Positioning of TB Diagnostics within a Tiered System Integrated Approach from Reference to District Laboratory. Giorgio Roscigno CEO FIND

Transcription

1 Positioning of TB Diagnostics within a Tiered System Integrated Approach from Reference to District Laboratory Giorgio Roscigno CEO FIND

2 Integrated Laboratory Network Definition An integrated laboratory network can be defined as one that has the ability to provide all needed primary diagnostic services for care and treatment of patients without requiring them to go to different laboratory facilities for specific tests (under one roof ideally under one ceiling).

3 Integrated laboratory network Basic approaches An integrated laboratory network should: utilize common specimen collection and reporting systems increase capacity for the introduction and utilization of new and more complex technologies. utilize common diagnostic platforms (e.g. molecular) that can be used across diseases within the same facility 3

4 Different levels of integrated laboratory services Integration of reference laboratories Integration of molecular services Integration of microscopy services Integration of specimen collections and transportation 4

5 Lab strengthening framework Input Output Objectives Outcome Impact Hardware Infrastructure Equipment Reagents and supplies Software Human resources Quality Assurance systems Management systems Functioning laboratory networks at: National reference lab Referral level District hospital Peripheral health center Access to diagnostic services rapid speciation Improved case management Decreased morbidity and mortality from treatable diseases

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7 DOTS reaching its limits e.g. Peru Introduction of DOTS (1990) Pulmonary TB cases / 100,000 Case finding PTB falling at 6%/year Morbidity TB incidence TB incidence S+ Ref: Estrategia Sanitaria Nacional de Prevencion y Control de la Tuberculosis/DGSP/MINSA, Peru

8 The shortfalls of DOTS (I): HIV TB notification in Zambia, The impact of HIV on the epidemiological situation of TB is so large that the tools available at present for TB control will fail to restrain the increase in the incidence of TB caused by HIV infection. Karel Styblo, Bull. IUATLD, Vol.65, N 1, March 1990

9 The shortfalls of DOTS (II): MDR-TB Ref: WHO Report 2010: Distribution of proportion of MDR-TB among previously treated TB cases,

10 The slow road to TB diagnosis 10

11 Importance of early diagnosis: Sensitivity (cfu/ml) of pulmonary TB tests in portfolio Target sensitivity range of FIND antigen detection tests LAMP-TB /ml iled* fluorescent microscope 10,000/ml Line-probe* 10,000/ml Capilia* speciation dipstick (of culture) 1,000,000/ml MGIT* /ml Xpert MTB* /ml Log cful/ml 11 * Development completed

12 Prior to FIND / Since FIND Central reference lab Solid culture (30days)/ DST (60days) Liquid culture (15days)/ DST (30days) Regional level Solid culture (30days)/ DST (60days) LPA/Rif & INH (2 days) Solid culture (30days)/ DST (60days) Ziehl-Neelsen (2-3 days) District level Microscopy level Health post / community level Integrated NAAT + 40% (<2 hrs) 2011: Manual NAAT + 25% (<2 hrs) LED FM + 10% faster (TB+HAT) 2011: Manual NAAT + 25% (<2 hrs) QA malaria RDTs 2013: TB RDT gen1/gen2

13 Liquid culture (approved by WHO 2007) M.tb grows rapidly in liquid culture 15 days to obtain growth in liquid Inhibitors need to be added to reduce growth of commensals Liquid culture is more sensitive than solid culture MGIT 960 uses fluorochrome tubes, which glow on depletion of oxygen, whereas MB/BacT detects CO2 production MGIT 960 approved by US FDA for culture & DST 13

14 Capilia TB: Speciation (approved by WHO 2007) Simple, rapid Immunochromatographic method No sample processing/instrumentation required Sensitivity of M.tb/M.africanum detection 100% 14

15 Line probe assay (WHO endorsement: 2008) DNA extraction + PCR + reverse hybridization of amplified DNA to oligonucleotide probes Identifies M.tb and detects Rif & INH resistance in 1-2 days Detection of rpob gene for Rifampicin & inha and catg gene for INH 15

16 Integrating HIV-TB diagnostics platforms: Lesotho MDR-TB LPA EID for HIV by PCR Molecular laboratory in Maseru Demonstration (Evidence) March 2007 LC April 2008 LPA WHO (Policy) June 2007 LC June 2009 LPA Implementation (Practice) November 2007 LC November 2008 LPA April 2009 EID for HIV by PCR Partners WHO PIH MOH (Lesotho)

17 Line Probe Assay Rapid molecular test for MDR-TB DNA extraction equipment Preparation for amplification

18 Early infant Diagnosis of HIV using Dried Blood samples Punching of DBS cards DNA extraction Hybridization reading of plate 18

19 Challenges of implementing new diagnostics Establishing strong partnerships is key Feasibility, contract, development phases Evaluation phase Demonstration phase Access phase Global Impact Evidence for regulatory approval Evidence for making policy Global Policy Evidence for scaling up Evidence for measuring impact Moving from demonstration to access and impact requires that new diagnostic tools are integrated into functional laboratory services Essential instruments, reagents, supplies Additional components to ensure quality diagnostic services

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21 Worldwide commitment

22 Evolution in TB diagnosis HIV / MDR-TB s Koch X-ray Tuberculin Culture 1 st TB drugs Shortcourse therapy Smear & X-ray Sanatoria Centralised programs Decentralisation to district level (based on Styblo model) Need for new tools & strategies

23 Driven by technology; e.g. PCR and Immunoassay From centralised big laboratory machines To self-contained simple-touse test systems PCR; microfluidics and miniaturisation + ++ Immunoassay; microfluidics, material science and miniaturisation 23

24 Integration of technologies lead to breakthrough-2010 Real-Time PCR Molecular beacons RT PCR Resistance-associated mutations Fluorimetric probes Microfluidics Sonic bacterial lysis Microfluidics TB DNA sequence

25 Automated NAAT: Xpert MTB/RIF

26 Introducing high tech in low tech settings Major advantages in workflow Automated Sample Prep, Amplification and Detection <120 minutes A technology platform: TB & Rif Resistance Potential for HIV viral load Potential for HPV STD GeneXpert fully automated with 1-step external sample prep. time-to-result 1 1/2 h (walk away test) throughput: up to 16 tests / module / run no bio-safety cabinet closed system (no contamination risk) Performance specific for MTB sensitivity close to culture detection of rif-resistance via rpob gene 26

27 A Better Way to Platform Design GeneXpert Infinity-48 GeneXpert Module GX-1 GX-4 GX-16

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29 Thank you 29