Map displaying BCG vaccination policy by country.
A: The country currently has universal BCG vaccination program. B: The                         country used to recommend BCG vaccination for everyone, but currently does                         not. C: The country never had universal BCG vaccination programs.

Map displaying BCG vaccination policy by country. A: The country currently has universal BCG vaccination program. B: The country used to recommend BCG vaccination for everyone, but currently does not. C: The country never had universal BCG vaccination programs.

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Madhu Pai and colleagues introduce the BCG World Atlas, an open access, user friendly Web site for TB clinicians to discern global BCG vaccination policies and practices and improve the care of their patients.

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A more effective tuberculosis (TB) vaccine is needed to eliminate TB disease. Many new vaccine candidates enhance the immunogenicity of the existing vaccine, Bacillus Calmette-Guérin (BCG). Understanding BCG induced immune variation is key to developing a new vaccine. We aimed to establish if individual-level covariates were associated with cell-...
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Background: The duration of the protective efficacy of BCG vaccine plays an important role in the establishment of vaccination policies particularly for tuberculosis endemic countries. The effectiveness of revaccination with two or more doses is still a controversial issue. In this systematic review, we qualitatively appraised available epidemiolog...
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... We classified a country's policy on BCG vaccination by using the 2020 BCG World Atlas. 25 Two reviewers (LM and OC) conducted the searches and independently reviewed the articles for eligibility in two stages. First, they evaluated titles and abstracts and then they reviewed the full text. ...
... Age was adjusted within each age stratum. The number of events for the vaccinated and unvaccinated groups in each stratification can be found in the appendix (appendix pp [24][25]. Analysing raw numbers might not translate well into adjusted odds ratios due to the mixed-effects model. ...
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Background BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. Methods In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included “mycobacterium tuberculosis”, “TB”, “tuberculosis”, and “contact”. We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. Findings We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74–0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49–0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69–0·96), participants younger than 5 years (0·68, 0·47–0·97), and participants aged 5–9 years (0·62, 0·38–0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32–0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70–0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65–1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13–0·49). Interpretation Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. Funding National Institutes of Health.
... Developed by Albert Calmette and Camille Guérin in the early twentieth century through cultivation and attenuation of the living strain of Mycobacterium bovis, the BCG vaccine was first used in humans in l921 [4]. It is currently administered in 154 TB-endemic countries including Brazil [5,6]. The vaccine prevents the disseminated and high mortality forms of the disease, such as tuberculous meningitis and miliary TB, especially in infants and young children [1,2,6]. ...
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Objective The Bacille Calmette-Guérin (BCG) vaccine is routinely applied in Brazil. Adverse events (AE) may occur in patients with inborn or acquired immunodeficiencies, varying between local (BCGitis) or disseminated (BCGosis) reactions. We evaluated 53 individuals with local or disseminated adverse events to BCG vaccination to assess if they had inborn errors of immunity (IEI). Methods Patients diagnosed with an adverse event following BCG vaccination between 2014 and 2017 were included in the study. We collected clinical data, immunophenotyped T and B lymphocytes, and natural killer cells (NK), assessed oxidative function of neutrophils through dihydrorhodamine (DHR) 123 testing, and genotyped 361 genes related to IEI through targeted (panel) sequencing. Results The median age of the 53 individuals was four months (IQ 1.5–12), and 52.8% were male. Forty-eight (90.6%) individuals presented only locoregional AE and five (9.4%) presented both locoregional and disseminated AE. Nine (16.9%) patients were diagnosed with an IEI. Four of them presented BCGitis and five presented BCGosis after BCG vaccination. Clinically, four presented chronic granulomatous disease (CGD), three Mendelian susceptibility to mycobacterial disease (MSMD), and two severe combined immunodeficiency (SCID). Patients with IEI had a higher frequency of systemic symptomatology (p = 0.002), history of other infections (p < 0.001), parental consanguinity (p = 0.01), familial history of sick siblings (p < 0.001), or early deaths in the family (p < 0.01). Conclusion There is a high frequency of IEI in patients with locoregional and disseminated adverse events to BCG vaccination, revealing the need for the investigation of IEI accompanied by clinical and familial inquiry.
... In 1974, the WHO created the Expanded Programme on Immunization to ensure universal access for mothers and children to routinely recommended vaccines; intradermal BCG vaccination at birth has been included in this program since its inception. However, national BCG vaccination policies vary broadly in terms of dosing and strains [43] and are cataloged in the BCG World Atlas [44]. The BCG vaccination policy in China has also progressed through different stages. ...
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The BCG vaccine is prepared from a weakened strain of Mycobacterium bovis (M. bovis), a bacterium closely related to Mycobacterium tuberculosis (MTB), which causes tuberculosis (TB). The vaccine was developed over 13 years, from 1908 to 1921, in the French Institut Pasteur by Léon Charles Albert Calmette and Jean-Marie Camille Guérin, who named the product Bacillus Calmette–Guérin (BCG). BCG, the only licensed vaccine currently available to prevent TB, is given to infants at high risk of TB shortly after birth to protect infants and young children from pulmonary, meningeal, and disseminated TB. The BCG vaccine, one of the safest and most widely used live attenuated vaccines in the world, recently celebrated its 100th anniversary (from 1921 to 2021); its record of use in preventing TB in China is also approaching 100 years. In 2022, a new century of BCG vaccine immunization will begin. In this article, we briefly review the history of BCG vaccine use in China, describe its current status, and offer a preliminary outlook on the future of the vaccine, to provide BCG researchers with a clearer understanding of its use in China.
... In China, neonatal BCG vaccination has become a routine as suggested by the World Health Organization. According to the literature, the incidence of BCG complication is less than 1% in immunocompetent hosts, most of which are presented as local lymph nodes diseases 5,6 . However, there are concerns about the safety of BCG among PID patients including CGD. ...
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In China, tuberculosis (TB) is endemic and the Bacillus Callmette–Güerin (BCG) vaccine is administered to all the newborns, which may lead to BCG infection in patients with chronic granulomatous disease (CGD). Infection of BCG/TB in CGD patients can be fatal and pulmonary is the most affected organ. Our objective was to assess the imaging of pulmonary BCG/TB infection in CGD. We screened 169 CGD patients and identified the patients with pulmonary BCG/TB infection. BCG infection was diagnosis according to the vaccination history, local infection manifestation, acid-fast bacilli staining, specific polymerase chain reaction, and/or spoligotyping. PPD, T-SPOT and acid-fast bacilli staining were used for diagnosis of TB. Totally 58 patients were identified, including TB (n = 7), solely BCG (n = 18), BCG + bacterial (n = 20), and BCG + fungi (n = 13). The onset of BCG disease was much earlier than TB. For those patients only with BCG, lymphadenopathy was the first and most prevalent feature. The most found location was the left axilla, followed by the ipsilateral cervical areas and mediastinal or hilar area. On chest CT, ground-glass opacities, multiple nodules and pulmonary scarring were the most common findings. For TB patients, the pulmonary infections were more serious, including large masses, severe lymphadenopathy, and extensive pulmonary fibrosis. Pulmonary infection of BCG were more common than TB in CGD patients, but much less severe.
... However, the coverage of these vaccines was not much different in the studied countries. BCG is routinely administered to all people in almost 90% of countries in the world; in some countries only at-risk groups are vaccinated (30). Controlling these covariates is complicated, mainly because of the nature of our study. ...
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Background Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is an important global health issue. We hypothesized that the live attenuated poliovirus existing in oral polio vaccine (OPV) may protect uninfected neonates born to HIV-positive mothers through the stimulation of innate immune system. Objective To test the hypothesis that countries using OPV have a lower MTCT rate (due to postnatal protection provided by the vaccine) compared with those using only inactivated polio vaccine (IPV). Methods In an ecological study, the incidence of HIV/AIDS in children aged <1 year (IncHIV1), considered a surrogate index for MTCT rate, was compared between countries using OPV vs. IPV. The aggregated population data were retrieved for 204 countries from the Global Burden of Disease (GBD 2019) Collaborative Network website, “Our World in Data” website, the World Bank website, and the WHO Global Polio Eradication Initiative (GPEI). We used a negative binomial regression model with IncHIV1 as the dependent variable and the prevalence of HIV/AIDS in women aged 15–49 years (PrevHIV), antiretroviral therapy (ART) coverage, human development index (HDI), and the type of vaccine used in each country as independent variables. Multivariate imputation by chained equations was used to treat missing values. Analyses were performed for both the original dataset (with missing values) and the five imputed datasets. Results IncHIV1 and PrevHIV were available for all 204 countries; vaccine type, 194 countries; HDI, 182 countries; and ART coverage, 133 countries. One-hundred and twenty-nine countries in the original dataset had complete data for all the above-mentioned variables; the imputed datasets had complete data for all 204 countries. The results obtained from the analysis of the original dataset had no overall difference with the pooled results obtained from the analysis of the five imputed datasets. Countries with higher HDI mainly use IPV; those with lower HDI commonly use OPV. PrevHIV, HDI, and the type of vaccine were independent predictors of IncHIV1. Use of OPV compared to IPV, was independently associated with an average decrease of 17% in IncHIV1 at the median HDI of 0.75. The protection provided by OPV increased in countries with lower HDI. Conclusions Use of OPV compared with IPV, was independently associated with lower MTCT rate.
... 27 In Vietnam, a BCG vaccine manufactured locally at the Pasteur Institute in HCMC from the BCG-Pasteur 1173P 2 strain was used, whereas the BCG-Danish strain produced by the Statens Serum Institute in Denmark was used in Tanzania. 11 Genetically different BCG vaccine strains could induce different immune responses due to differences in the underlying mechanism and magnitude of the immune response, potentially leading to variations in the protective efficacy against TB, [28][29][30] and to differences in delayed type hypersensitivity responses, the underlying mechanism for the induration caused by the TST. 31 A study conducted in Turkey using the same strain as in Vietnam showed a decreased odds for infection with M. tuberculosis in BCG-vaccinated children compared to non-vaccinated children 32 when using IGRA, but not when assessed with TST, unless a larger TST induration size cut-off was applied for the children with a BCG scar (15 mm) than for those without a BCG scar (10 mm). However, using a larger induration size cut-off for children with a BCG scar may bias the association between BCG status and TST positivity as crossreactivity to NTM could cause false-positive TST results. ...
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BACKGROUND: Protection against infection by the bacille Calmette-Guérin vaccine against Mycobacterium tuberculosis remains a subject of controversy. We investigated the association between BCG vaccination at birth and infection by M. tuberculosis.MATERIAL and METHODS: This was a secondary analysis of data from tuberculin skin test (TST) surveys in Vietnamese schoolchildren between 1988 and 2001. We investigated whether a BCG scar was associated with a lower prevalence of TST positivity, adjusting for BCG-induced variation by varying cut-off values for a positive TST.RESULTS: We found a positive association between BCG scar and TST positivity. The strength of the association decreased with increasing TST cut-off values; however, it never inverted significantly, irrespective of geographic region and survey year.CONCLUSION: In Vietnam, BCG vaccination was not associated with reduced M. tuberculosis infection prevalence as measured using TST. This in contrary to a similar study conducted in Tanzania. These contradictory findings may be explained by geographical differences and the relatively high prevalence in Vietnam of the M. tuberculosis Beijing genotype, which is reported to be capable of circumventing BCG-induced immunity.
... However, it is to some degree a preventable disease mainly through vaccination with the live-attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG), whose use as a vaccine has constituted an important measure to prevent childhood tuberculosis, but less efficiently confers protection against pulmonary tuberculosis in adults [8]. Moreover, BCG has been shown to impart a variable protective efficacy, possibly due to the application of different BCG sub-strains and vaccination policies across the world [9,10]. ...
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Bovine tuberculosis (bTB) is a zoonotic disease caused mainly by Mycobacterium bovis, which is associated with major economic losses for milk and meat producers. The objective of this trial was to assess the efficacy of the BCG Russia strain in a cohort study performed under field conditions, with the vaccination of calves in seven dairy farms from a high prevalence area in central Chile. The trial was performed with 501 animals, subcutaneously vaccinated with 2-8 × 105 colony-forming units of BCG, whilst 441 matched control animals received a saline placebo. Peripheral blood was collected at 6, 12 and 18 months post-vaccination, and infection status was determined using the IFNγ release assay in conjunction with the DIVA (Detecting Infected amongst Vaccinated Animals) antigens ESAT-6, CFP-10 and Rv3615c. The BCG vaccine showed a low but significant level of protection of 22.4% (95% CI 4.0 to 36.4) at the end of the trial. However, diverse levels of protection and a variable duration of immunity were observed between trial herds. This diverse outcome could be influenced by the general health condition of calves and their exposition to non-tuberculous mycobacteria. These results suggest that BCG vaccination of dairy calves in a natural transmission setting confers variable protection to animals against bTB in a high prevalence area.
... Whereas T1D is an autoimmune disorder that is mostly diagnosed at a young age, MS is a neurological disorder that is usually diagnosed in a later stage of life and progresses during the course of life (Milo and Miller, 2014). For T1D, several published articles provided data on the incidence in the included countries or representative regions thereof during varying time periods [United States: 2001-2015(Rogers et al., 2017), Netherlands: 1999and 2011(Fazeli Farsani et al., 2016), Finland: 1984-2005(Harjutsalo et al., 2008), 2006-2011(Harjutsalo et al., 2013, 2014 and 2018 (Parviainen et al., 2020), France: 2010-2015 (Piffaretti et al., 2019), Germany and United Kingdom: 1993-2013(Patterson et al., 2019), Italy: 1992-2003(Bruno et al., 2010]. When the incidences of T1D in representative regions were provided, a weighted average was calculated to estimate the incidence rate for the entire country. ...
... Whereas T1D is an autoimmune disorder that is mostly diagnosed at a young age, MS is a neurological disorder that is usually diagnosed in a later stage of life and progresses during the course of life (Milo and Miller, 2014). For T1D, several published articles provided data on the incidence in the included countries or representative regions thereof during varying time periods [United States: 2001-2015(Rogers et al., 2017), Netherlands: 1999and 2011(Fazeli Farsani et al., 2016), Finland: 1984-2005(Harjutsalo et al., 2008), 2006-2011(Harjutsalo et al., 2013, 2014 and 2018 (Parviainen et al., 2020), France: 2010-2015 (Piffaretti et al., 2019), Germany and United Kingdom: 1993-2013(Patterson et al., 2019), Italy: 1992-2003(Bruno et al., 2010]. When the incidences of T1D in representative regions were provided, a weighted average was calculated to estimate the incidence rate for the entire country. ...
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Infectious, autoimmune, and metabolic diseases put an enormous pressure on both quality of life and the economy. For all three disease types, it is known that the quality of the gut microbiota composition is correlated to both onset and progression of disease. Hence, maintaining eubiosis and preventing gradual irreversible loss of beneficial microbes within the gut microbial ecosystem is of utmost importance. As such, the epidemiological trends of these disease types may serve as proxies for the integrity of the human gut microbiota. Here, we present incidence data covering the last decades for prototypical infectious diseases (tuberculosis and measles), autoimmune disorders (type-1 diabetes and multiple sclerosis), and the prevalence of metabolic syndrome. Our findings reveal that vaccination efforts correlate with relatively low levels of archetypal infectious disease incidence. However, autoimmune and metabolic disorders are, together with the usage of antibiotics, steeply on the rise. These findings suggest that the status of the gut microbiota is persistently deteriorating, as reflected by the proxies. As such, the epidemiological trends shown here may serve as a starting point for a mechanistic understanding of the interplay between these different disease types that can be used for future prevention and mitigation strategies like targeted stimulation and suppletion of microorganisms by means of, e.g., fermented foods, prebiotics and probiotics.
... tuberculosis) (1,2). Bacillus Calmette-Guerin (BCG) is commonly applied in newborns and has proved to be effective in protecting children from severe tuberculosis infection (3,4), but the protective immunity wanes and shows limited protection against tuberculosis in adults (5,6). T cellmediated immune responses are critical for host defense against M. tuberculosis infection (7)(8)(9). ...
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Boosting Bacillus Calmette-Guérin (BCG) with subunit vaccine is expected to induce long-term protection against tuberculosis (TB). However, it is urgently needed to optimize the boosting schedule of subunit vaccines, which consists of antigens from or not from BCG, to induce long-term immune memory. To address it two subunit vaccines, Mtb10.4-HspX (MH) consisting of BCG antigens and ESAT6-CFP10 (EC) consisting of antigens from the region of difference (RD) of Mycobacterium tuberculosis (M. tuberculosis), were applied to immunize BCG-primed C57BL/6 mice twice or thrice with different intervals, respectively. The long-term antigen-specific immune responses and protective efficacy against M. tuberculosis H37Ra were determined. The results showed that following BCG priming, MH boosting twice at 12-24 weeks or EC immunizations thrice at 12-16-24 weeks enhanced the number and function of long-lived memory T cells with improved protection against H37Ra, while MH boosting thrice at 12-16-24 weeks or twice at 8-14 weeks and EC immunizations twice at 12-24 weeks or thrice at 8-10-14 weeks didn’t induce long-term immunity. It suggests that following BCG priming, both BCG antigens MH boosting twice and “non-BCG” antigens EC immunizations thrice at suitable intervals induce long-lived memory T cell-mediated immunity.
... -see Figure 1). 47 However, if uncertainty remains regarding BCG vaccination and its timing, it is best to use an IGRA, if available, as the proportion of people testing false positive is expected to be lower. ...