Is tuberculosis elimination a reality?

Multidrug-resistant (MDR) tuberculosis is a public health emergency and a challenging scenario for both patients and clinicians. In 2012, there were more than 450 000 incident cases and 170 000 deaths worldwide. Treatment of MDR tuberculosis is complex and expensive (€100 000 or more for drugs for one patient), especially its most severe, extensively drug-resistant forms. Treatment is long (at least 2 years), the drugs are toxic (specific expertise is needed to manage adverse reactions), and the outcomes are poor (with low success and high death rates). New drugs will soon be available that will probably shorten and simplify treatment for MDR tuberculosis and increase effectiveness, and public health strategies have been developed to prevent the occurrence of drug resistance. The traditional approach of national tuberculosis programmes, focused on tuberculosis control (ie, rapid diagnosis and early, effective treatment of newly detected infectious cases), which was advocated by the WHO Stop TB Strategy, will soon be replaced by the post-2015 strategy focused on the concept of tuberculosis elimination (ie, fewer than one new sputum smear-positive tuberculosis case per 1 million population). Whereas traditional contact tracing (eg, looking for the contacts of individuals with tuberculosis and MDR tuberculosis in progressive circles) recommends identification and treatment of latently infected individuals and additional tuberculosis cases, new approaches recommend genotypic identification of the causative strain, monitoring of the epidemic, and initiation of adequate measures to manage it. One such approach is mycobacterial interspersed repetitive-unit-variable-number tandem repeat (MIRU-VNTR) strain typing. In The Lancet Infectious Diseases, Laura F Anderson and colleagues report an assessment of transmission of MDR tuberculosis in the UK between 2004 and 2007, using the 24-loci MIRU-VNTR method together with epidemiological data collected through the national surveillance system and an ad-hoc cluster investigation questionnaire. The scope was to identify the relative frequency of MDR tuberculosis cases transmitted nationwide. 204 patients were diagnosed with MDR tuberculosis in the study period of whom 189 (92·6%) had an MIRU-VNTR profile. 15% of these cases were clustered. Furthermore, Anderson and colleagues analysed the risk factors associated with MDR tuberculosis transmission: being born in the UK (odds ratio 4·81; 95% CI 2·03—11·36, p=0·0005) and having a history of illicit drug use (4·75; 1·19—18·96, p=0·026) significantly increased the probability of transmission. Most cases (21 of 22) were transmitted in the household. The occurrence of MDR tuberculosis transmission in the UK is lower than in other European and non-European settings, probably as a consequence of scarce transmission occurring between specific population groups. The study is an excellent example of nationwide implementation of one of the European Centre for Disease Prevention and Control (ECDC) recommendations to eliminate tuberculosis in the European Union. Moreover, the identification of risk factors allows the prioritisation of the public health investigations, reducing the probability of transmission related to health-care system delay. The core strength of the study is the high proportion of MDR tuberculosis cases assessed with the novel diagnostic approach (ie, 24-loci MIRU-VNTR) and the ability to increase sensitivity compared with the traditional epidemiological investigations. However, other more sensitive techniques such as whole genome sequencing analysis could also have increased the ability to identify additional epidemiological links, which means that a potential underestimation of MDR tuberculosis transmission should be considered. Low culture confirmation (about 60% in the UK) could also have underestimated the true prevalence of transmission. Molecular methods have several public health applications, including identification of outbreaks, population groups at highest risk of transmission, transmission across jurisdictions, transmission chains, reinfected and relapsing cases, and laboratory cross-contamination. However, several technical problems currently hinder their integration into national tuberculosis programmes, including the absence of a gold standard to effectively assess their discriminatory power. The ECDC recommends monitoring and assessment of transmission of drug-susceptible and drug-resistant mycobacterial strains by adoption of sensitive and specific molecular methods. Molecular fingerprinting, alongside classic epidemiological studies, will be helpful to discriminate real clusters of tuberculosis cases (ie, individuals infected by the same genotypes) and to (indirectly) assess the efficacy of a tuberculosis control programme implemented at a national or regional level. If we are to make tuberculosis elimination a reality, this UK experience needs to be followed up in other European Union countries. The implementation of molecular methods with increased sensitivity allows the bypassing of low discriminatory power associated with traditional contact tracing procedures, scaling up part of the European Union's tuberculosis elimination package.</br

Effect of the short-course regimen on the global epidemic of multidrug-resistant tuberculosis

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prevention of tuberculosis transmission through medical surveillance systems

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Better data, more tailored tuberculosis therapies

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Predicting the effect of improved socioeconomic health determinants on the tuberculosis epidemic

Two important public health documents have recently established programmatic goals for tuberculosis control. The first is WHO's End TB Strategy, which represents the evolution of previous DOTS (directly observed treatment, short-course) and Stop TB strategies.1 End TB is built around three pillars: pillar 1 focuses on diagnosis, treatment, and prevention; pillar 2 on ways to tackle socioeconomic factors (eg, poverty reduction, social protection, and universal access); and pillar 3 on scientific research

Screening for tuberculosis in migrants : a survey by the global tuberculosis network

Tuberculosis (TB) does not respect borders, and migration confounds global TB control and elimination. Systematic screening of immigrants from TB high burden settings and-to a lesser degree TB infection (TBI)-is recommended in most countries with a low incidence of TB. The aim of the study was to evaluate the views of a diverse group of international health professionals on TB management among migrants. Participants expressed their level of agreement using a six-point Likert scale with different statements in an online survey available in English, French, Mandarin, Spanish, Portuguese and Russian. The survey consisted of eight sections, covering TB and TBI screening and treatment in migrants. A total of 1055 respondents from 80 countries and territories participated between November 2019 and April 2020. The largest professional groups were pulmonologists (16.8%), other clinicians (30.4%), and nurses (11.8%). Participants generally supported infection control and TB surveillance established practices (administrative interventions, personal protection, etc.), while they disagreed on how to diagnose and manage both TB and TBI, particularly on which TBI regimens to use and when patients should be hospitalised. The results of this first knowledge, attitude and practice study on TB screening and treatment in migrants will inform public health policy and educational resources

Regimens to treat multidrug-resistant tuberculosis:past, present and future perspectives

Over the past few decades, treatment of multidrug-resistant (MDR)/ extensively drugresistant (XDR) tuberculosis (TB) has been challenging because of its prolonged duration (up to 2024 months), toxicity, costs and sub-optimal outcomes. After over 40 years of neglect, two new drugs (bedaquiline and delamanid) have been made available to manage difficult-to-treat MDR-/XDR-TB cases. World Health Organization (WHO) guidelines published in March 2019 endorsed the possibility of treating MDR-TB patients with a full oral regimen, following previous guidelines published in 2016 which launched a shorter regimen lasting 9-10 months.The objectives of this article are to review the main achievements in MDR-TB treatment through the description of the existing WHO strategies, to discuss the main ongoing trials and to shed light on potential future scenarios and revised definitions necessary to manage drug-resistant TB.</p

Tuberculosis and the strategy for the New Millennium: not simply “more of same”

Since the beginning of human history, tuberculosis (TB) has threatened the wellbeing of mankind. The last Global Tuberculosis Report, published by the World Health Organization (WHO) in 2013, highlighted the significant burden in morbidity and mortality that Mycobacterium tuberculosis still bears in the world today [1]...

Clinical standards for drug-susceptible pulmonary TB

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB). METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants. RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB. CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.CONTEXTE : L’objectif de ces normes cliniques est de fournir des conseils sur les ‘‘meilleures pratiques’’ en matière de diagnostic, de traitement et de prise en charge de la tuberculose pulmonaire (PTB) pharmacosensible. MÉTHODES : Un panel de 54 experts mondiaux dans le domaine des soins antituberculeux, de la santé publique, de la microbiologie et de la pharmacologie a été identifié ; 46 ont participé à un processus Delphi. Une échelle de Likert en 5 points a été utilisée pour noter les projets de normes. Le document final représente le large consensus et a été approuvé par les 46 participants. RÉSULTATS : Sept normes cliniques ont été définies : Norme 1, tous les patients (adultes ou enfants) qui présentent des symptômes et des signes compatibles avec une PTB doivent subir des examens pour parvenir a un diagnostic ; Norme 2, des tests bactériologiques adéquats doivent être effectués pour exclure une TB résistante aux médicaments ; Norme 3, un régime convenable recommandé par l’OMS et les directives nationales pour le traitement de la PTB doit être identifié ; Norme 4, une éducation et des conseils sur la santé doivent être dispensés à chaque patient commençant le traitement ; Norme 5, un suivi du traitement doit être effectué pour évaluer l’adhésion, suivre les progrès du patient, identifier et gérer les effets indésirables et détecter le développement de la résistance ; Norme 6, une série recommandée d’examens du patient doit être effectuée à la fin du traitement ; Norme 7, les actions de santé publique nécessaires doivent être menées pour chaque patient. Nous avons également identifié les priorités pour les recherches futures sur la PTB. CONCLUSION : Ces normes cliniques consensuelles contribueront á améliorer la prise en charge des patients en guidant les cliniciens et les responsables de programmes dans la planification et la mise en œuvre de mesures localement appropriées pour un traitement optimal de la PTB centré sur la personne