BCG Study at a State School for Mentally Retarded

Bettag, Otto L.; Kaluzny, Alexander A.; Morse, Dan; Radner, David B.

doi:10.1378/chest.45.5.503

Cited by 20 publications

(12 citation statements)

References 3 publications

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“…For these trials, no protective ef cacy was observed (12,13). However, BCG Tice also failed to provide protection in a clinical trial of children in a Chicago home for the mentally retarded (14). This change of ef cacy in the same geographical region, in conjunction with Rosenthal's own concerns about excessive attenuation of his strain, suggest that, at least in the case of BCG Tice, some of the variability in trial outcome may be explained by over-attenuation of the BCG strain.…”

Section: Origin and Use Of Bcg Strainsmentioning

confidence: 99%

Correlation between BCG Genomics and Protective Efficacy

Behr¹

2001

Scandinavian Journal of Infectious Diseases

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Between the derivation of bacille Calmette -Guérin (BCG) vaccine in 1921 and the lyophilization of BCG daughter strains in the 1960s, a number of clinical trials were performed looking at the protective ef cacy of BCG vaccination against tuberculosis. These trials differed from one another in a number of ways: they employed different methodologies for delivering the vaccine and interpreting outcomes; they were performed on population s with different genetic backgrounds and different levels of exposure to environmental Mycobacteria; and, nally, they used different BCG vaccine strains. The results of these trials were estimates of protective ef cacy against pulmonary tuberculosis ranging from about 80% to nil. Because of the differences in outcomes and confounding variables, it is dif cult to conclude whether differences in interventions alone may have contributed to the remarkably variable results. Analysis of BCG vaccines used in clinical trials suggests a trend towards decreasing ef cacy with increased passage in the laboratory ; however, trials that used relatively ''older'' BCG strains were generally performed at different sites than trials which used ''younger'' BCG strains. Genomic analysis of BCG vaccines demonstrates that during the half-century of ongoing passage of BCG vaccines in vitro there have been numerous genetic changes, comprising single nucleotide polymorphisms, duplications and deletions. The impact of these changes in the BCG genome on the protective ef cacy observed in eld trials remains to be determined. M. A. Behr, MD, A5 -156,

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Section: Origin and Use Of Bcg Strainsmentioning

confidence: 99%

Correlation between BCG Genomics and Protective Efficacy

Behr¹

2001

Scandinavian Journal of Infectious Diseases

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“…32 34 The trial in Lincoln State School describes an adult cohort followed in a high transmission setting and suggested a trend towards more cases in the vaccinated, particularly after 5 years of follow-up (figure 3). 40 The Chengalpattu trial was the largest BCG vaccination trial ever undertaken and was among the best reported, although it employed one-stage TST screening. 41 It enrolled participants aged 1 month and above, followed for 15 years in a very high transmission setting and found slightly higher TB rates in the BCG vaccinated, although protection was suggested in children.…”

Section: Trials Recruiting Across All Ages With Extended Follow-upmentioning

confidence: 99%

Timing ofMycobacterium tuberculosisexposure explains variation in BCG effectiveness: a systematic review and meta-analysis

Trauer

Kawai

Coussens

et al. 2021

Thorax

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RationaleThe heterogeneity in efficacy observed in studies of BCG vaccination is not fully explained by currently accepted hypotheses, such as latitudinal gradient in non-tuberculous mycobacteria exposure.MethodsWe updated previous systematic reviews of the effectiveness of BCG vaccination to 31 December 2020. We employed an identical search strategy and inclusion/exclusion criteria to these earlier reviews, but reclassified several studies, developed an alternative classification system and considered study demography, diagnostic approach and tuberculosis (TB)-related epidemiological context.Main resultsOf 21 included trials, those recruiting neonates and children aged under 5 were consistent in demonstrating considerable protection against TB for several years. Trials in high-burden settings with shorter follow-up also showed considerable protection, as did most trials in settings of declining burden with longer follow-up. However, the few trials performed in high-burden settings with longer follow-up showed no protection, sometimes with higher case rates in the vaccinated than the controls in the later follow-up period.ConclusionsThe most plausible explanatory hypothesis for these results is that BCG protects against TB that results from exposure shortly after vaccination. However, we found no evidence of protection when exposure occurs later from vaccination, which would be of greater importance in trials in high-burden settings with longer follow-up. In settings of declining burden, most exposure occurs shortly following vaccination and the sustained protection observed for many years thereafter represents continued protection against this early exposure. By contrast, in settings of continued intense transmission, initial protection subsequently declines with repeated exposure to Mycobacterium tuberculosis or other pathogens.

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“…The trial in Muscogee and Russell Counties, USA, achieved broad community participation in those aged >5 in a setting of low and declining transmission, finding slightly fewer cases in the vaccinated (30, 32). The trial in Lincoln State School describes an adult cohort followed in a high transmission setting and suggested a trend towards more cases in the vaccinated, particularly after five years of follow-up ( Figure 3 ) (38).…”

Section: Resultsmentioning

confidence: 99%

“…Among paediatric and adolescent trials, two larger studies in settings of declining burden showed substantial protection and one suggested short-term protection in a high-burden setting. In adults, four high-quality studies with long-term follow-up have been undertaken, with the two performed in high transmission settings suggesting an null or adverse effect (38, 39), while one in a low transmission setting (30, 32) and one linked to case finding (41) found modest protection. Methodologically heterogeneous trials with short follow-up of participants were also consistent with short-term protection in adults.…”

Section: Discussionmentioning

confidence: 99%

Timing ofM. tuberculosisexposure explains variation in BCG effectiveness: A systematic review and meta-analysis

Trauer

Kawai

Coussens

et al. 2020

Preprint

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BackgroundThe variable efficacy observed in studies of BCG vaccination is incompletely explained by currently accepted hypotheses, such as latitudinal gradient in non-tuberculous mycobacteria exposure. We investigated heterogeneity in BCG vaccination in the context of participant demography, diagnostic approach and TB-related epidemiological context.MethodsWe updated previous systematic reviews of the effectiveness of BCG vaccination to 31st December 2018. We employed an identical search strategy and inclusion/exclusion criteria to past reviews, but reclassified several studies and developed an alternative classification system.ResultsOf 21 included trials, those recruiting neonates and children aged under five were consistent in demonstrating considerable protection for several years. Trials in high-burden settings with shorter follow-up also showed considerable protection, as did most trials in settings of declining burden with longer follow-up. However, the few trials performed in high-burden settings with longer follow-up showed no protection, sometimes with higher case rates in the vaccinated than the controls in the later follow-up period.ConclusionsThe most plausible explanatory hypothesis is that BCG protects against TB that results from exposure shortly after vaccination. However, risk is equivalent or increased when exposure occurs later from vaccination, a phenomenon which is predominantly observed in adults in high-burden settings with longer follow-up. In settings of declining burden, most exposure occurs shortly following vaccination and the sustained protection thereafter represents continued protection against this early exposure. By contrast, in settings of continued intense transmission, initial protection subsequently declines due to repeated exposure to M. tuberculosis or other pathogens.

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BCG Study at a State School for Mentally Retarded

Cited by 20 publications

References 3 publications

Correlation between BCG Genomics and Protective Efficacy

Correlation between BCG Genomics and Protective Efficacy

Timing ofMycobacterium tuberculosisexposure explains variation in BCG effectiveness: a systematic review and meta-analysis

Timing ofM. tuberculosisexposure explains variation in BCG effectiveness: A systematic review and meta-analysis

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