Special Report of the Canadian Tuberculosis Committee

Drug Resistant Tuberculosis Among the Foreign-born in Canada

Background

The emergence of drug resistant strains of tuberculosis (TB) is a global threat to tuberculosis prevention and control efforts. In a study conducted by the World Health Organization (WHO) and the International Union against Tuberculosis and Lung Disease (IUATLD), strains of TB resistant to first line anti-TB drugs were found in 74 of 77 countries surveyed. The WHO estimates that 300,000 individuals are infected with strains of drug resistant TB each year.¹

Through the Canadian Tuberculosis Reporting System (CTBRS), Tuberculosis Prevention and Control (TBPC), Public Health Agency of Canada collects information on all new and relapsed cases of TB disease diagnosed in Canada. Included in the CTBRS is information on country of birth (origin) and primary and secondary (acquired) resistance to first-line anti-tuberculous drugs. Since the collection of the data variable “origin” began in 1970, (Canadian-born Aboriginal, Canadian-born non-Aboriginal and foreign-born), a steady increase in the proportion of reported TB cases among the foreign-born population has been noted. Currently, over 65% of all TB disease in Canada occurs among the foreign-born and drug resistance is significantly more prevalent among this population group. All previous Canadian studies have noted foreign birth to be a significant factor associated with drug resistance.^2-8

The purpose of this report is quantify the burden of primary and acquired drug resistant TB among the foreign-born in Canada and to identify trends in primary drug resistance based on country of origin, year of arrival in Canada, year of diagnosis and immigration status.

Methods

TB case data reported to the CTBRS from 1992*-2002 were examined. The reporting system is designed to capture information on every new active or relapsed^† case of TB diagnosed in Canada in all provinces and territories. Cases within the CTBRS meet the Canadian Tuberculosis Standards case definition.⁹ The case report collects information on selected characteristics including country of birth, the year of arrival in Canada and immigration status at the time of diagnosis.

Annual population estimates by origin, including estimates for specific age and sex groups, were obtained from Statistics Canada.

Primary drug resistance applies to previously untreated patients who are found to have drug- resistant organisms, presumably because they have been infected from an outside source of resistant Mycobacterium tuberculosis. Acquired (or secondary) drug resistance applies to patients who initially have drug-susceptible bacteria that become drug-resistant due to inadequate, inappropriate, or irregular treatment or, more importantly, because of non-adherence in drug taking.

* 1992 represents the year the primary drug resistance was first reliably reported to the CTBRS. Secondary drug resistance reporting began in 1997.

† Relapsed (reactivated) case refers to cases with documented evidence (in Canada) or history of previously active tuberculosis that became inactive.

Results

Overall trends in primary drug resistance

From 1992-2002, 11% of all foreign-born cases were resistant to one or more first line anti- tuberculosis drugs and foreign-born cases were three times more likely to be drug resistant than are Canadian born non-aboriginal cases. While multiple drug resistant TB (MDR-TB) cases, which is defined as resistance to at least isoniazid and rifampin, account for only 1% (1.6% in 2002) of all cases in Canada, foreign-born cases were six times more likely to be MDR. Resistance to isoniazid (INH) was by far the most frequently reported and was present in 34% of all drug resistant cases. Patterns of drug resistance over time have shown no significant changes, with the exception of a slight increase in MDR-TB in the last reporting year.

Country of origin

Individuals from ten countries accounted for over 75% of all drug resistance reported. The top three countries reporting primary drug resistance included Viet Nam, the Philippines and the People’s Republic of China (Table SR-1).

Table SR-1
Distribution of foreign-born primary drug-resistant tuberculosis cases by country of origin, 1992–2002, Canada

Figure SR-1 Trends in drug resistance reporting among the foreign-born, 1992-2002

Time since arrival in Canada

The majority of drug resistant cases were reported among the recently arrived (five years or less in Canada). This corresponds to the reporting trend of the majority of all cases of TB among the foreign-born being diagnosed in those individuals recently arrived to Canada (Figure SR-2).

Age, sex and reporting province/territory

Over 90% of the foreign-born drug resistant TB cases reported to this system originated from four provinces: Alberta, British Columbia, Ontario and Quebec (Figure SR-3).

The distribution by age and sex for drug resistant cases was equal for males and females. 53% of drug resistant cases were male with a median age of 37 years. Female cases accounted for 47% of the drug resistance reported with a median age of 35 years (Figure SR-4).

Treatment outcomes

Treatment outcomes for drug resistant cases with respect to cure and treatment completion were slightly less favourable as compared to non-resistant cases (71%; 80% cure or treatment completed respectively). Death as a result of TB (TB was the underlying cause of death or TB contributed to death) was similar between those with non-resistant strains of the disease as to those with reported drug resistance (7% versus 8%).

Figure SR-2 Proportion of all drug resistance by year of diagnosis and time since arrival in Canada

Figure SR-3 Primary drug resistance reporting - Alberta, British Columbia, Ontario and Quebec, 1992-2002

Figure SR-4 Foreign-born TB cases by age and sex, 1992-2002

Primary drug resistance and HIV

Primary drug resistance was reported in only eight HIV-positive TB cases. Only two cases of treatment acquired drug resistance among HIV-positive individuals were reported to this system for the years 1997-2002.

Acquired drug resistance

Resistance acquired during treatment was infrequent. From 1997-2002, 58 cases of secondary drug resistance were reported (less than one percent of all cases). The most common treatment acquired resistance was resistance to INH, accounting for 69% of all secondary resistance. Developing resistance during treatment to more than one drug was exceedingly rare. Only 19 individuals developed resistance to two drugs, eight to three drugs and five individuals developed resistance to four first-line tuberculous drugs.

Discussion

In the latest report of the global TB drug resistance surveillance project jointly conducted by the World Health Organization (WHO) and the IUATLD, the median prevalence of overall TB drug resistance for new cases among the participating countries was 10.2% and the median prevalence of MDR-TB was 1.1%.¹ Within this report countries with high prevalence of both primary and secondary drug resistance are listed with the highest prevalence of primary drug resistance and MDR in drug sensitivity reporting from Kazakhstan.¹ Further international studies indicate a higher incidence of drug resistant TB in males, those previously treated for TB and age greater than 65 years.^10,11

Determining the incidence of TB-HIV co-infection and its impact on drug resistant TB from the CTBRS is not yet possible. From 1997-2002, HIV status was reported for an average of only 10% of foreign-born cases. The importance of screening and reporting of HIV status for all TB cases cannot be overemphasized. These practices are essential for prevention and control of future TB cases in Canada.

The results observed to date in this surveillance system are for the most part, consistent with previous national data and with international data with respect to drug resistance trends. Additional national data on TB drug resistance are available through the TB Drug Resistance in Canada series, which reports drug sensitivity results for individual TB isolates. This series provides timely annual information on emerging drug resistance trends, but contains little epidemiological information. Although not an exact match to case data the results of TB Drug Resistance in Canada are consistent with this report in the overall prevalence of primary drug resistance.¹²

Foreign birth was a significant predictor of drug resistance. Although the rate of MDR-TB has increased slightly since 2001, this is not a cause for alarm, as the rate remains under 2%. Close monitoring of this upward trend is important; but several more years of collected data will be necessary to examine the unfolding trend of TB drug resistance in Canada. The presence of any level of drug resistance demonstrates the need for adequate and appropriate treatment of all cases.

Members: Dr. V. Hoeppner (Chair); Dr. M Baikie; Dr. C Balram; Ms. C. Case; Dr. E. Ellis (Executive Secretary); Dr. R.K. Elwood (Past Chair); Ms. E. Randall; Dr. B. Graham; Dr. S Martin; Ms. C. Helmsley; Dr. E.S. Hershfield; Dr. A. Kabani; Dr. B. Kawa; Dr. M. Lem; Dr. R. Long; Dr. F. Stratton; Dr. L. Sweet; Dr. T.N. Tannenbaum.

This report was prepared by Ms. Melissa Phypers, Senior Epidemiologist, Tuberculosis Prevention and Control, Public Health Agency of Canada

References

1. World Health Organization. Anti-tuberculosis drug resistance in the world. Report No. 3. The WHO/IUATLD project on anti-tuberculosis drug resistance surveillance. Available at: www.who.int.gtb/publications/drugresistance/2004/drs_report_exec.pdf.  

2. Rivest P, Tannenbaum T, Bedard L. Epidemiology of tuberculosis in Montreal. CMAJ 1998;158(5):605-609.

3. Remis R, Jamieson F, Chedore P, et al. Increasing drug resistance of Mycobacterium tuberculosis isolates in Ontario, 1987-1997. Clin Infect Dis 2000; 31(2):427-432.  

4. Long R, Manfreda J, Mendella L, et al. Antituberculosis drug resistance in Manitoba from 1980-1989. CMAJ 1993; 148(9):1489-1495.  

5. Manns BJ, Fanning EA, Cowie RL. Antituberculosis drug resistance in immigrants to Alberta, Canada, with tuberculosis, 1982-1994. Int J Tuberc Lung Dis 1997; 1(3):225-230.  

6. Long R, Fanning EA, Cowie RL, et al. Antituberculosis drug resistance in Western Canada (1993 to 1994). Can Respir J 1997; 4(2):71-75.  

7. Hersi A, Elwood K, Cowie R, Kunimoto D, Long R. Multidrug-resistant tuberculosis in Alberta and British Columbia, 1989 to 1998. Can Respir J 1999; 6(2):155-160.  

8. Long R, Chui L, Kakulphimp J, Zielinski M, Talbot J, Kunimoto D. Postsanatorium pattern of antituberculous drug resistance in the Canadian-born population of western Canada: effect of outpatient care and immigration. Am J Epidemiol 2001; 153(9): 903-911.  

9. Long R, ed. Canadian Tuberculosis Standards, 5th edition. Ottawa: Canadian Lung Association and Health Canada, 2000.  

10. Zwolska Z, Augustynowicz-Kopec E, Klatt M. Primary and acquired drug resistance in Polish tuberculosis patients: results of a study of the national drug resistance surveillance programme. Int J Tuberc Lung Dis 2000; 4(9):832-838.  

11. Helbling P, Altpeter E, Raeber PA, et al. Surveillance of antituberculosis drug resistance in Switzerland 1995-1997: the central link. Eur Respir J 2000; 16(2):200-202.  

12. Tuberculosis Drug Resistance in Canada, 2003. Available online at: http://www.phac-aspc.gc.ca/ publicat/tbdrc03/index.html.