Improving diagnosisImproving diagnosis

TB laboratory strengthening TB laboratory strengthening

Role of laboratory services in TB control

Laboratory services perform crosscutting activities for the threeimplementation 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

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

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

Stop TB Strategy and laboratory

1. 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

2. Addressing TB/HIV and MDR-TB

3. Contributing to health system strengthening

4. Engaging all care providers

6. Empowering patients and communities

7. Enabling and promoting research

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

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: 100-200K

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: 500 - 1,500K

Central level (Level 3)Central level (Level 3)

Part of the central public health laboratory, research laboratory, or upgraded laboratory in the country’s principal tuberculosis institution

Activities:Activities: National reference laboratory for the TB program, Development of standardized manuals and guidelines Training External Quality Assurance Perform: smear microscopy, culture and DST

Generally 3 levels in a TB lab network

LEVEL 2 LEVEL 3

• 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: 100-200K

• 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

• 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

LEVEL 1

Internal and External Quality Assurance at all levels

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)

Quality Assurance Programme Components

Supervision

Rechecking/panel testing

Internal quality control

Strengthen the national capacity to perform

culture for diagnostic purposes

Epidemiological and programmatic Epidemiological and programmatic conditions have changedconditions 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

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

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)

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)

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 furtherevaluate applicability, sustainability of this technology

Fluorescent microscopy

Close collaboration with FIND and WHO on evaluation of the LED portable fluorescent microscope

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.

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)