Control of Hepatitis B: To Be or Not To Be?

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of Medical School Pediatric Department Chairmen (AMSPDC) needs to begin to work on this issue with their colleagues in the basic sciences. Identification of critical basic science concepts that relate to the prob-lems of infants and children should be identified and mechanisms developed for bringing these concepts into our teaching rounds. One of us (F.D.B.) has found it possible to have a basic scientist conduct “co-rounds” once a week on selected patients, so that the knowledge of the basic scientist can be shared with the clinical team. Each of us has the freedom to act autonomously within our own academic institutions to instill this important philosophy into the learning experience of our students and housestaff.

Similarly, in regard to clinical epidemiology, behav-ioral sciences, and the information sciences, both AMSPDC and each of us involved in the education of medical students can take advantage of the enor-mous amount of new and important knowledge and skills in these areas and find ways to incorporate them into our clinical teaching experience. As the

Ambulatory Pediatric Association accomplished in

their document,

Educational

Guidelines

for Training

in

General/Ambulatory Pediatrics, specific objectives and

teaching methodologies in this arena can first be defined and then implemented to enhance this ele-ment of our teaching programs for both medical students and residents.2 We believe that a national effort by one of our national organizations to produce specific material for all our educational programs (such as curricula, videotapes, and computer

pro-grams) might be more efficient than each school

independently reinventing the wheel. Coordination between AMSPDC, the American Pediatric Society, the Ambulatory Pediatric Association, and the Amer-ican Academy of Pediatrics might be the most effi-cient way to proceed.

In the area of evaluation, the time has come for the new leadership of the American Board of Pediatrics to use its outstanding technical staff to become in-volved in the problems of undergraduate medical education and provide assistance to medical schools in meeting the challenge of The Robert Wood Johnson Foundation Commission to improve internal evalua-tion systems. The creation of the new computerized approach to recertification will have enormous impli-cations and value to the pediatrician as an evaluator

of the undergraduate student’s competency.

Al-though it was eventually dropped, we strongly sup-ported a preliminary position of the commission3 to do away with Part I of the United States Medical Licensing Examination and integrate the sciences basic to the practice of medicine into one single ex-amination at the end of medical school. This rational,

but politically volatile, recommendation seems

appro-priate as a means for motivating faculties to integrate

science throughout the curriculum and to eliminate a barrier to innovation and change in medical educa-tion.

Finally, as major participants and leaders in the development of educational programs in medical school, pediatricians have to recognize the value of an institutional approach to planning, implementing, and monitoring the quality of the program of

educa-lion leading to the MD degree. Fighting for

depart-mental time and autonomy at the expense of high-quality integrated educational programs to produce competent physicians is not rational. We believe a central authority needs to carry out the functions described.

Pediatricians who are leaders in academic medicine need to have the courage to facilitate this evolution

of the organization of medical school educational

programs if we are to develop the highest caliber

physicians for the 21 century.

ROBERT J. HACCERTY, MD W.T. Grant Foundation

New York, NY

Dept of Pediatrics Cornell Medical College New York, NY

FREDRIc D. Btmc, MD Dept of Pediatrics University of Pennsylvania

School of Medicine

Philadelphia, PA

REFERENCES

1 The Robert Wood Johnson Foundation Commission on Medical Educa-tion: The Sciences of Medical Practice. Medical Education in Transition.

Princeton, NJ: The Robert Woodjohnson Foundation: 1992

2. Educational Guidelinesfor Training in General/Ambulatory Pediatrics. Am-bulatory Pediatric Association; 1984

3. The Robert Wood Johnson Foundation Commission on Medical Educa-tion: The Sciences of Medical Practice. Environment for Learning: An Interim Report. Princeton, NJ: The Robert Wood Johnson Foundation; 1991

Control

of Hepatitis

B: To Be or Not

To Be?

ABBREVIATIONS. AAP, American Academy of Pediatrics; HBV,

hepatitis B virus; HBsAg, hepatitis B surface antigen.

The needs of children should not be made to wait.

-John F. Kennedy, 1963 The recent recommendations of the American Academy of Pediatrics (AAP) Committee on Infec-tious Diseases and the Immunization Practices Advi-sory Committee of the Centers for Disease Control to immunize all infants against hepatitis B virus (HBV)

infection have engendered concerns and questions

which should not eclipse the import and intent of these recommendations.”2 Behind these statements

lay much deliberation and expertise drawn from those

in pediatrics, medicine, infectious diseases, and public health. The undeniable conclusions of both commit-tees are that control of HBV infection and its

conse-quences (1) is necessary, (2) requires a new approach,

and (3) must include universal infant immunization and should include immunization of adolescents

whenever resources permit.

Received for publication Apr 29, 1992; accepted Apr 29, 1992.

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Commentaries 275 The consternations of pediatricians and others

car-ing for children center on the need and exigency for such sweeping recommendations, the costs, means of implementation, and schedules. By answering the

following commonly asked questions, we hope to

explain better the gestation of these recommenda-lions.

Why initiate these recommendations now, considering

current financial constraints and the recent introduction of other new vaccines?

Hepatitis Bvirus infection is currently a major cause of morbidity and mortality in the United States, al-though we’ve had an effective vaccine for 10 years.3 In 1990 the incidence of HBV infection was greater than that in the years just prior to licensure of the vaccine. An estimated 200 000 to 300 000 acute HBV infections occur each year, and an additional 1 million Americans are chronic carriers.3’4 Although many of the acute infections are mild and unrecognized, the long-term complications result in more than 5000 deaths from chronic liver disease each year. Despite the magnitude of this problem, the impact of HBV infection on our health care system is difficult for most of us to comprehend. These figures, however,

may be compared with those for other diseases we

currently prevent by immunization (Table).5

The previously recommended strategy for control of HBV infection, which focused on identification and immunization of high-risk individuals, clearly has not succeeded. High-risk behavior is not easily defined or detected, and those most likely to be in jeopardy may be those least likely to receive preventive health care. Indeed, no risk factor is identified in 30% to 40% of the cases of acute HBV infection.3’4 All children, there-fore, must be protected before such risks, known and unknown, are encountered when they are teenagers or adults. Furthermore, the current and ongoing hu-man and financial costs of HBV infection and its chronic consequences emphasize the need to offer protection against this disease now. For every year we delay implementing these policies, up to 5000 people may succumb from the complications of HBV disease.

I do not see hepatitis B infection in my pediatric

practice and live in a low-risk area; is immunization of

all infants really necessary in my practice?

Hepatitis B virus infection is almost always asymp-tomatic in infancy and in most children. These asymp-tomatic infections in childhood, nevertheless, presage the highest rate of sequelae and death 20 or more years later. Even an infant whose mother is hepatitis

B surface antigen (HB5Ag)-negative has a 5% chance

of acquiring HBV infection during his or her lifetime.5 Although rates vary in different locales and popula-lions, by 25 to 34 years of age 3.3% to 25% of those in the United States have had HBV infection, and the younger the infection is acquired the greater the like-lihood of the individual’s becoming chronically in-fected with HBV. The incidence and the rate of se-quelae of HBV infection generally are not appreciated but are as great or greater than those from other infections for which we currently immunize. We are notably poor as soothsayers in predicting which chil-then will be at high risk by future behavior, environ-ment, or moving to a new locale. In 60% of adolescent cases the source is unknown.4 Pediatricians, therefore, must initiate an insurance policy for their young patients which matures in adulthood.

Why should we universally immunize infants rather than adolescents, since adolescents are at maximal risk?

The AAP recommends both universal infant im-munization and adolescent immunization whenever feasible. The AAP recognizes that in areas where resources are limited, universal infant immunization should be given priority. The major impact of univer-sal infant immunization alone will not be realized for 20 or more years. Universal vaccination of both in-fants and adolescents would reduce significantly the time to control of HBV disease and the interim health care costs.

Universal immunization initiated at adolescence was also considered by the Commiftee, but achieving adequate coverage and compliance was thought to be problematic. Although the Academy is promoting means of providing routine medical care for adoles-cents, the current feasibility of capturing all

adoles-TABLE. Comparison of Number of Current Cases of Hepatitis B Infection to

Vaccine-Preventable Diseases of Children in Years Before Vaccines’ Routine Use5

Reported Cases of

Year Cases/ No. of No. of

100 000 Cases Deaths

Hepatitis B 1989

Acute 54.00 132700 5820”

(acute and

chronic)

Haemophilus influenzae type b

Invasivedisease 1986 5.40 13014 531

Meningitis 3.60 8676 354

Poliomyelitis 1954

All 35.00 56784

Paralytic 11.00 18308

Measles 1964 240 458083 380

Rubella 1970 29.00 57686

Congenital rubella 1970 0.04 77

SThis includes an estimated 320 deaths from acute hepatitis B cases and 5500 from chronic hepatitis

B infections.

at Viet Nam:AAP Sponsored on September 1, 2020 www.aappublications.org/news

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cents for three doses of vaccine over 6 months is low, and the least accessible adolescents may be those most at risk.

It is important to remember that younger children also need protection against HBV infection. Sixteen percent of acute HBV infections in this country are acquired during infancy through adolescence but ac-count for 42% of the chronic disease seen in adults.4

One fourth of these infections acquired before

adult-hood are in children between the ages of 1 and 10 years and cause about 30% of the chronic infections of adults.

How long will protection from the vaccine last? Will boosters be necessary for those immunized during infancy?

Since vaccines have been available only for 10 years, the long-term duration of protection is not

known, whether immunization is given during

in-fancy or adolescence. However, follow-up studies of healthy adults and infants and of infants of chronic carrier mothers have indicated that immunologic memory with the plasma-derived vaccine persists for at least 10 years in normal adults and infants and at least 5 years in infants born to chronic carrier moth-ers.#{176}Also, the rate of antibody decline tends to be lower in children than in adults. Even in individuals in whom antibody levels have declined below the detectable level, the vaccine has conferred protection against chronic HBV infection. Booster doses, there-fore, are not recommended currently for normal chil-dren, nor is routine testing of antibody levels after vaccination. The possible need for booster doses after 10 or more years will be assessed as more information becomes available. Even if a booster dose should become necessary, administration to adolescents of a single dose of vaccine is likely to be more feasible than initiation of a three-dose series.

Why does the AAP statement recommend starting

immunization at birth when the Immunization

Practices Advisory Committee recommends as equally acceptable a schedule starting at birth or at 1 to 2 months?

Both committees wished to allow some degree of

schedule flexibifity for HBsAg-negative infants to en-hance the feasibility and acceptability of the three-dose series. The AAP Committee felt that initiation of immunization of newborns before hospital dis-charge would achieve better coverage rates as well as hospital participation in providing preventive serv-ices. In addition, the need of administering more than two injections at a single visit may be diminished by giving the first immunization before hospital dis-charge. This schedule, however, may be molded to fit best the practices of individual physicians. Some

who routinely see newborns before 1 to 2 months of

age may wish to initiate hepatitis B immunization at this first visit. When considering how best to integrate hepatitis B vaccine into the routine of their practice, physicians should understand first that hepatitis B vaccine has proved highly effective and immunogenic in a variety of schedules and may be administered with other vaccines. Second, the first two doses

should be at least 1 month apart, but increasing the

interval beyond 1 month adds no immunogenic

ad-vantage. Third, the second and third doses should be separated by a minimum of 2 months, and an interval of 4 months or more is optimal. The goal is complete coverage, and the potential pliancy of the recom-mended schedules is a means for the individual phy-sician best to achieve this.

When should premature infants be immunized?

Premature infants generally should receive hepati-tis B vaccine at the same chronologic age as recom-mended for term infants. Immunization of premature infants with other vaccines generally has resulted in an adequate immune response and no increase in side effects. Hepatitis B immunization of premature in-fants born to HBsAg-positive mothers has been effec-live and should be equally effective in premature infants of noncarrier mothers. In neonatal intensive care units the more severely ill and very low birth weight infants born to HBsAg-negative mothers should have immunization delayed, as dictated by good clinical judgment.

Should young children who missed hepatitis B immunization during infancy be immunized?

Routine “catch-up’ immunization of children with-out risk factors currently is not recommended because of feasibility and the desire to target resources to the universal immunization of infants and adolescents. Such children, in accordance with the AAP recom-mendations, would be immunized at adolescence. However, if resources are available, children between infancy and adolescence may be immunized now or

as they enter adolescence. Since a lower dose of

vaccine is used for children younger than 1 1 years of age, the resulting lower cost of the three-dose series may make some physicians prefer immunizing their patients before they reach their 1 ith birthday.

Should informed consent be obtained for hepatitis B immunization?

For hepatitis B vaccine a signed consent form is required as for other vaccines if the vaccine is ob-tamed through public-sector funds. Informed con-sent, however, is advisable for all vaccines, and a brochure containing information on the potential side effects and benefits of hepatitis B vaccine has been prepared by the Centers for Disease Control and should be available within weeks. The AAP also has available a brochure and fact sheet for parents on

hepatitis B vaccine.

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Commentaries 277 Is the cost of hepatitis B vaccine and its administration

justified?

Hepatitis B vaccine can be less expensive than most of the other vaccines routinely administered to in-fants. A single dose obtained from a multidose vial for infants born to HBsAg-negative mothers has a current retail cost of about $9 to $12. The benefits and costs of hepatitis B immunization compared to

the costs of HBV disease has been studied by the

Centers for Disease Control.2 Prevention of a single case of chronic HBV infection, cirrhosis, or hepato-cellular carcinoma provides significant benefits in health care costs and is as or more cost-effective than the prevention of a case of the other diseases for which we currently vaccinate, such as measles and

Haemophilus influenzae type b infection.

What can be done to decrease the cost of hepatitis B

immunization?

Vaccine purchased in multidose vials is less expen-sive, and once opened the remaining vaccine need not be discarded until the expiration date. Although this contrasts with the practice of some facilities, the vaccine remaining in an open vial is stable and may be used for subsequent immunizations until the ex-piration date.

Vaccine purchased through the public sector is less expensive than that purchased by private physicians. In some states private physicians are able to purchase vaccine at public costs through their state and local health facilities. Bulk purchases by medical societies and other medical groups may also result in dimin-ished cost. The AAP has designed a bill called the “Childhood Vaccine Act’ which would authorize all 50 states to purchase vaccines at federal contract prices and distribute them free to physicians. The proposed bill would prohibit physicians from charg-ing for the vaccine but would allow an administration charge, providing the patient is able to pay. Such a plan would permit all children to benefit from the reduced cost whether they receive their vaccines in public clinics or private offices.

The costs of vaccines in general may also be re-duced if the excise tax required by the National Child-hood Vaccine Injury Act is lessened. This may be possible as the cost of litigation cases is expected to

diminish. In addition, combination vaccines are being developed which may reduce the cost and increase

the acceptability of the vaccine.

Lastly, medical groups and health and government officials need to bring organized pressure on third-party payers to cover the cost of recommended pre-ventive measures such as childhood immunizations. Current immunization costs are certain to conserve the coming coffers of health care.

Caour BREESE HALL, MD

Dept of Pediatrics and Medicine University of Rochester School

of Medicine and Dentistry Rochester, NY

NEAL A. HALSEY, MD

Dept of International Health Johns Hopkins University School

of Hygiene and Public Health Baltimore, MD

REFERENCES

1. American Academy of Pediatrics, Commiftee on Infectious Diseases. Universal hepatitis B immunization. American Academy of Pediatrics News. February 1992:13-15

2. 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 Commiftee (ACIP). MMWR. 1991;40(RR-13):1-25

3. Alter MJ, Hadler SC, H-Margolis HS, et al. The changing epidemiology

of hepatitis Bin the United States: need for alternative vaccination

strategies.JAMA. 1990;263:1218-1222

4. Margolis HS, Alter MJ, Hadler SC. Hepatitis B:evolving epidemiology and implications for controL Semin Liver Dis. 1991;11:84-92

5. West DJ, Margolis HS. Prevention of hepatitis B virus infection in the

United States: pediatric perspective. Pediatr Infect Dis I. In press

6. Hadler SC, Francis DP, Maynard JE, et al. Long-term immunogenidty and efficacy of hepatitis B vaccine in homosexual men. N Engl I Med. 1986;315:209-214

7. Wainwright RB, McMahon BJ, Bulkow LR, et al. Duration of

immuno-genicity and efficacyofhepatitis B vaccine in a Yupik Eskimo population.

JAMA. 1989;261:2362-2366

8. Lo K-Y, Lee S-D, Tsai Y-T, et al. Long-term immunogenicity and efficacy

of hepatitis B vaccine in infants born to HBeAg-positive HBsAg-carrier

mothers. Hepatology. 1988;8:1647-1650

9. Hwang L-Y, Lee C-Y, Beasley PP. Five year follow-up of HBV

vaccina-tion with plasma-derived vaccine in neonates: evaluation of

immuno-genicity and efficacy against perinatal transmission. In: Hollinger PB, Lemon SM, Margolis HS, eds. Viral Hepatitis and Liver Diseases. Balti-more, MD: Williams & Wilkins; 1991:759-761

10. Stevens CE, Toy PT, Taylor PE, et al. Prospective for control of hepatitis

B virus infection: implications of childhood vaccination and long-term

protection. IPediatr. In press

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1992;90;274

Pediatrics

CAROLINE BREESE HALL and NEAL A. HALSEY