Overview of current case and treatment outcome definitions Malgosia Grzemska TB Operations and Coordination Stop TB Department Consultation Impact of WHO-endorsed molecular diagnostics on TB and MDR-TB case- and treatment outcomes definitions Geneva, May 2011

Outline History of case and treatment outcome definitions Current case definitions and treatment outcome definitions Commentary on current definitions Next steps

History of case and treatment outcome definitions First introduced by Karel Styblo in Africa in pilot projects of short-course chemotherapy Confirmed by WHO in 1994 in the "Framework for effective tuberculosis control" and recommended for use in DOTS programmes worldwide 1998 – Europe started revision to facilitate use of culture in diagnosis and monitoring Each edition of WHO Treatment guidelines – slight revision of definitions to "accommodate" new developments in TB control

Current case definitions (WHO) Definite TB case –A patient with M. tuberculosis complex identified from a clinical specimen, either by culture or by a newer method such as molecular line probe assay. –Pulmonary case with 1 or more initial sputum smear examinations positive for acid-fast bacilli (AFB) - in countries lacking lab. capacity to routinely identify M. tuberculosis complex and with functional EQA system. TB case –A definite case of TB (as above); but also –Patient in whom health worker (clinician or other practitioner) has diagnosed TB and decided to treat the patient with the whole course of anti-TB treatment Treatment of tuberculosis: guidelines -- 4th edition, Geneva, WHO, 2009

Current case definitions (WHO) - 2 Classification according to –Anatomical site of disease (P and EP) –Bacteriological results (including drug resistance) Culture positive or Culture negative (both P and EP) Smear positive, smear negative, smear not done (only P) –History of previous treatment New Previously treated: relapse, failure, default Transfer in Other –HIV status

Commentary on case definitions Definite case –Smear microscopy not considered confirmatory test (though used in resource poor settings) –HIV positive patients – often smear negative –Culture and newer tests added to "accommodate" availability of tools other than smear microscopy Previously treated –Difference between relapses (new episode - incident) and other retreatment's (same episode requiring change of regimen - prevalent) –Relapse true relapse or re-infection

Commentary on case definitions (2) No one knows what to do with "transfer –in" – not evaluated Other – no standard interpretation No information on groups with high risk of TB – which may be required for decision making on appropriate diagnostic and prevention intervention Disaggregation according to social or other determinants does not exist No information on co-morbidities (other than HIV)

Current treatment outcome definitions (WHO) Cure. –A patient whose sputum smear (or culture) was positive at the beginning of the treatment but who was smear- (or culture-) negative in the last month of treatment and on at least one previous occasion. Completed. –A patient who completed treatment but who does not have a negative sputum smear (or culture) result in the last month of treatment and on at least one previous occasion. Treatment success –is the sum of cure and completed. Treatment of tuberculosis: guidelines -- 4th edition, Geneva, WHO, 2009

Current treatment outcome definitions (WHO) Failure. –A patient whose sputum smear (or culture) is positive at 5 months or later during treatment. –Also included in this definition are patients found to harbour a multidrug-resistant (MDR) strain at any point of time during the treatment, whether they are smear-negative or -positive Default. –A patient whose treatment was interrupted for 2 consecutive months or more. Died. –A patient who dies for any reason during the course of treatment Transfer out. –A patient who has been transferred to another recording and reporting unit and whose treatment outcome is unknown.

Commentary on treatment outcome definitions Originally only smear positive cases were evaluated Addition of "culture"; recommendations to evaluate smear-negative and EP cases Cure – only for smear positive (and culture positive); Failure – only for smear positive (+ culture) and too late into the treatment course If Xpert is the initial diagnostic test – less cases would be classified cured (treatment monitoring with smear and/or culture) Transfer – out – excuse for not following up (often default, sometimes death, - but perceived a "better" outcome Individual NTPs or regions (EU) revised case-or outcome definitions Non-evaluated – added for the purpose of global reporting

Conclusions – next steps Transition from DOTS to Stop TB Strategy did not result in changes in the definitions Programmes add their own modifications, which may create confusion and would hamper global reporting Introduction of molecular tools in diagnosis of TB requires modifications of case definitions and treatment outcome definitions, else many cases may be not evaluated Preparation for the introduction of new (shorter) treatment regimens in the future