Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi

Pe, Fine; Pönnighaus, J. M.; Warndorff, D. K.; Pjk., Gruer; Oxborrow, S.M.; Pd, Pharoah; Lucas, Sebastian; McDougall, A C; Jenkins, Peter; Chavula, D.; Msiska, Glyn; Msosa, E; Munthali, M.; Mwamondwe, B; Ngoma, D; Nkhosa, Prince; Phiri, H; Simfukwa, M; Chihana, A.; Kawaonja, D; Malema, Simon; Mwinuka, Venance; Mkandawire, Paul; Nyasulu, S.; Tegha, H; Kalambo, M; Kileta, S; Simwaka, M; Bliss, L.; Saul, Jacky; Maine, N.; Sterne, Jonathan A C; Glynn,; Bell, D; Clayton, David; Pike, Marilyn C.; Cree, I A; Desikan, K. V.; Gupte,; Jacobson, Raymond L.; Nyangulu, D S; Darbyshire, Janet; Peto, R

doi:10.1016/s0140-6736(96)02166-6

Cited by 318 publications

(21 citation statements)

References 14 publications

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“…11,12 Although the World Health Organization 13 recommends not to re-vaccinate, mostly because of lack of evidence of the efficacy of revaccination, many countries implement re-vaccination programmes. Trials in Malawi 14 and more recently in Brazil 15 found no increase in effectiveness or a modest increase in effectiveness associated with repeat BCG vaccination.…”

Section: Tuberculosis Epidemiologymentioning

confidence: 96%

Observational study to estimate the changes in the effectiveness of bacillus Calmette–Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK

Mangtani

Nguipdop-Djomo

Keogh

et al. 2017

Health Technol Assess

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Background Until recently, evidence that protection from the bacillus Calmette–Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK’s universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced. Objectives To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK. Methods Two case–control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0–19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10–29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case–cohort analysis based on Cox regression. Results In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5–10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10–15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10–15 years after vaccination and 57% (95% CI 33% to 72%) 15–20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading. Limitations The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination. Conclusions Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading. Funding The National Institute for Health Research Health Technology Assessment programme. During the conduct of the study, Jonathan Sterne, Ibrahim Abubakar and Laura C Rodrigues received other funding from NIHR; Ibrahim Abubakar and Laura C Rodrigues have also received funding from the Medical Research Council. Punam Mangtani received funding from the Biotechnology and Biological Sciences Research Council.

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Section: Tuberculosis Epidemiologymentioning

confidence: 96%

Observational study to estimate the changes in the effectiveness of bacillus Calmette–Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK

Mangtani

Nguipdop-Djomo

Keogh

et al. 2017

Health Technol Assess

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“…Previous observational studies had evaluated PoD by BCG revaccination based on epidemiologic data. Generally, they did not find significant differences between controls and BCG revaccinated individuals (79)(80)(81).…”

Section: Recent Findings With the Canonical Bacille Calmette-guérin Vmentioning

confidence: 82%

Vaccination Against Tuberculosis: Revamping BCG by Molecular Genetics Guided by Immunology

Kaufmann

2020

Front. Immunol.

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Tuberculosis (TB) remains a major health threat. Although a vaccine has been available for almost 100 years termed Bacille Calmette-Guérin (BCG), it is insufficient and better vaccines are urgently needed. This treatise describes first the basic immunology and pathology of TB with an emphasis on the role of T lymphocytes. Better understanding of the immune response to Mycobacterium tuberculosis (Mtb) serves as blueprint for rational design of TB vaccines. Then, disease epidemiology and the benefits and failures of BCG vaccination will be presented. Next, types of novel vaccine candidates are being discussed. These include: (i) antigen/adjuvant subunit vaccines; (ii) viral vectored vaccines; and (III) whole cell mycobacterial vaccines which come as live recombinant vaccines or as dead whole cell or multi-component vaccines. Subsequently, the major endpoints of clinical trials as well as administration schemes are being described. Major endpoints for clinical trials are prevention of infection (PoI), prevention of disease (PoD), and prevention of recurrence (PoR). Vaccines can be administered either pre-exposure or post-exposure with Mtb. A central part of this treatise is the description of the viable BCG-based vaccine, VPM1002, currently undergoing phase III clinical trial assessment. Finally, new approaches which could facilitate design of refined next generation TB vaccines will be discussed.

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“…The trial in Venezuela focused on household contacts of patients; the trial in Malawi included participants from a leprosy endemic population in the Karonga District. 53,54 A large two-and-a-half-year double-blind controlled trial performed by Gupte et al, starting in 1991 in South India, included 171,400 people, who were not specifically described as contacts of leprosy patients, to test four different vaccines in comparison with placebo: BCG; BCG plus heat-killed M. leprae; the Indian Cancer Research Center (ICRC) vaccine, which is an M. leprae-related cultivable mycobacterium; and Mycobacterium w (Mw). 51 A first survey shortly after the intake period suggested a non-significant negative protective effect, most dominant in BCG, that disappeared at the second survey moment.…”

Section: Other Immunoprophylactic Agentsmentioning

confidence: 99%

<p>The State of Affairs in Post-Exposure Leprosy Prevention: A Descriptive Meta-Analysis on Immuno- and Chemo-Prophylaxis</p>

Schoenmakers

Mieras

Budiawan³

et al. 2020

RRTM

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Objective: Annually, over 200,000 people are diagnosed with leprosy, also called Hansen's disease. This number has been relatively stable over the past years. Progress has been made in the fields of chemoprophylaxis and immunoprophylaxis to prevent leprosy, with a primary focus on close contacts of patients. In this descriptive meta-analysis, we summarize the evidence and identify knowledge gaps regarding post-exposure prophylaxis against leprosy. Methods: A systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was conducted by searching the medical scientific databases Cochrane, Embase, Pubmed/MEDLINE, Research Gate, Scopus and Web of Science on Jan. 22, 2020, using a combination of synonyms for index terms in four languages: "leprosy" and "population" or "contacts" and "prevention" or "prophylaxis." Subsequently, Infolep.org and Google Scholar were searched and the "snowball method" was used to retrieve other potentially relevant literature. The found articles were screened for eligibility using predetermined inclusion and exclusion criteria. Results: After deduplication, 1,515 articles were screened, and 125 articles were included in this descriptive meta-analysis. Immunoprophylaxis by bacillus Calmette-Guérin (BCG) vaccination is known to provide protection against leprosy. The protection it offers is higher in household contacts of leprosy patients compared with the general population and is seen to decline over time. Contact follow-up screening is important in the first period after BCG administration, as a substantial number of new leprosy patients presents three months postvaccination. Evidence for the benefit of re-vaccination is conflicting. The World Health Organization (WHO) included BCG in its Guidelines for the Diagnosis, Treatment and Prevention of Leprosy by stating that BCG at birth should be maintained in at least all leprosy high-burden regions. Literature shows that several vaccination interventions with other immunoprophylactic agents demonstrate similar or slightly less efficacy in leprosy risk reduction compared with BCG. However, most of these studies do not exclusively focus on post-exposure prophylaxis. Two vaccines are considered future candidates for leprosy prophylaxis: Mycobacterium indicus pranii (MiP) and LepVax. For chemoprophylaxis, trials were performed with dapsone/acedapsone, rifampicin, and ROM, a combination of rifampicin, ofloxacin, and minocycline. Single-dose rifampicin is favored as post-exposure prophylaxis, abbreviated as SDR-PEP. It demonstrated a protective effect of 57% in the first two years after administration to contacts of leprosy patients. It is inexpensive, and adverse events are rare. The risk of SDR-PEP inducing rifampicin resistance is considered negligible, but continuous monitoring in accordance with WHO policies should be encouraged. The integration of contact screening and SDR-PEP administration into different leprosy control programs was found to be feasible and well accep...

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Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi

Cited by 318 publications

References 14 publications

Observational study to estimate the changes in the effectiveness of bacillus Calmette–Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK

Observational study to estimate the changes in the effectiveness of bacillus Calmette–Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK

Vaccination Against Tuberculosis: Revamping BCG by Molecular Genetics Guided by Immunology

<p>The State of Affairs in Post-Exposure Leprosy Prevention: A Descriptive Meta-Analysis on Immuno- and Chemo-Prophylaxis</p>

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