Bacillus Calmette-Guérin Immunization Research Articles

Spectrum and Incidence of Adverse Reactions Post Immunization in the Taiwanese Population (2014-2019): An Analysis Using the National Vaccine Injury Compensation Program.

Background: Post-marketing surveillance is crucial for gathering data on vaccine reactogenicity, enhancing public trust in immunization, and promoting vaccine uptake. This study aims to characterize adverse events following immunization (AEFIs) and estimate the incidence rates of adverse reactions (ARs) associated with vaccines included in Taiwan's Expanded Program on Immunization (EPI). This study utilizes data from Taiwan's Vaccine Injury Compensation Program (VICP). Methods: Vaccine injury claims submitted to the VICP between 2014 and 2019 were analyzed. ARs were defined as AEFIs adjudicated as "related" or "indeterminate" by the VICP committee. Data on the annual number of vaccine doses administered were obtained from the Taiwan CDC, which helped calculate the AR incidence rates. Results: A total of 491 AEFI claims were reviewed, with 327 (66.6%) categorized as ARs. The AEFIs were mainly associated with the Bacillus Calmette-Guérin (BCG) vaccine (43.4%) and the seasonal influenza vaccine (22.0%). Most EPI vaccines demonstrated low AR incidence rates, ranging from 1.68 to 13.6 per million doses, with the exception of BCG, which exhibited 162.5 ARs per million doses. Shifting BCG immunization from below 5 months to at least 5 months reduced osteomyelitis incidence significantly, from 41.4 to 7.9 (p = 0.0014), but increased abscess and lymphadenitis cases. Conclusions: EPI vaccines in Taiwan are highly safe, with minimal AR incidences in the general population. The BCG vaccine remains an exception, occasionally causing severe ARs like osteomyelitis. Adjusting the immunization schedule to an older age may mitigate some of these adverse effects.

BCG immunization induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-γ-mediated trained immunity.

After a century of using the Bacillus Calmette-Guérin (BCG) vaccine, our understanding of its ability to provide protection against homologous (Mycobacterium tuberculosis) or heterologous (for example, influenza virus) infections remains limited. Here we show that systemic (intravenous) BCG vaccination provides significant protection against subsequent influenza A virus infection in mice. We further demonstrate that the BCG-mediated cross-protection against influenza A virus is largely due to the enrichment of conventional CD4+ effector CX3CR1hi memory αβ T cells in the circulation and lung parenchyma. Importantly, pulmonary CX3CR1hi T cells limit early viral infection in an antigen-independent manner via potent interferon-γ production, which subsequently enhances long-term antimicrobial activity of alveolar macrophages. These results offer insight into the unknown mechanism by which BCG has persistently displayed broad protection against non-tuberculosis infections via cross-talk between adaptive and innate memory responses.

Bacillus Calmette-Guérin-Trained Macrophages Elicit a Protective Inflammatory Response against the Pathogenic Bacteria Brucella abortus.

The bacillus Calmette-Guérin (BCG) can elicit enhanced innate immune responses against a wide range of infections, known as trained immunity. Brucella abortus is the causative agent of brucellosis, a debilitating disease that affects humans and animals. In this study, we demonstrate that C57BL/6 mouse bone marrow-derived macrophages under BCG training enhance inflammatory responses against B. abortus. BCG-trained macrophages showed increased MHC class II and CD40 expression on the cell surface and higher IL-6, IL-12, and IL-1β production. The increase in IL-1β secretion was accompanied by enhanced activation of canonical and noncanonical inflammasome platforms. We observed elevated caspase-11 expression and caspase-1 processing in BCG-trained macrophages in response to B. abortus compared with untrained cells. In addition, these BCG-trained cells showed higher NLRP3 expression after B. abortus infection. From a metabolic point of view, signaling through the Akt/mammalian target of rapamycin/S6 kinase pathway was also enhanced. In addition, BCG training resulted in higher inducible NO synthase expression and nitrite production, culminating in an improved macrophage-killing capacity against intracellular B. abortus. In vivo, we monitored a significant reduction in the bacterial burden in organs from BCG-trained C57BL/6 mice when compared with the untrained group. In addition, previous BCG immunization of RAG-1-deficient mice partially protects against Brucella infection, suggesting the important role of the innate immune compartment in this scenario. Furthermore, naive recipient mice that received BM transfer from BCG-trained donors showed greater resistance to B. abortus when compared with their untrained counterparts. These results demonstrate that BCG-induced trained immunity in mice results in better control of intracellular B. abortus invivo and invitro.

Bacillus Calmette-Guérin-induced interleukin-10 inhibits S100A8/A9 production and hinders development of T helper type 1 memory in mice.

Tuberculosis caused by Mycobacterium tuberculosis (M.tb)is one of the main causes of human death in the world. Bacillus Calmette-Guérin (BCG) provides limited protection in adolescents and adults. To explore the factors reducing efficacy of BCG vaccine, we assess the impacts of interleukin (IL)-10 and alarmins S100A8/A9 on T-cell memory. We found that BCG-induced IL-10 inhibited production of S100A8/A9 in human peripheral blood mononuclear cells (PBMCs) and murine splenocytes. S100A9 deficiency inhibited IFN-γ production by CD4+ T cells in the early phase of BCG immunization and hindered the development of effector memory T helper type 1 (Th1) cells, while IL-10 deficiency promoted Th1 memory and blocking IL-10 signaling enhanced Th1 protective recall response against M.tb. IL-10 inhibited the binding of transcription factor CCAAT enhancer binding protein beta to S100a8/a9 promoter leading to S100A8/A9 reduction. S100A8/A9 heterodimer enhanced the IFN-γ production via receptor for advanced glycation end products signaling in CD4+ T cells. Our results demonstrate a hurdle to development of Th1 memory after BCG immunization and clarify the mechanism of the regulation of Th1 memory by IL-10 and S100A8/A9.

Changes in dendritic complexity and spine morphology following BCG immunization in APP/PS1 mice

ABSTRACT Bacillus Calmette – Guerin (BCG) is an immune regulator that can enhance hippocampal synaptic plasticity in rats; however, it is unclear whether it can improve synaptic function in a mouse model with Alzheimer’s disease (AD). We hypothesized that BCG plays a protective role in AD mice and investigated its effect on dendritic morphology. The results obtained show that BCG immunization significantly increases dendritic complexity, as indicated by the increased number of dendritic intersections and branch points, as well as the increase in the fractal dimension. Furthermore, the number of primary neurites and dendritic length also increased following BCG immunization, which increased the number of spines and promoted maturation. IFN-γ and IL-4 levels increased, while TNF-α levels decreased following BCG immunization; expression levels of p-JAK2, P-STAT3, SYN, and PSD-95 also increased. Therefore, this study demonstrates that BCG immunization in APP/PS1 mice mitigated hippocampal dendritic spine pathology, especially after the third round of immunization. This effect could possibly be attributed to; changes in dendritic arborization and spine morphology or increases in SYN and PSD-95 expression levels. It could also be related to mechanisms of BCG-induced increases in IFN-γ or IL-4/JAK2/STAT3 levels.

Covid-19 vs. BCG Universal Immunization: Statistical Significance in the Early Phase of the Pandemics

A possible correlation between the impact of Covid-19 and universal immunization program against tuberculosis with Bacillus Calmette-Guérin (BCG) vaccine was suggested previously, based on apparent correlation between lower impact of the epidemics and a record of national BCG immunization program. In this work a time-adjusted dataset of Covid-19 statistical data by national and subnational health jurisdictions at the time point of six months after the local arrival of the epidemics was used to perform a statistical analysis of the significance of the correlation hypothesis between universal BCG immunization and a milder early phase Covid-19 scenario. With the data accumulated up to the point of the analysis, the significance of the correlation hypothesis was evaluated both qualitatively and quantitatively with the conclusion that it has achieved statistically significant level of confidence. The conclusions of this research can be used in development of epidemiological policy as well as the rationale to investigate the origin and mechanisms of a broad immunity protection that can be associated with an early-age exposure to BCG vaccine. Doi: 10.28991/SciMedJ-2021-03-SI-8 Full Text: PDF

Specificity of tuberculin skin test improved by BCG immunization schedule change in Japan

IntroductionTuberculin skin test (TST) has been used to diagnose tuberculosis (TB) and latent tuberculosis infection (LTBI). However, in Bacillus Calmette-Guérin (BCG) vaccinated patients, TST tends to produce false-positive results. According to the previous vaccination schedule, Japanese people were mandated to receive up to three doses of BCG-vaccine. The vaccination schedule was changed in 2003 and as per the new schedule, only infants are administered a dose of BCG vaccine. Our hypothesis is that this change can lead to a reduction in the cross-reaction to TST. MethodsWe evaluated the TST results obtained from 1097 recruits from six defense camps and 667 recruits from an air base. These TST data were divided into two groups according to the date of birth: a new group and an old group according to the BCG immunization schedule. We then analyzed positive and negative reaction of TST and erythema sizes. ResultsWe confirmed that the change in BCG-vaccination schedule significantly decreased TST false-positive reaction (Pmeta = 1.4 × 10−18; risk ratio = 0.83; 95% confidence interval: 0.80–0.87) and erythema size (Pmeta = 1.1 × 10−4; mean difference = 6.6 mm; 95% confidence interval: 3.2 mm–9.9 mm). ConclusionsWe showed the reduction in BCG cross-reaction to TST, in the new BCG vaccination schedule group, compared to the old group, we also have extracted information on the improvement in the specificity of TST for LTBI and TB diagnosis, which resulted from BCG schedule change.

BCG Against SARS-CoV-2: Second Youth of an Old Age Vaccine?

The sudden outbreak of the COVID-19 pandemic, caused by SARS-CoV-2, has put the whole world into a difficult situation, asking for the immediate development of therapeutics and vaccines against the disease. Bacillus Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, has been administered for decades in many countries against tuberculosis. Today, when a solution against SARS-CoV-2 is urgently needed, the BCG vaccine has again come into the limelight owing to its earlier prevention of non-specific diseases. Data suggest a higher mortality rate of COVID-19 in non-BCG vaccinated countries, whereas the nations opting for BCG immunization have a comparatively lower mortality rate. The BCG vaccine is known to induce ‘trained immunity’ and generate ‘non-specific’ heterologous immune responses. It can confer anti-viral immunity by eliciting the production of pro-inflammatory cytokines, IL-6, TNF-α, IFN-γ, and IL-1β. Though the initial results look promising, a long trail still needs to be followed to avoid false promises. The accuracy of nationwide data, the role of an already activated immune system against ‘cytokine storms’, optimization and timing of vaccine dosage, and balancing demand-supply are some of the relevant issues that must be resolved before reaching a final conclusion.

BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic?

Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2). In the light of its rapid global spreading, on 11 March 2020, the World Health Organization has declared it a pandemic. Interestingly, the global spreading of the disease is not uniform, but has so far left some countries relatively less affected. The reason(s) for this anomalous behavior are not fully understood, but distinct hypotheses have been proposed. Here we discuss the plausibility of two of them: the universal vaccination with Bacillus Calmette–Guerin (BCG) and the widespread use of the antimalarial drug chloroquine (CQ). Both have been amply discussed in the recent literature with positive and negative conclusions: we felt that a comprehensive presentation of the data available on them would be useful. The analysis of data for countries with over 1000 reported COVID-19 cases has shown that the incidence and mortality were higher in countries in which BCG vaccination is either absent or has been discontinued, as compared with the countries with universal vaccination. We have performed a similar analysis of the data available for CQ, a widely used drug in the African continent and in other countries in which malaria is endemic; we discuss it here because CQ has been used as the drug to treat COVID-19 patients. Several African countries no longer recommend it officially for the fight against malaria, due to the development of resistance to Plasmodium, but its use across the continent is still diffuse. Taken together, the data in the literature have led to the suggestion of a possible inverse correlation between BCG immunization and COVID-19 disease incidence and severity.

Prevention of tuberculosis in macaques after intravenous BCG immunization

Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide1. The only available vaccine, BCG (Bacillus Calmette–Guérin), is given intradermally and has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission1,2. Here we show that intravenous administration of BCG profoundly alters the protective outcome of Mtb challenge in non-human primates (Macaca mulatta). Compared with intradermal or aerosol delivery, intravenous immunization induced substantially more antigen-responsive CD4 and CD8 T cell responses in blood, spleen, bronchoalveolar lavage and lung lymph nodes. Moreover, intravenous immunization induced a high frequency of antigen-responsive T cells across all lung parenchymal tissues. Six months after BCG vaccination, macaques were challenged with virulent Mtb. Notably, nine out of ten macaques that received intravenous BCG vaccination were highly protected, with six macaques showing no detectable levels of infection, as determined by positron emission tomography–computed tomography imaging, mycobacterial growth, pathology and granuloma formation. The finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques has important implications for vaccine delivery and clinical development, and provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against tuberculosis.

Cutting Edge: Bacillus Calmette-Guérin-Induced T Cells Shape Mycobacterium tuberculosis Infection before Reducing the Bacterial Burden.

Growing evidence suggests the outcome of Mycobacterium tuberculosis infection is established rapidly after exposure, but how the current tuberculosis vaccine, bacillus Calmette-Guérin (BCG), impacts early immunity is poorly understood. In this study, we found that murine BCG immunization promotes a dramatic shift in infected cell types. Although alveolar macrophages are the major infected cell for the first 2 weeks in unimmunized animals, BCG promotes the accelerated recruitment and infection of lung-infiltrating phagocytes. Interestingly, this shift is dependent on CD4 T cells, yet does not require intrinsic recognition of Ag presented by infected alveolar macrophages. M. tuberculosis-specific T cells are first activated in lung regions devoid of infected cells, and these events precede vaccine-induced reduction of the bacterial burden, which occurs only after the colocalization of T cells and infected cells. Understanding how BCG alters early immune responses to M. tuberculosis provides new avenues to improve upon the immunity it confers.

Induction of mycobacterial protective immunity by sublingual BCG vaccination

Tuberculosis (TB) remains a tremendous global health problem, with 1/4 of the world’s population infected and causing > 1 million deaths annually. Intradermal Bacillus Calmette-Guérin (BCG) vaccine given during infancy protects against severe forms of acute disease but does not prevent chronic infection or development of pulmonary TB. TB vaccine mucosal targeting potentially could induce mucosal resident immune cells with increased protective capacity against pulmonary infection and disease. Sublingual (SL) administration of vaccines may be an optimal mucosal delivery platform based on the high absorptive capacity of this mucosal surface, the extensive lymphoid tissue, and published preclinical studies demonstrating efficacy of SL vaccination against other pathogens. To this end, we performed preliminary testing of sublingual TB vaccines. Vaccination of mice with SL BCG elicited potent mycobacteria-specific T cell responses which persisted 16 weeks post-immunization. The magnitudes of the T cell responses were similarly induced after sublingual, intranasal, and subcutaneous BCG vaccination. Interestingly, serum mycobacteria-specific antibody responses and systemic recovery of BCG post-vaccination were lower after SL BCG compared with systemic BCG immunization. However, more importantly, SL BCG vaccinated mice were significantly protected against an aerosolized virulent M. tuberculosis challenge (P < 0.0001 compared to unvaccinated mice). Furthermore, this protection was long-lived, persisting for 16 weeks with >1 log CFU reduction compared with naïve challenged mice in both lungs and spleens (P < 0.0001 and P < 0.0028, respectively). These exciting results provide strong support for further studies exploring the mechanisms of protective immunity induced by sublingual BCG vaccination.

Stimulation of Nucleotide Oligomerization Domain and Toll-Like Receptors 2 to Enhance the Effect of Bacillus Calmette Guerin Immunization for Prevention of Mycobacterium Tuberculosis Infection: Protocol for a Series of Preclinical Randomized Controlled Trials.

BackgroundBacillus calmette guerin (BCG) immunization has been associated with a reduction in Mycobacterium tuberculosis (MTB) infection. BCG immunization has been shown to enhance innate immunity. This effect of BCG can be explained by an enhancing effect on innate immunity.ObjectiveThis study aimed to test the following hypotheses: (1) BCG immunization can prevent infection with MTB, (2) prevention of infection occurs via stimulation of NOD2 (nucleotide oligomerization domain) and toll-like receptors 2 (TLR2), and (3) the effect of BCG immunization on prevention of infection with MTB can be enhanced by giving stimulators of NOD2 and TLR2.MethodsTo detect the influence of immunization on infection rates, the ultralow dose (ULD) infection model is used. The infection rate of mice vaccinated with BCG and exposed after 6 weeks to ULD of MTB and unvaccinated mice are compared via cultures of lung homogenates and interferon (IFN) gamma release assay. If a reduced infection rate by BCG immunization is confirmed, the experiment is repeated by giving BCG combined simultaneously or in time sequence with the enhancers of innate immunity murabutide or beta-glycan. The influence of murabutide or beta-glycan alone on infection rates is investigated. To quantify the contribution of innate immunity levels of tumor necrosis factor, IFN gamma expression, histone H3 K4me3 trimethylation, and concentrations of monocytes with features of activation of innate immunity as defined by the Ly6Chigh as well as CD11b positive phenotype in immunized versus unimmunized infected and uninfected mice in the various immunization protocols is compared. The experiments will be repeated with prior application of the inhibitors of epigenetic programming of innate immunity histone methyltransferase inhibitor 5’-deoxy-5’-methylthio-adenosine and histone acetyl transferase inhibitor epigallocatechin-3-gallate. The influence of BCG on innate immunity is further corroborated by a prospective observational study in human infants.ResultsInvestigations of derivatives of muramyl dipeptide (MDP) to enhance early immunity in the C57BL/6 mouse strain (mice aged 7 weeks) by another group used 300 micrograms per mouse of oil-associated 6-0-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP) 50/50 mixed with Freund’s incomplete adjuvant. Comparison of colony-forming unit (CFU) count in the lungs 3 weeks after aerosol challenge with Mycobacterium bovis of groups (n=5) between groups receiving mycol-MDP in oil emulsion (see above) versus controls (n=5) showed a significantly lower CFU count of 94.5 x106 (SD 22.0) in cases versus controls with 204.0 X 106 (SD 77.6). It is important to note that after elimination of T-cells in this model, a reduction of CFU in lungs of mice treated with mycol-MDP persisted albeit without statistical significance, which was possibly related to the small number of animals used.ConclusionsDemonstration of a reduction of MTB infection by enhancement of innate immunity could show a new approach to improving vaccine efficacy against this pathogen.International Registered Report Identifier (IRRID)PRR1-10.2196/13045

Potential role of Bacillus Calmette-Guérin (BCG) vaccination in COVID-19 pandemic mortality: Epidemiological and Immunological aspects.

SARS-CoV-2 had already killed more than 400,000 patients around the world according to data on 7 June 2020. Bacillus Calmette-Guérin (BCG) vaccine is developed from live-attenuated Mycobacterium bovis, which is a microorganism found in a cow. Discovered by Dr. Albert Calmette and Camille Guérin since 1921, the BCG has served as a protection against tuberculosis and its complications. It is noticeable that countries which use mandatory BCG vaccination approach had lower COVID-19 infection and death rate. Current review aims to clarify this issue through epidemiological illustration of correlation between national BCG immunization and COVID-19 mortality, in addition to biological background of BCG-induced immunity Epidemiological data shows that universal BCG policy countries have lower median mortality rate compare to countries with past universal BCG policy and non-mass immunization BCG. (18 May 2020). Still, the links between BCG vaccination and better COVID-19 situation in certain countries are unclear, and more data on actual infection rate using SAR-CoV-2 antibody testing in large population sample is crucial for disease spreading comparison. Two immunological mechanisms, heterologous effects of adaptive immunity and trained innate immunity which induced by BCG vaccination, may explain host tolerance against COVID-19 infection, however, there is no direct evidence to support this biological background. Clinical trials related to BCG vaccination against COVID-19 are under investigation. Without a strong evidence, BCG must not be recommended for COVID-19 prevention, although, this should not be absolute contraindication. Risk of local and systemic complications from the vaccine should be informed to individual, who request BCG immunization.

761. Age-Related Incidence of TB Infection Supporting Efficacy of BCG Vaccination

Background Mycobacterium tuberculosis (MTB) is a major, and potentially preventable, cause of morbidity and mortality worldwide. Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine for TB, and while efficacy has been demonstrated in some populations, many uncertainties remain. Three BCG vaccination policies were implemented across bordering geographical regions in the South West of Ireland from 1972; neonatal vaccination (vaccinated region-a), vaccination of children aged 10–12 years (vaccinated region-b) and no vaccination (unvaccinated region-c). The aim of this study was to investigate the impact of BCG vaccination on incidence of MTB during the study period.MethodsSurveillance data were used to identify all M. tuberculosis complex (MTC) isolates from 2003 to 2016. Residential addresses for each case were geocoded using the Google Maps API. Case locations were spatially linked to 2011 census population data and to Local Health Offices (LHO) BCG coverage data for study regions a–c. The 13-year incidence of TB was calculated assuming a steady-state population. Using SatScan (v9.4.4), spatial clusters were identified at the small area level with the spatial scan statistic based on the discrete Poisson probability distribution.ResultsOf 638 MTC infections identified (621 MTB, 16 M. bovis, 1 M. africanum), 510 occurred in study regions a–c (median age 42 years (4 months–94 years), 65% male and 66% Irish born). The incidence of MTB was higher in the unvaccinated population, region-c 132/100,000 (95% CI 116–150) vs. vaccinated region-a 56/100,000 (95% CI 45–69) and region-b 44/100,000 (95% CI 29–63). A single high-risk cluster of 138 cases within a population of 46,000 was identified in unvaccinated region-c (relative risk 4.94 (95% CI 4–6). The year-on-year incidence rates in the 20- to 35-year-old age range suggested a decreasing risk consistent with a beneficial impact of vaccination policies.ConclusionPrevention and treatment of TB remains a significant challenge worldwide. Our study demonstrates significant differences in incidence of MTC infection in demographically similar populations based on BCG immunization policy and thus further supports efficacy of BCG for prevention of tuberculosis infection.Disclosures All authors: No reported disclosures.

Corrigendum: Bacillus Calmette–Guérin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice

[This corrects the article DOI: 10.3389/fimmu.2018.00869.].

Bacillus Calmette-Guérin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice.

Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available. Therefore, in case of a pandemic outbreak, alternative preventive approaches are needed, ideally even independent of the type of influenza virus outbreak. Bacillus Calmette–Guérin (BCG) is known to induce strong heterologous immunological effects, and it has been shown that BCG protects against non-related infection challenges in several mouse models. BCG immunization of mice as well as human induces trained innate immune responses, resulting in increased cytokine responses upon subsequent ex vivo peripheral blood mononuclear cell restimulation. We investigated whether BCG (Statens Serum Institut-Denmark)-induced trained immunity may protect against a lethal avian influenza A/Anhui/1/2013 (H7N9) challenge. Here, we show that isolated splenocytes as well as peritoneal macrophages of BCG-immunized BALB/c mice displayed a trained immunity phenotype resulting in increased innate cytokine responses upon ex vivo restimulation. However, after H7N9 infection, no significant differences were found between the BCG immunized and the vehicle control group at the level of survival, weight loss, pulmonary influenza A nucleoprotein staining, or histopathology. In conclusion, BCG-induced trained immunity did not result in protection in an oseltamivir-sensitive influenza A/Anhui/1/2013 (H7N9) challenge mouse model.

The Effectiveness of BCG (Bacillus-Calmette Guerin) Immunization to the Tuberculosis Incidence on Children at Banyuasin Regency

Bacillus Calmette Guerin (BCG) vaccine is still the only licensed vaccine against Tuberculosis (TB), with an estimated global coverage of 85%. However, although the vaccine has been established, discussions about its benefits and shortcomings continue.The coverage of immunization is appropriate with the target, but still the occurrence of child TB cases raises a problem of its own. This studywas a non-experimental study with study design was Case Control Study by retrospective. The effectiveness of BCG immunization in this study is 85%, meaning that children are given BCG 85% immunization will be protected from Tuberculocis (TB) disease. If the child does not get BCG immunization will increase the chances for the child, with OR = 6.87 (95% CI; 2.2 – 21.1) with p value = 0.000. It is suggested to Banyuasin regency Health Office to conduct the contact examination of house of children who are around TB positive patients periodically (monthly / at posyandu).

Social Activity Patterns Drive High Rates of Latent Tuberculosis Infection among Adolescents in Urban Tanzania&amp;lt;br/&amp;gt;—Latent TB Infection in Adolescents, Tanzania

SETTING: Dar es Salaam, Tanzania. OBJECTIVE: To determine the prevalence of latent tuberculosis (TB) infection (LTBI) among adolescents in a country with a high TB burden, and examine risks of LTBI according to their social activity patterns. METHODS: A cross-sectional study nested within a phase 2b randomised, placebo controlled, double blind study and consisted of 824 adolescents, 13 - 15 years old who had received Bacillus Calmette-Guerin (BCG) vaccine, were attending public secondary schools and had no evidence of active tuberculosis (TB). Anthropometric measurements were obtained, a questionnaire administered, and phlebotomy performed for a T spot interferon-γ release assay (IGRA) to detect LTBI. RESULTS: Among 824 subjects, 149 (18%) had a positive IGRA. After adjusting for the influence of household socioeconomic status, history of TB contact, living environment and nutritional status, LTBI risk was higher in subjects with than without regular informal encounters with traditional alcoholic beverage drinkers (AOR, 6.37 [1.84 - 22.00]). Other significant factors for LTBI risk included contact with TB patient at school (AOR, 3.34 [1.14 - 9.80]), and living close to a health facility, as was observed among those from houses within a 10 - 30-minute walking distance to the nearest health facility, who were less likely to be IGRA-positive than those who were living within a 10-minute walking distance (AOR, 0.30 [95%CI, 0.13 - 0.69]). CONCLUSION: This IGRA study revealed a high prevalence of LTBI among adolescents in Dar es Salaam, Tanzania with prior BCG immunization. Informal social encounters were identified as independent risk factors for LTBI, along with a history of contact with TB patients, living environment characteristics and household socioeconomic status. Efforts focusing on risk of MTB transmission in adolescents at informal social gatherings will improve interventions to reduce LTBI in this population and consequently the subsequent risk of developing active TB disease.

Clinical and economic impact of a specific BCG vaccination program implemented in Prato, central Italy, involving foreign newborns on hospitalizations

ABSTRACTIn Tuscany (Central Italy), the average annual notification rate of tuberculosis (TB) in the years 2007–2012 was 7.5–9.8 per 100,000 people, with the Local Health Unit of Prato (LHU4) showing the highest rate compared to the other regional area. Therefore, in order to reduce the burden of TB, foreign newborns in the LHU4 are being given the Bacillus Calmette-Guérin (BCG) vaccine since 2000. The aim of this study is to assess the impact of BCG vaccination in Prato, in terms of TB-related hospitalizations and costs.The regional archive containing all TB-related discharges and costs in the period 2007–2014 was consulted. Data regarding foreigners living in the LHU4 who have been vaccinated since 2000 were compared with those living in the other Tuscan LHUs and never vaccinated. These populations were then disaggregated by a threshold age of 15 y.After calculating the standardized hospitalization rates, the expected number of hospitalizations for TB among unvaccinated adults (in both populations) was found to be similar in the LHU4 and the other LHUs (165 vs. 156). However, expected number of hospitalizations among children in the other Tuscan LHUs (67) was double that of the LHU4 (34). If the same vaccine had been administrated everywhere, each year 29 hospitalizations could have been avoided and EUR 343,525 saved. Overall, BCG vaccinations cost EUR 14,879 in the LHU4, but 69 hospitalizations were avoided and EUR 107,435 saved.The introduction of the BCG immunization program in the LHU4 of Prato has led to significant reductions in the clinical and economic impact of TB.