The Next 65 years: TB Technology and Innovation. Bob Belknap M.D. Director, Denver Metro TB Program

Transcription

1 The Next 65 years: TB Technology and Innovation Bob Belknap M.D. Director, Denver Metro TB Program

2 Disclosures 1. CDC funding for TBTC and TBESC 2. No conflicts of interest

3 Objectives After the talk, you should be able to: 1. List 3 barriers to TB elimination 2. Describe how technology and innovations may overcome these barriers in the future

4 The last 65 years:

5 Global Trends in TB Dye et al Ann Rev Public Health 2013

6 Barriers to TB Elimination Poor diagnostic tests for latent and active tuberculosis Relatively weak and poorly tolerated medications Limited availability and acceptability of LTBI diagnosis and treatment by patients and providers

7 54 y/o male with hematemesis From MX, in U.S. for 11 years HIV negative New diagnosis of cryptogenic cirrhosis Would you test and treat for LTBI?

8 Whole blood RNA sequencing Zak, Lancet :

9 Zak, Lancet :

10 Zak, Lancet :

11 54 y/o male with cryptogenic cirrhosis Would you test and treat for LTBI if you knew the risk of active TB was high?

12 60 y/o with cryptogenic cirrhosis s/p TIPS in 2010 and 2014 New onset chest and abdominal pain INR 2.43 Pleural Fluid 48k RBC 1.8k WBC (73% L) Prot 2.2 (serum4.6) LDH 279 (serum 422)

13 60 y/o with cryptogenic cirrhosis AFB smear 1+ GeneXpert Hain (+) TB (+) rpob mutation (+) rpob mutation (-) INH or second line

14 NTCA/APHL Consensus Statement on GeneXpert for Airborne Isolation 2 negative GeneXpert to stop AII Emphasizes wellcollected sputa Not for monitoring response to treatment

15 Frick, Lessem and McKenna TAG

16 4 y/o household contact Would you start the 4 y/o on TB treatment?

17 Multi-cohort analysis 14 data sets, 2,572 samples, 10 countries 3 data sets for discovery and 11 for validation 3 genes identified Lancet Respir Med 2016; 4:

18 Validated in cohorts or adults and children Not confounded by HIV, drug resistance or BCG Could be used to monitor Tx response Lancet Respir Med 2016; 4:

19 Scientific Reports 2015; 4:

20 PET/CT scans and TB Skoura, Int J Infect Dis 2015; 32: 87-93

21 4 y/o household contact CT scan no adenopathy

22 Barriers to TB Elimination Poor diagnostic tests for latent and active tuberculosis Relatively weak and poorly tolerated medications Limited availability and acceptability of TB preventive treatment by patients and providers

23 Drug-discovery Pipeline Wallis Lancet 2016; 16: e34-44

24 New/newer compounds for TB

25 Clinical Trials for Active TB Wallis Lancet 2016; 16: e34-44

26 Chen, Science Translational Med 2014; 6: 265ra166

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28 Wallis Lancet 2016; 16: e34-44

29 Increased autonomy Take meds at preferred times / weekends / holidays Focus resources on those who need more intensive monitoring IJTLD 2016; 20(5):

30 Barriers to TB Elimination Poor diagnostic tests for latent and active tuberculosis Relatively weak and poorly tolerated medications Limited availability and acceptability of TB preventive treatment by patients and providers

31 Ann Rev Public Health 2013

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33 U.S. Preventive Services Task Force

34 54 y/o male with cryptogenic cirrhosis Would you test and treat for LTBI if you knew the risk of active TB was high?

35 Treatment of LTBI

36 Tuberculosis teaching in our medical schools is an unsolved problem... What do you think would be the situation if 50 years from now every practicing physician appreciated the relations between infection and disease What if in thinking of tuberculosis every physician s instinct immediately sensed curability of infection Annual Meeting of the National Association for the Study and Prevention of TB, May 11, 1917

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39 Treatment Acceptance: Connecting with the Community

40 TB Vaccine?

41 Objectives 1. List 3 barriers to TB elimination 1. Accuracy of our diagnostic tests 2. Strength and tolerability of our medications 3. Under utilized diagnosis and treatment of latent TB infection

42 Objectives 2. Describe how technology and innovations may overcome some of these barriers PCR-based technology will become increasingly used (and replace smear) Genome-wide expression profiles of proteins and mrna will yield better diagnostics and help in drug discovery Electronic and communications advances will provide more options for monitoring therapy and alerting when someone is at risk