Tuberculosis: Drug resistance in Canada, 2002

Reported susceptibility results of the Canadian Tuberculosis Laboratory Surveillance System

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TABLE OF CONTENTS

INTRODUCTION
METHODOLOGY
RESULTS
DISCUSSION
LIMITATIONS
CONCLUSIONS
REFERENCE
FIGURES
Figure 1.	Reported TB drug resistance in Canada by province/territory – 2002
Figure 2.	Reported MTB isolates in Canada by province/territory – 2002
Figure 3.	Overall pattern of reported TB drug resistance in Canada – 2002
Figure 4.	Reported TB drug resistance in Canada by type of drug - 2002
Figure 5.	Any resistance to first-line anti-TB drugs in Canada – 1998-2002
Figure 6.	Overall pattern of reported TB drug resistance in Canada – 1998-2002
TABLES
Table A.	Minimal inhibitory concentrations for routine testing of first-line anti-tuberculosis drugs
Table B.	Proficiency panel results for anti-microbial susceptibility testing of M. tuberculosis to first-line drugs
Table 1.	Overall pattern of reported TB drug resistance in Canada – 1998-2002
Table 2.	Reported MTB isolates by “reporting” and “originating” province/territory, Canada – 2002
Table 3.	Reported MDR-TB isolates by province/territory, Canada – 2002
Table 4.	Reported TB drug resistance by gender and age group, Canada – 2002
Table 5.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Alberta – 1998-2002
Table 6.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, British Columbia – 1998-2002
Table 7.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Manitoba – 1998-2002
Table 8.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, New Brunswick – 1998-2002
Table 9.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Newfoundland and Labrador  – 1998-2002
Table 10.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Northwest Territories – 1998-2002
Table 11.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Nova Scotia – 1998-2002
Table 12.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Nunavut – 1998-2002
Table 13.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Ontario – 1998-2002
Table 14.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Prince Edward Island – 1998-2002
Table 15.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Québec – 1998-2002
Table 16.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Saskatchewan – 1998-2002
Table 17.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Yukon Territory – 1998-2002
APPENDICES
Appendix 1 -	Participating Laboratories of the Canadian Tuberculosis Laboratory Surveillance System (CTBLSS)
Appendix 2 -	M. tuberculosis Complex Antimicrobial Susceptibility Reporting Form

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INTRODUCTION

Tuberculosis Prevention and Control (TBPC) at the Centre for Infectious Disease Prevention and Control, Health Canada, 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 1), 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 2002 and adjusted 2001, 2000 and 1999 (to reflect duplicate removal and late reporting) drug susceptibility data for TB isolates across Canada as of February 28, 2003. 

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. Data are collected either through manual completion of a standard reporting form (Appendix 2) 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 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, Northwest Territories and some Nunavut isolates; Quebec: Quebec, New Brunswick, Northwest Territories and some Nunavut isolates; Ontario: Ontario and some 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 Bactec^® 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. Results of susceptibility testing for second-line anti-tuberculous drugs are not included in this report. 

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. 

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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 and Nunavut isolates tested in Quebec.
Pyrazinamide (PZA)	100.0	Routine testing is not performed for isolates from British Columbia, Saskatchewan and the Yukon Territory.

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In 2002, 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. Three strains of M. tuberculosis were submitted for testing. Participant results are presented in Table B.

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Table B: Proficiency panel results for anti-microbial susceptibility testing  of M. tuberculosis to first-line drugs1
Antibiotic	Strain D (201-221)	Strain K (237-260)	Strain M (266-284)
SM 2 µg/mL	Sensitive 6/6 (100% consensus)	Sensitive 6/6 (100% consensus)	Sensitive 6/6 (100% consensus)
INH 0.1 µg/mL	Sensitive 9/9 (100% consensus)	Sensitive 9/9 (100% consensus)	Sensitive 9/9 (100% consensus)
RMP 2.0 µg/mL	Sensitive 9/9 (100% consensus)	Sensitive 9/9 (100% consensus)	Sensitive 9/9 (100% consensus)
EMB 2.5 µg/mL	Sensitive 9/9 (100% consensus)	Resistant 9/9 (100% consensus)	Sensitive 9/9 (100% consensus)
PZA 100 µg/mL	Sensitive 6/7 (85.7% consensus)	Sensitive 7/7 (100% consensus)	Resistant 8/8 (100% consensus)
1    Eight laboratories used the BACTEC® TB 460 as their test method. One laboratory used the MGIT 960 as its test method.  SM: Six laboratories included results for streptomycin. Current National Committee for Clinical Laboratory Standards (NCCLS) guidelines no longer recommend that streptomycin be tested as a first-line anti-tuberculous agent.  INH: No resistant strain was included in the 2002 panel. Current NCCLS guidelines recommend testing a higher concentration of INH for strains resistant to the critical concentration of INH.  EMB: All laboratories using the BACTEC® TB 460 tested EMB at 2.5 µg/mL. The laboratory using the MGIT 960 tested EMB at 5.0 µg/mL, the manufacturer's recommended critical concentration. Two laboratories also tested EMB at the higher concentration of 7.5 µg/mL. The 2002 panel included a rare strain showing mono-resistance to EMB. Madison et al. reported that EMB resistance was coupled with INH resistance in 96.6% of strains and recommend that EMB mono-resistance based on BACTEC® 460TB results be confirmed with another NCCLS method (Madison et al. J Clin Microbiol 2000;40:3976-3979). Current NCCLS guidelines recommend confirmation of resistance by agar proportion or repeat testing following the manufacturer's instructions concerning EMB testing.  PZA: All laboratories correctly identified PZA resistance. One laboratory reported a sensitive strain as showing low level resistance and indicated that the strain would be referred to the reference laboratory.

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RESULTS

Of the 1,385 isolates in 2002 included for analysis, 172 (12.7%) were resistant to one or more first-line anti-tuberculous drug(s). Resistance to INH was the most common type of drug resistance (8.2%). Twenty-two isolates (1.5%) were multi-drug resistant tuberculosis (MDR- TB) strains (defined as resistance to at least INH and RMP), of which 15 isolates demonstrated resistance to four or five first-line anti-tuberculous drugs tested. Reporting of these isolates was from Ontario, Manitoba and British Columbia. In addition, Alberta, British Columbia, Manitoba, Ontario and Quebec reported isolates with other patterns of multi-drug resistance. Five provinces and territories (Nunavut, Northwest Territories, Yukon, Newfoundland and Labrador 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 1,323 isolates for which the year of birth reporting was complete, 40% were between the ages 25 and 44. Males accounted for 53% of all the isolates and 49% of the drug resistant isolates. 

DISCUSSION

The number of reported TB isolates in 2002 decreased by 8.3% from the previous year (1,475 to 1,385 isolates). However, the percentage of isolates demonstrating any type of drug resistance increased from 10% in 2001 to 12.7% in 2002 and the proportion of isolates classified as MDR-TB increased slightly from 1.0% in 2001 to 1.5% in 2002. 

Over 90% of the reported laboratory TB isolates in Canada in 2002 originated from five provinces. The three largest provinces (Ontario, Quebec and British Columbia) have consistently reported the majority of isolates and MDR-TB in the five years of data collection. Since the initiation of this laboratory-based surveillance system, which began January 1, 1998, 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 overall TB drug resistance among the participating countries was 11.1 % (as compared with 12.7 % for Canada) and the median prevalence of MDR-TB was 1.8%¹ (as compared with 1.5% for Canada). 

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. Analysis reveals a slight increase in the reporting of MDR-TB for the latest reporting year; however, several more years of data will be required to determine whether this is a trend. 

REFERENCE

 1.    The WHO/IUATLD Global Project on Anti-tuberculous Drug Resistance Surveillance. Anti-tuberculous drug resistance in the world. Report No. 2. (WHO/CDS/TB/2000.278). Geneva: World Health Organization, 2000. 

Tuberculosis: Drug resistance in Canada, 2002 Reported susceptibility results of the Canadian Tuberculosis Laboratory Surveillance System (220 KB) in PDF Format

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HOW TO REACH US

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 Health Canada Room 0108 B, Brooke Claxton Building Tunney's Pasture, Ottawa, Ontario K1A 0K9 

    Internal Postal Address: 0900B-1 

    Telephone:    (613) 941-0238 Facsimile:    (613) 946-3902
 

This report can also be accessed on the internet at: 

    http://www.hc-sc.gc.ca/hpb/lcdc
 

The following text, figures and tables were prepared by: 

Edward Ellis, MD, MPH, FRCPC Chief Tuberculosis Prevention and Control	Melissa Phypers, MSc Senior Epidemiologist Tuberculosis Prevention and Control
Adam Medaglia, BSM Surveillance Officer Tuberculosis Prevention and Control	Chris Sheardown, BA Tuberclosis Database Manager Tuberculosis Prevention and Control

ACKNOWLEDGEMENT

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). 

Published by authority of the Minister of Health 

©    Her Majesty the Queen in Right of Canada, represented by the Minister of Public Works and Government Services Canada, 2003. 

Cat. H49-110/2002
ISBN 0-662-67307-7 

This publication can be made available in alternative formats.