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.

Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Migration, TB control and elimination: Whom to screen and treat.

Tuberculosis (TB) in migrants represents an important clinical and public health threat, particularly in low TB incidence countries. The current review is aimed to assess issues related to screening and treatment of migrants with latent TB infection or TB disease.

Implementation of isoniazid preventive therapy in children aged under 5 years exposed to tuberculosis in Benin.

SETTINGS: Two large tuberculosis (TB) centres under a well-functioning National TB Programme (NTP) in Benin, West Africa. OBJECTIVE: To assess the feasibility and results of integrating a programme of isoniazid preventive therapy (IPT) in children aged <5 years exposed to TB as part of the existing routine activities of the NTP. METHOD: All children aged <5 years living in the household of a patient with smear-positive pulmonary TB were examined by a doctor and received IPT if no evidence of TB was detected. The children were followed clinically by a nurse for 6 months. RESULTS: From January 2013 to June 2014, 496 children were examined and prescribed IPT among 499 notified contacts; 86% adhered to IPT for at least 6 months. There were six deaths and three cases of active TB among the children, all during the first 3 months of follow-up. CONCLUSIONS: In an African country with moderate TB incidence and a well-functioning NTP, the integration of IPT into the NTP for children aged <5 years exposed to TB in the family was feasible based on simple tools associated with the follow-up of index cases. The rate of adherence to IPT was high.

Current issues in the management of tuberculosis in Europe.

Tuberculosis is a rare disease in Europe, so that most medical doctors never see a case and, although they know that the disease exists, they usually do not include it among the differential diagnosis of many respiratory or general disorders. Why is it, therefore, still important to speak about TB? This paper analysis some reasons: 1) TB is rare but has not disappeared. In Europe, some 400,000 cases are registered each year, with a slight decreasing tendency over the last few years but great disparities between countries and regions; 2) TB is more frequent in some risk groups, particularly among patients born in a country with a high incidence of disease or in persons exposed to the contact with TB, like close relatives of infectious patients. In EU/EEA, the majority of TB cases are observed among foreign-born persons; 3) if infected, some persons have a higher risk to develop TB. Small children and persons with viral or drug-induced immunosuppression (for instance anti-TNF) must be screened and protected if infected; 4) cases of TB among migrants generally occur after the entry in the country, from reactivation of latent TB acquired before. The border screening does not offer a garantee that the disease has been detected. Due attention to incurring symptoms and easy access to care must be maintained during the whole stay in the country for all foreign-born persons; 5) one of the major threats for the future is the progressive increase in the number of cases resistant to first-line drugs (Multidrug-resistant TB or MDR-TB) in several regions of the world, particularly in Eastern Europe; 6) due to decreasing knowledge and experience with the diagnosis and management of TB, many cases are diagnosed at a late stage. Medical doctors are encouraged to share their questions with experts and refer to existing Guidelines.

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.

TB and MDR/XDR-TB in European Union and European Economic Area countries: managed or mismanaged?

In spite of the growing awareness of emerging drug-resistant Mycobacterium tuberculosis, the extent of inappropriate tuberculosis (TB) case management may be underestimated, even in Europe. We evaluated TB case management in the European Union/European Economic Area countries, with special focus on multidrug-resistant (MDR) and extensively drug-resistant (XDR)-TB, using a purposely developed, standardised survey tool. National reference centres in five countries representing different geographical, socioeconomic and epidemiological patterns of TB in Europe were surveyed. 40 consecutive, original clinical TB case records (30 MDR/XDR-TB cases) were reviewed in each of the five countries. The findings were recorded and, through the survey tool, compared with previously agreed and identified international standards. Deviations from international standards of TB care were observed in the following areas: surveillance (no information available on patient outcomes); infection control (lack of respiratory isolation rooms/procedures and negative-pressure ventilation rooms); clinical management of TB, MDR-TB and HIV co-infection (inadequate bacteriological diagnosis, regimen selection and treatment duration); laboratory support; and diagnostic/treatment algorithms. Gaps between present international standards of care and the management of MDR/XDR-TB patients were identified. Training, increased awareness, promotion of standards and allocation of appropriate resources are necessary to ensure appropriate care and management as well as to prevent further emergence of drug resistance.

[Multidrug resistant tuberculosis -- its extent, hazard and possible solutions]. / La tuberculose multirésistante : extension, menace et solutions.

Multidrug resistant tuberculosis (MDR-TB) has spread to most regions of the world and represents a serious threat to the success of the struggle against tuberculosis. It can result from errors in management that favour the selection of drug resistant organisms and can in the worst case lead to the development of extremely resistant organisms (XDR-TB) which are practically untreatable. The current strategies for combating this problem are, on the one hand, the rapid identification and tracking of resistant strains using molecular genetic techniques and, on the other hand, careful drug management in individual cases using second line agents. At the level of public health, the most important measures are those which prevent or correct the processes which can drive the creation of new cases of MDR-TB. This can have implications for the modification and development of national strategies. The future of the fight against tuberculosis depends in part on the success of strategies to combat the development and spread of MDR-TB.

[New recommendations for contact tracing in tuberculosis]. / Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose*1.

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.

[New recommendations for contact tracing in tuberculosis. German Central Committee against Tuberculosis]. / Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose. Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose.

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.

Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to compare the accuracy of the QuantiFERON-TB® Gold In-Tube (QFT-G-IT) and the T-SPOT®.TB assays with the tuberculin skin test (TST) for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). The Medline, Embase and Cochrane databases were explored for relevant articles in November 2009. Specificities, and negative (NPV) and positive (PPV) predictive values of interferon-γ release assays (IGRAs) and the TST, and the exposure gradient influences on test results among bacille Calmette-Guérin (BCG) vaccinees were evaluated. Specificity of IGRAs varied 98-100%. In immunocompetent adults, NPV for progression to tuberculosis within 2 yrs were 97.8% for T-SPOT®.TB and 99.8% for QFT-G-IT. When test performance of an immunodiagnostic test was not restricted to prior positivity of another test, progression rates to tuberculosis among IGRA-positive individuals followed for 19-24 months varied 8-15%, exceeding those reported for the TST (2-3%). In multivariate analyses, the odd ratios for TST positivity following BCG vaccination varied 3-25, whereas IGRA results remained uninfluenced and IGRA positivity was clearly associated with exposure to contagious tuberculosis cases. IGRAs may have a relative advantage over the TST in detecting LTBI and allow the exclusion of M. tuberculosis infection with higher reliability.