[Show abstract][Hide abstract] ABSTRACT: Delays in diagnosis of tuberculosis (TB) have been associated with previous use of antibiotics, and in particular fluoroquinolones (FQ), for suspected pulmonary infections.
We conducted a population-based cohort study with 2232 patients who had active TB between 1997 and 2006 (records obtained from the British Columbia Linked Health Databases). Patients with a record of an initial health care contact preceding the diagnosis of TB were identified for inclusion. Health care delay was defined as the time between initial health care contact and the initiation of anti-tuberculosis medication, and was compared between patients prescribed antibiotics and those not exposed to any antibiotics.
A total of 1544 patients were included. After adjusting for covariates, average health care delay for patients exposed to antibiotics was found to be significantly greater, by a factor of 2.10 (95%CI 1.80-2.44), with a median delay of 41 days in the antibiotic group compared to 14 days in the non-antibiotic group. Sex, age, foreign-born status and socio-economic status were non-significant factors. Health care delay increased with the number of antibiotic courses received, but not with the type of antibiotic.
Previous treatment with any antibiotic, and not only a FQ, is associated with a delay in TB diagnosis.
The International Journal of Tuberculosis and Lung Disease 08/2011; 15(8):1062-8. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To quantify patient preferences when making decisions as to whether to accept latent tuberculosis infection (LTBI) preventive treatment, using a discrete choice experiment (DCE).
A DCE survey was developed and administered to LTBI patients. Each patient was given 10 random choices along with two fixed choices to check consistency. Two hypothetical treatment options and one opt-out option were presented in each choice task. Latent class analysis was conducted to estimate preferences for six key treatment attributes.
Among the 214 respondents, 194 (90.7%) who provided valid DCE responses and complete sociodemographic information were included. Results consistently suggested that respondents were averse to higher risk of active tuberculosis and side effects and longer treatment. A three-latent-class model with five covariates was chosen. Forty-seven percent of the respondents were assigned to class 1, 32% to class 2, and 21% to class 3. Although all six attributes were shown to significantly influence the respondents' treatment decision, the risk of active tuberculosis, chance of liver damage, and frequency of clinic visits were the most important ones. Significant preference heterogeneity was observed in two attributes: frequency of clinic visits (P < 0.01) and chance of liver damage developing (P < 0.01). Class 1 individuals were most likely to have children. Class 2 had the highest employment rate. Class 3 respondents tended to choose the opt-out option on DCE tasks and were more likely to be born outside Canada, have higher education, and be unemployed.
Respondents consistently preferred preventive treatment with higher effectiveness, fewer side effects, and shorter length. Substantial preference heterogeneity existed among respondents.
Value in Health 01/2011; 14(6):937-43. · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: British Columbia (BC), Canada.
To determine the risk factors for pulmonary colonization by non-tuberculous mycobacteria (NTM).
Retrospective study of subjects colonized by NTM from 1990 to 2006. Subjects without mycobacterial disease and with at least three negative cultures served as controls.
Mycobacterium avium complex (MAC) species were the most common NTM. Risk factors of colonization included age > or = 60 years (aOR 2.3), female sex (aOR 1.2), residency in Canada for at least 10 years (aOR 3.8), Canadian-born aboriginal (aOR 1.8), and Canadian-born non-aboriginal (aOR 1.4). Predictors of MAC colonization included White race (aOR 1.6) and residency in Canada for at least 10 years, which was the strongest predictor (aOR 6.7). Aboriginal origin was associated with non-MAC colonization (aOR 1.8), and Canadian-born people from the East/South-East Asian ethnic groups were protected from MAC colonization (aOR 0.2), all aOR P < 0.05.
Older age, female sex, having been born in Canada, long residency in BC and White race predict pulmonary NTM colonization, while Aboriginal origin predicts non-MAC colonization. Further research is needed to identify environmental NTM sources in BC and to determine their relation to colonization and disease.
The International Journal of Tuberculosis and Lung Disease 01/2010; 14(1):106-12. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: TB is a serious global public health problem. Isoniazid, a key drug used to treat latent TB, can cause hepatotoxicity in some patients. This pilot study investigated the effects of genetic variation in NAT2 and CYP2E1 on isoniazid-induced hepatotoxicity in TB contacts in British Columbia, Canada.
DNA re-sequencing was used to establish the spectrum of genetic variation in the exons, promoter and conserved regions of NAT2 in all subjects. For CYP2E1, the CYP2E1*1C polymorphism was genotyped by PCR-RFLP. Association tests of NAT2 variants and haplotypes, as well acetylator types were performed.
We enrolled 170 subjects on isoniazid treatment (23 cases and 147 controls). Systematic re-sequencing of NAT2 revealed 18 known and 10 novel variants.
No single genetic variant of NAT2 and CYP2E1 showed a significant association with isoniazid-induced hepatotoxicity in this highly heterogeneous population. There was evidence of a trend for increasing hepatotoxicity risk across the rapid, intermediate and slow acetylator groups (p = 0.08).
[Show abstract][Hide abstract] ABSTRACT: British Columbia Centre for Disease Control (BCCDC), Vancouver, Canada.
To determine the incidence of non-tuberculous mycobacteria (NTM) and to assess the impact of new laboratory techniques.
Population-based study of all subjects with positive cultures for NTM from 1990 to 2006.
Mycobacterium avium complex (MAC) was the most common NTM isolate (77%). The median incidence rates per 100 000 population in the total sample were respectively 6.7, 4.5 and <0.7 for all NTMs, MAC and all non-MAC species; for NTM-treated subjects the rates were respectively 1.6, 1.4 and <0.08; and for the NTM-colonised they were respectively 4.7, 2.7 and <0.5. In the period after the introduction of new laboratory techniques, all NTM isolates, the overall MAC rate and the MAC-colonised rate increased by respectively 24%, 35.4% and 76% (P < 0.05). All NTM isolates and rates for all NTMs, NTM-treated and M. tuberculosis subjects (used as comparison group) decreased over time (P < 0.05).
The most common NTM species was MAC. Episodic increases in the number of isolates and incidence rates of subjects colonised with MAC are likely to be associated with the implementation of new laboratory techniques, which may represent an artefact. The decrease in rates of NTM-treated subjects is reassuring.
The International Journal of Tuberculosis and Lung Disease 09/2009; 13(9):1086-93. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent approval of interferon-gamma release assays that are more specific for Mycobacterium tuberculosis has given new options for the diagnosis of latent tuberculosis infection (LTBI).
To assess the cost-effectiveness of Quanti-FERON-TB Gold (QFT-G) vs. the tuberculin skin test (TST) in diagnosing LTBI in contacts of active TB cases using a decision analytic Markov model.
Three screening strategies--TST alone, QFT-G alone and sequential screening of TST then QFT-G--were evaluated. The model was further stratified according to ethnicity and bacille Calmette-Guérin (BCG) vaccination status. Data sources included published studies and empirical data. Results were reported in terms of the incremental net monetary benefit (INMB) of each strategy compared with the baseline strategy of TST-based screening in all contacts.
The most economically attractive strategy was to administer QFT-G in BCG-vaccinated contacts, and to reserve TST for all others (INMB CA$3.70/contact). The least cost-effective strategy was QFT-G for all contacts, which resulted in an INMB of CA$-11.50 per contact. Assuming a higher prevalence of recent infection, faster conversion of QFT-G, a higher rate of TB reactivation, reduction in utility or greater adherence to preventive treatment resulted in QFT-G becoming cost-effective in more subgroups.
Selected use of QFT-G appears to be cost-effective if used in a targeted fashion.
The International Journal of Tuberculosis and Lung Disease 01/2009; 12(12):1414-24. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) referral clinic in Vancouver, British Columbia, Canada.
Screening for and treatment of latent TB infection (LTBI) in at-risk populations are the cornerstone of TB control in low-incidence countries. Persons at low risk often undergo the tuberculin skin test (TST) for reasons other than contact. Little information exists on the actual risk of TB in this population.
To determine the risk of TB in screened subjects without known risk factors.
Retrospective descriptive analysis of demographics, TST reaction size and TB disease occurrence in 98333 low-risk subjects screened from 1990 to 2002.
The average annual disease rate was 0.4 per 100000 population (cumulative rate 7.4/100000) from 1990 to 2006, and TB was diagnosed only in the foreign-born. Risk of TB in the foreign-born increased with larger TST reaction size (P < 0.03). Completion of treatment for LTBI was not documented for any of the subsequent active TB cases.
In a low-risk screened population, active TB disease was found only in the foreign-born. Treatment of LTBI is not recommended in persons with a positive TST and no additional risk factors. Local screening programs should focus on populations with confirmed risk factors for disease.
The International Journal of Tuberculosis and Lung Disease 08/2008; 12(8):903-8. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) remains a major public health threat worldwide. Numerous cost-effectiveness analyses of TB screening and treatment strategies have been recently published, but none have utilized quality-adjusted life-years as recommended because of the lack of utilities for TB health states.
To characterize and compare utility scores from either active TB or latent TB infection (LTBI) participants.
Consenting patients attending a population-based screening and treatment clinic were administered the Short Form 36 (SF-36), the Health Utilities Index 2/3 (HUI2/3), and a general health visual analog scale (VAS) along with demographic questions. SF-36 scores were converted to Short Form 6D (SF-6D) utility scores using an accepted algorithm. Utility results were compared across scales, and construct validity was assessed.
A total of 162 TB patients (78 LTBI and 84 active TB) with available SF-36 and all four utility scores (Health Utilities Index 2, Health Utilities Index 3, SF-6D and VAS) were included in the analysis. Those with active TB had significantly lower SF-36 and utility scores than those with LTBI. Although all appeared to exhibit construct validity, the HUI2/3 and the VAS appeared to have significant ceiling effects, whereas the SF-6D had significant floor effects.
Health state utility values for active TB and LTBI have been determined using different instruments. The three measures did not generate identical utility scores. The HUI2/3 was limited by ceiling effects, whereas the SF-6D appeared to display floor effects.
Value in Health 06/2008; 11(7):1154-61. · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) remains a public health threat with significant annual impacts on morbidity and mortality. However, few studies have examined the impact of active and latent TB infection (LTBI) on health-related quality of life (HRQL).
Patients with recently diagnosed active TB or LTBI patients were administered the Short Form-36 (SF-36) and the Beck depression inventory (DI) at baseline, 3 months, and 6 months. Mixed-effect linear regression was used to compare the trajectory of HRQL over time in the two patient groups after adjusting for potential confounders. Ordinal logistic regression was used to determine the relationship between changes in HRQL of at least the minimal important difference.
One hundred four active TB and 102 LTBI patients participated. At baseline, participants with active TB had significantly lower SF-36 mean domain and component scores (4 to 12 points lower, p < 0.03) and higher mean Beck DI scores (4 points higher, p < 0.0001) when compared to LBTI participants. In the responder analysis, those with active TB were associated with reporting improved scores at 6 months of at least the minimal important difference in vitality (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.3 to 5.6), role physical (OR, 3.1; 95% CI, 1.4 to 6.5), mental component score (OR, 3.2; 95% CI, 1.5 to 6.9), social functioning (OR, 11.1; 95% CI, 3.8 to 33), and role emotional (OR, 2.7; 95% CI, 1.2 to 6.0).
Active TB patients had large improvements in most HRQL domains by 6 months. However, when compared to LTBI participants and US norms, HRQL was still low at completion of therapy.
[Show abstract][Hide abstract] ABSTRACT: No previous studies have estimated the rates of tuberculin positivity (TP) in noncontact populations within the same community, which is important for prioritizing and implementing preventive measures.
To estimate the prevalence and predictors of TP in noncontact populations.
A retrospective analysis of tuberculin results of noncontact populations screened in British Columbia from 1990 to 2002 was conducted.
The period prevalence of TP in 59,791 screened subjects was 12.7% (95% CI 12.4% to 13.0%), 30.4% (95% CI 28.2% to 32.7%) and 60.9% (95% CI 60.3% to 61.6%) for Canadian-born non-Aboriginals (CBNAs), Canadian-born Aboriginals (CBAs) and foreign born (FB), respectively. After controlling for age and sex, independent predictors of TP included Bacille Calmette-Guérin (BCG) vaccination (OR 19.6, 95% CI 17.9 to 21.5), country of birth (CBA: OR 2.87, 95% CI 2.44 to 3.37; FB: OR 3.67, 95% CI 3.34 to 4.03) and the following populations: correctional centre residents (OR 4.14, 95% CI 1.87 to 9.15), residents of long-term care and community care facilities (OR 1.79, 95% CI 1.44 to 2.23), immigrants (OR 1.75, 95 % CI 1.50 to 2.04), health centre employees (OR 1.71, 95 % CI 1.56 to 1.88), volunteers (OR 1.38, 95% CI 1.14 to 1.68), self-referred healthy subjects (OR 1.30, 95% CI 1.15 to 1.48) and students (OR 1.27, 95% CI 1.19 to 1.35). CBAs, FB and male subjects were less likely to react to tuberculin than CBNAs and female subjects among those vaccinated with Bacille Calmette-Guérin (P<0.05).
Rates of TP correlate with disease rates by sex and origin. The continuation of tuberculin screening programs is warranted in noncontact populations with high TP rates, where unknown exposure to active cases is more likely to occur. Further research is needed to determine the reasons why a higher response to tuberculin occurs in BCG-vaccinated women and CBNAs.
Canadian respiratory journal: journal of the Canadian Thoracic Society 01/2008; 15(4):181-7. · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Standard treatment of active tuberculosis (TB) consists of isoniazid (INH), rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB). Although this regimen is effective in treating active TB, it is associated with many adverse drug reactions (ADRs) and poses a significant challenge to completion of treatment.
To examine the incidence of major ADRs and risk factors associated with first-line anti-tuberculosis medications.
This study evaluated patients receiving treatment for active TB from a population-based database (2000-2005). The nature of the ADRs, likelihood of association with the study medications and severity were evaluated.
A total of 1061 patients received treatment, of whom 318 (30%) had at least one major ADR. The overall incidence of all major ADRs was 7.3 events per 100 person-months (95%CI 7.2-7.5): 23.3 (95%CI 23.0-23.7) when on all four first-line drugs, 13.6 (95%CI 13.3-14.0) when on RMP, INH and PZA, and 2.4 (95%CI 2.3-2.6) when on INH and RMP. Adjusted hazard ratio (HR) revealed that combination regimens containing PZA, females, subjects aged 35-59 and >or=60 years, baseline aspartate aminotransferase >or=80 U/l and drug resistance were associated with any major event.
First-line anti-tuberculosis drugs are associated with significant ADRs. There are several risk factors associated with the development of ADRs, including exposure to regimens containing PZA.
The International Journal of Tuberculosis and Lung Disease 08/2007; 11(8):868-75. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Estimations of prevalence of latent tuberculous infection (LTBI) are confounded by factors known to influence the results of the tuberculin skin test (TST) such as age, contact history and bacille Calmette-Guerin (BCG) vaccination. Appropriate interpretation of TST results is necessary to ensure LTBI treatment for those at greatest risk.
To document the prevalence of LTBI in Aboriginal people living on a reserve in British Columbia (BC) and to determine the influence of BCG.
A population-based, retrospective descriptive analysis of all epidemiological data collected for the on-reserve Aboriginal programme in BC (1951-1996).
Of 17615 persons who received a TST during the study period, 42% had received BCG. During the study period, an average of 2517 TSTs were completed per year (SD = 1228) among persons with an average age of 26 years (SD = 16). Among all subjects, the average prevalence of LTBI was 25% (95 %CI 24-25). The presence of BCG (OR = 3.1, 95%CI 2.8-3.4) and multiple BCGs (OR = 10.2, 95%CI 7.7-13.6) were both associated with a positive TST. A positive TST was also associated with a shorter duration in years between the most recent BCG and the TST.
The average prevalence of LTBI in a sequential sample of Aboriginal people living on a reserve in BC was estimated at 25%. BCG, especially in multiple doses, increased the likelihood of a positive TST.
The International Journal of Tuberculosis and Lung Disease 01/2007; 10(12):1347-53. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Restriction fragment length polymorphism (RFLP) analysis can be used to assess genetic relatedness of Mycobacterium tuberculosis isolates. This study reports a collaborative investigation of false-positive cultures for M. tuberculosis, suspected when the DNA fingerprint from an index case matched an epidemiologically improbable source case. RFLP analysis matched fingerprints in ten of 16 cases of suspected laboratory contamination to four separate smear-positive sources that were processed on the same day in the same laboratory. All single smear-negative, positive cultures processed on the same day as smear-positive specimens should be reviewed on a case-by-case basis to identify possible false-positive cultures.
Clinical Microbiology and Infection 11/2006; 12(10):1042-5. · 4.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Provincial tuberculosis (TB) services, British Columbia, Canada.
To estimate the risk of drug resistance among foreign-born TB patients and to identify risk factors associated with drug resistance.
Using the provincial TB database, we examined all culture-positive foreign-born TB patients for the years 1990-2001. The risk of having a drug-resistant isolate was estimated according to country and region of origin.
Of 1940 foreign-born patients identified, 247 (12.7%, 95%CI 11.3-14.3) cases had isolates resistant to at least one of the first-line drugs, with 160 (8.3%) isolates showing monoresistance, 24 (1.2%) multidrug resistance (resistance to at least isoniazid and rifampin) and 63 (3.3%) polyresistance (resistance to two or more drugs, excluding MDR). Country-specific analysis showed that immigrants from Vietnam (adjusted OR 2.12, 95%CI 1.37-3.27) and the Philippines (adjusted OR 1.71, 95%CI 1.10-2.66) had a significantly higher risk of resistance than other immigrants. In addition, the risk was the highest for younger TB patients and patients with reactivated disease (adjusted OR 2.12, 95%CI 1.09-4.09).
The risk of drug resistance was the highest among foreign-born patients from Vietnam and the Philippines. These findings should assist clinicians in prescribing and tailoring anti-tuberculosis regimens for immigrants more appropriately.
The International Journal of Tuberculosis and Lung Disease 09/2006; 10(8):844-50. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Provincial tuberculosis (TB) services, British Columbia, Canada.
To investigate risk factors associated with resistance to anti-tuberculosis drugs in British Columbia and to determine if there are differences in risk factor characteristics among different resistance categories.
Using population-based data from provincial TB services, all patients with positive culture for Mycobacterium tuberculosis from 1990 to 2001 were identified and included in the study. Logistic regression analyses were performed to assess risk factors for drug resistance.
Among 3041 eligible TB cases, 295 (10%) were found to be drug-resistant. Significant risk factors for resistance were younger age, foreign birth, ethnicity, reactivated TB and place of initial diagnosis. Foreign-born subjects (OR 3.18, 95%CI 2.26-4.49) were three times more likely to present with resistance than Canadian-born subjects. Among ethnic groups, Chinese (OR 2.32, 95%CI 1.51-3.57), South-East Asian (OR 2.92, 95%CI 1.88-4.52) and Other Asian subjects (OR 4.40, 95%CI 2.77-7.01) were 2-4 times more likely to present with resistance than Caucasians. Reactivated cases (OR 2.69, 95%CI 1.91-3.77) were three times as likely to have resistance as new cases.
These results document and quantify the risk of drug-resistant disease in a large population-based cohort, and highlight patient groups who should be identified as at risk for drug-resistant disease in the industrialised world.
The International Journal of Tuberculosis and Lung Disease 07/2006; 10(6):631-8. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fluoroquinolones are commonly used in the treatment of tuberculosis (TB) for drug-sensitive patients who are intolerant to first-line antituberculous agents or who are infected with drug-resistant organisms. Despite increasing use of these agents, there is little information on their tolerance outside of clinical trial settings.
To compare overall rate of major adverse events associated with levofloxacin-containing regimen to standard therapy.
Cases (levofloxacin-containing regimen) were matched by age and sex to their control subjects (standard first-line TB drugs). Eligible patients were identified from the provincial TB database from 2001 to 2004. Drug safety was assessed by evaluation of the nature of the adverse event, the likelihood of association with the study medications, and severity. Only major side effects, that is, those who had a severe or moderate adverse event that was categorized to be definitely, probably, or possibly related to the TB medications, were considered for the analysis.
During the 3-year study period, 102 patients received levofloxacin, and 358 patients received first-line agents for treatment of active TB. There were no significant differences between the two groups except for indication (82% of patients in the levofloxacin group had an antecedent adverse event to first-line TB drugs, whereas 18% received levofloxacin because of resistance) and concurrent use of first-line drugs (majority of patients in the levofloxacin arm were not receiving concurrent isoniazid or rifampin). The rate of any major adverse event was almost half among those using levofloxacin as among those on standard therapies (rate ratio, 0.60; 95% confidence interval [CI], 0.44 to 0.82). After adjustment for the differences in exposure of concomitant medications, the rate of any major adverse event was similar between the levofloxacin and control arms (adjusted rate ratio, 0.83; 95% CI, 0.66 to 1.03). Furthermore, there was no difference between the levofloxacin and control arms with respect to CNS (adjusted rate ratio, 0.94; 95% CI, 0.61 to 1.43), GI tract (adjusted rate ratio, 0.81; 95% CI, 0.58 to 1.13), skin (adjusted rate ratio, 0.65; 95% CI, 0.38 to 1.10), or musculoskeletal (MSK) [adjusted rate ratio, 0.87; 95% CI, 0.48 to 1.60] related adverse events when adjusted for concomitant drugs. The results of the secondary analysis for the rate of major adverse events within the first 100 days were similar to the primary analysis. The time to the first major adverse event was similar between the levofloxacin group and the control group (adjusted hazards ratio, 1.01; 95% CI, 0.76 to 1.34).
Concomitant use of a levofloxacin-containing regimen resulted in a similar rate of adverse events compared with conventional first-line regimens when used for treatment of active TB, despite a history of adverse events.
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) remains a major health problem for Aboriginal people in Canada, with high rates of clustering of active TB cases. Bacille Calmette-Guerin (BCG) vaccination has been used as a preventive measure against TB in this high-risk population.
The study was designed to determine if BCG vaccination in Aboriginal people influenced recent TB transmission through an analysis of the clustering of TB cases.
A retrospective analysis of all culture-positive Mycobacterium tuberculosis cases in Aboriginal people in western Canada (1995 to 1997) was performed. Isolates were analyzed using standard methodology for restriction fragment length polymorphism and spoligotyping.
Of 256 culture-positive Aboriginal TB cases, BCG status was confirmed in 216 (84%) cases; 34% had been vaccinated with BCG, 57% were male and 56% were living on-reserve. Patients who had been vaccinated with BCG were younger than unvaccinated individuals (mean age 32.4+/-1.65 years versus 45.0+/-1.8 years, P<0.0001). Clustering was found in 62% of cases: 59% of non-BCG vaccinated cases were clustered versus 68% of those vaccinated with BCG (P=0.16). Younger patients (younger than 60 years of age) were more likely to be clustered in the univariate analysis (P<0.01). When age, sex, province, and HIV and reserve status were controlled for, BCG vaccination was not associated with clustering (OR 1.3, 95% CI 0.7 to 2.6).
BCG vaccinated Aboriginal people were no less likely to have active TB from recently transmitted disease. BCG vaccination appears to have limited value in preventing clustering of TB cases within this high-risk community.
Canadian respiratory journal: journal of the Canadian Thoracic Society 04/2005; 12(3):134-8. · 1.29 Impact Factor