Informe de rotación electiva: Coordinación de Tuberculosis y Lepra. Dirección de Respuesta al VIH, ITS, HV y TB. Ministerio de Salud de la Nación

El presente informe da cuenta de los objetivos propuestos y las actividades realizadas en el marco de la rotación electiva en la Coordinación de Tuberculosis y Lepra del Ministerio de Salud de la Nación, llevada adelante desde el 2 de marzo hasta el 13 de mayo de 2022. La elección de este espacio está vinculada al proceso de inserción en el área de tuberculosis iniciado en la rotación interna en el CeSAC 24 el primer cuatrimestre de 2021. Luego de haber participado en el consultorio interdisciplinario, se propuso conocer las acciones implementadas a nivel central y programático para el abordaje de la tuberculosis, con el objetivo de comprender los puntos de encuentro y desencuentro entre las intervenciones del primer nivel de atención y las particularidades de la gestión y la política pública. (AU)

The effect of BCG revaccination on all-cause mortality beyond infancy: 30-year follow-up of a population-based, double-blind, randomised placebo-controlled trial in Malawi.

BACKGROUND: Trials of BCG vaccination to prevent or reduce severity of COVID-19 are taking place in adults, some of whom have been previously vaccinated, but evidence of the beneficial, non-specific effects of BCG come largely from data on mortality in infants and young children, and from in-vitro and animal studies, after a first BCG vaccination. We assess all-cause mortality following a large BCG revaccination trial in Malawi. METHODS: The Karonga Prevention trial was a population-based, double-blind, randomised controlled in Karonga District, northern Malawi, that enrolled participants between January, 1986, and November, 1989. The trial compared BCG (Glaxo-strain) revaccination versus placebo to prevent tuberculosis and leprosy. 46 889 individuals aged 3 months to 75 years were randomly assigned to receive BCG revaccination (n=23 528) or placebo (n=23 361). Here we report mortality since vaccination as recorded during active follow-up in northern areas of the district in 1991-94, and in a demographic surveillance follow-up in the southern area in 2002-18. 7389 individuals who received BCG (n=3746) or placebo (n=3643) lived in the northern follow-up areas, and 5616 individuals who received BCG (n=2798) or placebo (n=2818) lived in the southern area. Year of death or leaving the area were recorded for those not found. We used survival analysis to estimate all-cause mortality. FINDINGS: Follow-up information was available for 3709 (99·0%) BCG recipients and 3612 (99·1%) placebo recipients in the northern areas, and 2449 (87·5%) BCG recipients and 2413 (85·6%) placebo recipients in the southern area. There was no difference in mortality between the BCG and placebo groups in either area, overall or by age group or sex. In the northern area, there were 129 deaths per 19 694 person-years at risk in the BCG group (6·6 deaths per 1000 person-years at risk [95% CI 5·5-7·8]) versus 133 deaths per 19 111 person-years at risk in the placebo group (7·0 deaths per 1000 person-years at risk [95% CI 5·9-8·2]; HR 0·94 [95% CI 0·74-1·20]; p=0·62). In the southern area, there were 241 deaths per 38 399 person-years at risk in the BCG group (6·3 deaths per 1000 person-years at risk [95% CI 5·5-7·1]) versus 230 deaths per 38 676 person-years at risk in the placebo group (5·9 deaths per 1000 person-years at risk [95% CI 5·2-6·8]; HR 1·06 [95% CI 0·88-1·27]; p=0·54). INTERPRETATION: We found little evidence of any beneficial effect of BCG revaccination on all-cause mortality. The high proportion of deaths attributable to non-infectious causes beyond infancy, and the long time interval since BCG for most deaths, might obscure any benefits. FUNDING: British Leprosy Relief Association (LEPRA); Wellcome Trust.

Bacille Calmette Guérin (BCG) and new TB vaccines: Specific, cross-mycobacterial and off-target effects.

The Bacille Calmette Guérin (BCG) vaccine was developed over a century ago and has become one of the most used vaccines without undergoing a modern vaccine development life cycle. Despite this, the vaccine has protected many millions from severe and disseminated forms of tuberculosis (TB). In addition, BCG has cross-mycobacterial effects against non-tuberculous mycobacteria and off-target (also called non-specific or heterologous) effects against other infections and diseases. More recently, BCG's effects on innate immunity suggest it might improve the immune response against viral respiratory infections including SARS-CoV-2. New TB vaccines, developed over the last 30 years, show promise, particularly in prevention of progression to disease from TB infection in young adults. The role of BCG in the context of new TB vaccines remains uncertain as most participants included in trials have been previously BCG immunised. BCG replacement vaccines are in efficacy trials and these may also have off-target effects.

BCG: a vaccine with multiple faces.

BCG has been recommended because of its efficacy against disseminated and meningeal tuberculosis. The BCG vaccine has other mechanisms of action besides tuberculosis protection, with immunomodulatory properties that are now being discovered. Reports have shown a significant protective effect against leprosy. Randomized controlled trials suggest that BCG vaccine has beneficial heterologous (nonspecific) effects on mortality in some developing countries. BCG immunotherapy is considered the gold standard adjuvant treatment for non-muscle-invasive bladder cancer. BCG vaccine has also been tested as treatment for diabetes and multiple sclerosis. Erythema of the BCG site is recognized as a clinical clue in Kawasaki disease. BCG administration in the immunodeficient patient is associated with local BCG disease (BCGitis) or disseminated BCG disease (BCGosis) with fatal consequences. BCG administration has been associated with the development of autoimmunity. We present a brief review of the diverse facets of the vaccine, with the discovery of its new modes of action providing new perspectives on this old, multifaceted and controversial vaccine.

Explaining the successes and failures of tuberculosis treatment programs; a tale of two regions in rural eastern Uganda.

BACKGROUND: Optimally performing tuberculosis (TB) programs are characterized by treatment success rate (TSR) of at least 90%. In rural eastern Uganda, and elsewhere in sub Saharan Africa, TSR varies considerably across district TB programs and the reasons for the differences are unclear. This study explored factors associated with the low and high TSR across four districts in rural eastern Uganda. METHODS: We interviewed District TB and Leprosy Supervisors, Laboratory focal persons, and health facility TB focal persons from four districts in eastern Uganda as key informants. Interviews were audio recorded, transcribed verbatim, and imported into ATLAs.ti where thematic content analysis was performed and results were summarized into themes. RESULTS: The emerging themes were categorized as either facilitators of or barriers to treatment success. The emerging facilitators prevailing in the districts with high rates of treatment success were using data to make decisions and design interventions, continuous quality improvement, capacity building, and prioritization of better management of people with TB. The barriers common in districts with low rates of treatment success included lack of motivated and dedicated TB focal persons, scarce or no funding for implementing TB activities, and a poor implementation of community-based directly observed therapy short course. CONCLUSION: This study shows that several factors are associated with the differing rates of treatment success in rural eastern Uganda. These factors should be the focus for TB control programs in Uganda and similar settings in order to improve rates of treatment success.

Evaluation of the performance of the National Tuberculosis Program of Liberia during the 2014-2015 Ebola outbreak.

BACKGROUND: Liberia is among the three west African countries which were crippled by the Ebola Virus Disease (EVD) outbreak of 2014. One of the programs which was affected by the EVD outbreak was the National Leprosy and Tuberculosis Control Program (NLTCP). Determining the magnitude of the impact of EVD on the NLTCP performance is crucial in restoring the service and in devising effective post EVD strategies. The purpose of the study was to analyse the impact of EVD outbreak on the performance of the NLTCP of the Ministry of Health (MOH) OF Liberia. METHODS: A cross sectional study design was conducted in 2016 using both quantitative and qualitative methods. Quantitative data was used for the Tuberculosis (TB) program evaluation before EVD (2012-2013) and during EVD (2014-2015). Qualitative data was used to complement the data obtained for the quantitative study. Descriptive statistical analyses of quantitative data were conducted using Microsoft Excel. RESULTS: Notified TB cases of all forms decreased from 7822 in 2013 to 4763 and 6118 in 2014 and 2015 respectively. The number increased to 7180 and 7728 in 2016 and 2017 respectively. The TB treatment success rate was 71 and 61% in 2014 and 2015 respectively compared to the 83% in 2013. The treatment success rate was 77% in 2016. The loss to follow up (LTFU) was as high as 47% in some regions which were highly affected by the EVD outbreak. The national average LTFU was 5-10% in 2012-2013 and 16 and 21% in 2014 and 2015 respectively. The percentage of TB patients with known HIV result decreased from 75% in 2013 to 74 and 42% in 2014 and 2015 respectively. TB culture and drug susceptibility testing service was interrupted throughout the outbreak. The results of the focal group discussions and interviews conducted in our study also indicated that the TB case finding and the TB treatment outcome was significantly affected by the EVD outbreak. CONCLUSION: Notified TB cases and treatment outcome was significantly affected by the EVD outbreak which occurred in 2014 and 2015 in Liberia. Effective restoration strategies should be developed in order to improve the TB case finding and treatment outcome.

The National Tuberculosis Control Programme of Liberia Laboratory Programme Performance.

Background: Tuberculosis (TB) is a major public health problem in Liberia. Little is known about the TB laboratory performance of Liberia and the challenges after the 14 years of civil war which ended in 2003. The purpose of the study was to evaluate the TB laboratory performance of Liberia. Methods: A cross-sectional study was conducted from 2014 to 2015. The study was conducted using quantitative data of TB case findings, sputum microscopy proficiency testing, and on-site assessment of sputum microscopy laboratories in Liberia. 80 laboratories participated in the proficiency testing. Besides, four years' (2012-2015) TB case finding data obtained from the National Leprosy and Tuberculosis Control Programme (NLTCP) were used to complement the study. The data were analysed using descriptive statistics. Results: From the 80 TB sputum microscopy testing laboratories participating in proficiency testing, only 20 (25%) scored acceptable performance. 46 (58%) TB microscopy laboratories reported quantification errors for the proficiency panel slide 6 which was 3+. The national TB smear-positive cases notified were 4342 in 2012 but decreased to 3820 and 2448 in 2013 and 2014, respectively. The TB smear case detection rate showed an increase from 68% in 2010 to 78% in 2011 and a decrease to 60%, 57%, and 42% in 2012, 2013, and 2014, respectively. Conclusion: Between 2010 and 2013, the NLTCP succeeded in increasing the number of TB sputum microscopy laboratories. At most of the TB microscopy sites, the TB laboratory quality system was not implemented. The NLTCP of Liberia should develop strategies to overcome its challenges in TB laboratory testing.

Infect and Inject: How Mycobacterium tuberculosis Exploits Its Major Virulence-Associated Type VII Secretion System, ESX-1.

Mycobacterium tuberculosis is an ancient master of the art of causing human disease. One important weapon within its fully loaded arsenal is the type VII secretion system. M. tuberculosis has five of them: ESAT-6 secretion systems (ESX) 1 to 5. ESX-1 has long been recognized as a major cause of attenuation of the FDA-licensed vaccine Mycobacterium bovis BCG, but its importance in disease progression and transmission has recently been elucidated in more detail. This review summarizes the recent advances in (i) the understanding of the ESX-1 structure and components, (ii) our knowledge of ESX-1's role in hijacking macrophage function to set a path for infection and dissemination, and (iii) the development of interventions that utilize ESX-1 for diagnosis, drug interventions, host-directed therapies, and vaccines.

Correlates of GLA family adjuvants' activities.

Lipopolysaccharide (LPS) is a well-defined agonist of Toll-like receptor (TLR) 4 that activates innate immune responses and influences the development of the adaptive response during infection with Gram-negative bacteria. Many years ago, Dr. Edgar Ribi separated the adjuvant activity of LPS from its toxic effects, an effort that led to the development of monophosphoryl lipid A (MPL). MPL, derived from Salmonella minnesota R595, has progressed through clinical development and is now used in various product-enabling formulations to support the generation of antigen-specific responses in several commercial and preclinical vaccines. We have generated several synthetic lipid A molecules, foremost glucopyranosyl lipid adjuvant (GLA) and second-generation lipid adjuvant (SLA), and have advanced these to clinical trial for various indications. In this review we summarize the potential and current positioning of TLR4-based adjuvant formulations in approved and emerging vaccines.

Rheumatology science and practice in India.

The practice of rheumatology in a country like India presents its own unique challenges, including the need to manage patients in a cost-constrained setting, where the lack of uniform government funding for healthcare merits the need to optimize the use of cheaper medicines, as well as devise innovative strategies to minimize the use of costlier drugs such as biologic disease-modifying agents. Use of immunosuppressive agents is also associated with increased risks of infectious complications, such as the reactivation of tuberculosis. In this narrative review, we provide a flavor of such challenges unique to Rheumatology practice in India, and review the published literature on the management of common rheumatic diseases from India. In addition, we critically review existing guidelines for the management of rheumatic diseases from this part of the world. We also discuss infectious etiologies of rheumatic complaints, such as leprosy, tuberculosis, and Chikungunya arthritis, which are often encountered here, and pose a diagnostic as well as therapeutic challenge for clinicians. There remains a need to identify and test more cost-effective strategies for Indian patients with rheumatic diseases, as well as the requirement for more government participation to enhance scant facilities for the treatment of such diseases as well as foster the development of healthcare services such as specialist nurses, occupational therapists and physiotherapists to enable better management of these conditions.

Performance of the National Tuberculosis Control Program in the post conflict Liberia.

BACKGROUND: Tuberculosis is a major public health problem in Liberia. According to the World Health Organization (WHO), the incidence of tuberculosis in Liberia is significantly increasing from year to year. However, little is known about the performance of the programme and the challenges after the 14 years of civil war which ended in 2003.The purpose of the study was to evaluate the performance of the TB programme of Liberia. METHODS: The study utilised mixed research design; both quantitative and qualitative methods were used in this study conducted from 2013 to 2014. For the quantitative part of the study, a questionnaire, laboratory performance and eleven years TB programme data (2003-2013) were used. For the performance of tuberculosis laboratory testing, all the 107 functional tuberculosis microscopy centers in Liberia were included. For the qualitative part of the study, an interview of 10 informants and two focus group discussions (FGDs) were also conducted, each comprising of eight people. Themes and subthemes emerged from the two FGDs. Data was analysed in line with the Donabedian model. Quantitative findings were analysed and presented using both descriptive and inferential statistics. RESULTS: The study findings pointed out that there was overall improvement in the performance of the tuberculosis control programme in Liberia from 2003 to 2013. The percentage of cured patients was 60% in 2005 and 62% in 2013. Percentage of treatment completed was 16% in 2005 and 21% in 2013. The case detection rate was 57% and treatment success rate 80% in 2013. The default rate was 11% in 2013. Of the 139 participants, 120 (86%) completed TB treatment while 19 (14%) did not. CONCLUSION: Between 2003 and 2013, the National Leprosy and Tuberculosis Control Programme (NLTCP) succeeded in restoring the TB services and improving some of the TB treatment outcomes including the Directly observed treatment short courses(DOTS) coverage. Despite these improvements, the TB treatment, laboratory services and human resource capacity lagged behind. The TB programme of Liberia needs to develop new strategies to address its challenges.

BCG vaccine: WHO position paper, February 2018 - Recommendations.

This article presented the World Health Organization's (WHO) recommendations on the use of on Bacille Calmette-Guérin (BCG) vaccine excerpted from the BCG vaccines: WHO position paper - February 2018 published in the Weekly Epidemiological Record [1]. This position paper replaces the 2004 WHO position paper on Bacille Calmette-Guérin (BCG) vaccine [2] and the 2007 WHO revised BCG vaccination guidelines for infants at risk for human immunodeficiency virus (HIV) infection [3]. It incorporates recent developments in the tuberculosis (TB) field, provides revised guidance on the immunization of children infected with HIV, and re-emphasizes the importance of the birth dose. This position paper also includes recommendations for the prevention of leprosy. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation tables. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of cholera vaccines were discussed by the Strategic Advisory Group of Experts (SAGE) in October 2017; evidence presented at these meetings can be accessed at: http://www.who.int/immunization/sage/meetings/2017/october/presentations_background_docs/en/.

Synthesis and immunogenicity of PG-tb1 monovalent glycoconjugate.

A PG-tb1 hapten from the West Beijing strains of Mycobacterium tuberculosis cell wall has been efficiently synthesized and conjugated to CRM197 in a simple way as linker-equipped carbohydrate by applying squaric acid chemistry for an original neoglycoprotein, creating a potent T-dependent conjugate vaccine. The intermediate monoester can be easily purified and the degree of incorporation can be monitored by MALDI-TOF mass spectrometry. After administered systemically in mice without any adjuvant, the conjugate induced high antigen-specific IgG levels in serum. Furthermore, following the third immunization, significant antibody titers frequently exceeding 0.8 million were observed in the sera of mice vaccinated with PG-CRM197 conjugate which showed the potential for preparation of TB vaccine.

Feasibility of a combined camp approach for vector control together with active case detection of visceral leishmaniasis, post kala-azar dermal leishmaniasis, tuberculosis, leprosy and malaria in Bangladesh, India and Nepal: an exploratory study.

BACKGROUND: We assessed the feasibility and results of active case detection (ACD) of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and other febrile diseases as well as of bednet impregnation for vector control. METHODS: Fever camps were organized and analyzed in twelve VL endemic villages in Bangladesh, India, and Nepal. VL, PKDL, tuberculosis, malaria and leprosy were screened among the febrile patients attending the camps, and existing bednets were impregnated with a slow release insecticide. RESULTS: Among the camp attendees one new VL case and two PKDL cases were detected in Bangladesh and one VL case in Nepal. Among suspected tuberculosis cases two were positive in India but none in the other countries. In India, two leprosy cases were found. No malaria cases were detected. Bednet impregnation coverage during fever camps was more than 80% in the three countries. Bednet impregnation led to a reduction of sandfly densities after 2 weeks by 86% and 32%, and after 4 weeks by 95% and 12% in India and Nepal respectively. The additional costs for the control programmes seem to be reasonable. CONCLUSION: It is feasible to combine ACD camps for VL and PKDL along with other febrile diseases, and vector control with bednet impregnation.

A public-private partnership to reduce tuberculosis burden in Akwa Ibom State, Nigeria.

BACKGROUND: Tuberculosis (TB) infection and spread are preventable, and TB disease is curable depending on individual and community knowledge of causes of the disease, mode of prevention and cure. An earlier educational intervention carried out in Akwa Ibom State (AKS) of Nigeria in 2006 created awareness of the disease and improved utilization of orthodox medical facilities of residents in 34 communities who had symptoms of TB. OBJECTIVE: The overall aim of this program is to reduce the burden of TB disease in 18 communities of AKS through educational intervention, TB case detection and integration into the State National Tuberculosis and Leprosy Control Programme (NTBLCP), as well as build laboratory capacity to improve TB case detection and control. METHODS: Prior to the educational intervention in each community, standard pretested questionnaires were administered to residents to test their knowledge, attitudes and practices concerning TB. Information about causes, symptoms and prevention of TB was disseminated in community town halls, churches, markets and schools. Individuals who were coughing for three weeks or more were investigated for TB following clinical examination by a physician. Three sputum samples (spot-morning-spot) were obtained from each individual and examined microscopically for the presence of acid-fast bacilli (AFB) using the Ziehl-Neelson staining technique. Those with positive AFB results were integrated into the existing NTBLCP treatment facilities for immediate commencement of Directly-Observed Therapy Short Course (DOTS). Treatment outcome was monitored by retesting patients' sputum after two, five and seven months. Two new laboratories were facilitated while existing laboratory capacity was built by providing higher resolution microscopes, power generating plants, refrigerators, locally-fabricated incinerators and furnishing of staff offices. The program was facilitated by a public-private partnership. Effective Health Care Alliance Research Programme (EHCARP-Nigeria), in collaboration with Nigeria National Petroleum Cooperation and Mobil Producing Nigeria Unlimited (NNPC/MPN) Joint Venture, utilized health personnel from the Akwa Ibom State NTBLCP who conducted laboratory testing and supervised the treatment. RESULTS: The 916 responses to the questionnaires showed that 65.3% (549/841) correctly identified that TB is airborne, and 86% (749/871) were aware that TB could be cured by anti-TB medication. Responses to care-seeking attitudes were provided by 123 respondents. Of this number, fear of stigmatization was the reason for 31% (38) seeking care in unorthodox facilities, while 43.1% (53) did not believe that orthodox medicine could cure their symptoms. Of the 374 detected cases, 9 did not commence treatment. Hence, 365 were placed on DOTS; 36 defaulted, while 11 either died or failed to convert after the seventh month. At the end of month 8, cure was achieved for 87.1% (318). CONCLUSION: Although the previous intervention may have contributed to the good knowledge about TB and care-seeking attitudes displayed by respondents in the communities, sustaining active case finding through public-private partnership can go a long way to reduce TB burden, especially in rural communities where healthcare systems are generally weak or inadequate. Adequate funding of TB control activities is critical in eliminating TB as a public health problem, and the private sector participation such as this is a welcome development.

rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy.

Mycobacterium tuberculosis: approach to development of improved strategies for disease control through vaccination and immunodiagnosis.

Tuberculosis is a major health problem throughout the world causing large number of deaths, more than that from any other single infectious disease. Estimates till date ascertain the fact that Tuberculosis (TB) is continuing to be the leading cause of death worldwide. The infection from single infectious agent Mycobacterium tuberculosis is killing about 3 million individuals every year and accounts for around 18.5% of all deaths in adults between the age group of 15 and 65. An average of 1.79 billion people, which constitutes roughly one-third of the world's population, is infected with the causative agent M. tuberculosis and is at risk of developing the disease. This situation highlights the relative shortcomings of the current treatment and diagnosis strategies for TB and the limited effectiveness of public health systems, particularly in resource-poor countries where the main TB burden lies. The timely identification of persons infected with Mycobacterium tuberculosis and rapid laboratory confirmation of tuberculosis are two key factors for the treatment and prevention of the disease. Novel molecular assays for diagnosis and drug susceptibility testing offer several potential advantages over the above methods including faster turnaround times, very sensitive and specific detection of nucleic acids, and minimal, or possibly no, prior culture. The need for new technologies for rapid diagnosis of tuberculosis is clear. Most studies of mycobacterial immunity attributes focus on proliferation of T cells, production of cytokines and cytolytic activity. A proper vaccine for tuberculosis can be developed by using a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. Development of new vaccines against TB should include some important aspects learned from BCG use such as mucosal routes of immunization; revaccination of BCG immunized subjects, booster immunization and prime-boost strategy with wild-type BCG, and other vaccine candidates. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future.