Protection by BCG Vaccine Against Tuberculosis: A Systematic Review of Randomized Controlled Trials

Mangtani, Punam; Abubakar, Ibrahim; Ariti, Cono; Beynon, Rebecca; Pimpin, Laura; Fine, Paul E. M.; Rodrigues, Laura C.; Smith, P. G.; Lipman, Marc; Whiting, Penny; Sterne, Jonathan A C

doi:10.1093/cid/cit790

Cited by 770 publications

(716 citation statements)

References 27 publications

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“…This potential appears largest if the vaccine is targeted at adolescents/adults, providing further evidence, along with the report on increased efficacy against pulmonary TB in screened adults (31), for a recently suggested strategy (32) of giving bacillus Calmette-Guérin to screened adults. However, for those individuals already infected with TB or other environmental Mycobacteria (i.e., who fail the screen), there is still a need, and a large market, for a new TB vaccine.…”

Section: Discussionmentioning

confidence: 78%

Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries

Knight¹,

Griffiths

Sumner³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

167

183

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To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in lowand middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40-80% efficacy, and to be targeted at "infants" or "adolescents/adults." Vaccine prices were tiered by income group (US $1.50-$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024-2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11-24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42-1.58) million TB cases could be prevented at $1,692 ($634-$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle-, and upper-middleincome countries, respectively. Increased investments in adulttargeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies. mathematical modeling | epidemiology | threshold analysis T he bacterium Mycobacterium tuberculosis was responsible for ∼8.6 million cases of tuberculosis (TB) disease and ∼1.3 million deaths in 2012 (1), of which over 80% were in lowincome countries (LICs) and middle-income countries. This burden remains despite the widespread use of the infant TB vaccine, bacille Calmette-Guérin (bacillus Calmette-Guérin) (2). Dramatic levels of control are required to reach the World Health Organization (WHO) targets of TB elimination as a public health problem by 2050 (3). Previous mathematical modeling has suggested elimination can only be achieved through the use of new vaccines (4-7).In 2013, there were more than a dozen new TB vaccines in clinical trials, using a large range of antigens and adjuvants (8). A variety of modes of action and target populations are being researched (9, 10). The most recent TB vaccine tested in a largescale phase II trial reported a nonsignificant impact on TB disease of 17.3% [95% confidence interval (CI): −31.9 to 48.2] (11). However, such an undertaking highlights the progress that has been made in TB vaccine clinical trials, as well as the need for a reevaluation of the potential impact and need for increased investment in new TB vaccines (12).Estimates of the likely impact and cost-effectiveness of new products before and during development are useful for informing target product profiles and guiding produc...

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Section: Discussionmentioning

confidence: 78%

Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries

Knight¹,

Griffiths

Sumner³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

167

183

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“…[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] A recent meta-analysis of the efficacy of BCG vaccine against the pulmonary, meningeal and disseminated forms of TB included 21 randomized or quasi-randomized clinical trials: 18 involving patients with pulmonary TB, and 6 involving patients with meningeal and/or military forms. 30 The panel marginally supports a recommendation for use subjects vaccinated at birth (RR 0.41, 95% CI 0,29-0.58). There were some differences related to latitude; average protection was lower in the studies conducted in places at latitudes of 0-20 and 20-40 than in those conducted at higher latitudes.…”

Section: What Is the Current Role Of Bcg Vaccination?mentioning

confidence: 99%

“…This led to the emergence of genetic and antigenic differences among the marketed strains, 3 which gave rise to concerns about the safety and efficacy of the different vaccines. 4,5 BCG vaccine is widely used in countries in which TB is highly endemic, and where all newborns receive a single intradermal dose immediately after birth or later in infancy. [6][7][8] It is estimated that it has so far been administered more than 4 billion times, and that 120 million children are vaccinated every year.…”

Section: Introductionmentioning

confidence: 99%

Recommendations for pediatric tuberculosis vaccination in Italy

Montagnani

Esposito

Galli

et al. 2015

Human Vaccines & Immunotherapeutics

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Bacillus Calmette-Guerin (BCG) vaccine is still the only vaccine approved for the prevention of tuberculosis (TB), and is widely used in highly endemic countries, where all newborns receive a single intradermal dose immediately after birth; however, the recommendations concerning its use in Europe vary widely from country to country. This document describes the recommendations of a group of Italian scientific societies concerning its pediatric use in Italy, the persistence of the protection it provides, its safety, its interference with tuberculin skin test (TST) responses, and the children who should be vaccinated. The experts conclude that BCG vaccination provides a good level of protection against tuberculous meningitis and disseminated forms, and a fair level of protection against pulmonary disease; the protective effective lasts at least 10 years, and revaccination offers no advantages over a single administration. The vaccine is safe in immunocompetent subjects, and affects the response to a TST for at least 6 y On the basis of these observations, we recommend its use in Italy in all TST-negative immunocompetent newborns and breastfeeding infants aged <6 months, and all TST-negative children aged between 6 months and 5 y who come from highly epidemic areas, or whose parents come from highly endemic areas, or who have been in contact with a family member with active TB without contracting the disease themselves.

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“…[17][18][19][20] The variation of protection by BCG may be attributed to different types of BCG, to genetic differences between populations, and to coldchain maintenance of BCG. 18 In addition, another important issue affecting this variability is the exposure to environmental mycobacteria.…”

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confidence: 99%

“…18 In addition, another important issue affecting this variability is the exposure to environmental mycobacteria. 20 A systematic review of 21 randomized controlled trials evaluating the protection by BCG revealed that BCG imparted greater protection in northern latitudes, which may be due to less exposure to non-tuberculous mycobacteria (NTM) faced by vaccine recipients in these areas. 20 In another study from China, the researchers also found that the immune response to BCG vaccination varied according to the NTM exposure among neonates.…”

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confidence: 99%

Current status of new tuberculosis vaccine in children

Pang

Zhao

Cohen³

et al. 2016

Human Vaccines & Immunotherapeutics

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Pediatric tuberculosis contributes significantly to the burden of TB disease worldwide. In order to achieve the goal of eliminating TB by 2050, an effective TB vaccine is urgently needed to prevent TB transmission in children. BCG vaccination can protect children from the severe types of TB such as TB meningitis and miliary TB, while its efficacy against pediatric pulmonary TB ranged from no protection to very high protection. In recent decades, multiple new vaccine candidates have been developed, and shown encouraging safety and immunogenicity in the preclinical experiments. However, the limited data on protective efficacy in infants evaluated by clinical trials has been disappointing, an example being MVA85A. To date, no vaccine has been shown to be clinically safer and more effective than the presently licensed BCG vaccine. Hence, before a new vaccine is developed with more promising efficacy, we must reconsider how to better use the current BCG vaccine to maximize its effectiveness in children.

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Protection by BCG Vaccine Against Tuberculosis: A Systematic Review of Randomized Controlled Trials

Cited by 770 publications

References 27 publications

Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries

Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries

Recommendations for pediatric tuberculosis vaccination in Italy

Current status of new tuberculosis vaccine in children

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