Burden Of Drug-resistant Tuberculosis Research Articles

Mycobacterium tuberculosis Biofilms: Immune Responses, Role in TB Pathology, and Potential Treatment.

Tuberculosis (TB) is a major public health problem worldwide, and the burden of drug-resistant TB is rapidly increasing. Although there are literatures about the Mtb biofilms, their impact on immune responses has not yet been summarized. This review article provides recent knowledge on Mycobacterium tuberculosis (Mtb) biofilm-immunity interactions, their importance in pulmonary TB pathology, and immune-based therapy targeting Mtb biofilms. Pellicle/biofilm formation in Mtb contributes to drug resistance, persistence, chronicity, surface attachment, transfer of resistance genes, and modulation of the immune response, including reduced complement activation, changes in the expression of antigenic proteins, enhanced activation of T-lymphocytes, elevated local IFNγ+ T cells, and strong antibody production. The combination of anti-TB drugs and anti-biofilm agents has recently become an effective strategy to improve TB treatment. Additionally, immune-targeted therapy and biofilm-based vaccines are crucial for TB prevention.

The clinical profile and outcomes of drug resistant tuberculosis in Central Province of Zambia

BackgroundThe emergence of Drug Resistant Tuberculosis (DR-TB) is one of the main public health and economic problems facing the world today. DR-TB affects mostly those in economically productive years and prevents them from being part of the workforce needed for economic growth. The aim of this study was to determine the Clinical Profile and Outcomes of DR-TB in Central Province of Zambia.MethodsThis was a retrospective cross sectional study that involved a review of records of patients with confirmed DR-TB who were managed at Kabwe Central Hospital’s Multi-Drug Resistant TB (MDR-TB) Ward from the year 2017 to 2021. 183 patients were managed during this period and all were recruited in the study. Data was collected from DR-TB registers and patient files and then entered in SPSS version 22 where all statistical analyses were performed.ResultsThe study revealed that the prevalence of DR-TB among registered TB patients in Central Province was 1.4%. Majority of those affected were adults between the ages of 26 and 45 years (63.9%). The study also found that more than half of the patients were from Kabwe District (60.7%). Other districts with significant number of cases included Kapiri Mposhi 19 (10.4%), Chibombo 12 (6.6%), Chisamba 10 (5.5%), Mumbwa 7 (3.8%) and Mkushi 7 (3.8%). Furthermore, the analysis established that most of the patients had RR-TB (89.6%). 9.3% had MDR-TB, 0.5% had IR-TB and 0.5% had XDR-TB. RR-TB was present in 93.8% of new cases and 88.9% of relapse cases. MDR-TB was present in 6.2% of new cases and 10% of relapse cases. With regard to outcomes of DR-TB, the investigation revealed that 16.9% of the patients had been declared cured, 45.9% had completed treatment, 6% were lost to follow up and 21.3% had died. Risk factors for mortality on multivariate analysis included age 36–45 years (adjusted odds ratio [aOR] 0.253, 95% CI [0.70–0.908] p = 0.035) and male gender (aOR 0.261, 95% CI [0.107–0.638] p = 0.003).ConclusionThe research has shown beyond doubt that the burden of DR-TB in Central Province is high. The study recommends putting measures in place that will help improve surveillance, early detection, early initiation of treatment and proper follow up of patients.

The epidemiology, transmission, diagnosis, and management of drug-resistant tuberculosis-lessons from the South African experience.

Drug-resistant tuberculosis (DR-TB) threatens to derail tuberculosis control efforts, particularly in Africa where the disease remains out of control. The dogma that DR-TB epidemics are fueled by unchecked rates of acquired resistance in inadequately treated or non-adherent individuals is no longer valid in most high DR-TB burden settings, where community transmission is now widespread. A large burden of DR-TB in Africa remains undiagnosed due to inadequate access to diagnostic tools that simultaneously detect tuberculosis and screen for resistance. Furthermore, acquisition of drug resistance to new and repurposed drugs, for which diagnostic solutions are not yet available, presents a major challenge for the implementation of novel, all-oral, shortened (6-9 months) treatment. Structural challenges including poverty, stigma, and social distress disrupt engagement in care, promote poor treatment outcomes, and reduce the quality of life for people with DR-TB. We reflect on the lessons learnt from the South African experience in implementing state-of-the-art advances in diagnostic solutions, deploying recent innovations in pharmacotherapeutic approaches for rapid cure, understanding local transmission dynamics and implementing interventions to curtail DR-TB transmission, and in mitigating the catastrophic socioeconomic costs of DR-TB. We also highlight globally relevant and locally responsive research priorities for achieving DR-TB control in South Africa.

An insight into the burden of drug-resistant tuberculosis in children.

An insight into the burden of drug-resistant tuberculosis in children.

Burden of drug-resistant tuberculosis among contacts of index cases: a protocol for a systematic review

IntroductionPeople having close contact with drug-resistant tuberculosis (DR-TB) patients are at increased risk of contracting and developing the disease. However, no comprehensive review has been undertaken to estimate the burden...

Drug-Resistant Tuberculosis Stigma Among HealthCare Workers Toward the Development of a Stigma-Reduction Strategy: A Scoping Review.

Drug-resistant tuberculosis (DRTB) is a growing concern worldwide. The poor rate of service delivery exacerbates the severity, leading to an increase in community transmission, which is further amplified by stigma. Health care workers (HCWs) are at the forefront lines of service delivery; their efforts are suspected of resulting in stigmatization, negatively impacting patient-centered care. However, little is known about DRTB-related stigma among these HCWs, and interventions are limited. Our scoping review is significant because it provides an overview of the DRTB stigma confronting HCWs and informs subsequent stigma-reduction initiatives. Utilizing Arksey and O'Malley framework, we exhaustively searched electronic databases for relevant English-language studies published from 2010 to 2022, identifying the drivers and facilitators of DRTB-related stigma among HCWs from high-TB and -DRTB burden countries, and compiling recommendations that could reduce DRTB stigma. From 443 de-duplicated papers, 11 articles on HCWs' DRTB-related stigma were reviewed and synthesized. Fear was mentioned across included articles as a stigma driver. Other reported stigma drivers identified included feelings of discrimination, isolation, danger, lack of support, shame, and stress. Poor infection control (IC) was the leading stigma facilitator. Other stigma facilitators identified were differing IC interpretations, workforce culture, and workplace inequality facilitating to stigmatization of HCWs. Three key recommendations identified were addressing infection control issues; increase the competence of healthcare workers; and provide psychosocial assistance, emphasizing HCW safety during DRTB activities. DRTB stigma among HCWs is multifaceted, largely driven by fear and facilitated by varying implementation or interpretations of policies within the workplace. Making HCWs feel safe while conducting DRTB activities is a priority issue that should be addressed by improving IC, training and psychosocial support. More studies investigating country-specific and multilevel DRTB-related stigma among HCWs are required to inform the development of an effective stigma intervention strategy.

Impact of Strategic Adaptations Due to COVID-19 Pandemic on a Capacity Building Program: Insights From a DRTB Program Under NTEP in India

Introduction: India has experienced high burden of drug resistant tuberculosis, under par treatment success rate and very high loss to follow-up despite continuous efforts to develop evidence-based policy to treat DRTB patients. However, it is challenging to translate policies into practice. The goal of this program was to build capacity of the program staff for effective management of DRTB in public sector through workshops, capacity building exercises, creation and dissemination of information, education and communication materials. Methodology: The program was implemented in seven states; 11 state-level kick-off trainings were planned to reach 660 National TB Elimination Program staffs. Due to COVID-19 pandemic, on-field activities were replaced with virtual trainings with a set of 4-5 webinars per state. Pre and post training assessments were done to evaluate uptake of knowledge. Number of trainings conducted, staff trained and knowledge improvement were the indicators used to assess the outcome. Results: A total of 34 webinars were conducted on revised Programmatic Management of Drug- Resistant Tuberculosis guidelines and 3000 staff was trained. The program organized three times more training and five times more staff were trained. Although retention of participants and their attention was challenging, transition to virtual platform provided increased coverage and targeted outputs. Proportion of participants answering correctly in pre/post-training assessments, increased from 47% to 65%. Conclusion: Use of virtual trainings is an efficient high yielding method to build capacity of NTEP staff. Lessons learnt can help improve such interventions, benefit health programs and the end beneficiaries - the patients.

Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management.

Drug resistant tuberculosis contributes significantly to the global burden of antimicrobial resistance, often consuming a large proportion of the healthcare budget and associated resources in many endemic countries. The rapid emergence of resistance to newer tuberculosis therapies signals the need to ensure appropriate antibiotic stewardship, together with a concerted drive to develop new regimens that are active against currently circulating drug resistant strains. Herein, we highlight that the current burden of drug resistant tuberculosis is driven by a combination of ongoing transmission and the intra-patient evolution of resistance through several mechanisms. Global control of tuberculosis will require interventions that effectively address these and related aspects. Interrupting tuberculosis transmission is dependent on the availability of novel rapid diagnostics which provide accurate results, as near-patient as is possible, together with appropriate linkage to care. Contact tracing, longitudinal follow-up for symptoms and active mapping of social contacts are essential elements to curb further community-wide spread of drug resistant strains. Appropriate prophylaxis for contacts of drug resistant index cases is imperative to limit disease progression and subsequent transmission. Preventing the evolution of drug resistant strains will require the development of shorter regimens that rapidly eliminate all populations of mycobacteria, whilst concurrently limiting bacterial metabolic processes that drive drug tolerance, mutagenesis and the ultimate emergence of resistance. Drug discovery programs that specifically target bacterial genetic determinants associated with these processes will be paramount to tuberculosis eradication. In addition, the development of appropriate clinical endpoints that quantify drug tolerant organisms in sputum, such as differentially culturable/detectable tubercle bacteria is necessary to accurately assess the potential of new therapies to effectively shorten treatment duration. When combined, this holistic approach to addressing the critical problems associated with drug resistance will support delivery of quality care to patients suffering from tuberculosis and bolster efforts to eradicate this disease.

Characteristics and Trend of Drug-Resistant Tuberculosis at a Major Specialized Hospital in Chongqing, China: 2016 Versus 2019.

The epidemic of drug-resistant tuberculosis (DR-TB) has become a major concern in global TB control. This study aimed to investigate the patterns and trend of DR-TB epidemic between different time periods in Chongqing. A total of 985 and 835 culture positive TB patients with drug susceptibility testing (DST) results admitted to the hospital in 2016 and 2019, respectively, were included. Chi-square testing was used to compare the prevalence and trends of DR-TB in 2016 and 2019. The proportion of previously treated TB cases with culture positivity was 45.7% in 2019, significantly higher than that in 2016 (39.1%, P = 0.004). The overall rate of drug resistance in 2019 was 43.1%, higher than that in 2016 (40.2%). The rates of multi-drug resistant TB (MDR-TB) and pre-extensively drug resistant TB (pre-XDR-TB) increased significantly from 2016 to 2019 among all TB cases (MDR: 25% vs 33.4%, P < 0.001 and pre-XDR: 7.1% vs 12.8%, P < 0.001, respectively) and previously treated TB cases (MDR: 46.5% vs 56%, P = 0.008 and pre-XDR: 13.2% vs 21.5%, P = 0.003, respectively). Our findings indicated that the prevalence of DR-TB remains high in Chongqing. The trend of resistance to anti-TB drugs beccame worse between 2016 and 2019. Moreover, acquired MDR may play a major role in MDR-TB epidemic in Chongqing. Therefore, rapid diagnosis and effective treatment of TB patients will be important to reduce the burden of DR-TB in Chongqing.

A longitudinal community-based ototoxicity monitoring programme and treatment effects for drug-resistant tuberculosis treatment, Western Cape.

BackgroundSouth Africa has a high burden of drug-resistant tuberculosis (DRTB) and until recently, ototoxic aminoglycosides were predominant in treatment regimens. Community-based ototoxicity monitoring programmes (OMPs) have been implemented for early detection of hearing loss and increased patient access.ObjectivesA longitudinal study was conducted to describe the service delivery characteristics of a community-based OMP for DRTB patients facilitated by CHWs as well as observed ototoxic hearing loss in this population.MethodA descriptive retrospective record review of longitudinal ototoxicity monitoring of 194 DRTB patients undergoing treatment at community-based clinics in the city of Cape Town between 2013 and 2017.ResultsFollow-up rates between consecutive monitoring assessments reached as high as 80.6% for patients assessed by CHWs. Few patients (14.2% – 32.6%) were assessed with the regularity (≥ 6 assessments) and frequency required for effective ototoxicity monitoring, with assessments conducted, on average, every 53.4–64.3 days. Following DRTB treatment, 51.5% of patients presented with a significant ototoxic shift meeting one or more of the American Speech-Language-Hearing Association (ASHA) criteria. Deterioration in hearing thresholds was bilateral and most pronounced at high frequencies (4 kHz – 8 kHz). The presence of pre-existing hearing loss, human immunodeficiency virus co-infection and a history of noise exposure were significant predictors of ototoxicity in patients.ConclusionDRTB treatment with kanamycin resulted in significant deterioration of hearing longitudinally, predominantly at high frequencies. With ongoing training and supportive supervision, CHWs can facilitate community-based ototoxicity monitoring of DRTB patients. Current protocols and guidelines may require reassessment for appropriate community-based ototoxicity monitoring.

Prediction of different interventions on the burden of drug-resistant tuberculosis in China: a dynamic modelling study

Tuberculosis (TB) is one of the top 10 causes of death worldwide. The World Health Organization adopted the 'End TB Strategy' to end the global TB epidemic by 2035. However, achieving this goal will be difficult using current measures. A Susceptible-Exposed-Infectious-Recovered (SEIR) model that distinguishes drug-sensitive (DS) and drug-resistant (DR) TB in the entire Chinese population was established. Goodness-of-fit tests and sensitivity analyses were used to assess model performance. Predictive analysis was performed to assess the effect of different prevention and control strategies on DR-TB. We used parameter fitting to determine the basic reproduction number of the model as R0 = 0.6993. The predictive analysis led to two major projections that can achieve the goal by 2035. First, if the progression rate of latently infected people reaches 10%, then there will be 92.2% fewer cases than in 2015. Second, if the cure rate of DR-TB increases to 40%, then there will be 91.5% fewer cases than in 2015. A combination of five interventions could lead to earlier achievement of the 2035 target. We found that reducing the probability of transmission and the rate of disease progression in patients with DR-TB and improving treatment compliance and the cure rate of patients with DR-TB can contribute to attaining the goal of the End TB Strategy.

Effectiveness and Safety of 9-Month Treatment Regimen for Multidrug-Resistant Tuberculosis in the Philippines

Background: The Philippines has a burden of drug-resistant tuberculosis (DR-TB). One of the key challenges in the programmatic management of DR-TB (PMDT) is the high rate of loss to follow-up (38% in the 2010 cohort). An urgent need for a shorter, more tolerable, less expensive treatment regimen exists. The aim of the operational study is to determine the efficacy and safety of the short treatment regimen among drug resistant TB. Methods: This is a prospective single-arm cohort study evaluating the effectiveness and safety of a shorter 9 - 11-month treatment regimen (9MTR) for rifampicin-resistant/multi-drug resistant TB (RR/MDR-TB) in 10 PMDT facilities. All eligible consenting adult patients with rifampicin-resistant TB were enrolled and received the standardized 9-month treatment regimen (9MTR), including injectables, with a follow-up after 12 months of treatment completion. Results: A total of 329 patients were enrolled from July 2015 to December 2016. At the 6th month post-enrollment, 256 (77.8%) of them had culture-negative test results. The end-of-treatment success rate was 74.1% (224 [68.0%] were cured and 20 [6.1%] completed the treatment). On the other hand, 10 (3.0%) died, 41 (12.5%) lost to follow-up, 33 (10.0%) withdrawn, 1 (0.3%) treatment failure. In the 12th month after 9MTR completion, among the 244 patients with successful treatment, 198 (81.1%) had culture-negative results, while there were 46 patients whose culture tests were not done. One patient developed TB relapse with fluoroquinolone resistance. The majority of the adverse events were mild that occurred mostly during the first 6 months of treatment. Conclusion: The 9-month treatment regimen had a high treatment success rate with a favorable safety profile. The loss to follow-up was reduced; however, it was still a challenge. The introduction of the 9MTR via operational research had a major impact on building national capacity and infrastructure for the programmatic adoption of a new regimen. Ten PMDT centers received training and experience, created diagnostic pathways, and active drug safety monitoring and management were built.

Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates-Chennai, India, 2013-2016.

India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013–2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of rpoB mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB.

Drug resistance and its risk factors among extrapulmonary tuberculosis in Ethiopia: A systematic review and meta-analysis

Drug-resistant tuberculosis and extrapulmonary tuberculosis are the world major public health issues. Although some primary studies have been reported on the burden of drug-resistant tuberculosis in extrapulmonary tuberculosis patients in Ethiopia, there is no systematic review and meta-analysis that attempt to summarize the available literature. Thus, we aimed to estimates the prevalence of drug-resistance in extrapulmonary tuberculosis patients and summarize the risk factors associated with the occurrence of extrapulmonary tuberculosis in Ethiopia. We conducted a systematic review of the published primary studies on extrapulmonary drug-resistant tuberculosis in Ethiopia. Eight observational studies were included in this review from different regions of Ethiopia. The overall pooled prevalence of rifampicin resistance was 6% (95% CI 0.03-0.10), while isoniazid resistance was 7% (95% CI 0.03-0.12). The pooled prevalence of multidrug-resistant tuberculosis was 4% (95% CI 0.01-0.07). Previous tuberculosis treatment history and male gender are frequently reported risk factors for developing drug-resistant tuberculosis in extrapulmonary tuberculosis patients. The current review has identified a high proportion of resistance to rifampicin, isoniazid, and multidrug-resistant tuberculosis in patients with extrapulmonary tuberculosis in Ethiopia. Clinicians should request drug susceptibility testing for all patients with presumptive extrapulmonary tuberculosis to detect drug-resistance.

The burden of drug resistant tuberculosis in a predominantly nomadic population in Uganda: a mixed methods study

BackgroundEmergence of drug resistant tuberculosis (DR-TB) has aggravated the tuberculosis (TB) public health burden worldwide and especially in low income settings. We present findings from a predominantly nomadic population in Karamoja, Uganda with a high-TB burden (3500 new cases annually) and sought to determine the prevalence, patterns, factors associated with DR-TB.MethodsWe used mixed methods of data collection. We enrolled 6890 participants who were treated for tuberculosis in a programmatic setting between January 2015 and April 2018. A cross sectional study and a matched case control study with conditional logistic regression and robust standard errors respectively were used to the determine prevalence and factors associated with DR-TB. The qualitative methods included focus group discussions, in-depth interviews and key informant interviews.ResultsThe overall prevalence of DR-TB was 41/6890 (0.6%) with 4/64,197 (0.1%) among the new and 37/2693 (1.4%) among the previously treated TB patients respectively. The drug resistance patterns observed in the region were mainly rifampicin mono resistant (68.3%) and Multi Drug-Resistant Tuberculosis (31.7%). Factors independently associated with DR-TB were previous TB treatment, adjusted odds ratio (aOR) 13.070 (95%CI 1.552–110.135) and drug stock-outs aOR 0.027 (95%CI 0.002–0.364). The nomadic lifestyle, substance use, congested homesteads and poor health worker attitudes were a great challenge to effective treatment of TB.ConclusionDespite having the highest national TB incidence, Karamoja still has a low DR-TB prevalence. Previous TB treatment and drug stock outs were associated with DR-TB. Regular supply of anti TB medications and health education may help to stem the burden of TB disease in this nomadic population.

Drug-Resistant Tuberculosis Among Children: A Systematic Review and Meta-Analysis.

Background: Drug-resistant tuberculosis (DR-TB), especially multidrug-resistant tuberculosis (MDR-TB) is a public health threat. Little is known about estimates of different profiles and rates of DR-TB among children globally.Methods: We did a systematic review and meta-analysis of observational studies reporting DR-TB among children by searching Embase, PubMed, and Scopus databases from January 1, 2000 to October 1, 2020. Publications reporting more than 60 children with bacteriological confirmed tuberculosis and phenotypical drug susceptibility testing (DST) results were included. Pooled proportions of MDR-TB and sub-analysis by age subgroups, regions, economical levels were performed.Results: We identified 4,063 studies, of which 37 were included. Of 23,652 pediatric TB patients, the proportions of DR-TB, MDR-TB, mono-resistant TB, polydrug resistant TB, extensively drug-resistant TB were 13.59% (1,964/14,453), 3.72% (881/23,652), 6.07% (529/8,719), 1.61% (119/7,361), 0.44% (30/6,763), respectively. The pooled proportion of MDR-TB among 23,652 children of 37 studies was 3.7% (95% CI, 3.5–4.0%). Rate of MDR-TB was much lower in high-income countries (1.8%) than that in lower-middle-income countries (6.3%) and upper-middle-income countries (7.3%). More specifically, the rates of MDR-TB were 1.7% in USA, 1.7% in UK, 2.9% in India, 6.0% in South Africa, 9.8% in China, respectively.Conclusions: The burden of DR-TB remains high in children, and there are potential associations between rates of pediatric MDR-TB and national economical levels. More interventions on child TB cases in low-income countries may be urgently needed in future.

The Relevance of Genomic Epidemiology for Control of Tuberculosis in West Africa.

Tuberculosis (TB), an airborne infectious disease caused by Mycobacterium tuberculosis complex (MTBC), remains a global health problem. West Africa has a unique epidemiology of TB that is characterized by medium- to high-prevalence. Moreover, the geographical restriction of M. africanum to the sub-region makes West Africa have an extra burden to deal with a two-in-one pathogen. The region is also burdened with low case detection, late reporting, poor treatment adherence leading to development of drug resistance and relapse. Sporadic studies conducted within the subregion report higher burden of drug resistant TB (DRTB) than previously thought. The need for more sensitive and robust tools for routine surveillance as well as to understand the mechanisms of DRTB and transmission dynamics for the design of effective control tools, cannot be overemphasized. The advancement in molecular biology tools including traditional fingerprinting and next generation sequencing (NGS) technologies offer reliable tools for genomic epidemiology. Genomic epidemiology provides in-depth insight of the nature of pathogens, circulating strains and their spread as well as prompt detection of the emergence of new strains. It also offers the opportunity to monitor treatment and evaluate interventions. Furthermore, genomic epidemiology can be used to understand potential emergence and spread of drug resistant strains and resistance mechanisms allowing the design of simple but rapid tools. In this review, we will describe the local epidemiology of MTBC, highlight past and current investigations toward understanding their biology and spread as well as discuss the relevance of genomic epidemiology studies to TB control in West Africa.

Prevalence and molecular characteristics of drug-resistant Mycobacterium tuberculosis in Hainan, China: from 2014 to 2019

BackgroundThe emergence of antimicrobial resistance against Mycobacterium tuberculosis (M. tuberculosis) has become the major concern in global tuberculosis control due to its limited therapy options and high mortality. However, the clinical and molecular characteristics of drug-resistant strains vary in different geographical areas. Hainan Island located in southern China, is a high drug-resistant tuberculosis burden area. This study aimed to determine the dynamic changes of drug-resistance patterns and drug-related gene mutation types of M. tuberculosis in Hainan from 2014 to 2019.ResultsA total of 1484 culture-confirmed M. tuberculosis were included in this study. It was found that the proportions of drug resistance to isoniazid and rifampin were 31.3 and 31.1% respectively. Overall the proportion of multidrug resistant M. tuberculosis was 24.9%. Multivariate logistic regression analysis showed that age and the treatment history were independent influencing factors of drug resistant tuberculosis. The proportions of drug-resistant tuberculosis in retreatment patients were considerably higher than those in new patients. The most common mutation types of isoniazid were Ser315 → Thr (66.3%), and the most common mutation types of rifampin were Ser531 → Leu (41.5%).ConclusionsOur data suggests that the prevalence of drug resistant TB remains high in Hainan, and the risks for developing drug resistance with diversified mutation types increased significantly in retreatment patients. These results contribute to the knowledge of the prevalence of drug resistance in Hainan Province and expand the molecular characteristics of drug resistance in China simultaneously.

Situational analysis of 10 countries with a high burden of drug-resistant tuberculosis 2 years post-UNHLM declaration: progress and setbacks in a changing landscape

ObjectivesGlobally, drug-resistant tuberculosis (DR-TB) is the leading cause of death globally related to antimicrobial resistance, affecting 500,000 emergent cases annually. In 2018, the first United Nations High-Level Meeting (UNHLM) on tuberculosis declared DR-TB a global public health priority. Bold country targets were established for 2018–2022. This study reviews the DR-TB situation in 2018, and the UNHLM target accomplishments in 10 high-burden countries (HBCs). MethodsAn ecological descriptive analysis of the top 10 DR-TB HBCs (Bangladesh, China, India, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, Russian Federation, and South Africa), which share 70% of the global DR-TB burden, was undertaken, complemented by a cascade-of-care analysis and a survey gathering additional information on key advances and setbacks 2 years after the UNHLM declaration. ResultsMost countries are showing historic advances and are on track for the 2018 and 2019 targets. However, according to the cascade-of-care, none of the countries are capable of providing effective care for 50% of the estimated patients. Increasing levels of fluoroquinolone resistance and access to timely susceptibility testing can jeopardize ongoing adoption of shorter, all-oral treatment regimens. The programmatic management of DR-TB in children remains minimal. Achievements for 2020 and beyond may be affected significantly by the coronavirus disease 2019 (COVID-19) pandemic. ConclusionTriggered by the COVID-19 pandemic, there is a global risk of recoil in DR-TB care with long-term consequences in terms of deaths, suffering and wider transmission. Investment to support DR-TB services is more important now than ever to meet the aspirations of the UNHLM declaration.

Situational Analysis of the 10 High Drug Resistant Tuberculosis Burden Countries Two Years Post-UNHLM Declaration: Progress and Setbacks in a Changing Landscape

Drug-resistant tuberculosis (DR-TB) is the greater exponent and, leading global cause of death related to antimicrobial resistance comprising close to 500,000 cases per year. In 2018 the first United Nations high level meeting (UNHLM) on tuberculosis was held, declaring TB and, its resistant forms a first order world public health concern. Bold country targets were established for 2018-2022. Currently 10 countries account for the 70% of the global DR-TB burden (Bangladesh, China, India, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, Russian Federation, and, South Africa). The present study reviews these 10 countries situation in 2018, the levels of DR-TB related UNHLM target accomplishment and, it is complemented with a survey to ascertain key advances and, setbacks at 2 years from the UNHLM declaration. Although most countries are showing an historical advance and, were on track for the 2018 and, 2019 targets, according to the DR-TB country cascade of care, no country is capable of providing care for even 50% of the estimated patients. Increasing levels of fluoroquinolone resistance and, the difficulties in obtaining timely susceptibility results can jeopardize ongoing adoption of shorter, all-oral regimens. Proportions of diagnoses and, enrolled on treatment of children with DR-TB remain minimal. Achievements for 2020 and, beyond are going to be affected by COVID-19 pandemic and, the measures to contain it.Triggered by COVID-19 pandemic, there is a risk of a step back in DR-TB care, with long-term consequences in deaths, suffering and, antimicrobial resistant transmission. Investing in and, supporting DR-TB services is more important than ever to meet the UNHLM aspirations.Funding Information: The study was funded by a GDI initiative with no involvement of any pharmaceutical company or, other agency.Declaration of Interests: No author declared any conflicts of interest.