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Background Diabetes mellitus (DM) patients are three times more likely to develop tuberculosis (TB) than the general population. Active TB screening in people with DM is part of a bidirectional approach. The aim of this study was to conduct pragmatic active TB screening among DM patients in four countries to inform policy. Methods DM patients were recruited in Indonesia (n=809), Peru (n=600), Romania (n=603) and South Africa (n=51). TB cases were diagnosed using an algorithm including clinical symptoms and chest X-ray. Presumptive TB patients were examined with sputum smear and culture. Results A total of 171 (8.3%) individuals reported ever having had TB (South Africa, 26%; Indonesia, 12%; Peru, 7%; Romania, 4%), 15 of whom were already on TB treatment. Overall, 14 (0.73% [95% confidence interval 0.40 to 1.23]) TB cases were identified from screening. Poor glucose control, smoking, lower body mass index, education and socio-economic status were associated with newly diagnosed/current TB. Thirteen of the 14 TB cases diagnosed from this screening would have been found using a symptom-based approach. Conclusions These data support the World Health Organization recommendation for routine symptom-based screening for TB in known DM patients in high TB-burden countries. DM patients with any symptoms consistent with TB should be investigated and diagnostic tools should be easily accessible. [ABSTRACT FROM AUTHOR]

Background People with diabetes have an increased risk of developing active tuberculosis (TB) and are more likely to have poor TB-treatment outcomes, which may impact on control of TB as the prevalence of diabetes is increasing worldwide. Blood transcriptomes are altered in patients with active TB relative to healthy individuals. The effects of diabetes and intermediate hyperglycemia (IH) on this transcriptomic signature were investigated to enhance understanding of immunological susceptibility in diabetes-TB comorbidity. Methods Whole blood samples were collected from active TB patients with diabetes (glycated hemoglobin [HbA1c] ≥6.5%) or IH (HbA1c = 5.7% to <6.5%), TB-only patients, and healthy controls in 4 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 TB, notably showing an increase in genes associated with innate inflammatory and decrease in adaptive immune responses. Strikingly, patients with IH and TB exhibited blood transcriptomes much more similar to patients with diabetes-TB than to patients with only TB. Both diabetes-TB and IH-TB patients had a decreased type I interferon response relative to TB-only patients. Conclusions Comorbidity in individuals with both TB and diabetes is associated with altered transcriptomes, with an expected enhanced inflammation in the presence of both conditions, but also reduced type I interferon responses in comorbid patients, suggesting an unexpected uncoupling of the TB transcriptome phenotype. These immunological dysfunctions are also present in individuals with IH, showing that altered immunity to TB may also be present in this group. The TB disease outcomes in individuals with IH diagnosed with TB should be investigated further. [ABSTRACT FROM AUTHOR]

Background Diabetes mellitus (DM) increases active tuberculosis (TB) risk and worsens TB outcomes, jeopardizing TB control especially in TB-endemic countries with rising DM prevalence rates. We assessed DM status and clinical correlates in TB patients across settings in Indonesia, Peru, Romania, and South Africa. Methods Age-adjusted DM prevalence was estimated using laboratory glycated hemoglobin (HbA1c) or fasting plasma glucose in TB patients. Detailed and standardized sociodemographic, anthropometric, and clinical measurements were made. Characteristics of TB patients with or without DM were compared using multilevel mixed-effect regression models with robust standard errors. Results Of 2185 TB patients (median age 36.6 years, 61.2% male, 3.8% human immunodeficiency virus–infected), 12.5% (267/2128) had DM, one third of whom were newly diagnosed. Age-standardized DM prevalence ranged from 10.9% (South Africa) to 19.7% (Indonesia). Median HbA1c in TB–DM patients ranged from 7.4% (Romania) to 11.3% (Indonesia). Compared to those without DM, TB–DM patients were older and had a higher body mass index (BMI) (P value <.05). Compared to those with newly diagnosed DM, TB patients with diagnosed DM had higher BMI and HbA1c, less severe TB, and more frequent comorbidities, DM complications, and hypertension (P value <.05). Conclusions We show that DM prevalence and clinical characteristics of TB–DM vary across settings. Diabetes is primarily known but untreated, hyperglycemia is often severe, and many patients with TB–DM have significant cardiovascular disease risk and severe TB. This underlines the need to improve strategies for better clinical management of combined TB and DM. [ABSTRACT FROM AUTHOR]

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Background The global epidemiology of parasitic helminths and mycobacterial infections display extensive geographical overlap, especially in the rural and urban communities of developing countries. We investigated whether co-infection with the gastrointestinal tract-restricted helminth, Trichuris muris, and the intracellular bacterium, Mycobacterium bovis (M. bovis) BCG, would alter host immune responses to, or the pathological effect of, either infection. Results We demonstrate that both pathogens are capable of negatively affecting local and systemic immune responses towards each other by modifying cytokine phenotypes and by inducing general immune suppression. T. muris infection influenced non-specific and pathogenspecific immunity to M. bovis BCG by down-regulating pulmonary TH1 and Treg responses and inducing systemic TH2 responses. However, co-infection did not alter mycobacterial multiplication or dissemination and host pulmonary histopathology remained unaffected compared to BCG-only infected mice. Interestingly, prior M. bovis BCG infection significantly delayed helminth clearance and increased intestinal crypt cell proliferation in BALB/c mice. This was accompanied by a significant reduction in systemic helminthspecific TH1 and TH2 cytokine responses and significantly reduced local TH1 and TH2 responses in comparison to T. muris-only infected mice. Conclusion Our data demonstrate that co-infection with pathogens inducing opposing immune phenotypes, can have differential effects on compartmentalized host immune protection to either pathogen. In spite of local and systemic decreases in TH1 and increases in TH2 responses co-infected mice clear M. bovis BCG at the same rate as BCG only infected animals, whereas prior mycobacterial infection initiates prolonged worm infestation in parallel to decreased pathogen-specific TH2 cytokine production. [ABSTRACT FROM AUTHOR]