Point-of-care urine tests for smoking status and isoniazid treatment monitoring in adult patients

Abstract

Background: Poor adherence to isoniazid (INH) preventive therapy (IPT) is an impediment to effective control of latent tuberculosis (TB) infection. TB patients who smoke are at higher risk of latent TB infection, active disease, and TB mortality, and may have lower adherence to their TB medications. The objective of our study was to validate IsoScreen and SmokeScreen (GFC Diagnostics, UK), two point-of-care tests for monitoring INH intake and determining smoking status. The tests could be used together in the same individual to help identify patients with a high-risk profile and provide a tailored treatment plan that includes medication management, adherence interventions, and smoking cessation programs.

Methodology/principal findings: 200 adult outpatients attending the TB and/or the smoking cessation clinic were recruited at the Montreal Chest Institute. Sensitivity and specificity were measured for each test against the corresponding composite reference standard. Test reliability was measured using kappa statistic for intra-rater and inter-rater agreement. Univariate and multivariate logistic regression models were used to explore possible covariates that might be related to false-positive and false-negative test results. IsoScreen had a sensitivity of 93.2% (95% confidence interval [CI] 80.3, 98.2) and specificity of 98.7% (94.8, 99.8). IsoScreen had intra-rater agreement (kappa) of 0.75 (0.48, 0.94) and inter-rater agreement of 0.61 (0.27, 0.90). SmokeScreen had a sensitivity of 69.2% (56.4, 79.8), specificity of 81.6% (73.0, 88.0), intra-rater agreement of 0.77 (0.56, 0.94), and inter-rater agreement of 0.66 (0.42, 0.88). False-positive SmokeScreen tests were strongly associated with INH treatment.

Conclusions: IsoScreen had high validity and reliability, whereas SmokeScreen had modest validity and reliability. SmokeScreen tests did not perform well in a population receiving INH due to the association between INH treatment and false-positive SmokeScreen test results. Development of the next generation SmokeScreen assay should account for this potential interference.

Conflict of interest statement

Competing Interests: None of the authors have conflicts of interest with the exception of M. Pai. M. Pai serves on the editorial boards of PLOS ONE and PLOS Medicine. He is a Section Editor with PLOS One. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Example of a IsoScreen and SmokeScreen negative test result.

Original urine colour (no colour change)  =  negative test result. Dark blue-purple IsoScreen test  =  positive test result. Orange-pink SmokeScreen test  =  positive test result. Any other colour change  =  indeterminate test result.

Figure 2. Example of a IsoScreenpositive test result.

Original urine colour (no colour change)  =  negative test result. Dark blue-purple IsoScreen test  =  positive test result. Orange-pink SmokeScreen test  =  positive test result. Any other colour change  =  indeterminate test result.

Figure 3. Example of a SmokeScreenpositivetest result.

Original urine colour (no colour change)  =  negative test result. Dark blue-purple IsoScreen test  =  positive test result. Orange-pink SmokeScreen test  =  positive test result. Any other colour change  =  indeterminate test result.

Figure 4. Example of an indeterminate IsoScreen result.

Original urine colour (no colour change)  =  negative test result. Dark blue-purple IsoScreen test  =  positive test result. Orange-pink SmokeScreen test  =  positive test result. Orange IsoScreen test (not dark blue)  =  indeterminate test result.

Figure 5. Example of an indeterminate SmokeScreen result.

Original urine colour (no colour change)  =  negative test result. Dark blue-purple IsoScreen test  =  positive test result. Orange-pink SmokeScreen test  =  positive test result. Dark blue SmokeScreen test (not orange-pink)  =  indeterminate test result.

Figure 6. Flow chart of the study selection process, smoking status and isoniazid intake based on medical charts and questionnaire responses.