Rapid Responses to:

PAPERS: Hilton Whittle, Shabbar Jaffar, Michael Wansbrough, Maimuna Mendy, Uga Dumpis, Andrew Collinson, and Andrew Hall Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children BMJ 2002; 325: 569 [Abstract] [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

Vaccine induced immunity to hepatitis B

Len D Moaven   (18 September 2002)

Wait for administration

Kevin W. Ross   (24 September 2002)

vaccine-induced protection to hepatitis B

pierre van damme, jangu banatvala   (8 October 2002)

Vaccine induced immunity to hepatitis B 18 September 2002
Len D Moaven, Head of department, Microbiology Laverty Pathology, 60 Waterloo Road, North Ryde, NSW 2113 Australia Send response to journal: Re: Vaccine induced immunity to hepatitis B	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
Wait for administration 24 September 2002
Kevin W. Ross 85282 Send response to journal: Re: Wait for administration	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?
vaccine-induced protection to hepatitis B 8 October 2002
pierre van damme, university of antwerp antwerp 2610 belgium, jangu banatvala Send response to journal: Re: 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.