COMPREHENSIVE APPROACH TO TB DIAGNOSIS

Catherine Mundy, PhD, FIBMSManagement Sciences for Health

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Today’s presentation

1. The global burden of tuberculosis2. The role of the laboratory in TB diagnosis3. TB microscopy4. TB culture5. New diagnostic technologies6. The TBCAP toolbox7. What it takes to roll out the toolbox

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What causes Tuberculosis (TB)?

• TB – ancient disease demonstrated in the bones of some Egyptian mummies

• A highly contagious infection caused by Mycobacterium tuberculosis

• The causative organism discovered by Robert Koch in 1882

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How is TB spread?

• Inhalation of tubercle bacilli in droplet nuclei created when infected person coughs, sneezes, or speaks

• Nuclei <5µ - reach alveoli of lung – primary infection established

• Only 5 – 10 % of individuals progress from infection to disease

• For HIV infected individuals, the lifetime risk of disease is up to 50%

• 80% of all TB disease manifests as a pulmonary infection

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How efficient was case detection in 2008?

• 1993 – TB declared “a global emergency” by WHO• 2008 – Estimated incidence – 9.4 million cases –

about 95% drug susceptible• Cases detected – 5.7 million• Over 3 million cases undetected• In addition, many cases often detected late

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How is TB diagnosed?

• Clinical symptoms – chronic cough, hemoptysis, weight loss, night sweats.

• Skin test• X-ray• Direct demonstration of acid fast bacilli in sputum by

microscopy• Growth of TB bacilli in culture

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How are laboratory services in developing countries organized to diagnose TB?

• Laboratory network to serve the national TB control program: a national referral laboratory providing TB culture service

and overseeing the microscopy labs microscopy centres sputum collection points

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Challenges with microscopy• Technical – poor sensitivity (30% – 40 %)• Operational:

– Patient access and time to diagnosis– Workload– Human resources– Quality and reliability of results– Infrastructure– Supplies and equipment– Information management

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TB culture

• Culture = the gold standard• Greater need for

infrastructure, qualified staff, equipment & safety measures

• Only routinely used for treatment failures and relapse cases

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TB culture and sensitivity testing

Additional challenges• Time consuming – incubation period up to 8

weeks• Additional time for sensitivity testing• Turn around time to diagnose drug resistant

TB = 4 – 6 months (from the time of specimen collection)

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New diagnostic technologies for diagnosing TB

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Technologies approved by WHO for diagnosing TB (See handout)

• Automated liquid culture and sensitivity testing (2007)• Rapid strip speciation (2007)• Line probe assays (2008)• 2nd line drug susceptibility testing (2008)• LED fluorescence microscopy (2009)• Selected non-commercial culture and DST methods

(2009 – 2010)• Cepheid Gene Xpert (2010)• Serodiagnostics (2010)• Molecular testing for 2nd line DST (2010)

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Providing technologies and diagnostics is not enough

Need:• Policy reform and adoption• Laboratory quality management• Procurement and supply chain management• Standard operating procedures• Biosafety standards• Technology transfer and training• Information management systems

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TB CAP Toolboxto strengthen laboratory services

1. Directly supports Stop TB Strategy objectives: • ‘To achieve universal access to high-quality diagnosis

and patient-centered treatment’• ‘To pursue high quality DOTS expansion and

enhancement of case detection through quality assured bacteriology’.

2. Enables countries to: • Strengthen their TB laboratory network• Adopt national standards in accordance with

international guidelines.

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TBCAP Laboratory Tools

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TB CAP Laboratory Toolsin progress

• Manual on biosafety for laboratories

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Road Map for Laboratory Strengthening A structured framework for scaling-up

TB laboratory services Based on

WHO-recommended norms and standards documented country best-practicesgrowing lessons learnt from field

experiences by many partners involved in the Global Laboratory Initiative (GLI).

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Standard Operating Procedures

Section I. Guidance for countries to develop (or modify) and implement country-specific Standard Operating Procedures

Section II. Generic TB laboratory Standard Operating Procedures : Safety Use and maintenance of equipment Preparation of reagents Test procedures

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Logistics, Equipment and Supply Management

Part A: Guidelines for effective management of TB laboratory commodities Procurement mechanisms, logistics, quantification

and management systems. Part B: Technical specifications for equipment,

consumables and reagents Additional requirements for specialized

equipment (e.g. Fluorescence microscopes, Microbiological safety cabinets)

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External Quality Assurance

Training package for AFB microscopy EQA for Light and Fluorescence Microscopy Training package for EQA

Panel TestsBlinded recheckingAnalysis and reporting of results

Supervision

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Culture and DST TrainingPackage

Covers all aspects of culture and DST 12 modules

Trainers’ manual Participants’ manual

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Laboratory ManagementInformation Systems

Tools for reporting and monitoring of AFB smears, culture/DST and supplies

Promotes correct analysis, re-checking EQA parameters and culture internal quality control

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Dissemination andimplementation of the

laboratory tools

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Timetable

• December 2009 – Official Launch in Cancun• March 2010 – TOT workshop – The Hague• April 2010 – Regional workshop, Nairobi for

TBCAP supported countries in Africa• July 2010 – Regional Workshop, Jakarta for

TBCAP supported countries in Asia• ONGOING: Implementation of country action

plans by teams attending the workshops

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Regional Workshops in Africa and Asia

Participating Country teams: Kenya Uganda Ethiopia Nigeria Ghana Namibia

Afghanistan Bangladesh Cambodia Indonesia Pakistan Vietnam

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Objectives of the workshops

• To orientate country teams and develop their skills for effective decision making, planning and implementation of the TBCAP lab Tools Package in their respective countries

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Workshop organization and content

• Team approach – ‘interactive’• Baseline situation analysis• Identification and prioritization of

current TB lab challenges• Tool orientation• Action planning

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Challenges with in-countryimplementation of lab tools

• Numerous lab challenges, particularly in Africa

• Political will, motivation & commitment

• Relationship between NTP and labs• Leadership capacity• Human and financial resources

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How could countries adopt,adapt and implement the toolbox?

• Questions and open discussion

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