International TB Diagnostic Strategies - aphl.org · International TB Diagnostic Strategies Heather Alexander, PhD International Laboratory Branch ... TB Diagnostics Pathway Stop

International TB Diagnostic Strategies

Heather Alexander, PhD

International Laboratory Branch

Division of Global HIV/AIDS

Centers for Disease Control and Prevention

7th National Conference on Laboratory Aspects of TB

14 June 2011

Center for Global Health

Division of Global HIV/AIDS

Outline

Global epidemiology of TB

Diagnostic pathway and WHO approval process

Recent WHO diagnostic policies

Introduction of new diagnostic assays and algorithms

The Global Burden of TB - 2008

Estimated number of

cases (range)

Estimated number of

deaths (range)

1.8 million

(1.6–2.3 million)

9.4 million

(8.9–9.9 million)

440,000

(0.39–0.51 million)

All forms of TB

Multidrug-resistant TB (MDR TB)

HIV-associated TB 1.4 million (1.3–1.6 million)

520,000(0.45–0.62 million)

150,000(0.05–0.27 million)

Direct Sputum Smear Microscopy

Images Courtesy John Ridderhof

Primary TB diagnostic test

Insufficient for detection of: Smear-negative TB

Drug-resistant TB

TB Diagnostics Pathway

Stop TB New Diagnostics Working Group: A blueprint for the development of TB Diagnostics, 2009

Identifying the needfor policy change

Reviewing the evidence

Convening an Expert Group

Assessing policy proposal

and recommendations

Formulating anddisseminating policy

WHO TB Diagnostics Policy Formulation

• WHO strategic monitoring of country needs• Partners (researchers, industry, etc)• Body of evidence available

• Commissioning of systematic reviews• QUADAS or other diagnostic accuracy tool• Meta-analyses (where feasible)

• Experts, methodologists, end-users • Guidelines Review Committee• GRADE process for evidence synthesis

• Strategic and Technical Advisory Group • Endorsement/revision/addition• Advise WHO to proceed/not with policy

• Guidelines Review Committee • Dissemination to Member States• Promotion with stakeholders & funders• Phased implementation & scale-up plan

Courtesy WHO/GLI

WHO-Endorsed Tools (I) LED microscopy

Peripheral laboratory and higher

Coverage: 1 per 100,000 population (depending on distribution and specimen transport)

Required for TB treatment monitoring

Culture (liquid, solid, rapid speciation) Regional or national level laboratory

Coverage: 1 per 500,000-1million population

Required for MDR TB treatment monitoring

Phenotypic DST Regional or national level laboratory

Coverage: 1 per 500,000-1million population

Required for laboratory diagnosis of XDR TB

WHO-Endorsed Tools (II)

Molecular Line Probe Assay (LPA) Regional or national level laboratory

Smear positive sputum or MTB culture isolates

Coverage: 1 per 500,000-1million population

Xpert MTB/RIF Sub-district and district hospital level laboratory

Smear positive or negative sputum or processed sputum pellet

Coverage: dependent on local epidemiology

Courtesy WHO and FIND

Implementation of New Technologies and Diagnostic Algorithms

Decided by Ministries of Health Coordination of partners and funding mechanisms

• Avoid duplication of efforts

• Maximize resources

National strategic plans for: Laboratory strengthening

Management of TB, MDR-TB and HIV-associated TB

Phased approach

Linked to drug access and programmatic capacity

Based on local epidemiology

Requires continuous monitoring and evaluation

Example: Introduction of Xpert MTB/RIF

Xpert MTB/RIF Costs in Low Resource Settings

Equipment Xpert 4-module $17,000-17,500

Shipment, UPS, printer $1,700*

Maintenance Annual calibration $1,800**

Consumables Cartridges $16.86***

HR costs Tech annual salary To be determined locally

Training and TA To be determined locally

*approximate costs depending on local situation

**current cost; may decrease

***current cost; will decrease depending on volume sales

At capacity operating costs

Year 1: 100,000 USD

Year 2+: 80,000 USD

Xpert MTB/RIF Considerations (I)

Initial diagnostic test Individuals with suspected HIV-associated TB

Individuals with suspected MDR TB

Placement District and sub-district hospitals

Central /Reference laboratories for support, training and quality assurance

Use close to operating capacity (12-20 per day)

Specimen transport < 24 hours

Serving high prevalent TB/HIV and MDR TB populations

Xpert MTB/RIF Considerations (II)

Laboratory infrastructure Temperature control

• storage (2-28ºC)

• testing (max 30ºC)

Stable power supply

• UPS, generator, or batteries

Biosafety

• similar to direct sputum smear microscopy

Security

• minimize theft of machine and computer

Adequate waste management

• similar to microscopy

• greater volume of solid waste including plastics

Xpert MTB/RIF Considerations (III)

Programmatic and laboratory systems factors Epidemiology

Legal and regulatory requirements and policies

Inventory and supply management systems

Assay validation at each testing site

Quality assurance

Specimen transport and patient referral systems

Rapid reporting of results to clinicians and local public health authorities

Xpert MTB/RIF Considerations (IV)

Programmatic and laboratory systems factors (cont.) Quality-assured first- and second-line DST

Availability of quality first- and second-line anti-TB drugs

Quality-assured sputum smear microscopy and culture for treatment monitoring

Monitoring and evaluation

Budget for

• equipment

• operating costs

• first- and second-line TB drugs

• microscopy, culture, and DST

Priority Populations for Xpert MTB/RIF

http://www.stoptb.org/wg/gli/assets/documents/Xpert%20Rapid%20Implementation%20Document.pdf

Summary

Since 2007 WHO has issued several evidnece-based TB laboratory policies

WHO-endorsed TB diagnostic tools are suitable for implementation at different levels of the laboratory network

Process for implementation should be driven by the Ministry of Health and coordinated with partners

Opportunity for coordination between and strengthening of laboratory systems and TB programs

Resources

http://www.stoptb.org/wg/gli/

GLI Roadmap for TB Laboratory Strengthening

WHO Policy Framework for Implementing TB Diagnostics

GLI Laboratory Tool Set

WHO Rapid Implementation of the Xpert MTB/RIF Diagnostic Test

USG Phased Implementation and Evaluation of XpertMTB/RIF (in review)

The findings and conclusions in this presentation have not been formally disseminated by [he Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy.

Acknowledgements

CDC Anand Date

Michael Iademarco

Bess Miller

John Nkengasong

Eric Pevzner

Thomas Shinnick

Angela Starks

USAID Amy Piatek

OGAC Bill Coggin

WHO Chris Gilpin

Karin Weyer

GLI Rick O’Brien