Letter/hepB/Dr.Waisbren

[Guest guest]

JAMA Letters - April 9, 1997

Perspectives on Hepatitis B Vaccination

To the Editor.--I read with interest and appreciation the recent Landmark

Perspective and the discussion regarding the hepatitis B vaccine by Dr

.[1] However, I find it somewhat disturbing that did not

mention the potential untoward results of viral vaccines, or those already

reported as presumably being due to the hepatitis B vaccine.

must be aware of the untoward results from the vaccine, not only

because of lawsuits his company has settled in which demyelinating disease

was involved, but also because of reports of adverse reactions linked to

vaccine use in the medical literature,[2-4] including multiple sclerosis-like

diseases, Guillain-Barre syndrome, optic neuritis, and transverse myelitis.

Despite these reports, the strategy of universal vaccination in the United

States has been promoted widely by Merck, the Centers for Disease Control and

Prevention, and others.[5,6] Should not the parents of infants be made aware

of the potential and reported dangers of the hepatitis B vaccine before they

are asked to give permission for the vaccination? After all, infants in many

areas of the United States are not at risk for infection with the hepatitis B

virus.

Furthermore, the much heralded strategy of eradicating hepatitis B disease by

universal vaccination is just that--a strategy rather than a proven

measure.[5,6] Should individuals who are at low risk for this disease forego

this vaccination until the strategy is proven successful in areas of the

country that have already mandated it, such as New York state?

In no way do these remarks denigrate the use of the present vaccine in

high-risk populations in both the United States and worldwide.

Burton A. Waisbren, Sr, MD

Milwaukee, Wis

References

1. RG Jr. The heritage of hepatitis B vaccine. JAMA.

1996;276:1796-1798.

2. Herroelen L, de Keyser J, Ebinger G. Central nervous system demyelination

after immunization with recombinant hepatitis B vaccine. Lancet.

1991;338:1174-1175.

3. Nadler JP. Multiple sclerosis and hepatitis B vaccination. Clin Infect

Dis. 1993;17:928-929.

4. Kaplanski G, Retornaz F, Durand J. Central nervous system demyelinization

after vaccination against hepatitis B and HLA haplotype. J Neurol Neurosurg

Psychiatry. 1995;25:758-759.

5. Centers for Disease Control. Hepatitis B virus, a comprehensive strategy

for eliminating hepatitus B virus transmission in the United States through

universal childhood vaccination: recommendations of the Immunization

Practices Advisory Committee (ACIP). MMWR CDC Surveill Summ.

1991;40(RR-13):1-25.

6. West DJ, Calandra GB, Hesley TM, Ioli V, WJ. Control of hepatitis B

through routine immunization of infants: the need for flexible schedules and

new combination vaccine formulations. Vaccine. 1993;11:S21-S27.

(JAMA. 1997;277:1124)

------------------------------------------------------------------------------

--

In Reply.--The Landmark Perspective article was written in response to a

request from the editors of JAMA to provide a historical perspective on the

Landmark Article by Buynak et al.[ 1] The purpose of the Perspective was to

trace the development of hepatitis B vaccines and to show how they can be

used to eliminate and eventually eradicate hepatitis B infection, and with it

many cases of cirrhosis and cancer of the liver, from the human population.

My article was not intended to provide complete information about hepatitis B

vaccines.

Dr Waisbren must know that lawsuits and isolated case reports of adverse

events occurring in temporal association with vaccination do not prove a

causal relationship. In fact, the Vaccine Safety Committee of the Institute

of Medicine examined 4 types of evidence to determine if a causal association

exists between the administration of certain types of vaccines and selected

adverse experiences. They considered biologic plausibility; case reports,

case series, and uncontrolled observational studies; controlled observational

studies; and controlled clinical trials. The committee concluded that the

evidence is inadequate to accept or reject a causal relation between

hepatitis B vaccine and Guillain-Barre syndrome, optic neuritis, multiple

sclerosis, or transverse myelitis.[2]

Furthermore, I would like to point out that the comprehensive strategy for

eliminating hepatitis B virus transmission through universal childhood

vaccination is a recommendation of the Advisory Committee on Immunization

Practices of the US Public Health Service.[3] This recommendation is also

endorsed by the American Academy of Pediatrics.[ 4] This strategy was

developed because the previous strategy of vaccinating persons in the major

risk groups has had limited success in preventing the transmission of

hepatitis B. This strategy recognizes that the reduction in hepatitis B

disease and hepatitis B-associated liver disease from universal infant

vaccination may not become apparent for a number of years.

I agree with Waisbren that parents should be advised by physicians of the

risks and the benefits for all vaccines that their children receive; however,

infrequent reports of adverse events with no demonstrated causal relationship

to the vaccine hardly justify a retreat from the universal childhood

hepatitis B vaccination strategy that has been so widely accepted. Public

health policy must be based on known risks and benefits, not on theoretical

possibilities.

R. Gordon , Jr, MD

Merck & Co Inc

Whitehouse Station, NJ

References

1. Buynak EB, Roehm RR, Tytell AA, Bertland AU II, Lampson GP, Hilleman MR.

Vaccine against human hepatitis B. JAMA. 1976;235:2832-2834.

2. Institute of Medicine, Vaccine Safety Committee. Adverse Events Associated

With Childhood Vaccines: Evidence Bearing on Causality. Washington, DC:

National Academy Press; 1994.

3. Centers for Disease Control. Hepatitis B virus, a comprehensive strategy

for eliminating hepatitis B virus transmission in the United States through

universal childhood vaccination: recommendations of the Immunization

Practices Advisory Committee (ACIP). MMWR CDC Surveill Summ.

1991;40(RR-13):1-25.

4. American Academy of Pediatrics, Committee on Infectious Diseases. Policy

statement: universal hepatitis B immunizations. Pediatrics. 1992;89:795-800.

(JAMA. 1997;277:1124)

------------------------------------------------------------------------------

--

In Reply.--Numerous studies indicate that hepatitis B vaccines have an

excellent safety profile and that adverse neurologic events following

hepatitis B vaccination are exceedingly rare.[ 1-4] Population-based studies

following large-scale hepatitis B immunization programs for infants in

Alaska, New Zealand, and Taiwan have not established an association between

hepatitis B vaccination and the occurrence of serious neurologic adverse

events.[3-4]

In the United States, data on adverse events associated with vaccination are

available through the national Vaccine Adverse Event Reporting System

(VAERS), a passive surveillance system. In 1993, the Institute of Medicine

(IOM) reviewed case reports in the medical literature and those reported to

VAERS between November 1990 through July 1992 and concluded that the evidence

to date was insufficient to assess a causal link between any serious

neurologic event and hepatitis B vaccination.[1] A more recent review by the

Food and Drug Administration of case reports in VAERS for 1991 through 1994

concluded that there have been no unexpected adverse events reported to occur

in neonates and infants given hepatitis B vaccine, despite the use of at

least 12 million doses of vaccine in these age groups.[2] The adverse events

cited by Dr Waisbren that he concludes are caused by hepatitis B vaccination

(eg, multiple sclerosis, Guillain-Barre syndrome) (1) are rare; (2) occur in

the absence of hepatitis B vaccinations; and (3) have their peak incidences

in the older age groups recommended to receive hepatitis B vaccinations prior

to the universal infant hepatitis B vaccination policy. Establishing or

disproving a causal relation between hepatitis B vaccination and these

adverse events is methodologically and logistically formidable. The evidence

to date suggests that even if there is a causal relation between hepatitis B

vaccination and adverse neurologic events, the occurrence is exceedingly rare

and is far outweighed by the benefits of vaccination.

In contrast to possible rare adverse events, infection with hepatitis B virus

(HBV) was a relatively common event prior to the implementation of hepatitis

B vaccination programs. During the late 1980s, between 200,000 and 300,000

persons were infected each year and the lifetime risk of HBV infection was

5%. It is estimated that each year between 5000 and 6000 persons die from

HBV-related chronic liver disease in the United States.[ 5] Recommendations

to vaccinate all infants have been made by the American Academy of

Pediatrics, the American Academy of Family Physicians, and the Advisory

Committee on Immunization Practices.

We disagree with Waisbren that the current plan to eliminate HBV transmission

in the United States is not a " proven strategy. " In fact, within the same

issue of JAMA as the article by Dr , there is a report on the

remarkable success of routine infant immunization in eliminating HBV

transmission in Taiwan and the Pacific.[ 6] There are numerous other reports

to support the conclusion that the current strategy to eliminate HBV

transmission in the United States is a well-conceived and reasonable public

health policy.

Mahoney, MD

C. Lloyd, DVM, MSPH

L. Euler, DrPH

Centers for Disease Control and Prevention

Atlanta, Ga

References

1. Stratton KR, Howe CJ, ston RB, eds. Adverse Events Associated With

Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: National

Academy Press; 1994.

2. Niu MT, DM, Ellenberg S. Recombinant hepatitis B vaccination of

neonates and infants: emerging safety data from the Vaccine Adverse Event

Reporting System. Pediatr Infect Dis J. 1996;15:71-76.

3. Centers for Disease Control and Prevention. Update, vaccine side effects,

adverse events, contraindications, and precautions: recommendations of the

Advisory Committee on Immunization Practices. MMWR CDC Survell Summ.

1996;45(RR-12):7-8.

4. McMahon BJ, Helminiak C, Wainwright RB, Bulkow L, Trimble BA. Frequency of

adverse reactions to hepatitis B vaccine in 43,618 persons. Am J Med.

1992;92:254-256.

5. Centers for Disease Control. Hepatitis B virus: a comprehensive strategy

for elimination of transmission through universal childhood vaccination:

recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR

Morb Mortal Wkly Rep. 1991;40(RR-13):1-20.

6. Durand AM, Sabino H Jr, Mahoney F. Success of mass vaccination of infants

against hepatitis B. JAMA. 1996;276;1802-1803.

(JAMA. 1997;277:1124-1125)