1. Improving diagnosis
TB laboratory strengthening

2. Role of laboratory services in TB control
Laboratory services perform crosscutting activities for the three
implementation working groups (DEWG, DOTS-Plus, TB/HIV)
Diagnosis of all TB cases (e.g., SM(+), SM (-), extrapulmonary, HIV co-infected, drug resistant)
Monitoring patient's response to treatment
Participation in TB surveillance; notification/prevalence of TB; DRS
Assistance in selecting effective treatment regimens: MDR-TB
Human resource development including training
Operational research

3. Consequences of poor lab performance
Unreliable diagnosis results: over/under diagnosing of TB patients
Individual level:
Undiagnosed TB cases: (disease transmission, death)
Mismanagement of patients (MDR-TB)
Over diagnosed patients: (bear the effects of long &
unnecessary treatment, disease stigma)
National/Global level:
Low case detection,
Continuous transmission and
Ultimately poorly performing TB control programme

4. Situation Analysis (22 HBCs)
18 countries have National Reference Laboratory (NRL) to oversee the organization and performance of the network; however some NRLs are weak and not fully functional
18 HBCs claim to have EQA scheme for smear microscopy; however, majority report it's limited coverage and suboptimal quality
14 countries perform culture at the national/regional level according to nationally-defined specifications, which are not always consistent with international recommendations. In addition, the quality of culture is unknown
Major impediments to perform diagnostic tests (especially culture and DST):
inadequate equipment and infrastructure
limited technical knowledge
Insufficient human and financial resources

5. Stop TB Strategy and laboratory
Pursuing quality DOTS expansion and enhancement
Political commitment
Case detection through quality-assured bacteriology
Standardised treatment, with supervision and patient support
Effective drug supply system
Monitoring system and impact evaluation
Addressing TB/HIV and MDR-TB
Contributing to health system strengthening
Engaging all care providers
Empowering patients and communities
Enabling and promoting research 14

6. Improving diagnosis- planning framework
Activities:
Organization of TB laboratory network (prevalence and population distribution)
Provide laboratory equipment supplies and reagents
Implement quality assurance programme for smear microscopy, culture and DST
Promote human resource development
Meetings and Workshops
Support technical assistance
Promote operational research
Expedite the diagnosis of smear negative & extrapulmonary TB in high HIV prevalence areas

7. Peripheral level (Level 1)
Located at primary health centers or district hospitals
Activities:
Sputum collection
Smear microscopy
Recording and reporting
Slide collection for EQA
Manpower: ≤ 1(2) worker(s); >2-3 / <20 smears per day
Population coverage: K

8. Intermediate level (Level-2)
Located at regional health institutions including hospitals
Activities:
Services to clinics: FM/ZN smear microscopy
Culture / ID of MTB; referral services
Support activities: (supply of reagents/materials, training; EQA for smear microscopy including supervision)
Manpower: 2-3 workers (only for TB work)
Population Coverage: ,500K

9. Central level (Level 3)
Part of the central public health laboratory, research laboratory, or upgraded laboratory in the country’s principal tuberculosis institution
Activities:
National reference laboratory for the TB program,
Development of standardized manuals and guidelines
Training
External Quality Assurance
Perform: smear microscopy, culture and DST

10. Generally 3 levels in a TB lab network
All functions of level 1 and 2
Identification of mycobacteria
other than MTB
DST of M. Tuberculosis
laboratory equipment services
and maintenance
Laboratory manuals and
guidelines for all lab services
Primary link with NTP
Supervision of intermediate QA
of culture and microscopy
Training of intermediate
organization of DRS
Operational and applied research
All functions of level 1
fluorescence microscopy (optional)
Digestion and decontamination
of specimens
Culture and identification of MTB
Training of staff
Support and supervision of
peripheral staff for microscopy
Preparation and distribution
of reagents
QA and panel testing of
microscopy
Manpower: 2-3 only for TB
Coverage: 500K-1.500K
Receipt of specimens
Preparation and staining
of smears
ZN microscopy /recording
Reporting of results
Maintenance of lab register
Management of reagents
and supplies
Internal QC
Participation in EQA system
Manpower: 1-2 staff
Coverage: K
Internal and External Quality Assurance at all levels

11. External Quality Assessment
Early warning-system for problems
Measure of laboratory quality
Valuable benchmarking tool (standardization and traceability)
Indicator of where to direct improvement efforts
Monitor of changes in technology and testing practices (evaluation component)

12. Quality Assurance Programme Components
Supervision
Rechecking/panel testing
Internal quality control

13. Strengthen the national capacity to perform
culture for diagnostic purposes

14. Epidemiological and programmatic conditions have changed
The number of repeatedly sputum negative TB cases is increasing,
mainly due to the HIV epidemic
Many countries are implementing DRS and monitoring MDR trends
Second line drugs are available and a growing number of countries
implement DOTS-Plus strategy
Culture is increasingly used even in resource limited countries

15. Estimated cost of culture (LJ method) & DST (proportion method) per laboratory
Capital investment per laboratory: 200,000$US
Consumables, media and pure substances for 1000 cultures and DST: 22,000$US
Training: national & international: 20,000$US
EQA for culture and DST: 5,000$US/ year
Staff salaries

16. Proposed approach to strengthen capacity to perform culture
Develop/strengthen the capacity to perform culture at the intermediate level as an essential component of DOTS expansion
Initially, 1 culture facility should be established per ~ 3 to 5 million population
Introducing culture in step wise approach to cover all eligible population by 2015 (number of facilities will depend on the national policy)

17. Smear microscopy optimizations
Outcomes of expert consultation meeting (1-2 September 2005)
The meeting was organized to discuss the outcomes of the systematic
literature review to determine the strength of existing data, identify
knowledge gaps, and define a research agenda regarding the following
issues:
Fluorescence microscopy (45 studies)
Sputum processing methods (83 studies)
Number of sputum smears per TB suspect (41 studies)

18. Fluorescent microscopy (FM)
Findings:
Improve the sensitivity of sputum microscopy by 10%
Shorten time of diagnosis
Reduce laboratory workload; FM recommended to be used in high volume settings >100 smears
Recommendations:
Countries wishing to implement FM at the peripheral level, in lower volume settings, should do so within the context of operational research
FM may be considered at all levels in high HIV prevalence countries
Collaboration with TDR, FIND on operation research to further
evaluate applicability, sustainability of this technology

19. Fluorescent microscopy
Close collaboration with FIND and WHO on evaluation
of the LED portable fluorescent microscope

20. Sputum processing methods
Findings:
Use of different chemicals and methodology
Moderate sensitivity improvement
Serious concerns regarding the use of centrifuge and bio-safety issues
Recommendations:
Concentration methods not recommended
Sedimentation may be promising and less problematic to implement; however, multi-centre studies are required to investigate the performance and feasibility with standardised method
Collaboration with TDR and FIND on design and implementation of
operational research to evaluate sedimentation methods.

21. Number of sputum smears per TB suspect
Findings:
The results indicated limited incremental yield of the 3rd sputum examination (2-5%)
However, there was some bias in studies design and difference in case definition
Points to be considered:
Dilemma on improving sensitivity (more false positive) or specificity
Workload issues (more time allocation for examination of slide => improved output)
Recommendation:
The questions should be studied in the context of case definition (this topic will be
presented and discussed during the upcoming STAG meeting)