Drug-resistant Tuberculosis Cases Research Articles

Long-term follow-up of contacts of drug-resistant tuberculosis cases in high-burden areas of Mumbai, India

BackgroundDrug-resistant tuberculosis (DRTB) is a significant public health threat particularly in high burden areas like Mumbai, India. Contacts of DRTB cases are highly vulnerable to infection and development of active disease. In this study we assess long-term outcomes of contacts of DRTB cases, focusing on active TB development and the potential role of IGRA, vitamin D status and supplementation. MethodsA cohort of 262 DRTB contacts identified from a prior case-control study conducted in Mumbai were enlisted for the study. Interviews were conducted, and data were analysed using descriptive statistics and logistic regression. ResultsOf the 262 contacts, 34.73% had LTBI. Three contacts (1.36%) developed active TB, with a crude incidence rate of 4.64 per 1000 people. Vitamin D deficiency was prevalent in 75.3% of contacts, and all three TB cases were vitamin D deficient. Vitamin D supplementation showed a non-significant trend in reducing TB risk (OR = 0.56, p = 0.492). IGRA status did not significantly predict TB development. ConclusionThis study provides valuable insights into the long-term outcomes of contacts of DRTB cases. While baseline IGRA did not prove to predict development of active TB, association between vitamin D deficiency and TB development highlights the need for larger studies and development of more effective screening tools. The study contributes valuable information to TB control strategies in high-burden areas.

Tuberculosis in people of Ukrainian origin in the European Union and the European Economic Area, 2019 to 2022.

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.

Associations of residential greenness exposure and ambient air pollutants with newly-diagnosed drug-resistant tuberculosis cases.

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250m and 500m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM10 model, 0.733 (0.544-0.986) in NDVI + PM2.5 model, 0.735(0.546-0.99) in NDVI + SO2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM10 model, 0.281 (0.111-0.713) in NDVI + PM2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO2 model, 0.294 (0.116-0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association.

Determinants of Treatment Delay in Drug-Resistant Tuberculosis Patients in Banten Province in 2020

Indonesia is currently ranked 2nd with the most tuberculosis cases in the world, after India and China. is ranked 2nd with the most tuberculosis sufferers in the world, after India and China.&#x0D; Tuberculosis control in Indonesia faces many challenges, one of which is the increase in patients&#x0D; with drug-resistant tuberculosis (DR TB). In 2019, the number of tuberculosis sufferers in Indonesia&#x0D; reached 543,874 cases, with drug-resistant tuberculosis cases reaching 11,463 (2.1%). Banten is&#x0D; one of the provinces with the highest number of Tuberculosis sufferers in Java, which is 223 people&#x0D; per 100,000 population, with a national TB rate of 203 people per 100,000 population, of which&#x0D; only 58.3% take medication regularly. This study aims to determine the determinants of treatment&#x0D; delay in drug-resistant tuberculosis patients in Banten province in 2020. The study design was a&#x0D; retrospective cohort. The sampling technique was a total sampling of the list of DR TB cases at&#x0D; South Tangerang city General Hospital and dr. Drajat Prawiranegara Serang. Secondary data&#x0D; search was carried out on the TB Information System (SITB) and patient medical records. The study&#x0D; population was 114 respondents, obtained 90 respondents who fit the inclusion and exclusion&#x0D; criteria. Univariate, bivariate analysis with chi-square test and multivariate with logistic regression&#x0D; statistical test were performed to obtain a fit final model. The results of the bivariate analysis&#x0D; showed a significant relationship between age (p=0.030) and employment status (p=0.003). The&#x0D; final multivariate model, showing employment status with delayed treatment (p = 0.008), with OR&#x0D; 18,788 (95% CI: 2,122 – 166.329), meaning that respondents who have jobs have 18.8 times risk for&#x0D; late treatment compared to respondents who do not have jobs after being controlled by variables&#x0D; of age, gender, history of TB, and education level. The researcher concludes that the determinants&#x0D; of delay in treatment of DR TB patients in Banten province in 2020 are employment status and age.&#x0D; It is recommended that the Banten Provincial Health Office can coordinate cross sectors, to ensure the treatment of DR TB patients until they are cured.&#x0D; Keywords: epidemiology, tuberculosis, drug-resistant

DETERMINING THE DEMOGRAPHIC PATTERNS OF DRUG-RESISTANT AND DRUG-SUSCEPTIBLE TUBERCULOSIS IN KPK, PAKISTAN THROUGH A RETROSPECTIVE SURVEY

Objectives: The objective of this research was to find out the demographic characteristics of drug-susceptible and drug-resistant Tuberculosis in Khyber Pakhtunkhwa, Pakistan. Material and Methods: A retrospective survey was conducted on data from the TB Control Program Khyber Pakhtunkhwa recorded between 1st January 2021 to 3rd June 2022. 7 sentinel sites and 5 Programmatic Management of Drug-resistant Tuberculosis sites report the data to the TB control program. The data was entered into Excel and analyzed through frequency tables, histograms, and bar charts. Results: A total of 39,210 Tuberculosis cases were reported to TB control program KPK from 1st January 2021 to 3rd June 2022; 38,723 were drug-susceptible while 487 were drug-resistant TB cases. The highest percentage of TB was found in the age group 15-24 years. Males were more affected than females with drug-susceptible TB. In contrast, drug-resistant TB was affecting females more than males. 58% of cases were reported in the public sector while 42% cases in the private sector. The households of only 2,412 (6.22%) patients of drug-susceptible Tuberculosis were screened out of 38,723 patients. In 2815 Tuberculosis patients screened for HIV, 4 drug-susceptible and 5 drug-resistant cases were positive for HIV. 8.41% of drug-resistant TB patients were diabetic. Conclusion: The frequency of TB cases is high in Khyber Pakhtunkhwa, especially among 15-24-year-olds. Household contact screening is inadequate in Khyber Pakhtunkhwa. There is a high percentage of coexisting drug-resistant TB and diabetes. Keywords: Drug susceptible TB, Drug-resistant TB, HIV co-infection, Household contact.

Trends of Drug-Resistant Tuberculosis in an Urban and a Rural Area in China: A 10-Year Population-Based Molecular Epidemiological Study.

Drug resistance is the critical determinant for appropriate tuberculosis (TB) treatment regimens and an important indicator of the local TB burden. We aimed to investigate and compare trends in TB drug resistance in the urban Songjiang District of Shanghai from 2011 to 2020, and the rural Wusheng County of Sichuan Province from 2009 to 2020, to assess the effectiveness of local TB control and treatment programs. Whole-genome sequencing data of Mycobacterium tuberculosis were used to predict drug-resistance profiles and identify genomic clusters. Clustered, retreated cases of drug-resistant TB with identical resistance mutations, as well as all new resistant cases, were defined as transmitted resistance. The Cochran-Armitage trend test was used to identify trends in the proportions. Differences between groups were tested using the Wilcoxon rank sum or chi-square tests. The annual proportions of rifampicin-resistant (RR), isoniazid-resistant (INH-R) and multidrug-resistant (MDR) TB cases did not change significantly in Songjiang. In Wusheng, however, the percentage of total TB cases that were RR decreased from 13.2% in 2009 to 3.7% in 2020, the INH-R cases decreased from 16.5% to 7.3%, and the MDR cases decreased from 10.7% to 3.7%. In retreated cases, the percentage of drug resistance decreased in both Songjiang and Wusheng, suggesting improved treatment programs. Transmitted resistance accounted for more than two thirds of drug-resistant cases over the entire study periods, and in recent years this proportion has increased significantly in Songjiang. In both urban Songjiang and rural Wusheng, drug-resistant TB is mostly the result of transmission of drug resistant strains and the percentage of transmitted resistance will likely increase with on-going improvements in the TB treatment programs. Reducing the prevalence of drug resistance depends principally upon decreasing transmission through the prompt diagnosis and effective treatment of drug-resistant TB cases.

Usability of simplified audiometry and electrocardiogram during treatment of drug-resistant tuberculosis in Mozambique: a qualitative study

BackgroundIn 2021, there were approximately 450,000 cases of drug-resistant tuberculosis (DR-TB) worldwide. The treatment of DR-TB historically included expensive and toxic injectable drugs leading to adverse effects including ototoxicity and Electrocardiogram (ECG) abnormalities. This study described the perspectives of healthcare providers and people with DR-TB on the usability of simplified audiometry and ECG for monitoring treatment adverse effects.MethodsA qualitative study was conducted in December 2019 across four provinces in Mozambique, namely Maputo, Gaza, Zambézia, and Nampula. Sixteen outpatient primary care health facilities equipped with simplified Audiometry and/or ECG devices (specifically, SHOEBOX Audiometer® and/or SmartHeart Pro ECG®) installed for at least 6 months before the study initiation were selected. The data was collected using in-depth interviews (IDI) and Focus Group Discussions (FGD) techniques. Interviews were audio-recorded, transcribed verbatim in Portuguese, coded, and analyzed using Nvivo 12 software®. We generated two themes and fit our results into a conceptual framework consisting of three domains in the implementation of technological innovations in health.ResultsA total of 16 healthcare providers and 91 people undergoing treatment for DR-TB were enrolled in the study. Most people with DR-TB had experienced audiometry testing and demonstrated a good understanding of the assessments. Conversely, while most healthcare providers demonstrated robust knowledge of the importance of both audiometry and ECG assessments, they were not confident in managing ECG devices and interpreting the results.ConclusionsWhile healthcare providers demonstrated a consolidated understanding of the importance of audiometry, the limited number of devices and lack of training were constraints, impeding optimal usage and service delivery.

Transmission dynamics of drug-resistant tuberculosis in Ningbo, China: an epidemiological and genomic analysis.

Tuberculosis (TB), particularly drug-resistant TB (DR-TB), remains a significant public health concern in Ningbo, China. Understanding its molecular epidemiology and spatial distribution is paramount for effective control. From December 24, 2020, to March 12, 2023, we collected clinical Mycobacterium tuberculosis (MTB) strains in Ningbo, with whole-genome sequencing performed on 130 MTB strains. We analyzed DR-related gene mutations, conducted phylogenetic and phylodynamic analyses, identified recent transmission clusters, and assessed spatial distribution. Among 130 DR-TB cases, 41% were MDR-TB, 36% pre-XDR-TB, 19% RR-TB, and 3% HR-TB. The phylogenetic tree showed that 90% of strains were Lineage 2 (Beijing genotype), while remaining 10% were Lineage 4 (Euro-American genotype). The spatial analysis identified hotspots of DR-TB in Ningbo's northern region, particularly in traditional urban centers. 31 (24%) of the DR-TB cases were grouped into 7 recent transmission clusters with a large outbreak cluster containing 15 pre-XDR-TB patients. Epidemiological analyses suggested a higher risk of recent DR-TB transmission among young adult patients who frequently visited Internet cafes, game rooms, and factories. Our study provides comprehensive insights into the epidemiology and genetics of DR-TB in Ningbo. The presence of genomic clusters highlights recent transmission events, indicating the need for targeted interventions. These findings are vital for informing TB control strategies in Ningbo and similar settings.

Risk Factor Analysis of Drug-Resistant Tuberculosis in Tuberculosis Patients at Level II Health Facilities in Depok City

Based on Global Tuberculosis Report In 2022, Indonesia will be among the 10 countries contributing to the highest incidence of drug-resistant tuberculosis each year. There are 12,794 cases of drug-resistant tuberculosis in Indonesia with 7,884 cases starting treatment. The number of drug-resistant tuberculosis cases involves a variety of risk factors. This study aims to analyze the risk factors associated with drug-resistant tuberculosis. The research method is observational analytic design case control study. The research samples were patients with drug-resistant tuberculosis and drug-sensitive tuberculosis in Depok City Health Facilities for the period March 2022–May 2023. Data were collected using questionnaires and SITB (Tuberculosis Information System). Bivariate analysis using Chi Square, while multiple logistic regression multivariate analysis. The results of the study of 73 cases and 73 controls showed that the majority were aged 18 - 65 years, 89% of cases and 62% of controls, male gender was the most dominant, 64.4% of cases and 52% of controls, most of the respondents did not work 68.5 % of cases and 53.4% ​​of controls, most of them had low income, 82.8% of cases and 62% of controls. Most of the case group had a high level of education, namely 58.5%. Meanwhile, most of the control group had low education, 50.7%. Bivariately, risk factors associated with drug-resistant tuberculosis are HIV, history of previous treatment, adherence to taking medication and the role of drug swallowing supervisor (PMO). Based on multivariate analysis, the dominant variable associated with the incidence of drug-resistant tuberculosis is history of previous treatment (OR6.021 with CI 2.055-18.721) meaning that patients with a history of previous treatment have a 6 times risk of developing drug-resistant tuberculosis compared to patients without a history of previous treatment.

The Interplay between Mycobacterium tuberculosis and Human Microbiome.

Tuberculosis (TB), a respiratory disease caused by Mycobacterium tuberculosis (Mtb), is a significant cause of mortality worldwide. The lung, a breeding ground for Mtb, was once thought to be a sterile environment, but has now been found to host its own profile of microbes. These microbes are critical in the development of the host immune system and can produce metabolites that aid in host defense against various pathogens. Mtb infection as well as antibiotics can shift the microbial profile, causing dysbiosis and dampening the host immune response. Additionally, increasing cases of drug resistant TB have impacted the success rates of the traditional therapies of isoniazid, rifampin, pyrazinamide, and ethambutol. Recent years have produced tremendous research into the human microbiome and its role in contributing to or attenuating disease processes. Potential treatments aimed at altering the gut-lung bacterial axis may offer promising results against drug resistant TB and help mitigate the effects of TB.

Healthcare seeking behavior and delays in case of Drug-Resistant Tuberculosis patients in Bangladesh: Findings from a cross-sectional survey.

The emergence of Drug-Resistant Tuberculosis (DR-TB) has become a major threat globally and Bangladesh is no exception. Delays in healthcare seeking, proper diagnosis and initiation of treatment cause continuous transmission of the resistant tubercule bacilli through the communities. This study aimed to assess the different health care-seeking behaviors and delays among DR-TB patients in Bangladesh. A prospective cross-sectional study was conducted from November to December 2018, among 92 culture positive and registered DR-TB patients in four selected hospitals in Bangladesh. Data were collected through face-to-face interviews with survey questionnaire as well as record reviews. Among the 92 study participants, the median patient delay was 7 (IQR 3, 15) days, the median diagnostic delay was 88 (IQR 36.5, 210), the median treatment delay was 7 (IQR 4,12) days, and the median total delay among DR-TB patients was 108.5 (IQR 57.5, 238) days. 81.32% sought initial care from informal healthcare providers. The majority (68.48%) of the informal healthcare providers were drug sellers while 60.87% of patients sought care from more than four healthcare points before being diagnosed with DR-TB. The initial care seeking from multiple providers was associated with diagnostic and total delays. In Bangladesh, DR-TB cases usually seek care from multiple providers, particularly from informal providers, and among them, alarmingly higher healthcare-seeking related delays were noted. Immediate measures should be taken both at the health system levels and, in the community, to curb transmission and reduce the burden of the disease.

Comparison of Nucleotide MALDI-TOF MS with Xpert MTB/RIF for Rifampicin Susceptibility Identification and Associated Risk Factors of Rifampicin Resistance Among Drug Resistant Mycobacterium tuberculosis.

Nucleotide-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry (nucleotide MALDI-TOF MS) is an emerging molecular technology used for the diagnosis of tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB)and its drug resistance. This study aimed to compare the ability of nucleotide MALDI-TOF MS to detect rifampicin (RIF) resistance in drug-resistant TB (DR-TB) patients with Xpert MTB/RIF and to analyze the disparate results individually. Additionally, potential factors associated with rifampicin resistance among DR-TB patients in Qingdao were investigated. A retrospective study was conducted at Qingdao Chest Hospital, and patients with DR-TB were enrolled. Corresponding frozen isolates were recovered and subjected to nucleotide MALDI-TOF MS, Xpert MTB/RIF, and phenotypic drug susceptibility testing (pDST). Sanger sequencing was performed for the discordant results of nucleotide MALDI-TOF MS and Xpert MTB/RIF. Univariate and multivariate logistic regression analyses were used to identify potential factors associated with rifampicin resistance among patients with DR-TB. A total of 125 patients with DR-TB (18.8%, 125/668) were enrolled in this study from May 1 to July 31, 2023. Rifampicin-resistant (DR-TB/RR, 29) and rifampicin-sensitive (DR-TB/RS, 96) groups were divided according to the pDST results. Nucleotide MALDI-TOF MS performed better than Xpert MTB/RIF in terms of sensitivity, specificity, accuracy, and agreement with pDST. Only six cases had inconsistent results, and the sequencing results of five cases were identical to nucleotide MALDI-TOF MS. Furthermore, chest pain (aOR=12.84, 95% CI, 2.29-91.97, p=0.005), isoniazid sensitivity (aOR=0.14, 0.02-0.59, p=0.013), and ethambutol sensitivity (aOR=0.02, 0.00-0.10, p=0.000) were potential factors associated with rifampicin resistance among DR-TB patients in Qingdao. The overall concordance between nucleotide MALDI-TOF MS and Xpert MTB/RIF was 95.2%, with the former performing better in determining rifampicin susceptibility among DR-TB cases in Qingdao. Chest pain, isoniazid, and ethambutol resistance might be factors associated with RIF resistance among patients with DR-TB in Qingdao.

A TB free India is far away

TB is a major health issue in many countries including India. In India, the burden of TB is the highest and the number of drug resistant TB (DR-TB) cases is very high. But there is an acute shortage of drugs for treating the DR-TB. The world is not able to eliminate TB due to the infections caused by antimicrobial resistance. The resistance is caused by repeated or continuous use of antibiotics. It is advised by the WHO that there should be limited prescriptions from the ‘Watch” and ‘Reserve’ categories. But in India more than 50% of the antibiotics prescribed are from the ‘Watch’ group. Resistance results in the mutation of single-cell pathogens and the mutated pathogens have evolved their own defence mechanisms to inactivate or evade the drugs. But there is limited/no development of new antibiotics to combat antimicrobial resistance, particularly DR-TB. The total investment made in R&amp;D on antibiotics by major companies is only 17.5% of the total revenue. In India, to eradicate TB the Health Ministry rolled out the National Strategic Plan (NSP) 2017–2025, which aims at increasing the number of individuals who have been undergone precision test from 0.04 million to 13.4 million in 2022. Instead of this target the achieved number is only 4.1 million. And so a new strategic plan 2020 – 2025 was launched; the revised NSP has raised the bar even further. But in India, there are only limited facilities to conduct the precision test and so India is not able to achieve even the diagnostic target. The reasons for this state of affairs are: poor quality/non-availability of drugs, delayed treatment/missing TB cases (there are a few millions of non-notified TB patients in the private sector) and high load of drug resistant pathogens. There are also a number of other vulnerable groups of people who have to be tested immediately with presumptive TB. All these mean that India requires huge resources to combat TB. But in India resources available are very limited. It means that India failed in all aspects and so no one can expect a TB-free India even in 2030 without a comprehensive multifaceted approach.

Strengthening Multidrug-Resistant Tuberculosis Epidemiological Surveillance in Rio de Janeiro: a multidimensional analysis.

This study aimed to reinforce the importance of the epidemiological surveillance of multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State (RJ). Here, we reviewed seven articles we published between 2018 and 2022. This study had two phases. The quantitative phase where frequency was used to describe patient characteristics and regressions were used to evaluate the relationship between treatment outcomes and covariates. The qualitative phase where content analysis of the narratives was performed. Secondary (electronic systems) and primary (semi-structured interviews) data were used. We analyzed 2,269 MDR-TB, 58.1% MDR-TB, and 18.6% extensively drug-resistant TB (XDR-TB) cases, of which 44.3% exhibited unfavorable outcomes. Among the 140 patients with XDR-TB, 29.3% had not undergone prior treatment for MDR-TB. The primary resistance rate in MDR-TB cases was 14.7%, revealing significant demographic and clinical disparities, particularly among women, Caucasians, and those with higher education levels. The number of cases increased from 7.69% in 2000 to 38.42% in 2018, showing an increasing trend (AAPC = 9.4; 95% CI 1.4-18.0, p < 0.001), with 25.4% underreporting. A qualitative study confirmed a high proportion of primary resistance (64.5%) and delayed diagnosis of MDR-TB. In RJ, the diagnostic and therapeutic cascade of MDR-TB must be improved using molecular tests to achieve an early diagnosis of resistance and immediate initiation of appropriate treatment, promote social protection for MDR/XDR-TB patients and their families, enhance TB contact tracing, establish and monitor hospital surveillance centers integrated with Primary Care, and unify various information systems through interoperability for better integration.

Improvement in Outcomes with a New Bedaquiline-based Regimen in Postoperative Cases of Drug-resistant Tuberculosis of the Spine: A Case Series

The incidence of drug-resistant strains of Tuberculosis (TB) is rising at an alarming rate. With the emergence of newer drug-resistant strains, managing the disease with existing antitubercular agents is becoming increasingly difficult. Few studies exist regarding the treatment of drug-resistant TB of the spine using a Bedaquiline-based regimen. Therefore, the efficacy of shorter regimens with novel drugs such as Bedaquiline and Delamanid in drug-resistant TB of the spine must be analysed. The present case series highlights the outcomes of a newer Bedaquiline-based antitubercular regimen in postoperative cases of drug-resistant TB of the spine. All three cases discussed in this study-54-year-old female, 12-year-old female, and 19-year-old female patients-had a clinical and radiological diagnosis of TB of the spine with significant neurodeficits. They underwent decompression and instrumentation surgery. Postoperatively, all three were diagnosed with drug-resistant TB and were started on a Bedaquiline-based antitubercular regimen. Subsequently, all the patients showed significant improvement in neurodeficits with no radiological evidence of recurrence. Therefore, Bedaquiline might play an important role in the future management of drug-resistant spinal TB.

Effect of delamanid on interim outcomes of bacteriological conversion amongst pediatric drug resistant tuberculosis cases in India.

To determine the bacteriological conversion rate after 6 months of Delamanid (DLM) based treatment in children with drug-resistant tuberculosis (DR-TB) and determine factors associated with bacteriological conversion. This is a descriptive retrospective study done in children between the age of 6-17 years with DR-TB who received DLM-based therapy from October 2018 to May 2021. The drug resistance pattern of TB was detected using Xpert RIF/MTB and phenotypic drug sensitivity testing (DST) on TB-MGIT culture reports. Follow-up sputum TB MGIT culture was carried out monthly after DLM initiation for 6 months. Factors associated with sputum bacteriological conversion such as age, gender, pulmonary TB (PTB) versus disseminated TB, unilateral or bilateral lung involvement, type of DR-TB, prior treatment failure, and type of DR-TB regimen were analyzed. Sixty patients received DLM of which two had extrapulmonary TB (EPTB) and sputum conversion could not be assessed. The mean age at presentation was 12.69 ± 3.03 years. Five patients (8.3%) died while on DLM treatment. On follow-up, 8 (13.7%) out of 58 patients had no sputum bacteriological conversion after 6 months of DLM initiation of which three patients were on salvage therapy; 46 (79.3%) had sputum bacteriological conversion within 6 months of DLM initiation. Sputum bacteriological conversion rate was almost 80% at the end of 6 months of DLM-based treatment.

Genotypic and phenotypic drug resistance patterns of Mycobacterium tuberculosis isolated from presumptive pulmonary tuberculosis patients in Ethiopia: A multicenter study.

The emergence of drug-resistant tuberculosis (DR-TB) has been a major obstacle to global tuberculosis control programs, especially in developing countries, including Ethiopia. This study investigated drug resistance patterns and associated mutations of Mycobacterium tuberculosis Complex (MTBC) isolates from the Amhara, Gambella, and Benishangul-Gumuz regions of Ethiopia. A cross-sectional study was conducted using 128 MTBC isolates obtained from patients with presumptive tuberculosis (TB). Phenotypic (BACTEC MGIT 960) and genotypic (MTBDRplus and MTBDRsl assays) methods were used for drug susceptibility testing. Data were entered into Epi-info and analyzed using SPSS version 25. Frequencies and proportions were determined to describe drug resistance levels and associated mutations. Of the 127 isolates recovered, 100 (78.7%) were susceptible to four first-line anti-TB drugs. Any drug resistance, polydrug resistance, and multi-drug resistance (MDR) were detected in 21.3% (27), 15.7% (20), and 15% (19) of the isolates, respectively, by phenotypic and/or genotypic methods. Mono-resistance was observed for Isoniazid (INH) (2, 1.6%) and Streptomycin (STR) (2, 1.6%). There were two genotypically discordant RIF-resistant cases and one INH-resistant case. One case of pre-extensively drug-resistant TB (pre-XDR-TB) and one case of extensively drug-resistant TB (XDR-TB) were identified. The most frequent gene mutations associated with INH and rifampicin (RIF) resistance were observed in the katG MUT1 (S315T1) (20, 76.9%) and rpoB (S531L) (10, 52.6%) genes, respectively. Two MDR-TB isolates were resistant to second-line drugs; one had a mutation in the gyrA MUT1 gene, and the other had missing gyrA WT1, gyrA WT3, and rrs WT1 genes without any mutation. The detection of a significant proportion of DR-TB cases in this study suggests that DR-TB is a major public health problem in Ethiopia. Thus, we recommend the early detection and treatment of DR-TB and universal full first-line drug-susceptibility testing in routine system.

Promising Ursolic Acid as a Novel Antituberculosis Agent: Current Progress and Challenges.

Tuberculosis (TB) stands as the second most prevalent cause of global human mortality from infectious diseases. In 2022, the World Health Organization documented an estimated number of global TB cases reaching 7.5 million, which causes death for 1.13 million patients. The continuous growth of drug-resistant TB cases due to various mutations in the Mycobacterium tuberculosis (MTB) strain, raises the urgency of the exploration of novel anti-TB treatments. Ursolic acid (UA) is a natural pentacyclic triterpene found in various plants that has shown potential as a novel anti-TB agent. This review aims to provide an overview of the therapeutic prospects of UA against MTB, with a particular emphasis on in silico, in vitro, and in vivo studies. Various mechanisms of action of UA against MTB are briefly recapped from in silico studies, such as enoyl acyl carrier protein reductase inhibitors, FadA5 (Acetyl-CoA acetyltransferase) inhibitors, tuberculosinyl adenosine transferase inhibitors, and small heat shock protein 16.3 inhibitor. The potential of UA to overcome drug resistance and its synergistic effects with existing antituberculosis drugs are briefly explained from in vitro studies using a variety of methods, such as Microplate Alamar Blue Assay, Mycobacteria Growth Indicator Tube 960 and Resazurin Assays, morphological change evaluation using transmission electron microscopy, and in vivo studies using BALB/C infected with multi drug resistant clinical isolates. Besides its promising mechanism as an antituberculosis drug, its complex chemical composition, limited availability and supply, and lack of intellectual property are also reviewed as those are the most frequently occurring challenges that need to be addressed for the successful development of UA as novel anti-TB agent.

Drug-resistant Tuberculosis in Pediatric

Introduction: Drug-resistant tuberculosis (DR TB) is a condition where Mycobacterium tuberculosis is resistant to isoniazid, rifampicin or resistant to isoniazid and rifampin as well as other first-line anti-tuberculosis drugs (OAT). Tuberculosis (TB) is a contagious infectious disease, caused by Mycobacterium tuberculosis germs where the source of transmission is through droplets containing TB germs. Case Report: A 10 years 7 months girl, came to the MDR Polyclinic at the Haji Adam Malik Medan Central General Hospital (RSUP HAM Medan) on March 21 2023 bringing the results of the TB Molecular Rapid Test (TCM-TB) examination from the Teladan Barat Health Center with Rifampicin results were resistant and on March 24 2023 the patient was hospitalized. Currently, the patient is complaining of a cough that has been experiencing for ± 3 weeks. Cough with the impression of a dry cough and is continuous so that it interferes with daily activities. The cough does not improve even though the patient has taken cough medicine. There is no fever, there is also no history of previous fever. According to the anamnesis from the patient's parents, there has been a weight loss in the last 2 months, around ± 4 kg. There is no family history of long-term cough, but according to parents, there is a neighbor of the patient who suffers from pulmonary TB and is undergoing treatment. Discussion: After the diagnosis of drug-resistant tuberculosis is confirmed, an evaluation is carried out whether the patient meets the criteria for drug-resistant TB treatment guided by short-term or long-term oral drug-resistant tuberculosis. Patients who meet the evaluation criteria for treatment can immediately be given short-term oral drug-resistant tuberculosis therapy. If the patient does not meet the criteria for short-term treatment, long-term drug-resistant tuberculosis treatment is given. Routine evaluations are carried out during treatment and when the results of drug sensitivity tests are available, treatment is adjusted according to the examination results. Conclusion: A case of drug-resistant tuberculosis in a girl aged 10 years 7 months has been reported which was diagnosed based on anamnesis, physical examination, and supporting examinations, there was also a history of close contact with TB sufferers, and the results of TCM examination of sputum fluid showed rifampicin resistant MTB growth. Patients are treated as drug-resistant TB cases with a short-term regimen with regular monitoring of treatment response and side effects.

Extrapulmonary and Drug-Resistant Childhood Tuberculosis: Unveiling the Disease to Adopt the Optimal Treatment Strategy.

Paediatric tuberculosis (TB) is a substantial threat among infectious diseases, particularly considering the high risk of extrapulmonary tuberculosis (EPTB), severe forms of the disease, and the spreading of drug-resistant strains. Describing the characteristics of children with EPTB and those with drug-resistant tuberculosis (DR-TB) and analysing the role of second-line drugs could facilitate the management of these cases. This retrospective study was conducted on 271 children diagnosed with active TB disease (44 EPTB cases, 9 DR-TB cases), originating from diverse geographic areas, who were referred to the infectious disease unit at Meyer Children's Hospital, Florence, Italy, from 2006 to 2022. In most patients, the management of therapies was complicated by the impossibility to obtain drug susceptibility testing (DST) results, which improved over the years: 17/154 (11.04%) children had DST results between 2006 and 2013, and 50/117 (42.73%, p < 0.001) between 2014 and 2022. Second-line drugs were not exclusively administered to DR-TB cases, but also to EPTB cases (20/44, 45.45%). Drugs were generally well tolerated; adverse events occurred in 13 children (13/271, 4.80%) and were generally mild and reversable. Therapies were successful in 267 children (98.52%) considered cured, while 4 (1.48%) presented sequelae. Both univariate and multivariate logistic regression analyses were conducted to investigate factors associated with EPTB, DR-TB, and second-line drugs administration. Originating from Asia emerged as a risk factor associated with both EPTB and DR-TB (p = 0.013 and p = 0.045, respectively). The introduction of GeneXpert tests has significantly improved TB diagnosis and the obtaining of DST results. The administration of second-line therapies should be limited primarily to DR-TB cases, but it is possible that these drugs may also be beneficial in selected EPTB cases.