Tuberculosis Infection Prevention Research Articles

Bacillus Calmette-Guérin (BCG) Revaccination and Protection Against Tuberculosis: A Systematic Review.

Bacillus Calmette-Guérin (BCG) vaccination remains a cornerstone in global efforts to combat tuberculosis (TB), a persistent public health threat worldwide. The purpose of this systematic review is to find out how well BCG revaccination protects against TB. This systematic review synthesized recent studies investigating the efficacy of BCG vaccination in preventing TB infection and disease. A total of 15 relevant publications were identified through a comprehensive search across multiple databases, including Cochrane Library, PubMed, Medline, and Scopus. The inclusion criteria encompassed studies involving humans, written in English, and categorized as case-control, cohort, meta-analysis, or full-text. Studies were selected based on their relevance to BCG revaccination and protection against TB, and a standardized data extraction form was used to gather pertinent information from each study. Quality assessment was conducted using established tools to evaluate the rigor, study design, and risk of bias in each included study. The findings revealed significant insights into BCG's effectiveness across different populations and age groups. Several studies demonstrated a substantial reduction in latent TB infection (LTBI) and incidence rates of TB following BCG vaccination. However, the protective efficacy of BCG revaccination varied across studies and populations, with some indicating modest protection against TB disease development, particularly in high-risk populations like healthcare workers. Furthermore, investigations into the immunological mechanisms underlying BCG's protective efficacy provided valuable insights into cytokine/chemokine profiles and immunomodulatory properties.

Investigating socio-ecological factors influencing implementation of tuberculosis infection prevention and control in rural Papua New Guinea.

Tuberculosis (TB) is a highly transmissible infectious disease killing millions of people yearly, particularly in low-income countries. TB is most likely to be transmitted in healthcare settings with poor infection control practices. Implementing TB infection prevention and control (TB-IPC) is pivotal to preventing TB transmission in healthcare settings. This study investigated diverse stakeholders' perspectives relating to barriers and strategies for TB-IPC in rural hospitals in Papua New Guinea. Multiple qualitative case studies were conducted with 32 key stakeholders with experience in TB services. Data collection drew on three primary sources to triangulate data: semi-structured interviews, document reviews and field notes. The data were analyzed using hybrid deductive-inductive thematic analysis. Our results reveal that key stakeholders perceive multiple interdependent factors that affect TB-IPC practice. The key emerging themes include strategic planning for and prioritizing TB-IPC guidelines; governance, leadership and accountability at the provincial level; community attitudes towards TB control; institutional capacity to deliver TB care, healthcare workers' safety, and long-term partnership and integration of TB-IPC programmes into the broad IPC programme. The evidence suggests that a multi-perspective approach is crucial for TB-IPC guidelines in healthcare institutions. Interventions focusing on addressing health systems strengthening may improve the implementation of TB-IPC guidelines.

Implementing a continuous quality-improvement framework for tuberculosis infection prevention and control in healthcare facilities in China, 2017-2019.

Tuberculosis (TB) infection prevention and control (IPC) in healthcare facilities is key to reducing transmission risk. A framework for systematically improving TB IPC through training and mentorship was implemented in 9 healthcare facilities in China from 2017 to 2019. Facilities conducted standardized TB IPC assessments at baseline and quarterly thereafter for 18 months. Facility-based performance was assessed using quantifiable indicators for IPC core components and administrative, environmental, and respiratory protection controls, and as a composite of all control types We calculated the percentage changes in scores over time and differences by IPC control type and facility characteristics. Scores for IPC core components increased by 72% during follow-up when averaged across facilities. The percentage changes for administrative, environmental, and respiratory protection controls were 39%, 46%, and 30%, respectively. Composite scores were 45% higher after the intervention. Overall, scores increased most during the first 6 months. There was no association between IPC implementation and provincial economic development or volume of TB services. TB IPC policies and practices showed most improvement early during implementation and did not differ consistently by facility characteristics. The training component of the project helped increase the capacity of healthcare professionals to manage TB transmission risks. Lessons learned here will inform national TB IPC guidance.

Knowledge, Attitude and Practice towards Prevention of Tuberculosis amongst Healthcare Workers in Dr. Lawrence Henshaw’s Memorial Hospital, Calabar, Cross River State

Despite the availability of tuberculosis (TB) infection control guidelines, research evidence suggests that its implementation seems to be inadequate in many settings including healthcare facilities. This is particularly due to inadequate knowledge and inappropriate attitude of healthcare workers towards TB prevention and control. This study was conducted as an attempt to investigate knowledge, attitude and practice towards prevention of TB among healthcare workers in Dr. Lawrence Henshaw’s Memorial Hospital, Calabar, Cross River State. Three (3) research questions were raised and two (2) hypotheses formulated to direct the course of this study. A descriptive cross-sectional survey was used to study a total of 87 healthcare workers selected from the Healthcare Facility using stratified random sampling technique. The instrument for data collection was validated and reliable questionnaire constructed in consonance with the objectives of the study. Data collected were described using frequency counts, simple percentage, mean, and standard deviation, while the study hypotheses were tested using Pearson Product Moment Correlation Coefficient significant at p<0.05. Results of the study revealed that majority of the respondents had adequate knowledge, positive attitude, and fairly good practice towards prevention of TB infection. There is a statistically significant and positive relationship between knowledge of TB, attitude towards prevention of TB; and practice towards prevention of TB among healthcare workers in Dr. Lawrence Henshaw’s Memorial Hospital, Calabar (p<0.05). It was therefore recommended that healthcare workers should be trained and re-trained through prompt participation in seminars, workshops, and conferences on TB infection prevention and control as an avenue to improve their knowledge and promote practice towards prevention and control of TB in the Hospital.

Cost of inaction: a framework to estimate the economic cost of missing a patient with tuberculosis in the Indian context

ObjectivesTo estimate the economic impact of failure to find and treat tuberculosis disease and prevent tuberculosis infection from progressing to active disease.DesignEstimating the economic cost of not finding and treating...

Design and development of a multi‐epitope vaccine for the prevention of latent tuberculosis infection

AbstractBackgroundLatent tuberculosis infection (LTBI) often progresses to active tuberculosis, necessitating the development of novel vaccine to prevent LTBI. In this study, we aimed to design a Mycobacterium tuberculosis (M. tuberculosis) vaccine that could elicit a potent immune response to prevent LTBI.MethodsWe used bioinformatics and immunoinformatics techniques to develop a multi‐epitope vaccine (MEV) called C624P. The vaccine contained six cytotoxic T lymphocytes (CTL), two helper T lymphocytes (HTL), and four B‐cell epitopes derived from six antigens associated with LTBI and the Mycobacterium tuberculosis region of difference. We added Toll‐like receptor (TLR) agonists and PADRE peptide to the MEV to enhance its immunogenicity. We then analyzed the C624P vaccine's physical and chemical properties, spatial structure, molecular docking with TLRs, and immunological features.ResultsThe C624P vaccine displayed good antigenicity and immunogenicity scores of 0.901398 and 3.65609, respectively. The vaccine structure was stable, with 42.82% α‐helix content, a Z‐value of −7.84, and a favored Ramachandran plot area of 85.84% after majorization. Molecular docking analysis showed that the C624P vaccine could bind tightly to TLR2 (−1011.0 kcal/mol) and TLR4 (−941.4 kcal/mol). Furthermore, the C624P vaccine effectively stimulated T and B lymphocytes, resulting in high levels of Th1 cytokines such as IFN‐γ and IL‐2.ConclusionsThe C624P vaccine represents a promising MEV for preventing LTBI. The vaccine's good antigenicity, immunogenicity, stability, and ability to activate immune responses suggest its effectiveness in preventing LTBI. Our study demonstrated the utility of bioinformatics and immunoinformatics techniques in designing safe and effective tuberculosis vaccines.

Tuberculosis infection prevention and control in rural Papua New Guinea: an evaluation using the infection prevention and control assessment framework

Tuberculosis infection prevention and control in rural Papua New Guinea: an evaluation using the infection prevention and control assessment framework

Right to Occupational Safety: Prevalence of Latent Tuberculosis Infection in Healthcare Workers. A 1-Year Retrospective Survey Carried out at Hospital of Lecce (Italy).

Prevention of latent tuberculosis infection (LTBI) in healthcare workers (HCWs) to ensure the "Right to Occupational Safety" is a special challenge globally, as HCWs have a higher risk of acquiring the infection in hospital settings because of frequent close exposure to patients suffering from tuberculosis (TB). Aretrospective study was performed with the aim of assessing the prevalence of LTBI related to demographical and occupational risk factors among HCWs employed in a large hospital in Italy. The study involved 1461 HCWs screened for LTBI by Mantoux tuberculin skin test (TST) and then confirmed with Interferon Gamma Release Assay (IGRA) test in case of positivity. Immunosuppressed and BGC-vaccinated workers were tested directly with IGRA. LTBI was diagnosed in 4.1% of the HCWs and the prevalence resulted lower than other studies conducted in low TB incidence countries. The variables significantly linked with higher frequency of the infection were: age ≥40 years (OR = 3.14; 95% CI: 1.13-8.74; p < 0.05), length of service ≥15 years (OR = 4.11; 95% CI: 1.48-11.43; p < 0.05) and not being trained on TB prevention (OR = 3.46; 95% CI: 1.85-6.46; p < 0.05). Not trained HCWs presented a higher risk of LTBI also after adjustment for age and length of service, compared to trained HCWs. screening of HCWs for LTBI should be always considered in routinely occupational surveillance in order to early diagnose the infection and prevent its progression. Safety policies in hospital settings centered on workers' training on TB prevention is crucial to minimize LTBI occurrence in HCWs.

Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung

Intravesical administration of Bacillus Calmette-Guérin (BCG) was one of the first FDA-approved immunotherapies and remains a standard treatment for bladder cancer. Previous studies have demonstrated that intravenous (IV) administration of BCG is well-tolerated and effective in preventing tuberculosis infection in animals. Here, we examine IV BCG in several preclinical lung tumor models. Our findings demonstrate that BCG inoculation reduced tumor growth and prolonged mouse survival in models of lung melanoma metastasis and orthotopic lung adenocarcinoma. Moreover, IV BCG treatment was well-tolerated with no apparent signs of acute toxicity. Mechanistically, IV BCG induced tumor-specific CD8+ T cell responses, which were dependent on type 1 conventional dendritic cells, as well as NK cell-mediated immunity. Lastly, we also show that IV BCG has an additive effect on anti-PD-L1 checkpoint inhibitor treatment in mouse lung tumors that are otherwise resistant to anti-PD-L1 as monotherapy. Overall, our study demonstrates the potential of systemic IV BCG administration in the treatment of lung tumors, highlighting its ability to enhance immune responses and augment immune checkpoint blockade efficacy.

Tuberculosis medication adherence in a secondary care center in SouthEastern Nigeria

Adherence to a treatment strategy known as Directly Observed Treatment Short course (DOTS) by patients diagnosed of tuberculosis is essential in the effective treatment of the disease. This is in order to avoid recurrence, resistance and complications that results from non-adherence. This paper assessed the adherence to anti-tuberculosis medications among tuberculosis patients in a secondary healthcare facility in Anambra State, Nigeria. This was a descriptive crosssectional study and a semi-structured interviewer-administered questionnaire was used. The study population comprised of tuberculosis patients who has been on anti-TB medications for at least four weeks at the Tuberculosis clinic. A systematic random sampling technique was used to enrol the respondents into the study. The mean age of the respondents was 39.68±16.66 years. Majority of the respondents correctly alluded to tuberculosis as being caused by bacteria (91.7%); and that the duration of treatment was at least six months (100.0%). A great proportion of the respondents affirmed that a vaccine is available for prevention of tuberculosis infection (91.7%); also all the respondents agreed that covering mouth and nose while coughing/sneezing is a preventive measure of TB spread (100.0%). About 15.2% of the respondents sometimes stop taking their medications when they feel their health condition is under control, however, a great proportion of the respondents had good adherence to medications (76.0%). Major reasons for missing medication among the non-adherent were that they forgot (91.8%) and that there were too much medication to take at once (1.2%). Statistically significant associations existed between drug adherence and age, sex and educational qualification; as respondents within the age range of 60-69 years, female and those who had completed tertiary education had better adherence to anti-TB medications. TB medication non-adherence is a potential risk factor for poor health outcomes, hence more effort is needed to increase the rate of adherence.

Role of Attitude in Influencing Compliance with Tuberculosis Infection Prevention and Control Guidelines among Healthcare Workers

Role of Attitude in Influencing Compliance with Tuberculosis Infection Prevention and Control Guidelines among Healthcare Workers

A CRISPR-Cas12a-based platform for ultrasensitive rapid highly specific detection of Mycobacterium tuberculosis in clinical application.

Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is the second leading cause of death after COVID-19 pandemic. Here, we coupled multiple cross displacement amplification (MCDA) technique with CRISPR-Cas12a-based biosensing system to design a novel detection platform for tuberculosis diagnosis, termed MTB-MCDA-CRISPR. MTB-MCDA-CRISPR pre-amplified the specific sdaA gene of MTB by MCDA, and the MCDA results were then decoded by CRISPR-Cas12a-based detection, resulting in simple visual fluorescent signal readouts. A set of standard MCDA primers, an engineered CP1 primer, a quenched fluorescent ssDNA reporter, and a gRNA were designed targeting the sdaA gene of MTB. The optimal temperature for MCDA pre-amplification is 67°C. The whole experiment process can be completed within one hour, including sputum rapid genomic DNA extraction (15 minutes), MCDA reaction (40 minutes), and CRISPR-Cas12a-gRNA biosensing process (5 minutes). The limit of detection (LoD) of the MTB-MCDA-CRISPR assay is 40 fg per reaction. The MTB-MCDA-CRISPR assay does not cross reaction with non-tuberculosis mycobacterium (NTM) strains and other species, validating its specificity. The clinical performance of MTB-MCDA-CRISPR assay was higher than that of the sputum smear microscopy test and comparable to that of Xpert method. In summary, the MTB-MCDA-CRISPR assay is a promising and effective tool for tuberculosis infection diagnosis, surveillance and prevention, especially for point-of-care (POC) test and field deployment in source-limited regions.

Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicenter phase 3 double-blind randomized placebo-controlled trial (ViDiKids)

To determine whether weekly oral supplementation with 10,000 IU vitamin D3for 3 years reduces the risk of sensitization toM. tuberculosisin South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline. We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect. 829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D3 vs. placebo, respectively. Mean end-study 25(OH)D concentrations in participants randomized to vitamin D vs. placebo were 104.3 vs 64.7 nmol/l, respectively (95% confidence interval for difference, 37.6 to 41.9 nmol/l). A total of 76/667 (11.4%) participants allocated to vitamin D vs. 89/687 (13.0%) participants allocated to placebo tested QFT-Plus positive at 3-year follow-up (adjusted odds ratio 0.86, 95% confidence interval 0.62-1.19, P=0.35). Weekly oral supplementation with 10,000 IU vitamin D3 for 3 years elevated serum 25(OH)D concentrations among QFT-Plus-negative Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion.

Predicting the Progress of Tuberculosis by Inflammatory Response-Related Genes Based on Multiple Machine Learning Comprehensive Analysis.

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, affects approximately one-quarter of the global population and is considered one of the most lethal infectious diseases worldwide. The prevention of latent tuberculosis infection (LTBI) from progressing into active tuberculosis (ATB) is crucial for controlling and eradicating TB. Unfortunately, currently available biomarkers have limited effectiveness in identifying subpopulations that are at risk of developing ATB. Hence, it is imperative to develop advanced molecular tools for TB risk stratification. The TB datasets were downloaded from the GEO database. Three machine learning models, namely LASSO, RF, and SVM-RFE, were used to identify the key characteristic genes related to inflammation during the progression of LTBI to ATB. The expression and diagnostic accuracy of these characteristic genes were subsequently verified. These genes were then used to develop diagnostic nomograms. In addition, single-cell expression clustering analysis, immune cell expression clustering analysis, GSVA analysis, immune cell correlation, and immune checkpoint correlation of characteristic genes were conducted. Furthermore, the upstream shared miRNA was predicted, and a miRNA-genes network was constructed. Candidate drugs were also analyzed and predicted. In comparison to LTBI, a total of 96 upregulated and 26 downregulated genes related to the inflammatory response were identified in ATB. These characteristic genes have demonstrated excellent diagnostic performance and significant correlation with many immune cells and immune sites. The results of the miRNA-genes network analysis suggested a potential role of hsa-miR-3163 in the molecular mechanism of LTBI progressing into ATB. Moreover, retinoic acid may offer a potential avenue for the prevention of LTBI progression to ATB and for the treatment of ATB. Our research has identified key inflammatory response-related genes that are characteristic of LTBI progression to ATB and hsa-miR-3163 as a significant node in the molecular mechanism of this progression. Our analyses have demonstrated the excellent diagnostic performance of these characteristic genes and their significant correlation with many immune cells and immune checkpoints. The CD274 immune checkpoint presents a promising target for the prevention and treatment of ATB. Furthermore, our findings suggest that retinoic acid may have a role in preventing LTBI from progressing to ATB and in treating ATB. This study provides a new perspective for differential diagnosis of LTBI and ATB and may uncover potential inflammatory immune mechanisms, biomarkers, therapeutic targets, and effective drugs in the progression of LTBI into ATB.

Tuberculosis infection prevention and control in rural Papua New Guinea: an evaluation using the infection prevention and control assessment framework

BackgroundPapua New Guinea (PNG) is one of the 14 countries categorised as having a triple burden of tuberculosis (TB), multidrug-resistant TB (MDR TB), and TB-human immunodeficiency virus (HIV) co-infections. TB infection prevention and control (TB-IPC) guidelines were introduced in 2011 by the National Health Department of PNG. This study assesses the implementation of this policy in a sample of district hospitals in two regions of PNG.MethodsThe implementation of TB-IPC policy was assessed using a survey method based on the World Health Organization (WHO) IPC assessment framework (IPCAF) to implement the WHO’s IPC core components. The study included facility assessment at ten district hospitals and validation observations of TB-IPC practices.ResultsOverall, implementation of IPC and TB-IPC guidelines was inadequate in participating facilities. Though 80% of facilities had an IPC program, many needed more clearly defined IPC objectives, budget allocation, and yearly work plans. In addition, they did not include senior facility managers in the IPC committee. 80% (n = 8 of 10) of hospitals had no IPC training and education; 90% had no IPC committee to support the IPC team; 70% had no surveillance protocols to monitor infections, and only 20% used multimodal strategies for IPC activities. Similarly, 70% of facilities had a TB-IPC program without a proper budget and did not include facility managers in the TB-IPC team; 80% indicated that patient flow poses a risk of TB transmission; 70% had poor ventilation systems; 90% had inadequate isolation rooms; and though 80% have personal protective equipment available, frequent shortages were reported.ConclusionsThe WHO-recommended TB-IPC policy is not effectively implemented in most of the participating district hospitals. Improvements in implementing and disseminating TB-IPC guidelines, monitoring TB-IPC practices, and systematic healthcare worker training are essential to improve TB-IPC guidelines’ operationalisation in health settings to reduce TB prevalence in PNG.

NATCON 2022 Panel discussion: “TB vaccination - Going Forward”

Vaccination is important tuberculosis (TB) preventive strategy that is essential to achieve the goals of the End TB strategy. The BCG vaccination at birth offers protection against TB in young children but not in adolescents and adults. New TB vaccines are the need of the hour. The TB vaccine development pipeline in the past years is encouraging with newer TB vaccines in clinical trials in humans. The focus of the newer TB vaccine is the prevention of infection, disease, and recurrence of TB disease. Therapeutic vaccines focus on better treatment outcomes and prevention of TB recurrence. BCG revaccination is of current interest. Novel, safe, and efficient TB vaccines that prevent TB infection and disease if introduced in 2025 could drastically reduce the rate of TB incidence. However, the development of an effective vaccine for TB is challenging. Engagement of stakeholders, mobilizing funding, and advocacy could accelerate the newer TB vaccine development process.

Cost-effectiveness of tuberculosis infection prevention and control interventions in South African clinics: a model-based economic evaluation informed by complexity science methods

IntroductionNosocomial Mycobacterium tuberculosis (Mtb) transmission substantially impacts health workers, patients and communities. Guidelines for tuberculosis infection prevention and control (TB IPC) exist but implementation in many settings remains suboptimal. Evidence...

Implementation of WHO guideline on tuberculosis infection prevention and control in Kaduna State, Nigeria

Implementation of WHO guideline on tuberculosis infection prevention and control in Kaduna State, Nigeria

Association of knowledge and practice of Tuberculosis infection prevention and control policies among health care personnel at a regional hospital, in Gauteng province of South Africa

BackgroundTuberculosis (TB) remains an occupational health risk among healthcare personnel (HCP) globally, with the risk of transmission present throughout healthcare settings. The presence of undiagnosed and untreated highly infectious patients poses a great risk to the HCP who are often the forefront healthcare providers of any epidemic. Genotypic analysis of infected HCP revealed similar strains to the ones identified from the patient profile of their facilities, suggestive of nosocomial transmission. The aim of the study was to determine healthcare personnel’s knowledge and practices regarding protective wear on TB prevention in Gauteng province. MethodsA non-experimental descriptive quantitative survey was used for this study. The sample was a cohort of healthcare professionals from a selected regional hospital located in Gauteng province of South Africa. Ethical approval was obtained from the University of Pretoria and the Gauteng Provincial Department of Health. Data were collected using a self-administered structured questionnaire which was distributed to the different categories of HCP at the selected facility. All analysis was conducted using Stata 15 and p-values less than 0.05 were considered statistically significant. ResultsKnowledge of infection control policies was not significantly associated with practice. However, knowledge was significantly associated with level of education. HCP with higher levels of education demonstrated good knowledge but poor practice. Conclusion and recommendationsGood knowledge of infection prevention and control policies did not result in good practice. Hence, strategies to create knowledge translation towards IPC practices among HCP need to be devised.

Tuberculosis Infection Control and Prevention in Bulgaria

Tuberculosis Infection Control and Prevention in Bulgaria