CDC neutral on thimerosal in flu vaccine for toddlers

May 6, 2004 (CIDRAP News) – Almost 5 years ago, the American Academy of Pediatrics (AAP) and the US Public Health Service joined in calling for removal of the mercury-containing preservative thimerosal from vaccines. By 2001, all the vaccines recommended for children under age 7 were available without thimerosal or with only trace amounts.

But this year, in recommending for the first time that 6- to 23-month-old children routinely get flu shots, the Centers for Disease Control and Prevention (CDC) did not go on record in favor of a thimerosal-free formulation of the vaccine. Instead, the CDC said the risk of flu complications far outweighs any possible risk from thimerosal in the vaccine. At the same time, the agency said a few million doses of flu vaccine without thimerosal will probably be available for those who want them.

"No scientifically conclusive evidence exists of harm from exposure to thimerosal preservative–containing vaccine, whereas evidence is accumulating of lack of any harm resulting from exposure to such vaccines," the CDC said in its annual recommendations on influenza control, published last week. "Therefore, the benefits of influenza vaccination outweigh the theoretical risk, if any, of thimerosal exposure through vaccination."

Thimerosal, which is 49.6% mercury by weight, has been used in vaccines since the 1930s to control bacteria and fungi. The call to remove it from vaccines in 1999 was prompted by the recognition that babies in their first 6 months could receive a cumulative dose of mercury exceeding federal guidelines. Injectable flu vaccine contains 25 mcg of thimerosal per 0.5-mL dose.

CDC position stirs opposition
Parental and watchdog groups have long been concerned about the risk of autism and other neurodevelopmental problems from exposure to mercury, a neurotoxin. And the government has taken steps to reduce other mercury exposures, most recently by warning that nursing mothers, pregnant women, and small children should limit their consumption of certain fish.

The prospect of thousands or millions of small children receiving a flu vaccine with thimerosal has stirred opposition from groups concerned about mercury exposure. Opposition to the CDC's position—which was made known well before the flu vaccine recommendations came out last week—has surfaced in Congress in the form of a bill to ban thimerosal from all vaccines.

The bill was introduced Apr 5 by Rep. Dave Weldon, R-Fla., who is a physician, and Rep. Carolyn Maloney, D-N.Y. The bill (HR 4169) would specifically limit mercury in this year's flu vaccine for children to 1 mcg and would set the same limit for all childhood vaccines starting in January 2005.

Weldon's office stated in an Apr 5 news release, "The government is poised to recommend the flu vaccine later this year without recommending that infants and pregnant women get the mercury-free version of the inoculation." Weldon asserted, "This legislation is necessary to make sure that we don't roll back the clock when it comes to eliminating this mercury exposure to developing fetuses and infants. We can eliminate this exposure now and it's inexcusable not to."

The bill has been praised by activist groups working to prevent mercury exposure, such as SafeMinds, NoMercury.org, and the Mercury Policy Project.

Weldon asked in a recent speech at an autism conference, "Vaccines can be made without mercury, so why not remove the mercury and remove any doubt?"

Thimerosal and vaccine supply
In the case of flu vaccine, the answer to that question apparently relates in part to concerns about the cost and supply of vaccine. Curtis Allen, a spokesman for the CDC's National Immunization Program, told CIDRAP News that thimersoal-free vaccine costs more than the thimerosal-containing vaccine—about $12 versus $8.50 per dose. And though he declined to comment on how a thimerosal ban might affect the supply of vaccine, indications are that it could mean less vaccine to go around.

In a policy statement on flu immunization for children, the AAP states, "Removal of thimerosal results in wastage of one third of doses produced. Most experts view the protection of more children against the known risks of influenza [as] more important than the theoretic risk of small amounts of thimerosal in influenza vaccine."

Thimerosal is used in manufacturing the vaccine and must be removed afterward to provide a thimerosal-free product, according to Len Lavenda, a spokesman for Aventis Pasteur in Swiftwater, Pa. Aventis makes Fluzone, the only flu vaccine currently licensed for use in children under age 4.

Lavenda explained that flu vaccine is normally sold in 10-dose vials. Each time a dose is withdrawn, some contamination can be introduced, so a preservative is necessary. If the thimerosal is removed, the vaccine can be sold only in single doses, which requires more packaging. And the process of producing single doses results in some unavoidable loss of vaccine. "So for every three doses of preservative-containing vaccine, we can only produce two doses of preservative-free vaccine," Lavenda told CIDRAP News.

No matter what the CDC recommends, parents can ask for thimerosal-free flu vaccine for their children. "What we recommend is that parents discuss the issue with their provider, and if they want a thimerosal-free vaccine, they should request it from their doctor," said Allen.

Lavenda said Aventis takes preliminary orders for flu vaccine from December until mid-May, and this year the demand for preservative-free vaccine has been picking up. "We certainly don't anticipate having a problem" meeting the demand, he said. The shortage of injectable flu vaccine last winter was an anomaly, he added. "Every other year we end up with millions of doses unsold."

In its official recommendations last week, the CDC said 6 million to 8 million single-dose syringes of flu vaccine without thimerosal will probably be available for the coming flu season. That would be a substantial increase over the 3.2 million doses that were available in 2003-04, the agency said. However, the supply available for 6- to 23-month-old children could be smaller, because that estimate includes vaccine from both Aventis and Chiron, but only the Aventis vaccine has been approved for that age-group.

Thimerosal studies
The most recent major assessment of the evidence on thimerosal was done by the Institute of Medicine in 2001. The IOM's Committee on Immunization Safety concluded that there was not enough evidence either to prove or to disprove that thimerosal-containing vaccines cause neurodevelopmental problems in children. But the IOM said the idea was "biologically plausible" and urged government agencies to carefully consider removing thimerosal from vaccines for infants, children, and pregnant women.

The IOM committee noted that thimerosal is metabolized to ethylmercury, rather than methylmercury, the metabolite resulting from mercury exposure via food. At high doses, thimerosal, ethylmercury, and methylmercury all are known to be toxic to the kidneys and central nervous system, the report said. But the limited data on low doses of thimerosal and ethylmercury have indicated no harm other than some hypersensitivity reactions.

On the other hand, the clear evidence of harm from high doses of thimerosal and other mercury compounds makes the hypothesis of a hazard from lower exposures plausible, the IOM panel said. Further, the committee said, "Some children who received the maximum number of thimerosal-containing vaccines on the childhood immunization schedule had exposures to ethylmercury that exceeded some estimated limits of exposure based on federal guidelines for methylmercury intake."

Besides urging consideration of removing thimerosal from vaccines, the IOM called for research to find a safe alternative to the compound and for studies on the neurodevelopmental effects of ethylmercury in animals.

Marie C. McCormick, MD, ScD, who chaired the IOM committee, told CIDRAP News she could not comment on whether the evidence on thimerosal risks has changed significantly since the report was published in 2001. In an e-mail, she said the committee recently completed a report on vaccines and autism that addresses some of the issues concerning evidence on thimerosal, and it may be released soon. McCormick is Sumner and Esther Feldberg Professor of maternal and child health at the Harvard School of Public Health in Boston.

Recent epidemiologic studies have revealed some inconsistent evidence on thimerosal-containing vaccines and autism or related disorders in children. In a study published last fall, Danish researchers examined the rates of autism in children vaccinated with thimerosal-containing and thimerosal-free vaccines. The study included all Danish children born from 1990 through 1996, totaling 467,450. (Denmark stopped using thimerosal-containing vaccines in 1992.) The investigators found no significant difference in the incidence of autism between the two groups, nor did they find a dose-response relationship between thimerosal exposure and the risk of autism. The study was published in the Journal of the American Medical Association.

In another study, published last fall in Pediatrics, CDC researchers examined records at three health maintenance organizations (HMOs) and came up with inconsistent findings. The authors first looked for links between neurodevelopmental disorders and thimerosal in children in two HMOs who were born between 1992 and 1999. In one HMO, thimerosal exposure at 3 months was significantly associated with tics (relative risk [RR], 1.89; 95% confidence interval [CI], 1.05-3.38). At the second HMO, an increased risk of language delay was associated with cumulative thimerosal exposure at 3 months (RR, 1.13; 95% CI, 1.01-1.27) and at 7 months (RR, 1.07; 95% CI, 1.01-1.13).

The investigators then looked at a third HMO's records of 16,717 children born from 1991 through 1997 to identify any association between thimerosal exposure and tics or language delay. This time they found no significant associations. Further, there was no evidence at any of the HMOs of a link between thimerosal and autism or attention-deficit disorder.

A pediatrician's view
Charles N. Oberg, MD, a pediatrician at Hennepin County Medical Center in Minneapolis and a pediatrics professor at the University of Minnesota, said most studies have not shown any clear link between thimerosal and neurodevelopmental problems. But he said he would prefer to use a thimerosal-free flu vaccine for young children if it's available.

"I'll follow the recommendations regarding the use of flu vaccine for younger children," given their increased risk of serious flu complications, he said. "However, if there was a choice between thimerosal vaccine and thimerosal-free, I'd definitely choose the thimerosal-free. If a parent was reluctant to use the vaccine because of thimerosal, I'd defer to their wishes."

He added that, given the limited supply of thimerosal-free vaccine, "I might be a little more proactive about making sure that option is available to my patients and their parents as soon as possible."

"I suspect this is really a transitional issue," said Oberg, who is president of the AAP's Minnesota Chapter. "Very shortly I'd expect that the flu vaccine will be thimerosal-free, or at least an adequate supply of the thimerosal-free version will be available for infants and children."

See also:

1999 joint statement of Public Health Service and American Academy of Pediatrics on thimerosal in vaccines
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4826a3.htm

CDC report "Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices," from Apr 30, 2004, Morbidity and Mortality Weekly Report
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr53e430a1.htm

Table of contents for 2001 IOM report Thimerosal-Containing Vaccines and Developmental Disorders
http://www.nap.edu/books/0309076366/html/

Abstract of Danish study published in JAMA, Oct, 1, 2003

Abstract of CDC study published in Pediatrics, Nov 5, 2003

CDC National Immunization Program's "Mercury and Vaccines" page
http://www.cdc.gov/nip/vacsafe/concerns/thimerosal/default.htm

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