Masoud Dara

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone. Guidelines on LTBI for low TB incidence countries – essential element of the @WHO #EndTB strategy and TB elimination http://ow.ly/RW8xn

European union standards for tuberculosis care.

The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society (ERS) jointly developed European Union Standards for Tuberculosis Care (ESTC) aimed at providing European Union (EU)-tailored standards for the diagnosis, treatment and prevention of tuberculosis (TB). The International Standards for TB Care (ISTC) were developed in the global context and are not always adapted to the EU setting and practices. The majority of EU countries have the resources and capacity to implement higher standards to further secure quality TB diagnosis, treatment and prevention. On this basis, the ESTC were developed as standards specifically tailored to the EU setting. A panel of 30 international experts, led by a writing group and the ERS and ECDC, identified and developed the 21 ESTC in the areas of diagnosis, treatment, HIV and comorbid conditions, and public health and prevention. The ISTCs formed the basis for the 21 standards, upon which additional EU adaptations and supplements were developed. These patient-centred standards are targeted to clinicians and public health workers, providing an easy-to-use resource, guiding through all required activities to ensure optimal diagnosis, treatment and prevention of TB. These will support EU health programmes to identify and develop optimal procedures for TB care, control and elimination.

Old ideas to innovate tuberculosis control: preventive treatment to achieve elimination

The introduction of new rapid diagnostic tools for tuberculosis (TB) and the promising TB drugs pipeline together with the development of a new World Health Organization Strategy post 2015 allows new discussions on how to direct TB control. The European Respiratory Society’s European Forum for TB Innovation was created to stimulate discussion on how to best take advantage of old and new opportunities, and advances, to improve TB control and eventually progress towards the elimination of TB. While TB control is aimed at reducing the incidence of TB by early diagnosis and treatment of infectious cases of TB, TB elimination requires focus on sterilising the pool of latently infected individuals, from which future TB cases would be generated. This manuscript describes the three core components that are necessary to implement the elimination strategy fully. 1) Improve diagnosis of latent TB infected individuals. 2) Improve regimens to treat latent TB infection. 3) ensure public health commitment to make both 1) and 2) possible. Old and new evidence is critically described, focusing on the European commitment to reach elimination and on the innovative experiences and best practices available. Diagnosis and treatment of latent TB infection is the core intervention to reach elimination http://ow.ly/mjW0R

Tuberculosis elimination: theory and practice in Europe

Although Europe identified the pathway to tuberculosis (TB) elimination in 1990, no information on programmes for country preparedness is available. A questionnaire investigating TB elimination activities was submitted to 38 national TB programme representatives of low TB incidence (<20 cases per 100 000 population) European countries/territories of the World Health Organization European region. Out of 31 providing a complete answer, 17 (54.8%) reported to have a dedicated national TB programme, 20 (64.5%) a national plan including TB elimination (13 (41.9%) including targets), 22 (71%) guidelines, 14 (45.2%) a specific budget for TB activities, and 23 (74.2%) TB reference centres. All countries reported having case-based electronic TB surveillance, 19 (61.3%) perform regular supervision, 12 (38.7%) have a monitoring and evaluation plan and five (16.1%) perform modelling. In three countries (9.7%), TB health services are free for insured individuals only. In 22 countries/territories (71%) not all TB drugs were available, while in 12 (38.7%) drug stock-outs have been described. Although high-risk group screening for latent TB infection is performed by the majority of countries, only 6 (19.4%) provided figures on preventive treatment completion rates. Not all elements identified as essential for country preparedness to achieve TB elimination are available in the countries surveyed. As TB elimination interventions are sub-optimally applied, more training, awareness and political commitment are necessary http://ow.ly/ru6PV

Multidrug-resistant tuberculosis in Belarus: the size of the problem and associated risk factors

OBJECTIVE To assess the problem of multidrug-resistant tuberculosis (MDR-TB) throughout Belarus and investigate the associated risk factors. METHODS In a nationwide survey in 2010-2011, 1420 tuberculosis (TB) patients were screened and 934 new and 410 previously treated cases of TB were found to meet the inclusion criteria. Isolates of Mycobacterium tuberculosis from each eligible patient were tested for susceptibility to anti-TB drugs. Sociobehavioural information was gathered in interviews based on a structured questionnaire. FINDINGS MDR-TB was found in 32.3% and 75.6% of the new and previously treated patients, respectively, and, 11.9% of the 612 patients found to have MDR-TB had extensively drug-resistant TB (XDR-TB). A history of previous treatment for TB was the strongest independent risk factor for MDR-TB (odds ratio, OR: 6.1; 95% confidence interval, CI: 4.8-7.7). The other independent risk factors were human immunodeficiency virus (HIV) infection (OR: 2.2; 95% CI: 1.4-3.5), age < 35 years (OR: 1.4; 95% CI: 1.0-1.8), history of imprisonment (OR: 1.5; 95% CI: 1.1-2.0), disability sufficient to prevent work (OR: 1.9; 95% CI: 1.2-3.0), alcohol abuse (OR: 1.3; 95% CI: 1.0-1.8) and smoking (OR: 1.5; 95% CI: 1.1-2.0). CONCLUSION MDR-TB is very common among TB patients throughout Belarus. The numerous risk factors identified for MDR-TB and the convergence of the epidemics of MDR-TB and HIV infection call not only for stronger collaboration between TB and HIV control programmes, but also for the implementation of innovative measures to accelerate the detection of TB resistance and improve treatment adherence.

ERS/WHO Tuberculosis Consilium assistance with extensively drug-resistant tuberculosis management in a child: case study of compassionate delamanid use

To the Editor: The European Respiratory Society (ERS) and the World Health Organization (WHO) Regional Office for Europe implemented a consultation body, the ERS/WHO Tuberculosis (TB) Consilium, in late April 2013 [1–4]. This is a novel, high-priority initiative, as part of the 2012–2013 Presidential plan, to face the growing problem of drug-resistant TB in Europe and globally to support clinicians in managing difficult-to-treat TB cases. Clinicians are increasingly challenged by difficult-to-treat cases of multidrug-resistant (MDR)-TB ( i.e. TB caused by Mycobacterium tuberculosis strains resistant to isoniazid and rifampicin) and extensively drug-resistant (XDR)-TB ( i.e. TB caused by MDR-TB strains that are also resistant to at least one fluoroquinolone and one injectable second-line anti-TB drug) [5–8]. MDR/XDR-TB is seriously hampering TB control and elimination in Europe [9–11], as patients require long and expensive regimens with significant adverse effects, while cure rates remain low [7, 8, 12–14]. Clinicians can upload a case description and queries via the ERS/WHO TB Consilium website (www.tbconsilium.org), the process of which takes up to 20 minutes. The case is then assigned to global experts who provide feedback to the clinician’s questions in a limited timeframe, free of charge. At the time of writing, the TB Consilium has provided expert opinion on 51 cases (and two outbreaks from 11 countries), with an average response time of 36 h. The most frequently posed questions are related to the design and duration of the most appropriate regimens for difficult-to-treat patients [4]. In the absence of a sufficient number of medicines to which a strain is sensitive in vivo , life-saving treatment may rely on the use of new medicines (bedaquiline or delamanid) either under conditional or through compassionate use [15– …

Minimum package for cross-border TB control and care in the WHO European region: a Wolfheze consensus statement

The World Health Organization (WHO) European region estimates that more than 400,000 tuberculosis (TB) cases occur in Europe, a large proportion of them among migrants. A coordinated public health mechanism to guarantee TB prevention, diagnosis, treatment and care across borders is not in place. A consensus paper describing the minimum package of cross-border TB control and care was prepared by a task force following a literature review, and with input from the national TB control programme managers of the WHO European region and the Wolfheze 2011 conference. A literature review focused on the subject of TB in migrants was carried out, selecting documents published during the 11-yr period 2001–2011. Several issues were identified in cross-border TB control and care, varying from the limited access to early TB diagnosis, to the lack of continuity of care and information during migration, and the availability of, and access to, health services in the new country. The recommended minimum package addresses the current shortcomings and intends to improve the situation by covering several areas: political commitment (including the implementation of a legal framework for TB cross-border collaboration), financial mechanisms and adequate health service delivery (prevention, infection control, contact management, diagnosis and treatment, and psychosocial support).

Multidrug-resistant tuberculosis in children: evidence from global surveillance

Multidrug-resistant tuberculosis (MDR-TB) can affect persons of any age, but it remains unknown whether children are more or less likely than adults to have MDR-TB. Representative drug resistance surveillance data reported to the World Health Organization between 1994 and 2011 were analysed to test the association between MDR-TB and age group (children aged <15 years versus adults aged ≥15 years), using odds ratios derived by logistic regression with robust standard errors. Of 85 countries with data from nationwide surveys or surveillance systems, 35 reported at least one paediatric MDR-TB case. Aggregated data on age and drug susceptibility testing for 323 046 tuberculosis cases notified in these 35 countries were analysed. Odds ratios for MDR-TB in children compared to adults varied widely between countries. In Germany, Namibia, South Africa, the UK and the USA, MDR-TB was positively associated with age <15 years. In the remaining countries no association was established. Despite the limitations intrinsic to the use of surveillance data and to the challenges of diagnosing childhood tuberculosis, our analysis suggests that proportions of MDR-TB in children and adults are similar in many settings. Of particular concern is the association found between age <15 years and MDR-TB in southern African countries with high HIV prevalence. Surveillance data from 35 countries suggest that proportions of MDR-TB in children are not lower than those in adults http://ow.ly/kPgPH

Harmonisation of TB control in the WHO European region: the history of the Wolfheze Workshops

In 1990 a workshop was organised in the village of Wolfheze (the Netherlands), where experts discussed the critical interventions that would foster elimination of TB in Europe. This event has been followed by several more over the following two decades to become known as the “Wolfheze Workshops”. This article provides a brief overview of the history and the impact the Wolfheze Workshops have had on the commitment of European governments to standardise definitions, recording and reporting systems and, thus, permitted comparison of interventions and improving TB control across borders. The Wolfheze Workshops have been and still are an essential platform for this exchange of experiences, promoting common approaches.

Supporting TB clinicians managing difficult cases: the ERS/WHO consilium

Multidrug-resistant tuberculosis (MDR-TB), defined as active TB cases infected by Mycobacterium tuberculosis strains that are resistant to isoniazid and rifampicin (the two most important anti-TB drugs currently in use), and extensively drug resistant tuberculosis (XDR-TB), defined as active TB cases caused by infection with strains that are resistant to at least one fluoroquinolone and one injectable second-line anti-TB drug in addition to resistance to isoniazid and rifampicin, attract interest at different levels [1–5]. In recent years the alarming rates of MDR- or XDR-TB in Eastern Europe and some other parts of the world, have resulted in strong expressions of concern from national and international partners, health authorities, and professional societies. At the media level, the key words MDR-TB and XDR-TB attract spikes of citations and consistent interest, as a simple Google search can testify (fig. 1). Figure 1– Web search interest for “MDR-TB”, “XDR-TB”, “totally drug resistant” and “resistant tuberculosis” worldwide from 2004 to present (source: Google Trends). On the y-axis the number 100 represents the peak search volume. From the public health point of view, MDR- and XDR-TB is considered a serious threat for TB control and elimination. Therefore, the international community and national governments prioritise monitoring and evaluating prevalence rates and trends of drug resistant TB at both the global and the regional level [2, 3]. Recent evidence suggests that of the estimated 310,000 MDR-TB cases among notified TB patients with pulmonary TB in 2011, 60% occurred in India, China and the Russian Federation. XDR-TB is, at present, notified in 84 countries, although representative data on these difficult-to-treat cases are only available in 13 of them [2, 3]. The proportion of MDR-TB cases harbouring XDR-TB strains of M. tuberculosis was highest in Azerbaijan, Belarus, Estonia, Latvia, Lithuania and Tajikistan. …