Increase in multidrug-resistant tuberculosis (MDR-TB) in Alberta among foreign-born persons: implications for tuberculosis management.
Long, Richard ; Langlois-Klassen, Deanne
The burden of tuberculosis (TB) in Canada is increasingly shifting
to foreign-born persons and, in particular, to those who emigrated from
high-incidence countries. (1,2) Foreign-born persons accounted for 66%
of the TB cases in Canada in 2010, nearly four times the proportion of
foreign-born cases reported in 1970. (3,4) At the same time, resistance
to one or more of the first-line anti-tuberculosis drugs (isoniazid,
rifampin, pyrazinamide and ethambutol) is more common in foreign-born
than Canadian-born cases. In 2006, the proportion of culture-positive
foreign-born TB cases with resistance to one or more first-line drugs
was more than twice that of Canadian-born cases (11% and 5%,
respectively). (5) The combination of a high burden of TB and increased
drug resistance resulted in 80% of drug-resistant cases in Canada being
foreignborn. (5) Moreover, 83-95% of multidrug-resistant (MDR;
resistance to at least isoniazid and rifampin) TB cases reported in
Canada are foreign-born. (6-8) Immigrants to Canada from the Western
Pacific may be at a higher risk for MDR-TB due to Beijing/W strains of
Mycobacterium tuberculosis. (9)
Drug resistance and especially MDR-TB are increasing globally,
mainly on account of drugs being improperly prescribed (e.g.,
insufficient number of active agents in the regimen; suboptimal dosage),
properly prescribed but unavailable (e.g., interrupted supply;
prohibitive patient cost), inadequately supervised (e.g., erratic drug
ingestion; omission of one or more active agents), or, more rarely,
malabsorbed. (10-12) Historically, high rates of drug resistance have
been observed in countries with high rates of TB and widely available
but poorly organized access to health care and medications. (13)
Unintentionally, the use of standardized regimens in these low- and
middle-income countries in place of individualized regimens based upon
drug susceptibility test results may have exacerbated the problem of
drug resistance. In a systematic review and meta-analysis of the
standardized treatment of previously untreated patients with
culture-confirmed pulmonary TB, the cumulative incidence of acquired
drug resistance with initially pan-sensitive strains was 0.8% (95% CI
0.5-1.0) compared to 6% (95% CI 4-8) with initially single
drug-resistant strains and 14% (95% CI 9-20) with initially
polydrug-resistant strains. (14)
Drug-resistant TB and MDR-TB in particular represent grave threats
to TB prevention and control. To treat it, one must use longer, more
costly and often more toxic drug regimens. Presumably, low-incidence
countries like Canada will not remain isolated from global increases in
MDR-TB as emigrants from high MDR-TB burden countries (Table 1) may be
infected with MDR strains prior to immigration and develop active
disease after arrival in Canada. (15) This study sought to identify
trends in MDR-TB among foreignborn persons in a major
immigrant-receiving province of Canada over the last 30 years.
METHODS
A retrospective cohort study design was used to investigate the
prevalence of MDR-TB in foreign-born culture-positive TB cases reported
in the province of Alberta between 1982 and 2011. Study cases were
identified through the provincial TB Registry and their demographic and
clinical features abstracted. Laboratory data were abstracted from the
Provincial Laboratory for Public Health, where all mycobacteriology in
the province is performed. Demographic data included age at diagnosis,
sex, country of birth, and year of arrival. Clinical data included
disease type (new active versus relapse/retreatment as defined in the
Canadian Tuberculosis Standards), (1) disease site (respiratory versus
non-respiratory),
and for MDR-TB cases, human immunodeficiency virus (HIV) sero-status.
Laboratory data included susceptibilities to isoniazid, rifampin,
ethambutol, and streptomycin on all initial isolates dating from 1982
and to pyrazinamide on all initial isolates dating from 1991. From 1982
to 1990, the resistance ratio method was used to determine
susceptibilities. (16) Strains with a resistance ratio of [less than or
equal to] 2 were considered sensitive, while strains with a ratio of
[greater than or equal to] 8 were considered resistant. From 1991 to
2010, the BACTEC radiometric system (BACTEC 460TB(tm), Becton-Dickinson
Diagnostic Instrument Systems, Towson, MD), and from 2010 to 2011, the
BACTEC non radiometric system (BACTEC MGIT 960[TM], Becton, Dickinson
and Company, Sparks, MD), were used to determine susceptibilities. All
strains found to be resistant by BACTEC 460TB[TM] or BACTEC MGIT 960(tm)
were retested using the resistance-ratio method to confirm drug
resistance.
During the last two decades (1992-2001 and 2002-2011), all initial
isolates of M. tuberculosis in Alberta were DNA fingerprinted using
IS6110 restriction fragment length polymorphism, supplemented by
spoligotyping in isolates with less than six copies of IS6110. (17-19)
The DNA fingerprints of MDR-TB isolates were compared to each other and
to that of non-MDR-TB isolates.
As informed by the study results and in order to provide insight
into the potential feasibility and cost-effectiveness of genotypic drug
susceptibility tests for MDR-TB, estimated costs were calculated overall
and for groups of foreign-born persons with a high prevalence of MDR-TB
based on country of birth. Estimated laboratory costs for the genotypic
drug susceptibility tests included consumables, miscellaneous laboratory
supplies, laboratory personnel, and overhead costs but excluded the
initial purchase of equipment, personnel training, and specimen shipping
costs. (20) It was assumed that CAD $1 was equivalent to US $1.
The trends and related observations are summarized below, the
two-sided p-values corresponding to the chi-square test or Fisher's
exact test using a 5% level of significance. In the analysis, the
potential association between calendar year of arrival in Canada (a
proxy for calendar year of departure from the country of birth) and
MDR-TB was of interest for three reasons: MDR strains of M. tuberculosis
are a relatively recent and increasing phenomenon, rifampin therapy
having been introduced in 1968; (21) most foreign-born TB cases result
from infections that were acquired prior to immigration; (19) and the
genotypic profiles of M. tuberculosis strains among foreign-born persons
largely reflect the M. tuberculosis epidemiology of their countries of
birth/origin. (22,23) These factors reasonably suggest that foreign-born
persons who more recently departed their countries of birth would have
higher rates of MDR-TB than longer-standing residents in Canada.
The reporting of this longitudinal data was approved by the Health
Research Ethics Board of the University of Alberta.
RESULTS
Twenty-seven (1.2%) of the 2,234 culture-positive foreign-born TB
cases in Alberta in 1982-2011 were MDR-TB cases (Table 2). Overall, MDR
was associated with younger age (<65 years) and TB
relapse/retreatment but not sex, country of birth, or disease site
(Table 2).
There was a trend of foreign-born individuals who arrived in more
recent calendar years having an increased risk of MDR-TB (Figure 1). In
particular, the prevalence of MDR-TB was greatest in the most recent
decade of diagnosis (2.11% in 2002-2011) and this was significantly
higher than the prevalence in 1992-2001 (0.56%; p=0.009) and 1982-1991
(0.65%; p=0.022) (Table 3). For each decade of diagnosis, the prevalence
of MDR-TB increased between 1.5 and 2.3 times when the analysis was
limited to cases that arrived in the decade of diagnosis (Table 3).
However, the association between prevalence of MDR-TB and decade of
diagnosis was of borderline significance when limited to cases that
arrived in the decade of diagnosis (p=0.05).
Twenty-two (81.5%) of the 27 foreign-born MDR-TB cases reported
over the three decades were from high MDR-TB burden countries (Table 2)
(7 from the Philippines; 4 from China; 4 from Vietnam; 3 from India; 2
from Ethiopia; 1 from Pakistan; and 1 from Nigeria). (15) Fifteen
(68.1%) of these 22 cases were diagnosed in the last decade (2002-2011)
and 13 (86.7%) of these 15 cases had also arrived in Canada during the
2002-2011 period (Table 3). All of the 13 MDRTB cases that arrived and
were diagnosed in the last decade were younger than 65 years at the time
of diagnosis.
[FIGURE 1 OMITTED]
The prevalence of MDR-TB among cases born in high MDR-TB countries
increased from 0.7% in the first two decades (1982-2001) to 2.4% in the
last decade (2002-2011) (p=0.008). A similar increase in prevalence was
observed among cases born in high MDR-TB burden countries that had
arrived in the decade of diagnosis (from 1.4% in the first two decades
to 4.6% in the last decade; p=0.016). More specifically, a significant
increase in the prevalence of MDR-TB between the first two decades and
the last decade was only observed among cases born in the Philippines
(from 0% to 4.1%, p=0.017) and Vietnam (from 0.4% to 3.5%, p=0.040). The
prevalence of MDR-TB among cases in the last decade from the Philippines
and Vietnam increased to 6.5% and 6.3%, respectively, if only TB cases
that had arrived in 2002-2011 were considered (Table 3).
Compared to MDR-TB cases reported in the first two decades
(1982-2001), those reported in the last decade (2002-2011) were more
frequently younger than 35 years of age (p=0.265), new active versus
relapse/retreatment cases (p=0.102) and diagnosed with non-respiratory
versus respiratory disease (p=0.068) (Table 4). None of the MDR-TB cases
with known HIV status were co-infected with HIV in either time period.
Cases diagnosed in the first two decades were resistant to a mean of 3.1
first-line drugs out of an average of 4.5 drugs tested per case and, in
the last decade, a mean of 3.5 first-line drugs out of an average of 5
drugs tested per case.
In 1992-2011, all but one of the MDR-TB isolates had unique DNA
fingerprints. The exception was an isolate with an IS6110
low-copy-number that shared a DNA fingerprint with one non-MDR-TB
isolate; a link between these cases could not be established through
conventional contact tracing.
In Canada, the optimal cost-effectiveness of genotypic drug
susceptibility tests requires that the subset of the foreign-born
culture-positive TB cases at greatest risk for MDR-TB be identified. The
results of the current study suggest that this subset would include
individuals born in the Philippines or Vietnam who arrived in Canada in
2002 or later and who were aged <65 years, and especially aged <35
years, at the time of diagnosis. If this approach had been used in
Alberta in 2002-2011, 116 TB cases would have been tested and 8 (53.3%)
of 15 MDR-TB cases in the period potentially detected at an estimated
laboratory cost of $1740 to $2088 per MDR case detected (Table 5).
Expansion of the subset to include the 256 TB cases born in high MDR-TB
burden countries would have potentially identified 13 (86.7%) of the
MDR-TB cases diagnosed during the 2002-2011 period for an additional
estimated laboratory cost of $623 to $748 per MDR-TB case detected
(Table 5). Although MDR TB was significantly associated with
relapse/retreatment cases during the 30-year study period, MDR-TB was
more frequent among new active TB cases in 2002-2011 (p=0.102). If the
optimal subset for genotypic drug susceptibility testing was further
defined to include only relapse/retreatment cases, 6 (75.0%) of 8 MDR-TB
cases among Philippine- or Vietnam-born cases and 11 (84.6%) of 13 cases
born in any high MDR-TB burden country would not have been tested.
DISCUSSION
The increased prevalence of MDR-TB among foreign-born TB patients
in the past decade, the very high prevalence of MDR-TB among recent
emigrants from the Philippines and Vietnam, and the trend towards
younger, new active and non-respiratory MDRTB cases have important
implications for TB programming in Alberta and other major
immigrant-receiving provinces of Canada (notably Quebec, Ontario and
British Columbia). These implications relate to when a foreign-born TB
case patient should be suspected of having MDR-TB and the need for a
timely diagnosis of MDR-TB. If, prior to the availability of the drug
susceptibility test results, a patient with MDR-TB is treated with a
standard regimen of isoniazid, rifampin, pyrazinamide and ethambutol,
their treatment cannot be expected to succeed. This is because the
combination of pyrazinamide and ethambutol, assuming the isolate is
susceptible to these drugs, is not a curative regimen. Moreover, our
investigation demonstrates that resistance to pyrazinamide and/or
ethambutol is not uncommon in MDR-TB isolates (43.5% and 55.6%,
respectively, as per Table 4) and pyrazinamide is known to be
ineffective at preventing resistance to companion drugs. (1,24)
Consequently, administration of the standard regimen to MDR-TB cases
that are also resistant to either pyrazinamide or ethambutol is
essentially mono-therapy. If administered long enough, this treatment
approach will produce resistance to the fourth drug
("amplified" resistance) given the selective advantage that a
naturally occurring mutant, resistant to the fourth drug, has in the
presence of mono-therapy. (1)
Foreign-born persons contribute more than 82% of MDR-TB cases in
low TB incidence high-income countries. (6-8,25,26) Despite this
commonality, the prevalence of MDR-TB cases among foreign-born
individuals in these countries varies markedly due to differences in the
countries from which the majority of new immigrants arrive (i.e.,
immigration patterns). For example, the prevalence of MDRTB in this
study (1.4% in 1992-2011) was similar to that of the United States (1.7%
in 1993-2009). (27) However, foreign-born persons in Alberta had a
markedly lower prevalence of MDR-TB than those in Italy (1.6% and 6.2%
in 2008-2010, respectively). (25) This difference reasonably relates to
Italy receiving a larger proportion of foreign-born persons from higher
MDR-TB incidence countries, such as the Ukraine and Moldova, than Canada
(data not shown).
The finding that MDR-TB cases in this study had unique DNA
fingerprint patterns argues against the likelihood of local transmission
that progressed to culture-positive disease. Importantly, local
transmission also does not appear to be responsible for the four
Canadian-born MDR-TB cases that occurred in the 30-year study period
(data not shown). Two of these Canadian-born cases had unique DNA
fingerprints on account of being infected with MDR strains while
traveling abroad; the other two started with an initially susceptible
isolate and became drug-resistant during treatment. (6,7,28)
The challenge of suspecting and diagnosing MDR-TB in foreign-born
TB patients is great given the increasing proportion of younger, new
active MDR-TB cases in recent years. These trends, which presumably
reflect the ongoing transmission of MDR isolates from MDR source cases
to susceptible contacts in their country of origin, (29) dictate that
being a new active case (as opposed to a relapse/retreatment case which
is well known to carry a risk of drug resistance)1 does not reliably
exclude, or make less likely, the probability of MDR-TB. This contrasts
with the usual predictors of MDRTB, namely: failed treatment with a
standard four-drug regimen; previous TB treatment, particularly if it
was associated with program or patient non-adherence; treatment of
isoniazid-resistant TB in the past; or exposure to a patient who is
known to have infectious MDR-TB.1 The shift toward non-respiratory
disease further complicates matters as a diagnosis of MDR-TB cannot be
made unless an appropriate specimen is submitted for culture. That is,
the provision of an empiric treatment regimen in lieu of specimen
collection through an invasive procedure increases the likelihood of a
missed diagnosis of MDR-TB.
Genotypic drug susceptibility tests provide an unprecedented
opportunity to diagnose MDR-TB prior to the commencement of treatment.
(30) These tests, which have >98% sensitivity and specificity for
rifampin, (31) target the 81 bp region of the rpoE gene of M.
tuberculosis known as the rifampin resistance determining region where
95% of the rifampin-resistant conferring mutations are located. In
Canada, the presence of such a mutation strongly suggests the presence
of MDR-TB given that only 10% of foreign-born rifampin-resistant TB
cases in 2006-2010 had isoniazid-susceptible disease (Custom Report;
Canadian Tuberculosis Reporting System, Public Health Agency of Canada,
Health Canada). Importantly, however, negative genotypic drug
susceptibility test results should not supplant phenotypic drug
susceptibility testing in the presence of a high clinical suspicion for
MDR-TB. (32)
The genotypic drug susceptibility tests that are currently
available and recommended by the World Health Organization for the early
detection of MDR-TB are i) line probe assays (two commercial kits are
currently available: the INNO-LiPA Rif.TB test [Innogenetics NV, Gent,
Belgium] and the GenoType MTBDRplus test [Hain Lifescience GmbH, Nehren,
Germany]) (33) and ii) the Xpert MTB/RIF test (GeneXpert [Cepheid,
Sunnyvale, California, USA]). (34) The GenoTypeMTBDRplus test and the
Xpert MTB/RIF test are currently approved for use in Canada. (35)
When attempting to identify the high-yield target population for
genotypic drug susceptibility tests, both feasibility and
cost-effectiveness analyses must at least take into account the
performance characteristics of the tests (31) as well as the
patient's country of birth, year of arrival, age at diagnosis, and
possibly disease type (new active versus relapse/retreatment). Even so,
in practice, there are only three management options when faced with a
possible MDR-TB case: i) delay treatment altogether until phenotypic
drug susceptibility test results are available--not an acceptable option
if the patient is very ill or highly infectious; ii) within reason, make
certain that an empiric regimen is sufficiently surfeit to cover off the
possibility of MDRTB; or iii) use one of the genotypic drug
susceptibility tests. Decisions about each of these options are best
made by physicians experienced in the management of drug-resistant TB.
(1)
Received: March 28, 2012 Accepted: December 8, 2012
Acknowledgements: The authors thank the staff of Alberta Health
Services and the Provincial Laboratory for Public Health for their
assistance with data abstraction. We also extend our gratitude to the
staff of the TB Program Evaluation and Research Unit, University of
Alberta, for their assistance in preparing this manuscript. This study
was supported in part by a grant from the University Hospital
Foundation.
Disclaimer: The opinions, results and conclusions reported in this
paper are those of the authors. No endorsement by the University of
Alberta or Alberta Health Services is intended or should be inferred.
Conflict of Interest: None to declare.
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Richard Long, MD, Deanne Langlois-Klassen, PhD
Author Affiliations
Department of Medicine, University of Alberta, Edmonton, AB
Correspondence: Dr. Richard Long, TB Program Evaluation and Research
Unit, Department of Medicine, Division of Pulmonary Medicine, University
of Alberta, 8333
Aberhart Centre, 11402 University Avenue, Edmonton, AB T6G 2J3,
Tel: 780-4071427, Fax: 780-407-1429, E-mail: richard.long@ualberta.ca
Table 1. Estimated Proportion of MDR-TB Cases Among Incident TB
Cases in the 27 High MDR-TB Burden Countries, 2008 *([dagger])
WHO Region Country Source of
Estimates
Africa DR Congo model
Ethiopia DRS, 2005
Nigeria model
South Africa DRS, 2002
Europe Armenia DRS, 2007
Azerbaijan DRS, [double dagger] 2007
Belarus model
Bulgaria model
Estonia DRS, 2008
Georgia DRS, 2006
Kazakhstan DRS, 2001
Kyrgyzstan model
Latvia DRS, 2008
Lithuania DRS, 2008
Republic of Moldova DRS, 2006
Russian Federation DRS, [double dagger] 2008
Tajikistan DRS, [double dagger] 2008
Ukraine DRS, [double dagger] 2002
Uzbekistan DRS, [double dagger] 2005
Eastern Pakistan model
Mediterranean
South-East Asia Bangladesh model
India DRS, [double dagger] 2005
Indonesia DRS, [double dagger] 2004
Myanmar DRS, 2007
Western Pacific China DRS, 2007
Philippines DRS, 2004
Vietnam DRS, 2006
WHO Region % MDR Among % MDR Among Previously
New TB Cases (95% CI) Treated TB Cases (95% CI)
Africa 1.8 (0.0-4.3) 7.7 (0.0-18.1)
1.6 (0.9-2.7) 11.8 (6.4-21.0)
1.8 (0.0-4.3) 7.7 (0.0-18.1)
1.8 (1.5-2.3) 6.7 (5.5-8.1)
Europe 9.4 (7.3-12.1) 43.2 (38.1-48.5)
22.3 (19.0-26.0) 55.8 (51.6-59.9)
12.5 (0.0-25.3) 42.1 (11.9-72.2)
12.5 (0.0-25.3) 42.1 (11.9-72.2)
15.4 (11.6-20.1) 42.7(32.1-53.9)
6.8 (5.2-8.7) 27.4 (23.7-31.4)
14.2 (11.0-18.2) 56.4 (50.9-61.8)
12.5 (0.0-25.3) 42.1 (11.9-72.2)
12.1 (9.9-14.8) 31.9 (24.9-39.9)
9.0 (7.5-10.7) 47.5 (42.9-52.2)
19.4 (16.8-22.2) 50.8 (48.7-53.0)
15.8 (11.9-19.7) 42.4 (38.1-46.7)
16.5 (11.3-23.6) 61.6 (52.9-69.7)
16.0 (13.8-18.3) 44.3 (40.0-48.7)
14.2 (10.4-18.1) 49.8 (35.8-63.8)
Eastern 2.9 (0.0-8.0) 35.4 (0.0-75.1)
Mediterranean
South-East Asia 2.2 (0.0-5.6) 14.7 (0.0-39.6)
2.3 (1.8-2.8) 17.2 (14.9-19.5)
2.0 (0.5-6.9) 14.7 (0.0-39.6)
4.2 (3.2-5.6) 10.0 (7.1-14.0)
Western Pacific 5.7 (5.0-6.6) 25.6 (22.6-28.3)
4.0 (3.0-5.5) 20.9 (14.8-28.7)
2.7 (2.0-3.6) 19.3 (14.5-25.2)
Abbreviations: WHO=World Health Organization;
MDR-TB=multidrug-resistant TB; CI=confidence interval;
DR=Democratic Republic; DRS=drug resistance surveillance or survey
data.
* This table is a modified version of Table 6 in the WHO
publication Multidrug and Extensively Drug-Resistant TB (M/XDR-TB)
2010 Global Report on Surveillance and Response and is used with
permission (See reference 12).
([dagger]) The 27 high MDR-TB burden countries refer to WHO Member
States that were estimated by the WHO in 2008 to have had an annual
incidence of at least 4,000 MDR-TB cases and/or at least 10% of
newly registered TB cases with MDR-TB.
([double dagger]) Estimates were based on subnational drug
resistance data.
Table 2. Characteristics of Foreign-born MDR and Non-MDR
Tuberculosis Cases in Alberta, 1982-2011
Case Characteristic Cases MDR RR p-values
n %
Overall 2234 27 1.21
Age (years) 0.025
<35 766 13 1.70 6.07
35-64 765 12 1.57 5.61
>64 703 2 0.28 1.00
Sex 0.89
Female 1130 14 1.24 1.05
Male 1104 13 1.18 1.00
Country of birth * 0.092
High MDR-TB burden 1571 22 1.40 1.84
([dagger])
Other 659 5 0.76 1.00
Disease type <0.0001
([double dagger])
Relapse/Retreatment 151 10 6.62 7.88
New active 2034 17 0.84 1.00
Disease site 0.62
Respiratory 1560 20 1.28 1.23
Non-respiratory 674 7 1.04 1.00
Abbreviations: MDR=multidrug-resistant; RR=relative risk.
* The country of birth was unknown for four cases that were not MDR.
([dagger]) The high MDR-TB burden countries that were associated with
MDR-TB cases in this study were: Philippines (7 cases); China,
Including Hong Kong, Macau and Taiwan (4 cases); Vietnam (4 cases);
India (3 cases); Ethiopia (2 cases); Pakistan (1 case); and Nigeria
(1 case).
([double dagger]) Disease type was missing for 49 non-MDR cases.
Table 3. Prevalence of MDR-TB in Foreign-born TB Cases
in Alberta, 1982-2011 *
Foreign-born TB Case Grouping Decade of Diagnosis
1982-1991 1992-2001
TB cases 617 718
MDR-TB cases 4 4
Group MDR-TB prevalence (%) 0.65 0.56
TB cases that arrived in the decade 200 239
MDR-TB cases that arrived in the decade 2 3
Group MDR TB prevalence (%) 1.00 1.26
TB cases born in HMTBC ([dagger]) 410 525
MDR-TB cases born in HMTBC 3 4
Group MDR-TB prevalence (%) 0.73 0.76
TB cases born in HMTBC that arrived in 164 187
the decade
MDR-TB cases born in HMTBC that arrived 2 3
in the decade
Group MDR-TB Prevalence (%) 1.22 1.60
Philippine-born TB cases 54 91
Philippine-born MDR-TB cases 0 0
Group MDR-TB prevalence (%) 0 0
Philippine-born TB cases that arrived in 27 39
the decade
Philippine-born MDR-TB cases that arrived 0 0
in the decade
Group MDR-TB prevalence (%) 0 0
Vietnam-born TB cases 137 144
Vietnam-born MDR-TB cases 0 1
Group MDR-TB prevalence (%) 0 0.69
Vietnam-born TB cases that arrived in 57 43
the decade
Vietnam-born MDR-TB cases that arrived 0 1
in the decade
Group MDR-TB prevalence (%) 0 2.33
Decade of
Foreign-born TB Case Grouping Diagnosis
2002-2011 Total
TB cases 899 2234
MDR-TB cases 19 27
Group MDR-TB prevalence (%) 2.11 1.21
TB cases that arrived in the decade 406 845
MDR-TB cases that arrived in the decade 15 20
Group MDR TB prevalence (%) 3.69 2.37
TB cases born in HMTBC ([dagger]) 636 1571
MDR-TB cases born in HMTBC 15 22
Group MDR-TB prevalence (%) 2.36 1.40
TB cases born in HMTBC that arrived in 281 632
the decade
MDR-TB cases born in HMTBC that arrived 13 18
in the decade
Group MDR-TB Prevalence (%) 4.63 2.85
Philippine-born TB cases 170 315
Philippine-born MDR-TB cases 7 7
Group MDR-TB prevalence (%) 4.12 2.22
Philippine-born TB cases that arrived in 108 174
the decade
Philippine-born MDR-TB cases that arrived 7 7
in the decade
Group MDR-TB prevalence (%) 6.48 4.02
Vietnam-born TB cases 85 366
Vietnam-born MDR-TB cases 3 4
Group MDR-TB prevalence (%) 3.53 1.09
Vietnam-born TB cases that arrived in 16 116
the decade
Vietnam-born MDR-TB cases that arrived 1 2
in the decade
Group MDR-TB prevalence (%) 6.25 1.72
* Refers to culture-positive TB cases only.
([dagger]) HMTBC=High MDR-TB burden countries.
Table 4. Characteristics of Foreign-born MDR-TB Cases in
Alberta, 1982-2001 and 2002-2011
Case Characteristics Time Period p-values
1982-2001 2002-2011
N=8 N=19
No. (%) No. (%)
Age (years) 0.265
<35 2 (25.0) 11 (57.9)
35-64 5 (62.5) 7 (36.8)
>64 1 (12.5) 1 (5.3)
Sex 0.901
Male 4 (50.0) 9 (47.4)
Female 4 (50.0) 10 (52.6)
Disease type 0.102
New active 3 (37.5) 14 (73.7)
Relapse/Retreatment 5 (62.5) 5 (26.3)
Disease site 0.068
Respiratory 8 * (100) 12 (63.2)
Non-respiratory 0 (0.0) 7 ([dagger])
First-line drug resistance (36.8) 0.451
Isoniazid 8 (100.0) 19 (100.0)
Rifampin 8 (100.0) 19 (100.0)
Pyrazinamide 2 (50.0) 8 (42.1)
([double
dagger])
Ethambutol 3 (37.5) 12 (63.2)
Streptomycin 4 (0.5) 8 (42.1)
* One case was culture-positive from both pleural fluid and urine.
([dagger]) Five cases were culture-positive from a cervical lymph
node, one from an intra-thoracic lymph node and one from a
vertebral body. The case of intrathoracic lymph node TB is grouped
here under "non-respiratory" as it had no co-existent respiratory
disease and required an invasive procedure for diagnosis.
([double dagger]) Only 4 of the 8 MDR-TB cases were tested for
susceptibility to pyrazinamide, with 2 (50.0%) of these cases
having resistance.
Table 5. Estimated Costs of Targeted Genotypic Drug Susceptibility
Testing Among Foreign-born TB Cases (Aged <65 Years at Diagnosis)
That Arrived in Alberta in 2002-2011 and Were Diagnosed With TB
During That Same Decade
Variables of Interest Country of Birth
Philippines
or Vietnam
TB cases 116
% of all TB cases 28.6
MDR-TB cases 8
% of all MDR-TB cases 53.3
NNT per MDR-TB case diagnosed 14.5
Laboratory cost per test *([dagger]) $120 to $144
Total laboratory costs in 2002-2011 $13,920 to $16,704
Laboratory costs per MDR case diagnosed $1740 to $2088
Variables of Interest Country of Birth
Any High MDR-TB
Burden Country
TB cases 256
% of all TB cases 63.1
MDR-TB cases 13
% of all MDR-TB cases 86.7
NNT per MDR-TB case diagnosed 19.7
Laboratory cost per test *([dagger]) $120 to $144
Total laboratory costs in 2002-2011 $30,720 to $36,684
Laboratory costs per MDR case diagnosed $2363 to $2836
Country of Birth
Variables of Interest Any Country
406
100.0
15
TB cases 100.0
% of all TB cases 27.1
MDR-TB cases $120 to $144
% of all MDR-TB cases $48,720 to $58,464
NNT per MDR-TB case diagnosed $3248 to $3898
Laboratory cost per test *([dagger])
Total laboratory costs in 2002-2011
Laboratory costs per MDR case diagnosed
Abbreviations: TB=tuberculosis; MDR-TB=multidrug-resistant TB;
NNT=number needed to test.
* The estimated laboratory costs for the genotypic drug
susceptibility tests include consumables ($10 to $30 per sample
tested), miscellaneous laboratory supplies ($10 per sample tested),
laboratory personnel ($80 per sample tested), overhead costs ($20
to $24 per sample tested). Costs for the initial purchase of
equipment, personnel training, or specimen shipping costs were not
included in the cost estimates. It was also assumed that CAD $1 was
equivalent to US $1.
([dagger]) CDC. Report of Expert Consultations on Rapid Molecular
Testing to Detect Drug-resistant Tuberculosis in the United States.
Available at:
http://www.cdc.gov/tb/topic/laboratory/rapidmoleculartesting/
MolDSTreport.pdf (Accessed October 3, 2012).
