Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children
BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7364.569 (Published 14 September 2002) Cite this as: BMJ 2002;325:569All rapid responses
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In evaluating the data presented it seem logical that if the efficacy
of the groups did not vary for chronic carriage, would it not make sense
to delay the initial vaccine until some risk of exposure is present such
as sexual activity or drug use? Indeed this study presented the fact that
the the larger the time from vaccine to exposure (later in life) the
greater risk for infection. Our literature is ripe with contradictions
and questions. Almost 40% of the exposed had no immune reaction to the
injection? Is it time to err to the side of conservative?
Competing interests: No competing interests
To the editor
I enjoyed the article by Whittle et al which in many respects is a
unique study (1).
My concern in Australia and many other countries is that the
consensus opinion regarding hepatitis B immunity is that a hepatitis B
virus (HBV) surface antibody (HBsAb) response greater than 10mIU/ml to HBV
vaccine equates to life long immunity (2).
I have two major issues with this opinion. The first is scientific
which I believe is supported by Whittle et al.
My interpretation of this article is that this is the clearest
evidence yet that HBV vaccine induced immunity wanes with time and that
lower levels of HBsAb are associated with increased risk of acquiring HBV
and possibly chronic infection. It is worth noting that the protection
from chronic carriage will be a difficult to measure in this (or any)
study because only 5% of adult males and 2% of adult females that acquire
HBV will become chronic carriers.
Furthermore, this is one of the longest follow-up studies and it only
covers 14 years – so how can we assume that this vaccine confers life-long
immunity? Indeed, the HBV vaccine is currently the only vaccine that after
a single course - if the patient seroconverts - it is claimed provides
life-long immunity. Have we not learnt the lessons from the other
childhood vaccines?
My other issue is ‘technical’. I believe that at low levels of
detection, perhaps as 'high' as 40mIU/ml of HBsAb, that one has reduced
confidence in the result. Results close to the cut-off may be ‘false
positive’ results. Furthermore, the reproducibility of results close to
the cut-off is poor for any serological assay i.e. the same sample with a
value close to the cut-off when repeatedly tested will give a variety of
positive and negative results.
Taking these points into account, I do not believe that a medical
student with a HbsAb value of, say, 20mIU/ml will be immune to HBV now or
indeed in 20 years time when they may be practising as a surgeon. Our
society has a high expectation that health care workers (HCW) performing
procedures are not chronic HBV carriers. And even if a HCW does acquire
and resolve their HBV infection there will still be a significant window
period where they will be very infectious and potentially have significant
disease.
Until there is clear evidence otherwise, my strong recommendation is
that people have boosters every 10-15 years and that people with
relatively low level immunity have boosters. The vaccine is cheap, safe
and effective - lets use it.
References:
1) Whittle H, Jaffar S, Wansbrough M, Mendy M, Dumpis U, Collinson A,
et al. Observational study of vaccine efficacy 14 years after trialof
hepatitis B vaccination in Gambian children. BMJ 2002; 325: 569-573
2) European Consensus Group on Hepatitis B Immunity Are booster
immunisations needed for lifelong hepatitis B immunity? Lancet 2000; 355:
561-65
Competing interests: No competing interests
vaccine-induced protection to hepatitis B
Dear Sir,
We congratulate Whittle et al (1) on their report of one of the few
long-term follow up studies of children vaccinated against hepatitis B,
particularly as it was conducted in a hepatitis B endemic country. The
vaccine regimens reduced the HBsAg carrier rate in two villages, from 13
to 1% and from 35 to 2%, which represents a major achievement in public
health medicine. However, we are concerned that those with an interest in
HBV vaccines, particularly those, who influence policy decisions, may not
appreciate that the electronic version of their paper differs from the one
printed in the Journal itself. Thus, important paragraphs on methodology
and outcome were missing in the somewhat abridged version printed in the
Journal. The electronic version states that several vaccines, vaccine
dosages and routes of administration were used, most of which differed
from the currently recommended infant or child vaccination dose or route
of administration in universal hepatitis B vaccination programmes.Thus,
despite the use of low dose hepatitis B vaccines intradermally, and
without mentioning whether the results of the study might have been
influenced by malnutrition, infection with HIV or other underlying
disease, the overall vaccine efficacy against HBsAg carriage was 94%,
which fulfils the objective of a universal hepatitis B vaccination
programme admirably.
The distinction between protection against subclinical (anti-HBc
seroconversion) and breakthrough infection (HBsAg seroconversion) needs to
be appreciated (2). Not surprisingly, most vaccinees who had a
breakthrough infection (8/10), seemed to have peak antibody response of
less than 10 mIU/ml, but only a concentration at or above this level can
be regarded as an indicator of immunological priming or immunocompetence
(2). In addition, although no breakthrough infections due to HBV escape
mutants have been observed in successfully vaccinated individuals so far,
the possibility of such infections was not ruled out in this study. A
number of subclinical infections has also been reported in other studies
but these do not result in persistent carriage with its attendant risk of
chronic liver disease. Thus, the observations reported in the paper are
consistent with not only a Chinese 15 year follow-up study (3), but also
with the accumulated data from a number of studies demonstrating the
persistence of immune memory after the disappearance of humoral antibody
responses (4,5). This data provided the basis for the recent European
consensus statement which concluded that, as immunological memory lasts
for at least 15 years in immunocompetent subjects, hepatitis B booster
doses are not recommended in those who have responded to a completed
primary vaccination course (2).
We are concerned those who still feel that hepatitis B boosters
should be part of hepatitis B immunisation programmes, will be convinced
that the results of the study in Gambia provides evidence that vaccine-
induced protection wanes with time, whereas others will use the same
results to argue that hepatitis B vaccines confer long-term protection
against the chronic carrier state. What is important in terms of today’s
techniques for assessing protection, is that investigations are carried
out not only to ensure that vaccinees taking part in long-term follow up
studies respond adequately, but also that attention is given to assessing
immunological memory in those whose antibody responses, although
initially present, have declined to undetectable levels.
Pierre Van Damme, University of Antwerp, Epidemiology and Social
Medicine, WHO Collaborating Centre for Prevention and Control of Viral
Hepatitis, Antwerp, Belgium
Jangu E. Banatvala, Emeritus
Professor of Clinical Virology Guys, Kings and St Thomas 'School of
Medicine
and Dentistry, London, United Kingdom
References:
1. Whittle H, Jaffar S, Wansbrough M et al. Observational study of
vaccine efficacy 14 years after trial of hepatitis B vaccination in
Gambian children. Brit Med J 2002; 325:569-73.
2. European Consensus Group on Hepatitis B immunity. Are booster
immunizations needed for lifelong hepatitis B immunity? Lancet
2000;355:561-5.
3. Liao SS, Li RC, Li H, Yang JY, Aeng XJ, Gong J, et al. Long-term
efficacy of plasma derived vaccine: a 15-year follow-up study among
Chinese children. Vaccine 1999;17:2661-6.
4. West DJ, Watson B, Lichtman J, Hesley TM, Hedberg K. Persistence of
immunological memory for twelve years in children given hepatitis B
vaccine in infancy. Ped Inf Dis J 1994;13:745-7.
5. Wainwright RB, Bulkow LR, Parkinson AJ, Zanis C, McMahon BJ. Protection
provided by hepatitis B vaccine in a Yupik Eskimo population: results of a
10-year study. J Infect Dis 1997; 175: 674-7.
Competing interests: No competing interests