Tuberculosis: Drug resistance in Canada - 2005

Reported susceptibility results of the Canadian Tuberculosis Laboratory Surveillance System

Table Of Contents

• Introduction
• Methods
• Results
• Discussion
• Limitations
• Conclusions
• Reference

Figures
	Figure 1.	Reported TB drug resistance in Canada by province/territory - 2005
	Figure 2.	Reported Mycobacterium tuberculosis isolates in Canada by province/territory - 2005
	Figure 3.	Overall pattern of reported TB drug resistance in Canada - 2005
	Figure 4.	Reported TB drug resistance in Canada by type of drug - 2005
	Figure 5.	Any resistance by type of drug in Canada - 1998-2005
	Figure 6.	Any resistance by type of drug in Canada as a proportion of the number of isolates tested - 1998-2005.
	Figure 7.	Overall pattern of reported TB drug resistance in Canada - 1998-2005
	Figure 8.	Overall pattern of reported TB drug resistance in Canada as a proportion of isolates tested - 1998-2005.
Tables
	Table 1.	Overall pattern of reported TB drug resistance in Canada - 1998-2005
	Table 2.	Reported Mycobacterium tuberculosis isolates by "reporting" and "originating" province/territory, Canada - 2005
	Table 3.	Reported MDR-TB isolates by province/territory, Canada - 2005
	Table 4.	Reported TB drug resistance by gender and age group, Canada - 2005
	Table 5.	. Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Alberta - 1998-2005
	Table 6.	Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, British Columbia – 1998-2005
	Table 7.	Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Manitoba – 1998-2005
	Table 8.	Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, New Brunswick – 1998-2005
	Table 9.	Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Newfoundland and Labrador – 1998-2005
	Table 10.	. Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Northwest Territories – 1998-2005
	Table 11.	Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Nova Scotia – 1998-2005
	Table 12.	Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Nunavut – 1998-2005
	Table 13.	Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Ontario – 1998-2005
	Table 14.	. Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Prince Edward Island – 1998-2005
	Table 15.	Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Quebec – 1998-2005
	Table 16.	Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Saskatchewan – 1998-2005
	Table 17.	Reported results for routine drug susceptibility testing of Mycobacterium tuberculosis isolates, Yukon – 1998-2005
Appendices
	Appendix 1 -	Participating Laboratories of the Canadian Tuberculosis Laboratory Surveillance System (CTBLSS)
	Appendix 2 -	M. tuberculosis Complex Antimicrobial Susceptibility Reporting Form
	Appendix 3 -	Proficiency panel results for anti-microbial susceptibility testing of Mycobacterium tuberculosis 2005

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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.

Laboratories report annually to TBPC the results of anti-tuberculosis drug susceptibility testing for every patient for whom a specimen or an isolate is received within the calendar year. TBPC subsequently produces this annual report.

Methods

TBPC maintains a database containing drug susceptibility test results of Mycobacterium tuberculosis (MTB) and other tuberculosis species as well as MTB complex (MTBC) isolates as laboratories report identification of isolates either at the complex level (MTBC)or at the species level. 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 were not uniformly reported from the provinces/territories and are not included in this report. Streptomycin was reclassified in 2005 as a second line TB drug in Canada; however it will continue to appear in the report to maintain historical continuity.

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 specimen originated, province/territory where the tests were performed, and susceptibility results. TBPC, in collaboration with the provinces/territories 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.

Some provinces perform drug testing for other provinces/territories. British Columbia tests British Columbia and Yukon isolates; Alberta tests Alberta and Northwest Territories isolates; and Nova Scotia tests isolates for Nova Scotia and Prince Edward Island. Both Ontario and Alberta test isolates for Nunavut. Cross validation with both Ontario and Alberta is performed to ensure that the results for the Nunavut isolates are not being reported twice.

Laboratories perform routine susceptibility testing of MTB or MTBC to first-line antituberculous drugs using either the radiometric proportion method Bactec ® 460 or MGIT ® 960. New Brunswick, Nova Scotia and Saskatchewan used MGIT ® 960; Newfoundland and Labrador used a combination of both. All other provinces/territories used Bactec ® 460. Table A lists the first-line anti-tuberculosis drugs and the critical concentrations in mg/L used by the participating laboratories. 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 2005 are reported in Table 1, and Tables 5-17.

Table A: Critical concentrations for routine testing of anti-tuberculosis drugs
Anti-TB drugs	Critical Concentrations* (mg/L)		Comments
	Bactec 460	MGIT 960
Isoniazid (INH)	0,1	0,1	When resistance to INH is found at the critical concentration, tests are repeated with INH 0.4mg/L to determine the level of resistance.
Rifampin (RMP)	2,0	1,0
Ethambutol (EMB)	2,5	5,0	British Columbia uses a CC of 4.0 mg/L.
Pyrazinamide (PZA)	100,0	100,0	Routine testing is not performed for isolates from British Columbia, Saskatchewan and the Yukon Territory.
Streptomycin (SM)	2,0	2,0	Routine testing is not performed for isolates from New Brunswick, Nova Scotia, Prince Edward Island and Quebec.
* Critical concentrations: the lowest concentration of drug that will inhibit 95% of wild strains of MTB that have never been exposed to drugs while at the same time not inhibiting strains of MTB that have been isolated from patients who are not responding to therapy, and that are considered resistant.

As noted in Table A, the number and specific anti-tuberculous drugs that are subject to routine susceptibility testing differ among the provinces and territories. Accordingly, the number of isolates drugs included in the descriptive analyses varies.

In 2005, a total of 10 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 Laboratory in Winnipeg. Participant results are presented in Appendix 3.

This report presents drug susceptibility data for TB isolates tested in 2005 and adjusted results for 2004 isolates (to reflect duplicate removal and late reporting) across Canada as of May 2006.

Results

Of the 1,308 isolates in 2005 included for analysis, 163 (12.5%) were resistant to at least one of the antituberculosis drugs: INH, RMP, EMB, PZA or SM. For Canada as a whole, INH resistance was 8.3%. Twenty-one isolates (1.6%) were multidrug-resistant (MDR- TB) strains (defined as resistance to at least INH and RMP). Twelve isolates demonstrated resistance to more than three of the five anti-tuberculous drugs tested. MDR-TB isolates were reported from Alberta, British Columbia, Ontario and Quebec. Of the 1,062 isolates tested for resistance to SM, 77 (7.3%) were resistant.

The Northwest Territories, Nunavut, Prince Edward Island and Yukon Territory reported that all isolates tested were susceptible to all the anti-tuberculous drugs.

Demographic information on the individual patients from whom the isolates originated is limited in this laboratory-based surveillance system. Of the 1,296 isolates for which the age at time of testing and/or sex reporting was complete, 37% were between the ages 25 and 44 and males accounted for 55% of all the isolates and 57% of the drug resistant isolates.

Discussion 

The number of reported TB isolates in 2005 was slightly lower than for the previous year (1,381 isolates in 2004 compared to 1,308 in 2005). The percentage of isolates demonstrating any type of drug resistance was 12.5%, equal to the value reported in 2004. The proportion of isolates classified as MDR-TB increased from 0.9% in 2004 to 1.6% in 2005. Although the reported increase in MDR-TB from 2004 is of some concern it is comparable to the average reported over the past 5 years (1.2%).

Seventy-three percent of the reported laboratory TB isolates in Canada in 2005 originated from three provinces. British Columbia, Ontario and Quebec have consistently reported the majority of isolates and MDR-TB in the eight years of data collection. Since the initiation of this laboratory-based surveillance system the Atlantic Provinces, the Northwest Territories, Saskatchewan, and the Yukon 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) ¹ , 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 12.5% 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 1.6% overall in Canada)^*. ¹

“Extensively drug-resistant TB” (XDR-TB) refers to TB isolates resistant to INH and RMP and at least three of the six main classes of second-line drugs (aminoglycosides, polypeptides, fluoroquinolones, thioamides, cycloserine, and para -aminosalicylic acid). XDR-TB carries a worse prognosis than MDR-TB and accordingly, the Morbidity and Mortality Weekly Report for March 24, 2006 stated that XDR-TB is emerging as a worldwide threat to public health and TB control, raising concerns of a future epidemic of virtually untreatable TB. ²

For 2005, only reports of resistance testing for first-line TB drugs along with streptomycin were routinely reported to the Public Health Agency of Canada. Discussions are underway with the provincial/territorial laboratories regarding second line drug resistance reporting to begin with the Tuberculosis Drug Resistance in Canada 2006 report.

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 examine more critically drug resistance patterns in Canada. However, this information is difficult to collect as isolates are often submitted to the laboratories with only the sex and year of birth of the case. As well, no differentiation can be made between primary and secondary/acquired drug resistance from the data. The annual Tuberculosis in Canada report 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 presence of TB drug resistance in this country is similar to the global average.

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 GroupMeeting. France 16, October 2005.
2. Emergence of Mycobacterium tuberculosis with Extensive Resistance to Second-Line Drugs - Worldwide, 2000-2004. Morbidity and Mortality Weekly. 2006; 55 (10): 301-305.

* Unlike IULTD that provides the prevalence of TB drug resistance for both new and retreated cases, TBPC only reports prevalence overall as isolates are not separated into new and retreated.

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Tuberculosis: Drug resistance in Canada, 2005 Reported susceptibility results of the Canadian Tuberculosis Laboratory Surveillance System 26 pages (368 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
100 Eglantine Driveway, Health Canada Building
A.L. 0603B, Tunney's Pasture
Ottawa, ON K1A 0K9

Internal Postal Address: 0603B
Telephone:    (613) 941-0238
Facsimile:    (613) 946-3902
EMAIL: TB.1@phac-aspc.gc.ca

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

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© Her Majesty the Queen in Right of Canada, 2006.

Cat. HP37-4/2005 ISBN 0-662-49315-X

Cat. HP37-4/2005E-PDF ISBN 0-662-43627-X