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, 12-13 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