Bob Roehr

May 04, 2010

May 4, 2010 (Bethesda, Maryland) — Surveillance data on the 2009/10 H1N1 influenza virus pandemic from Canada show that the H1N1 infection rate was highest in school-aged children, "but mortality rates were actually higher in the elderly, those over 65," according to Danuta M. Skowronski, MD, from the British Columbia Centre for Disease Control in Vancouver.

The findings on age, gathered by Canada's sentinel vaccine monitoring system, were part of a quartet of presentations here at the National Foundation for Infectious Diseases 13th Annual Conference on Vaccine Research.

The studies were published as a single paper online April 6 in PloS Medicine.

Analysis using hemagglutination inhibition (HI) and microneutralization (MN) assays for antibodies to the A/California/07/2009 (pH1N1) and A/Brisbane/59/2007 (seasonal H1N1) viruses found that titers for the former were highest in the older cohorts, particularly in those older than 90, whereas titers for the latter were highest in schoolchildren.

"About 4% to 5% of our population [younger than 60 to 70 years pf age] had preexisting HI antibodies to pandemic H1N1. That increased to 27% in those 79 years of age, and to a whopping 88% in those 90 to 99 years of age," Dr. Skowronski reported.

"The Th1/Th2 ratios were actually lower for pandemic than for seasonal strains. That might explain more severe outcomes in general with this virus, even in the younger groups," she said.

As for the higher mortality rates among older people who become infected, she believes they probably have a preexisting antibody, likely from the 1918 pandemic, which protects them from initial infection. "But if they acquire infection, then they suffer more severe outcomes. That may have something to do with impaired viral clearance. That is not necessarily new" for any exposure to influenza, Dr. Skowronski explained.

The researchers also identified differences in antibody responses to immunization. The response to seasonal virus was lower for Fluviral than for Vaxigrip, which constitute about 75% and 25%, respectively, of all vaccines used in Canada. Both vaccines exhibited lower HI than MN titers.

The rise in antibodies to the pandemic virus was higher with HI than with MN for Fluviral (1.44 vs 1.02), but not for Vaxigrip (1.02 vs1.17). Fluviral showed greater variability, generating a more than 2-fold rise in antibody titers with HI than MN (26% vs 4%), whereas Vaxigrip showed less variance (13% vs 8%).

Seasonal Flu Vaccine Might Increase Risk for H1N1 Infection

Studies from around the world have reached conflicting conclusions about whether previous vaccination with the 2008/09 seasonal trivalent influenza vaccine has any protective effect against H1N1 infection.

Six studies from Canada consistently found that vaccination in 2008/09 for seasonal influenza was associated with a 1.4- to 2.5-fold increased risk for hospitalization for H1N1 infection, said Naveed Z. Janjua, MD, also from the British Columbia Centre for Disease Control.

He suggested that the different rates of risk seen in their studies might be explained, at least in part, by the vaccine used in those areas. A province tends to purchase just 1 brand of vaccine for use in that jurisdiction

As for the mechanism behind those differences, studies in swine suggest that a vaccine that induces "nonneutralizing or subneutralizing concentrations of antibody can enhance the infection rather than protect from that infection," Dr. Janjua said.

David S. Fedson, MD, took a different approach. "We need to think beyond antibody, beyond cell-mediated signals that come after the virus infects a cell," he urged from the floor during the discussion. He is a former academician who served as medical director of Aventis Pasteur MSD before retiring. He suggested taking a closer look at host factors, particularly those that control inflammation.

In response to a question from the audience, Dr. Janjua said that they are looking at whether there were differences between the first and second waves of the pandemic, but that analysis has not yet been completed.

Dr. Skowronski acknowledged the limitations of case–controlled studies. She suggested that the Canadian findings might be more rigorous than similar studies from the United States and Mexico that reached different conclusions on the effect of vaccination for seasonal influenza on H1N1 infection.

Good immunization records and the use of a single brand of vaccine within a geographic region also are factors contributing to the rigor of the Canadian analysis, she pointed out.

The studies were conducted with funding from various Canadian government agencies. None of the presenters disclosed no relevant financial relationships.

PLoS Med. 2010;7:e1000258. Abstract

National Foundation for Infectious Diseases (NFID) 13th Annual Conference on Vaccine Research: Abstracts S10 and S11, presented April 26, 2010; abstracts S19 and S20, presented April 27, 2010.


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