Drug-susceptible Tuberculosis Research Articles

The global, regional, and national burden of tuberculosis in 204 countries and territories, 1990–2019

Tuberculosis (TB) is the leading cause of death from a single infectious disease and ranks 13th among the leading causes of death worldwide. In this study, we aimed to report the burden of TB in 204 countries and territories from 1990 to 2019 by sex, age, and socio-demographic index (SDI). Annual death number, age-standardized mortality rates (ASMR), and age-standardized disability-adjusted life year (DALY) rates (ASDR) with a 95% uncertainty interval (UI) of TB were derived from the global burden of disease (GBD) 2019 for the time period between 1990 and 2019. The association between the burden of TB and SDI was also investigated. The total death number related to TB decreased by 33.6%, from 1777.5 in 1990-1179.8 in 2019, per 1000 individuals. The global ASMR and ASDR for TB were 14.64 (13.39-16.03) and 590.42 (536.85-646.42), which were 63.5% and 62.8% lower than in 1990, respectively. South Asia, Eastern Sub-Saharan Africa, Southeast Asia, and Western Sub-Saharan Africa had the largest number of TB deaths in 2019. Central Sub-Saharan Africa was the region with the highest ASMR and ASDR in 2019. India had the highest number of TB deaths, and the Central African Republic and Switzerland had the highest and lowest ASMR per 100,000 individuals, respectively. The number of deaths and DALYs were higher in males than in females and the ASDR significantly increased from the 10-14-year-old age group to the 80-84-year-old age group in both sexes. Most cases of TB were caused by drug-susceptible TB. A negative association between the regional SDI and the ASDR of TB was found. From 1990-2019, TB death number, ASMR, and ASDR decreased. It is important to note that, despite the decreasing burden of TB, it remains a major public health problem, especially in low SDI countries. It is necessary to design and implement suitable strategies to address the current situation.

Contact screening and management in a high-transmission MDR-TB setting in Papua New Guinea: Progress, challenges and future directions

Daru, South Fly District, Papua New Guinea is a high transmission setting for multidrug-resistant tuberculosis (MDR-TB). An emergency response by the Government in 2014 established a high-quality model for treatment and care. Household contact screening and management commenced in 2016 with TB preventive treatment (TPT) for well young child (<5 years) contacts of people with drug-susceptible TB and later expanded to young child contacts of MDR-TB. The model of care is community-based and led by non-specialist health workers, under supervision. An electronic medical record system supports care, reporting and operational research. Community engagement and education has been central, with a concerted focus on peer-led counselling and patient-centred services to improve TPT uptake and completion. Challenges include the application of households as the unit of intervention for detection of active TB and TPT provision. Our implementation experience in Daru has highlighted significant population mixing dynamics with most transmission likely occurring outside the household. We propose a community-wide screening approach with the provision of TPT based on testing to include older children, adolescents, and young adults. As there is the possibility of MDR-TB infection irrespective of the drug susceptibility of the household index case, a novel option is a combination TPT regimen of 6 months of daily isoniazid and levofloxacin (6HLfx). A sensitive aged-related algorithm to detect and exclude active TB is being developed. Ongoing community engagement, quality data systems with operational research to evaluate approaches are critical in high transmission MDR-TB settings.

Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis.

Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether children treated using World Health Organization-recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic (PK) exposures. Titles, abstracts, and full-text articles were screened. We searched PubMed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children aged <18 years being treated for drug-susceptible tuberculosis with rifampicin (RIF), pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO (no. CRD42021274222). Of 304 studies identified, 46 were eligible for full-text review, and 12 and 18 articles were included for the efficacy and PK analyses, respectively. Of 1830 children included in the efficacy analysis, 82% had favorable outcomes (range, 25%-95%). At World Health Organization-recommended doses, exposures to RIF, pyrazinamide, and ethambutol were lower in children than in adults. Children ≤6 years old have 35% lower areas under the concentration-time curve (AUCs) than older children (mean of 14.4 [95% CI 9.9-18.8] vs 22.0 [13.8-30.1] μg·h/mL) and children with human immunodeficiency virus (HIV) had 35% lower RIF AUCs than HIV-negative children (17.3 [11.4-23.2] vs 26.5 [21.3-31.7] μg·h/mL). Heterogeneity and small sample sizes were major limitations. There is large variability in outcomes, with an average of 82% favorable outcomes. Drug exposures are lower in children than in adults. Younger children and/or those with HIV are underexposed to RIF. Standardization of PK pediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing.

FUNCTIONAL STATE OF THE LIVER IN PULMONARY TUBERCULOSIS IN THE DYNAMICS OF PATHOGENETIC TREATMENT WITH A COMPLEX OF AMINO ACIDS.

The aim: To investigate the in!uence of prescribing a complex of amino acids in pathogenetic therapy in patients with pulmonary tuberculosis on liver function. Materials and methods: The study included 50 patients with drug susceptible TB and 50 patients with drug-resistant TB (multidrug-resistant and extensively drug-resistant). Results: The study included 50 patients with drug susceptible tuberculosis (TB) and 50 patients with drug-resistant TB. When comparing biochemical pa-rameters characterizing liver function in patients with drug-susceptible TB after 1 month of anti-tuberculosis therapy, it was found that patients receiving additional therapy with a complex of amino acids had a lower level of bilirubin, p <0.05. After 60 doses, patients receiving additional therapy with amino acids had significantly lower bilirubin levels alanine aminotransferase (ALT) and aspartate aminotransferase (AST), p <0.05. When comparing the biochemical parameters characterizing liver function in patients with drug-resistant tuberculosis after a month of anti-tuberculosis therapy, significantly higher protein level was found in the groups of patients receiving additional therapy with amino acids, as well as significantly lower ALT level, AST and creatinine p <0.05. Conclusions: The additional appointment of the complex of amino acids in the pathogenetic therapy of patients with pulmonary tuberculosis makes it possible to reduce the severity of hepatotoxic reactions manifested by the main parameters (AST, ALT, total bilirubin) and to increase the protein-synthetic function of the liver, which allows us to recommend their appointment to improve the tolerance of anti-tuberculosis therapy.

ЭФФЕКТИВНОСТЬ ВЕРИФИКАЦИИ ТУБЕРКУЛЕЗА ОРГАНОВ ДЫХАНИЯ У БОЛЬНЫХ СО ЗЛОКАЧЕСТВЕННЫМИ НОВООБРАЗОВАНИЯМИ ВНЕЛЕГОЧНОЙ И ЛЕГОЧНОЙ ЛОКАЛИЗАЦИЙ

Aim: to analyze effectiveness of the algorithm for verification of pulmonary TB and the structure of clinical forms of pulmonary TB in patients with malignancies of extrapulmonary or pulmonary localizations. Materials and methods. A cohort retrospective study included 126 patients with malignancies and the diagnosis of active TB or residual post-TB changes or other lung diseases verified by sputum studies (stage 1), bronchoscopy (stage 2), and diagnostic surgery (stage 3).Results. The effectiveness of diagnosis verification based on three stages was 96%. The diagnosis of TB was significantly more frequent – in 40.5% (р &lt; 0.001) than sarcoid reactions – 11.1%, metastatic tumors in the lungs – 15.1%, newly detected malignancies with comorbid TB – 6.3%, or bronchiectasis – 27% of cases. Stage 1 was effective for diagnosis verification in 30.9%, stage 2 – 61.6%, and stage 3 – 100% of cases. In 51 TB patients extrapulmonary malignancies prevailed – 84.3% vs lung cancer – 15.7% (р = 0.001); the most common were breast cancer (25.4%) and gastrointestinal cancer (15.7%). In 60.8% of cases TB was detected during complete/incomplete remission of cancer, in 21.5% – during new detection of cancer/TB comorbidity, in 17.6% – during cancer recurrence (р &lt; 0.001). Active TB was diagnosed in 60.8%, residual post-TB changes – 39.2% of cases (р &lt; 0.05). We established the prevalence of infiltrative pulmonary TB (25.8%) and intrathoracic lymph node TB (25.8%) vs other forms of pulmonary TB (р &lt; 0.05). The detection of M. tuberculosis (MTB) DNA by molecular genetic methods was higher (77.4% of observations) than the detection of AFB by luminescent microscopy (58.1%) or MTB by cultural methods (38.7%) (р &lt; 0.05). We obtained results of drug susceptibility testing in 67.9% of cases. TB was caused by drug susceptible MTB in в 68.4% and drug resistant MTB – 31.6% of cases (р &lt; 0.05). Extensive drug resistance was determined in 15.7%, multiple drug resistance – 5.2%, and poly/monoresistance – 5.2% of cases. Conclusion. Among patients with malignancies, pulmonary TB was commonly detected during cancer remission; in two thirds of observations TB was confirmed by detection of MTB in sputum samples and bronchobiopsies, predominantly by molecular genetic methods; two thirds of cases had drug susceptible TB.

Clinical utility of target-based next-generation sequencing for drug-resistant TB.

BACKGROUND: In high TB burden countries, access to drug susceptibility testing is a major bottleneck. Targeted next-generation sequencing (tNGS) is a promising technology for rapid resistance detection. This study assessed the role of tNGS for the diagnosis of drug-resistant TB (DR-TB).METHODS: A total of 161 samples from bacteriologically confirmed TB cases were subjected to tNGS using the Deeplex® Myc-TB kit and sequenced using the MiSeq platform. These samples were also processed for conventional phenotypic DST (pDST) using 13 drugs on Mycobacteria Growth Indicator Tube and line-probe assays (MTBDRplus and MTBDRsl).RESULTS: There were 146 DR-TB and 15 drug-susceptible TB (DS-TB) samples. About 70% of patients with DR-TB had no previous TB treatment history. Overall, 88.2% had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB), 58.5% pre-extensively drug-resistant TB (pre-XDR-TB) and 9.2% had XDR-TB as defined by the WHO (2020). Around 8% (n = 13) of samples were non-culturable; however, identified 8 were resistant to first and second-line drugs using tNGS. Resistance frequency was similar across methods, with discordance in drugs less reliable using pDST or with limited mutational representation within databases. Sensitivities were aligned with literature reports for most drugs. We observed 10% heteroresistance, while 75% of strains were of Lineages 2 and 3.CONCLUSIONS: Programme data supported tNGS in the diagnosis of DR-TB for early treatment using individualised regimens.

Risk factors of multidrug resistant tuberculosis among patients with tuberculosis at selected multidrug resistance treatment initiative centres in southern Ethiopia: a case-control study

ObjectiveTo identify the risk factors for multidrug resistant tuberculosis (MDR-TB) among patients with TB at selected MDR-TB treatment initiative centres, southern Ethiopia, 2021.DesignAn unmatched case-control study was employed.SettingMultidrug resistance treatment...

TB treatment non-adherence in São Tomé and Príncipe.

Sao Tomé and Principe (STP) is a lower middle-income country in the Gulf of Guinea that has a persistent high loss of TB patients on treatment. To investigate factors associated with patient loss to follow-up (LTFU) and to assess health worker perceptions on non-adherence. A retrospective cohort study was conducted using data from the national database. Factors associated with LTFU were investigated using univariable and multivariable logistic regression. In-depth interviews were conducted with TB health workers to identify perceived barriers for treatment completion. A total of 822 registered patients with drug-susceptible TB were included, of whom 82 (10.0%) were lost to follow-up. Male sex (adjusted OR [aOR] 1.7, 95% CI 1.0-3.0; P = 0.048), as well as living in the Mé-Zóchi and Caué Districts (aOR 2.60, 95% CI 1.58-4.26; P < 0.001) were associated with an increased odds of LTFU. The main barriers to treatment completion were related to lack of food, stigma, and lack of patient information and personal support. The study indicates the need to address multiple issues related to LTFU during TB treatment. Enhanced efforts to personalise care, especially for information, nutrition and encouragement will better support patients in STP.

Safety of Rifampicin at High Dose for Difficult-to-Treat Tuberculosis: Protocol for RIAlta Phase 2b/c Trial.

Previous clinical trials for drug-susceptible tuberculosis (DS-TB) have shown that first-line treatment with doses of rifampicin up to 40 mg/kg are safe and increase the early treatment response for young adults with pulmonary tuberculosis. This may lead to a shorter treatment duration for those persons with TB and a good baseline prognosis, or increased treatment success for vulnerable subgroups (age > 60, diabetes, malnutrition, HIV, hepatitis B or hepatitis C coinfection, TB meningitis, stable chronic liver diseases). Here, we describe the design of a phase 2b/c clinical study under the hypothesis that rifampicin at 35 mg/kg is as safe for these vulnerable groups as for the participants included in previous clinical trials. RIAlta is an interventional, open-label, multicenter, prospective clinical study with matched historical controls comparing the standard DS-TB treatment (isoniazid, pyrazinamide, and ethambutol) with rifampicin at 35 mg/kg (HR35ZE group) vs. rifampicin at 10 mg/kg (historical HR10ZE group). The primary outcome is the incidence of grade ≥ 3 Adverse Events or Severe Adverse Events. A total of 134 participants will be prospectively included, and compared with historical matched controls with at least a 1:1 proportion. This will provide a power of 80% to detect non-inferiority with a margin of 8%. This study will provide important information for subgroups of patients that are more vulnerable to TB bad outcomes and/or treatment toxicity. Despite limitations such as non-randomized design and the use of historical controls, the results of this trial may inform the design of future more inclusive clinical trials, and improve the management of tuberculosis in subgroups of patients for whom scientific evidence is still scarce. Trial registration: EudraCT 2020-003146-36, NCT04768231.

Case-Finding Strategies for Drug-Resistant Tuberculosis: Protocol for a Scoping Review.

Transmission of drug-resistant tuberculosis (DR-TB) is ongoing. Finding individuals with DR-TB and initiating treatment as early as possible is important to improve patient clinical outcomes and to break the chain of transmission to control the pandemic. To our knowledge systematic reviews assessing effectiveness, cost-effectiveness, acceptability, and feasibility of different case-finding strategies for DR-TB to inform research, policy, and practice have not been conducted, and it is unknown whether enough research exists to conduct such reviews. It is unknown whether case-finding strategies are similar for DR-TB and drug-susceptible TB and whether we can draw on findings from drug-susceptible reviews to inform decisions on case-finding strategies for DR-TB. This protocol aims to describe the available literature on case-finding for DR-TB and to describe case-finding strategies. We will screen systematic reviews, trials, qualitative studies, diagnostic test accuracy studies, and other primary research that specifically sought to improve DR-TB case detection. We will exclude studies that invited individuals seeking care for TB symptoms, those including individuals already diagnosed with TB, or laboratory-based studies. We will search the academic databases including MEDLINE, Embase, The Cochrane Library, Africa-Wide Information, CINAHL, Epistemonikos, and PROSPERO with no language or date restrictions. We will screen titles, abstracts, and full-text articles in duplicate. Data extraction and analyses will be performed using Excel (Microsoft Corp). We will provide a narrative report with supporting figures or tables to summarize the data. A systems-based logic model, developed from a synthesis of case-finding strategies for drug-susceptible TB, will be used as a framework to describe different strategies, resulting pathways, and enhancements of pathways. The search will be conducted at the end of 2021. Title and abstract screening, full text screening, and data extraction will be undertaken from January to June 2022. Thereafter, analysis will be conducted, and results compiled. This scoping review will chart existing literature on case-finding for DR-TB-this will help determine whether primary studies on effectiveness, cost-effectiveness, acceptability, and feasibility of different case-finding strategies for DR-TB exist and will help formulate potential questions for a systematic review. We will also describe case-finding strategies for DR-TB and how they fit into a model of case-finding pathways for drug-susceptible TB. This review has some limitations. One limitation is the diverse, inconsistent use of intervention terminology within the literature, which may result in missing relevant studies. Poor reporting of intervention strategies may also cause misunderstanding and misclassification of interventions. Lastly, case-finding strategies for DR-TB may not fit into a model developed from strategies for drug-susceptible TB. Nevertheless, such a situation will provide an opportunity to refine the model for future research. The review will guide further research to inform decisions on case-finding policies and practices for DR-TB. DERR1-10.2196/40009.

Consensus statement on the use of a four-month treatment regimen for drug susceptible tuberculosis in children (&lt; 10 years of age) with uncomplicated disease

Consensus statement on the use of a four-month treatment regimen for drug susceptible tuberculosis in children (&lt; 10 years of age) with uncomplicated disease

1431. Evaluation of Drug-induced Liver Injury in Patients Receiving Anti-tuberculosis Medications and Subsequent Management

Abstract Background For anti-tubercular medications, the risk of drug-induced liver injury (DILI) ranges from 5-33%. DILI may be asymptomatic or may present with fever, nausea, vomiting, anorexia, and lethargy. The objective of this review is to describe the incidence of hepatotoxicity occurring with anti-tuberculosis medications, management of DILI, and re-initiation of therapy. Methods Adult patients prescribed pyrazinamide during their hospital stay at Long Island Jewish Medical Center were screened for inclusion criteria of DILI (liver enzymes ≥ 3x upper limit of normal [ULN] from 7/2017 to 2/2022. IRB classified this analysis as a quality improvement project. Using the electronic medical record, retrospective data was collected for those meeting criteria for DILI which included baseline demographics, concomitant hepatotoxic medications, laboratory values (e.g., alanine aminotransferase [ALT], aspartate aminotransferase [AST], timing of drug interruption, and sequence of re-initiation. Results A total of 108 patients were screened and then 17 were included in the analysis. DILI was found in 16% of patients. The mean age was 57 years and 53% were female. None of the patients with liver injury had a history of hepatic disease, prior DILI, or alcohol consumption. Mean baseline laboratory values were total bilirubin 0.52 mg/dL, alkaline phosphatase 166 U/L, AST 54 U/L, and ALT 40 U/L. All patients were initiated on first-line treatment for drug-susceptible tuberculosis. Thirteen patients had concomitant hepatotoxic drugs (11 acetaminophen, 4 statins, 2 azole antifungals, 1 trimethoprim/sulfamethoxazole). Fourteen patients (82%) developed DILI where AST was ≥ 10 times the ULN. Drug interruption was necessary in 16 of the 17 patients (94%). Seven patients (58%) were re-initiated on treatment according to the American Thoracic Society recommendations with a mean of 8 days after drug interruption. Conclusion In conclusion, the management of DILI related to anti-tubercular medications in our institution can further be standardized to reintroduce a rifamycin analog with or without ethambutol. Education on the avoidance of concomitant hepatotoxic medications such as acetaminophen and selecting the most appropriate agents to sequentially re-initiate treatment is warranted. Disclosures All Authors: No reported disclosures.

Optimized LC-MS/MS quantification of tuberculosis drug candidate macozinone (PBTZ169), its dearomatized Meisenheimer Complex and other metabolites, in human plasma and urine

Tuberculosis, and especially multidrug-resistant tuberculosis (MDR-TB), is a major global health threat which emphasizes the need to develop new agents to improve and shorten treatment of this difficult-to-manage infectious disease. Among the new agents, macozinone (PBTZ169) is one of the most promising candidates, showing extraordinary potency in vitro and in murine models against drug-susceptible and drug-resistant Mycobacterium tuberculosis. A previous analytical method using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed by our group to support phase I clinical trials of PBTZ169. These plasma sample analyses revealed the presence of several additional metabolites among which the most prominent was H2PBTZ, a reduced species obtained by dearomatization of macozinone, one of the first examples of Meisenheimer Complex (MC) metabolites identified in mammals.Identification of these new metabolites required the optimization of our original method for enhancing the selectivity between isobaric metabolites as well as for ensuring optimal stability for H2PBTZ analyses. Sample preparation methods were also developed for plasma and urine, followed by extensive quantitative validation in accordance with international bioanalytical method recommendations, which include selectivity, linearity, qualitative and quantitative matrix effect, trueness, precision and the establishment of accuracy profiles using β-expectation tolerance intervals for known and newer analytes.The newly optimized methods have been applied in a subsequent Phase Ib clinical trial conducted in our University Hospital with healthy subjects. H2PBTZ was found to be the most abundant species circulating in plasma, underscoring the importance of measuring accurately and precisely this unprecedented metabolite. Low concentrations were found in urine for all monitored analytes, suggesting extensive metabolism before renal excretion.

Factors influencing drug susceptible tuberculosis outcomes in Eastern Europe

Objective — to conduct a retrospective analysis of factors that affect the results of treatment of patients with tuberculosis.&#x0D; Materials and methods. A retrospective multi-center study was conducted on adult (&gt; 18 years) patients diagnosed with drug-sensitive susceptible TB of any form and initiated treatment between 1st of January 2019 — 31st of December 2019. The Bucharest Marius Nasta Institute, the Iasi Lung Hospital in Romania, and Chernivtsi TB Centre in Ukraine participated in this study. The study was approved by the ethics committee of each centre (Iassi: 5483/2021, Bucharest: 10592/2019, Chernivtsi: 234/2021,). The need for written informed consent was waived due to the retrospective nature of this study.&#x0D; Results and discussion. It is important to study the factors that influence the course and effectiveness of TB treatment, as they can be useful for the development of new methods of diagnosis and treatment. Our retrospective study identified such factors in an Eastern European population. The risk of adverse consequences increases for the elderly, people without a permanent place of residence, patients with already diagnosed chronic kidney disease, the presence of cavities on a chest X-ray, rapid relapse of TB, under­weight or obesity.These factors may help tailor care to specific populations and may lead to improved TB scoring systems to identify patients at risk of treatment failure.&#x0D; Conclusions. Our study presented common risk factors for unfavourable outcomes with previous research, including age, sex, nutritional status, lifestyle, comorbidities, TB-related parameters, but introduced a new, paraclinical parameter, and highlighted differences for East Europe.

Mass spectrometry-based identification of new serum biomarkers in patients with latent infection pulmonary tuberculosis

Noninvasive and simple indicators for diagnosing latent tuberculosis (TB) infection (LTBI) and tracking progression from latent infection to active TB infection are still desperately needed. The aim of this study was to screen and identify possible biomarkers for diagnosing LTBI and monitoring the progression from latent infection to active TB infection, as well as to investigate the underlying processes and functions. To assess changes in metabolite composition associated with active tuberculosis infection in humans, whole blood supernatants were collected from patients with LTBI, drug-susceptible TB patients, drug-resistant TB patients, and healthy controls. The metabolites in all serum samples were extracted by oscillatory, deproteinization, and then detected by liquid chromatography-tandem mass spectrometry/MS analysis. Normalization by Pareto-scaling method, the difference analysis was carried out by Metaboanalyst 4.0 software, and 1-way analysis of variance analysis among groups showed that P-value < 0.05 was regarded as a different metabolite. To clarify the dynamic changes and functions of differential metabolites with disease progression, and explore its significance and mechanism as a marker by further cluster analysis, functional enrichment analysis, and relative content change analysis of differential metabolites. 65 metabolites were substantially different in four groups. Differential metabolites such as Inosine and Prostaglandin E1 may be important blood indicators for diagnosing mycobacterium tuberculosis latent infection, which were all tightly connected to amino acid metabolism, Biosynthesis of various secondary metabolites, Nucleotide metabolism, Endocrine system, Immune system, Lipid metabolism, and Nervous system. This study screened and identified Inosine, 16, 16-dimethyl-6-keto Prostaglandin E1, Theophylline, and Cotinine as potential serum biomarkers for diagnosing latent TB infection, and Cotinine as potential biomarkers for monitoring disease progression from healthy population to LTBI and then to active TB including drug-resistant TB infection and sensitive TB infection. Furthermore, this research provides a preliminary experimental basis to further investigate the development of metabolomics-based diagnosis of LTBI and monitoring the progress from latent infection to active TB infection.

Genotypic Distribution and the Epidemiology of Multidrug Resistant Tuberculosis in Upper Northern Thailand.

The epidemiology and genotypes of multidrug-resistant tuberculosis (MDR-TB), a global public health threat, remain limited. The genotypic distribution and factors associated with MDR-TB in upper northern Thailand between 2015 and 2019 were investigated. The DNA sequencing of rpoB, katG, and inhA promoter of 51 multidrug-resistant Mycobacterium tuberculosis isolates revealed nine patterns of the rpoB gene mutation distributed in seven provinces. The S531L mutation was the most common mutation in all provinces. The rpoB mutation in Chiang Rai, Chiang Mai, and Lampang was highly diverse compared to other areas. Here, the mutation profiles that have yet to be reported in northern Thailand (H526P, Q513P, and H526C) were detected in Chiang Rai province. The S315T katG mutation was the most common genotype associated with INH resistance, especially in Chiang Mai and Lampang. Further analysis of data from 110 TB patients (42 MDR-TB and 68 drug-susceptible TB) revealed that &lt;60 years of age was a significant factor associated with MDR-TB (OR = 0.316, 95% CI 0.128-0.784, p = 0.011) and ≥60 years of age was a significant factor associated with the S315T katG-mutation (OR = 8.867, 95% CI 0.981-80.177, p = 0.047). This study highlighted the necessity for continuous surveillance and risk factor monitoring for effective control of MDR-TB.

Social Determinants and Risk Factors Associated with Multi-Drug Resistant Tuberculosis Among Tuberculosis Patients in Tamilnadu – A Case-Control Study

Introduction: The emergence of Multi-drug Resistant Tuberculosis (MDR- TB) is a challenge for global control and prevention mainly in developing countries. Socio-economic conditions, social vulnerability, and behavioral factors to be considered as risk factors in identifying MDR-TB. The objective of the study was to identify independent risk factors of MDR-TB among Tuberculosis patients. Methods: An unmatched Case-control study was conducted from January 2021 to June 2021 among tuberculosis (TB) patients registered under RNTCP in Kanchipuram district during the study period. ‘Cases’ were consecutive MDR TB patients aged 15 and older, diagnosed with MDR-TB. ‘Controls’ were patients aged 15 and older, diagnosed with drug susceptible TB. Data was collected using pretested semi-structured questionnaire with face-to- face interview. Univariate and multi-variate analysis were used to identify associated determinants of MDR-TB. Results: A total of 80 subjects, 20 cases and 60 controls (1:3) were recruited. Mean age of ‘cases’ was 32±9.3 years, and for controls was 31± 8.3 years. Multiple logistic regression analysis identified five significant risk factors for the occurrence of MDR TB as follows: passive smoking [OR = 8.449, 95% CI (6.791–30.27)], overcrowding [OR= 2.062,95% CI (1.004-4.005)], low socio-economic status [OR=11.362,95% CI (10.312-35.174)] and previous TB treatment [OR =13.72 with 95% CI (8.599-35.118)]. Inadequate ventilation [OR=4.6434(.217-13.906)] Conclusion: To reduce the burden of drug-resistance, these risk factors can be used as screening tool in identifying individuals with MDR-TB in resource limited settings.

Clinical and economic burden of drug-susceptible tuberculosis in Indonesia: national trends 2017–19

The global incidence of tuberculosis is decreasing, yet it remains high in Indonesia. The Indonesian National Tuberculosis Program facilitates mandatory notification, which enables early detection and treatment, minimises complications, prevents transmission, and decreases deaths. This study aimed to assess the characteristics, trends, and economic burden of notified drug-susceptible tuberculosis cases registered in this system from 2017 to 2019. We performed a multiyear cross-sectional study focusing on drug-susceptible tuberculosis notified cases, incidence, geographical tuberculosis case distribution, treatment outcomes, and costs in Indonesia using data from Sistem Informasi Tuberkulosis (2017-19). The settings were Indonesian health-care facilities that provide tuberculosis control programmes and services. Eligible patients were those who were diagnosed with drug-susceptible tuberculosis and notified to Sistem Informasi Tuberkulosis. Between 2017 and 2019, notified cases increased from 429 219 to 523 614 individuals, corresponding to an increase in incidence from 167 cases per 100 000 to 196 cases per 100 000. In 2019, more than 250 cases per 100 000 inhabitants were notified in Jakarta, North Sulawesi, Gorontalo, and Papua. Treatment success rate increased from 363 098 (84·60%) of 429 219 in 2017 to 452 966 (86·51%) of 523 614 in 2019, with a relatively stable mortality, changing from 3·15% to 3·05%. HIV status was increasingly confirmed, with unknown status decreasing from 66·21% to 43·68%. The costs of visits and monitoring and drug regimens were relatively stable, with total direct medical costs slightly increasing from US$39·40 to $40·40 per case. Progress was made on drug-susceptible tuberculosis management in Indonesia. However, further intensified efforts, including case-finding, optimising diagnosis, and cost-effective tuberculosis management are required if Indonesia is to achieve the 2025 WHO End Tuberculosis Strategy target incidence of fewer than 55 cases per 100 000 people. These data are an important starting point for understanding drug-susceptible tuberculosis dynamics in Indonesia and optimising its management. Directorate General of Higher Education; Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia.

Tuberculosis and Sexual and Reproductive Health of Women in Four African Countries.

Tuberculosis (TB) is a major reason of maternal mortality in low-income countries, and it increases the probability of adverse sexual and reproductive health (SRH) outcomes, including ectopic pregnancy and perinatal mortality. The data presented here is from the TB Sequel observational cohort conducted in four African countries. For this sub-study, we selected only female participants, who were diagnosed with drug susceptible TB and followed-up until the end of anti-TB treatment. The data collection included questionnaires, clinical examination and laboratory tests at TB diagnosis, day 14, month 2, 4 and 6. A total of 486 women, with 88.3% being 18-49 years old, were included in the analysis. Around 54.7% were HIV positive. Most of the participants (416/486; 85.6%) in our cohort were considered cured at month 6. Only 40.4% of non-pregnant women of reproductive age used contraception at TB diagnosis. A total of 31 out of 486 women experienced pregnancy during TB treatment. Pregnancy outcomes varied between live birth (16/31; 51.6%), induced abortion (6/31; 19.4%), miscarriage (4/31; 12.9%) and stillbirth (3/31; 9.6%). Integration and linking of SRH services with TB programmes are vital to increase contraception use and protect women from obstetric risks associated with pregnancy during TB treatment.

How Do Private Providers Unaffiliated With the Nigeria National TB Program Diagnose and Treat Drug-Susceptible TB Patients? A Cross-Sectional Study.

TB diagnosis and treatment practices among private providers not affiliated with the Nigeria National TB Program (NTP) have implications for TB control efforts. Studies evaluating these practices among non-NTP providers are scarce. We aimed to investigate TB diagnosis and treatment practices among non-NTP private providers in urban Lagos State, Nigeria. We conducted a cross-sectional study among doctors and nurses operating private facilities not formally affiliated with the NTP for TB case notification. Between May 2018 and January 2019, we implemented a survey using a pretested questionnaire among 152 doctors and nurses attending TB sensitization seminars in Lagos, Nigeria. We used descriptive statistics to summarize the sociodemographic information and proportion of non-NTP providers with different self-reported TB diagnostic, prescription, and monitoring practices. Private non-NTP doctors and nurses self-reported diagnosing TB using 8 different types of tests. Acid-fast bacilli was the most common (39.8%) means of diagnosing TB. Private non-NTP providers also self-reported prescribing 23 different TB regimens, including streptomycin, to treat TB. Only 32.4% of providers self-reported using the correct combinations of anti-TB drugs to treat TB. Additionally, 58.3% of providers prescribed the standard 6-month treatment duration for pulmonary TB patients, and the remaining 41.7% either undertreated or overtreated TB. A large proportion of private doctors and nurses not formally affiliated with the NTP in Nigeria were not following the NTP guidelines in the diagnosis and treatment of TB. Overtreatment and undertreatment were common. Engagement of these practitioners by the NTP in the form of supervision, on-the-job mentorship, and other strategies can mitigate the negative effects of their current practices on TB case notification and the spread of drug-resistant strains in Nigeria.