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

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

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

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

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

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

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

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

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

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)

New diagnostic technologies for diagnosing TB

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)

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

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.

TBCAP Laboratory Tools

TB CAP Laboratory Tools in progress Manual on biosafety for laboratories

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).

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

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)

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

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

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

Dissemination and implementation of the laboratory tools

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

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

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

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

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

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