Control Of Drug-resistant Tuberculosis Research Articles

Drug resistance in drug-resistant tuberculosis patients with and without diabetes mellitus: a comparative analysis

BackgroundThis dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a global public health concern. This study aims to compare drug resistance in drug-resistant tuberculosis (DR-TB) patients with and without DM and analyse the risk factors of multidrug-resistant tuberculosis (MDR-TB).MethodsA total of 893 DR-TB patients were admitted to Wenzhou Central Hospital between January 2018 and December 2022. After excluding 178 cases with incomplete clinical and laboratory data, 715 patients were included in the study. These patients were then categorized into two groups based on the presence of type 2 DM: the DM group (160 cases) and the non-DM group (555 cases). Demographic information, baseline clinical characteristics, laboratory and imaging test results, clinical diagnoses, and other relevant data were collected for analysis. Statistical analysis was conducted on demographic information, clinical parameters, drug resistance spectrum, and risk factors for multidrug resistance.ResultsIn both the DM and non-DM groups, the order of resistance to first-line anti-tuberculosis drugs is isoniazid, streptomycin, rifampicin, and ethambutol. There is no significant difference in the proportion of mono-resistant tuberculosis, polydrug-resistant tuberculosis, and multidrug-resistant tuberculosis between the two groups (P > 0.05). The prevalence of MDR-TB in both groups shows a downward trend between 2018 and 2022, but the trend is not statistically significant (P > 0.05). Among patients without DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and uric acid ≥ 346 µmol/L are identified as independent risk factors for MDR-TB. Among patients with DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and HbA1c ≥ 9.8% were identified as independent risk factors for MDR-TB.ConclusionIsoniazid is the most resistant drug among DR-TB patients with and without DM. There is no statistically significant difference in drug resistance patterns between the two groups. Some progress has been made in the prevention and control of DR-TB in this area, but the effect is not very significant. There are differences in the risk factors of MDR-TB between patients with and without DM.

The Role of Rapid Molecular Tests, Whole-genome Sequencing, and Phenotypic Drug Susceptibility Testing in the Detection and Control of Drug-resistant Tuberculosis

The Role of Rapid Molecular Tests, Whole-genome Sequencing, and Phenotypic Drug Susceptibility Testing in the Detection and Control of Drug-resistant Tuberculosis

Evaluation of drug-resistant tuberculosis treatment outcome in Limpopo province, South Africa.

South Africa has the second-highest tuberculosis (TB) incidence globally. Drug-resistant TB (DR-TB) treatment has less successful treatment outcomes as compared with susceptible TB, and it hinders TB control and management programmes. This study aimed to evaluate drug-resistant TB treatment outcomes and factors associated with successful treatment outcomes. The study was conducted in five districts in Limpopo province. The study design was retrospective and descriptive. Patients' demographic data, data on clinical characteristics and treatment outcomes data were extracted from the electronic drug-resistant tuberculosis register (EDRWeb) database system for the period, 2010-2018, in Limpopo province. Frequency, percentages and bivariate and multivariate logistic regression were used to analyse data using Statistical Package for Social Sciences version 27.0. The significance difference was determined at a 95% confidence interval and p 0.05. A total of 385 drug-resistant records were included in this study. The treatment success rate was 223 (57.9%). A total of 197 (51.2%) patients were cured, 26 (6.8%) completed treatment, 19 (4.9%) treatment failure, 62 (16.1%) died, 78 (20.6%) were recorded as the loss to follow-up, 1 (0.3%) moved to another country and 2 (0.5%) were transferred out. The treatment success rate was 57.9%, which is still below targets set by National Strategic Plan in South Africa and World Health Organization End TB targets.Contribution: The findings of the study reveal that to achieve successful DR-TB control programme and attain End TB targets, monitoring of treatment outcomes is crucial.

Molecular Characterization of Mutations in Isoniazid- and Rifampicin-Resistant Mycobacterium tuberculosis Isolated in Thailand.

The control of drug-resistant tuberculosis (TB) is a major challenge. The frequency and mutation characteristics indicate the efficiency of molecular tests for the rapid detection of TB drug resistance. This study examined the existence of katG and inhA mutations for isoniazid (INH) resistance and rpoB mutations for rifampicin (RFP) resistance. In total, 178 drug-resistant Mycobacterium tuberculosis (MTB) isolates were analyzed. Mutations in katG encoding and inhA regulatory regions were detected in 136/168 (81.0%) and 29/168 (17.3%), respectively, with the most prominent mutation of Ser315Thr substitution in katG in 126/168 (75.0%), and -15 C to T substitution in the regulatory region of the inhA (26/168; 15.5%). Two distinct katG mutations (Tyr337Cys, 1003InsG) were identified. Of 125 RFP-resistant isolates, 118 (94.4%) carried mutations affecting the 81-bp RFP resistance-determining region, with the most commonly affected codons 450, 445, and 435 identified in 74 (59.2%), 26 (20.8%), and 12 (9.6%) isolates, respectively. Genetic mutations were highly associated with phenotypic INH and RFP resistance, and the majority shared similarities with those reported in previous studies in Thailand and other Asian countries. These data are useful for guiding the use and improvement of molecular tests for TB drug resistance.

Empowering the Critical Role of Public Health Center on Communicable Disease Prevention and Control of Drug-Resistant Tuberculosis

Tuberculosis has become an infectious disease with a high prevalence in developing countries, requiring serious handling from all stakeholders. Public health centers in this context have a critical role in relation to their function as first-level health care facilities. This study seeks to analyze the empowerment of the role of public health centers in the control of drug-resistant tuberculosis (DR-TB) in Central Java, Indonesia. This study was conducted using a field research method through a survey with the method of observation and interviews with respondents. The analysis technique is done by using the mixing method. Quantitative techniques are extracted from data related to the treatment of tuberculosis in Central Java, and are equipped with qualitative methods to get feedback from doctors and nurses at public health centers regarding strategies and challenges in treating tuberculosis. The results of the study show opportunities for empowering the role of public health centers through regulatory channels to give greater authority to the public health center to handle drug-resistant TB. The results of this study are practically useful for stakeholders and policymakers to elaborately place the important functions of the public health center in handling drug-resistant TB.

Strengthening resistance testing for tuberculosis in India - Investment cost, throughput, and efficiency of new laboratories

A lack of laboratory capacity for drug-resistant tuberculosis (DR-TB) testing is a major barrier to DR-TB control. To overcome this barrier, the Central Tuberculosis Division (CTD), Ministry of Health and Family Welfare (MoHFW), Government of India (GoI), and FIND India established a partnership under the National Tuberculosis Elimination Program (NTEP) to strengthen and expand tuberculosis (TB) laboratory diagnostic capabilities. This partnership has led to the establishment of 61 culture & DST laboratories, increasing the testing capacity to a capability of performing over 200,000 liquid cultures and over 170,000 molecular drug sensitivity tests annually. In this study, we assess the data on throughput, efficiency, investment cost, and the capacity of the laboratory services supported by this partnership to understand impact and inform future resource allocation. We estimated the technical efficiency using Stochastic Frontier Analysis (SFA). Our results show that the established laboratory network is operating at 69% efficiency, with the capacity to perform an additional 450,000 cultures and 180,000 first-line molecular drug-susceptibility tests by 2025. This additional capacity, together with current efforts to enhance the laboratory network, has the potential to make a significant contribution to NTEP's TB elimination target by 2025.

Geo-Spatial Distribution of Frequencies of MTB/RIF Detected Specimens based on Requesting Health Facilities in Manicaland Zimbabwe for 2017 and 2018

Objectives: The aim of this study was to produce Geo Spatial Distribution of Frequencies of MTB/RIF Detected Specimens based on Requesting Health Facilities in Manicaland Zimbabwe for 2017 and 2018, so as to give insight to TB program managers. Focusing elimination interventions on hot pockets of Tuberculosis (TB) strengthens rationale use of resources in resource limited countries like Zimbabwe. Early detection and early treatment is backbone of breaking TB transmission. Drug resistant tuberculosis (DRTB) control interventions like Programmatic Management of Drug Resistant TB or mentoring on Short, all Oral Regimen for Rifampicin resistant Tuberculosis (ShORRT) will be driven by science.Materials and Methods: The retrospective study was carried out in Manicaland, Zimbabwe. Manicaland one of the 10 provinces in Zimbabwe, has 7 districts with 308 health facilities. During this retrospective cross sectional study 2221 MTB detected results of 2017 and 2018, downloaded from 14 of the 15 Genexpert sites in Manicaland were employed to generate hotspot maps. Fifteenth Genexpert site lost its electronic records when Genexpert CPU crushed. Geographical Positioning System (GPS) of the health facilities were recorded. The study used MTB detected frequencies at a facility in relation to surrounding facilities in Manicaland, then ran optimised hotspot analysis function in Arc Map 10.5 to implement the Gi*statistic.Results: Overall provincial MTB detected positivity was 2221/36055 (6.2%).Overall provincial Rifampicin Resistant (RR) positivity was .111.2221(5.0%).Geo-spatial map of Manicaland showed 10 facilities that are RR hotspots with 7/10 (70%) of the facilities in Buhera district. Chipinge district had facilities that were MTB detected high hotspots.For the whole of Manicaland, Buhera district had100% MTB detected low hotspots facilities. Ninety percent hotspots were clustered around 2 of the 15 Genexpert Sites in Manicaland, namely Murambinda Mission Hospital and Chipinge District Hospital.Conclusion: Study identified health facilities with high frequencies of RR areas. For the identified health facilities with high frequencies of RR specimens, NTP may focus DRTB control interventions like PMDT, or mentoring on ShORRT. For the health facilities with high frequencies of MTB detected NTP can focus trainings in TB Case Management. Instead of uniformly spreading the limited resources to all 325 facilities, efforts streamlined to manageable number of 20 facilities in commensurate with identified gap( e.g. objective selection of cadres for training, data driven supportive supervision & targeted awareness campaigns).

Geo-Spatial Distribution of Frequencies of MTB/RIF Detected Specimens based on Requesting Health Facilities in Manicaland Zimbabwe for 2017 and 2018

Objectives: The aim of this study was to produce Geo Spatial Distribution of Frequencies of MTB/RIF Detected Specimens based on RequestingHealth Facilities in Manicaland Zimbabwe for 2017 and 2018, so as to give insight to TB program managers. Focusing elimination interventions onhot pockets of Tuberculosis (TB) strengthens rationale use of resources in resource limited countries like Zimbabwe. Early detection and earlytreatment is backbone of breaking TB transmission. Drug resistant tuberculosis (DRTB) control interventions like Programmatic Management of Drug Resistant TB or mentoring on Short, all Oral Regimen for Rifampicin resistant Tuberculosis (ShORRT) will be driven by science.
 Materials and Methods: The retrospective study was carried out in Manicaland, Zimbabwe. Manicaland one of the 10 provinces in Zimbabwe, has 7 districts with 308 health facilities. During this retrospective cross sectional study 2221 MTB detected results of 2017 and 2018, downloaded from 14 of the 15 Genexpert sites in Manicaland were employed to generate hotspot maps. Fifteenth Genexpert site lost its electronic records when Genexpert CPU crushed. Geographical Positioning System (GPS) of the health facilities were recorded.The study used MTB detected frequencies at a facility in relation to surrounding facilities inManicaland, then ran optimised hotspot analysis function in Arc Map 10.5 to implement the Gi* statistic. 
 Results: Overall provincial MTB detected positivity was 2221/36055 (6.2%).Overall provincial Rifampicin Resistant (RR) positivity was .111.2221(5.0%).Geo-spatial map of Manicaland showed 10 facilities that are RR hotspots with 7/10 (70%) of the facilities in Buhera district. Chipinge district had facilities that were MTB detected high hotspots.For the whole of Manicaland, Buhera district had100% MTB detected low hotspots facilities. Ninety percent hotspots were clusteredaround 2 of the 15 Genexpert Sites in Manicaland, namely Murambinda Mission Hospital and Chipinge District Hospital.
 Conclusion: Study identified health facilities with high frequencies of RR areas. For the identified health facilities with high frequencies of RR specimens, NTP may focus DRTB control interventions like PMDT, or mentoring on ShORRT. For the health facilities with high frequencies of MTB detected NTP can focus trainings in TB Case Management. Instead of uniformly spreading the limited resources to all 325 facilities, efforts streamlined to manageable number of 20 facilities incommensurate with identified gap( e.g. objective selection of cadres for training, data driven supportive supervision & targeted awarenesscampaigns).

Molecular Detection of Drug-Resistant Mycobacterium tuberculosis in Sputum Specimens from the New and Previously Treated Tuberculosis Cases at the National Reference Chest Diseases Laboratory in Lusaka, Zambia

Background: Drug-Resistant Tuberculosis (DR-TB) is one of the major public health issues globally. Zambia is highly burdened by TB and multi-drug resistant TB. In this study, sputum samples obtained from the new and previously treated cases of TB were examined for drug-resistant Mycobacterium tuberculosis (MTB). Methods: Sputum specimens were processed using the N-acetyl-L-cysteine-sodium hydroxide method, stained and examined using fluorescent technique and microscopy respectively. Mycobacterial DNA was extracted using the Genolyse kit, then subjected to multiplex polymerase chain reaction amplification and reverse hybridization. Drug-resistance and mutations in MTB genes were detected using the Genotype MTBDRplus VER 2.0 and MTBDRsl VER 2.0 assays. Results: A total of 329 MTB-positive sputum specimens, 102 from the new TB cases and 227 from previously treated TB cases, were analysed for drug-resistance. Among the new TB cases, 3.9% had Rifampicin (RIF) mono-resistance, 12.8% Isoniazid (INH) mono-resistance, and 17.7% had Multi-Drug Resistance (MDR). For the previously treated TB cases, 10.1% had RIF mono-resistance, 6.6% INH mono-resistance, 33.0% MDR, 1.8% poly-drug resistance, and 0.8% had pre-Extensively Drug-Resistance (pre-XDR). Mutations identified were rpoB (Ser531Leu, His526Asp, Asp516Val, His526Tyr, and Glu510His), katG (Ser315Thr 1 and Ser315Thr 2), InhA (Cys15Thr), gyrA (Ala90Val and Asp94Gly), and eis (Cys14Thr), each with a varying frequency. Conclusion: DR-TB is prevalent, especially MDR-TB, which is currently the most worrisome form of DR-TB and an emerging threat hampering efforts in the control of TB in Zambia. The early detection and effective treatment of TB cases are key in the control of DR-TB.

Impact of multiple policy interventions on the screening and diagnosis of drug-resistant tuberculosis patients: a cascade analysis on six prefectures in China

BackgroundThe detection of drug-resistant tuberculosis (DR-TB) is a major health concern in China. We aim to summarize interventions related to the screening and detection of DR-TB in Jiangsu Province, analyse their impact, and highlight policy implications for improving the prevention and control of DR-TB.MethodsWe selected six prefectures from south, central and north Jiangsu Province. We reviewed policy documents between 2008 and 2019, and extracted routine TB patient registration data from the TB Information Management System (TBIMS) between 2013 and 2019. We used the High-quality Health System Framework to structure the analysis. We performed statistical analysis and logistic regression to assess the impact of different policy interventions on DR-TB detection.ResultsThree prefectures in Jiangsu introduced DR-TB related interventions between 2008 and 2010 in partnership with the Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund) and the Bill & Melinda Gates Foundation (Gates Foundation). By 2017, all prefectures in Jiangsu had implemented provincial level DR-TB policies, such as use of rapid molecular tests (RMT), and expanded drug susceptibility testing (DST) for populations at risk of DR-TB. The percentage of pulmonary TB cases confirmed by bacteriology increased from 30.0% in 2013 to over 50.0% in all prefectures by 2019, indicating that the implementation of new diagnostics has provided more sensitive testing results than the traditional smear microscopy. At the same time, the proportion of bacteriologically confirmed cases tested for drug resistance has increased substantially, indicating that the intervention of expanding the coverage of DST has reached more of the population at risk of DR-TB. Prefectures that implemented interventions with support from the Global Fund and the Gates Foundation had better detection performance of DR-TB patiens compared to those did not receive external support. However, the disparities in DR-TB detection across prefectures significantly narrowed after the implementation of provincial DR-TB polices.ConclusionsThe introduction of new diagnostics, including RMT, have improved the detection of DR-TB. Prefectures that received support from the Global Fund and the Gates Foundation had better detection of DR-TB. Additionally, the implementation of provincial DR-TB polices led to improvements in the detection of DR-TB across all prefectures.

Drug-resistance of MDR-TB in Xi'an between 2018 and 2020 and the impact of COVID-19 epidemic prevention and control on it

Objective: To understand the epidemic status of drug-resistant Mycobacteriun tuberculosis in Xi'an in the past three years, and the impact of COVID-19 epidemic during 2020 so as to provide basic information for local multidrug-resistant tuberculosis (MDR-TB) prevention and treatment. Methods: Tuberculosis (TB) detected by sputum culture, the corresponding drug susceptibility tests data, and basic clinical information of TB patients diagnosed in Xi'an from January 2018 to October 2020 were collected from the management system;then the epidemic status and the drug resistance status were analyzed. Multinomial logistic regression was used to analyze the relationship between the patients' treatment history and the drug resistance of TB strains, and the trend of changes in the drug resistance rate in retreated patients. Results: In the past three years, there was a total drug resistance rate of 25.3% in 5 146 strains of MTB, and 24.8% in treatment initiation and 38.22% in retreatment, respectively. The treatment initiation patients showed a decreased MDR-TB detection rate, and the retreated patients had an increased MDR-TB detection rate. The spectrum of MDR-TB in the retreated patients gradually became more complicated, and the resistance rate of second-line drugs such as Kanamycin and Ofloxacin gradually increased. There were 10 drug-resistant combinations mainly in H+R+S and H+R+S+E. During the year 2020 of COVID-19 epidemic, the number of initial and retreated patients decreased significantly compared with that in 2018 and 2019, but with no difference in the drug-resistance rate. There was an increasing detection rate of PDR and MDR-TB strains in the retreated patients. Multinomial logistic regression results showed that in 2020 the retreated patients had 4.28 times of developing PDR-TB (P=0.001, 95% CI=1.417-12.930), and 5.378 times of developing MDR-TB (P< 0.001, 95% CI=2.641-10.952) than patients of treatment initiation. Conclusion: In the past three years, the prevention and control of drug-resistant TB in Xi'an has achieved some progress, but drug resistance in retreated patients is still serious. To avoid and reduce the development of drug-resistant TB, precise and active intervention measures should be taken, and health management of TB patients should be strengthened, especially during the current period of COVID-19 epidemic prevention and control. © 2021, Editorial Board of Journal of Xi'an Jiaotong University (Medical Sciences). All right reserved.

Sputum microbiota as a potential diagnostic marker for multidrug-resistant tuberculosis.

The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains makes disease control more complicated, which is the main cause of death in tuberculosis (TB) patients. Early detection and timely standard treatment are the key to current prevention and control of drug-resistant TB. In recent years, despite the continuous advancement in drug-resistant TB diagnostic technology, the needs for clinical rapid and accurate diagnosis are still not fully met. With the development of sequencing technology, the research of human microecology has been intensified. This study aims to use 16 rRNA sequencing technology to detect and analyze upper respiratory flora of TB patients with anti-TB drug sensitivity (DS, n = 55), monoresistance isoniazide (MR-INH, n = 33), monoresistance rifampin (MR-RFP, n = 12), multidrug resistance (MDR, n = 26) and polyresistance (PR, n = 39) in southern China. Potential microbial diagnostic markers for different types of TB drug resistance are searched by screening differential flora, which provides certain guiding significance for drug resistance diagnosis and clinical drug use of TB. The results showed that the pulmonary microenvironment of TB patients was more susceptible to infection by external pathogens, and the infection of different drug-resistant Mtb leads to changes in different flora. Importantly, seven novel microorganisms (Leptotrichia, Granulicatella, Campylobacter, Delfitia, Kingella, Chlamydophila, Bordetella) were identified by 16S rRNA sequencing as diagnostic markers for different drug resistance types of TB. Leptotrichia, Granulicatella, Campylobacter were potential diagnostic marker for TB patients with INH single-resistance. Delftia was a potential diagnostic marker for TB patients with RFP single drug-resistance. Kingella and Chlamydophila can be used as diagnostic markers for TB patients with PR. Bordetella can be used as a potential diagnostic marker for identification of TB patients with MDR.

Exploring local realities: Healthcare workers’ perspectives on the management and control of drug-resistant tuberculosis in Addis Ababa, Ethiopia

Background: Drug-resistant tuberculosis (DR-TB) remains a major health security threat worldwide. The effectiveness of implementation of DR-TB control strategies has been a subject of research and controversy. In resource-limited settings, using conventional medicine as the only framework to explain DR-TB gives a rather incomplete picture of the disease. This study intended to explore the perceptions and experiences of healthcare workers on the management and control of DR-TB in Addis Ababa, Ethiopia. Methods and materials: The study employed a qualitative methodology with an inductive approach and a thematic analysis. It involved in-depth interviews with healthcare workers providing clinical services to DR-TB patients in 10 public healthcare facilities in Addis Ababa, Ethiopia. Results: A total of 18 healthcare workers participated until data saturation, which included 12 clinical nurses, four health officers and two medical laboratory technicians. The findings show that healthcare workers perceive DR-TB as a growing public health threat in Ethiopia, due to factors such as poverty, poor nutrition, crowded settings, healthcare worker and general public awareness of DR-TB, lack of good governance and culture. Conclusion: The perspectives drawn from the healthcare workers shed more light on the image of DR-TB in a developing country context. It has been shown that understanding DR-TB is not confined to what can be drawn from the sphere of biomedicine. There are also interconnected barriers, which predict a dystopia in the epidemiology of DR-TB. Bringing DR-TB under control requires taking a step back from an overwhelming focus on the biomedical facets of the disease, and employ critical thinking on the wider social and structural forces as equally important targets.

\u201cSide effects--part of the package\u201d: a mixed methods approach to study adverse events among patients being programmatically treated for DR-TB in Gujarat, India

BackgroundHigh rates of Adverse Events (AEs) during treatment is one of the leading causes of unsuccessful treatment outcomes among patients with drug resistant tuberculosis (DR-TB). However, information related to AEs is not systematically collected and managed under programmatic setting. The present study assessed the a) incidence and pattern of adverse events in first three months of DR-TB treatment initiation; b) treatment seeking behaviour for AE management; and c) explore the challenges in seeking treatment and reporting AEs.MethodsThis mixed methods study included all patients diagnosed and initiated on treatment under RNTCP during July–September 2018 at Ahmedabad DR-TB centre. The patients were interviewed telephonically and assessed for all AEs experienced by them. In-depth interviews and key-informant interviews were conducted among patients, DOTS supervisors and programme staff (treatment supervisors, medical officer and district program managers).ResultsTotal 207 AEs were reported by the 74 DR-TB patients. All patients experienced at least one AE during initial treatment period. Incidence rate of AEs (experienced) was 3.11 (1st month-4.6, 2nd month-2.7, 3rd month-2.02) per 100 person days. Of the 207 AEs, gastro-intestinal (59, 28.3%), ophthalmic (32, 15.4%) and otolaryngology (25, 11.9%) system related AEs were commonly experienced. Treatment was not sought in two-fifths of the AEs. Themes and sub-themes related to challenges in treatment seeking or reporting of AEs were 1) Patient related-Misconceptions, accessibility and affordability of management, lack of counselling support, stigma and discrimination, and past treatment experience; 2) Health system related- lack of guidelines and training for AE management, 3) Poor coordination between hospital and tuberculosis centre.ConclusionThe incidence of AEs was high among patients with DR-TB in the first three months of treatment and treatment seeking/reporting was low. Adequate health education and counselling of the patient and orientation of the health systems is the need of the hour. An efficient real-time reporting and management of AE should be developed and tested for effective DR-TB control.

A Study on Molecular Detection of Mutations Associated with Second Line Anti-tuberculosis Drug Resistance

Background: Efficient tuberculosis (TB) control is based on an early diagnosis followed by the rapid identification of drug resistance, in order to treat patients adequately, break the chain of transmission, and avoid the spread of resistant strains. Multidrug-resistant (MDR) Mycobacterium tuberculosis have emerged worldwide and seriously threaten TB control and prevention programs. At the same time, the emergence of extensively drug-resistant tuberculosis (XDR TB) has also become an important global health problem.&#x0D; Objectives: To detect common gene mutation pattern associated with drug resistance against second line anti-tuberculosis drugs in TB patients by SL-LPA as a rapid and early diagnostic test.&#x0D; Materials and Methods:total 652 sputum samples were received from 30 districts at culture district laboratory, Jamnagar from October 2018 to December 2018, and were included in the study. Second line Second line- line probe assay (SL-LPA) was used to detect mutations associated with resistance for anti-tuberculosis drugs.&#x0D; Results: Out of the 652 samples analyzed for mutations associated with second line anti-tuberculosisdrug resistance, 43% of the samples exhibited various forms of mutations. Out of these samples, mutations associated with gyrA gene were detected in 36.6% samples, gyrB gene mutation in 0.7% samples, rrs gene mutation in 4.4% samples and eis gene mutation in 1.2% samples.&#x0D; Conclusion: The present study provide information on the mutation pattern of drug resistant strains present in the geographical area and help to provide the basis for effective strategies for control of drug resistant TB in this region. It also re-emphasizes the importance of second line LPA which can diagnose TB and drug resistance in a single day and allows earlier administration of appropriate treatment as compared to culture result which take 1-2 months.

Exploring local realities: Perceptions and experiences of healthcare workers on the management and control of drug-resistant tuberculosis in Addis Ababa, Ethiopia.

BackgroundDrug-resistant tuberculosis (DR-TB) remains a major health security threat worldwide. The effectiveness of implementation of DR-TB control strategies has been a subject of research and controversy. In resource-limited settings, using conventional medicine as the only framework to explain DR-TB gives a rather incomplete picture of the disease. This study intended to explore the perceptions and experiences of healthcare workers on the management and control of DR-TB in Addis Ababa, Ethiopia.MethodsThe study employed a qualitative methodology with an inductive approach and a thematic analysis. It involved in-depth interviews with healthcare workers providing clinical services to DR-TB patients in 10 public healthcare facilities in Addis Ababa, Ethiopia.ResultsA total of 18 healthcare workers participated until data saturation, which included 12 clinical nurses, four health officers and two medical laboratory technicians. The findings show that healthcare workers perceive DR-TB as a growing public health threat in Ethiopia, due to factors such as poverty, poor nutrition, crowded settings, healthcare worker and general public awareness of DR-TB, lack of good governance and culture.ConclusionThe perspectives drawn from the healthcare workers shed more light on the image of DR-TB in a developing country context. It has been shown that understanding DR-TB is not confined to what can be drawn from the sphere of biomedicine. There are also interconnected barriers, which predict a dystopia in the epidemiology of DR-TB. Bringing DR-TB under control requires taking a step back from an overwhelming focus on the biomedical facets of the disease, and employ critical thinking on the wider social and structural forces as equally important targets.

A Retrospective Analysis of Multi-Drug Resistant Tuberculosis among Presumptive Pulmonary Drug-Resistant Tuberculosis Patients in Andaman &amp; Nicobar Islands

Introduction: Tuberculosis is a contagious bacterial infection affecting more than 10 million people worldwide. It is a major public health concern in India especially with the increasing numbers of drug-resistant cases of tuberculosis. Lack of early diagnosis, inadequate and inappropriate treatment are the major contributors to the development of drug resistance. PMDT strategy strives for early diagnosis and appropriate treatment of drug-resistant TB. This study was undertaken to estimate the rate of occurrence of MDR-TB among presumptive DR-TB patients in Andaman &amp; Nicobar Islands. Materials and Methods: A retrospective data based study for the calendar year 2018 was done by the state TB centre of the Union Territory of Andaman and Nicobar Islands. All patients with presumptive pulmonary DR-TB (as defined by the PMDT guidelines 2017) were included in the study. The drug resistance was confirmed by phenotypic and genotypic methods. Result: The total number of presumptive DR-TB cases during the calendar year 2018 was 235. Forty eight of the cases were confirmed to be MDR-TB cases. Additional drug resistance to Second Line Injectable aminoglycosides (SLI) and Fluoroquinolones (FQ) was found in 2 and 6 of the cases respectively. Two cases of extreme drug resistant tuberculosis were also found (MDR+SLI+FQ resistance). Conclusion: The best strategy for the control of drug resistant tuberculosis is prevention, which can only be achieved by timely diagnosis and early initiation of appropriate treatment of drug resistant TB cases as per drug susceptibility results, thereby preventing their further transmission.

Brazilian cities profile, the occurence of tuberculosis an its drug-resistant form.

Tuberculosis is closely related to living conditions. This study classifies Brazilian municipalities according to the occurrence of tuberculosis (TB) and drug-resistant TB (DR-TB) cases and describes them with regard to the population's health conditions, tuberculosis control indicators, demographic and socioeconomic profile. In 2014, 327 municipalities reported DR-TB cases. Integrated regions of development or metropolitan regions accounted for 80.1% of national DR-TB cases. Municipalities with DR-TB cases had worse TB outcome indicators, but higher culture test percentages, and more inhabitants and better socioeconomic indicators. The 3,644 municipalities with TB cases, but without DR-TB cases, had the worst socioeconomic indicators among the three groups. The 1,594 municipalities without TB cases had the lowest rates of unemployment and AIDS detection and greater coverage of primary healthcare. The different profiles found in the study can sustain improved national interventions for TB and drug-resistant TB control in Brazil.

Detection of rifampicin resistance of Mycobacterium tuberculosis using multiplex allele specific polymerase chain reaction (MAS-PCR) in Pakistan

Drug resistance in tuberculosis (TB) is a major public health challenge in developing countries such as Pakistan. Multiplex allele specific polymerase chain reaction (MAS-PCR) is a DNA amplification method that could contribute to rapid detection and control of drug resistant tuberculosis (DR-TB) in Pakistan. The purpose of this study was to test the utility of MAS-PCR to detect resistance in Pakistan. Drug susceptibility testing (DST) was used to identify rifampicin resistant and susceptible clinical isolates from TB cases in Pakistan. MAS-PCR was used to detect the most frequent mutations in the gene rpoB among 213 resistant and 37 susceptible isolates. Among 213 clinical isolates, MAS-PCR identified mutation D435Y (Asp435Tyr) in 24 (11.3%) cases, H445Y (His445Tyr) in 14 (6.6%), S450L (Ser450Leu) in 124 (58.2%) and S450W (Ser450Trp) in 18 (8.4%) cases. MAS-PCR did not detect known mutations in 33 (15.5%) cases. Among 12 cases, a novel mutation at codon 434 (Met434Ile) and a common variant at codon 435 (Asp435Tyr) was detected in rpoB gene which is indicative of double mutation. In 4 isolates, a novel mutation at codon 432 (Gln432Pro) was identified. In an additional 4 isolates, mutations Met434Val and His445Asn were identified. Moreover, a mutation in rpoB (Leu452Pro) was found in 5 isolates. DNA sequencing confirmed the absence of mutations in rpoB in the 8 remaining isolates. MAS-PCR had 88.3% sensitivity and 100% specificity using DST as the reference, which suggested that this method could be implemented as an initial marker for screening of multi-drug resistant tuberculosis (MDR-TB) in Pakistan.

Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase

Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) (https://github.com/CPTR-ReSeqTB/UVP) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis.