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Hepatitis A routine childhood immunization recommendations published
The recommendations are for universal immunization of all children starting at age 12 months.
In the July issue of Pediatrics, recommendations for universal childhood immunization against hepatitis A were published. The Advisory Committee on Immunization Practices recommendations had been published in May of last year.
These incorporated the FDA approval in 2005, which changed the minimal age for the use of these vaccines from 24 months to 12 months. Routine immunization for children starting at age 2 years has been recommended since 1999 in 11 states with the highest rates of hepatitis (more than 20 per 100,000) and six states with slightly lower rates. It is estimated that about half the eligible children had been immunized under this program.
I cannot write about this disease without recalling my old chief, Saul Krugman, MD. Unfortunately, his Willowbrook experiments remain a footnote in the infectious disease literature, but they are a case study in medical ethics books.
In studies during the early 1960s, Krugman demonstrated that “infectious hepatitis,” or hepatitis A, could be differentiated from “serum hepatitis,” or hepatitis B. He also characterized the incubation period and the clinical and epidemiologic features of these two entities. Furthermore, Krugman’s work laid the groundwork for the development of the first vaccine against hepatitis B.
Unfortunately, these studies on children with mental retardation were done before more stringent regulations governing clinical research were promulgated. In retrospect, most of these studies would not have been necessary had the technologic advances we now enjoy been available. Also unfortunate was that these studies were judged in the climate of the 1960s, when the wrath of the radicals of the left was approaching that of the right from the McCarthy era a decade earlier. I had worked for Saul Krugman for 11 years, and I can attest to the fact that he was respected and loved by his colleagues and was not a malicious person.
At the time of these experiments, none of the agents that caused hepatitis had been propagated in the laboratory. The subsequent growth in tissue culture facilitated the development of diagnostic tests and a vaccine.
The early field trials with the vaccines demonstrated that they were remarkably effective, between 96% and 100%. There now are two products, which are given in a two-dose series at intervals of at least six months.
Although a preference is expressed for staying with the same vaccine for both doses, they are interchangeable. In 1995 and 1996, when these vaccines were licensed, they were recommended for children “in communities with the highest disease rates” and for individuals at increased risk (eg, travelers to endemic areas and those with chronic liver disease).
In 1999, the recommendations to immunize children starting at age 2 years in states that had a high rate of hepatitis A were remarkably successful. The rates of hepatitis in these states fell below those of states considered to have low incidence, and the rates of disease in adults – who were not routinely immunized – also fell.
The total number of cases in the United States has been reduced by 72%.
New recommendations are for universal immunization of all children starting at 12 months of age. States that had programs in place previously should continue those programs, and catch-up programs in states just starting a universal immunization program “can be considered.”
Those in high-risk groups should be immunized. It is well to remember that 50% of the travel-related cases in the United States occur in children.
As noted, there are two licensed vaccines for the pediatric age group. The pediatric preparations, which are licensed for those aged 1 to 18 years, should not be confused with the adult preparations, which contain considerable more antigen and are administered in twice the volume.
Twinrix (GlaxoSmithKline), which is a combined hepatitis A and B vaccine, is licensed for those aged older than 19 years. The FDA has recently approved an accelerated schedule for this vaccine for travelers, which calls for doses at 0, 7, 21 to 30 days and at 12 months. The vaccines must be well shaken before administration and will appear cloudy.
The pediatric preparations are Vaqta (Merck) and Havrix (GlaxoSmithKline). They are given in a volume of 0.5 mL intramuscularly in a two-dose series. The second dose is given at least six months after the first; Havrix is approved for administration six to 12 months later, and Vaqta is approved for six to 18 months after the first dose. Although the units in which the antigens are expressed differ, the efficacy is the same. They can be administered with other vaccines, and protection appears to be durable.
Dr. Brunell, as many of you know, is an accomplished academic pediatrician and editor of Infectious Disease News’ sister publication, Infectious Diseases in Children. The recommendation for universal childhood immunization with hepatitis A vaccine is following more or less the same schedule as that for universal infant immunization with hepatitis B vaccine, and using more or less the same rationale. Many predicted this would eventually happen when the vaccine was first introduced, although I thought it would take closer to two decades than just a little more than one decade.
I am taking this opportunity to comment further on a giant of pediatric research, Dr. Saul Krugman, and his landmark studies at Willowbrook State School. I had the opportunity to become well-acquainted with Dr. Krugman through IDSA governance activities. By the ethical standards of the time, the Willowbrook studies were judged to be completely ethical, and they opened the door to an understanding of the two major types of viral hepatitis that were believed to exist, bloodborne and foodborne, each with different incubation periods and clinical characteristics.
Later on in the 1960s and 1970s, of course, the ethical standards in clinical research, especially that involving mentally retarded participants, changed dramatically. Sadly, Krugman’s studies were singled out by critics as exactly the kind of excesses that needed to be curbed. His research was placed by some in the same category as the most egregious examples of unethical research in the United States, eg, the Tuskegee syphilis studies. This was, and is, a grave injustice to the memory of a respected, thoughtful, and caring pediatric investigator.
– Theodore C. Eickhoff, MD
Chief Medical Editor
For more information:
- Philip A. Brunell, MD, is a Special Volunteer at the National Institutes for Allergy and Infectious Disease at the NIH and Professor Emeritus at the University of California, Los Angeles. He is also a Member of the Infectious Disease News Editorial Advisory Board.
- AAP Committee on Infectious Diseases. Hepatitis A vaccine recommendations. Pediatrics. 2007;120:189-199.
- Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the ACIP. MMWR. 2006;55:1-23.