Tuberculosis: Drug resistance in Canada - 2004

Reported susceptibility results of the Canadian Tuberculosis Laboratory Surveillance System

Mission :
To promote and protect the health of Canadians through leadership, partnership, innovation and action in public health.

Table Of Contents

Introduction Methodology Results Discussion Limitations Conclusions Reference
Figures
	Figure 1.	Reported TB drug resistance in Canada by province/territory - 2004
	Figure 2.	Reported MTB isolates in Canada by province/territory - 2004
	Figure 3.	Overall pattern of reported TB drug resistance in Canada - 2004
	Figure 4.	Reported TB drug resistance in Canada by type of drug - 2004
	Figure 5.	Any resistance to first-line anti-TB drugs in Canada - 1998-2004
	Figure 6.	Overall pattern of reported TB drug resistance in Canada - 1998-2004
Tables
	Table A.	Minimal inhibitory concentrations for routine testing of first-line anti-tuberculosis drugs
	Table 1.	Overall pattern of reported TB drug resistance in Canada - 1998-2004
	Table 2.	Reported MTB isolates by "reporting" and "originating" province/territory, Canada - 2004
	Table 3.	Reported MDR-TB isolates by province/territory, Canada - 2004
	Table 4.	Reported TB drug resistance by gender and age group, Canada - 2004
	Table 5.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Alberta - 1998-2004
	Table 6.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, British Columbia - 1998-2004
	Table 7.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Manitoba - 1998-2004
	Table 8.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, New Brunswick - 1998-2004
	Table 9.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Newfoundland and Labrador - 1998-2004
	Table 10.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Northwest Territories - 1998-2004
	Table 11.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Nova Scotia - 1998-2004
	Table 12.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Nunavut - 1998-2004
	Table 13.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Ontario - 1998-2004
	Table 14.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Prince Edward Island - 1998-2004
	Table 15.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Québec - 1998-2004
	Table 16.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Saskatchewan - 1998-2004
	Table 17.	Reported results for routine drug susceptibility testing of MTB isolates to first-line anti-tuberculosis drugs, Yukon Territory - 1998-2004
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

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Introduction

Tuberculosis Prevention and Control (TBPC) at the Centre for Infectious Disease Prevention and Control, Public Health Agency of 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.

For each calendar year, laboratories report results of anti-tuberculosis drug susceptibility testing to TBPC for every patient for whom they receive a specimen or an isolate. TBPC subsequently produces this annual report.

Methods

TBPC maintains a computerized database containing drug susceptibility test results of Mycobacterium tuberculosis (MTB) and MTB complex (MTBC) isolates. Isolates identified as Mycobacterium bovis BCG are included in the CTBLSS but are excluded from this report. M. bovis (BCG) is intrinsically resistant to pyrazinamide (PZA) and the identity of the majority of isolates of M. bovis (BCG) can be inferred from the history of recent vaccination. Results of susceptibility testing for second-line anti-tuberculosis drugs, although reported, are also not included in 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 and Labrador identifies the species and tests all isolates for drug resistance in Newfoundland and Labrador. 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; 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 antituberculosis drugs and the concentrations in mg/L used by the participating laboratories.

For this and subsequent annual reports a modification in the method used to calculate the proportion of isolates susceptible to each drug has been made. As not all isolates were tested for resistance to all drugs, the proportion of isolates showing monoresistance is expressed as the number of isolates resistant to the drug over the total number of isolates tested for sensitivity to that particular drug. An adjustment based on this method has been made to all data starting from 1998. These proportions for 1998 through 2004 are reported in Table 1, and Tables 5–17.

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.
Pyrazinamide (PZA)	100.0	Routine testing is not performed for isolates from British Columbia, Saskatchewan and the Yukon Territory.
Streptomycin (SM)	2.0	Routine testing is not performed for isolates from Quebec, Nova Scotia, New Brunswick, Prince Edward Island.

In 2004, a total of ten laboratories participated in the proficiency for anti-microbial susceptibility testing of M. tuberculosis to isoniazid (INH), rifampin (RMP), ethambutol (EMB), pyrazinamide (PZA) and streptomycin (SM) conducted by the National Reference Centre for Mycobacteriology, National Microbiology Laboratories in Winnipeg. Six strains of M. tuberculosis were submitted for testing. Participant results are presented in Appendix 3.

This report presents 2004 and adjusted 2003 (to reflect duplicate removal and late reporting) drug susceptibility data for TB isolates across Canada as of December 2005.

Results

Of the 1,358 isolates in 2004 included for analysis, 168 (12.4%) were resistant to at least one of the following: INH, RMP, EMB, PZA or SM. Resistance to SM was the most common type of drug resistance (7.8%). The Ontario isolates showed a significant jump in SM resistance from the previous years (2.9% to 6.2%). For Canada as a whole, INH resistance was 7.4%. Twelve isolates (0.9%) were multi-drug resistant (MDR- TB) strains (defined as resistance to at least INH and RMP). Four isolates demonstrated resistance to more than three of the five anti-tuberculous drugs tested.

MDR-TB isolates were reported from Ontario, British Columbia, Alberta and Quebec. The Yukon Territory, Northwest Territories, Nunavut, Nova Scotia, Prince Edward Island, and Newfoundland and Labrador 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 limited in this laboratory-based surveillance system. Of the 1,307 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 53% of the drug resistant isolates.

Discussion 

The number of reported TB isolates in 2004 was relatively unchanged from the previous year (1,379 isolates in 2003 to 1,358 in 2004). In addition, the percentage of isolates demonstrating any type of drug resistance was also unchanged between the two reporting years (12.5% in 2003 to 12.4% in 2004). However, the proportion of isolates classified as MDR-TB was below that of the previous years (1.5% in 2003 and 0.9% in 2004). Although the drop in MDR-TB is encouraging, the overall, levels of TB drug resistance have shown no significant difference since the inception of this reporting system in 1998.

Seventy-eight percent of the reported laboratory TB isolates in Canada in 2004 originated from three provinces. Ontario, Quebec and British Columbia have consistently reported the majority of isolates and MDR-TB in the seven 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 10.5 (Range 0.0–57.1%) for new cases and 22.7% (Range 0.0–82.1%) for previously treated cases (as compared with 12.2% overall in Canada). The median prevalence of MDR-TB was 1.2% (Range 0.0–14.2%) for new cases and 7.6% (Range 0.0–58.3%) for previously treated cases (as compared with 0.9% 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. However, this is difficult to collect as isolates often come to the lab with only sex and year of birth. As well, no differentiation can be made between primary and secondary/acquired drug resistance from the data. The annual Tuberculosis in Canada report (http://www.publichealth.gc.ca/tuberculosis) includes additional drug resistance data for each reported TB case.

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.

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Reference

1. The WHO/IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance. Anti- TB drug resistance in the world History, Coverage, Issues, Future. Joint Working Group meeting HIV and drug resistance surveillance and testing. Versailles, France 16, October 2005.

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Tuberculosis: Drug resistance in Canada, 2004 Reported susceptibility results of the Canadian Tuberculosis Laboratory Surveillance System (1,238 KB) in PDF Format

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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
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 Manager Tuberculosis Prevention and Control	Derek Scholten, MSc A/Senior Epidemiologist Tuberculosis Prevention and Control
	Victor Gallant, MA Tuberculosis Database Manager Tuberculosis Prevention and Control	Mindy Miron Surveillance Officer Tuberculosis Prevention and Control

Acknowledgments

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).