Multidrug-resistant Tuberculosis Cases Research Articles

Studying the efficacy of isolation as a control strategy and elimination of tuberculosis in India: A mathematical model

India has the highest burden of both tuberculosis (TB) and multidrug-resistant TB (MDR-TB) based on the WHO Global TB Report 2019. Although the available data suggest that the total TB incidence has declined, the absolute number of new cases is still increasing. The number of reported TB cases in India in 2018 was 2.2 million, which was 1.5 million in 2009. About 47% increment in TB case notification in India within a decade shows a persistent public health problem. India contributes about 22% of the World's TB burden. Indian National Strategic Plan 2017-2025, sets out the government plans to eliminate TB by 2025. However, the milestone seems unrealistic to achieve the TB eradication goal by 2025. We developed a five-dimensional mathematical model to understand the TB dynamics in India and investigate the possibility of the earliest TB eradication time frame. The model stratifies the entire TB class into three different classes as drug-sensitive (DS), MDR, and isolated classes. The effective reproduction number, equilibrium points, and stability analysis of the model were carried out. This model predicts the total estimated cases of DS-TB and MDR-TB from 2018 to 2035 through numerical simulation and suggests that TB may be eliminated by 2035 in India if the treatment success rate could be achieved to 95%, by contact tracing and isolating at least 50% of MDR-TB.

Characteristics of TB/HIV Co-Infection and Patterns of Multidrug-Resistance Tuberculosis in the Northwest Amhara, Ethiopia.

Multidrug-resistant tuberculosis (MDR-TB) has continued to be a serious public health threat and significantly challenges global TB control and prevention efforts, where the TB/HIV co-infection epidemic makes the situation much worse. The aim of the study was to determine the determinant factors associated with patterns of MDR-TB among pulmonary TB patients in the Northwest Amhara, Ethiopia. A hospital-based cross-sectional study was conducted from May 2022 to February 2023 in the Northwest Amhara, Ethiopia. Data on the participants' socio-demographics and clinical characteristics were obtained using a pre-tested checklist. Phenotypic susceptibility testing to first-line anti-TB drugs was performed on 180 isolates by automated BD BACTEC MGIT 960 system. Logistic regression analysis was performed to determine the association of risk factors with patterns of MDR-TB. A p-value ≤0.05 was considered statistically significant. The overall proportion of TB with HIV co-infected cases was 19.8% (50/252). Culture positivity was confirmed in 203/252 (80.6%) of sputum samples. Among 168 isolates, the DST showed that 119 (70.8%) isolates were pan-susceptible to all first-line drugs and prevalence of any resistance to first-line drugs was 49,168 (29.2%). Among the resistant isolates, 28 (16.7%) were any mono-resistance and 12 (7.1%) were determined to be resistant to MDR-TB. TB with a previous TB treatment (aOR = 6.73, 95% CI: 1.78-25.47, p = 0.005) and HIV co-infected (aOR = 0.252, 95% CI: 0.73-0.875, p = 0.03) were significantly associated with MDR-TB. Higher prevalence of TB and MDR-TB was examined among TB patients in the study area. In the study, history of previous TB treatment was the strongest risk factor MDR-TB infection followed by TB with HIV co-infected cases. Therefore, there is a need of strengthening TB control and prevention programs to reduce the increase of TB incidence, further emergence and transmission of a public health threat of MDR-TB cases.

Cartridge Based Nucleic Acid Amplification Test, an Important Diagnostic Tool for Tuberculosis both Pulmonary and Extra-Pulmonary Tuberculosis

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), one of the top 10 causes of death worldwide (ranking above HIV/AIDS). About a quarter of the world's population is infected with TB and thus at risk of developing TB disease. The Global TB Report 2019 states that in 2018 a total of 1.5 million people died from TB, an estimated 10 million (range, 9.0–11.1 million) people fell ill worldwide.(1) Eight countries accounted for two-thirds of the total, with India leading the count, followed by China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh, and South Africa.(1) Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. The WHO estimates that there were 484 000 new cases with resistance to rifampicin (RIF) – the most effective first-line drug, which accounts for 78% MDR-TB cases. The MDR-TB burden largely falls on three countries – India, China, and the Russian Federation. About 6.2% of MDR-TB cases had extensively drug-resistant TB (XDR-TB) in 2018. Worldwide, only 56% of MDR-TB patients are currently successfully treated. Globally, TB incidence is falling at about 2% per year. This needs to accelerate to a 4%–5% annual decline to reach the 2020 milestones of the End TB Strategy.

Epidemiological characteristics and risk factors of multidrug-resistant tuberculosis in Luoyang, China.

We aimed to examine the prevalence of multidrug-resistant tuberculosis (MDR-TB) in Luoyang, China, identify related risk factors, inform clinical practices, and establish standardized anti-tubercular treatment regimens. We conducted a retrospective analysis of high-resolution melting curve (HRM) data from 17,773 cases (2,748 of which were positive) between June 2019 and May 2022 to assess the prevalence of MDR-TB and to identify its associated risk factors. Between June 2019 and May 2022, out of the 17,773 HRM results, 2,748 were HRM-positive, and 312 were MDR-TB cases. The detection rates for HRM-positive and MDR-TB were 17.0 and 12.1% for males, and 12.4 and 8.2% for females, respectively. The MDR-TB detection rate was higher in the urban areas (14.6%) than in the rural areas (10.6%) and more common among individuals under 51 years of age (14.1%) than those over 50 years of age (9.3%). Notably, the rate of detecting MDR-TB was 18.3% higher in new male patients than in new female patients, which was at 10.6%, and this difference was statistically significant (p < 0.001). Moreover, the rate of MDR detection in females who had received anti-tuberculosis treatment (21.3%) was higher than that in males (16.9%). In the multivariate model that considered the results of the sputum smear and detection time, MDR-TB was positively correlated with a history of tuberculosis (TB) treatment, being male, being younger than 51 years, and living in urban areas. Local TB infections are complex and diverse; therefore, more comprehensive monitoring methods are needed to curb the spread of MDR-TB.

Diagnostic performance of the GenoType MTBDRplus VER 2.0 line probe assay for the detection of isoniazid resistant Mycobacterium tuberculosis in Ethiopia.

Isoniazid (INH) resistant Mycobacterium tuberculosis (Hr-TB) is the most common type of drug resistant TB, and is defined as M tuberculosis complex (MTBC) strains resistant to INH but susceptible to rifampicin (RIF). Resistance to INH precedes RIF resistance in almost all multidrug resistant TB (MDR-TB) cases, across all MTBC lineages and in all settings. Therefore, early detection of Hr-TB is critical to ensure rapid initiation of appropriate treatment, and to prevent progression to MDR-TB. We assessed the performance of the GenoType MTBDRplus VER 2.0 line probe assay (LPA) in detecting isoniazid resistance among MTBC clinical isolates. A retrospective study was conducted among M. tuberculosis complex (MTBC) clinical isolates obtained from the third-round Ethiopian national drug resistance survey (DRS) conducted between August 2017 and December 2019. The sensitivity, specificity, positive predictive value, and negative predictive value of the GenoType MTBDRplus VER 2.0 LPA in detecting INH resistance were assessed and compared to phenotypic drug susceptibility testing (DST) using the Mycobacteria Growth Indicator Tube (MGIT) system. Fisher's exact test was performed to compare the performance of LPA between Hr-TB and MDR-TB isolates. A total of 137 MTBC isolates were included, of those 62 were Hr-TB, 35 were MDR-TB and 40 were INH susceptible. The sensitivity of the GenoType MTBDRplus VER 2.0 for detecting INH resistance was 77.4% (95% CI: 65.5-86.2) among Hr-TB isolates and 94.3% (95% CI: 80.4-99.4) among MDR-TB isolates (P = 0.04). The specificity of the GenoType MTBDRplus VER 2.0 for detecting INH resistance was 100% (95% CI: 89.6-100). The katG 315 mutation was observed in 71% (n = 44) of Hr-TB phenotypes and 94.3% (n = 33) of MDR-TB phenotypes. Mutation at position-15 of the inhA promoter region alone was detected in four (6.5%) Hr-TB isolates, and concomitantly with katG 315 mutation in one (2.9%) MDR-TB isolate. GenoType MTBDRplus VER 2.0 LPA demonstrated improved performance in detecting INH resistance among MDR-TB cases compared to Hr-TB cases. The katG315 mutation is the most common INH resistance conferring gene among Hr-TB and MDR-TB isolates. Additional INH resistance conferring mutations should be evaluated to improve the sensitivity of the GenoType MTBDRplus VER 2.0 for the detection of INH resistance among Hr-TB cases.

Epidemiology of extensively drug-resistant tuberculosis among patients with multidrug-resistant tuberculosis: A systematic review and meta-analysis

ObjectivesTo estimate the pooled proportion of extensively drug-resistant tuberculosis (XDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) in patients with multidrug-resistant TB (MDR-TB). MethodsWe systematically searched articles from electronic databases: MEDLINE (PubMed), ScienceDirect, and Google Scholar. We also searched gray literature from the different literature sources main outcome of the review was either XDR-TB or pre-XDR-TB in patients with MDR-TB. We used the random-effects model, considering the substantial heterogeneity among studies. Heterogeneity was assessed by subgroup analyses. STATA version 14 was used for analysis. ResultsA total of 64 studies that reported on 12,711 patients with MDR-TB from 22 countries were retrieved. The pooled proportion of pre-XDR-TB was 26% (95% confidence interval [CI]: 22-31%), whereas XDR-TB in MDR-TB cases was 9% (95% CI: 7-11%) in patients treated for MDR-TB. The pooled proportion of resistance to fluoroquinolones was 27% (95% CI: 22-33%) and second-line injectable drugs was 11% (95% CI: 9-13%). Whereas the pooled resistance proportions to bedaquiline, clofazimine, delamanid, and linezolid were 5% (95% CI: 1-8%), 4% (95% CI: 0-10%), 5% (95% CI; 2-8%), and 4% (95% CI: 2-10%), respectively. ConclusionThe burden of pre-XDR-TB and XDR-TB in MDR-TB were considerable. The high burdens of pre-XDR-TB and XDR-TB in patients treated for MDR-TB suggests the need to strengthen TB programs and drug resistance surveillance.

Tuberculosis in Poland in 2020.

To evaluate the main features of epidemiology of tuberculosis (TB) in 2020 in Poland and to compare with the situation in the European Union and European Economic Area (EU/EEA) countries. Analysis of case-based data on TB patients from National TB Register, data on anti-TB drug susceptibility in cases notified in 2020, data from Statistics Poland on deaths from tuberculosis in 2019, data from National Institute of Public Health NIH - National Research Institute (NIPH NIH - NRI) on HIV-positive subjects for whom TB was an AIDS-defining disease, data from the report "European Centre for Disease Prevention and Control, WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2022 - 2020 data. Copenhagen: WHO Regional Office for Europe and Stockholm: European Centre for Disease Prevention and Control; 2022." In 2020, 3,388 TB cases were reported in Poland. The incidence rate was 8.8 cases per 100,000 with large variability between voivodeships from 5.5 to 13.3 per 100,000. A decrease in the incidence was found in 15 voivodeships, the most significant in Śląskie voivodship (63.9%). The number of all pulmonary tuberculosis cases was 3,237 i.e. 8.4 per 100,000. Pulmonary cases represented 95.5% of all TB cases. In 2020, 151 extrapulmonary TB cases were notified (4.5% of all TB cases). Pulmonary tuberculosis was bacteriologically confirmed in 2,573 cases (79.5% of all pulmonary TB cases, the incidence rate 6.7 per 100,000). The number of smear-positive pulmonary TB cases was 1,771 i.e. 4.6 per 100,000 (54.7% of all pulmonary TB cases). In 2020, there were 38 cases (15 of foreign origin) with multidrug resistant TB (MDR-TB) representing 1.6% of cases with known drug sensitivity. The incidence rates of tuberculosis were growing along with increasing age from 0.7 per 100,000 among children (0-14 years) to 15.0 per 100,000 among subjects in the age group 45-64 years, the incidence rate in the age group ≥65 years was 12.1 per 100,000. There were 39 cases in children up to 14 years of age (1.2% of the total) and 49 cases in adolescents between 15 and 19 years of age - rates 0.7 and 2.7 per 100,000 respectively. In 2020, there were 2,506 cases of tuberculosis in men and 882 in women. The TB incidence in men - 13.5 per 100,000 was 3.0 times higher than among women - 4.5. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 50-54 years - 26.8 vs. 4.1 and in age group 55 to 59 years - 28.7 vs. 4.8. In 2020, there were 116 patients of foreign origin among all cases of tuberculosis in Poland (3.4%). In 2019, TB was the cause of death for 456 people (mortality rate - 1.2 per 100,000). TB incidence in Poland in 2020 was 36.7% lower than in 2019. Such significant declines in the incidence have not been observed in the last two decades. As in previous years, there were differences in incidence rates between voivodeships with an unexpectedly sharp decrease in incidence in Silesia (Śląskie voivodeship). The percentage of tuberculosis cases with bacteriological confirmation exceeded 78%, more than in EU/EEA countries (67.3%). The percentage of MDR-TB cases was still lower than the average in EU/EEA countries (1.6% vs. 3.8%). The highest incidence rates were found in Poland in the older age groups (EU/EEAaged 25 to 44). The percentage of children up to 14 years of age among the total number of TB patients was 1.2%, less than the average in EU/EEA countries (3.8%). The incidence of tuberculosis in men was three times higher than in women in Poland, and six times higher in patients aged 50 to 59. The impact of migration on the TB pattern in Poland has not yet become significant in 2020. The percentage of foreigners among TB patients was 3.4% (33% in EU/EEA countries).

Monitoring the progress achieved towards ending tuberculosis in the European Union/European Economic Area, 2018 to 2021.

We report progress in the European Union/European Economic Area (EU/EEA) towards the Sustainable Development Goal target for tuberculosis (TB) and for the associated global/regional targets. The TB notification rate and the number of TB deaths declined since 2015 but, if current trends continue, the EU/EEA will not reach the 2030 targets. Performance on treatment initiation targets declined sharply during 2020-2021, while the percentage of TB cases with successful treatment outcomes remains low, at 47.9% of the multidrug-resistant TB cases.

Tuberculosis notifications in regional Victoria, Australia: Implications for public health care in a low incidence setting.

Regionality is often a significant factor in tuberculosis (TB) management and outcomes worldwide. A wide range of context-specific factors may influence these differences and change over time. We compared TB treatment in regional and metropolitan areas, considering demographic and temporal trends affecting TB diagnosis and outcomes. Retrospective analyses of data for patients notified with TB in Victoria, Australia, were conducted. The study outcomes were treatment delays and treatment outcomes. Multivariable Cox proportional hazard model analyses were performed to investigate the effect of regionality in the management of TB. Six hundred and eleven (7%) TB patients were notified in regional and 8,163 (93%) in metropolitan areas between 1995 and 2019. Of the 611 cases in the regional cohort, 401 (66%) were overseas-born. Fifty-one percent of the overseas-born patients in regional Victoria developed TB disease within five years of arrival in Australia. Four cases of multidrug-resistant tuberculosis were reported in regional areas, compared to 97 cases in metropolitan areas. A total of 3,238 patients notified from 2012 to 2019 were included in the survival analysis. The time follow-up for patient delay started at symptom onset date, and the event was the presentation to the healthcare centre. For healthcare system delay, follow-up time began at the presentation to the healthcare centre, and the event was commenced on TB treatment. Cases with extrapulmonary TB in regional areas have a non-significantly longer healthcare system delay than patients in metropolitan (median 64 days versus 54 days, AHR = 0.8, 95% CI 0.6-1.0, P = 0.094). Tuberculosis in regional Victoria is common among the overseas-born population, and patients with extrapulmonary TB in regional areas experienced a non-significant minor delay in treatment commencement with no apparent detriment to treatment outcomes. Improving access to LTBI management in regional areas may reduce the burden of TB.

Isolation and Characterization of Anti-Mycobacterial Natural Products from a Petrosia sp. Marine Sponge.

Tuberculosis (TB) is a dreadful infectious disease and a leading cause of mortality and morbidity worldwide, second in 2020 only to severe acute respiratory syndrome 2 (SARS-Cov-2). With limited therapeutic options available and a rise in multidrug-resistant tuberculosis cases, it is critical to develop antibiotic drugs that display novel mechanisms of action. Bioactivity-guided fractionation employing an Alamar blue assay for Mycobacterium tuberculosis strain H37Rv led to the isolation of duryne (13) from a marine sponge Petrosia sp. sampled in the Solomon Islands. Additionally, five new strongylophorine meroditerpene analogues (1-5) along with six known strongylophorines (6-12) were isolated from the bioactive fraction and characterized using MS and NMR spectroscopy, although only 13 exhibited antitubercular activity.

Determinan Faktor Terjadinya Multidrug Resistant pada Pengobatan TB Paru (MDR-TB) di Rumah Sakit Umum Daerah dr. Zainoel Abidin

Cases of multidrug resistant tuberculosis (MDR-TB) continue to increase. MDR-TB is the biggest problem in the prevention and eradication of TB, this is thought to have something to do with characteristics, environment, behavior and other disease factors. This study will examine the determinants of MDR-TB in RSUDZA Banda Aceh because it is a referral hospital for MDR-TB examination and treatment in Aceh Province. This type of research is analytic observational with case control design. The population is MDR-TB patients who seek treatment at RSUZA in 2018 as many as 37 people. By using a ratio of 1:1, the number of samples is 74 people consisting of 37 cases and 37 people as controls. Data collection was carried out from 20 to 30 August 2019 using questionnaires and observations. Data analysis used logistic regression test using the Stata program. The results showed that the variables that had significant values ​​were as follows: occupation with the occurrence of MDR-TB (P value = 0.036; OR = 5.6 95%CI: 1.12-28.1), smoking with the occurrence of MDR-TB (P value = 0.034; OR = 2.8, 95% CI: 95% CI: 1.07-7.52), side effects with the occurrence of MDR-TB (P value = 0.006; OR = 5.6, 95% CI: 1.64-1920) and history of diabetes with the occurrence of MDR-TB (P value = 0.001; OR = 4.9, 95% CI: 1.85-13.42). The results of the multivariate analysis obtained a history of DM (OR = 9; 95% CI: 2.53-37.47), (p = 0.0001) meaning that respondents who had a history of DM tended to be 9 times more at risk for MDR-TB compared to other variables. . The Aceh Health Office needs to improve the discovery of MDR-TB cases by conducting gene-expert examinations on TB patients suspected of having MDR-TB.

Can resistance to either isoniazid or rifampicin predict multidrug resistance tuberculosis (MDR-TB)

BackgroundPrevious studies have shown significant differences and lack clarity on whether resistance to either isoniazid or rifampicin can predict multidrug resistance tuberculosis (MDR-TB). Some consider rifampicin resistance to be a surrogate for MDR-TB. We, therefore, conducted this study to determine resistance to either isoniazid or rifampicin can predict MDR-TB.ResultsA total of 315 Mycobacteria tuberculosis isolates were tested for resistance against isoniazid, rifampicin, ethambutol and streptomycin using the phenotypic proportion method on Lowenstein–Jensen media. Results showed most isolates (88.9%, 280/315) were not resistant to any anti-TB tested, 5.7% (18/315) were resistant to both isoniazid and rifampicin, 2.5% (8/315) were resistant to rifampicin only and 1.3% (4/315) were resistant to all four first-line anti-tuberculosis. Prediction of MDR TB basing on rifampicin results showed sensitivity of 100.0%, specificity of 96.3%, diagnostic accuracy of 96.5%, and positive and negative predictive values of 62.1% and 100.0%, respectively. Isoniazid had sensitivity of 100.0%, specificity of 98.3%, diagnostic accuracy of 98.4%, and positive and negative predictive values of 78.3% and 100.0%, respectively. Prediction of rifampicin resistance based on isoniazid results had sensitivity of 62.1%, specificity of 98.3%, diagnostic accuracy of 94.9%, a positive predictive value of 78.3% and a negative predictive value of 96.2%.ConclusionsResistance to either rifampicin or isoniazid sub-optimally predicts MDR-TB. Despite having high sensitivity and specificity, the positive predictive value of rifampicin was only 62.1% and for isoniazid was 78.3%, suggesting that if either is tested in isolation both could result in false positives MDR-TB cases, resulting into patients being unnecessarily subjected to the more toxic and expensive second-line anti-TB drugs, which are less effective compared to first-line anti-TB drugs.

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.

Surveillance of multidrug-resistant tuberculosis in Taiwan, 2008-2019.

Drug-resistant tuberculosis (DR-TB) is a major contributor to global cases of antimicrobial resistance and remains a public health challenge. To understand the extent and trend of DR-TB under an enhanced multidrug-resistant TB (MDR-TB) management program, we conducted a population-based retrospective study of 1511 Taiwanese MDR-TB cases reported from 2008 to 2019. We obtained patient demographics and clinical and bacteriological information from the National TB Registry and the Infectious Disease Notification System. Of the 1511 MDR-TB patients, 941 were new cases, 485 were previously treated, and 85 had an unknown history of treatment. The male to female ratio was 2.75, and the median age of the patients was 57 years (IQR: 45-72). We observed a significant decline in MDR-TB cases, with annual percentage change (APC) of -4.17%. However, new and previously treated MDR-TB cases had APCs of -1.41% and -9.18%, respectively. The rates of MDR-TB resistance to ethambutol, streptomycin and pyrazinamide were 47.2%, 42.4% and 28.9%, respectively, whereas the rates of resistance to fluoroquinolones and second-line injectable drugs (SLIDs) were 4.1-7.1%, 9.0-14.1%; and the rate of extensively drug-resistant TB was 1.9%, respectively. Furthermore, we observed a decreasing trend of resistance to SLIDs (APCs -7.0% to -8.2%) in new cases and a significant decreasing trend of resistance to moxifloxacin (-24.6%) and levofloxacin (-23.3%) in previously treated cases. The decreasing trend of MDR-TB and resistance to second-line drugs suggested that our programmatic management of TB was effective and that the impact on TB control was profound.

Prevalence and Determinants of Depression Among Multi Drug Resistant (MDR) TB Cases

Aim: We aimed this study to find the prevalence of depression among multi drug resistant (MDR) TB patients and its related determinants. Material and methods: An observational cross-sectional study was conducted at Jinnah Postgraduate Medical Center Karachi hospital, we enrolled 107 MDR-TB patients using non-probability consecutive sampling. Patients were evaluated for depression using Patient Health Questionnaire-9 (PHQ-9). Prevalence of depression along with its determinant were assessed. We used Chi Square test for association between depression and its determinants keeping P value &lt; 0.05 was taken as statistically significant. Results: Patients’ mean age was 32.10±6.19, male patients were higher in number as compared to female patients. In our study we found that depression was present in 52 (48.6%) patients. Depression had significant association with financial issues, family problems, treatment duration and increasing age. Practical implication: Current study assess the determinants of depression in TB patients and spreads public awareness in community about Multidrug resistance in TB and ways to avoid TB in local population. Conclusion: From our study we conclude that 52 (48.6%) patients had depression in MDR-TB patients which is an alarming situation. Financial issues, family problems, treatment duration and increasing age were found to the determinants of depression in MDR-TB patients. Keywords: Tuberculosis, Multi Drug Resistance, Depression, Truenat, Xpert, Mental disorders, psychiatric comorbidity

Utilization of Nikshay Poshan Yojna in tuberculosis patients in two tuberculosis units of North India

Background: Nikshay Poshan Yojana (NPY) was launched in 2018 aiming to provide nutritional incentive of INR 500 per month to all tuberculosis (TB) patients till they complete their treatment. Aim of present study is to determine the number (proportion) of patients being treated for tuberculosis who received the benefits of NPY and to explore the ways incentives were utilized by the patients. Methods: This cross-sectional study was conducted in two tuberculosis units of North India from June 2022 to Dec 2022. All newly diagnosed TB patients registered and receiving treatment in these two Units were included in the study. Defaulters, relapse, failure and multidrug-resistant TB cases were excluded. Data was collected from Nikshay portal. All the patients were contacted telephonically to know whether the incentive was utilized for nutrition. Results: Total 189 patients were included in the study. All patients received benefit under NPY. But only 26 (13.7%) received incentive in scheduled time. Out of 189 patients 56 refused to give telephonic interview about the utilization of incentives. Out of 133 patients who gave interview 85 (64%) patients utilized incentive entirely for nutrition. Conclusions: Government should assure timely availability of funds so that patients can be benefitted timely particularly during initial months of their treatment. Also, there is a need of counselling of patients receiving treatment for tuberculosis about the importance of nutrition in their treatment so that they can utilize financial incentive for nutrition.

The Targeted Maximum Likelihood estimation to estimate the causal effects of the previous tuberculosis treatment in Multidrug-resistant tuberculosis in Sudan.

This study used Targeted Maximum Likelihood Estimation (TMLE) as a double robust method to estimate the causal effect of previous tuberculosis treatment history on the occurrence of multidrug-resistant tuberculosis (MDR-TB). TMLE is a method to estimate the marginal statistical parameters in case-control study design. The aim of this study was to estimate the causal effect of the previous tuberculosis treatment on the occurrence of MDR-TB using TMLE in Sudan. A case-control study design combined with TMLE was used to estimate parameters. Cases were MDR-TB patients and controls were and patients who cured from tuberculosis. The history of previous TB treatment was considered the main exposure, and MDR-TB as an outcome. A designed questionnaire was used to collect a set of covariates including age, time to reach a health facility, number of times stopping treatment, gender, education level, and contact with MDR-TB cases. TMLE method was used to estimate the causal association of parameters. Statistical analysis was carried out with ltmle package in R-software. Result presented in graph and tables. A total number of 430 cases and 860 controls were included in this study. The estimated risk difference of the previous tuberculosis treatment was (0.189, 95% CI; 0.161, 0.218) with SE 0.014, and p-value (<0.001). In addition, the estimated risk ratio was (16.1, 95% CI; 12.932, 20.001) with SE = 0.014 and p-value (<0.001). Our findings indicated that previous tuberculosis treatment history was determine as a risk factor for MDR-TB in Sudan. Also, TMLE method can be used to estimate the risk difference and the risk ratio in a case-control study design.

Pharmacokinetic analysis of linezolid for multidrug resistant tuberculosis at a tertiary care centre in Mumbai, India.

Linezolid is an oxazolidinone used to treat multidrug-resistant tuberculosis (MDR-TB), including in the recently-endorsed shorter 6-month treatment regimens. Due to its narrow therapeutic index, linezolid is often either dose-adjusted or discontinued due to intolerance or toxicity during treatment, and the optimal balance between linezolid efficacy and toxicity remains unclear. India carries a significant burden of MDR-TB cases in the world, but limited information on the pharmacokinetics of linezolid and minimum inhibitory concentration (MIC) distribution is available from Indian MDR-TB patients. We enrolled participants from a tertiary care centre in Mumbai, India, treated for MDR-TB and receiving linezolid daily doses of 600 or 300mg. Pharmacokinetic visits were scheduled between 1 and 15 months after treatment initiation to undergo intensive or sparse blood sampling. Linezolid concentration versus time data were analysed using non-linear mixed-effects modelling, with simulations to evaluate doses for different scenarios. We enrolled 183 participants (121 females), with a median age of 26 years (interquartile range [IQR] 21-35), weight 55.0kg (IQR 45.6-65.8), and fat-free mass 38.7kg (IQR 32.7-46.0). Linezolid pharmacokinetics was best described by a one-compartment model with first-order elimination allometrically scaled by fat-free mass and transit compartment absorption. The typical clearance value was 3.81L/h. Simulations predicted that treatment with 300mg daily achieves a high probability of target attainment (PTA) when linezolid MIC was ≤0.25mg/L (61.5% of participant samples tested), while 600mg daily would be required if MIC were 0.5mg/L (29% of samples). While linezolid 300mg daily is predicted to achieve effective targets for the majority of adults with MDR-TB, it failed to achieve the therapeutic target for 21% participants. A dose of 600mg had a PTA >90% for all susceptible samples, but with a higher likelihood of exceeding toxicity thresholds (31% vs 9.6%). These data suggest potential benefit to individualized dosing taking host and microbial characteristics into account to improve the likelihood of treatment efficacy while minimizing risk of toxicity from linezolid for the treatment of MDR-TB. Further prospective evaluation in different clinical settings is urgently needed to inform safety and efficacy of these lower doses.

Pre-extensively drug-resistant tuberculosis among pulmonary multidrug-resistant tuberculosis patients in Eastern Nigeria.

Pre-extensively drug-resistant tuberculosis (Pre-XDR-TB), an emerging form of drug-resistant tuberculosis, is challenging efforts at tuberculosis control, leading to treatment failure among multidrug-resistant tuberculosis (MDR-TB) patients and progression to extensively drug-resistant tuberculosis (XDR-TB). We determined the rate of Pre-XDR-TB among multidrug-resistant patients in Southeast, Nigeria. A prospective laboratory-based study was carried out at the South East Zonal Tuberculosis Reference Laboratory from January 2021 to December 2021. Second-line drug (SLD) resistance was performed on 225 sputum samples of multidrug-resistant patients prior to treatment initiation using GenoType MTBDRsl genotypic drug susceptibility testing (DST) method. The rate of Pre-XDR-TB among 225 MDR-TB cases was 3.1%. Fluoroquinolone-resistant Pre-XDR-TB was observed (100%) in previously treated tuberculosis cases. Only one (0.4%) case showed resistance to both fluoroquinolone (FQ) and one second-line injectable drug (XDR-TB). The extensively drug-resistant case observed was a de-novo resistance. Exactly 0.9% of the multidrug-resistant cases showed resistance to second-line injectables. The prevalence of Pre-XDR-TB among MDR-TB cases was high. There is need for rapid detection of Pre-XDR-TB among MDR-TB cases before treatment initiation.

Comparison of different diagnostic modalities for isolation of Mycobacterium Tuberculosis among suspected tuberculous lymphadenitis patients

Tuberculosis is a communicable disease with high morbidity and mortality rates in developing countries. The study's primary objective is to compare conventional methods such as acid-fast bacillus (AFB) culture and microscopy with rapid diagnostic methods. The secondary objective is to compare histopathological and microbiological findings in suspected patients with tubercular lymphadenitis. A total of 111 samples (August 2018 to September 2019) of lymph nodes were processed for AFB microscopy, AFB cultures, drug-susceptibility testing (DST), histopathology, and Xpert Mycobacterium Tuberculosis (MTB)/resistance to Rifampin (RIF) assays. Out of 111 lymph node samples, 6 (5.4%) were positive for AFB smear microscopy, 84 (75.6%) were positive for AFB culture, 80 (70.7%) were positive on Gene Xpert, and 102 (91.8%) were indicative of tuberculosis for histopathology studies. Mycobacteria growth indicator tube (MGIT) culture positivity was 84 (75.6%) higher than solid Lowenstein-Jensen (LJ) culture 74 (66.6%). Positive cultures underwent phenotypic DST. Two cases were Multidrug-resistant (MDR) on DST, while three cases were Rifampicin resistant on Gene Xpert. The sensitivity of Genexpert was (62%) against the conventional AFB culture method. The poor performance of conventional lymphadenitis diagnostic methods requires early and accurate diagnostic methodology. Xpert MTB/RIF test can help in the treatment of multidrug-resistant TB cases. Nonetheless, rapid and conventional methods should be used for complete isolation of Mycobacterium tuberculosis.