Risk factors for pulmonary tuberculosis recurrence, relapse and reinfection: a systematic review and meta-analysis.

BACKGROUND: The rate of pulmonary tuberculosis (TB) recurrence is substantial. Identifying risk factors can support the development of prevention strategies. METHODS: We retrieved studies published between 1 January 1980 and 31 December 2022 that assessed factors associated with undifferentiated TB recurrence, relapse or reinfection. For factors reported in at least four studies, we performed random-effects meta-analysis to estimate a pooled relative risk (RR). We assessed heterogeneity, risk of publication bias and certainty of evidence. RESULTS: We included 85 studies in the review; 81 documented risk factors for undifferentiated recurrence, 17 for relapse and 10 for reinfection. The scope for meta-analyses was limited given the wide variety of factors studied, inconsistency in control for confounding and the fact that only few studies employed molecular genotyping. Factors that significantly contributed to moderately or strongly increased pooled risk and scored at least moderate certainty of evidence were: for undifferentiated recurrence, multidrug resistance (MDR) (RR 3.49; 95% CI 1.86 to 6.53) and fixed-dose combination TB drugs (RR 2.29; 95% CI 1.10 to 4.75) in the previous episode; for relapse, none; and for reinfection, HIV infection (RR 4.65; 95% CI 1.71 to 12.65). Low adherence to treatment increased the pooled risk of recurrence 3.3-fold (95% CI 2.37 to 4.62), but the certainty of evidence was weak. CONCLUSION: This review emphasises the need for standardising methods for TB recurrence research. Actively pursuing MDR prevention, facilitating retention in treatment and providing integrated care for patients with HIV could curb recurrence rates. The use of fixed-dose combinations of TB drugs under field conditions merits further attention. PROSPERO REGISTRATION NUMBER: CRD42018077867.

Cost-effectiveness of active tuberculosis screening among high-risk populations in low tuberculosis incidence countries: a systematic review, 2008 to 2023.

BackgroundIn countries with a low TB incidence (≤ 10 cases/100,000 population), active pulmonary tuberculosis (PTB) mostly affects vulnerable populations with limited access to healthcare. Thus, passive case-finding systems may not be successful in detecting and treating cases and preventing further transmission. Active and cost-effective search strategies can overcome this problem.AimWe aimed to review the evidence on the cost-effectiveness (C-E) of active PTB screening programmes among high-risk populations in low TB incidence countries.MethodsWe performed a systematic literature search covering 2008-2023 on PubMed, Embase, Center for Reviews and Dissemination, including Database of Abstracts of Reviews of Effects (DARE), National Health Services Economic Evaluation Database (NHS EED), Global Index Medicus and Cochrane Central Register of Controlled Trials (CENTRAL).ResultsWe retrieved 6,318 articles and included nine in this review. All included studies had an active case-finding approach and used chest X-ray, tuberculin skin test, interferon-gamma release assay and a symptoms questionnaire for screening. The results indicate that screening immigrants from countries with a TB incidence > 40 cases per 100,000 population and other vulnerable populations as individuals from isolated communities, people experiencing homelessness, those accessing drug treatment services and contacts, is cost-effective in low-incidence countries.ConclusionIn low-incidence countries, targeting high-risk groups is C-E. However, due to the data heterogenicity, we were unable to compare C-E. Harmonisation of the methods for C-E analysis is needed and would facilitate comparisons. To outline comprehensive screening and its subsequent C-E analysis, researchers should consider multiple factors influencing screening methods and outcomes.

Using timeliness metrics for household contact tracing and TB preventive therapy in the private sector, India.

Although screening of household contacts (HHCs) of TB patients and provision of TB preventive therapy (TPT) is a key intervention to end the TB epidemic, their implementation globally is dismal. We assessed whether introducing a '7-1-7' timeliness metric was workable for implementing HHC screening among index patients with pulmonary TB diagnosed by private providers in Chennai, India, between November 2022 and March 2023.This was an explanatory mixed-methods study (quantitative-cohort and qualitative-descriptive).There were 263 index patients with 556 HHCs. In 90% of index patients, HHCs were line-listed within 7 days of anti-TB treatment initiation. Screening outcomes were ascertained in 48% of HHCs within 1 day of line-listing. Start of anti-TB treatment, TPT or a decision to receive neither was achieved in 57% of HHC within 7 days of screening. Overall, 24% of screened HHCs in the '7-1-7' period started TPT compared with 16% in a historical control (P < 0.01). Barriers to achieving '7-1-7' included HHC reluctance for evaluation or TPT, refusal of private providers to prescribe TPT and reliance on facility-based screening of HHCs instead of home visits by health workers for screening.Introduction of a timeliness metric is a workable intervention that adds structure to HHC screening and timely management..

Saponin TQL1055 adjuvant-containing vaccine confers protection upon Mycobacterium tuberculosis challenge in mice.

Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), affects the lungs of infected individuals (pulmonary TB) but can also affect other sites (extrapulmonary TB). The only licensed vaccine Mycobacterium bovis bacillus Calmette-Guerin (BCG) protects infants and young children but exhibits variable efficacy in protecting against adult pulmonary TB. Poor compliance and prolonged treatment regimens associated with the use of chemotherapy has contributed to the development of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb. Thus, there is an urgent need for the design of more effective vaccines against TB. The development of safe and novel adjuvants for human use is critical. In this study, we demonstrate that saponin-based TQL1055 adjuvant when formulated with a TLR4 agonist (PHAD) and Mtb specific immunodominant antigens (ESAT-6 and Ag85B) and delivered intramuscularly in mice, the SA-TB vaccine induced potent lung immune responses. Additionally, the SA-TB vaccine conferred significant protection against Mtb infection, comparable with levels induced by BCG. These findings support the development of a SA-TB vaccine comprising TQL1055, as a novel, safe and effective TB vaccine for potential use in humans.

Recurrence of pulmonary tuberculosis in India: Findings from the 2019-2021 nationwide community-based TB prevalence survey.

Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019-2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107-131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management.

Effectiveness of a community-based approach for the investigation and management of children with household tuberculosis contact in Cameroon and Uganda: a cluster-randomised trial.

BACKGROUND: Globally, the uptake of tuberculosis-preventive treatment (TPT) among children with household tuberculosis contact remains low, partly due to the necessity of bringing children to health facilities for investigations. This study aimed to evaluate the effect on TPT initiation and completion of community-based approaches to tuberculosis contact investigations in Cameroon and Uganda. METHODS: We did a parallel, cluster-randomised, controlled trial across 20 clusters (consisting of 25 district hospitals and primary health centres) in Cameroon and Uganda, which were randomised (1:1) to receive a community-based approach (intervention group) or standard-of-care facility-based approach to contact screening and management (control group). The community-based approach consisted of symptom-based tuberculosis screening of all household contacts by community health workers at the household, with referral of symptomatic contacts to local facilities for investigations. Initiation of TPT (3-month course of rifampicin-isoniazid) was done by a nurse in the household, and home visits for TPT follow-up were done by community health workers. Index patients were people aged 15 years or older with bacteriologically confirmed, drug-susceptible, pulmonary tuberculosis diagnosed less than 1 month before inclusion and who declared at least one child or young adolescent (aged 0-14 years) household contact. The primary endpoint was the proportion of declared child contacts in the TPT target group (those aged <5 years irrespective of HIV status, and children aged 5-14 years living with HIV) who commenced and completed TPT, assessed in the modified intention-to-treat population (excluding enrolled index patients and their contacts who did not fit the eligibility criteria). Descriptive cascade of care assessment and generalised linear mixed modelling were used for comparison. This study is registered with ClinicalTrials.gov (NCT03832023). FINDINGS: The study included nine clusters in the intervention group (after excluding one cluster that did not enrol any index patients for >2 months) and ten in the control group. Between Oct 14, 2019 and Jan 13, 2022, 2894 child contacts were declared by 899 index patients with bacteriologically confirmed tuberculosis. Among all child contacts declared, 1548 (81·9%) of 1889 in the intervention group and 475 (47·3%) of 1005 in the control group were screened for tuberculosis. 1400 (48·4%) child contacts were considered to be in the TPT target group: 941 (49·8%) of 1889 in the intervention group and 459 (45·7%) of 1005 in the control group. In the TPT target group, TPT was commenced and completed in 752 (79·9%) of 941 child contacts in the intervention group and 283 (61·7%) of 459 in the control group (odds ratio 3·06 [95% CI 1·24-7·53]). INTERPRETATION: A community-based approach using community health workers can significantly increase contact investigation coverage and TPT completion among eligible child contacts in a tuberculosis-endemic setting. FUNDING: Unitaid. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Differences in responses to the intracellular macrophage environment between Mycobacterium bovis BCG vaccine strains Moreau and Pasteur.

BACKGROUND: The Bacille Calmette-Guérin (BCG) vaccine comprises a family of strains with variable protective efficacy against pulmonary tuberculosis (TB) and leprosy, partly due to genetic differences between strains. OBJECTIVES: Previous data highlighting differences between the genomes and proteomic profiles of BCG strains Moreau and Pasteur led us to evaluate their behaviour in the macrophage microenvironment, capable of stimulating molecular responses that can impact the protective effect of the vaccine. METHODS: Strain infectivity, viability, co-localisation with acidified vesicles, macrophage secretion of IL-1 and MCP-1 and lipid droplet biogenesis were evaluated after infection. FINDINGS: We found that BCG Moreau is internalised more efficiently, with significantly better intracellular survival up to 96 h p.i., whereas more BCG Pasteur bacilli were found co-localised in acidified vesicles up to 6 h p.i. IL-1ß and MCP-1 secretion and lipid droplet biogenesis by infected macrophages were more prominent in response to BCG Pasteur. MAIN CONCLUSION: Overall, our results show that, compared to Pasteur, BCG Moreau has increased fitness and better endurance in the harsh intracellular environment, also regulating anti-microbial responses (lower IL-1b and MCP-1). These findings contribute to the understanding of the physiology of BCG Moreau and Pasteur in response to the intraphagosomal environment in a THP-1 macrophage model.

[Epidemiological characteristics of pulmonary tuberculosis in Motuo County, Tibet Autonomous Region from 2012 to 2021].

To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in Motuo County from 2012 to 2021 and provide evidence for the prevention and control of PTB. A total of 223 cases of PTB were reported from 2012 to 2021 in Motuo County, with an average annual reported incidence rate of 171.39/100 000. Joinpoint regression model analysis showed that the average decline rate was 9.2% (P<0.001) from 2012 to 2021. Among the various types of PTB patients reported from 2012 to 2021, there were 69 cases of etiologic-positive cases which increased from 28.57% to 52.63%. Results from the circular distribution methods showed that there was no obvious peak time of PTB in Motuo County. There was no statistical difference in the average annual incidence of PTB between different genders (χ2=0.108, P=0.743). Among all age groups, the 20-29 years group had the highest proportion (26.91%, 60/223). The Monpa ethnic group (153 cases, 68.61%) had the largest number of cases, followed by the Lhoba people (44 cases, 19.73%) and the Tibetan (22 cases, 9.87%). Farmers (168 cases, 75.34%) had the highest occupational composition ratio, followed by students (40 cases, 17.94%). The main detection methods of PTB were clinical consultation and transferring consultation. Overall, the incidence rate of PTB decreased from 2012 to 2021. The majority of PTB patients were young adults with high transmission risk. It is necessary to pay more attention to the key populations and strengthen the comprehensive prevention and control for reducing the risk of PTB.

Elimination of tuberculosis requires prior control of silicosis including sub-radiological silicosis.

India is committed to the elimination of tuberculosis by 2025. But its achievement appears to be difficult as India has a huge burden of silicosis as well as sub-radiological silicosis, which was never given its required attention. Silicotic subjects are highly vulnerable to pulmonary tuberculosis due to the progressive decline of lung immunity. A study among vulnerable glass factory workers in Firozabad, Uttar Pradesh, revealed that silicotic workers were 7.5 times more at risk of pulmonary tuberculosis compared to non-silicotic subjects. Since India has a huge burden of silicosis and sub-radiological silicosis, the elimination of tuberculosis needs prior attention on silicosis. This article may be viewed as an eye-opener for understanding the necessity of dual control of both silicosis as well as tuberculosis by integrating both together.

Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial.

BACKGROUND: In India, tuberculosis and undernutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of undernutrition in patients and in the population. The aim of this study was to determine the effect of nutritional supplementation on tuberculosis incidence in household contacts of adults with microbiologically confirmed pulmonary tuberculosis. METHODS: In this field-based, open-label, cluster-randomised controlled trial, we enrolled household contacts of 2800 patients with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units of the National Tuberculosis Elimination Programme in four districts of Jharkhand, India. The tuberculosis units were randomly allocated 1:1 by block randomisation to the control group or the intervention group, by a statistician using computer-generated random numbers. Although microbiologically confirmed pulmonary tuberculosis patients in both groups received food rations (1200 kcal, 52 grams of protein per day with micronutrients) for 6 months, only household contacts in the intervention group received monthly food rations and micronutrients (750 kcal, 23 grams of protein per day with micronutrients). After screening all household contacts for co-prevalent tuberculosis at baseline, all participants were followed up actively until July 31, 2022, for the primary outcome of incident tuberculosis (all forms). The ascertainment of the outcome was by independent medical staff in health services. We used Cox proportional hazards model and Poisson regression via the generalised estimating equation approach to estimate unadjusted hazard ratios, adjusted hazard ratios (aHRs), and incidence rate ratios (IRRs). This study is registered with CTRI-India, CTRI/2019/08/020490. FINDINGS: Between Aug 16, 2019, and Jan 31, 2021, there were 10 345 household contacts, of whom 5328 (94·8%) of 5621 household contacts in the intervention group and 4283 (90·7%) of 4724 household contacts in the control group completed the primary outcome assessment. Almost two-thirds of the population belonged to Indigenous communities (eg, Santhals, Ho, Munda, Oraon, and Bhumij) and 34% (3543 of 10 345) had undernutrition. We detected 31 (0·3%) of 10 345 household contact patients with co-prevalent tuberculosis disease in both groups at baseline and 218 (2·1%) people were diagnosed with incident tuberculosis (all forms) over 21 869 person-years of follow-up, with 122 of 218 incident cases in the control group (2·6% [122 of 4712 contacts at risk], 95% CI 2·2-3·1; incidence rate 1·27 per 100 person-years) and 96 incident cases in the intervention group (1·7% [96 of 5602], 1·4-2·1; 0·78 per 100 person-years), of whom 152 (69·7%) of 218 were patients with microbiologically confirmed pulmonary tuberculosis. Tuberculosis incidence (all forms) in the intervention group had an adjusted IRR of 0·61 (95% CI 0·43-0·85; aHR 0·59 [0·42-0·83]), with an even greater decline in incidence of microbiologically confirmed pulmonary tuberculosis (0·52 [0·35-0·79]; 0·51 [0·34-0·78]). This translates into a relative reduction of tuberculosis incidence of 39% (all forms) to 48% (microbiologically confirmed pulmonary tuberculosis) in the intervention group. An estimated 30 households (111 household contacts) would need to be provided nutritional supplementation to prevent one incident tuberculosis. INTERPRETATION: To our knowledge, this is the first randomised trial looking at the effect of nutritional support on tuberculosis incidence in household contacts, whereby the nutritional intervention was associated with substantial (39-48%) reduction in tuberculosis incidence in the household during 2 years of follow-up. This biosocial intervention can accelerate reduction in tuberculosis incidence in countries or communities with a tuberculosis and undernutrition syndemic. FUNDING: Indian Council of Medical Research-India TB Research Consortium.

Assessment of Family Tuberculosis Contact Screening Practice and its Associated Factors Among Pulmonary Tuberculosis Positive Patients in South Wollo Zone, Amhara Region, Ethiopia.

Objectives: The objective of this study was to assess the prevalence and the associated factors of family contact screening practice. Methods: An institution-based cross-sectional study was conducted among 403 randomly selected pulmonary tuberculosis index cases from 1st May to 30th June 2020. Data were collected through a face-to-face interviewer-administered questionnaire. Multivariable logistic regression was performed. Results: The prevalence of family contact screening was 55.3%, (CI: 60-50). Having family support for care and treatment (AOR = 2.21, 95% CI: 1.16-4.21), waiting time of less than 60 min (AOR = 2.03, 95% CI: 1.28-3.21), receiving health education on TB prevention and treatment (AOR = 1.86), 95% CI: 1.05-3.29), and having good knowledge about TB prevention (AOR = 2.76, 95% CI: 1.77-4.294) were factors associated with family TB contact screening practice. Conclusion: This study revealed that the prevalence of family contact screening was low as compared to national and global targets. Factors associated with family contact screening practice were: the presence of family support, shorter waiting time, health education offered by healthcare workers, and a good level of knowledge of the index cases.

Declining incidence rate of tuberculosis among close contacts in five years post-exposure: a systematic review and meta-analysis.

BACKGROUND: Individuals in close contact with active pulmonary tuberculosis (TB) patients showed a high risk of recent infection and, once infected, higher risk of developing active TB in the following years post-exposure. But the peak time of active disease onset is unclear. This study aims to estimate post exposure TB incidence risk among close contacts to provide reference for clinical and public health strategies. METHODS: We searched PubMed, Web of Science, and EMBASE for articles published until December 1, 2022. The incidence rates were quantitatively summarized by means of meta-analysis using the random-effect model. RESULTS: Of the 5616 studies, 31 studies included in our analysis. For baseline close contacts results, the summarized prevalence of Mycobacterium tuberculosis (MTB) infection and active TB was found to be 46.30% (95% CI: 37.18%-55.41%) and 2.68% (95% CI: 2.02%-3.35%), respectively. During the follow-up, the 1-year, 2-year and 5-year cumulative incidence of TB in close contacts were 2.15% (95% CI: 1.51%-2.80%), 1.21% (95% CI: 0.93%-1.49%) and 1.11% (95% CI: 0.64%-1.58%), respectively. Individuals with a positive result of MTB infection testing at baseline showed significantly higher cumulative TB incidence as compared to those negatives (3.80% vs. 0.82%, p < 0.001). CONCLUSIONS: Individuals with close contact to active pulmonary TB patients are bearing significant risk of developing active TB, particularly within the first-year post-exposure. Population with recent infections should be an important priority for active case finding and preventive intervention worldwide.

Epidemiological characteristics of pulmonary tuberculosis among students in Guizhou, China: a retrospective study from 2010 to 2020.

OBJECTIVE: We described epidemiological characteristics of pulmonary tuberculosis (PTB) among students and evaluated susceptible populations and areas in Guizhou province and also to provide scientific suggestions for prevention and control. SETTING: Guizhou, China. DESIGN: This is a retrospective epidemiological study on PTB in students. METHODS: Data are from the China Information System for Disease Control and Prevention. We collected all PTB cases among the student population from 2010 to 2020 in Guizhou. Incidence, composition ratio and hotspot analysis were used to describe epidemiological and some clinical characteristics. RESULTS: A total of 37 147 new student PTB cases were registered among the population aged 5-30 years during 2010-2020. The proportions of men and women were 53.71% and 46.29%, respectively. Cases aged 15-19 years dominated (63.91%), and the proportion of ethnic groups was increasing during the period. Generally, the raw annual incidence of PTB among the population was increasing from 32.585 per 100 000 persons in 2010 to 48.872 per 100 000 persons in 2020 (c 2 trend=1283.230, p<0.001). March and April were the peak months of a year, and cases were clearly grouped in Bijie city. New cases were mainly identified via physical examination, and cases from active screening were still low (0.76%). Additionally, secondary PTB accounted for 93.68%, positive rate of pathogen was only 23.06%, and the recovery rate was 94.60%. CONCLUSIONS: The population aged 15-19 years is the vulnerable population, and Bijie city is the susceptible area. BCG vaccination and promotion for active screening should be the priority of futural PTB prevention and control. Tuberculosis laboratory capacity should be improved.

TB patients: Is sputum disinfection important?

BACKGROUND: Patients with pulmonary tuberculosis (TB) may produce large amount of infectious sputum which needs to be handled carefully both in health care and household settings. As mycobacteria may survive for long duration in sputum; proper collection, disinfection and disposal is necessary to avoid potential disease transmission. We aimed to assess the efficacy of bedside disinfectant treatment of sputum produced by TB patients using easily available disinfectants that can be used both in TB wards and household settings, to sterilize the infected sputum and compared it with sputum without disinfectant treatment. METHODS: It was a prospective case control study. Sputum of total 95 patients with sputum smear positive pulmonary tuberculosis was collected in sputum containers with lids. Patients on anti-tubercular treatment for more than 2 weeks were excluded. Each patient was given 3 sterile sputum containers to expectorate, Container A containing 5% Phenol solution, Container B containing 4.8% Chloroxylenol and Container C without any disinfectant, acting as a control. Thick sputum was liquified with Mucolytic agent N-acetyl cysteine (NAC). Aliquots of the sputum were sent for culture in Lowenstein-Jensen medium on day 0 (to confirm alive mycobacteria) and on day 1 i.e., after 24 hours (to evaluate effective sterilization). Drug resistance testing was done on all grown mycobacteria. RESULTS: If the samples on day 0 did not grow mycobacteria (indicating non-viable mycobacteria) or day 1 sample grew contaminants in any of the three containers, they were excluded from the analysis (15/95). In remaining 80 patients, bacilli were alive on day 0 and remained alive even after 24 hours (day 1) in control samples (without disinfectants). The sputum was effectively disinfected resulting in no growth after 24 hours (day 1) in 71/80 (88.75%) containing 5% Phenol and 72/80 (90%) with 4.8% Chloroxylenol. The efficacy of disinfection was 71/73 (97.2%) and 72/73 (98.6%) for drug sensitive mycobacteria respectively. The mycobacteria however remained alive with these disinfectants in all 7 samples of drug-resistant mycobacteria with an efficacy of 0%. CONCLUSION: We recommend use of simple disinfectants like 5% Phenol or 4.8% Chloroxylenol for safe disposal of sputum of pulmonary tuberculosis patients. It is necessary as sputum collected without disinfection remained infectious after 24 hours. Resistance of all drug resistant mycobacteria to disinfectants was a novel chance finding. This needs further confirmatory studies.

In silico EsxG EsxH rational epitope selection: Candidate epitopes for vaccine design against pulmonary tuberculosis.

Rational design of new vaccines against pulmonary tuberculosis is imperative. Early secreted antigens (Esx) G and H are involved in metal uptake, drug resistance, and immune response evasion. These characteristics make it an ideal target for rational vaccine development. The aim of this study is to show the rational design of epitope-based peptide vaccines by using bioinformatics and structural vaccinology tools. A total of 4.15 µs of Molecular Dynamics simulations were carried out to describe the behavior in solution of heterodimer, single epitopes, and epitopes loaded into MHC-II complexes. In order to predict T and B cell epitopes for antigenic activation, bioinformatic tools were used. Hence, we propose three epitopes with the potential to design pulmonary tuberculosis vaccines. The possible use of the proposed epitopes includes subunit vaccines, as a booster in BCG vaccination to improve its immune response, as well as the generation of antibodies that interfere with the Mycobacterium tuberculosis homeostasis, affecting its survival.

Prevention of relapse in drug sensitive pulmonary tuberculosis patients with and without vitamin D3 supplementation: A double blinded randomized control clinical trial.

BACKGROUND: The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. METHODS: This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. RESULTS: A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. CONCLUSIONS: The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. TRIAL REGISTRATION: CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

Tuberculosis preventive treatment in children and adolescents: an observational study of secondary data.

OBJECTIVE: To analyze the effectiveness, safety, outcomes, and associated factors of tuberculosis preventive treatment (TPT) in children and adolescents in Paraná, southern Brazil. METHOD: This was an observational cohort study with a retrospective collection of secondary data from the TPT information systems of the state of Paraná from 2009 to 2016, and tuberculosis in Brazil from 2009 to 2018. RESULTS: In total, 1,397 people were included. In 95.4% of the individuals, the indication for TPT was a history of patient-index contact with pulmonary tuberculosis. Isoniazid was used in 99.9% of the cases with TPT, and 87.7% completed the treatment. The TPT protection was 98.7%. Among the 18 people who had TB, 14 (77.8%) became ill after the second year of treatment, and four (22.2%) in the first two years (p < 0.001). Adverse events were reported in 3.3% of cases, most of them were gastrointestinal and medication was discontinued in only 2 (0.1%) patients. No risk factors associated with the illness were observed. CONCLUSIONS: The authors observed a low rate of illness in pragmatics routine conditions in TPT for children and adolescents, especially within the first two years after the end of treatment, with good tolerability and a good percentage of adherence to the treatment. TPT should be encouraged to achieve the goals of the End TB Strategy of the World Health Organization as an essential strategy to reduce the incidence rate of the disease, but studies with new schemes must continue to be carried out in real-life scenarios.

Guia para Controle de Tuberculose em Instituições de Acolhimento para População em Situação de Rua / Guide to Tuberculosis Control in Reception Institutions for Population in Street Situation

Este guia se destina a profissionais que atuam, principalmente, nas Instituições de Acolhimento destinadas à População em Situação de Rua (PSR). Entretanto, vários conceitos e informações que serão apresentados aqui podem ser usados em outros espaços de acolhimento e de oferta de cuidados a esta população, como os de grupos informais e de organizações públicas, governamentais ou não-governamentais.

Limited effect of reducing pulmonary tuberculosis incidence amid mandatory facial masking for COVID-19.

Although the incidence and mortality rates associated with tuberculosis (TB) have been decreasing in many countries, TB remains a major public health concern. Obligatory facial masking and reduced health-care capacity because of COVID-19 may substantially influence TB transmission and care. The Global Tuberculosis Report 2021 published by the World Health Organization indicated a TB rebound at the end of 2020, which coincided with the COVID-19 pandemic. We explored this rebound phenomenon in Taiwan by investigating whether TB incidence and mortality are affected by COVID-19 because of their common route of transmission. In addition, we investigated whether the incidence of TB varies across regions with different incidences of COVID-19. Data (2010-2021) regarding annual new cases of TB and multidrug-resistant TB were collected from the Taiwan Centers for Disease Control. TB incidence and mortality were assessed in Taiwan's seven administrative regions. Over the last decade, TB incidence decreased continually, even during 2020 and 2021, the years coinciding with the COVID-19 pandemic. Notably, TB incidence remained high in regions with low COVID-19 incidence. However, the overall decreasing trends of TB incidence and mortality remained unchanged during the pandemic. Facial masking and social distancing may prevent COVID-19 transmission but exhibit limited efficacy in reducing TB transmission. Thus, during health-related policymaking, policymakers must consider TB rebound, even in the post-COVID-19 era.