Oct 30, 2008 WASHINGTON (CIDRAP News) The benefits conferred by influenza vaccinationto recipients and to their close contactswere hotly disputed at an international medical meeting this week.
Presenters at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy and the 46th annual meeting of the Infectious Diseases Society of America (ICAAC-IDSA) presented abundant but often contradictory evidence regarding flu vaccine's direct and indirect protective abilities.
The question whether flu vaccine protects recipients both from developing flu and from serious complications of flu, as well as whether its administration protects contacts of recipients, has been an active research topic over the past year.
A study published earlier this month in the New England Journal of Medicine (and placed online in September) found that giving the flu shot to pregnant women lowered both their risk of flu and also the risk for their newborns, who were too young to be vaccinated themselves. Reports in the American Journal of Respiratory and Critical Care Medicine in September and the Lancet in August contended that flu vaccine's ability to protect the elderly from death and from pneumonia has been overstated, and several papers have pointed out that, while vaccination in the elderly has increased, the mortality rate has not declined.
Flu vaccine came in for additional critical examination during ICAAC-IDSA, which drew 15,000 people to Washington, DC, and concluded Oct 28.
Observational studies faulted
"Observational studies have greatly exaggerated vaccination benefits in the elderly," Lone Simonsen, PhD, of George Washington University said Tuesday afternoon (Oct 28). She wrote a controversial paper challenging flu-mortality estimates for the elderly in 2005 while serving as a National Institutes of Health senior scientist.
Such studies distort reality, she said, by assigning any deaths in winter to fluincluding deaths that occur before the flu season beginsand do not make sense given what is known about age-related decay of the immune system. She proposed that flu researchers tackle the problem of making separate, more immunogenic vaccine formulas for seniors, and stressed the importance of indirect protection via vaccines given to child and adult contacts of the elderly.
But vaccinating children to protect others was challenged in a separate presentation, with Catherine Weil-Oliver of the Universite de Paris arguing that indirect benefit "has not been demonstrated in schoolchildren in any European study. . . . In children younger than two, no indirect benefit has been recorded at all."
Looking to flu vaccine to prevent death among the elderly may be focusing on the wrong benefit, Dr. Kristin Nichol of the University of Minnesota said Tuesday. While studies of reductions in mortality may have been clouded by selection bias, she said, studies that show decreases in rates of respiratory diseases and hospitalizations look solid.
"We need to remember that the vaccine also reduces influenza illness and it reduces hospitalization, and so while we explore the controversy we need to continue to vaccinate the elderly," she said.
Age and immunization rates
A poster presentation earlier in the conference explored one of the hypotheses behind the distrust of flu-mortality studies: that they are subject to a "healthy recipient" design defect. Several Kaiser Permanente researchers looked at medical records for recipients of flu vaccine older than 65 who are members of Kaiser Permanente of Northern California, a healthcare organization with about 3 million members. They found a statistical oddity: The likelihood of an elderly person's taking the flu shot rose along with their age and risk of flu mortality, but only up to a certain age. Once women passed 80 and men passed 85, they stopped taking the shot, even though their risk of dying from flu complications continued to rise.
The authors theorized that the very old are so frail that they are unable to get the shots by themselves, while attendants or healthcare workers deem the shot not useful for them. The result, the authors said, is that the oldest old and most at risk from flu complications are excluded from analyses of flu-shot effectiveness and age, so that results are distorted. (Baxter R, Fireman B, Lee J. "Who gets flu vaccines? A look at bias in flu vaccine effectiveness studies" [Abstract G1-1206])
Meanwhile, however, other age-groups for whom the flu vaccine is most recommended continue to go unvaccinated.
That includes children, according to a team from the Centers for Disease Control and Prevention (CDC), Vanderbilt University, and the University of Rochester. They examined the medical histories of 772 children younger than 5 and 401 children aged 5 to 12 who were brought to outpatient care for flu-like symptoms and fever. Among the older children, 133 had at least one characteristic that put them at high risk for serious flu complications, but only 32 of them (24%) had gotten a flu shot. Among the younger children, 549 had at least one high-risk indication, but only half275 or 51%had gotten at least one dose of flu vaccine. (Shinde V, Iwane M, Prill M, et al. Influenza among outpatient children: US, 2006-07. [Abstract G1-1700])
The concern about low immunization rates also includes pregnant women. An analysis from Bridgeport Hospital and Yale University Medical School in Connecticut found that, out of 520 women who were pregnant during flu season, 19% had been vaccinated, though 28% had discussed vaccination with their physicians during prenatal care. (Panda B, Stiller R, Bruce L, et al. Influenza vaccination in pregnancy: compliance with current CDC guidelines for prevention and control of influenza pertaining to vaccination during pregnancy. [Abstract K-4202])
And healthcare workers also continue to have low vaccination rates. Researchers from the Chinese University of Hong Kong reported that among 133 acute-care nurses who responded to a questionnaire, 38% said they had received flu vaccinebut 23% of the group developed flu-like illness themselves, and most missed work as a result. (Ng K, Lee N, Hui D. A Survey on ILI among health-care workers during a peak 'flu' season What are the risk factors? [Abstract K-4204])
The answer to improving protection against flu and flu complications, one group of scientists said, might be an additional vaccineand not just for ordinary seasons, but for an influenza pandemic as well.
Researchers from Emory University and the biotech companies i3 Innovus and Wyeth Research modeled the potential effect of vaccinating infants during a flu season with Prevnar, the 7-valent pneumococcal conjugate vaccine, in hopes of preventing the secondary bacterial infections that frequently cause flu-season deaths.
They found that in a typical flu season, preventing post-flu bacterial pneumonia saves $1.4 billion in healthcare spending. In a flu pandemic such as 1918, however, vaccination's effect would be much larger: It would prevent 1.24 million cases of pneumonia and 357,000 pneumococcal-related deaths and reduce costs by $7 billion. (Rubin JL, McGarry LJ, Klugman KP, et al. Public health and economic impact of 7-valent pneumococcal conjugate vaccination in an influenza pandemic in the US. [Abstract K-4210])
Sep 18 CIDRAP News story "Study: Flu shots in pregnant women benefit newborns"
Aug 29 CIDRAP News story "Study: Flu vaccine doesn't lower death rates in elderly"