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1. Thank you for viewing this presentation. • We would like to remind you that this material is the property of the author.It is provided to you by the ERS for your personal use only, as submitted by the author. • 2011 by the author

2. Guidance for implementation of TB care in the EU: the ESTC G. B. Migliori, G. Sotgiu WHO Collaborating Centre for TB and Lung Disease, Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy A. Sandgren, E. Huitric, D. Manissero ECDC (European Centre for Disease prevention and Control), Stockolm, Sweden

6. Disclaimer • The content of this presentation has been prepared on the basis of the evidence collected under ECDC supported survey on management of TB-/MDR-TB cases in the EU. • The conclusions of this presentation are the sole responsibility of the author (representing the ERS Task Force) and do not represent the ECDC position on the matter of Standards for Diagnosis and Treatment. • ECDC has responsibility on the Public Health Standards only

7. Outline • The key areas behind the ESTC • The pre-final EU Standards • The supporting enablers

8. Key Areas (1) • a) Surveillance. - Information on the final outcomes of the patients discharged should be available in the treating clinical centre as this represents a key managerial tool.

9. Key areas (2) • b) Infection control (a) - Sufficient respiratory isolation rooms for all new patients admitted (at least till the exact resistance pattern is identified and/or the patient is rendered non-infectious) and adequate isolation procedures needs to be available in all European countries. No evidence of secondary cases among health staff (1 case in one country in 10 yrs). - New European Standards need to look for the evidence and recommend this procedure if it is really justified.

10. Key areas (2) • b) Infection control (b) - Adequate administrative and personal protection measures (masks for patients or respirators for staff) . - Adequate health education practices for patients (e.g. cough etiquette) + regular training of health staff are necessary . - Respirator fit testing needs to be urgently implemented, for all health workers wearing respirators, as evidence exists that inadequate respirator wearing renders individual respiratory protection useless.

12. Key areas (3) • c) Clinical management of TB and MDR-TB - needs to be strengthened so that complete information on previous treatment(s), adequate contact tracing procedures, adequate bacteriological diagnosis, prescription of at least 4 active drugs, correct drug choice, adequate dose prescription, sufficient treatment duration and adequate management of AE of treatment are urgently implemented in the EU • d) Clinical management of HIV - should also be strengthened, as part of the development of the TB/HIV collaborative activities in Europe. This is particularly relevant in the following areas: HIV-testing and counselling of TB cases; prescription of ARVs and management of combined TB/HIV treatment.

13. Clinical management

14. Key areas (4) • e) Laboratory support - including optimal laboratory practices and quality assurance procedures, particularly for second-line drugsremains a key priority in Europe. • f) Diagnostic and treatment algorithms - need to be promoted in Europe to reduce as much as possible the existing differences. New tools (NAAT, IGRAS, rapid MDR-TB tests) should be promoted according to clear evidence-based guidelines.

15. Laboratory support

16. Diagnostic and treatment algorythms

17. International technical assistance

18. Standards for Diagnosis: focus on rapid methods

19. Standard 1 (Replaced ISTC 1) All persons presenting with signs, symptoms, history or risk factors compatible with tuberculosis should be evaluated for pulmonary and / or extrapulmonary tuberculosis.

20. History • Risk factors • As chronich cough not necessarily is the leading symptom

21. Standard 2 (Replaced ISTC 2) All patients (adults, adolescents, and children who are capable of producing sputum) suspected of having pulmonary tuberculosis should have at least two sputum specimens submitted for microscopic examination, culture and drug susceptibility testing (DST) in a quality-assured laboratory. When possible, at least one early morning specimen should be obtained. In countries, settings or populations in which MDR-TB is suspected in a patient, rapid testing for the identification of rifampicin-resistance and when possible isoniazid-resistance, using validated tools in a quality-assured laboratory, should be done.

22. Culture + DST • Rapid test for R and H-resistance • GeneXpert and Line Probe Assays • Contacts and previoulsy treated cases!!! • Quality assured laboratory • Specialised MDR-TB management

23. Gene Xpert

24. Standard 3 (Replaced ISTC 3) For all patients (adults, adolescents, and children) suspected of having extrapulmonary tuberculosis, appropriate specimens from the suspected sites of involvement should be obtained for microscopy, culture, DST and histopathological examination in a quality-assured laboratory. In countries, settings or populations, in which MDR-TB is suspected in a patient, rapid testing for the identification of rifampicin- and isoniazid-resistance in a quality-assured laboratory could be done.

25. EP TB: same laboratory approach • Aggressive trial to get a specimen suitable for bacteriology • Surgeons: not in formaline only!

26. Standard 4 (Replaced ISTC 4) All persons with chest radiographic findings suggestive of pulmonarytuberculosis should have sputum specimens submitted for microscopic examination, culture and DST in a quality-assured laboratory. In countries, settings or populations, in which MDR-TB is suspected in a patient, rapid testing for the identification of rifampicin-resistance and when possible isoniazid-resistance in a quality-assured laboratory should be done.

27. When CXR is the entry point… • …bacteriological examinations should be done (see Standard 2)

28. Standard 5 (ISTC 5 valid, EU adapted integration needed) The diagnosis of culture-negative pulmonary tuberculosis should be based on the following criteria: all bacteriological tests are negative (including direct sputum smear examinations, cultures and rapid molecular testing); chest radiographic findings compatible with tuberculosis; and lack of response to a trial of broad spectrum antimicrobial agents. (Note: Because the fluoroquinolones are active against M. tuberculosis complex and, thus, may cause transient improvement in persons with tuberculosis, they should be avoided.) In persons who are seriously ill or have known or suspected HIV infection or have any immune-compromising conditions, the diagnostic evaluation should be expedited and if clinical evidence strongly suggests tuberculosis, a course of anti-tuberculosis treatment should be initiated.

29. Culture negative cases: • Negative to: direct sputum smear examinations, cultures and rapid molecular testing • Using all diagnostic tools to collect the specimens • New diagnostics: within evidence based guidelines

30. Standard 6 (ISTC 6 valid until specific EU paediatric standards are available, EU adapted integration needed) In all children, suspected of having intrathoracic (i.e., pulmonary, pleural, and mediastinal or hilar lymph node) tuberculosis, bacteriological confirmation should be sought through examination of appropriate biological samples (by expectoration or induced sputum, bronchial secretions, pleural fluid or gastric washings) for smear microscopy culture and DST in a quality-assured laboratory. In the event of negative bacteriological results, a diagnosis of tuberculosis should be based on the presence of abnormalities consistent with tuberculosis on chest radiography, a history of exposure to an infectious case, evidence of tuberculosis infection (positive tuberculin skin test-TST and/or interferon-gamma release assay- IGRA), and clinical findings suggestive of tuberculosis. For children suspected of having extrapulmonary tuberculosis, appropriate specimens from the suspected sites of involvement should be obtained for microscopy and for culture and histopathological examination.

31. Waiting for new paediatric ESTC, previous ISTC valid • Same laboratory diagnostic approach than for adults (as per Standard 2-5) • Try to obtain the sample!

32. Standards for Treatment: attention to retreatments!

33. Standard 7 (ISTC 7 maintained) Any practitioner treating a patient for tuberculosis is assuming an important public health responsibility to prevent ongoing transmission of the infection and the development of drug resistance. To fulfill this responsibility the practitioner must not only prescribe an appropriate regimen, but also utilize local public and/or community health services, agencies and resources when necessary, to perform contact investigation, to assess the adherence of the patient and to address poor adherence when it occurs.

34. Public health “jacket” of the pratictioner • Role of civil society and community emphasized

35. Standard 8 (ISTC 8 valid, EU adapted integration needed) All patients (including those with HIV-infection) who have not been previously treated and without any risk factors for drug-resistance should receive an internationally accepted first-line treatment regimen using drugs of known bioavailability. The initial phase should consist of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol. The continuation phase should consist of isoniazid and rifampicin given for four months (2HRZE/4HR). The doses of antituberculosis drugs used should conform to international recommendations. Fixed dose combinations of two (isoniazid and rifampicin), three (isoniazid, rifampicin, and pyrazinamide) and four (isoniazid, rifampicin, pyrazinamide, and ethambutol) drugs are highly recommended.

36. Retreatment cases should be managed according to the individual risk to be MDR-TB until MDR is excluded

37. Standard 9 (ISTC 9 maintained) To assess and foster adherence, a patient-centered approach to administration of drug treatment, based on the patient’s needs and mutual respect between the patient and the provider, should be developed for all patients. Supervision and support should be individualized and should draw on the full range of recommended interventions and available support services, including patient counseling and education. A central element of the patient-centered strategy is the use of measures to assess and promote adherence to the treatment regimen and to address poor adherence when it occurs. These measures should be tailored to the individual patient’s circumstances, based on a detailed anamnesis of the patient’s clinical and social history, and be mutually acceptable to the patient and the provider. Such measures may include direct observation of medication ingestion (directly observed treatment or DOT) and identification and training of a treatment supporter (for tuberculosis and, if appropriate, for HIV-infection) who is acceptable and accountable to the patient and to the health system. Appropriate incentives and enablers, including financial, social and psycho-social supports, may also serve to enhance treatment adherence

38. Adherence • Patient-centred approach • DOT and treatment supporter

39. Standard 10 (ISTC 10 valid, EU adapted integration needed) Response to therapy in patients with pulmonary tuberculosis should be monitored by follow-up smear microscopy and culture at the time of completion of the initial phase of treatment (two months for drug-susceptible TB). If the sputum smear and culture are positive at completion of the initial phase, sputum smears should be examined again at 3 months and, if positive, drug susceptibility testing should be performed. In patients with extrapulmonary tuberculosis and in children unable to produce sputum, the response to treatment is assessed clinically.

40. Treatment monitoring: • Monthly SS and culture

41. Standard 11(Replaced ISTC 11, see also ESTC 1, 2 and 3) An assessment of the likelihood of drug resistance, based on history of prior treatment, exposure to a possible source case having drug-resistant organisms, and the community prevalence of drug resistance, should be obtained for all patients. Rapid testing, including rapid rifampicin resistance or rifampicin- and/or isoniazid-resistance testing should be done for all patients suspected of resistance as defined in standard 2 and 8. Furthermore, patient counseling and education should begin immediately for all TB patients, in order to minimize the potential for transmission. Infection control measures appropriate to the setting should be applied as recommended in ESTC public health standard 20.

42. Rapid testing once more! • Immediate counselling and education for infection control purposes • Rapid testing does not rule out the need for DST

43. Standard 12 (ISTC 12 valid, EU adapted integration needed) Patients with, or highly likely to have, tuberculosis caused by drug-resistant (especially MDR/XDR) organisms should be treated with specialized regimens containing second-line anti-tuberculosis drugs. The regimen chosen may be standardized or based on suspected or confirmed drug susceptibility patterns. At least four drugs to which the organisms are known, or presumed, to be susceptible to, including an injectable agent, should be used. Treatment should be given for at least 20 months, the intensive phase of treatment recommended to be 8 months beyond culture conversion (instead of 6 months as in previous recommendations; see below the EU Adaptations for further detail). As the treatment of MDR/XDR-TB is the last chance for these patients to be cured and survive and, often, as previous defaulters belong to the socio-vulnerable groups, a full range of patient-centred measures, including counselling, education of patients and family members, observation of treatment, identification of patient-entrusted treatment supporter, psycho-social support and other incentives and enablers, are required to ensure adherence in order to avoid development of XDR-TB.

44. Specialized centres • 4 active drugs, 20 months total, intensive phase 8 moths beyond culture conversion • Aggressive management of AE • “Cosillium”

45. Standard 13 (ISTC 13 valid, EU adapted integration needed) A written record of all medications given, bacteriologic response, and adverse reactions should be maintained for all patients.

46. Standards for addressing HIV Infection and Co-morbid Conditions:- universal access to diagnosis & treatment - remind other conditions!!!- focus on LTBI

47. Standard 14 (ISTC 14 maintained) HIV-testing and counseling should be recommended to all patients with, or suspected of having, tuberculosis. Testing is of special importance as part of the routine management of all patients in areas with a high prevalence of HIV-infection in the general population, in patients with symptoms and/or signs of HIV-related conditions. Because of the close relationship of tuberculosis and HIV-infection, integrated approaches to prevention and treatment of both infections are recommended.

48. Setting of choice cancelled • Integrated TB/HIV management approaches to all cases

49. Standard 15 (ISTC 15 valid, EU adapted integration needed) All patients with tuberculosis and HIV-infection should be evaluated to determine if antiretroviral therapy is indicated during the course of treatment for tuberculosis, according to the severity of their immunodeficiency. Appropriate arrangements for access to antiretroviral drugs should be made for patients who meet indications for treatment. However, initiation of treatment for tuberculosis should not be delayed.

50. General prophylactic treatment against other infections not relevant in the EU