Drug Susceptibility Patterns in MDR-TB Patients:Challenges for Future Regimen Design. A Cross-Sectional Study

Globally, there is substantial concern regarding the challenges of treating complex drug resistance patterns in multidrug resistant tuberculosis cases. Utilising data from three different settings (Estonia, Latvia, Romania) we sought to contrast drug susceptibility profiles for multidrug resistant tuberculosis cases, highlight the difficulties in designing universal regimen, and inform future regimen selection. Demographic and microbiological surveillance data for multidrug resistant tuberculosis cases from 2004-13 were analysed. High levels of additional resistance to currently recommended second line drugs were seen in all settings, with extensive variability between countries. Accurate drug susceptibility testing and drug susceptibility testing data are vital to inform the development of comprehensive, flexible, multidrug resistant tuberculosis guidance

Diagnostic performance of the AID line probe assay in the detection of Mycobacterium tuberculosis and drug resistance in Romanian patients with presumed TB.

BACKGROUND: The AID line probe assay has shown promising evaluation data on the detection of Mycobacterium tuberculosis as well as 1st- and 2nd-line drug resistance, using isolates and selected clinical samples in previous studies. METHODS: The diagnostic performance of three AID-modules (AID INH/RIF, AID FQ/EMB and AID AG) was analyzed in sputum samples from patients with presumed tuberculosis against culture methods and phenotypic drug resistance as reference standards.Results59 patients had culture-confirmed tuberculosis. All AID modules showed moderate sensitivity (46/59, 78.0%, 65.3-87.7) and very good specificity (100%, 95.5%, 93.7%). There was a high proportion of invalid tests, resulting in 32.6%, 78.3% and 19.6% of 46 AID-positive tuberculosis cases, who could not be assessed for drug resistance by the AID INH/RIF-, AID FQ/EM- and AID AG-module, respectively. A small number of patients showed drug resistance by reference standards: Three MDR-TB cases plus three, one and one patients with resistance to streptomycin, fluoroquinolones and aminoglycosides, respectively. The AID-assay detected all MDR-TB cases, two of three streptomycin-resistant TB cases, one of one of fluoroquinolone-resistant and missed one aminoglycoside-resistant TB case. DISCUSSION: The high proportion of invalid results precludes the use of the AID-assay from direct sputum-based tuberculosis and drug-resistance testing

Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement.

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence. This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking

The Bidirectional Relationship between Pulmonary Tuberculosis and Lung Cancer

Lung cancer and pulmonary tuberculosis are two significant public health problems that continue to take millions of lives each year. They may have similar symptoms and, in some cases, are diagnosed simultaneously or may have a causal relationship. In tuberculosis disease, the chronic inflammation, different produced molecules, genomic changes, and fibrosis are believed to be important factors that may promote carcinogenesis. As a reverse reaction, the development of carcinogenesis and the treatment may induce the reactivation of latent tuberculosis infection. Moreover, the recently used checkpoint inhibitors are a debatable subject since they help treat lung cancer but may lead to the reactivation of pulmonary tuberculosis and checkpoint-induced pneumonitis. Pulmonary rehabilitation is an effective intervention in post-tuberculosis patients and lung cancer patients and should be recommended to improve outcomes in these pathologies

Drug susceptibility testing results for multidrug resistant tuberculosis patients in Estonia, Latvia and Romania in 2013.

<p>^aDenominator 28</p><p>^bdenominators (new cases, retreatment cases) ethambutol 97, 255; amikacin 66, 154; capreomycin 70, 164; kanamycin 87, 234; ofloxacin 69, 152; cycloserine 28, 105; PAS 60, 151</p><p>^cdenominator 48</p><p>^ddenominator 49</p><p>^edenominator 19 new, 12 retreatment</p><p>^fethionamide DST undertaken in Latvia and Romania (denominators for new Romanian cases 89, retreatment cases 220)</p><p>^gdenominator 21 new, 14 retreatment. DST- drug susceptibility testing; PAS- p-aminosalicylic acid.</p><p>Drug susceptibility testing results for multidrug resistant tuberculosis patients in Estonia, Latvia and Romania in 2013.</p

Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model

Background The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)-and multidrug-resistant (MDR)-TB. Methods Adult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points. Results 50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS-and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9-0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001). Conclusion Biomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB

Tuberculosis incidence in foreign-born people residing in European countries in 2020

Background: European-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening. Aim: We aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening. Methods: The Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin. Results: Data on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both &gt; 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea. Conclusions: Country of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks