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Recurrence of active tuberculosis following treatment of an initial disease episode can occur due to endogenous re-activation or exogenous re-infection. Cases of recurrent tuberculosis in the Australian state of New South Wales between 1994 and 2006 were identified by data linkage analysis with confirmatory review of case notes. Patients with more than one culture-positive disease episode during that time period who had completed treatment for the initial disease episode were included. Genotyping of Mycobacterium tuberculosis was used to determine whether recurrence was likely to be due to re-activation or re-infection. There were 5,723 tuberculosis notifications between 1994 and 2006, 3,731 of which were culture-positive. Fifteen (0.4%) patients had recurrent culture-positive disease over a mean 5.7 yrs of follow-up (crude annual incidence 71 per 100,000 population). Recurrent tuberculosis was attributable to re-activation (indistinguishable strains) in 11 (73%) cases and to re-infection (different strains) in four (27%). In a low-incidence setting of tuberculosis, a control programme incorporating directly observed therapy for active disease resulted in a very low rate of recurrent tuberculosis over a long period of follow-up. Re-infection is less likely than re-activation, but still contributes significantly to the number of cases with recurrent disease.

Background.Healthcare workers have an increased risk of latent tuberculosis infection (LTBI), but previous studies suggested that they might be reluctant to accept preventive tuberculosis (TB) treatment. We aimed to examine doctors’ and nurses’ experience of TB screening and to explore their attitudes towards preventive TB treatment.Methods.We conducted a survey among randomly selected healthcare workers at a tertiary hospital in Sydney, Australia, using a paper-based questionnaire.Results.A total of 1,304 questionnaires were distributed and 311 (24%) responses were received. The majority of hospital staff supported preventive TB treatment in health care workers with evidence of latent TB infection (LTBI) in general (74%, 164/223) and for them personally (81%, 198/244) while 80 and 53 healthcare workers respectively had no opinion on the topic. Staff working in respiratory medicine were significantly less likely to support preventive TB treatment in health care workers in general or for them personally if they would have evidence of LTBI compared to other specialties (p= 0.001). Only 13% (14/106) of respondents with evidence of LTBI indicated that they had been offered preventive TB treatment. Twenty-one percent (64/306) of respondents indicated that they did not know the difference between active and latent TB. Among staff who had undergone testing for LTBI, only 33% (75/230) felt adequately informed about the meaning of their test results.Discussion.Hospital staff in general had positive attitudes towards preventive TB treatment, but actual treatment rates were low and perceived knowledge about LTBI was insufficient among a significant proportion of staff. The gap between high support for preventive TB treatment among staff and low treatment rates needs to be addressed. Better education on the concept of LTBI and the meaning of screening test results is required.

Background This study examined potential risk factors of lymph node tuberculosis (LNTB), including phylogenetic lineages of Mycobacterium tuberculosis (MTB), in comparison to pulmonary tuberculosis (PTB) in a setting with an ethnically diverse population. Methods We conducted a case-control study at a major tuberculosis clinic in Sydney, Australia, which included all patients with peripheral LNTB seen at the clinic between 2000 and 2012. Controls were randomly selected patients with PTB seen at the same clinic during the study period. Epidemiological data were extracted from the hospital electronic database and medical records. Associations between LNTB and age, sex, ethnicity, comorbidities and phylogenetic lineages of MTB in comparison to PTB were examined using logistic regression in univariate and multivariate analyses. Results There were 212 cases with LNTB and 424 randomly selected controls with PTB. Among patients with LNTB, 74% were female and the mean age (standard deviation, SD) was 42 (16) years. Among patients with PTB, 43% were female and the mean age was 44 (22) years. Females, 45 to 64-year-olds and Southern Asians had an increased risk for LNTB (OR 3.13, 95% CI 2.10-4.67; OR 2.50, 95% CI 1.29-4.84; OR 3.95, 95% CI 1.54-10.12 respectively). Patients with diabetes were at a higher risk of PTB (OR 0.40, 95% CI 0.19 – 0.83 for LNTB). A subset analysis showed that patients infected with the East African Indian strain of MTB were more likely to develop LNTB (OR 10.07, 95% CI 2.37-42.77). Conclusions An increased risk for LNTB (but still lower rates than for PTB) was found among females, people aged 45 to 64 years and people born in Southern Asia. An increased risk for PTB was found among patients with diabetes. The East African Indian strain of MTB was significantly associated with a higher likelihood of LNTB compared to other MTB strains.

To the Editor: Contact investigations, which are designed to identify and investigate people who have been exposed to patients with active tuberculosis (TB), are regarded an important component of TB control in low-incidence settings, such as Australia [1], where the incidence of TB is 6.0 per 100 000 and 88% of all cases of TB occur in people born overseas [2]. We aimed to estimate the prevalence of active TB at the time of initial screening and the subsequent incidence of TB among contacts of patients with TB living in Sydney, New South Wales (NSW), Australia. The study population comprised all persons who were screened as contacts of patients with TB between January 2000 and December 2009, at TB clinics within the Sydney West and Sydney South West Area Health Services. Contact screening and management in this jurisdiction is guided by state policy directives. Cases of active TB among the study population were identified by linking a database containing details for all identified contacts and the NSW notifiable diseases database (which includes the TB registry) using a combination of probabilistic and deterministic linkage methods [3]. TB was defined as any case that was notified as a case of active TB in the NSW notifiable diseases database. TB diagnosis at initial screening (period prevalence of TB) was defined as a TB diagnosis within 90 days of the first healthcare contact for contact screening. Incident cases of TB were ascertained for a period starting 90 days after the first healthcare contact for contact screening and continuing until December …

Background Directly observed therapy (DOT), as recommended by the World Health Organization, is used in many countries to deliver tuberculosis (TB) treatment. The effectiveness of community-based (CB DOT) versus clinic DOT has not been adequately assessed to date. We compared TB treatment outcomes of CB DOT (delivered by community health workers or community volunteers), with those achieved through conventional clinic DOT. Methods We performed a systematic review and meta-analysis of studies before 9 July 2014 comparing treatment outcomes of CB DOT and clinic DOT. The primary outcome was treatment success; the secondary outcome was loss to follow-up. Results Eight studies were included comparing CB DOT to clinic DOT, one a randomised controlled trial. CB DOT outperformed clinic DOT treatment success (pooled odds ratio (OR) of 1.54, 95% confidence interval (CI) 1.01 – 2.36, p = 0.046, I2 heterogeneity 84%). No statistically significant difference was found between the two DOT modalities for loss to follow-up (pooled OR 0.86, 95% CI 0.48 to 1.55, p = 0.62, I2 83%). Conclusions Based on this systematic review, CB DOT has a higher treatment success compared to clinic DOT. However, as only one study was a randomised controlled trial, the findings have to be interpreted with caution. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-0945-5) contains supplementary material, which is available to authorized users.

Objective The study aimed to determine factors that are associated with physicians’ decision to offer treatment for latent tuberculosis infection (LTBI) in contacts of patients with tuberculosis. Methods We performed a nested case-control study in a cohort of contacts of patients with pulmonary tuberculosis who had a tuberculin skin test (TST) ≥ 10 mm. Cases were those who were offered treatment for LTBI. Controls were randomly selected from those who were not offered treatment for LTBI by the reviewing physician. Odds ratios were estimated by multivariate logistic regression. Results There were 195 cases and 279 controls. The following factors were significantly (positively or negatively) associated with being offered LTBI treatment in the multivariate analysis: female gender (OR 2.9; 95% CI 1.6–5.5), TST conversion (OR 3.9; 2.0–7.9), TST > 20 mm (OR 4.1; 1.8–9.1, for TST of 21–30 mm and OR 7.9; 2.6–23.8, for TST >30 mm), sputum smear positive index case (OR 12.7; 4.5–36.1), being overseas-born and immigration more than 2 years ago (OR 0.1; 0.06–0.3), being a health care worker (OR 0.2; 0.1–0.6), being a non-household contact of the TB index case (OR 0.3; 0.2–0.6) and age >35 years (OR 0.2; 0.1–0.5 for age 35 to 54.9 years and OR 0.04; 0.01–0.2 for age ≥55 years). Previous BCG vaccine and chest x-ray findings were not significantly associated with physicians’ decision to offer treatment for LTBI. Conclusions Most factors that influenced physicians’ decisions on treatment for LTBI were based on evidence of an association with risk of developing TB or risk of having an adverse reaction to treatment for LTBI. However, the decreased likelihood of offering treatment for LTBI to people born overseas, men and health care workers, was apparently not based on any evidence of risk. Efforts should be made to ensure that these groups are given access to treatment for LTBI.

SETTING: An Australian metropolitan TB clinic where treatment for latent tuberculosis infection (LTBI) comprises six months of isoniazid, self-administered but dispensed monthly by the clinic. OBJECTIVE: To determine the proportion of patients who complete treatment for LTBI and to identify factors associated with non-completion. METHODS: Clinical files of all patients receiving treatment for LTBI between 01/2000 and 12/2010 were reviewed. The study population comprised all patients who were commenced on isoniazid as treatment for LTBI. Odds ratios (OR) for completing treatment were estimated by logistic regression. RESULTS: Of 216 patients who commenced isoniazid treatment for LTBI, 163 (75%) completed six months treatment [corrected]. Fifty-three percent of the 53 patients who did not complete treatment dropped out after three months treatment. The mean (SD) age of the patients was 27 (16) years and 123 (57%) were female. The majority of patients (59%) were born overseas and 69% received treatment for LTBI because they were contacts of patients with TB. Patients' sex, age, country of birth, time since immigration for overseas born people, health care worker status, TST conversion status, chest x-ray findings, language, employment status and the indication for which treatment of LTBI was prescribed were not significantly related to treatment completion. CONCLUSION: In a setting where isoniazid is dispensed monthly by the TB clinic, a relatively high proportion of patients who commence treatment for LTBI complete the six month scheduled course of treatment. The study did not identify any patient characteristics that predicted treatment completion. Interventions to improve completion rates should extend over the whole duration of treatment.

Background Tuberculosis is a major global health challenge that is caused by a bacteria which is spread by airborne droplets. Mostly patients are identified in high-burden countries when they visit health care facilities ('passive case finding'). Contacts of tuberculosis patients are a high-risk group for developing the disease. Actively screening contacts of people with confirmed tuberculosis may improve case detection rates and control of the disease. Objectives This study aims to compare whether active case finding among contacts of people with confirmed tuberculosis increases case detection compared to usual practice. Search methods In April 2011 we searched CENTRAL (The Cochrane Library 2011, Issue 2), MEDLINE, EMBASE, LILACS and mRCT. We also checked article reference lists, the International Journal of Tuberculosis and Lung Disease and contacted relevant researchers and organizations. Selection criteria Randomized and quasi-randomized trials of active case finding to detect tuberculosis disease among close and casual contacts of patients with microbiologically proven pulmonary tuberculosis (by sputum smear and/or culture). Data collection and analysis Two authors independently assessed eligibility and the methodological quality of the trials that were extracted using a search method that was outlined previously. Main results No trials met the inclusion criteria for this review. One RCT did test the effect of active case finding in contacts, but the intervention in that trial also included screening for, and treatment of, LTBI in contacts; and the separate effect of active case finding could not be estimated. Authors' conclusions There are currently insufficient data from randomized controlled trials or quasi-randomized controlled trials to evaluate the effect of active case finding for tuberculosis among contacts of patients with confirmed disease. While observational studies show that contacts have a higher risk of developing tuberculosis than the general population, further research is needed to determine whether active case finding among contacts significantly increases case detection rates.

Background The ability to identify individuals at increased risk of developing tuberculosis (TB) has important implications for public health policy and patient care. We conducted a general population historical cohort study in all Australian States and Territories to establish the risk of TB arising in people on chronic hemo- or peritoneal dialysis. Methodology/Principal Findings Cases of TB disease in patients receiving chronic dialysis were identified by record linkage using the Australia & New Zealand Dialysis and Transplant Registry (ANZDATA) and State and Territory TB notification databases 2001 to 2006. Main outcome measure was the relative risk of TB in people on dialysis, adjusted for TB incidence in country of birth, sex, age and indigenous status. A total of 6,276 cases of active TB were reported among 19,855,283 people living in Australia between 2001 and 2006. Among 14,506 patients on dialysis, 37 had a notification for TB disease after commencing dialysis, of whom 28 were culture positive. The incidence of TB was 66.8/100,000/year (95% CI 47.7 to 93.2) among people on dialysis and 5.7/100,000/year (95% CI 5.5 to 5.8) in the general population. The adjusted relative risk (aRR) of TB in people on dialysis was 7.8 (95% CI 3.3 to 18.7), and the aRR of culture positive TB was 8.6 (95% CI 3.9 to 19.3). Conclusions/Significance Patients on dialysis are at increased risk of TB. The final decision to screen for, and to treat, LTBI in individual dialysis patients will be influenced by a cumulative assessment of the risk of reactivation of TB and by assessment of risk factors for adverse effects of treatment.

Objective Previous studies that have found an increased risk for tuberculosis (TB) in people with diabetes mellitus (DM) have been conducted in segments of the population and have not adjusted for important potential confounders. We sought to determine the RR for TB in the presence of DM in a national population with data on confounding factors in order to inform the decision-making process about latent tuberculosis infection (LTBI) screening in people with diabetes. Design Whole population historical cohort study. Setting All Australian States and Territories with a mean TB incidence of 5.8/100 000. Participants Cases of TB in people with DM were identified by record linkage using the National Diabetes Services Scheme Database and TB notification databases for the years 2001–2006. Primary and secondary outcome measures Primary outcome was notified cases of TB. Secondary outcome was notified cases of culture-confirmed TB. RR of TB was estimated with adjustment for age, sex, TB incidence in country of birth and indigenous status. Results There were 6276 cases of active TB among 19 855 283 people living in Australia between 2001 and 2006. There were 271 (188 culture positive) cases of TB among 802 087 members of the DM cohort and 130 cases of TB among 273 023 people using insulin. The crude RR of TB was 1.78 (95% CI 1.17 to 2.73) in all people with DM and 2.16 (95% CI 1.19 to 3.93) in people with DM using insulin. The adjusted RRs were 1.48 (95% CI 1.04 to 2.10) and 2.27 (95% CI 1.41 to 3.66), respectively. Conclusions The presence of DM alone does not justify screening for LTBI. However, when combined with other risk factors for TB, the presence of DM may be sufficient to justify screening and treatment for LTBI., Article summary Article focus National, general population-based, historical cohort study to estimate the risk of tuberculosis (TB) among people with diabetes mellitus (DM). Adjustment for important potentially confounding risk factors including age, sex, indigenous status and TB incidence in country of birth. Key messages Overall, people with DM have a 1.5-fold increased risk of developing TB. The risk for TB is higher among people who are using insulin for DM. DM accounts for a small proportion of cases of TB in a low TB incidence setting. Strengths and limitations of this study The strengths of this study are the cohort design, the large population size, the general population base for the study cohort and the adjustment for important potential confounders, especially TB incidence in the country of birth. The study limitations are the unavailability of laboratory results to indicate if blood glucose levels were well or poorly controlled in people with DM and the inability to reliably distinguish between type 1 and type 2 DM in this data source.

Background Statins have anti-inflammatory and immunomodulating properties which could possibly influence inflammatory airways disease. We assessed evidence for disease modifying effects of statin treatment in patients with chronic obstructive pulmonary disease (COPD). Methods A systematic review was conducted of studies which reported effects of statin treatment in COPD. Data sources searched included MEDLINE, EMBASE and reference lists. Results Eight papers reporting nine original studies met the selection criteria. One was a randomized controlled trial (RCT), one a retrospective nested case-control study, five were retrospective cohort studies of which one was linked with a case-control study, and one was a retrospective population-based analysis. Outcomes associated with treatment with statins included decreased all-cause mortality in three out of four studies (OR/HR 0.48–0.67 in three studies, OR 0.99 in one study), decreased COPD-related mortality (OR 0.19–0.29), reduction in incidence of respiratory-related urgent care (OR 0.74), fewer COPD exacerbations (OR 0.43), fewer intubations for COPD exacerbations (OR 0.1) and attenuated decline in pulmonary function. The RCT reported improvement in exercise capacity and dyspnea after exercise associated with decreased levels of C-reactive protein and Interleukin-6 in statin users, but no improvement of lung function. Conclusion There is evidence from observational studies and one RCT that statins may reduce morbidity and/or mortality in COPD patients. Further interventional studies are required to confirm these findings.