International Vaccination Newsletter Dec 1995

 Vaccinating newborns from HB-positive mothers within the first weeks of life has become common practice. Alarming messages about the aggressive evolution of Hepatitis-B in those children later in life seem to excuse the potential risks of such a procedure.

However, in order to take a decision one has to take into account the following questions:

1. What is the general risk of babies and infants to be infected by HBV?

2. What is the risk of infected babies to develop acute disease?

3. What’s the risk of infected babies to develop chronic disease?

4. What is the benefit of vaccination for babies born from HBV-carriers compared to other strategies?

5. If the option is to vaccinate, what time schedule is to be followed?

I. A study in Senegal (1) shows that 7% of children of healthy mothers (of which 79% were HBcAg + and 13.8% were HBsAg +) were HBsAg + at birth.

"Perinatal exposure to high levels of maternal HBV DNA is the most important determinant of infection outcome in the infant" (2) . Thus, the risk of the child cannot be determined without measuring the maternal HBV DNA. Any decision to vaccinate a child without this test being done is premature.

II. During in vitro fertilisation, 22 embryos were exposed to HBV in contaminated human serum present in the culture medium. All mothers experienced hepatitis B during the first trimester of pregnancy. No HBV DNA was found in serum or lymphocytes from the exposed 22 infants (3) , indicating that the risk of infection even in this high risk situation was limited.

III. Moradpour & Wands (4) state that approximately 5 to 10 percent of infected patients become long-term carriers of the virus. Since not every carrier develops disease, it must be obvious that the percentage of patients who become ill is lower than this 5-10%.

In one study (5) , only 3.2% of the children were still HB Ag positive at 6 months of age. Chronic carriership beyond that age was expected but not established. Half of the babies HBsAg-positive at birth had become negative by the age of 6 months.

Another study (6) detected no chronic carriers in babies born to anti-HBeAg positive mothers.

Moradpour et al (7) admit that host factors also determine the variable clinical outcome of HBV-infection. Therefore, we can reasonably assume that a lack of hereditary burdens, good nutrition and immunity-supportive medical care diminish the risks of chronic impairment.

The presence of the HLA allele DRB1*1302 indicates a far lesser susceptibility to chronic HBV infection, and therefore abolishes the need for vaccination.

IV. The answer to question 4. is determined by outweighing the pros and contras of both options.

High seroconversion rates (89%) are mentioned after vaccination (including booster doses), although the range can also be as low as 45% after 1 year, and diminish further to 38% after 5 years (8).

Babies born to HBV carrier mothers with high HBV DNA-levels are more likely not to respond to vaccination (9) . Yet, exactly these infants are most likely to be persistently infected (10) . The conclusion here is that vaccination is is least effective in those babies who theoretically need it most!

2) Serologic protection

At 5 years of age, 9% of vaccinated children still prove to be infected (11).

"Individuals who are carriers of HBV and who are immunised without testing can remain carriers and transmit infection" (12) . This applies to babies of carrier mothers, and indicates that vaccination does not solve their state of infection.

3) Clinical protection

Vaccination and eventually sero-conversion does not automatically mean clinical protection. One article even describes a fatal outcome in a vaccinated child (13).

The mechanism of an effective reaction to HBV-infection is described by Moradpour & Wands. They say that "these findings suggest that a prompt, vigorous, and broad-based cellular immune response results in clearance of the virus from the liver, whereas a qualitatively or quantitatively less efficient or restricted immune response may permit the persistence of the virus and the development of ongoing, immunologically mediated livercell injury."

The question thus is: does HBV vaccination provide such a ‘prompt, vigorous, and broad-based immune response’?

There are reasons to believe that this is not the case.

Repeatedly medical literature emphasised that the full course of three to four vaccinations is absolutely necessary to elicit clinical protection. This vaccination procedure takes several months, although the newborn, if infected, is likely to be so at birth or shortly after. He is challenged with the virus before full artificial immunity is established and therefore is more likely to develop a ‘qualitatively or quantitatively less efficient or restricted immune response’, with chronic infection as a result.

The main result targeted by vaccination, the production of antibodies (immun-globulines), is not significant for a healthy immune response, since it is the cellular immune response which appears to be crucial in eliminating the virus (cfr Moradpour & Wands). The virus may persist and replicate at low levels in the presence or absence of antibodies to hepatitis B surface antigen, hepatitis B core antigen and hepatitis B e antigen (14).

Experience with other vaccines has shown that even as to the production of antibodies, the quantitative results of vaccination are poor compared to natural infection.

4) Surplus benefit of vaccination to other strategies

As far as I have discovered no studies have been undertaken to compare the effect of perinatal vaccination to other health measures. Yet, the general health situation of the baby is perhaps even more important for the outcome of infection than is the case in adults.

B. The risk of vaccination

The set of risks of vaccination with HBV-vaccine was described in another publication, IVN 1/95.

C. The benefit of not vaccinating

Not vaccinating may have a number of advantages, such as

-avoiding the risks of vaccination (cfr summary article by me);

-avoiding the creation of a reservoir of carriers which may continue to spread the disease among individuals;

-to give the infant’s immune system the opportunity to develop natural immunity, which as a rule is more accurate and lasts longer than vaccine-induced immunity. Not immunising saves the reserves of the early, immature immune system for the challenge of natural infections.

It is a fact that passive immunisation (immune globulin treatment) protects the infant during five months after administration. Thus, the child can be protected during the first year of life (after a repetition of IG at six months of age), after which the risks are considerably lower.

A number of alternative therapies which effectively support natural immunity are widely available.

Vaccination may lead to the induction of escape mutants of HBV (15), which can then spread among a population with no immunity against the new strain at all. The pathogenic properties of such mutant strains cannot be forseen. They persist more easily within the liver cells, leading to chronic infection and all of it’s consequences:

cirrhosis, carcinoma.

Anti-HBs antibody levels produced by vaccination appear to decline in time. In that case there seems to be an increased risk of anti-HBc conversion indicative of subclinical infection with a potentially oncoqenic virus (16).

There is a certain risk that if a child at danger is not immunised, it may develop into a chronic carrier and eventually produce liver damage.

Vaccination itself, however, also may lead to liver damage. There are too little data available to accurately outweigh both risks.

V. The strategy of early vaccination is not generally adopted.

Pellizzer states: "Because maternal HBV transmission early in life appears to be of minor impact and children are mostly infected later in infancy, HBV vaccination at birth is not indicated..." (17)

Some sources proved that delayed vaccination schedules are not less effective than immunization beginning right after birth. A 1993 article (18) states that "late active immunization starting at 3 months of age appears to provide similar protective efficacy as active immunization starting at birth when combined with hepatitis B immune globulin at 0 and 3 months of age." Passively acquired antibodies at birth (immune globulines) remained present for about five months in most infants (19).

BOOSTER DOSES

Booster doses are given to assure sufficiently high antibody levels to obtain immunity, and to obtain longer lasting immunity. Several sources, however, underline that immunity has got little or nothing to do with antibody levels. A sufficient, tong lasting immunity can be present in the presence of antibody levels lower than 10 mlU/L. Immunity seems to be linked more to the cellular immunity than to antibody levels (20) . Tilzey continues: "The practice of whether or not to reinforce immunity is variable and based on dogma rather than scientific evidence."

Booster doses later than the regular schedules have no negative influence on the efficacy of the vaccination (21, 22).

Interrupted vaccination schemes can be completed later on without negative effects (23).

1. Medical data and opinions on the use of perinatal HBV vaccination vary widely. Perinatal vaccination can be postponed if immune globulines are used, without any increase in risk for developing pathology. Alternative strategies are conceivable.

2. The babies at highest risk of developing hepatitis respond least to the vaccine.

3. If a first child had an adverse reaction to vaccination, the risk of the next child also developing side-effects is considerably higher than it is with the average child.

1. Viral Immunol, 1993; 6/1:65-73

2. J infect dis, 1994; 170/6:1418-23

3. J Clin Microbiol, 1994; 32/4:1099-100

4. Moradpour, D.; Wands, J.R.; Understanding Hepatitis B Virus infection. NEJM, 1995; 332/16:1092-3

5. Viral Immunol, 1993; 6/1:65-73

6. J. Trop. Pediatr, 1992; 38/5:247-51

7. Moradpour, D.; Wands, J.R.; cfr supra

8. J infect dis, 1995; 171/1:54-60

9. J hepatol, 1994; 20/4:483-6

10. infect dis, 1994; 170/6:1418-23

11. Am J Dis Child, 1993; 147/12:1316-20

12. Burns, S.; Molyneau, P.; Acute hepatitis B infection after vaccination. Lancet, 1995; 345:261-3

13. Fatal fulminant hepatitis B in an infant despite appropriate prophylaxis. Rosh, JR.; et al; Arch Pediatr Adolesc Med, 1994; 148/

12:1349-51

14. Liang, T.J.; et at Hepatitis B virus infection in patients with idiopathic liver disease. Hepatology, 1991; 13:1044-51

Fong, T-L.; et al Persistence of hepatitis B virus DNA in the liver after loss of HBsAg in chronic hepatitis. Hepatology, 1991; 18:1313-8

15. Carman, W.F.; et at Vaccine-induced escape mutant of hepatitis B virus. Lancet, 1990; 336:325-9

16. Tilzey, A.J.; Hepatitis B vaccine boosting: the debate continues. Lancet, 1995; 345:1000

17. Public Health, 1994; 108/6:427-31

18. Am J Dis Child, 1993; 147/12:1316-20

19. Vaccine, 1994; 12/12:1059-63

20. Tilzey, A.J.; Hepatitis B vaccine boosting: the debate continues. Lancet, 1995; 345:1000

21. Jilg, w.; Immune responses to late booster doses of hepatitis B vaccine. J med virol, 1985; 17:249-54

22. Hadler, S.C.; Effect of timing of hepatitis B vaccine dose on response to vaccine in Yucpa Indians. Vaccine, 1989; 7:106-10

23. Committee on Infectious Diseases. Update on timing of hepatitis B vaccination for premature infants and for qhildren with lapsed immunization. Pediatirics, 1994; 94:403-4

[Vaccination]  [Gaublomme]  [Hepatitis B]