Preliminary studies show lower flu-shot effectiveness in Europe

Mar 21, 2011 (CIDRAP News) – Preliminary studies suggest that this year's trivalent seasonal flu vaccine used in Europe was less effective against the 2009 H1N1 virus than last year's monovalent H1N1 vaccine was, possibly because of some degree of mutation in the virus, according to recent reports in Eurosurveillance.

The 2009 H1N1 virus has been the dominant flu strain this season in Europe, unlike in North America, where H3N2, H1N1, and B strains have all been common.

A preliminary study based on surveillance in seven European countries estimated vaccine effectiveness (VE) against all strains at only 42.3%. At the same time, a separate preliminary study from Spain estimated VE at 50% for all flu strains and 72% for 2009 H1N1.

The two analyses don't cover the whole season, and both reports say more precise and reliable estimates should become available after data for the whole season can be studied.

The two reports and an accompanying editorial cite antigenic drift, or evolution of the virus, as one of several factors that may help explain the lower VE compared with last year's H1N1 vaccine.

Seven-country study
The seven-country study included data from sites in Hungary, Ireland, Italy, Romania, Poland, Portugal, and Spain that participate in the Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) network. Patients who sought care for influenza-like illness (ILI) were tested for flu and provided information on their vaccination status and other variables. The surveillance covered the season through the fourth week of 2011.

A total of 1,671 ILI patients were included in the analysis: 846 who tested positive for flu by polymerase chain reaction (PCR) or culture (the cases) and 825 who tested negative (the controls). Among the cases, 76.7% had the 2009 H1N1 virus, 1.1% had H3N2, 20.5% had type B, and 1.8% had type A viruses that could not be subtyped.

Of 1,658 patients who had vaccination information, 116 (7.0%), including 34 cases, had been vaccinated.

When the authors used statistical procedures to estimate missing values and to adjust for potential confounding variables, including age, sex, chronic conditions, and smoking history, they found that the VE against all flu strains was 42.3% (95% confidence interval [CI], -7.3% to 69.0%). The estimated VE against the H1N1 virus was 44.1% (95% CI, -7.3 to 72.7%).

The results suggest that the vaccine provided "moderate" protection against confirmed flu and was less effective than the monovalent 2009 H1N1 vaccine used in the previous season, the researchers write. "This may be explained by antigenic drift, by a different distribution of adjuvanted versus non-adjuvanted vaccines in some study sites or by a different study population," they state, adding that patients included in last year's study were younger than this year's sample.

But the researchers say the findings should be taken cautiously for several reasons, including low vaccine coverage and potential biases related to confounding factors and the small, partial-season sample size.

Findings from Spain
The study from Spain was conducted in eight regions of the Spanish Influenza Sentinel Surveillance System and covered the period from Dec 12, 2010 to Feb 12, 2011. Using PCR, participating physicians tested the first two patients each week who presented with ILI and collected data from them on their vaccination status and other details. The authors used three outcomes: any type of flu virus infection, 2009 H1N1 virus infection, and H3N2 or type B infection.

For the analysis pertaining to any type of flu, the researchers included 1,061 patients, including 618 cases and 443 controls. After adjusting for confounders (age-group, receipt of monovalent pandemic vaccine last season, seasonal flu vaccine in 2009-10, and week of testing), the estimated VE was 50% (95% CI, -6% to 77%).

The analysis using 2009 H1N1 virus infection as the outcome included 983 patients, of whom 540 had lab-confirmed cases. The VE estimate, after adjustment for age-group, receipt of monovalent vaccine, and week of testing, was 49% (95% CI, 3% to 73%).

When using H3N2 or type B infection as the outcome, the authors included 513 patients, of whom 64 had type B infections and 6 had H3N2 infections. Following adjustments for confounders (similar to those in the other two analyses), the VE estimate was 84% (95% CI, 16% to 97%).

The study included a genetic analysis of 33 2009 H1N1 isolates. They did not contain any of six mutations found in two previously identified drifted strains, but 3 of the 33 did have amino acid changes compared with the vaccine strain, the report says.

The results suggest the vaccine was protective against all flu strains, but the 49% VE against 2009 H1N2 was below the 75% VE seen with the monovalent H1N1 vaccine last season, the authors report. As possible reasons for the difference, they note that the monovalent vaccine contained an adjuvant and was not recommended for elderly people, resulting in a younger, more immunocompetent population of vaccinees. They cite genetic drift as a third possible factor.

Unadjusted estimates better?
In the accompanying editorial, J. Puig-Barbera of the Centre for Public Health Research in Valencia, Spain, generally agrees with the researchers' suggested explanations for the lower VE estimate seen this season compared with last, including antigenic drift and differing study populations.

"The reported observations point to a certain degree of mismatch between the circulating influenza A(H1N1) 2009 strains and the corresponding vaccine component," he comments.

But noting that the crude estimates of VE dropped after the researchers adjusted for confounders, Puig-Barbera suggests that the unadjusted estimates might actually be more plausible in this context. For the future, he suggests that researchers test the ILI patients for other common respiratory viruses, such as respiratory syncytial virus, rhinovirus, and coronavirus.

"A case-case approach comparing influenza-positive patients with those positive for other respiratory viruses, . . . with incidence sampling of both groups in periods of similar risk for influenza, would provide more realistic and convincing estimates of the influenza vaccination effect," he states. He adds that better flu vaccines are clearly needed.

Kissling E, Valenciano M, I-Move case-control studies team. Early estimates of seasonal influenza vaccine effectiveness in Europe, 2010-11: I-MOVE, a multicenter case-control study. Euro Surveill 2011 Mar 17;16(11):pii=19818 [Full text]

Savulescu C, Jimenez-Jorge S, de Mateo S, et al. Effectiveness of the 2010-2011 seasonal trivalent influenza vaccine in Spain: preliminary results of a case-control study. Euro Surveill 2011 Mar 17;16(11):pii=19820 [Full text]

Puig-Barbera J. 2010-2011 influenza seasonal vaccine, preliminary mid-season effectiveness estimates: reason for concern, confounding, or are we following the right track? (Editorial) Euro Surveill 2011 Mar 17;16(11):pii=19821 [Full text]

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