Beyond Bacillus Calmette-Guérin: A Multifaceted Strategy for Tuberculosis Prevention in the 21st Century
1. Kurmanaliev Nurlan
2. Advait Makode
Vinod Choudhari
Divya Sonje
Abhijeet Gaike
Chaitnya Gondkar
(1. Teacher, International Medical Faculty, Osh State University, Kyrgyzstan)
(2. Students, International Medical Faculty, Osh State University, Kyrgyzstan)
Abstract
The world continues to face tuberculosis (TB) as its main infectious disease which kills people, so societies must stop focusing only on treatment and adopt complete prevention programs. This article reviews the contemporary landscape of TB prevention, structured within the IMRAD (Introduction, Methods, Results, and Discussion) format. The intro- duction outlines the global burden of TB and the limitations of historical control methods. The methods section describes a narrative review of literature from 2015 to 2024, focusing on key preventive pillars: infection control, vaccination, and preventive treatment. The results are presented in three thematic areas: advances in airborne infection control and diagnostics, the status of the Bacillus Calmette-Guérin (BCG) vaccine and the promising pipeline of novel vaccines, and the expansion of Tuberculosis Preventive Treatment (TPT) regimens. The researchers used detailed discussion methods to combine their discoveries into an integrated “Prevention Ecosystem” model which explains the biomedical and social and structural health factors. The article concludes with a call to action for intensified research, equitable implementation, and global political will to bend the curve of the TB epidemic through comprehensive prevention.
INTRODUCTION
Tuberculosis (TB) originated as an ancient human disease which Mycobacterium tuberculosis bacillus causes. The World Health Organization (WHO) reported in 2022 that 10.6 million people contracted TB and 1.3 million people died from the disease which confirmed TB as the second deadliest infectious disease in the world after COVID-19 (WHO, Global Tuberculosis Report 2023 1). The global strategy to fight TB has spent decades establishing two main procedures which include active case detection and treatment delivery systems. The system saves millions of lives, yet functions through a reactive approach which requires people to become infectious before the system provides treatment. The current approach fails to meet End TB Strategy goals which require a 90% drop in TB cases and a 95% drop in TB fatalities by 2035 (WHO, The End TB Strategy 6).
The primary problem with treatment-based approaches to combat tuberculosis transmission emerges because these methods lack capacity to eliminate infection spread from original sources of disease. People who have active pulmonary tuberculosis without receiving medical diagnosis and treatment can transmit the disease to 10 to 15 individuals during one year (Pai et al. 176). The epidemic requires active preventive measures which establish a new approach to public health. The new approach demands multiple methods which need to replace the existing Bacillus Calmette-Guérin BCG vaccine that has existed for a century. The program must include stronger infection control measures and new vaccines that protect all age groups and safe short Tuberculosis Preventive Treatment TPT which all people with latent TB infection LTBI need to undergo.
The article provides an extensive academic assessment which evaluates all current methods used to prevent tuberculosis. The study will investigate the most recent developments and existing obstacles and upcoming research paths within three main fields of prevention which include (1) infection control methods that stop people from getting infected and (2) vaccination programs that protect people from becoming infected and (3) preventive treatment methods which stop infection spread to full-blown diseases. The article demonstrates through recent research findings and worldwide policy recommendations that an integrated prevention system which focuses on social justice represents the only effective solution to eliminate tuberculosis.
METHODS
The article provides a narrative review of all scholarly research and official tuberculosis prevention documents which have been published in scientific journals. The team executed a comprehensive search of PubMed Scopus and Web of Science databases to find articles which were published during the time period from January 2015 until March 2024. The search strategy used a mix of keywords and Medical Subject Headings (MeSH) terms which included “Tuberculosis/prevention and control” “Latent Tuberculosis” “BCG vaccine” “Tuberculosis Vaccines” “Infection Control” “Contact Tracing” “Isoniazid/therapeutic use” “Rifampin/ therapeutic use” and “Public Health”.
The research study required human subject research as the main inclusion requirement, while English language articles and research about main prevention pillars and World Health Organization guidelines and technical reports were allowed for inclusion. The research study used three exclusion criteria which included case reports and opinion pieces which lacked relevant evidence and research studies which examined tuberculosis treatment outcomes but did not include preventive measures.
The researchers obtained essential information about the effectiveness of different protective measures together with the obstacles to their implementation and their financial benefits and their effects on community health. The review uses primary research together with WHO Global Tuberculosis Reports (2015–2023) and WHO consolidated guidelines on tuberculosis preventive treatment as its main sources. The following section presents the findings through thematic synthesis work.
RESULTS
The analysis of recent literature reveals significant progress and persistent challenges across the three pillars of TB prevention. The results are presented here to establish a clear evidence base for the discussion.
Pillar I: Preventing Exposure - Infection Control and Contact Investigation
The main method to protect against M. tuberculosis transmission requires staff members to use protective equipment. The study shows that people contract the disease mostly in shared living spaces which include homes and medical centers and correctional institutions and mining sites.
Airborne Infection Control
The COVID-19 pandemic demonstrated to everyone the need for airborne infection control systems. The WHO infection control hierarchy which includes administrative controls and environmental controls and personal respiratory protection requires basic implementation in high- burden settings. Organizations must use administrative controls which include rapid triage and separation of infectious patients to achieve maximum cost savings but these controls face implementation challenges because of staff shortages and insufficient training. Natural ventilation systems serve as an effective environmental control method. Escombe et al. conducted research which showed that healthcare facilities can achieve air changes through window and door operation that match mechanical ventilation systems while decreasing airborne bacilli levels (Escombe et al. 635). This method proves impossible to execute because modern energy-efficient buildings maintain their windows in a closed position. GUV upper-room germicidal ultraviolet irradiation has returned as an efficient budget-friendly solution. GUV fixtures operate at their maximum efficiency to cut down TB transmission between guinea pigs which act as human risk surrogates by 70–80% through correct installation and maintenance (Mphaphele et al. 11).
Contact Investigation and Digital Technologies
Contact investigations serve as the fundamental method used for disease prevention efforts. The results obtained from contact investigations show significant differences throughout various situations. A systematic review by Fox et al. found that the prevalence of TB among household contacts is substantial, ranging from 1.4% to 12.3%, with the highest rates in young children and individuals with HIV (Fox et al. 10). This confirms the high-risk nature of this population. Digital health technologies are now enhancing these traditional methods. Geospatial map- ping has been used to identify transmission “hotspots”. The complete understanding of trans- mission patterns has experienced a significant change through the development of whole-genome sequencing (WGS) technology. WGS provides a higher resolution than traditional genotyping, allowing researchers to confirm or refute suspected transmission links and identify previously unknown community transmission chains (Gardy and Loman 181). Public health teams use this precision to create better-targeted intervention strategies.
Pillar II: Preventing Infection - Vaccination
The effectiveness of vaccination programs makes them the best method to protect public health by stopping infectious diseases. The existing medical system uses the BCG vaccine which has been approved since its introduction while researchers work on developing new vaccination op- tions.
The Current Standard: BCG
The BCG vaccine developed more than 100 years ago stands as the sole approved vaccine for tuberculosis. The vaccine demonstrates proven effectiveness because it prevents severe forms of tuberculosis which include TB meningitis and miliary TB in infants and young children with protection rates above 80% according to research by Mangtani and his team. The vaccine demonstrates variable effectiveness against pulmonary tuberculosis in adolescents and adults which ranges from 0% to 80% according to different geographical studies. Different strains of Mycobacterium tuberculosis and the genetic makeup of different populations.
The Vaccine Pipeline
The research and development process gained momentum after BCG failed to stop the tuberculosis epidemic. The most important recent advancement in science comes from the M72/AS01E candidate which exists as a potential vaccine. The Phase 2b trial results show 50% efficacy for TB disease prevention in latently infected adults which serves as the initial demonstration that post-infection vaccines can work (Van Der Meeren et al. 1621). This vaccine has potential to become a revolutionary treatment if ongoing Phase 3 trials confirm its effectiveness.
Pillar III: Preventing Progression - Tuberculosis Preventive Treatment (TPT)
The LTBI treatment approach serves as a vital method which protects high-risk populations from developing active tuberculosis. The medical community adopted daily isoniazid treatment (6–9H) for 6–9 months as the standard treatment for several decades but patients struggled to complete their treatment because of its extended duration and side effects. The field of tubercu- losis preventive treatment (TPT) has undergone major changes during recent years through the introduction of new shorter and safer treatment methods which have gained official recognition.
Newer, Shorter Regimens
WHO currently recommends several shorter regimens which clinical trials have proven effective.
The expansion of TPT has been particularly impactful for people living with HIV (PLHIV). According to studies TPT together with antiretroviral therapy (ART) helps this group achieve a 60–70% decrease in tuberculosis (TB) risk (TEMPRANO ANRS 12136 Study Group 21). The 1HP regimen development creates better methods for healthcare providers to apply TPT within HIV treatment programs.
Diagnostic Challenges for LTBI
The absence of a gold-standard diagnostic test for LTBI represents a major obstacle that hinders TPT implementation. The Tuberculin Skin Test (TST) and Interferon-Gamma Release Assays (IGRAs) represent the two main test types which both show major testing shortcomings. The tests assess immunological memory yet they fail to identify whether an individual has recovered from an infection or if they have reached true latency or if their condition is turning into an active infectious state. The tests show inadequate results for people who have weakened immune systems. Researchers are testing RNA sequencing (RNA-Seq) transcriptional signatures to discover a “risk signature” which will forecast upcoming active disease development for months ahead (Zak et al. 8). The system will provide targeted TPT treatment for individuals who show the highest risk level.
DISCUSSION
The results which we discussed before show that the field currently undergoes a process of transformation. Our organization now adopts a more specific and advanced method of prevention
which replaces the previous universal prevention method. The public health system still faces numerous difficulties which impede its ability to apply scientific progress into actual health benefits. The research proposes an implementation strategy which uses the findings to establish a TB Prevention Ecosystem which includes all necessary components.
Synthesis of Findings: The Interconnected Pillars
The three prevention pillars operate as interdependent components instead of existing as sep- arate entities. The first pillar of infection control fails to manage infections, which results in ongoing transmission that destroys vaccination benefits established by the second pillar. The M72/AS01E vaccine prevents disease but does not stop infection, which will lead to a decrease in morbidity yet requires TPT (Pillar III) for all who have already been exposed. The programs which provide TPT show high effectiveness, yet their poor implementation will result in ongoing disease transmission. Organizations need to integrate their operations to achieve successful results. The contact investigation process (Pillar I) discovers a person who has LTBI. The individual becomes eligible for short-course TPT (Pillar III) and can participate in a vaccine study or future vaccination program (Pillar II).
Building an Ecosystem to Solve the Implementation Gap Problem
The main obstacle which prevents progress from occurring exists because organizations do not implement their tools in an efficient and fair manner. We need to establish a comprehensive approach that works at multiple levels:
1. Biomedical Level: This includes the continuous optimization of tools. The medical field requires development of point-of-care testing which can identify individuals who will develop active tuberculosis and the implementation of TPT with ultra-short regimens that last under two weeks and the creation of a vaccine which protects all age groups after exposure to tuberculosis.
2. Health System Level: Health systems in high-burden countries face extreme pressure because their needs exceed their capacity and their resources remain insufficient. The implementation of tuberculosis preventive measures needs to take place through existing health services which include maternal and child health clinics and HIV treatment centers and primary healthcare facilities. The team needs to implement task-sharing because trained community health workers will handle contact investigations while they will also execute and monitor TPT procedures which will allow clinicians to manage more difficult situations. Digital adherence technologies like video-supported therapy (VOT) for 1HP treatment enable healthcare facilities to lower their operating costs.
3. Social and Structural Level: Tuberculosis exists as a disease which exists because of poverty and social discrimination. The combination of malnutrition and overcrowded housing and indoor air pollution and smoking and diabetes creates a health crisis which leads to both infection spread and disease development according to Lönnroth et al. 141. To create a prevention system for this issue each sector needs to work together to solve these social problems. The organization needs to connect tuberculosis prevention programs with food security initiatives and tobacco cessation programs and slum redevelopment projects.
4. Community and Individual Level: Stigma creates a major obstacle which prevents people from accessing healthcare services. People who experience isolation will avoid contact investigation and TPT because they fear being rejected by others. Community engagement is paramount. The process requires healthcare organizations to collaborate with community leaders and TB-affected individuals and civil society groups to develop interventions and share educational materials and establish confidence in the healthcare system.
The Challenge of Latent TB Infection
The LTBI field reaches an essential moment in its development. We have an estimated one- quarter of the world’s population infected, a massive reservoir for future disease. The treatment of these individuals stands as an impossible task which should not be attempted. The research into transcriptional risk signatures is the most promising avenue for solving this dilemma. The development of a low-cost point-of-care test which identifies the 5–10% of individuals with LTBI who will soon develop active TB will enable us to treat TPT with exacting accuracy. The new approach will allow treatment to start only for people who face immediate danger rather than all individuals who show potential risk.
Limitations of This Review
The article presents a narrative review which selects literature according to its own bias. The study does not provide a meta-analytic review of effect sizes which stem from the different interventions. The study’s requirement to use English-language literature results in the exclusion of significant research which exists in other languages.
CONCLUSION
The goal of ending the tuberculosis epidemic is ambitious but attainable, provided we embrace a radical shift toward prevention. The scientific foundation for this shift is stronger than ever. Our preventive treatment regimens which include 3HP and 4R and 1HP deliver shorter and safer treatment times which result in high success rates for curing latent infection. The M72/AS01E vaccine candidate marks the beginning of our first actual opportunity for developing a post- exposure vaccine which targets adults. Whole-genome sequencing functions as an advanced tool which enables us to track disease spread and determine effective control measures. The global community has renewed its dedication to infection control measures as a result of COVID-19 pandemic experiences.
The tools we have do not function as solutions which can instantly solve all problems. The system acquires its strength through the way its components get implemented. The approach which uses fragments of the project will lead to failure. We must move beyond pilot projects and small-scale studies to build comprehensive, integrated, and equitable national prevention programs. Health systems require funding to implement these programs at full capacity. The organization needs to address the social factors and structural aspects which create TB risk for individuals. The organization needs to establish partnerships with communities to work together on health initiatives.
The next decade will determine everything. People will closely monitor how the M72/AS01E vaccine performs during its Phase 3 trials. The invention of a point-of-care test that can detect people who are most likely to develop active tuberculosis from latent tuberculosis infection would transform the approach to targeted prevention. The new shorter TPT regimens which include the 1-month option will enable healthcare providers to deliver preventive treatment with the same ease as they handle common infections. The battle against tuberculosis functions as a demonstration of our combined determination. The challenge tests our ability to use existing scientific knowledge and create necessary tools and establish essential systems which will provide tuberculosis-free lives to all people throughout the world. Complete prevention measures must exist as the base that leads to a tuberculosis-free future.
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