Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings. We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%–85% to 95%–99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28–US$49 to US$133–US$146 and US$137–US$151 per TB case detected when Xpert is used “in addition to” and “as a replacement of” smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert “in addition to” smear microscopy, compared to the base case, range from US$41–$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert “as a replacement of” smear microscopy range from US$52–$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold. Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings. Please see later in the article for the Editors' Summary

Introduction Pulmonary tuberculosis (TB) is an important risk factor for chronic respiratory disease due to residual lung damage. Yet, the WHO End TB strategy does not mention post-TB chronic lung disorders (PTBLDs) and programmatic interventions to address PTBLD are lacking. This study assessed the scope of current guidelines and evidence on PTBLD to inform policy and research action. Methods A systematic literature search was conducted following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Eight databases (TRIP, International Guideline Library, MEDLINE/PubMed, EMBASE, Web of Science, Global Health, Cochrane Library) were searched for records on PTBLD published between 1 January 1990 and 1 December 2017. Non-English records, case series, conference abstracts and letters to editors were excluded. Data were extracted and charted on publication year, location, PTBLD condition(s) and main study outcome. Results A total of 212 guidelines and 3661 articles were retrieved. After screening, only three international TB guidelines mentioned TB sequelae, but none described how to identify or manage the condition. A total of 156 articles addressed PTBLD: 54 (35%) mentioned unspecified TB sequelae; 47 (30%) specific post-TB conditions including aspergillosis, bronchial stenosis or bronchiectasis; 52 (33%) post-TB obstructive disorders or lung function impairment; and 20 (13%) post-TB respiratory symptoms or chest X-ray abnormalities. The first two groups mostly assessed surgery or ventilation techniques for patient management, while the last two groups typically assessed prevalence or predictors of disease. Conclusion This is the first review to provide a comprehensive overview of the current literature on PTBLD. The scope of evidence around the burden of PTBLD warrants inclusion and recognition of the problem in international TB guidelines. Research is now needed on early detection of PTBLD and patient management options that are suitable for high-burden TB countries.

Xpert MTB/RIF is a major advance for TB diagnostics, especially for multidrug-resistant (MDR) TB and HIV-associated TB. But implementation concerns including cost, technical support requirements, and challenging demands of providing second-line TB drugs for diagnosed MDR-TB cases call for gradual, careful introduction based on country circumstances.

High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay. In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert. A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort. A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such.

Rationale: Adults may exhibit characteristics of both asthma and chronic obstructive pulmonary disease (COPD), a situation recently described as asthma–COPD overlap (ACO). There is a paucity of information about ACO in primary care. Objectives: To estimate the prevalence and describe characteristics of individuals with ACO in primary care practices among patients currently diagnosed with asthma, COPD, or both; and to compare the prevalence and characteristics of ACO among the three source populations. Methods: The Respiratory Effectiveness Group conducted a cross-sectional study of individuals ≥40 years old and with ≥2 outpatient primary care visits over a 2-year period in the UK Optimum Patient Care Research Database. Patients were classified into one of three source populations based on diagnostic codes: 1) COPD only, 2) both asthma and COPD, or 3) asthma only. ACO was defined as the presence of all of the following 1) age ≥40 years, 2) current or former smoking, 3) post-bronchodilator airflow limitation (forced expiratory volume in 1 second/forced vital capacity <0.7), and 4) ≥12% and ≥200 ml reversibility in post-bronchodilator forced expiratory volume in 1 second. Results: Among 2,165 individuals (1,015 COPD only, 395 with both asthma and COPD, and 755 asthma only), the overall prevalence of ACO was 20% (95% confidence interval, 18–23%). Patients with ACO had a mean age of 70 years (standard deviation, 11 yr), 60% were men, 73% were former smokers (the rest were current smokers), and 66% were overweight or obese. Comorbid conditions were common in patients with ACO, including diabetes (53%), cardiovascular disease (36%), hypertension (30%), eczema (23%), and rhinitis (21%). The prevalence of ACO was higher in patients with a diagnosis of both asthma and COPD (32%) compared with a diagnosis of COPD only (20%; P < 0.001) or asthma only (14%; P < 0.001). Demographic and clinical characteristics of ACO varied across these three source populations. Conclusions: One in five individuals with a diagnosis of COPD, asthma, or both asthma and COPD in primary care settings have ACO based on the Respiratory Effectiveness Group ACO Working group criteria. The prevalence and characteristics of patients with ACO varies across the three source populations.