UNIVERSAL NEONATAL HEPATITIS B IMMUNIZATION: CLASHING INTERESTS IN PUBLIC HEALTH CARE DELIVERY

The CDC Recommendation.

In November 1991, the Immunization Practices Advisory Committee of the Centers for Disease Control and Prevention (CDC) issued a recommendation for the universal immunization of newborns and infants against Hepatitis B virus (HBV)1, with similar recommendations following in 1992 by the American Academy of Pediatrics (AAP)2 and the American Academy of Family Physicians (AAFP)3.

I remember that when I, a Medical Technologist, first heard of this recommendation I was intrigued by the apparent conflict of vaccinating newborns to prevent an illness that primarily strikes adults, particularly given the question of long-term efficacy associated with infant immunization. What are the arguments for recommending universal immunization, and how have pediatricians and family physicians followed through on this recommendation?

Targeting Neonates.

HBV infection has major consequences at the level of both the individual patient and public health. From 1979 to 1989, the incidence of acute HBV hepatitis increased by 37%, and 200,000 to 300,000 new infections occurred annually from 1980 to 1991. More than 90% of patients with acute infection recover completely, but others (5 to 10% of adults and 80 to 90% of HBV-infected infants) appear to mount an inadequate immune response and become chronic carriers in whom Hepatitis B surface antigen (HBsAg) persists in the bloodstream indefinitely and anti-HBs antibody is not produced. Chronically-infected patients, of whom there are approximately one million in this country, are at risk of chronic liver disease and primary hepatocellular carcinoma (100 times more likely to develop in chronic carriers than in non-infected persons), with 4,000 to 5,000 dying each year.

What’s more, chronic HBV-infected patients are potentially infectious to others for the duration of their lives. Perinatal transmission is very efficient (up to 85% in selected populations). Besides blood, the virus is also found in body fluids including semen and saliva. HBV is often thought of as a blood-borne pathogen with routes of infection similar to those of HIV, but HBV is considerably more contagious than HIV is. Furthermore, it should be emphasized that as many as 30 to 40% of acute infections may occur in individuals without identifiable risk factors1.

Since the first HBV vaccine was made available, the CDC has recommended immunization of individuals at high risk (including male homosexuals, intravenous drug users, individuals with multiple sex partners, and renal dialysis patients) and universal screening of pregnant women; however, incidence of infection has continued to mount. This limited success of the earliest HBV immunization strategy resulted from such factors as the unfeasibility of vaccinating persons engaged in high-risk behaviors, lifestyles, or occupations prior to infection, the relatively high rate of infection in the absence of identifiable risk factors, and lingering public mistrust over the failed swine flu vaccine program of 1976 which left many inappropriately fearful of severe side effects resulting from vaccination. The vaccines sat unused on the shelves and the incidence of disease rose. Then, in 1991, the CDC issued its recommendation for a collateral program of universal infant immunization to supplement the continuing vaccination of certain adolescents and adults at risk.

Why the Controversy?

Perhaps the most reasoned criticism of the neonatal immunization program was published in 19934. Among the points raised:

·         The lifetime risk of HBV infection in the United States is probably less than 5%, and 60 to 70% of the disease occurs in high-risk populations. Also, the disease is uncommon in children, with only about 2,400 cases occurring annually before ten years of age, most of whom are high-risk infants who would be identified as such under a more selective program.

·         Insufficient evidence exists to conclude that newborn immunization will confer immunity in adulthood, when infection with HBV is most likely. Boosters later in life may well be required, but in part it was the desire to avoid targeting older groups for vaccination that prompted the creation of the newborn immunization program in the first place.

·         Assuming the three-dose schedule costs $50 and is 90% successful at preventing the disease and a person has a 5% lifetime risk of acquiring the disease, the universal immunization program would cost $1,100 per case of disease prevented. With 4 million infants born annually, the program will cost $200 million a year, and since the majority of the program’s effect will not be seen for 15 to 20 years, the nation will have spent $3 to $4 billion before a significant impact on incidence is seen. A program emphasizing high-risk newborns or mandatory immunization of teenagers (with mature immune systems) would cost less and yield a more immediately apparent impact on incidence.

Nevertheless, the recommendation for universal neonatal immunization is in place. How are physicians responding?

Perceptions of Practitioners.

Results of a cross-sectional survey involving 140 term nurseries, 152 NICUs, and 157 pediatricians published in May 1995 revealed that the principal reasons for not following the CDC recommendation included cost (primary reason) and a preference to allow the primary-care physician to initiate the series, as well as parents opting against vaccination5. Less than half of term nurseries routinely vaccinated before discharge, while 59% of NICUs did so and 85% of pediatricians initiated the series by two months of age.

A survey of 526 California pediatricians published two months later determined that 82% universally immunized infants, especially if they agreed with the recommendation, practiced in a health maintenance organization (HMO) vs. private group practice, or practiced in settings with predominantly low-income, at-risk patients6. Those who disagreed with the guidelines (more than one-fifth of those surveyed) cited doubts especially about long-term efficacy, as well as concern about cost and excessive numbers of childhood immunizations. It is instructive to note that HMO policies may compel physicians who object to the program to immunize neonates, contributing to changing dynamics in public health and its delivery of care.

Six months later results of a survey comparing the attitudes of 679 family practice physicians and 742 pediatricians were published7. More pediatricians were in agreement with the recommendation (83% vs. 57%) and were practicing it (90% vs. 64%), although importantly HMO policy once again resulted in more physicians in both specialties adopting the recommendation than agreed with it. Doubt about long-term efficacy remained a strong predictor of disagreeing with or not adopting the recommendation, as did parental resistance. Seventeen percent of pediatricians disagreed with the guideline, as did a full 43% of family physicians, suggesting that many physicians remain unconvinced that the program is in the best interest of their patients.

Individual vs. Public Health Implications.

If physician attitudes are a reliable outcome measure, then the case for universal neonatal Hepatitis B immunization has not been sufficiently made. In part this is because of immunological concerns (e.g., the question of long-term efficacy), as well as financial issues and the total number of newborn immunizations for all infectious disease agents. But also as is commonly the case, physicians appear to be focusing on the cost/benefit to individual patients to the exclusion of the public health, with many physicians still doubting that lifetime risk of disease acquisition for their individual patients justifies infant immunization. The appropriate balance between public health and individual patient concerns remains uncertain.

The fact that the universal neonatal immunization program from the beginning was intended to be only one component of the comprehensive strategy to combat HBV infection has, by and large, been forgotten in discussions of the merits and faults of newborn vaccination. In the context of the broader strategy, lower levels of efficacy might be more acceptable than would otherwise be the case, but this argument has not been enunciated clearly.

The ability of managed care organizations to influence the approach to public health delivery even in the presence of a nontrivial level of opposition by physicians is troubling, as is a report of more than a third (43%) of family physicians being in disagreement with a recommendation by the CDC for a national immunization program.

Unfortunately, many of the doubts held by physicians must remain unanswered for many years until today’s HBV-immunized children reach adulthood. In the meantime we can hope that the CDC and other groups will present physicians and parents with a more convincing rationale for the universal immunization of neonates against HBV.

About the author: Bob Bogle has previously worked as a clinical chemist and in histocompatibility testing. He is currently a clinical microbiologist at University Medical Center, Tucson, AZ. His e-mail address is aguldo@ix.netcom.com.

References.

1. Centers for Disease Control. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: recommendations of the Immunization Practices Advisory Committee (ACIP). Morbidity and Mortality Weekly Report 40:1-25. 1991.

2. Committee on Infectious Diseases, American Academy of Pediatrics. Universal Hepatitis B immunization. American Academy of Pediatrics News 8:13-22. 1992.

3. American Academy of Family Physicians. AAFP recommends Hepatitis B vaccinations for all infants. American Academy of Family Physicians Reporter 19:1. 1992.

4. Ganiats, TG, MT Bowersox, and LP Ralph. Universal neonatal Hepatitis B immunization – are we jumping on the bandwagon too early? The Journal of Family Practice 36(2):147-9. 1993.

5. Kim, SC, LN Sinai, R Casey, and JA Pinto-Martin. Universal Hepatitis B immunization. Pediatrics 95(5):764-6. 1995.

6. Wood, DL, P Rosenthal, and D Scarlata. California pediatricians’ knowledge of and response to recommendations for universal infant Hepatitis B immunization. Archives of Pediatric Adolescent Medicine 149:769-73. 1995.

7. Freed, GL, VA Freeman, SJ Clark, TR Konrad, and DE Pathman. Pediatrician and family physician agreement with and adoption of universal Hepatitis B immunization. The Journal of Family Practice 42(6):587-92. 1996.

HBV Vaccination and the AIDS Epidemic.

The story of how the original Hepatitis B vaccine was made possible largely from the contributions of the gay community in the late 1970s and early 1980s is recounted in the already classic eyewitness history of the early years of the AIDS epidemic, Randy Shilts’ And the Band Played On (St. Martin’s Press, 1987, Penguin Books, 1988). This early vaccine, manufactured at a cost of tens of millions of dollars from the plasma of chronically-infected persons, most of them altruistic gay men, is no longer produced in the United States.

To produce the recombinant vaccines now in use, a plasmid containing the gene for HBsAg is inserted into common bakers’ yeast, Saccharomyces cerevisiae. The yeast cells are lysed and the HBsAg is separated from other components in a series of biochemical and biophysical techniques. The vaccine thus obtained is packaged to contain 10 to 40 µg HBsAg protein/mL after adsorption to aluminum hydroxide (0.5 mg/mL). Thimerosal (1:20,000 concentration) is added as a preservative. Two recombinant vaccines are available: Recombivax HB and Engerix-B.

It was the enormous library of serum samples collected from a cohort of 6,875 gay men in San Francisco in the early HBV vaccine studies that later proved so useful in retrospectively tracking the progress of the AIDS epidemic in the years prior to its frightening emergence in 1981.