Background People living with diabetes have an increased risk of developing active tuberculosis and are more likely to have poor tuberculosis-treatment outcomes, which may impact on control of tuberculosis as the prevalence of diabetes is increasing worldwide. Blood transcriptomes are altered in active tuberculosis patients relative to healthy individuals. The effects of diabetes and intermediate hyperglycaemia on this transcriptomic signature were investigated to enhance understanding of immunological susceptibility in diabetes-tuberculosis comorbidity. Methods Whole blood samples were collected from active tuberculosis patients with diabetes (HbA1c ≥6.5%) or intermediate hyperglycaemia (HbA1c 5.7-6.5%), tuberculosis-only patients and healthy controls in four countries: South Africa, Romania, Indonesia and Peru. Differential blood gene expression was determined by RNA-seq (n=249). Results Diabetes increased the magnitude of gene expression change in the host transcriptome in tuberculosis, notably showing an increase in genes associated with innate inflammatory and decrease in adaptive immune responses. Strikingly, patients with intermediate hyperglycaemia and tuberculosis exhibited blood transcriptomes much more similar to diabetes-tuberculosis patients than to patients with only tuberculosis. Both diabetes-tuberculosis and intermediate hyperglycaemia-tuberculosis patients had a decreased type I interferon response relative to tuberculosis-only patients. Conclusions Co-morbidity in individuals with both tuberculosis and diabetes is associated with altered transcriptomes, with an expected enhanced inflammation in the presence of both conditions, but also reduced type 1 interferon responses in co-morbid patients, suggesting an unexpected uncoupling of the TB transcriptome phenotype. These immunological dysfunctions are also present in individuals with intermediate hyperglycaemia, showing that altered immunity to tuberculosis may also be present in this group. The TB disease outcomes in individuals with intermediate hyperglycaemia diagnosed with TB should be investigated further.

ObjectiveTo evaluate the performance of diagnostic tools for diabetes mellitus, including laboratory methods and clinical risk scores, in newly-diagnosed pulmonary tuberculosis patients from four middle-income countries.MethodsIn a multicentre, prospective study, we recruited 2185 patients with pulmonary tuberculosis from sites in Indonesia, Peru, Romania and South Africa from January 2014 to September 2016. Using laboratory-measured glycated haemoglobin (HbA1c) as the gold standard, we measured the diagnostic accuracy of random plasma glucose, point-of-care HbA1c, fasting blood glucose, urine dipstick, published and newly derived diabetes mellitus risk scores and anthropometric measurements. We also analysed combinations of tests, including a two-step test using point-of-care HbA1cwhen initial random plasma glucose was ≥ 6.1 mmol/L.FindingsThe overall crude prevalence of diabetes mellitus among newly diagnosed tuberculosis patients was 283/2185 (13.0%; 95% confidence interval, CI: 11.6–14.4). The marker with the best diagnostic accuracy was point-of-care HbA1c (area under receiver operating characteristic curve: 0.81; 95% CI: 0.75–0.86). A risk score derived using age, point-of-care HbA1c and random plasma glucose had the best overall diagnostic accuracy (area under curve: 0.85; 95% CI: 0.81–0.90). There was substantial heterogeneity between sites for all markers, but the two-step combination test performed well in Indonesia and Peru.ConclusionRandom plasma glucose followed by point-of-care HbA1c testing can accurately diagnose diabetes in tuberculosis patients, particularly those with substantial hyperglycaemia, while reducing the need for more expensive point-of-care HbA1c testing. Risk scores with or without biochemical data may be useful but require validation.

Objectives: We conducted a cluster-randomized feasibility trial of 90-minute Chlamydia trachomatis tests and same day on-site treatment ('Test n Treat/TnT') in six technical colleges in London, England, to assess TnT uptake rates; follow-up rates; prevalence of C. trachomatis at baseline and 7 months; time to treatment; acceptability of TnT. Methods: Participants completed questionnaires and provided genitourinary samples at baseline and 7 months. Participants were informed that baseline samples would not be tested for 7 months and were advised to get screened independently. Colleges were randomly allocated 1:1 to intervention (TnT) or control (no TnT). One month and 4 months post recruitment, participants at intervention colleges were texted invitations for on-site free C. trachomatis tests. A purposive sample of students who did/did not attend for screening were interviewed (n ¼ 26). Results: Five hundred and nine sexually active students were recruited: median age 17.9 years, 47% male, 50% black ethnicity, 55% reporting two or more sexual partners in the previous year. TnT uptake was 13% (33/259; 95% CI 8.9e17.4%) at 1 month and 10% (26/259; 6.7e14.4%) at 4 months with overall C. trachomatis positivity 5.1% (3/59; 1.1e14.2%). Follow-up at 7 months was 62% (317/509) for questionnaires and 52% (264/509) for samples. C. trachomatis prevalence was 6.2% (31/503) at baseline and 6.1% (16/264) at 7 months. Median time from test to treatment was 15 h. Interviews suggested low test uptake was associated with not feeling at risk, perceptions of stigma, and little knowledge of sexually transmitted infections (STIs). Conclusions: Despite high C. trachomatis rates at baseline and follow-up, uptake of testing was low. Like many countries, England urgently needs better sex education, including making STI testing routine/ normal.

Background: Low uptake of sexually transmitted infection testing by sexually active young people is a worldwide public health problem. Screening in non-medical settings has been suggested as a method to improve uptake. The "Test n Treat" feasibility trial offered free, on-site rapid chlamydia/gonorrhoea tests with same day treatment for chlamydia (and gonorrhoea treatment at a local clinic,) to sexually active students (median age 17 years) at six technical colleges in London. Despite high rates of chlamydia (6% prevalence), uptake of testing was low (< 15%). In a qualitative study we explored the acceptability, including barriers and facilitators to uptake, of on-site chlamydia screening. Methods: In 2016-17 we conducted a qualitative study in the interpretative tradition using face to face or telephone semi-structured interviews with students (n = 26), teaching staff (n = 3) and field researchers (n = 4). Interviews were digitally recorded, transcribed and thematically analysed. Results: From the student perspective, feelings of embarrassment and the potential for stigma were deterrents to sexually transmitted infection testing. While the non-medical setting was viewed as mitigating against stigma, for some students volunteering to be screened exposed them to detrimental judgements by their peers. A small financial incentive to be screened was regarded as legitimising volunteering in a non-discrediting way. Staff and researchers confirmed these views. The very low level of knowledge about sexually transmitted infections influenced students to not view themselves as candidates for testing. There were also suggestions that some teenagers considered themselves invulnerable to sexually transmitted infections despite engaging in risky sexual behaviours. Students and researchers reported the strong influence peers had on uptake, or not, of sexually transmitted infection testing.