The possibility of drug-resistant TB should be considered at the time of TB diagnosis and selection of the initial treatment regimen. Failure to consider the possibility of drug-resistant TB until conventional DST results become available weeks later can result in unnecessarily inadequate treatment regimens.
In patients who have not yet started their anti-TB drugs, the most important predictors of drug-resistant TB are the following:
1. Previous treatment for TB disease
Previous treatment (of at least 1 month of 1 or more anti-TB drugs) has been consistently shown to be a strong risk factor for drug-resistant TB, especially MDR-TB.2 This association may be explained by the acquisition of drug resistance during the prior treatment episode or, alternatively, reemergence of an already drug-resistant strain that was undiagnosed and/or inadequately treated. A detailed history of prior TB treatment and prior drug-susceptibility test results (if available) are essential. Patients previously treated in Canada may have records of previous treatment through the provincial/territorial TB program. If active TB disease is not adequately excluded beforehand, treatment of presumed LTBI, even if only for a month, can result in drug resistance.
2. Origin from, history of residence in or frequent or extended travel to a country with higher rates of drug resistance
Drug-resistant TB is more common in the foreign-born population than other population groups in Canada.7 Published prevalence estimates for drug-resistant TB from a foreign-born patient’s country of origin, such as those from the WHO, can be helpful to estimate an individual patient’s risk. However, it is important to keep in mind that some discordance between WHO estimates and actual rates of drug-resistant TB by country of origin in foreign-born patients may exist, as has been shown in the U.S.28 Table 3 shows the total TB disease incidence, and the prevalence of isoniazid resistance and MDR/rifampin resistance among new and previously treated TB cases by country, for the most common countries of birth among patients with TB in Canada. Fortunately, transmission of drug-resistant TB from the foreign-born population to the Canadian-born population is relatively uncommon.9,29
Table 3. Total TB incidence, prevalence of isoniazid resistance, and prevalence of MDR/RMP resistance among new and previously treated TB cases; reported by the country to WHO, for the most common countries of birth among foreign-born patients diagnosed with TB in Canada.
Country | Total TB incidence per 100,000 a | INH-R New b | INH-R Previously treated b | MDR/RR New a | MDR/RR Previously treated a |
---|---|---|---|---|---|
India | 193 (132-266) | 8.3% | 13.5% | 2.8% (2.3-3.5) | 14% (14-14) |
Philippines | 554 (311-866) | 12.1% | 14.9% | 1.8% (1.3-2.6) | 28% (27-29) |
China | 58 (50-67) | 7.5% | 8.2% | 7.1% (5.6-8.7) | 23% (23-24) |
Viet Nam | 176 (112-255) | 14.3% | 9.9% | 3.6% (3.4-3.8) | 17% (17-18) |
Pakistan | 263 (187-353) | 7.9% | 6.6% | 4.2% (3.2-5.3) | 7.3% (6.8-7.8) |
Ethiopia | 140 (98-188) | 6.1% | 13.2% | 0.71% (0.62-0.8) | 12% (11-13) |
Somalia | 258 (167-368) | 6.0% | 8.3% | 8.7% (6.1-12) | 88% (73-96) |
Haiti | 170 (130-215) | N/A | N/A | 2.1% (0.78-4.1) | 12% (7.4-17) |
China, Hong Kong SAR | 63 (54-72) | 5.2% | 7.2% | 0.81% (0.49-1.3) | 2.8% (0.93-6.5) |
Afghanistan | 189 (122-270) | N/A | N/A | 2.6% (1.1-4.7) | 24% (21-27) |
Abbreviations: TB, tuberculosis; INH-R, isoniazid resistance without rifampin resistance; MDR/RR, multidrug resistance or rifampin resistance without confirmed INH resistance; WHO, World Health Organisation; N/A, data not available; Hong Kong SAR, Hong Kong Special Administrative Region.
a Total TB incidence estimates and MDR/RR estimates are all for 2019, produced by WHO in consultation with countries; ranges represent uncertainty intervals. 6 See https://www.who.int/teams/global-tuberculosis-programme/data. . . for other country estimates.
b INH-R estimates are for the following years: India 2016, Philippines 2012, China 2013, Viet Nam 2012, Pakistan 2013, Ethiopia 2005, Somalia 2011, China, Hong Kong SAR 2017. Source Dean et al.30
3. Exposure to an individual with confirmed (or highly suspected) infectious drug-resistant TB
While some data suggest that drug-resistant bacteria are less transmissible or less pathogenic once transmitted than drug-susceptible bacteria31–39, other data indicate that this may not be so40 and the transmission risk is offset by longer periods of infectiousness in drug-resistant cases41,42 or compensatory mutations in drug-resistant bacteria.43–45 Clinical evidence of the transmissibility of drug-resistant strains is compelling.46–49 For clinical purposes, such as treatment regimens or contact tracing, drug-resistant bacteria should be considered just as transmissible and just as pathogenic as drug-susceptible bacteria.
In addition to exposure to documented drug-resistant TB, patients who report a history of exposure to a person with TB disease who had treatment resulting in treatment failure or relapse and whose DST results are not known should be considered at increased risk for drug-resistant TB.
4. HIV infection
Two meta-analyses have shown an association between HIV infection and MDR-TB, although the association is more significant for primary MDR-TB50,51 and may have more to do with shared risk factors, such as substance abuse or transmission in congregate settings, than biological factors.51,52
5. Other risk factors for drug-resistant TB
Other risk factors for drug-resistant TB include younger age2,53,54 and more recent arrival in Canada (among foreign-born patients).53,54
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