viral completo (e não apenas do gene da hemaglutinina). O presente estudo
teve como objectivo realizar a análise filogenética e mutacional do vírus
da gripe A(H3) de forma a pesquisar possíveis marcadores genéticos e padrões
de recombinação que estejam relacionados com a efectividade vacinal.
Foram obtidas sequências do genoma completo para 179 vírus A(H3),
detectados em casos de síndroma gripal no âmbito do projecto EuroEVA/IMOVE+
durante duas épocas de gripe: 2016/2017 e 2017/2018. Dos vírus
sequenciados, 28 pertenciam a vírus de casos vacinados (15,6%). Destes,
apenas 16 apresentaram mutações não encontradas em casos não vacinados,
no entanto, todas elas emergiram de forma esporádica. Foi revelada
a existência de recombinação genómica intrasubtípica, e identificados 4
perfis distintos de recombinação. O grupo em que todos os segmentos genómicos
são semelhantes a A/Singapore/INFIMH-16-0019/2016 foi o que
registou uma maior percentagem de falhas da vacina (20,3%).
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Funding agency
European Commission
Funding programme
FP7
Funding Award Number
267232
