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.

https://erj.ersjournals.com/content/erj/39/4/807.full.pdf

European Union Standards for Tuberculosis Care

Seven serological tests, two immunochromatographic tests, ICT Tuberculosis and RAPID TEST TB, and five enzyme-linked immunosorbent assays, TUBERCULOSIS IgA EIA, PATHOZYME-TB complex, PATHOZYME-MYCO IgG, PATHOZYME-MYCO IgA, and PATHOZYME-MYCO IgM, were evaluated simultaneously with 298 serum samples from three groups of individuals: 44 patients with active tuberculosis, 204 controls who had undergone the Mantoux test (89 Mantoux test-positive and 115 Mantoux test-negative controls), and 50 anonymous controls. The sensitivities of the tests with sera from patients with active tuberculosis were poor to modest, ranging from 16 to 57%. All the tests performed equally with sera from subgroups of those with active tuberculosis, those with pulmonary (33 patients) versus extrapulmonary (11 patients) disease, and those who were smear positive (24 patients) versus smear negative (12 patients) (P > 0.05). The specificities of the tests ranged from 80 to 97% with sera from the Mantoux test controls and 62 to 100% with sera from the anonymous controls. The TUBERCULOSIS IgA EIA had the highest sensitivity (57%) with sera from patients with active tuberculosis, with a high specificity of 93% with sera from the Mantoux test controls, but a very poor specificity of 62% with sera from the anonymous controls. Overall, ICT Tuberculosis followed by PATHOZYME-MYCO IgG had the best performance characteristics, with sensitivities of 41 and 55%, respectively, with sera from patients with active tuberculosis and specificities of 96 and 89%, respectively, with sera from the Mantoux test controls and 88 and 90%, respectively, with sera from the anonymous controls. By combining all the test results, a maximum sensitivity of 84% was obtained, with reciprocal drops in specificities to 55 and 42% for the Mantoux test controls and anonymous controls, respectively. The best combination was that of ICT Tuberculosis and PATHOZYME-MYCO IgG, with a sensitivity of 66% and a specificity of 86% for the Mantoux test controls and a sensitivity and specificity of 78% for the anonymous controls. While a negative result by any one of these tests would be useful in helping to exclude disease in a population with a low prevalence of tuberculosis, a positive result may aid in clinical decision making when applied to symptomatic patients being evaluated for active tuberculosis.

A Comparison of Seven Tests for Serological Diagnosis of Tuberculosis

In a population of Mycobacterium tuberculosis, random chromosomal mutation that results in genetic resistance to anti-tuberculosis (TB) drugs occurs at a relatively low frequency. Anti-TB drugs impose selection pressure so that mycobacterial mutants gradually outnumber susceptible bacilli and emerge as the dominant strains. Resistance to two or more anti-TB drugs represents cumulative results of sequential mutation. The fourth report on global anti-TB drug resistance provides the latest data on the extent of such problem in the world. The median prevalence of multi-drug-resistant TB (MDR-TB) in new TB cases was 1.6%, and in previously treated TB cases 11.7%. Of the half a million MDR-TB cases estimated to have emerged in 2006, 50% were in China and India. The optimal duration of any given combination of anti-TB drugs for treatment of MDR- and extensively drug-resistant TB (XDR-TB) has not been defined in controlled clinical trials. Standardized treatment may be feasible for MDR-TB patients not previously treated with second-line drugs, but a different strategy needs to be applied in the treatment of MDR-TB patients who have received second-line drugs before. Unfortunately, the reliability of drug susceptibility testing of most second-line anti-TB drugs is still questionable. Drug-resistant TB is not necessarily less virulent. Findings from modelling exercise warned that if MDR-TB case detection and treatment rates increase to the World Health Organization target of 70%, without simultaneously increasing MDR-TB cure rates, XDR-TB prevalence could increase exponentially. Prevention of development of drug resistance must be accorded the top priority in the era of MDR-/XDR-TB.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1440-1843.2010.01738.x

Drug-resistant tuberculosis: past, present, future.

One-third of the world population is estimated to have Mycobacterium tuberculosis infection. Accurate and timely identification of infected individuals is critical for treatment and control. The current diagnostic methods lack the desired sensitivity and specificity, require sophisticated equipment and skilled workforce or take weeks to yield results. Diagnosis of extrapulmonary TB, TB-HIV co-infection, childhood TB and sputum smear-negative pulmonary TB pose serious challenges. Interest in developing serodiagnostic methods is increasing because detection of antibody is rapid, simple and relatively inexpensive, and does not require a living cell for detection. Three types of tests, namely screening tests to overcome diagnostic delay, specific tests for diagnosis of extrapulmonary TB and other bacteriologically negative cases, and tests for vaccine-induced immunity need critical consideration. Several factors must be considered to develop serodiagnostic methods for TB. Antigen recognition by infected individuals is highly heterogeneous due to stage of disease, differences in HLA types, strain of the bacilli, health of the patient and bacillary load. With advances in molecular biological techniques, a number of novel antigens have been identified. Some of these antigens have proven valuable in detecting specific antibodies in some of the most challenging TB patients. The best example is a fusion protein containing several M. tuberculosis proteins (e.g. CFP-10, MTB8, MTB48, MTB81 and the 38-kDa protein) which showed encouraging results in detecting antibodies in sera of patients, including TB-HIV co-infection. This review presents progress made in the serodiagnosis of TB during the last decade.

Progress in serodiagnosis of Mycobacterium tuberculosis infection.

Immunologic diagnosis of tuberculosis: a review.

CADRE : Le Bureau de Lutte contre les Maladies Chroniques, Departement de la Sante, T'ai-wan. OBJECTIF : Evaluer le role de la resection pulmonaire dans le traitement des tuberculoses pulmonaires a germes resistant a la fois a l'isoniazide et a la rifampicine (TB-MR). SCHEMA : Cette etude retrospective de cohorte a passe en revue 27 patients TB-MR qui avaient subi une resection pulmonaire entre decembre 1990 et mars 1999. Les regimes de traitement individualises ont ete selectionnes lors de reunions hebdomadaires du personnel, apres revue de l'histoire du cas et des resultats de la sensibilite aux medicaments. On a pratique la chirurgie chez des patients selectionnes, essentiellement pour les raisons suivantes : 1) echec du traitement medical ou haute probabilite d'echec du traitement ou rechute paraissant probable apres traitement ; 2) maladie a predominance localisee ; 3) reserve cardio-pulmonaire adequate ; 4) reduction prealable de la charge mycobacterienne grâce a un regime de traitement comportant au moins deux produits efficaces. RESULTATS: La mortalite chirurgicale se limite a un deces peri-operatoire (4%). Des complications sont survenues chez trois patients (11%) et la negativation de l'expectoration ou la persistance de la negativite ont ete observees apres l'intervention chez 24 patients (92%). Le traitement est deja termine chez 23 patients et, au cours d'un suivi moyen de 42 ± 18 mois (extremes 15-80 mois), il n'y a eu qu'une seule rechute. Ce patient a ete stabilise apres une nouvelle cure. CONCLUSION : Chez les patients selectionnes, la resection pulmonaire peut ameliorer les resultats dans les tuberculoses pulmonaires a germes multiresistants.

Pulmonary resection in the treatment of patients with pulmonary multidrug-resistant tuberculosis in Taiwan.

CONTEXTE: La ville de Taipei, Taiwan. OBJECTIFS: Evaluer les pratiques de prescription des medicaments antituberculeux pour le traitement de la tuberculose (TB). METHODE: Audit medical des dossiers de traitement de tous les patients tuberculeux signales comme traites pour TB a Taiwan en 2003, pour determiner les prescriptions du traitement et les comparer aux dosages recommandes. RESULTATS: On a prescrit au total 24 regimes antituberculeux differents. Sur les 1700 patients, le poids corporel a ete enregistre chez 1096 (64,5%). Parmi les 506 patients auxquels on a prescrit une combinaison a dose fixes (FDC) de trois medicaments, le dosage a ete adequat chez 374 (73,9%), trop faible chez 100 (19,8%) et trop eleve chez 32 (6,3%). Parmi les 75 patients auxquels une FDC de deux medicaments a ete prescrite, le dosage a ete adequat chez 57 (76,0%), trop faible chez 15 (20,0%) et trop eleve chez trois (4,0%). Parmi les 481 patients auxquels on a prescrit la rifampicine, le dosage a ete adequat chez 302 (62,8%), trop faible chez 152 (31,6%) et trop eleve chez 27 (5,6%). Chez les 451 patients auxquels on a prescrit l'isoniazide, le dosage a ete adequat chez 396 patients (87,8%), trop faible chez 29 (6,4%) et trop eleve chez 26 (5,8%). CONCLUSION: Les pratiques de prescription des medicaments antituberculeux sont inferieures aux normes et doivent etre ameliorees ; ces observations ont des implications pour le renforcement du Programme National de la Tuberculose.

Inconsistent dosing of anti-tuberculosis drugs in Taipei, Taiwan.

Family factors affecting the outcome of tuberculosis treatment in Taiwan.

Initial drug resistance of Mycobacterium tuberculosis in Taiwan.

Morbidity and mortality trends of pulmonary tuberculosis in Taiwan.

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