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.

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.

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.

Tuberculosis is associated with increased lung cancer mortality.

SETTING: Elderly persons living in the community in Hong Kong. OBJECTIVE: To examine the association between tuberculosis (TB) and lung cancer. DESIGN: Elderly clients enrolled in a health programme from 2000 to 2003 were retrospectively cross-matched with the territory-wide TB notification registry for TB before enrolment. The cohort was followed up prospectively through linkage with the territory-wide death registry for cause of death until 31 December 2011. All subjects with suspected malignancy or recent weight loss (≥5%) at enrolment and deaths within the first 2 years of follow-up were excluded. RESULTS: Of the 61,239 subjects included, 516 had TB before enrolment. After 490,258 person-years of follow-up, respectively 1344, 910 and 2003 deaths were caused by lung cancer, other tobacco-related malignancies and non-tobacco-related malignancies. TB before enrolment was associated with death due to lung cancer (Mantel-Haenszel weighted relative risk 2.61, 95%CI 1.82-3.74, P < 0.001) but not other malignancies after stratification by sex. TB remained an independent predictor of lung cancer death (adjusted hazard ratio 2.01, 95%CI 1.40-2.90; P < 0.001), after adjustment for multiple potential confounders. CONCLUSIONS: TB was independently associated with subsequent mortality due to lung cancer. This finding calls for intensification of tobacco control and better targeting of lung cancer screening in high TB burden areas.

Obstructive lung disease does not increase lung cancer mortality among female never-smokers in Hong Kong.

SETTING: High lung cancer mortality is observed among female never-smokers in Hong Kong. OBJECTIVE: To examine the relationship between obstructive lung disease (chronic obstructive pulmonary disease and/or asthma) and lung cancer mortality by sex and smoking status. DESIGN: A cohort of elderly clients (aged ≥65 years) in a health maintenance programme were followed prospectively through linkage with the territory-wide death registry for causes of death, using identity card number as the unique identifier. RESULTS: After 516,055 person-years of follow-up, respectively 1297, 872 and 1908 deaths were caused by lung cancer, other tobacco-related malignancies and non-tobacco-related malignancies. In the overall analysis, obstructive lung disease was independently associated with mortality due to lung cancer (aHR 1.86, P < 0.001) after adjustment for potential confounders. However, no association was detected among female never-smokers (HR 0.97, P = 0.909), in sharp contrast with female ever-smokers, male never-smokers and male ever-smokers (HR 1.98, 2.34 and 2.09, respectively, P from 0.047 to <0.001). Consistent results were observed after exclusion of all deaths in the initial 3 years. CONCLUSION: Obstructive lung disease exerted differential effects on lung cancer mortality across different sex and smoking subgroups in this Asian population, with a conspicuous absence of effect among female never-smokers.

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.

Role of whole-blood interferon-gamma release assay in the diagnosis of smear-negative tuberculosis.

SETTING: Hong Kong Chest Clinics. OBJECTIVES AND METHODS: To conduct a prospective study investigating the role of a whole-blood interferon-gamma release assay, QuantiFERON®-TB Gold In-Tube (QFT-GIT), in the diagnosis of smear-negative tuberculosis (TB). The QFT-GIT result was compared with the final confirmed diagnosis after 12 months. RESULTS: Of 262 smear-negative subjects, 188 had active TB, 167 (88.8%) of whom were QFT-GIT-positive; 74 had inactive/non-TB, 30 (40.5%) of whom were QFT-GIT-negative. The positive (PPV) and negative predictive values for active TB were respectively 79.1% and 58.8%. For this target group with high TB prevalence (71.8%), a positive test increased the chance of active disease by only 7.3%. Despite a positive likelihood ratio (LR) of 1.49, the negative LR was 0.28, making the diagnosis of active TB much less likely after a negative test. Although sensitivity and specificity showed no difference across different age groups, the PPV decreased (P < 0.001) with increasing age, likely reflecting the increased prevalence of competing diagnoses. CONCLUSION: In an area with a high prevalence of latent TB infection, a positive QFT-GIT test does not add much to confirm the diagnosis of smear-negative TB, while a negative test indicates a need for further investigation.

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.

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.

Parameters for assessing recycled aggregate and their correlation.

Construction and demolition (C&D) waste has consumed a large portion of the landfill areas in Hong Kong. Among them, concrete occupies more than 70% of the total C&D waste by volume. Thus it is necessary to recycle concrete waste to preserve landfill areas. Various governmental departments of the Hong Kong Special Administrative Region (HKSAR) are encouraging the use of recycled aggregate (RA) in the Hong Kong construction industry by issuing various guidelines and specifications. Owing to uncertainty in their properties, however, practitioners are sceptical in using it as a substitute. In this study, an attempt has been made to look at relations among six main parameters that describe the behaviour of RA: (1) particle size distribution; (2) particle density; (3) porosity and absorption; (4) particle shape; (5) strength and toughness; and (6) chloride and sulphate contents. RA samples were obtained from nine demolition sites with service lives ranging from 10 to 40 years and another set of samples was collected from the Tuen Mun Area 38 recycling plant. The behaviour of these samples was compared with that of normal aggregate samples. This study revealed that there is a strong correlation among various parameters, and by measuring three of them: either 'particle density' or 'porosity and absorption' or 'particle shape', and 'strength and toughness', and 'chloride and sulphate contents', it is possible to assess the behaviour of RA. This can significantly help by reducing RA testing time and cost before using it as recycled aggregate concrete.

Physio-chemical reactions in recycle aggregate concrete.

Concrete waste constitutes the major proportion of construction waste at about 50% of the total waste generated. An effective way to reduce concrete waste is to reuse it as recycled aggregate (RA) for the production of recycled aggregate concrete (RAC). This paper studies the physio-chemical reactions of cement paste around aggregate for normal aggregate concrete (NAC) and RAC mixed with normal mixing approach (NMA) and two-stage mixing approach (TSMA) by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Four kinds of physio-chemical reactions have been recorded from the concrete samples, including the dehydration of C(3)S(2)H(3), iron-substituted ettringite, dehydroxylation of CH and development of C(6)S(3)H at about 90 degrees C, 135 degrees C, 441 degrees C and 570 degrees C, respectively. From the DSC results, it is confirmed that the concrete samples with RA substitution have generated less amount of strength enhancement chemical products when compared to those without RA substitution. However, the results from the TSMA are found improving the RAC quality. The pre-mix procedure of the TSMA can effectively develop some strength enhancing chemical products including, C(3)S(2)H(3), ettringite, CH and C(6)S(3)H, which shows that RAC made from the TSMA can improve the hydration processes.

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.

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.

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.

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.

Peak plasma rifampicin level in tuberculosis patients with slow culture conversion.

The clinical utility of therapeutic drug monitoring in tuberculosis has not been adequately evaluated by controlled clinical trials. To examine the relationship between slow culture conversion and peak plasma rifampicin level (Cmax-rfm) in a case-control study, patients with persistence of positive sputum smear despite at least 8 weeks of directly observed treatment with standard pyrazinamide-containing regimens were enrolled prospectively in government chest clinics from 16 December 2005 to 15 November 2006. Patients with multidrug-resistant tuberculosis, human immunodeficiency virus infection, or poor treatment adherence were excluded. Cases referred to patients with persistence of positive culture whereas controls had negative culture despite positive smear. Blood was checked at 2 and 4 hours post-dosing to capture Cmax-rfm. A cohort of 88 patients was identified. After excluding 16 patients, there were 36 controls and 36 cases. None had symptoms of malabsorption. Cmax-rfm was below 6 mg/l among 47% of controls and 44% of cases. Univariate and multiple logistic regression analyses showed no significant association between slow culture conversion and Cmax-rfm after logarithmic transformation. Thus, there is probably no association between Cmax-rfm and slow culture conversion.