STATEMENT FOR THE RECORD

FOR THE

U.S. HOUSE OF REPRESENTATIVES

COMMITTEE ON APPROPRIATIONS

SUBCOMMITTEE ON LABOR, HEALTH AND HUMAN SERVICES, EDUCATION
AND RELATED AGENCIES

HEARING ON

INFLUENZA VACCINE

ON BEHALF OF
THE AMERICAN ACADEMY OF PEDIATRICS

October 5, 2004

The American Academy of Pediatrics (AAP) is an organization of 60,000 primary care pediatricians, pediatric medical subspecialists, and pediatric surgical specialists dedicated to the health, safety, and well-being of infants, children, adolescents, and young adults.

INTRODUCTION

This statement is submitted on behalf of the American Academy of Pediatrics (AAP). The American Academy of Pediatrics is an organization of 60,000 primary care pediatricians, pediatric medical subspecialists and pediatric surgical specialists dedicated to the health, safety and well-being of infants, children, adolescents and young adults.

Our statement is premised on the importance of implementing the recommendations of the American Academy of Pediatrics, the Advisory Committee for Immunization Practices (ACIP) of the Centers for Disease Control, and the American Academy of Family Physicians (AAFP) regarding childhood immunization against influenza. All three have recommended that children 6 through 23 months of age, their close contacts, and other children with medical risk factors for severe influenza infection receive annual immunization against influenza. The recommendation to implement systematic protection of children under 2 years of age was made earlier this year in anticipation of the coming influenza season. It was made with the knowledge that the supply of thimerosal-free influenza vaccine would be inadequate to meet the increased demand for childhood vaccination prior to the 2004-2005 influenza season, and, in fact, possibly for the next several years as well. We would like to review the reasons for the recommendation in the context of efforts on the part of the U.S. Public Health Service and the American Academy of Pediatrics to reduce childhood exposure to mercury.

RISKS ASSOCIATED WITH INFLUENZA INFECTION DURING CHILDHOOD

As you know, influenza is a viral infection that circulates in the United States during the winter months of each year. The illnesses caused by influenza result in school and work absences, hospitalization, disability, and death. The impact of annual influenza epidemics on the elderly has been well documented, and much of the previous public health effort has emphasized immunization of individuals over 50 years of age. It has been difficult to isolate the impact of influenza infection among infants and children from the effects of other respiratory viral infections that circulate at the same time of year, but in recent years, improved diagnostic techniques and careful surveillance have demonstrated that influenza infection among children, particularly those younger than 2 years of age, results in hospitalization rates at least as high as those in elderly individuals. Influenza-related deaths are not systematically reported in the United States, but during the 2003 - 2004 influenza season the CDC received voluntary reports of over 150 childhood deaths due to influenza. The median age of those children was 3 years. Additional voluntary reports described 50 children with influenza encephalopathy -- that is, involvement of the brain -- 40% of whom suffered permanent disability such as paralysis and mental retardation. Improved surveillance efforts are needed to more clearly define the impact of influenza on infants and children, but evidence of the significant and disproportionate toll on those less than 2 years of age prompted the recommendation for annual immunization of this age group. The AAP notes that for infants younger than 6 months influenza vaccine is neither reliably effective nor licensed, and the best method for protecting these very young infants is immunization of their close contacts, including older siblings.

THIMEROSAL IN VACCINES

In July 1999, a joint statement issued by the AAP, AAFP, ACIP, and the United States Public Health Service established the goal of removing the mercury-containing preservative thimerosal, as a precaution, from vaccines routinely recommended for infants. Many vaccines recommended for children have never contained thimerosal, including the vaccines that protect against polio, measles, rubella, mumps, chicken pox and one of the kinds of bacteria that cause pneumonia and meningitis. Thimerosal has been used as a preservative in some vaccines and other medicinal products since the 1930's. Its use prevents bacterial or fungal contamination and permits production of vaccine in multiple-dose vials intended for repeated access. Thimerosal is 50% mercury by weight, and it is metabolized, or degraded, to ethylmercury and thiosalicylate. Ethylmercury is distinct from methylmercury. Methylmercury, an organomercurial resulting from pollution from coal burning power plants and other industries, accumulates in the aquatic food chain and is known to pose a health risk to humans. Extremely high levels of methylmercury lead to neurological damage and death. The fetus is thought to be more sensitive to these adverse effects than adults. A recent joint statement by the Environmental Protection Agency and the Food and Drug Administration (FDA) provides guidance on exposure to methylmercury from fish, particularly for women of childbearing age.

Information concerning potential adverse health effects of ethylmercury, the organomercurial in thimerosal, is limited. It is known, however, that ethylmercury is more poorly absorbed and more readily eliminated from the body than is methylmercury. A possible association between thimerosal-containing vaccines and increasing diagnoses of autism and autistic spectrum disorders has been investigated in studies in the United States and elsewhere. An Institute of Medicine committee reviewed those studies earlier this year. That committee concluded "the body of epidemiological evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism." To date, there is no scientific proof despite years of studies.

In the mid-1990's the FDA began a review of mercury in FDA-regulated products. That review revealed that, along with the ability to protect children from an increasing array of infectious diseases, additional vaccines recommended for pre-school children had resulted in increased exposure to ethylmercury. Health agency guidelines regarding acceptable exposure to ethylmercury have never been established, so the FDA review compared exposure to ethylmecury in thimerosal-containing vaccines to guidelines established for methylmercury exposure. By 1999 the total exposure of ethylmercury from vaccines recommended for infants under 6 months was less than the guideline for acceptable exposure to methylmercury as set by the FDA, the Agency for Toxic Substances and Disease Registry, and the World Health Organization, but could have exceeded Environmental Protection Agency guidelines, depending on the weight of the infant and the vaccine formulation used. It was this assessment that led the U.S. Public Health Service, including the FDA, the NIH, the CDC, the Health Resources Services Administration (HRSA), along with the AAP, to establish the goal of removing thimerosal as soon as possible from vaccines routinely recommended for infants. That goal was established as a precautionary measure, despite the absence of evidence of harm caused by low levels of thimerosal in vaccines and, as part of an effort to limit childhood exposure to mercury in all forms. By 2001 all vaccines routinely recommended for pre-school children were available in preparations that were completely free of thimerosal or contained negligible amounts, and by January 2003 all lots of previously-recommended thimerosal-containing vaccines had expired. Possible exposure to thimerosal for infants less than 6 months of age had been reduced from as much as 187.5 micrograms to < 3 micrograms.

THIMEROSAL-FREE INFLUENZA VACCINE AVAILABILITY

The recommendation for annual immunization of all children between 6 and 23 months creates a potential increase in demand for influenza vaccine of more than 12 million doses per year. Combining all at-risk groups for whom annual immunization is recommended yields a total potential demand of 286 million doses. Actual administration of influenza vaccine-for adults as well as for children-has regularly fallen far short of recommendations. Among children for whom vaccination has been recommended because of chronic medical conditions, such as asthma, well under 50% actually receive vaccine. The reasons administration falls short of recommendations are many and include logistical difficulties in identification and recall of at-risk patients, access to health care providers, cost to families, and inadequate vaccine supply. During the past 5 years, 77.2 to 95 million doses have been produced, compared to recommendations for administration to more than twice that number of at-risk individuals.

Production of safe vaccines is an exacting process. Extraction of thimerosal from the final vaccine product results in loss of approximately one third the original volume, and, thus, loss of one third of the vaccine doses. Matching distribution of limited supplies of vaccine to regional demands is an additional annual challenge. The earlier-than-usual appearance of influenza in some states during the 2003-2004 season, for example, led to unusual early demand in those states and shortages throughout the United States.

There are three United States manufacturers of influenza vaccine. One makes a live, attenuated, intranasal vaccine that is licensed only for healthy individuals between the ages of 5 and 49 years. Of the remaining two manufacturers producing inactivated vaccine indicated for use in young children and the elderly, only one has the capacity to produce vaccine without use of thimerosal as a preservative, and output of preservative-free doses during the coming year and for the next several years is anticipated to be far fewer than the number of doses required to accommodate the recommendations for administration to children 6-23 months of age. Added to insufficient total supply is the difficulty of matching distribution of the limited doses of thimerosal-reduced vaccine specifically to the health care providers who would use it to immunize young children and pregnant women.

Thimerosal is no longer used as a preservative in vaccines recommended for infants < 6 months of age, and all other vaccines recommended for pre-school aged children are now free of thimerosal. Inactivated influenza vaccine contains 12.5 micrograms of ethylmercury in doses used for children <3 years of age. The cumulative amount of ethylmercury to which a child would be exposed over 2 years following the new recommendations is 37.5 micrograms, well below the most conservative federal guidelines for methylmercury, and infants at greatest risk for mercury toxicity, those less than 6 months, would not be exposed at all.

The American Academy of Pediatrics continues to work with the U.S. Public Health Service to limit exposure of children and pregnant women to mercury, both from the methylmercury present in food and environmental sources, and from ethylmercury from thimerosal in vaccines. This effort includes encouraging vaccine manufacturers to continue revision of manufacturing processes to allow production of thimerosal-free vaccines. Meanwhile, risk from exposure to thimerosal remains theoretical despite multiple studies, and thimerosal has already been eliminated or is present in only trace amounts in all other vaccines for young children. Risks of hospitalization, disability and death from influenza infections are real and occur on a predictable, annual basis.

A requirement for exclusive use of thimerosal-free influenza vaccine for children would severely threaten influenza vaccine supply. It is the opinion of the American Academy of Pediatrics that health care providers should provide yearly influenza vaccination for all children between the ages of 6 and 23 months of age, as well as for close contacts of all infants and children less than 2 years of age. Influenza results in hospitalization and death of children in the United States, and yearly influenza vaccine can reduce that risk.

We appreciate the opportunity to express the opinion of the American Academy of Pediatrics. Thank you.