Experimental protocol for assessing the use of the IFNg test for btb sreening in France

Transcription

1 Experimental protocol for assessing the use of the IFNg test for btb sreening in France ML. Boschiroli Bovine Tuberculosis national and OIE reference Laboratory A. Praud, B. Dufour EPIMAI Unit

2 Rationale for the IFNg Experimental protocol btb epidemiological situation in France Reinforced control strategy: use of new diagnostic tests Aims of the IFNg experimental protocol Technique s harmonisation Type of IFNg test Employed interpretation formulae Employed interpretation criteria Lab-Network constitution Preliminary results Analysed data Se results Perspectives

3 Rationale for the IFNg Experimental protocol btb epidemiological situation in France Reinforced control strategy: use of new diagnostic tests Aims of the IFNg experimental protocol Technique s harmonisation Type of IFNg test Employed interpretation formulae Employed interpretation criteria Lab-Network constitution Preliminary results Analysed data Se results Perspectives

4 Bovine tuberculosis epidemiological situation in France (Bovine and swine diseases 2014 Annual report, EU) Source: ADNS Source: ADNS

5 Bovine tuberculosis epidemiological situation in France Reinforced national control program (nov. 2010, 107 measures) Axis 1: reinforce prevention measures Axis 2: eradication follow up Axis 3: strengthen, direct and remotivate field resources Biosecurity in the herd Control of wildlife ( d, vaccination ) Risk based surveillance (wildlife and cattlesylvatub) Total or partial slaughter (previous epidemiologic investigation) Herd management measures according to previous risk assessment Amelioration of diagnosis PPV Concertation of field actors, professional world, vets, scientists and administration (stakeholders) = Plat. ESA Communication, awareness, training Better compensation and development of cheaper control strategies Regional epidemiological coordination CIREV Follow up of results and adaptation if necessary

6 Bovine tuberculosis epidemiological situation in France Reinforced national control program (nov. 2010, 107 measures) Axis 1: reinforce prevention measures Biosecurity in the herd Control of wildlife ( d, vaccination ) Axis 2: eradication follow up Risk based surveillance (wildlife and cattlesylvatub) Total or partial slaughter (previous epidemiologic investigation) Herd management measures according to previous risk assessment Amelioration of diagnosis of diagnosis PPV PPV Axis 3: strengthen, direct and remotivate field resources Concertation of field actors, professional world, vets, scientists and administration (stakeholders) = Plat. ESA Communication, awareness, training Better compensation and development of cheaper control strategies Regional epidemiological coordination CIREV Follow up of results and adaptation if necessary

7 Amelioration of diagnostic predictive values IDS Diagnostic IDC cull HISTOLOGY CULTURE IDENTIFICATION & TYPING 6-8 weeks 8 days 8-10 days 3 months 1 month Loss of qualitfication ~ 6 months

8 Amelioration of diagnostic predictive values IDS Diagnostic IDC cull HISTOLOGY CULTURE IDENTIFICATION & TYPING 8-10 days 6-8 weeks 8 days 3 months 1 month Loss of qualitfication ~ 6 months PCR

9 Amelioration of diagnostic predictive values IDS Diagnostic IDC cull HISTOLOGY CULTURE IDENTIFICATION & TYPING 8-10 days 6-8 weeks 8 days 3 months 1 month IFN-g Loss of qualitfication ~ 6 months

10 Aims of the IFNg experimental protocol (EC Validated) non-negative skin test non-negative skin test IFN J3-J8 IDC J42 Assess the accuracy of IFNg after a non-negative ST screening result as an alternative to SICCT performed 42 days later: ensure that the sensitivity of IFN performed in the days following ST not lower than SICCT test performed 42 days after serial use did not endanger the safety of the trade 11

11 Rationale for the IFNg Experimental protocol btb epidemiological situation in France Reinforced control strategy: use of new diagnostic tests Aims of the IFNg experimental protocol Technique s harmonisation Type of IFNg test Employed interpretation formulae Employed interpretation criteria Lab-Network constitution Preliminary results Analysed data Se results Perspectives

12 Type of IFNg test Test Se Sp Ref IDS IDC IFG Bovigam 83,9% [63,2% ; 100%] 80% [52,0% ; 100%] 87,6% [73% ; 100%] Valeurs de 96,8% [75,5% ; 99,0%] 98,8% [78,8% ; 100%] 96,6% [85,0% ; 99,6%] PPD De la rua Domenech et al, 2006

13 Type of IFNg test Test Se Sp Ref IDS IDC IFG Bovigam 83,9% [63,2% ; 100%] 80% [52,0% ; 100%] 87,6% [73% ; 100%] Valeurs de 96,8% [75,5% ; 99,0%] 98,8% [78,8% ; 100%] 96,6% [85,0% ; 99,6%] IFG ESAT6 CFP10 85 % 97 % MIX PPD De la rua Domenech et al, 2006 Aagaard et al. 2006

14 Type of IFNg test PPD + MIX: SENSITIVITY & SPECIFICITY Test Se Sp Ref. IDS IDC IFG Bovigam 83,9% [63,2% ; 100%] 80% [52,0% ; 100%] 87,6% [73% ; 100%] Valeurs de 96,8% [75,5% ; 99,0%] 98,8% [78,8% ; 100%] 96,6% [85,0% ; 99,6%] IFG ESAT6 CFP10 85 % 97 % MIX PPD De la rua Domenech et al, 2006 Aagaard et al. 2006

15 Type of IFNg test PPD + MIX: SENSITIVITY & SPECIFICITY Test Se Sp Ref. IDS IDC IFG Bovigam 83,9% [63,2% ; 100%] 80% [52,0% ; 100%] 87,6% [73% ; 100%] Valeurs de 96,8% [75,5% ; 99,0%] 98,8% [78,8% ; 100%] 96,6% [85,0% ; 99,6%] IFG ESAT6 CFP10 85 % 97 % MIX PPD De la rua Domenech et al, 2006 Aagaard et al Batch / batch control

16 Employed interpretation formulae COUNTRY EURL Interpretation - Cut-off PPDb PBS ; PPDb > PPDa Member 1 PPDb PBS > 0.1; PPDb-PPDa > 0.1 Member 2 PPDb/PBS > 2.0 and PBS < 0.15 Member 3 PPDb PBS + 0.1; PPDb > PPDa Member 4 PPDb PBS + 0.1; PPDb PPDa Member 5 PPDb PBS + 0.1; PPDb > PPDa Member 6 PPDb PBS ; PPDb PPDa; PPDb > 0.1; PPDb > PPDa Member 7 PPDb /PBS 2; PPDb PPDa Member 8 Member 9 PPDb PBS ; PPDb > PPDa PPDb PBS ; PPDb > PPDa Member 10 PPDb PBS (eradication); PPDb PBS + 0.1(screening); Bov PPDb> PPDa Member 11 PPDb PBS ; PPDb > PPDa Member 12 Parallel test: PPDb - PPDa > 0.1; Serial test: PPDb-PPDa>0.1 and ESAT6/CFP10 - nil>0.1 France (PPDb-PPDa)/(PC-NC) > 0.05 (E/C- PBS)/(PC-NC)>0.3 UE: great variability on interpretation formulae among members using the test

17 Employed interpretation formulae COUNTRY EURL Interpretation - Cut-off PPDb PBS ; PPDb > PPDa Member 1 PPDb PBS > 0.1; PPDb-PPDa > 0.1 Member 2 PPDb/PBS > 2.0 and PBS < 0.15 Member 3 PPDb PBS + 0.1; PPDb > PPDa Member 4 PPDb PBS + 0.1; PPDb PPDa Member 5 PPDb PBS + 0.1; PPDb > PPDa Member 6 PPDb PBS ; PPDb PPDa; PPDb > 0.1; PPDb > PPDa Member 7 PPDb /PBS 2; PPDb PPDa Member 8 Member 9 PPDb PBS ; PPDb > PPDa PPDb PBS ; PPDb > PPDa Member 10 PPDb PBS (eradication); PPDb PBS + 0.1(screening); Bov PPDb> PPDa Member 11 PPDb PBS ; PPDb > PPDa Member 12 Parallel test: PPDb - PPDa > 0.1; Serial test: PPDb-PPDa>0.1 and ESAT6/CFP10 - nil>0.1 France (PPDb-PPDa)/(PC-NC) > 0.05 (E/C- PBS)/(PC-NC)>0.3

18 Employed interpretation formulae COUNTRY EURL Interpretation - Cut-off PPDb PBS ; PPDb > PPDa Member 1 PPDb PBS > 0.1; PPDb-PPDa > 0.1 Member 2 PPDb/PBS > 2.0 and PBS < 0.15 Member 3 PPDb PBS + 0.1; PPDb > PPDa Member 4 PPDb PBS + 0.1; PPDb PPDa Member 5 PPDb PBS + 0.1; PPDb > PPDa Member 6 PPDb PBS ; PPDb PPDa; PPDb > 0.1; PPDb > PPDa Member 7 PPDb /PBS 2; PPDb PPDa Member 8 Member 9 PPDb PBS ; PPDb > PPDa PPDb PBS ; PPDb > PPDa Member 10 PPDb PBS (eradication); PPDb PBS + 0.1(screening); Bov PPDb> PPDa Member 11 PPDb PBS ; PPDb > PPDa Member 12 Parallel test: PPDb - PPDa > 0.1; Serial test: PPDb-PPDa>0.1 and ESAT6/CFP10 - nil>0.1 France (PPDb-PPDa)/(PC-NC) > 0.05 (E/C- PBS)/(PC-NC)>0.3 France: only UE member using a normalised formulae as suggested by OIE

19 Employed interpretation formulae

20 Employed interpretation formulae ROBUSTNESS Amelioration of the test s robustness comparabiliy within and between labs

21 Employed interpretation criteria

22 Employed interpretation criteria WELL ADAPTED CUT OFF VALUES

23 Lab-Network constitution Stimulation step (20+12): Training by the NRL network of laboratories able to stimulate blood in the 8 hours after sampling Stimulation + Elisa (12): Training by NRL Use of ref. material Evaluated by ring trial organised by NRL

24 Stimulation step (20+12): Training by the NRL Lab-Network constitution REPRESENTATIVE & RELIABLE network of laboratories able to stimulate blood in the 8 hours after sampling Stimulation + Elisa (12): Training by NRL Use of ref. material Evaluated by ring trial organised by NRL

25 Rationale for the IFNg Experimental protocol btb epidemiological situation in France Reinforced control strategy: use of new diagnostic tests Aims of the IFNg experimental protocol Technique s harmonisation Type of IFNg test Employed interpretation formulae Employed interpretation criteria Lab-Network constitution Preliminary results Analysed data Se results Perspectives

26 Analysed data Gathered on a voluntary basis in farms where non-negative results to screening ST were observed STs performed as part of the usual official screening scheme (EC authorisation and ad hoc «note de service») :

27 Analysed data Gathered on a voluntary basis in farms where non-negative results to screening ST were observed STs performed as part of the usual official screening scheme (EC authorisation and ad hoc «note de service») : Animals with non-negative results to ST on day 0 (STD0) were subjected to IFN between days 3 and 8 after tuberculin injection (IFND3) and retested with SICCT test and IFN on day 42 (SICCTD42, IFND42) Animals with non-negative results to STD0, IFND3, SICCTD42 or IFND42 were slaughtered and M. bovis infection (bact/pcr) was studied

28 Analysed data Gathered on a voluntary basis in farms where non-negative results to screening ST were observed STs performed as part of the usual official screening scheme (EC authorisation and ad hoc «note de service») : Animals with non-negative results to ST on day 0 (STD0) were subjected to IFN between days 3 and 8 after tuberculin injection (IFND3) and retested with SICCT test and IFN on day 42 (SICCTD42, IFND42) Animals with non-negative results to STD0, IFND3, SICCTD42 or IFND42 were slaughtered and M. bovis infection (bact/pcr) was studied Database: 2851 animals Se: Results of the four tests available for 40 infected animals / 29 farms

29 Results

30 Results Results of 4 tests on the 40 infected animals NN ID J0 ID J0 ID J42 IFN J3 IFN J42 Nombre TOTAL 40 Légende : «+» = «Non négatif» (+, ou douteux or non conclusif) 31

31 Results Results of 4 tests on the 40 infected animals NN ID J0 Note: Se brute = only + ; Se UE = non négatif (+, ou douteux or non conclusif) Se UE IDC J42 ID J0 NN = 45% [30% ; 60%] IC95% (18/40) Se UE IFN J3 ID J0 NN = 95% [88% ; 100%] IC95% (38/40) Se brute IDC J42 ID J0 NN = 20% [8% ; 32%] IC95% (8/40) Se brute IFN J3 ID J0 NN = 88% [77% ; 98%] IC95% (35/4) Se IFN PPD J3 ID J0 NN = 89% [78% ; 100%] IC95% (25/28) Most non-negative results to SICCTD42 confirmed by IFND3 (89%; n=16/18) Among animals detected by IFND3, 22 animals were negative to SICCTD42 (58 %; n=22/38) sensitivity of IFND42 slightly higher than IFND3

32 Results IFN performed between 3 and 8 days after a non-negative result to screening STs was significantly more sensitive than the usual test (SICCT test, 42 days later).

33 Results IFN performed between 3 and 8 days after a non-negative result to screening STs was significantly more sensitive than the usual test (SICCT test, 42 days later). Most cases detected by SICCTD42 were also detected by IFND3 and a high number of cases undetected by SICCTD42 reacted to IFND3

34 Results IFN performed between 3 and 8 days after a non-negative result to screening STs was significantly more sensitive than the usual test (SICCT test, 42 days later). Most cases detected by SICCTD42 were also detected by IFND3 and a high number of cases undetected by SICCTD42 reacted to IFND3 The serial association of screening ST with IFND3 could thus be used to shorten the lock-up of suspect herds without subdetecting infected cattle

35 Rationale for the IFNg Experimental protocol btb epidemiological situation in France Reinforced control strategy: use of new diagnostic tests Aims of the IFNg experimental protocol Technique s harmonisation Type of IFNg test Employed interpretation formulae Employed interpretation criteria Lab-Network constitution Preliminary results Analysed data Se results Perspectives

36 Perspectives Submission of the complete report to Anses for evaluation and opinion Publication in scientific journal If favorable, submbission to the EC for requesting inclussion of the test as an alternative to the current ST-based scheme

37 Merci pour votre attention!