Strategic investment in tuberculosis control in the Republic of Bulgaria.

As Bulgaria transitions away from Global Fund grant, robust estimates of the comparative impact of the various response strategies under consideration are needed to ensure sustained effectiveness of the tuberculosis (TB) programme. We tailored an established mathematical model for TB control to the epidemic in Bulgaria to project the likely outcomes of seven intervention scenarios. Under existing programmatic conditions projected forward, the country's targets for achieving TB elimination in the coming decades will not be achieved. No interventions under consideration were predicted to accelerate the baseline projected reduction in epidemiological indicators significantly. Discontinuation of the 'Open Doors' program and activities of non-governmental organisations would result in a marked exacerbation of the epidemic (increasing incidence in 2035 by 6-8% relative to baseline conditions projected forward). Changing to a short course regimen for multidrug-resistant TB (MDR-TB) would substantially decrease MDR-TB mortality (by 21.6% in 2035 relative to baseline conditions projected forward). Changing to ambulatory care for eligible patients would not affect TB burden but would be markedly cost-saving. In conclusion, Bulgaria faces important challenges in transitioning to a primarily domestically-financed TB programme. The country should consider maintaining currently effective programs and shifting towards ambulatory care to ensure program sustainability.

Risk factors for infectiousness of patients with tuberculosis: a systematic review and meta-analysis.

We performed a systematic review and meta-analyses of studies assessing tuberculosis (TB) patient-related risk factors for transmission of Mycobacterium tuberculosis infection. Meta-analyses were conducted for sputum smear-positivity, lung cavitation and HIV seropositivity of index patients with both crude and adjusted odds ratios (AORs) pooled using random effect models. Thirty-seven studies were included in the review. We found that demographic characteristics such as age and sex were not significant risk factors, while behaviours such as smoking and alcohol intake were associated with infectiousness although inconsistently. Treatment delay of >28 days was a significant predictor of greater infectiousness. Contacts of sputum smear-positive index patients were found to be more likely to be infected than contacts of sputum smear-negative patients, with a pooled AOR of 2.15 (95% confidence interval (CI) 1.47-3.17, I 2 = 38%). Similarly, contacts of patients with the cavitary disease were around twice as likely to be infected as contacts of patients without cavitation (pooled AOR 1.9, 95% CI 1.26-2.84, I 2 = 63%). In contrast, HIV seropositive patients were associated with few contact infections than HIV seronegative patients (AOR 0.45, 95% CI 0.26-0.80, I 2 = 52%). In conclusion, behavioural and clinical characteristics of TB patients can be used to identify highly infectious patients for targeted interventions.

Literature Highlights.

Literature Highlights is a digest of notable papers recently published in the leading respiratory journals, allowing our readers to stay up-to-date with research advances. Coverage in this issue includes Vitamin D supplementation to prevent TB infection; network models of TB dynamics through enhanced data collection linked to active case-finding; hydrocortisone use for severe community-acquired pneumonia; and low-cost air quality sensors and individual exposure levels.

Literature Highlights.

Literature Highlights is a digest of notable papers recently published in the leading respiratory journals, allowing our readers to stay up-to-date with research advances. Coverage in this issue includes time to smear and culture conversion during TB treatment; probability of diagnosing ventilator-associated pneumonia in intensive care and use of antimicrobials; optimising computer-aided chest X-ray to diagnose intra-thoracic TB in children; and clinical standards for asthma in low- and middle-income countries.

Inability of single resting arterial blood gas to predict significant hypoxaemia in chronic obstructive pulmonary disease.

BACKGROUND: While point measurement of resting arterial partial pressure of oxygen (P(a)O(2)) is the traditional gold-standard for assessment of oxygenation in chronic obstructive pulmonary disease (COPD), 24-h oximetry may identify further patients with clinically significant hypoxaemia. We aimed to describe the relationship between these two parameters and identify other correlated variables. METHODS: All patients registered with the Barwon Health Hospital Admission Risk Program from 1 March to 31 October 2008 for the diagnosis of COPD were identified. The main inclusion criteria were obstructive spirometry, clinical stability and moderate resting hypoxaemia (P(a)O(2) 56-70 mmHg). All patients underwent 24-h oximetry, arterial blood gas, spirometry, anthropometry and telephone questionnaire, and 23 patients also completed polysomnography. RESULTS: Inclusion criteria were met in 35 of 287 patients. Mean recording time was 23.5 h, representing 97% of intended oximetry time. Nineteen patients (54%) spent greater than 30% of recorded oximetry time below 90%. There was a moderate inverse correlation between time below 90% saturations and P(a)O(2) (r=-0.40, P= 0.02), with body mass index (BMI) the only other independent predictor of the primary outcome identified (r= 0.39, P= 0.02). Correlations were similar for waking hours considered separately. However, for sleeping oximetry, BMI and age were the only independent predictors of time below 90%. Polysomnography demonstrated a high prevalence of rapid eye movement-related hypoventilation and obstructive sleep apnoea syndrome. CONCLUSIONS: Many patients with moderate hypoxaemia on resting P(a)O(2) desaturate significantly on ambulatory oximetry. The correlation between P(a)O(2) and proportion of saturations below 90% is moderate and similar to BMI, but this pattern does not hold during sleeping hours.

Gender differences in tuberculosis diagnosis, treatment and outcomes in Victoria, Australia, 2002-2015.

BACKGROUND: Gender has a significant impact on tuberculosis (TB) diagnosis and outcomes in many settings worldwide. We explored gender differences in Victoria, Australia, a low-incidence setting. METHODS: Retrospective cohort study: 2002-2015. Gender was included as an independent variable in multivariate statistical analyses assessing TB management. RESULTS: There were 2655 (54.5%) males and 2212 (45.5%) females notified (male:female ratio = 1.2:1). Among cases with pulmonary involvement, males underwent a chest X-ray or CT scan (CXR) sooner (hazard ratio [HR] 1.2, 95%CI 1.04-1.31, P = 0.010), began treatment sooner after presentation (HR 1.2, 95%CI 1.08-1.34, P = 0.001) and were more likely to have a sputum smear sample performed (OR 1.3, 95%CI 1.01-1.55, P = 0.037). Male cases with extra-pulmonary TB sought health care sooner after symptom onset (HR 1.3, 95%CI 1.03-1.58, P = 0.024) and were more likely to have an abnormal CXR (OR 1.9, 95%CI 1.54-2.32, P < 0.001). Males were more likely to die before or during treatment (OR 1.5, 95%CI 1.06-2.11, P = 0.024). CONCLUSIONS: Women experienced small delays in management compared with men, with no obvious detriment to assessment results or treatment outcomes. Differences were consistent with the hypothesis that males manifest more severe disease at presentation, which could be related to a range of biological and social factors.

Heterogeneity of distribution of tuberculosis in Sheka Zone, Ethiopia: drivers and temporal trends.

OBJECTIVE: To describe the distribution of tuberculosis (TB) and its drivers in Sheka Zone, a geographically remote region of Ethiopia. METHODS: We collected data on TB patients treated from 2010 to 2014 in the Sheka Zone. Predictors of TB incidence were determined using a multivariate generalised linear regression model. RESULTS: We found significant spatial autocorrelation of TB incidence by kebele (the smallest administrative geographical subdivision in Ethiopia) (Moran's I = 0.3, P < 0.001). The average TB incidence per kebele ranged from 0 to 453 per 100 000 population per year, and was significantly associated with average TB incidence across adjacent kebeles, TB incidence in the same kebele in the previous year and health facility availability. Each increment in TB incidence by 10/100 000/year in adjacent kebeles or in a previous year was associated with an increase in TB incidence of respectively 3.0 and 5.5/100 000/year. Availability of a health centre was associated with an increase in TB incidence of 84.3/100 000. CONCLUSIONS: TB incidence in rural Ethiopia is highly heterogeneous, showing significant spatial autocorrelation. Both local transmission and access to health care are likely contributors to this pattern. Identification of local hotspots may assist in developing and optimising effective prevention and control strategies.

Recurrence of tuberculosis in a low-incidence setting without directly observed treatment: Victoria, Australia, 2002-2014.

SETTING: Victoria, Australia, is an industrialised setting with low tuberculosis (TB) incidence and universal health care. Individually tailored adherence support for self-administered daily anti-tuberculosis treatment is provided. Directly observed treatment (DOT) is very rarely used. OBJECTIVE: To review the rate of recurrent TB in Victoria between 2002 and 2014. DESIGN: This was a retrospective cohort study. All recurrent episodes of TB were reviewed and 24-locus MIRU-VNTR (mycobacterial interspersed repetitive units-variable number of tandem repeats) molecular typing was used where possible to determine the likelihood of relapse or reinfection. RESULTS: Of 4766 notifications, 32 (0.7%) were recurrent episodes. Of 20 episodes that occurred in patients who had previously completed treatment, 11 were culture-positive (0.4% of 3012 culture-positive episodes): 9 were likely relapses (distinguishable at no more than one of 24 loci) and two were likely reinfections, giving a TB relapse rate among culture-positive episodes of 52.5/100 000 person-years (mean time to study end per patient of 5.7 years). The median time until relapse was 18 months (interquartile range 12-30). CONCLUSIONS: The low rate of relapse in our setting demonstrates that individually tailored adherence support for self-administered anti-tuberculosis treatment can achieve excellent treatment outcomes.

Is IPT more effective in high-burden settings? Modelling the effect of tuberculosis incidence on IPT impact.

SETTING: Isoniazid preventive therapy (IPT) is effective for preventing active tuberculosis (TB), although its mechanism of action is poorly understood and the optimal disease burden for IPT use has not been defined. OBJECTIVE: To describe the relationship between TB incidence and IPT effectiveness. METHODS: We constructed a model of TB transmission dynamics to investigate IPT effectiveness under various epidemiological settings. The model structure was intended to be highly adaptable to uncertainty in both input parameters and the mechanism of action of IPT. To determine the optimal setting for IPT use, we identified the lowest number needed to treat (NNT) with IPT to prevent one case of active TB. RESULTS: We found that the NNT as a function of TB incidence shows a 'U-shape', whereby IPT impact is greatest at an intermediate incidence and attenuated at both lower and higher incidence levels. This U-shape was observed over a broad range of parameter values; the optimal TB incidence was between 500 and 900 cases per 100 000 per year. CONCLUSIONS: TB burden is a critical factor to consider when making decisions about communitywide implementation of IPT. We believe that the total disease burden should not preclude programmatic application of IPT.