Debunking the thimerosal myth

PHILADELPHIA — The thimerosal controversy continues to be the most pressing vaccine safety issue facing immunization programs today.

There is no doubt that vaccines are effective in reducing diseases. Because of vaccines, smallpox has been eradicated from the wild, polio eliminated from most of the world, and diseases such as diphtheria, tetanus, pertussis and measles, once prevalent killers of children in the United States, are now rare.

But now vaccines have become a victim of their own success. Along with such success of immunization come doubts, about the risk of the diseases vaccines seek to prevent, but also about the safety of vaccines in general.

Before vaccines are introduced to U.S. children, they are put through rigorous clinical trials — testing for both efficacy and safety. The FDA will only license a vaccine after it is proven safe in its targeted population.

Yet vaccines remain controversial to some parents. A series of challenges through the media have brought to light serious allegations about the safety of U.S. children.

One of the most difficult challenges faced by vaccines these days is whether exposure to the preservative thimerosal, because it contains a form of mercury known as ethylmercury, can cause neurologic damage or autism.

Thimerosal was regularly used in vaccines until a 1999 recommendation from the AAP and the CDC called for its removal. According to reports at that time, the total mercury a child could be exposed to in the first year of life through thimerosal-containing vaccines exceeded safe levels of mercury exposure by the Environmental Protection Agency (EPA).

But the EPA guidelines were intentionally liberal in their estimation of what constitutes dangerous levels of mercury exposure. Furthermore, leading vaccine advocates say, the recommendation to remove thimerosal was based on flawed assumptions, meaning that thimerosal was never dangerous in the first place.

Still, the removal of the preservative from vaccines was sensationalized in the media as a conclusion that thimerosal was in fact dangerous. What started out as a cautionary decision thought to benefit the American public blew up in the face of the public health community.

Vaccine manufacturers are now facing the ramifications of that decision in the form of lawsuits that threaten their ability to stay in business. As well, parents are now frightened by a backlash of misinformation campaigns and some are even scared to have their children immunized.

The removal of thimerosal

Prior to the introduction of thimerosal, systemic infections from agents like Staphylococcus aureus were common in vaccine recipients. But the introduction of thimerosal, a bacteriostatic agent intended to kill those same bacteria, changed all that, according to Paul Offit, MD, director of infectious diseases at the Children’s Hospital of Philadelphia, and a professor of pediatrics at the University of Pennsylvania.

“Once we figured out a way to make bacteriostatic agents like ethylmercury, it really revolutionized our ability to make vaccines in multidose vials,” Offit explained.

Thimerosal was regularly used in vaccines throughout the 20th century to great success. Secondary bacterial infections in vaccine recipients dropped dramatically and vaccination coverage rates soared.

In 1997, when the Food and Drug Modernization Act was passed into law, federal agencies were required to list all foods and drugs that contained mercury. The law was part of an overall effort to reduce unnecessary mercury exposure to U.S. children.

“The impetus was certainly noble,” said Offit. “It was simply a way to make sure we understood just what contained mercury and how much mercury it contained.”

As a result of that analysis, it was found that the diphtheria-tetanus-acellular pertussis, hepatitis B and Haemophilus influenzae type b vaccines all contained trace amounts of thimerosal. When the amount of mercury was added up, however, public health officials realized that children could be exposed to levels of mercury deemed unsafe by the EPA.

The AAP and CDC issued a statement calling for the removal of thimerosal from all childhood vaccines based on the “precautionary principle,” or that if it is possible to remove a potentially harmful element from a product without doing harm to the integrity of that product, then that element should be removed.

The decision seemed simple enough. Thimerosal could reasonably be removed from vaccines, and vaccines could instead be manufactured in single-dose vials.

But, according to Offit, the cautionary principle does not apply in this case. “By precipitously removing thimerosal there were a number of consequences that were negative,” he said.

EPA guidelines

The EPA guidelines were based in large part on a study done in Iraq in 1971. The Iraqi government unknowingly imported 90,000 metric tons of grain that had been fumigated with methylmercury, a close chemical cousin of ethylmercury.

The grain was made into bread and distributed to farmers in Iraq. The result, however, was over 6,000 hospitalizations and 450 deaths due to excessive mercury exposure.

There were also babies born with neurologic damage to mothers who had eaten the tainted bread. Researchers took the opportunity to analyze hair samples from exposed mothers – an indicator of chronic exposure – to find the lowest level of mercury present in mothers who had children with mild neurologic damage.

Once they had that information, the researchers took an extra precautionary step and divided that number by 10. They recommended that children not be exposed to levels of mercury that exceed their liberal estimate so as to reduce the possibility of mercury poisoning.

The EPA, in establishing its guidelines for U.S. children, took that low number as their maximum allowable exposure limit. So, then, children who may have been exposed to mercury through vaccination were still exposed to levels of mercury 10 times below levels found to be harmful.

But the EPA estimates were based on two incorrect assumptions, according to Offit. First, the EPA assumed that methylmercury was the same as ethylmercury, which is used to make thimerosal.

Methylmercury, though, has a half-life of around 50 days, while for ethylmercury it is approximately seven days. As well, while methylmercury actively enters the central nervous system, ethylmercury does not.

“There is a critical difference between these two molecules,” said Offit.

Secondly, the EPA assumed that in utero exposure, as was the case in the Iraq study, would have the same harmful effects as exposure after birth, as would be the case in vaccinated children. But that is not the case, according to Offit.

“We know from teratogenic agents and viruses that they are far more likely to cause damage in utero than to an already developed central nervous system ex utero,” he said.

Bad results

The removal of thimerosal was played up in the media as a conclusion that thimerosal was dangerous. As a result, lawsuits have been filed across the country seeking hundreds of millions of dollars in damages and for medical monitoring.

The resulting litigation crisis has led several prominent vaccine manufacturers to speculate whether they can even stay in business. The thimerosal scare also led some hospitals to initially stop giving the hepatitis B vaccine to newborn children, a decision that resulted in chronic infections and deaths as a result of hepatitis B.

The controversy also scared many parents, many of whom are now afraid to have their children immunized, leaving them at risk for potentially serious diseases. While the removal of thimerosal was well intentioned, it had immediate fallout, and wound up doing more harm than good. “What we did, at best, was substitute a theoretical risk for a real risk, and did harm,” said Offit.