Drug-Resistant Tuberculosis Among the Foreign-born in Canada

Volume 31-04  15 February 2005

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 to 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.

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 (Figure 1).


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

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

Country of origin

Individuals from 10 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 1).


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

Country of origin

Total TB cases

Number of resistant cases

Percent of total

Number of MDR cases

Percent of total

Vietnam

1,354

308

22.7%

25

1.8%

Philippines

1,319

193

14.6%

17

1.3%

Peoples Republic of China

1,419

152

10.7%

22

1.6%

India

1,410

99

7.0%

10

0.7%

Somalia

605

79

13.1%

15

2.5%

Hong Kong

734

56

7.6%

3

0.4%

Haiti

313

54

17.3%

4

1.3%

Former Ethiopia*

295

36

12.2%

2

0.7%

Pakistan

291

30

10.3%

3

1.0%

Republic of Korea

160

27

16.9%

5

3.1%

* Includes Ethiopia and Eritrea for 1992.


Time since arrival in Canada

The majority of drug-resistant cases were reported among the recently arrived (< 5 years 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 2).


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

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

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 3).


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

Figure 3. Primary drug resistance reporting - Alberta, British Columbia,Ontario andQuebec, 1992-2002

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


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

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

Treatment outcomes

Treatment outcomes for drug-resistant cases with respect to cure and treatment completion were slightly less favourable when compared with non-resistant cases (71% and 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 and those with reported drug resistance (7% versus 8%).

Primary drug resistance and HIV

Primary drug resistance was reported in only eight HIV-positive TB cases. Only two cases with treatment among those who were HIV-positive acquired drug resistance during the years 1997- 2002.

Acquired drug resistance

Resistance acquired during treatment was infrequent. From 1997-2002, 58 cases of secondary drug resistance were reported (< 1% 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 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 reported from Kazakhstan(1). Further international studies indicate a higher incidence of drug-resistant TB in males, those previously treated for TB, and age > 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 epidemiologic 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 because 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.

The Executive Summary and Tuberculosis Among the Foreign- Born in Canada, prepared by Ms. Melissa Phypers, Senior Epidemiologist, Tuberculosis Prevention and Control, Public Health Agency of Canada, were taken from Tuberculosis in Canada 2002, a soon to be released annual report that will also be available online at the website given below.

For further information on tuberculosis in Canada, please visit
the Public Health Agency of Canada's Tuberculosis Prevention and Control website.

Members of the Canadian Tuberculosis Committee: Dr. V. Hoeppner (Chair); Dr. M Baikie; Dr. C. Balram; Ms. C. Case; Dr. E. Ellis (Executive Secretary); Dr. R.K. Elwood (Past Chair); 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.

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):605-9.

  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):427-32.

  4. Long R, Manfreda J, Mendella L et al. Antituberculosis drug resistance in Manitoba from 1980-1989. CMAJ 1993;148(9):1489-95.

  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):225-30. 

  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 et al. Multidrug-resistant tuberculosis in Alberta and British Columbia, 1989 to 1998. Can Respir J 1999;6(2):155-60.

  8. Long R, Chui L, Kakulphimp J et al. 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): 903-11.

  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):832-38.

  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):200-02.

  12. Tuberculosis Drug Resistance in Canada, 2003.

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