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Drug-resistant tuberculosis (TB) is emerging as a new and serious public health challenge. We present the first case with confirmed extensive drug-resistant TB in Tanzania in a patient who had prior exposure to anti-TB drugs and a history of imprisonment in South Africa. The addition of bedaquiline to the treatment regime resulted in positive to negative sputum conversion. After a total of 30 months on treatment he was declared cured, remaining clinically stable and culture-negative throughout the follow-up. Close monitoring is important in managing drug-resistant TB cases, and good surveillance is required to detect drug-resistant TB to prevent further transmission. [ABSTRACT FROM AUTHOR]

Abstract: The emergence of drug-resistant tuberculosis has brought with it diverse perspectives concerning the way in which the disease should be managed. The media is an important source of these perspectives, as they perform the dual role of reflecting and shaping public discourse. In this study, we are interested in how the media presents multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in South Africa, where both variants are a growing public health concern. We examined newspaper content from 310 South African newspaper articles from February 2004 to July 2009 that discussed MDR-TB and XDR-TB. Newspaper articles were collected from the Dow Jones Factiva database and imported into QDA Miner v3.2.1 for analysis. Using Attride-Stirling’s thematic network analysis method, articles were analyzed according to themes, sub-themes, and thematic networks. This analysis identified two main dimensions: causes of MDR/XDR-TB and treatment approaches/solutions. Causes of MDR/XDR-TB revolved around three main global themes: i) patient-centred causes (32.6%); ii) lack of infection control procedures (18.7%); and iii) health systems failures (19.4%). Treatment approaches or solutions to tackling MDR/XDR-TB focused on i) patient targeted solutions (38.4%); ii) improving infection control (12.3%); iii) systems restructuring (10.6%); and iv) new diagnostic and therapeutic options (10%). Our analysis identifies a trend in the South African media to identify a broad range of causes of MDR/XDR-TB, while emphasizing that treatment approaches should be directed primarily at the individual. Of particular importance is the fact that such a perspective runs contrary to the World Health Organization''s (WHO) recommendations for approaching the TB epidemic, in particular by insufficiently addressing systemic and social drivers of the epidemic. Due to the media''s potential influence on policy formation, how the media presents issues – especially issues pertaining to emerging public health concerns – should warrant more attention. [Copyright &y& Elsevier]

Abstract: Drug resistant tuberculosis (TB) has reached alarming proportions in South Africa, draining valuable resources that are needed to fight drug susceptible TB. It is currently estimated that 9.6% of all TB cases have multi-drug resistant (MDR)-TB, thereby ranking South Africa as one of the highest MDR-TB burden countries in the world. Molecular epidemiological studies have demonstrated the complexity of the epidemic and have clearly shown that the epidemic is driven by transmission as a consequence of low cases detection and diagnostic delay. The latter has in turn fueled the amplification of drug resistance, ultimately leading to the emergence of extensively drug resistant (XDR)-TB. Despite the introduction of new drugs to combat this scourge, culture conversion rates for XDR-TB remain below 20%. Failure to achieve cure may be explained from DNA sequencing results which have demonstrated mutations in 7 genes encoding resistance to at least 8 anti-TB drugs. This review shows how molecular epidemiology has provided novel insights into the MDR-TB epidemic in South Africa and thereby has highlighted the challenges that need to be addressed regarding the diagnosis and treatment of MDR-TB. An important step towards for curbing this epidemic will be collaboration between clinicians, laboratories and researchers to establish scientific knowledge and medical expertise to more efficiently guide public health policy. [Copyright &y& Elsevier]

Summary Despite the relevance of extensively drug-resistant tuberculosis (XDR-TB) to global TB control efforts, case reports on patients achieving cure are scarce. The case of a patient who was treated for more than 3 years as a multidrug-resistant TB (MDR-TB) case, and who was diagnosed retrospectively with XDR-TB, is presented herein. Soon after the initiation of a capreomycin and para-aminosalicylic acid-based regimen, the patient converted and treatment was completed successfully. [ABSTRACT FROM AUTHOR]

Extensively drug-resistant tuberculosis (XDR-TB), defined as resistance to at least isoniazid (INH), rifampicin (RIF), a fluoroquinolone (FQ) and a second-line injectable drug (SLID), is difficult to treat and poses a major threat to TB control. The transmission dynamics and distribution of XDR Mycobacterium tuberculosis ( Mtb ) strains have not been thoroughly investigated. Using whole genome sequencing data on 461 XDR- Mtb strains, we aimed to investigate the geographical distribution of XDR- Mtb strains in the Western Cape Province of South Africa over a 10 year period (2006-2017) and assess the association between Mtb sub-lineage, age, gender, geographical patient location and membership or size of XDR-TB clusters. First, we identified transmission clusters by excluding drug resistance-conferring mutations and using the 5 SNP cutoff, followed by merging clusters based on their most recent common ancestor. We then consecutively included variants conferring resistance to INH, RIF, ethambutol (EMB), pyrazinamide (PZA), SLIDs and FQs in the cluster definition. Cluster sizes were classified as small (2-4 isolates), medium (5-20 isolates), large (21-100 isolates) or very large (>100 isolates) to reflect the success of individual strains. We found that most XDR-TB strains were clustered and that including variants conferring resistance to INH, RIF, EMB, PZA and SLIDs in the cluster definition did not significantly reduce the proportion of clustered isolates (85.5-82.2 %) but increased the number of patients belonging to small clusters (4.3-12.4 %, P =0.56). Inclusion of FQ resistance-conferring variants had the greatest effect, with 11 clustered isolates reclassified as unique while the number of clusters increased from 17 to 37. Lineage 2 strains (lineage 2.2.1 typical Beijing or lineage 2.2.2 atypical Beijing) showed the large clusters which were spread across all health districts of the Western Cape Province. We identified a significant association between residence in the Cape Town metropole and cluster membership ( P =0.016) but no association between gender, age and cluster membership or cluster size ( P =0.39). Our data suggest that the XDR-TB epidemic in South Africa probably has its origin in the endemic spread of MDR Mtb and pre-XDR Mtb strains followed by acquisition of FQ resistance, with more limited transmission of XDR Mtb strains. This only became apparent with the inclusion of drug resistance-conferring variants in the definition of a cluster. In addition to the prevention of amplification of resistance, rapid diagnosis of MDR, pre-XDR and XDR-TB and timely initiation of appropriate treatment is needed to reduce transmission of difficult-to-treat TB.

Early detection of resistance to second-line antituberculosis drugs is important for the management of multidrug-resistant tuberculosis (MDR-TB). The GenoType MTBDR sl version 2.0 (VER 2.0) line probe assay has been redesigned for molecular detection of resistance-conferring mutations of fluoroquinolones (FLQ) ( gyrA and gyrB genes) and second-line injectable drugs (SLID) ( rrs and eis genes). The study evaluated the diagnostic performance of the GenoType MTBDR sl VER 2.0 assay for the detection of second-line drug resistance compared with phenotypic drug susceptibility testing (DST), using the Bactec MGIT 960 system on Mycobacterium tuberculosis complex isolates from South Africa. A total of 268 repository isolates collected between 2012 and 2014, which were rifampin monoresistant or MDR based on DST, were selected. MTBDR sl VER 2.0 testing was performed on these isolates and the results analyzed. The MTBDR sl VER 2.0 sensitivity and specificity indices for culture isolates were the following: FLQ, 100% (95% confidence interval [CI] 95.8 to 100%) and 98.9% (95% CI, 96.1 to 99.9%); SLID, 89.2% (95% CI, 79.1 to 95.6%) and 98.5% (95% CI, 95.7 to 99.7%). The sensitivity and specificity observed for individual SLID were the following: amikacin, 93.8% (95% CI, 79.2 to 99.2%) and 98.5% (95% CI, 95.5 to 99.7%); kanamycin, 89.2% (95% CI, 79.1 to 95.6%) and 98.5% (95% CI, 95.5 to 99.7%); and capreomycin, 86.2% (95% CI, 68.3 to 96.1%) and 95.9% (95% CI, 92.2 to 98.2%). An interoperator reproducibility of 100% and an overall interlaboratory performance of 93% to 96% were found. The overall improvement in sensitivity and specificity with excellent reproducibility makes the GenoType MTBDR sl VER 2.0 a highly suitable tool for rapid screening of clinical isolates for second-line drug resistance for use in high-burden TB/HIV settings., (Copyright © 2017 American Society for Microbiology.)

Background: Extensively drug-resistant (XDR) tuberculosis (TB) and HIV coinfection is associated with low cure rates and high mortality. Clofazimine has shown activity in vitro against Mycobacterium tuberculosis, but clinical experience with clofazimine in XDR-TB and HIV coinfection is limited., Methods: This was a retrospective cohort study of adult XDR-TB patients in KwaZulu-Natal, South Africa, treated with either a clofazimine- or non-clofazimine-containing XDR-TB treatment regimen. The primary outcome measure was TB culture conversion at 6 months. Survival analysis and multivariate logistic regression compared time to event in different strata and identified risk factors for TB culture conversion., Results: Between August 2009 and July 2011, eligible XDR-TB patients (n = 85) were initiated on treatment for XDR-TB. Most patients (86%) were HIV-infected and receiving antiretroviral therapy (90%). Patients receiving a clofazimine-containing regimen (n = 50) had a higher percentage of culture conversion (40%) compared with patients (n = 35) receiving a non-clofazimine regimen (28.6%). On multivariate analysis, there was a 2-fold increase in TB culture conversion at 6 months (hazard rate ratio 2.54, 95% CI 0.99-6.52, P = 0.05) in the group receiving a clofazimine-containing regimen. Adverse effects due to clofazimine were minor and rarely life-threatening., Conclusions: Clofazimine was associated with improved culture conversion in the treatment of XDR-TB/HIV. Adverse effects were minor and non-life-threatening. Based on these preliminary data, further study of clofazimine in XDR-TB/HIV treatment is warranted. Given the present low rates of culture conversion in XDR-TB treatment, we recommend empirical inclusion of clofazimine in treatment regimens for XDR-TB., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Extensively drug-resistant tuberculosis (XDR-TB) is emerging as a global public health problem. Its treatment is more expensive and difficult, and the outcomes much severe. The identification of risk factors for XDR-TB is of paramount importance to design effective TB control strategies., Objective: To review published articles on risk factors for XDR-TB., Methods: We identified 249 English articles on PubMed, and 182 were excluded by the abstract. The remaining articles were retrieved for full-text detailed evaluation by authors, and 27 relevant articles were selected for final review., Results: Some risk factors were consistently present, mainly previous TB treatment and its length. Other conditions often associated were immigration, alcoholism and HIV coinfection. Pre-XDR-TB points to an increased risk of XDR-TB., Conclusion: The information regarding determinants of XDR-TB is relatively weak. However, special emphasis should be given to minimize the risks of TB retreatment to prevent the emergence of highly resistant TB., (© 2013 John Wiley & Sons Ltd.)

Factors driving the increase in drug-resistant tuberculosis (TB) in the Eastern Cape Province, South Africa, are not understood. A convenience sample of 309 drug-susceptible and 342 multidrug-resistant (MDR) TB isolates, collected July 2008-July 2009, were characterized by spoligotyping, DNA fingerprinting, insertion site mapping, and targeted DNA sequencing. Analysis of molecular-based data showed diverse genetic backgrounds among drug-sensitive and MDR TB sensu stricto isolates in contrast to restricted genetic backgrounds among pre-extensively drug-resistant (pre-XDR) TB and XDR TB isolates. Second-line drug resistance was significantly associated with the atypical Beijing genotype. DNA fingerprinting and sequencing demonstrated that the pre-XDR and XDR atypical Beijing isolates evolved from a common progenitor; 85% and 92%, respectively, were clustered, indicating transmission. Ninety-three percent of atypical XDR Beijing isolates had mutations that confer resistance to 10 anti-TB drugs, and some isolates also were resistant to para-aminosalicylic acid. These findings suggest the emergence of totally drug-resistant TB.