Re: Re: Re: Further to Peter Flegg and the TB ref.
I have no real wish for this debate on MMR/autism to be sidetracked into a discussion about TB and BCG vaccination, and so this response on the matter will hopefully be my last. Other respondents have already pointed out the uncontrolled nature of this debate and I don’t want to see it balloon completely out of control. Hilary Butler keeps asking questions on this topic – perhaps these will also be her last?
It appears that in her haste to rubbish the BCG vaccine, Butler has failed to read my original intervention on 24th February (Re: Question for Flegg). In this I stated that “BCG obviously has a very minor role to play in preventing transmission of TB as a public health measure”. So actually we have some common ground here, and perhaps she could even have used me as another reference for how “bad” the BCG vaccine actually is! (The window of opportunity for her to do this has gone however – because she also makes it quite plain she thinks that I have no authority in the subject matter whatsoever, despite my credentials).
However, the reality of the situation is a bit more complex. With a vaccine like BCG that has dubious protective efficacy, there are plenty of sources in the medical literature that will point out this fact (as Ms Butler has done). But she is being highly selective, and it is not at all hard to find many good studies confirming the benefits of BCG. Rather than list endless references to them, I refer instead to the meta-analyses that collate information from all the available trials (and not just the ones Butler wishes us to hear about). One meta-analysis screened 1264 articles on BCG, and included 14 prospective trials and 12 case-controlled studies in its analysis, including Indian trial data (1). Butler would do well to look at this analysis, as well as the CDC document on the role of BCG in the USA (2). The overall protective effect of BCG is estimated to be 50%, which is quite substantial. Data from the subsequent Malawian trials, which Butler cites, showed no protection (3). This study adds a new perspective to the problem, but it took place against a background of increasing HIV prevalence, and it did not control for previous TB (how can you demonstrate protection from a vaccine against something you may already have?).
Subsequent studies in the same part of Malawi demonstrate that blunted responses to BCG are likely to be due to priming with environmental mycobacterial antigens, as shown by IFN-gamma responsiveness attributable to different mycobacterial antigens (5). The same group conducted comparative trials of this phenomenon between Malawi and British adolescents, and showed higher IFN-gamma and DTH responses at baseline in Malawi than the UK, with higher post-vaccination IFN-gamma responses to BCG in the, supporting an effect for prior sensitization by environmental mycobacteria in Malawi (6). [Bottom line: there are several plausible explanations for the failure of the Malawi trial to show protective efficacy.]
Though there may remain some uncertainty about BCG’s protective role against TB acquisition, absolutely no-one in the medical field doubts that BCG has another, crucially important role – that of helping prevent serious complications in those with TB, something I referred to previously and which has been studiously ignored by the anti-vaccine lobby. The Colditz meta-analysis details this, with an overall protective efficacy against death from TB of 71% and against TB meningitis of 64% (1). Another major meta-analysis also confirms this, with BCG conferring protection against miliary or meningeal TB in 86% of randomized controlled trials and 75% of case-controlled studies (4).
A “school report” on BCG might well end with the exhortation “Must try harder”. It may be a poor vaccine for prevention of TB, but it reduces deaths and severe complications, and deserves a place in the protective umbrella we try and place over our more vulnerable populations. TB more than any other infection is primarily a social disease of deprivation and poor nutrition, but that does not mean we should neglect to lessen its effects by stopping BCG vaccination. Butler hopes to live in a fantasy world where all infections would cease to exist the moment we all eat up our greens. That world does not exist.
(1). Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994;271:698-702.
(3). Randomised controlled trail of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi Karonga Prevention Trial Group. Lancet. 1996;348:17-24.
(4). Rodrigues LC; Diwan VK; Wheeler JG. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol 1993 Dec;22(6):1154-8.
(5). Black GF; Dockrell HM; Crampin AC; Floyd S; Weir RE; Bliss L; Sichali L; Mwaungulu L; Kanyongoloka H; Ngwira B; Warndorff DK; Fine PE. Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi. J Infect Dis 2001 Aug 1;184(3):322-9.
(6). Black GF; Weir RE; Floyd S; Bliss L; Warndorff DK; Crampin AC; Ngwira B; Sichali L; Nazareth B; Blackwell JM; Branson K; Chaguluka SD; Donovan L; Jarman E; King E; Fine PE; Dockrell HM BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies. Lancet 2002 Apr 20;359(9315):1393-401.
Competing interests: No competing interests