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Tuberculosis: Drug resistance in Canada - 2003
Reported susceptibility results of the Canadian Tuberculosis Laboratory Surveillance System
The results observed to date in this surveillance system are consistent with international data. In the latest report of the global TB drug resistance surveillance project jointly conducted by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD), the median prevalence of TB drug resistance among the participating countries was 10.2% for new cases and 18.4% for previously treated cases (as compared with 12.5% overall in Canada). The median prevalence of MDR-TB was 1.1% for new cases and 7.0% for previously treated cases (as compared with 1.5% overall in Canada).
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New - Appendices 1 and 2 were revised June 01, 2004. If you have previously downloaded this report, please replace the revised sections with this version.
| Methodology | |
| Results | |
| Discussion | |
| Limitations | |
| Conclusions | |
| Reference | |
| Figures | |
| Figure 1. | Reported TB drug resistance in Canada by province/territory - 2003 |
| Figure 2. | Reported MTB isolates in Canada by province/territory - 2003 |
| Figure 3. | Overall pattern of reported TB drug resistance in Canada - 2003 |
| Figure 4. | Reported TB drug resistance in Canada by type of drug - 2003 |
| Figure 5. | Any resistance to first-line anti-TB drugs in Canada - 1998-2003 |
| Figure 6. | Overall pattern of reported TB drug resistance in Canada - 1998-2003 |
TABLES |
|
| Minimal inhibitory concentrations for routine testing of first-line anti-tuberculosis drugs | |
| Table 1. | Overall pattern of reported TB drug resistance in Canada - 1998-2003 |
| Table 2. | Reported MTB isolates by "reporting" and "originating" province/territory, Canada - 2003 |
| Table 3. | Reported MDR-TB isolates by province/territory, Canada - 2003 |
| Table 4. | Reported TB drug resistance by gender and age group, Canada - 2003 |
| Table 5. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Alberta - 1998-2003 |
| Table 6. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, British Columbia - 1998-2003 |
| Table 7. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Manitoba - 1998-2003 |
| Table 8. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, New Brunswick - 1998-2003 |
| Table 9. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Newfoundland and Labrador - 1998-2003 |
| Table 10. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Northwest Territories - 1998-2003 |
| Table 11. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Nova Scotia - 1998-2003 |
| Table 12. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Nunavut - 1998-2003 |
| Table 13. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Ontario - 1998-2003 |
| Table 14. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Prince Edward Island - 1998-2003 |
| Table 15. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Québec - 1998-2003 |
| Table 16. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Saskatchewan - 1998-2003 |
| Table 17. | Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Yukon Territory - 1998-2003 |
| APPENDICES | |
| Appendix 1 - | Proficiency panel results for anti-microbial susceptibility testing of M. tuberculosis to first-line drugs |
| Appendix 2 - | Participating Laboratories of the Canadian Tuberculosis Laboratory Surveillance System (CTBLSS) |
| Appendix 3 - | M. tuberculosis Complex Antimicrobial Susceptibility Reporting Form |
Introduction
Tuberculosis Prevention and Control (TBPC) at the Centre for Infectious Disease Prevention and Control, in collaboration with the Canadian Tuberculosis Laboratory Technical Network and participating laboratories (representing all provinces and territories) in the Canadian Tuberculosis Laboratory Surveillance System (CTBLSS) (Appendix 2), established a laboratory-based national surveillance system in 1998 to monitor tuberculosis (TB) drug resistance patterns in Canada.
Laboratories report their results on anti-tuberculous drug susceptibility testing to TBPC for every patient that they receive a specimen or an isolate from each calendar year. TBPC subsequently produces an annual report. This report presents 2003 and adjusted 2002 (to reflect duplicate removal and late reporting) drug susceptibility data for TB isolates across Canada as of March 10, 2004.
Methodology
TBPC maintains a computerized database containing drug susceptibility test results of Mycobacterium tuberculosis (MTB) and MTB complex (MTBC) isolates. Isolates identified as M.bovis BCG are included in the CTBLSS but are excluded from this report. Results of susceptibility testing for second-line anti-tuberculous drugs, although reported, are also not included in this report. Data are collected either through manual completion of a standard reporting form (Appendix 3) or by electronic transmission. Information collected includes sex, year of birth, province/territory from which the report originates, province/territory from which the specimen originates and susceptibility results. TBPC makes every effort to eliminate duplicate specimens; only the most recent susceptibility results for a given patient in the current reporting year are included for analysis.
Newfoundland and Labrador identifies the species and tests all isolates for drug resistance in Newfoundland. Some provinces identify the species and test their own isolates and those of other provinces/territories (British Columbia: British Columbia and Yukon Territory isolates; Alberta: Alberta and Northwest Territories isolates; Quebec: Quebec and New Brunswick isolates; Ontario: Ontario and Nunavut isolates; Nova Scotia: Nova Scotia and Prince Edward Island isolates). Saskatchewan tests for drug resistance on all MTBC isolates. Other provinces and territories report results at the species level.
Laboratories generally perform routine susceptibility testing of MTB or MTBC to first-line anti-tuberculous drugs using the radiometric proportion method (Bactec®). Saskatchewan uses MGIT® 960 and all others use Bactec® 460. Table A lists the first-line anti-tuberculosis drugs and the concentrations in mg/L used by the participating laboratories.
As noted in Table A, the number and specific first-line anti-tuberculous drugs that are subject to routine susceptibility testing differ among the provinces and territories. Accordingly, the number of isolates included in the descriptive analyses varies.
| Table A: Minimal inhibitory concentrations for routine testing of first-line anti-tuberculosis drugs | ||
| Anti-TB drugs | MIC (mg/L) | Comments |
| Isoniazid (INH) | 0.1 | |
| Rifampin (RMP) | 2.0 | |
| Ethambutol (EMB) | 2.5 | British Columbia uses an MIC of 4.0 mg/L. |
| Streptomycin (SM) | 2.0 | Routine testing is not performed for isolates from Quebec, Nova Scotia, New Brunswick, Prince Edward Island. |
| Pyrazinamide (PZA) | 100.0 | Routine testing is not performed for isolates from British Columbia, Saskatchewan and the Yukon Territory. |
In 2003, a total of nine laboratories participated in the proficiency for anti-microbial susceptibility testing of M. tuberculosis to anti-tuberculous first line drugs conducted by the National Reference Centre for Mycobacteriology. Six strains of M. tuberculosis were submitted for testing. Participant results are presented in Appendix 2.
Results
Of the 1,379 isolates in 2003 included for analysis, 173 (12.5%) were resistant to one or more first-line anti-tuberculous drug(s). Resistance to INH was the most common type of drug resistance (9.3%). Twenty isolates (1.5%) were multi-drug resistant tuberculosis (MDR-TB) strains (defined as resistance to at least INH and RMP), of which seven isolates demonstrated resistance to four or five first-line anti-tuberculous drugs tested. Reporting of MDR-TB isolates was from British Columbia, Alberta, Manitoba, Ontario and Quebec. Five provinces and territories (Yukon Territory, Northwest Territories, Nunavut, Nova Scotia and Prince Edward Island,) reported that all isolates tested were susceptible to all the first-line anti-tuberculous drugs.
Demographic information on the individual patients from whom the isolates originated is limited in this laboratory-based surveillance system. Of the 1,354 isolates for which the year of birth and sex reporting was complete, 37% were between the ages 25 and 44. Males accounted for 53% of all the isolates and 57% of the drug resistant isolates.
Discussion
The number of reported TB isolates in 2003 was relatively unchanged from the previous year (1,420 in 2002 to 1379 in 2003 isolates). In addition, the percentage of isolates demonstrating any type of drug resistance was also unchanged between the two reporting years (12.6% in 2002 to 12.5% in 2003) and the proportion of isolates classified as MDR-TB was identical (1.5%) in both years. Overall, levels of TB drug resistance have shown no significant difference since the inception of this reporting system in 1998.
Over 75% of the reported laboratory TB isolates in Canada in 2003 originated from three provinces. Ontario, Quebec and British Columbia have consistently reported the majority of isolates and MDR-TB in the six years of data collection. Since the initiation of this laboratory-based surveillance system Saskatchewan, the Atlantic Provinces, the Yukon and Northwest Territories have not reported any MDR-TB isolates.
The results observed to date in this surveillance system are consistent with international data. In the latest report of the global TB drug resistance surveillance project jointly conducted by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD), the median prevalence of TB drug resistance among the participating countries was 1.1% for new cases and 7% for previously treated cases (as compared with 12.5% overall in Canada). The median prevalence of MDR-TB was 10.2% for new cases and 18.4% for previously treated cases (as compared with 1.5% overall in Canada).1
Limitations
Sensitivity testing for first-line anti-TB drugs is not uniform across the country. Therefore, there are limitations in interpreting the data, particularly the percentage of isolates that are resistant to SM and PZA.
More epidemiological information on the TB cases from which the isolates were submitted would be desirable to critically examine drug resistance patterns in Canada. Demographic information is sparse; only sex and year of birth are routinely reported in this surveillance system. As well, no differentiation can be made between primary and secondary/acquired drug resistance from the data.
Conclusions
With growing worldwide concern regarding TB drug resistance, this surveillance system is vital in providing the necessary data in a timely fashion to monitor trends in TB drug resistance in Canada. The surveillance data collected to date indicate that the prevalence of TB drug resistance in this country is similar to that in the overall global situation.
Reference
- The WHO/IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance (1999-2002). Anti-tuberculosis drug resistance in the world. Report No. 3. (WHO/CDS/TB/2000.278). Geneva: World Health Organization, 2004.
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For more information, copies of this report or other reports, please contact:
Tuberculosis Prevention and Control
Centre for Infectious Disease Prevention and Control
Public Health Agency of Canada
Room 3439, Building 6
Tunney's Pasture, Ottawa, Ontario K1A 0L2
Internal Postal Address: 0603B
Telephone: (613) 941-0238
Facsimile: (613) 946-3902
The following text, figures and tables were prepared by:
Edward Ellis, MD, MPH, FRCPC |
Melissa Phypers, MSc |
Louise Sauvé |
Merrilyn Allegakone |
Tuberculosis Prevention and Control would like to acknowledge the members of the Canadian Tuberculosis Laboratory Technical Network and their teams for their contribution to and their participation in the Canadian Tuberculosis Laboratory Surveillance System (CTBLSS).
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