Xpert MTB/RIF assay validation experience --- impact and plan in China

Transcription

1 Xpert MTB/RIF assay validation experience --- impact and plan in China Dr. Zhao Yanlin Chinese Center for Disease Control & Prevention Dr. Richard O Brien FIND April. 16, 2013

2 Progress Contribution for global TB control Cases detected and treated ( ) 8.29 million PTB 4.50 million SS+ PTB Cure rate of New SS+ >90% MDG target (compare with the data of 1990) SS+ prevalence decline over 50% Mortality decline about 80%

3 TB prevalence surveys, 2010 and 2000 Prevalence (1/100,000) Decline (%) Annual decline (%) All type of TB Sputum Smear positive Bact. positive

4 Prevalence by age group

5 Prevalence ( per 100,000) TB Prevalence in different areas Urban Rural Active TB Smear(+) TB Bacter(+) TB Diagnosis

6 Prevalence in different areas

7 Nationwide TB DRS in China ( ) Category MDR-TB(%) XDR-TB(%) New cases Retreatment cases Total Estimated number of total MDR-TB cases annually was 100,000 Estimated number of total XDR-TB cases annually was 9,000

8 PMDRT situation GF GATES DBF Others Total Time period Coverage Provinces Prefectures Diagnosed No. MDR/XDR- TB Enrolled Treatment No. MDR/XDR- TB (61.5%)

9 Challenges Changing landscape of the TB epidemic with high MDR- TB Sustainability issue (funding, post GF) Medical care cost for TB patient Engagement of hospitals

10 Funding Sources and gap for TB control from 2004 to 2010 (Unit: million Yuan) ,63 217,03 228,1 211,56 234, , ,35 249,55 191, , ,5 0 97,38 71,725 67, , ,336 74, ,837 88, ,7 394, , , , , , ,51 489,18 517,9 536,54 576,35 358,77 269,47 265, Gap Other JICA Global foundation World Bank Local government Central government Funds (RMB) for TB control was increased from 0.13 billion in 2001 to 1.34 billion in 2010

11 Medical care cost for patients Hospitalization cost of MDR-TB patient was analyzed in 4 cities covered by BMGF project Average hospitalization cost was 5,115 Yuan per MDR-TB patient The proportion of financing resource was supposed to be 5:4:1 designed by the project, while the actual implementation status was 41.2%, 34.8% and 24.0% Financing resource Designed plan local medical insurance Actual implementation 50% 41.2% BMGF project 40% 34.8% patient 10% 24.0%

12 China TB control structure Medical Administrative Network TB control network: CDC Ministry of Health Bureau of Disease Control Medical administration Health Policy & Regulation.. National CDC/CIS Provincial Dept of Health Prefecture Health Bureau County Health Bureau 48,000 health units Section of Disease Control Medical administration.. Section of Disease Control Medical administration.. Section of Disease Control Medical administration.. Provincial CDC/CIS Prefecture CDC/CIS County 3,200 TB dispensaries and designated hospitals

13 TB Control Network: current model Task National TB programme General hospitals Suspects identification Sputum microscopy + +/- Diagnosis + + Treatment initiation + Treatment supervision + Records keeping + Case notification + Drugs and supplies + Community health service station and village clinic Training, surveillance, health promotion, etc +

14 Task The responsibilities in new county TB control model CDC system Designated medical institutes General hospitals Suspects identification Sputum examination + +/- Diagnosis + + Treatment initiation + Treatment supervision + Records keeping + Case notification + Drugs and supplies + Community health service Planning, Training, surveillance, health promotion, monitoring,etc +

15 Validation study 1. Study Sites Four TB control agencies at county/district level were chosen as project sites: Xiangtan, Yueyang of Hubei province, Beilin, Lanxi of Heilongjiang province. 2. Study Timeline In-field implementation stage: March 2011~February Study Subjects (1)TB suspects; (2)DR-suspect: recurrence, return, initial treatment failure, the retreatment failure and cases of smearpositive after 2 months treatment; (3)informed consent; (4) newly diagnosed, initial treatment failure, the retreatment failure and relapse patients who can provide 3 qualified sputum specimens, return and follow-up patients who can provide 2 qualified sputum specimens.

16 Fig 1:Flowchart of cases inclusion and detection for Xpert validation Eligible patients N=2454 Analysed for MTB detection N=2392 Excluded patients n=52 Culture contamination: 17 Xpert for MTB detection failure:11 Subculture failure: 4 NTM:25 No sequencing results: 5 suspected cases of TB N=2094 Suspected cases of MDR TB N=298 Culture Negative N=1544 Culture Positive N=550 Culture Positive N=101 Culture Negative N=197 Excluded patients n=32 Xpert for RIF resistance detection failure:1 Xpert for MTB detection neative:31 Excluded patients n=3 Xpert for RIF resistance detection failure:1 Xpert for MTB detection neative:2 Analysed for RIF resistance detection N=616 suspected cases of TB N=518 Suspected cases of MDR TB N=98 RIF resistant N=31 RIF sensitive N=487 RIF resistant N=31 RIF sensitive N=67

17 TABLE 1 Demographic and Diagnosis group at enrollment of the recruited Patients Xiangtan Yueyang Beilin Lanxi Total Total cases Demographic characheristic Age scale-yr-no./total.no.(%) <20 13/662 (2.0) 21/677 (3.1) 20/553 (3.6) 8/562(1.4) 62/2454 (2.5) /662 (17.5) 175/677 (25.8) 104/553 (18.8) 105/562 (18.7) 500/2454 (20.4) /662 (45.3) 265/677 (39.1) 266/553 (48.1) 276/562 (49.1) 1107/2454 (45.1) /662 (35.2) 216/677 (31.9) 163/553 (29.5) 173/562 (30.8) 785/2454 (32.0) Female sex-no./total.no.(%) 131/662 (19.8) 182/677 (26.9) 184/553 (33.3) 216/562 (38.4) 713/2454 (29.1) Diagnosis group at enrollment for main analysis casesno./total.no.(%) Suspicion of pulmonary tuberculosis-no./total.no.(%) Suspicion of MDR-TBno./total.no.(%) 520/662 (78.5) 645/677 (95.3) 480/553 (86.8) 497/562 (88.4) 2142/2454 (87.3) 142/662 (21.5) 32/677 (4.7) 73/553 (13.2) 65/562 (11.6) 312/2454 (12.7)

18 TABLE 2 Sensitivity and Specificity of the MTB/RIF test for MTB detection from TB suspected patients, as Compared with Solid Culture and strain identification C+ (95%CI) Sensitivity S+C+ (95%CI) S-C+ (95%CI) Specificity (95%CI) PPV (95%CI) NPV (95%CI) XiangTan 94.2% ( ) 87.4% ( ) 90.6% ( ) 87.5% ( ) 95.7% ( ) YueYang 93.8% ( ) 89.2% ( ) 88.2% ( ) 63.1% ( ) 98.5% ( ) BeiLin 95.0% ( ) 90.4% ( ) 91.7% ( ) 85.4% ( ) 97.3% ( ) LanXi 94.2% ( ) 88.2% ( ) 91.2% ( ) 64.4% ( ) 98.9% ( ) Total 94.4% ( ) 88.8% ( ) 90.2% ( ) 77.4% ( ) 97.8% ( )

19 TABLE 3 Sensitivity and Specificity of the MTB/RIF test for MTB detection from MDR TB suspected patients, as Compared with Solid Culture and strain identification Sensitivity C+ (95%CI) S+C+ (95%CI) S-C+ (95%CI) Specificity (95%CI) PPV(95%CI) NPV(95%CI) XiangTan 96.8% ( ) 66.7% ( ) 82.0% ( ) 62.0% ( ) 98.9% ( ) YueYang 57.1% ( ) 55.0% ( ) BeiLin 97.7% ( ) 90.0% ( ) 56.0% ( ) 79.6% ( ) 93.3% ( ) LanXi 77.8% ( ) 58.3% ( ) Total 98.0% ( ) 87.5% ( ) 75.1% ( ) 66.9% ( ) 98.7% ( )

20 TABLE 4 MTB/RIF test for rifampicin resistance detection from TB suspected patients vs Conventional DST Sensitivity (95%CI) Specificity (95%CI) PPV (95%CI) NPV (95%CI) XiangTan % ( ) 98.95% ( ) 71.43% ( ) % ( ) YueYang 88.89% ( ) 95.88% ( ) 66.67% ( ) 98.94% ( ) BeiLin 87.50% ( ) 97.22% ( ) 58.33% ( ) % ( ) LanXi 77.78% ( ) % ( ) % ( ) 96.49% ( ) Total 87.10% ( ) 97.95% ( ) 71.05% ( ) 99.38% ( )

21 TABLE 5 MTB/RIF test for rifampicin resistance detection from MDR TB suspected patients Compared with Conventional DST Sensitivity (95%CI) Specificity (95%CI) PPV(95%CI) NPV(95%CI) XiangTan % ( ) % ( ) % ( ) % ( ) YueYang 88.89% ( ) % ( ) % ( ) 66.67% ( ) BeiLin 87.50% ( ) 85.29% ( ) 58.33% ( ) 96.67% ( ) LanXi 75.00% ( ) 83.33% ( ) 85.71% ( ) 71.43% ( ) Total 87.10% ( ) 91.04% ( ) 81.82% ( ) 93.85% ( )

22 Table 6 Cost per MTB identified by Xpert assay and traditional culture in project areas(unit: USD) Solid Culture &PNB Strain Identification Xpert Detection Rate Cost/each test Cost/each TB patient Detection Rate Cost/each test Cost/each TB patient 35.05% % Yueyang 17.13% % Beilin 36.35% % Lanxi 14.23% % Mean 25.63% %

23 Table 7 Cost per rifampicin-resistant patient identified by Xpert and conventional DST respectively in project sites Conventional DST Xpert Detection Rate Cost/each test Cost/each Rifampicinresistant TB patient Detection Rate Cost/each test Cost/each Rifampicinresistant TB patient Heilong jiang 3.14% % Hunan 1.72% % Mean 2.36% %

24 Main findings 1. Xpert detection was of relatively high sensitivity and specificity in detecting Mycobacterium tuberculosis and rifampicin resistance at district/county level. 2.TAT is shorter. 3.Xpert test was more in line with the requirements of costeffectiveness for rifampicin resistance TB detection. 4.Xpert instrument could not work under the temperature of 0 5.Module failure rate was about 6%

25 6. Technically Xpert could replace diagnostic smear microscopy. 7. It is recommended to primarily use the Xpert detection among high risk populations on drug resistance. 8. For RIF resistance cases, the sputum should be delivered to city laboratory for LPA and/or Genechip,conventional solid culture and DST. 9. For DR suspects, the patients should be treated and administered as directly based on output of Xpert RIF assay tests to keep proficient/technician and /or 1 month pilot. 11. one week training for technician.

26 Mechanism for new TB diagnostics evaluation Lab Expert Panel MOH Expert Advisory Committee NPT CDC Health Care Providers Lab Experts MOH China CDC Lab Expert Panel Screening of New Diagnostics Small-scale Field Evaluation Large-scale Field Evaluation Scaling Up National TB Reference Laboratory 3 Labs All Counties in 2 Designated Cities/6 City-level Labs in Eastern Central and Western China NTP China CDC TB Control Agencies

27 Current situation for Xpert in China Appraisal Xpert has a higher positive predictive value in multi-drug resistant suspects. Registration The kit does not get license from the SFDA up to now Research use only

28 PMDRT situation GF GATES DBF Others Total Time period Coverage Provinces Prefectures Diagnosed No. MDR/XDR- TB Enrolled Treatment No. MDR/XDR- TB (61.5%)

29 Plans To purchase 160 GeneXpert instruments and 110,000 cartridges Establishment of the EQA for NAAT including Xpert If Xpert gets the license from China SFDA, 760 GeneXpert instruments and 860,000 kits will be procured.

30 Diagnostics at different levels surveillance standard capacity buildingup NRL TB traditional/new techniques evaluation surveillance outbreak response training EQA QA training MDR-TB diagnosis and confirmation Diagnosis of TB outbreak response Screening MDR-TB suspects screening Primary health coumunity care CITY County level Symptom screening R D T FN PRL Smear microscopy ZN Rx Solid and liquid culture Liquid and solid culture Molecular test MDRTB/TB-MM iled Solid culture TB suspects LPA genechip genotyping new tech HIV/TB coinfection LAMP 等 Suspects for drug eistance R referral e Health management f e r r a l

31 Thanks for your attention!