1. COMPREHENSIVE APPROACH TO TB DIAGNOSIS
Catherine Mundy, PhD, FIBMS
Management Sciences for Health

2. Today’s presentation The global burden of tuberculosis
The role of the laboratory in TB diagnosis
TB microscopy
TB culture
New diagnostic technologies
The TBCAP toolbox
What it takes to roll out the toolbox

3. 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

4. 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

8. 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

9. 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

10. 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

12. 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

13. TB culture Culture = the gold standard
Greater need for infrastructure, qualified staff, equipment & safety measures
Only routinely used for treatment failures and relapse cases

14. 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)

15. New diagnostic technologies for diagnosing TB

16. 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)

17. 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

19. TB CAP Toolbox to 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.

20. TBCAP Laboratory Tools

21. TB CAP Laboratory Tools in progress
Manual on biosafety for laboratories

22. Road Map for Laboratory Strengthening
A structured framework for scaling-up TB laboratory services
Based on
WHO-recommended norms and standards
documented country best-practices
growing lessons learnt from field experiences by many partners involved in the Global Laboratory Initiative (GLI).

23. 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

24. 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)

25. External Quality Assurance
Training package for AFB microscopy
EQA for Light and Fluorescence Microscopy
Training package for EQA
Panel Tests
Blinded rechecking
Analysis and reporting of results
Supervision

26. Culture and DST Training Package
Covers all aspects of culture and DST
12 modules
Trainers’ manual
Participants’ manual

27. Laboratory Management Information 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

28. Dissemination and implementation of the laboratory tools

29. 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

30. Regional Workshops in Africa and Asia
Afghanistan
Bangladesh
Cambodia
Indonesia
Pakistan
Vietnam
Participating Country teams:
Kenya
Uganda
Ethiopia
Nigeria
Ghana
Namibia

31. 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

32. Workshop organization and content
Team approach – ‘interactive’
Baseline situation analysis
Identification and prioritization of current TB lab challenges
Tool orientation
Action planning

35. Challenges with in-country implementation of lab tools
Numerous lab challenges, particularly in Africa
Political will, motivation & commitment
Relationship between NTP and labs
Leadership capacity
Human and financial resources

36. How could countries adopt, adapt and implement the toolbox?
Questions and open discussion