Spanish study finds current flu vaccine gives limited protection

Spanish researchers estimate that this season's flu vaccine is only 24% effective so far, which is much lower than an estimate reported by a Canadian team last week., CDC / Judy Schmidt

A mid-season study from Spain suggests that this year's influenza vaccine provides only 24% protection, which contrasts with a recent Canadian study that showed the vaccine provided better than 70% protection.

In a study involving patients in Navarre, Spain, researchers found that the vaccine provided 40% protection against 2009 H1N1 viruses and 13% protection against H3N2 viruses, yielding an overall vaccine effectiveness (VE) of 24%. They couldn't estimate VE against influenza B because no cases were detected.

"These results suggest a moderate preventive effect against influenza A(H1)pdm09 [2009 H1N1] and low protection against influenza A(H3)," says the report, published yesterday in Eurosurveillance.

By comparison, a Canadian study published last week estimated that this year's vaccine provides 71% protection overall and 74% protection against 2009 H1N1, which is the overwhelmingly predominant strain in North America this season. Europe has been seeing a mix of 2009 H1N1, H3N2, and B.

The lead author of the Canadian study said that differences in the study population, along with differences in the circulating viruses, may help explain the contrasting findings.

No preliminary estimates of flu VE have been published yet this season in the United States, but they are expected soon.

Hospital patients included

The Spanish team, led by J. Castilla, used the test-negative study design, wherein patients who have a flu-like illness or acute respiratory illness are tested for flu and their vaccination status is determined. Those who test positive are classed as cases and those who test negative as controls.

The study included outpatients from a sentinel network of providers and hospital patients identified by public health nurses. The authors note that in Spain an inactivated trivalent vaccine is offered free to people 60 and older, those with major chronic health conditions, and those living in institutions.

A total of 775 patients were included in the analysis—431 hospital patients and 344 outpatients. Of the 775 patients, influenza was confirmed in 430 (56%), including 258 H3N2 cases and 164 H1N1 cases; subtyping was not done in 8 cases.

Ninety-eight (23%) of the 430 patients with confirmed infections had received this year's flu vaccine, compared with 113 (33%) of the 345 patients who tested negative—a significant difference.

In calculating VE, the team adjusted for differences in sex and age distribution, chronic conditions, month of sample collection, and healthcare setting. The overall adjusted estimate of VE was 24% (95% confidence interval [CI], –14% to 50%).

The overall VE numbers were nearly the same when the researchers looked separately at outpatients, hospital patients, and the target groups for vaccination. But the estimated VE in elderly people (65 and older) was only 11% (95% CI, –53% to 48%), versus 39% (95% CI, –1% to 68%) in younger people.

As noted, the VE against 2009 H1N1 was estimated at 40% (95% CI, –12% to 68%), whereas protection against H3N2 was only 13% (95% CI, –36% to 45%). The separate findings for outpatients, hospital patients, and target groups were generally similar.

As with the overall estimate, however, the vaccine was found to better protect against H1N1 in people younger than 65 (59%; 95% CI, 4% to 83%) than in the elderly (4%; 95% CI, –162% to 65%).

The authors also note that flu outbreaks were detected in five Navarre nursing homes during the study period. It was found that 20 of the 22 patients with confirmed cases had been vaccinated, which also suggests low VE, they observe.

The researchers mention the recent Canadian study and note that the 2009 H1N1 viruses circulating in Canada remain antigenically similar to the vaccine strain. "Our results suggest a lower VE against this serotype in Navarre, but as yet, we do not have final antigenic results," they write.

They also caution that the findings are preliminary and have limited statistical power with wide CIs, and that the final results for the season may turn out to be different.

The findings "should serve as a stimulus to design better influenza vaccines," the researchers comment. But they add that even when VE is low, "vaccination may appreciably reduce the number of cases and hospitalizations in high-risk persons."

Comparing Spanish, Canadian findings

Lead author of the Canadian study, Danuta Skowronski, MD, in an interview with CIDRAP News today, cited several factors that might contribute to the difference between the Spanish and Canadian estimates. She is the lead epidemiologist for flu and emerging respiratory pathogens at the British Columbia Centre for Disease Control in Vancouver.

"You have to think of things like methods, study populations, and viruses," she said, noting that more than 90% of flu viruses in both Canada and the United States this season have been 2009 H1N1, whereas Europe is seeing a mix.

"I think we've come a long way to convince people that a single estimate [of VE] doesn't capture the complexity in terms of subtypes," she said. "So if one region has mostly H1N1 and another has a mix, having a single estimate won't tell you about protection in a given region."

Further, "Having a subtype-specific estimate alone doesn't tell much unless you delve deeply into methods and populations," she added.

For example, she pointed out that about a third of the patients in the Spanish study were elderly people, who respond less well to vaccines, compared with only about 10% in the Canadian study.

In the Spanish results, she added, VE in those younger than 65 was close to 60%, compared with 40% overall. The 60% VE was much closer to the findings in her study, she noted.

"In terms of H1N1, I think we are aligned in seeing reasonable protection in the context of viruses that are antigenically and genetically well conserved," Skowronski said.

She noted that the difference in VE between younger and older people was not seen with H3N2 as it was with H1N1. "It may be a signal that we need to delve deep to understand why that H3 [VE] may be staying low." She said the finding could suggest something about the match between circulating H3N2 strains and the vaccine strain.

Skowronski noted that the numbers of H3N2 cases in North America have been too few this season to generate a reliable VE estimate for that subtype.

The World Health Organziation's committee that picks flu strains for next year's vaccine will be looking at this season's preliminary VE estimates as part of its process, Skowronski reported.

"The most important reason to provide these in support of vaccine strain selection is to indicate whether the usual lab indicators [such as antigenic match] actually play out in terms of vaccine field performance," she commented. "People don't necessarily conform to what you see in vitro in the lab."

She also commented that in assessing flu VE, long-term patterns are far more meaningful than individual numbers: "The point estimates per se are not what's important. We have to establish patterns over several years and look at the signals that emerge over that time."

Castilla J, Martinez-Bas I, Navascues A, et al. Vaccine effectiveness in preventing laboratory-confirmed influenza in Navarre, Spain: 2013/14 mid-season analysis. Eurosurveillance 2014 Feb 13;19(6) [Full text]

See also:

Feb 6 CIDRAP News story on Canadian VE study


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