Performance of the new automated Abbott RealTime MTB assay for rapid detection of Mycobacterium tuberculosis complex in respiratory specimens.

The automated high-throughput Abbott RealTime MTB real-time PCR assay has been recently launched for Mycobacterium tuberculosis complex (MTBC) clinical diagnosis. This study would like to evaluate its performance. We first compared its diagnostic performance with the Roche Cobas TaqMan MTB assay on 214 clinical respiratory specimens. Prospective analysis of a total 520 specimens was then performed to further evaluate the Abbott assay. The Abbott assay showed a lower limit of detection at 22.5 AFB/ml, which was more sensitive than the Cobas assay (167.5 AFB/ml). The two assays demonstrated a significant difference in diagnostic performance (McNemar's test; P = 0.0034), in which the Abbott assay presented significantly higher area under curve (AUC) than the Cobas assay (1.000 vs 0.880; P = 0.0002). The Abbott assay demonstrated extremely low PCR inhibition on clinical respiratory specimens. The automated Abbott assay required only very short manual handling time (0.5 h), which could help to improve the laboratory management. In the prospective analysis, the overall estimates for sensitivity and specificity of the Abbott assay were both 100 % among smear-positive specimens, whereas the smear-negative specimens were 96.7 and 96.1 %, respectively. No cross-reactivity with non-tuberculosis mycobacterial species was observed. The superiority in sensitivity of the Abbott assay for detecting MTBC in smear-negative specimens could further minimize the risk in MTBC false-negative detection. The new Abbott RealTime MTB assay has good diagnostic performance which can be a useful diagnostic tool for rapid MTBC detection in clinical laboratories.

Immigrants and tuberculosis in Hong Kong.

OBJECTIVE: To examine the impact of immigrant populations on the epidemiology of tuberculosis in Hong Kong. DESIGN: Longitudinal cohort study. SETTING: Hong Kong. PARTICIPANTS: Socio-demographic and disease characteristics of all tuberculosis notifications in 2006 were captured from the statutory tuberculosis registry and central tuberculosis reference laboratory. Using 2006 By-census population data, indirect sex- and age-standardised incidence ratios by place of birth were calculated. Treatment outcome at 12 months was ascertained from government tuberculosis programme record forms, and tuberculosis relapse was tracked through the notification registry and death registry up to 30 June 2013. RESULTS: Moderately higher sex- and age-standardised incidence ratios were observed among various immigrant groups: 1.06 (Mainland China), 2.02 (India, Pakistan, Bangladesh), 1.59 (Philippines, Thailand, Indonesia, Nepal), and 3.11 (Vietnam). Recent Mainland migrants had a lower sex- and age-standardised incidence ratio (0.51 vs 1.09) than those who immigrated 7 years ago or earlier. Age younger than 65 years, birth in the Mainland or the above Asian countries, and previous treatment were independently associated with resistance to isoniazid and/or rifampicin. Older age, birth in the above Asian countries, non-permanent residents, previous history of treatment, and resistance to isoniazid and/or rifampicin were independently associated with poor treatment outcome (other than cure/treatment completion) at 1 year. Birth outside Hong Kong was an independent predictor of relapse following successful completion of treatment (adjusted hazard ratio=1.76; 95% confidence interval, 1.07-2.89; P=0.025). CONCLUSION: Immigrants carry with them a higher tuberculosis incidence and/or drug resistance rate from their place of origin. The higher drug resistance rate, poorer treatment outcome, and excess relapse risk raise concern over secondary transmission of drug-resistant tuberculosis within the local community.

Treatment outcomes after early initiation of antiretroviral therapy for human immunodeficiency virus-associated tuberculosis.

OBJECTIVE: To evaluate the optimal timing for initiating antiretroviral therapy in patients with human immunodeficiency virus (HIV)-associated tuberculosis in Hong Kong. DESIGN: Historical cohort. SETTING. Tuberculosis and Chest Service and Special Preventive Programme, Public Health Service Branch, Centre for Health Protection, Department of Health, Hong Kong. PATIENTS: Consecutive patients with HIV-associated tuberculosis in a territory-wide TB-HIV registry encountered from 1996 to 2009. RESULTS: Of the 260 antiretroviral therapy-naïve patients with HIV-associated tuberculosis, 32 (12%) had antiretroviral therapy initiated within 2 months after starting anti-tuberculosis treatment (early antiretroviral therapy). Early antiretroviral therapy was associated with a more favourable outcome (cure or treatment completion without relapse) at 24 months (91% vs 67%; P=0.007) than those with antiretroviral therapy started later or not initiated, and remained an independent predictor of a favourable outcome after adjustment for potential confounders. Adverse effects from anti-tuberculosis drugs tended to occur more frequently in patients with early antiretroviral therapy (13/32 or 41%) compared with the remainder (59/228 or 26%; P=0.08). A significantly higher proportion of patients in the former group experienced immune reconstitution inflammatory syndrome than in the latter group (7/32 or 22% vs 9/228 or 4%; P<0.001). There was no death attributable to immune reconstitution inflammatory syndrome. CONCLUSIONS: Early initiation of antiretroviral therapy is associated with more favourable tuberculosis treatment outcomes in patients with HIV-associated tuberculosis with a low CD4 count (<200/µL). Drug co-toxicity and immune reconstitution inflammatory syndrome that may be increased by earlier initiation of antiretroviral therapy does not undermine tuberculosis treatment outcomes to a significant extent.

Treatment of patients with chronic obstructive pulmonary disease as practised in a defined Hong Kong community: a cross-sectional pilot survey.

OBJECTIVES: To examine the characteristics of chronic obstructive pulmonary disease patients of the Kwai-Tsing area, Hong Kong, and the chronic treatments they received. DESIGN. Cross-sectional survey. SETTING: Four clinic settings in Hong Kong: Respiratory Specialist Clinic, Princess Margaret Hospital (group 1); Medical Specialist Clinics, Princess Margaret Hospital (group 2); General Outpatient Clinics, Princess Margaret Hospital (group 3); South Kwai Chung Chest Clinic, Department of Health (group 4). PATIENTS: Thirty physician-diagnosed chronic obstructive pulmonary disease patients in each of the above groups with post-bronchodilator 1-second forced expiratory volume/forced vital capacity ratios of less than 70% predicted values, who had been followed up at any of the participating clinics for at least 6 months. RESULTS: There were 111 male and nine female patients. The median age was 72.5 years and 79% had at least one medical co-morbidity. The mean duration of their chronic obstructive pulmonary disease was 9.8 years, and their mean post-bronchodilator 1-second forced expiratory volumes were 45% (for males) and 58% (for females) of predicted values. There were significantly fewer stage I and more stage IV patients in group 1. Influenza vaccination coverage within the previous 1 year was 54% and did not differ significantly between groups. Chronic obstructive pulmonary disease education was given significantly more often to group 1 patients. Short-acting beta agonists were used to treat all patients but long-acting bronchodilators and pulmonary rehabilitation were used almost exclusively in group 1. Overall, long-acting bronchodilators and pulmonary rehabilitation were offered to 16% and 5%, respectively, of those for whom these were indicated (according to international guidelines). CONCLUSION: In general there was insufficient education and under-treatment for chronic obstructive pulmonary disease patients. Management of such patients warrants improvements by way of increased accessibility to structured education programmes, pulmonary rehabilitation programmes, long-acting bronchodilator drugs, and respiratory specialist care.

Newer fluoroquinolones for treating respiratory infection: do they mask tuberculosis?

Possible masking of tuberculosis (TB) in treatment of community-acquired respiratory infection by newer fluoroquinolones has not been examined in randomised controlled trials. We undertook a randomised, open-label controlled trial involving adults with community-acquired pneumonia or infective exacerbation of bronchiectasis encountered in government chest clinics in Hong Kong. 427 participants were assigned by random permutated blocks of 20 to receive either amoxicillin clavulanate (n = 212) or moxifloxacin (n = 215). Participants were followed for 1 yr for active pulmonary TB. Excluding three participants with positive baseline culture, 13 developed active pulmonary TB: 10 (4.8%) out of 210 were given amoxicillin clavulanate, and three (1.4%) out of 214 were given moxifloxacin. The difference was significant by both proportion and time-to-event analysis. Post hoc analysis showed a significant decrease in the proportion with active pulmonary TB from 4.8% to 2.4% and 0% among participants given amoxicillin clavulanate (n = 210), moxifloxacin for predominantly 5 days (n = 127) and 10 days (n = 87), respectively. The log rank test for trend also showed a significant difference between the three subgroups. Regression models reaffirmed the linear effect; the adjusted odds ratio (95% confidence interval) of active pulmonary TB after moxifloxacin exposure up to predominantly 10 days was 0.3 (0.1-0.9). Newer fluoroquinolones appear to mask active pulmonary TB.

The epidemiology and clinical manifestations of human immunodeficiency virus-associated tuberculosis in Hong Kong.

OBJECTIVE: To evaluate the epidemiology and clinical manifestations of human immunodeficiency virus-associated tuberculosis in Hong Kong. DESIGN: Retrospective study. SETTING: Tuberculosis and Chest Service and Special Preventive Programme, Public Health Services Branch, Centre for Health Protection, Department of Health, Hong Kong Special Administrative Region. PATIENTS: Cases reported to the TB/HIV Registry jointly kept by the Tuberculosis and Chest Service and Special Preventive Programme from 1996 to 2006 were reviewed. The Registry includes cases of human immunodeficiency virus-associated tuberculosis diagnosed in the two services, and cases referred from regional hospitals under the Hong Kong Hospital Authority and the private sector. RESULTS: Tuberculosis has become an increasingly important acquired immunodeficiency syndrome-defining illness in Hong Kong, and overtook Pneumocystis jiroveci pneumonia for the first time as the most common primary acquired immunodeficiency syndrome-defining illness in 2005 (accounting for 39% and 31% of all such illnesses, respectively in that year). The presentation of human immunodeficiency virus-associated tuberculosis is often atypical. In these patients moreover, there was a slightly higher rate of multidrug-resistant tuberculosis (2%) than in the general population (range, 0.7-1.5%). CONCLUSIONS: Programmes for the provider-initiated human immunodeficiency virus testing policy to reduce diagnostic delays should continue and be enhanced. Continual surveillance of both conditions is imperative, especially in view of a possible link between human immunodeficiency virus and multidrug-resistant tuberculosis.

Age-period-cohort analysis of tuberculosis notifications in Hong Kong from 1961 to 2005.

BACKGROUND: Despite its wealth, excellent vital indices and robust health care infrastructure, Hong Kong has a relatively high incidence of tuberculosis (TB) (85.4 per 100 000). Hong Kong residents have also experienced a very rapid and recent epidemiological transition; the population largely originated from migration by southern Chinese in the mid 20th century. Given the potentially long latency period of TB infection, an investigation was undertaken to determine the extent to which TB incidence rates reflect the population history and the impact of public health interventions. METHODS: An age-period-cohort model was used to break down the Hong Kong TB notification rates from 1961 to 2005 into the effects of age, calendar period and birth cohort. RESULTS: Analysis by age showed a consistent pattern across all the cohorts by year of birth, with a peak in the relative risk of TB at 20-24 years of age. Analysis by year of birth showed an increase in the relative risk of TB from 1880 to 1900, stable risk until 1910, then a linear rate of decline from 1910 with an inflection point at 1990 for a steeper rate of decline. Period effects yielded only one inflection during the calendar years 1971-5. CONCLUSIONS: Economic development, social change and the World Health Organisation's short-course directly observed therapy (DOTS) strategy have contributed to TB control in Hong Kong. The linear cohort effect until 1990 suggests that a relatively high, but slowly falling, incidence of TB in Hong Kong will continue into the next few decades.

Supervised and induced sputum among patients with smear-negative pulmonary tuberculosis.

Sputum culture is essential for monitoring drug resistance. Although sputum induction may optimise culture yield, better selection criteria and simpler algorithms are needed for countries with intermediate tuberculosis burdens. From a cohort of 660 patients who registered for antituberculosis treatment in a government chest clinic from May 21, 2005 to February 28, 2007, 187 patients with pulmonary disease and a negative smear in two unsupervised sputum specimens were enrolled prospectively for collection of one specimen each of supervised and induced sputum in succession. Among enrolled patients, induced sputum significantly improved ease of expectoration on a subjective five-point scale. Among 78 patients with culture-proven pulmonary tuberculosis, analysis of matched sputum culture results showed that: 1) induced sputum outperformed supervised sputum; 2) the second unsupervised sputum was significantly inferior to the first and redundant in the presence of the others; 3) adding one specimen each of supervised and induced sputum to two unsupervised specimens increased culture yield significantly; and 4) patients with either extent of disease less than right upper lobe or no respiratory symptoms were more likely to benefit. In summary, it may be practical to collect a sample of unsupervised, supervised and induced sputum for smear-negative patients with extent of disease less than the right upper lobe, especially when respiratory symptoms are absent.

Comparison of T-Spot.TB and tuberculin skin test among silicotic patients.

In the present study, T-Spot.TB and the tuberculin skin test (TST) were compared in the screening of latent tuberculosis infection among silicotic patients. A conditional probability model was used to compare the potential clinical utilities of T-Spot.TB and TST performed on 134 silicotic subjects from December 1, 2004 to January 31, 2007. Data from a historical cohort were also reanalysed for further comparison. Agreement with T-Spot.TB was best using a TST cut-off of 10 mm. Age >or=65 yrs independently predicted a tuberculin reaction <10 mm (odds ratio = 3), but not a negative T-Spot.TB response. Lower measures of agreement were observed among current smokers and those aged >or=65 yrs. Tuberculin reaction size was well correlated with both early secretary antigenic target 6 and culture filtrate protein 10 spot counts, except among current smokers. Within the current estimates of sensitivity (88-95%) and specificity (86-99%) for T-Spot.TB, the positive likelihood ratio for T-Spot.TB test would be substantially higher (6.29-95.0 versus 1.65-1.94) and negative likelihood ratio substantially lower (0.05-0.14 versus 0.32-0.41) than the corresponding ratios for the tuberculin test. A low tuberculosis risk differential was similarly observed between tuberculin-negative and untreated tuberculin-positive subjects in the historical cohort. T-Spot.TB is likely to perform better than tuberculin test in the screening of latent tuberculosis infection among silicotic subjects.

TB surveillance in correctional institutions in Hong Kong, 1999-2005.

OBJECTIVE: To understand the epidemiology of tuberculosis (TB) inside the prison system of Hong Kong. METHOD: Prospective territory-wide TB surveillance was conducted among prisoners in 24 correctional institutions. RESULTS: From 1999 to 2005, 622 prevalent TB cases diagnosed before or within 3 months of incarceration and 214 incident cases diagnosed after 3 months were reported by prison staff to a paper-based central prison TB registry. Both crude prevalence and incidence were falling (chi(2) for trend, both P < 0.001), despite a higher sex- and age-adjusted prison TB incidence as compared to the general population (indirectly standardised rate [ISR] 280.6 vs. 108.0/100000, P < 0.001). Illegal immigrants (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.8-7.4) and drug addicts (OR 2.04, 95%CI 1.13-3.7) were two major risk groups. The TB incident risk disappeared after their exclusion (ISR 117.1 vs. 108.0/100000, P = 0.52). No significant difference in the multidrug-resistant rate was found when comparing the group with the general population (3.5% vs. 1.0%, OR 3.6, 95%CI 0.5-28.4). No extensively drug-resistant (XDR) cases were identified. CONCLUSION: TB remains a significant disease in local prisons. Further strengthening of TB control programmes in prisons, especially targeting the higher risk groups, is recommended.

Risk factors for multidrug-resistant tuberculosis in Hong Kong.

SETTING: Previous anti-tuberculosis treatment is a widely reported risk factor for multidrug-resistant tuberculosis (MDR-TB), whereas other risk factors are less well described. In Hong Kong, the clinical characteristics of MDR-TB have not been systematically evaluated. OBJECTIVE: To explore the risk factors for MDR-TB in Hong Kong. DESIGN: MDR-TB patients treated between 1999 and 2003 were compared with non-MDR-TB patients by stratification of previous anti-tuberculosis treatment. RESULTS: One hundred and fifty-six MDR-TB patients, including 93 with and 63 without a previous history of anti-tuberculosis treatment, were identified. Among the 322 non-MDR-TB controls, respectively 192 and 130 patients did and did not have a previous history of anti-tuberculosis treatment. Using logistic regression analysis, non-permanent residents (OR 6.85, 95%CI 1.38-34.09), frequent travel (OR 2.48, 95%CI 1.07-5.74) and younger age were found to be independent predictors of MDR-TB in previously treated patients, whereas living on financial assistance just failed to reach statistical significance (OR 2.75, 95%CI 0.98-7.68, P=0.05). In the treatment-naïve group, despite significant differences in baseline characteristics among MDR-TB and non-MDR-TB patients, no independent predictor variables could be identified. CONCLUSION: In Hong Kong, non-permanent residents, frequent travel and young age were independent predictors of MDR-TB among previously treated patients.

Early and late tuberculosis risks among close contacts in Hong Kong.

SETTING: Tuberculosis (TB) notification is a statutory requirement in Hong Kong, where contact investigations are performed by the Tuberculosis and Chest Service. OBJECTIVES: 1) To evaluate the risk of active TB in close contacts within 5 years, and 2) to identify risk factors associated with early and late development of active TB disease. DESIGN: The characteristics of consecutive TB cases notified from 18 January to 17 April 2000 were collected together with those of their contacts. Contacts were prospectively followed up through the territory-wide TB notification registry for 5 years for the development of disease. RESULTS: A total of 1537 index cases and 4661 close contacts were analysed. Screening found 31 (0.67%) active TB cases within a 3-month period, and another 58 (1.24%) cases presented subsequently. Index cases with cough or pulmonary cavities and diabetic contacts were independent risk factors of early cases (all P<0.05). Adjusted at risk index characteristics for late TB development included positive sputum smear (2.79, 95%CI 1.31-5.95) and family history of TB (4.26, 95%CI 2.01-9.03). Contact risk factors included diabetes mellitus (3.44, 95%CI 1.04-11.33) and institutionalisation (3.61, 95%CI 1.70-7.65). CONCLUSION: Considerable TB risk remains after initial contact screening. A number of possible risk factors were identified.

Assessing relationships among properties of demolished concrete, recycled aggregate and recycled aggregate concrete using regression analysis.

Recycled demolished concrete (DC) as recycled aggregate (RA) and recycled aggregate concrete (RAC) is generally suitable for most construction applications. Low-grade applications, including sub-base and roadwork, have been implemented in many countries; however, higher-grade activities are rarely considered. This paper examines relationships among DC characteristics, properties of their RA and strength of their RAC using regression analysis. Ten samples collected from demolition sites are examined. The results show strong correlation among the DC samples, properties of RA and RAC. It should be highlighted that inferior quality of DC will lower the quality of RA and thus their RAC. Prediction of RAC strength is also formulated from the DC characteristics and the RA properties. From that, the RAC performance from DC and RA can be estimated. In addition, RAC design requirements can also be developed at the initial stage of concrete demolition. Recommendations are also given to improve the future concreting practice.

Delayed presentation and treatment of newly diagnosed pulmonary tuberculosis patients in Hong Kong.

OBJECTIVE: To measure patients' and providers' delays in the presentation and treatment of newly diagnosed pulmonary tuberculosis. DESIGN: Retrospective study using structured questionnaires. SETTING: Tuberculosis and Chest Service, Centre of Health Protection, Department of Health. PARTICIPANTS: Tuberculosis patients notified to the Department of Health, selected by systematic sampling of all notifications in the first 2 weeks of every even month in the year 2004. MAIN OUTCOME MEASURES: Health-seeking behaviour of pulmonary tuberculosis patients, including respective demographic, clinical, and disease factors. RESULTS: Of a total of 6262 notified tuberculosis patients in 2004, 1662 (26.5%) were recruited into the study; of these, 42.6% first presented to private doctors, and 57.4% to the public sector. The diagnosis of tuberculosis was made in 13.7% of these patients by the former and 86.3% by the latter. The median patient delay (elapsed time from symptoms to medical consultation) and provider delay (elapsed time from medical consultation to treatment) were both 20 days; 25th to 75th percentiles being 7-37 and 6-55 days, respectively. Longer patient delay was associated with positive sputum smear and culture, and more extensive radiological disease. On multiple regression analysis, unemployment independently predicted longer patient delay, while haemoptysis predicted shorter patient and total delay. Patients older than 60 years, with no initial sputum and chest X-ray examination predicted longer provider and total delays. CONCLUSIONS: Our patient and provider delays compared favourably with those of other countries, and very likely reflect easy service access. Adverse social factors and non-specific presentations prolong patient delay, whilst older age and unavailable bacteriological/radiological evidence delay diagnosis and treatment.

Prevalence and determinants of positive tuberculin reactions of residents in old age homes in Hong Kong.

OBJECTIVE: To determine the prevalence of tuberculous infection and the predictors of positive tuberculin reactivity in old age home residents in Hong Kong. DESIGN: Cross-sectional study. METHODS: A questionnaire-interview and review of medical records were carried out, together with measurement of weight and height/arm span and assessment of nutritional status. A one-stage tuberculin skin test (TST) was performed using two units of PPD RT23. An induration > or = 10 mm was considered as positive. RESULTS: Of 3682 residents (71.7% participation, mean age 82 years) who agreed to undergo a TST, 46.3% had a positive reaction. Factors associated with a significantly higher risk of a positive TST included being male, an ex- or current smoker and having a past history of tuberculosis (TB). Factors associated with reduced positive tuberculin reactivity included older age groups (> 70 years), a history of cancer and chronic obstructive pulmonary disease and low body mass index quartiles. CONCLUSION: In old age homes, the high prevalence of latent tuberculous infection is responsible for the high rate of active TB due to reactivation. Early diagnosis and treatment are necessary to prevent transmission of disease in these crowded environments with susceptible individuals.

Occupational tuberculosis: a review of the literature and the local situation.

OBJECTIVE: To review the risks and control of occupation-related tuberculosis. DATA SOURCES: Statutory notification data, local tuberculosis programme data, and census data were reviewed. Literature search of PubMed was performed up to December 2005. STUDY SELECTION: Original and major review articles related to tuberculosis among health care workers and guidelines for prevention were reviewed. DATA EXTRACTION: Relevant data were extracted from our literature review and local sources. DATA SYNTHESIS: Earlier experimental data demonstrated an airborne spread of tuberculosis and a steady state mathematical model for quantification of the transmission risk. In the post-chemotherapy era in developed countries, few studies demonstrated an occupational risk of tuberculin conversion outside of outbreak settings, and few studies were able to conclusively demonstrate an increased risk of active tuberculosis among health care workers. In countries with limited resource, the situation may be different, with a higher tuberculosis incidence among health care workers. Local tuberculosis programme and notification data from the Labour Department did not show an increased risk of active tuberculosis among health care workers. Although administrative control, engineering control, and personal protection are widely accepted control measures, it is difficult to quantify their cost-effectiveness. CONCLUSIONS: Although an increased liability to tuberculosis among health care workers is expected due to the concentration of infectious patients in their environment, prompt diagnosis and initiation of treatment may minimise the risk. A high background rate of disease and possible healthy worker effect may make it difficult to pick up a small risk differential. With the ongoing threat of a nosocomial outbreak, continuing vigilance is called for.

Directly observed treatment of tuberculosis in Hong Kong.

OBJECTIVE: To evaluate the local use of out-patient directly observed treatment (DOT) for tuberculosis (TB) control. SETTING: Seventeen government chest clinics managing around 80% of TB patients in Hong Kong. METHOD: A retrospective cohort. TB patients registered for treatment from 1 July to 31 August 2000 were followed up for 2 years. Baseline socio-demographic and clinical characteristics were correlated with adherence to DOT, mode of treatment and treatment outcomes. RESULTS: Of 988 patients, respectively 142, 140 and 21 switched to non-DOT within 2 months, 2-6 months and after 6 months. More Chinese patients than ethnic minorities switched to non-DOT within the first 2 months (15.2% vs. 0%, P = 0.001). Geographical inconvenience (31.7%) was the primary reason for switching initially, with increasing proportions giving no specific reason after the second month. Patients staying on DOT in the first 2 months had a significantly higher cure rate than those not on DOT, in both univariate (92.7% vs. 83.9%, P = 0.002) and multivariate analysis (OR = 2.5, P = 0.001). Subsequent switching, intermittent or daily regimen did not appear to affect the outcome. CONCLUSION: Significant numbers of patients failed to stay on DOT, and those staying initially had a better outcome.