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Biomedical subjects

R K Elwood

Publications and source records attributed to R K Elwood.

At least 19 recordsLinked to original sources

Investigation of suspected laboratory cross-contamination: interpretation of single smear-negative, positive cultures for Mycobacterium tuberculosis.

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.

Adult↗

A population-based study of risk factors for drug-resistant TB in British Columbia.

SETTING: Provincial tuberculosis (TB) services, British Columbia, Canada. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Adolescent↗

Impact of country of origin on drug-resistant tuberculosis among foreign-born persons in British Columbia.

SETTING: Provincial tuberculosis (TB) services, British Columbia, Canada. OBJECTIVES: To estimate the risk of drug resistance among foreign-born TB patients and to identify risk factors associated with drug resistance. DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

Adolescent↗

BCG vaccination and the prevalence of latent tuberculosis infection in an aboriginal population.

SETTING: 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. OBJECTIVE: To document the prevalence of LTBI in Aboriginal people living on a reserve in British Columbia (BC) and to determine the influence of BCG. DESIGN: A population-based, retrospective descriptive analysis of all epidemiological data collected for the on-reserve Aboriginal programme in BC (1951-1996). RESULTS: 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. CONCLUSION: 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.

Adolescent↗

Risk of tuberculosis in children from smear-negative source cases.

SETTING: British Columbia, Canada. OBJECTIVE: To determine the frequency of smear-negative tuberculosis (TB) transmission events from adults to children in epidemiologically linked pairs and to determine the predictors for identifying the source case. DESIGN: We extracted demographic, clinical and mycobacteriology information of 190 children with TB and their 83 source cases reported from 1990 to 2001 in the province of British Columbia. Smear-negative transmission events from adults to children were determined by identifying the smear results of epidemiologically linked source cases. We compared the sex, age, ethnicity, contact history, site of disease and tuberculin skin test (TST) results of children who had a source case identified with those who had not. RESULTS: Smear-negative source cases transmitted the disease to 10% of children (95%CI 5-17). Aboriginals (OR 4.9, 95%CI 1.5-13.4), those with primary TB (OR 7.3, 95%CI 3.3-16.0) and those with a positive TST (OR 2.9, 95%CI 1.2-7.0) were independent predictors for source case identification. CONCLUSION: This study suggests lower rates of transmission of disease to children from smear-negative sources compared to other studies involving all ages. Ethnicity of children, site of disease and a positive TST predict source case identification.

Adolescent↗

Transmission of tuberculosis from smear negative patients: a molecular epidemiology study.

BACKGROUND: While smear positive patients with tuberculosis (TB) are considered more infectious than smear negative patients, the latter can also transmit TB. METHODS: In a molecular epidemiology study of 791 patients in the Greater Vancouver regional district, the number of episodes of TB transmission from two groups of smear negative clustered patients by RFLP (assumed to be involved in recent transmission) was estimated after assessing for potential bias. Group 1 (n = 79) included patients with pulmonary TB or pulmonary + extrapulmonary disease (PTB or PTB+EPTB); group 2 (n = 129) included all patients in group 1 + extrapulmonary cases alone. RESULTS: In the total sample the mean (SD) age was 51 (21) years, 54.3% were male, and 17.0% of patients were clustered. Compared with smear negative patients, smear positive patients were more likely to be in a cluster (OR = 2.0, 95% CI 1.1 to 3.6) and to have had a history of ethanol abuse (OR = 2.7, 95% CI 1.0 to 6.7), diabetes mellitus (OR = 2.8, 95% CI 1.1 to 7.0), injection drug use (OR = 3.1, 95% CI 1.1 to 8.3), and to have had a previous hospital admission (OR = 8.5, 95% CI 5.1 to 14.0). The proportion of episodes of transmission from smear negative clustered patients ranged from 17.3% to 22.2% in group 1 and from 25% to 41% in group 2. CONCLUSION: In Greater Vancouver, smear negative cases appear responsible for at least one sixth of culture positive episodes of TB transmission.

Adolescent↗

Successful treatment of multidrug-resistant tuberculosis following drug-induced hepatic necrosis requiring liver transplant.

A 28-year-old female developed multidrug-resistant (MDR) tuberculous lymphadenitis following a trip to India. She was initially treated with a four-drug regimen of first-line anti-tuberculosis medications, but when sensitivities indicated resistance to isoniazid and rifampin, her regimen was altered to ciprofloxacin (CFX), pyrazinamide (PZA) and ethambutol. She subsequently developed a rash, flu-like symptoms and fever, which progressed to acute hepatic necrosis despite discontinuation of medication. The clinical presentation and subsequent investigations suggested a hypersensitivity reaction, possibly related to the quinolone. The patient subsequently had an orthoptic liver transplant; second-line anti-tuberculosis medications were restarted to which she responded clinically and radiologically. Our findings raise the possibility that the CFX and PZA combination was responsible for the hepatic necrosis. The patient also illustrates that active, even MDR tuberculosis is not a contraindication to hepatic transplant.

Adult↗

A meta-analysis of the effect of Bacille Calmette Guérin vaccination on tuberculin skin test measurements.

BACKGROUND: The accurate diagnosis of latent tuberculosis infection (LTBI) is an important component of any tuberculosis control programme and depends largely on tuberculin skin testing. The appropriate interpretation of skin test results requires knowledge of the possible confounding factors such as previous BCG vaccination. Uncertainty about the effect of BCG vaccination on tuberculin skin testing and the strength with which recommendations are made to individual patients regarding treatment of LTBI have identified a need to analyse the available data on the effect of BCG on skin testing. A meta-analysis of the evidence for the effect of BCG vaccination on tuberculin skin testing in subjects without active tuberculosis was therefore performed. METHODS: Medline was searched for English language articles published from 1966 to 1999 using the key words "BCG vaccine", "tuberculin test/PPD", and "skin testing". Bibliographies of relevant articles were reviewed for additional studies that may have been missed in the Medline search. Articles were considered for inclusion in the meta-analysis if they had recorded tuberculin skin test results in subjects who had received BCG vaccination more than 5 years previously and had a concurrent control group. Only prospective studies were considered. The geographical location, number of participants, type of BCG vaccine used, type of tuberculin skin test performed, and the results of the tuberculin skin test were extracted. RESULTS: The abstracts and titles of 980 articles were identified, 370 full text articles were reviewed, and 26 articles were included in the final analysis. Patients who had received BCG vaccination were more likely to have a positive skin test (5 TU PPD: relative risk (RR) 2.12 (95% confidence interval (CI)1.50 to 3.00); 2 TU RT23: 2.65 [corrected] (95% CI 1.83 to 3.85). The effect of BCG vaccination on PPD skin test results was less after 15 years. Positive skin tests with indurations of >15 mm are more likely to be the result of tuberculous infection than of BCG vaccination. CONCLUSIONS: In subjects without active tuberculosis, immunisation with BCG significantly increases the likelihood of a positive tuberculin skin test. The interpretation of the skin test therefore needs to be made in the individual clinical context and with evaluation of other risk factors for infection. The size of the induration should also be considered when making recommendations for treatment of latent infection.

BCG Vaccine↗

The significance of the persistent presence of acid-fast bacilli in sputum smears in pulmonary tuberculosis.

STUDY OBJECTIVES: Identification of acid-fast bacilli (AFB) in the sputum smear at the completion of tuberculosis therapy is in some settings considered evidence of treatment failure. However, some patients with pulmonary tuberculosis (TB) will have positive smear results with negative sputum culture results at the end of therapy. The objectives of this study were to estimate the prevalence of persisting positive sputum smear results in patients with TB and to identify characteristics that distinguish patients with persistently positive sputum smear results who also had negative sputum culture results from patients identified as treatment failures. DESIGN: A population-based, historical cohort study with nested case control study. SETTING: British Columbia Division of Tuberculosis Control central case registry. PATIENTS: All 428 patients with culture-proven pulmonary TB in British Columbia over 7 years with sputum that was positive for AFB. METHODS: Review of laboratory data of all 428 patients, as well as clinical data of a subset of 30 patients with persistently positive smear results beyond 20 weeks. RESULTS: Sputum smears were positive for AFB in 205 patients (48%) at 4 weeks, in 30 patients (7%) at 20 weeks, and in 12 patients (3%) at 36 weeks. Of the patients with smear results that were persistently positive at 20 weeks, 23 (77%) had negative sputum culture results and 7 (23%) had positive sputum culture results (ie, they were treatment failures). Patients identified as treatment failures had more localized disease as shown on chest radiographs, had less radiographic improvement at follow-up, had a higher prevalence of drug resistance, and were less compliant with medications than patients with persistently positive smear results and negative culture results. No subject with a negative culture result relapsed over the 6- to 48-month observation period. CONCLUSION: Sputum that is persistently positive for AFB in patients in developed countries is more likely to be associated with negative culture results than with treatment failure.

Adult↗

Use of incentives to increase compliance for TB screening in a population of intravenous drug users. Vancouver Injection Drug Use Study Group.

SETTING: Intravenous drug users (IDUs) represent a high risk group for dual human immunodeficiency virus (HIV) and tuberculosis (TB) infection. Screening with TB skin testing has therefore been suggested in this group. Subjects' compliance for returning to have TB skin test results read is a major problem. In the setting of a needle exchange program we evaluated the role of financial incentives to increase compliance. METHODS: We evaluated the role of giving a small financial incentive of Can $5 to subjects if they returned to have their purified protein derivative (PPD) skin test read. IDUs who had previously been skin-tested were compared with IDUs drawn from a similar population who, prospectively, were offered a financial incentive. RESULTS: During the initial period 558 subjects were evaluated and no incentive was offered. During the second phase of the study 549 IDUs were assessed but were also offered Can $5 if they returned to have their skin test read. Use of incentives increased compliance from 43% to 78% (P = 0.001). During the same period three active cases of TB were also diagnosed. CONCLUSIONS: We suggest that use of financial incentives can increase the return of IDUs to have their skin tests read. Further studies are required to assess the efficacy of follow-up interventions, especially the use of isoniazid chemoprophylaxis.

Adult↗

Acceptance and safety of directly observed versus self-administered isoniazid preventive therapy in aboriginal peoples in British Columbia.

OBJECTIVE: To document experience with directly observed chemoprophylaxis (DOPT) compared to self-administered isoniazid (INH) among aboriginal persons in British Columbia. DESIGN: DOPT was compared to self-administered delivery (SAD) over a 3-year period. All aboriginal persons who received INH chemoprophylaxis in British Columbia between 1992 and 1994 were evaluated. Therapy completion rates and adverse outcomes associated with SAD were compared with DOPT. Treatment allocation was by patient choice. RESULTS: Of 608 people who received INH prophylaxis, 443 received SAD (mean age 31.6 years) and 165 received DOPT (mean age 23.9 years). Two hundred and seventy (60.9%) SAD compared to 124 (75.2%) in the DOPT group completed 6 months of INH (P = 0.0011). The 12-month completion rates were 162/443 (36.6%) for the SAD group and 84/165 (50.9%) for the DOPT group (P = 0.0014). Adverse reactions requiring discontinuation of medication occurred in 13.5% of the patients on SAD and 9.7% of those receiving DOPT (P = 0.202). The most common reason cited for failure to complete therapy was non-cooperation in both groups. There were three deaths in the SAD group, one of which was due to suicide by self-ingestion of INH. CONCLUSIONS: These data demonstrate that in aboriginal people compliance with preventive therapy can be improved by DOPT. Non random allocation to treatment groups might have influenced our findings, and further prospective randomized trials and cost-effectiveness analyses are required.

Adult↗

Risk of tuberculosis in dialysis patients: a population-based study.

SETTING: Provincial tuberculosis (TB) and dialysis registries. OBJECTIVE: To document the risk of TB among patients on dialysis and to describe the clinical characteristics of these cases. METHODS: All cases of TB occurring among dialysis patients in British Columbia between January 1990 and December 1994 were reviewed, as were the age-specific rates for TB among the general population during the same period. RESULTS: During that period, a total of seven cases of TB occurred among 560 patients on hemo-dialysis and two cases among 326 patients on peritoneal dialysis. On an annual basis the rate of TB in the dialysis population was 253 per 100,000, compared to an age-matched rate of 10.1 per 100,000 in the general population, giving a relative risk of 25.3 (95% confidence interval 22.86-31.49, P = 0.0000001). CONCLUSIONS: The risk of TB in dialysis patients is significantly higher than previously reported from non population-based studies, indicating that dialysis patients should be considered a possible target population for systematic evaluation for the presence of TB infection and consideration for chemoprophylaxis.

Adult↗

HIV-related tuberculosis in British Columbia: indications of a rise in prevalence and a change in risk groups.

OBJECTIVES: To identify patients with coexisting HIV infection and tuberculosis (TB) and recent trends in prevalence and factors associated with coinfection. DESIGN: Case review. PARTICIPANTS: All known patients with TB and HIV infection in British Columbia, in whom TB was diagnosed between 1990 and 1994. This group was compared with those in whom TB was diagnosed between 1984 and 1990. OUTCOME MEASURES: Patients' demographic characteristics and risk factors for HIV infection, site of TB, occurrence of drug-resistant TB, treatment and outcome. RESULTS: Forty-four patients with HIV infection and TB were identified, of whom 16% were women, whereas non of those diagnosed from 1984 to 1990 were women, and 14 (32%) were aboriginal Canadians, compared with only 3 (8%) of those diagnosed from 1984 to 1990 (p < 0.01 for both). Forty patients had identifiable risk factors for HIV infection. A smaller proportion of the recent group than of the previous group were homosexual men (excluding those for whom risk factors were not known, 17/33 men [52%] in 1990 to 1994 v. 36/39 [92%] in 1984 to 1990), and a larger proportion were intravenous drug users (22/40 [55%] in 1990 to 1994 v. 8/39 [21%] in 1984 to 1990, p < 0.01 for both). Since 1984 an increasing proportion of patients with TB diagnosed each year have also had HIV infection (linear trend p < 0.001). Drug resistance was not found in any cultures taken at the time of diagnosis; however, rifampin resistance developed 7 months after therapy was initiated in one patient. Of the 40 patients who started therapy, 24 had directly observed therapy. Nine patients died while receiving therapy, and four died without receiving any antituberculous therapy. TB was the cause of death, or a contributing factor to death, in five cases. CONCLUSIONS: Significantly more intravenous drug users, aboriginal Canadians and women are now presenting with HIV-related TB in British Columbia. All HIV-positive patients need to be evaluated for TB, and HIV infection must be considered in assessing all newly diagnosed TB cases and in screening contacts of active cases, especially if patients have risk factors for HIV infection.

AIDS-Related Opportunistic Infections↗