Tuberculosis and diabetes mellitus: Relating immune impact of co-morbidity with challenges in disease management in high burden countries

Abbas, Uzair; Masood, Kiran Iqbal; Khan, Aalia; Irfan, Muhammad; Saifullah, Nausheen; Jamil, Bushra; Hasan, Zahra

doi:10.1016/j.jctube.2022.100343

Cited by 13 publications

(7 citation statements)

References 77 publications

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“…In exploring the potential links between serum metabolites and disease severity, our findings differed from previous studies that reported an association between inflammatory and prooxidant metabolites with tuberculosis severity. Surprisingly, we did not observe these associations, despite the anticipated increase in systemic low-grade inflammation and immune dysregulation associated to the high prevalence of diabetes among our patients ( 39 ). Moreover, we encountered three unexpected outcomes: notably low circulating levels of TNF-α, significantly lower IL-8 levels in patients with the poorest QoL, and considerably higher levels of total antioxidants in patients experiencing the worst QoL.…”

Section: Discussioncontrasting

confidence: 69%

Serum pro-inflammatory biomarkers associated with improvement in quality of life in pulmonary tuberculosis

Carreto-Binaghi,

Sartillo-Mendoza,

Muñoz-Torrico

et al. 2023

Front. Immunol.

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IntroductionPulmonary dysfunction is an underestimated complication in tuberculosis (TB) infection, affecting quality of life (QoL). Although respiratory function tests objectively reflect lung disturbances in a specific moment, predictors of illness severity at the time of diagnosis are still lacking.MethodsWe measured serum pro-inflammatory cytokines (TNF-α and IL-8), eicosanoids (PGE2, LTB4, RvD1, Mar1, and LXA4), a marker of tissue damage (cell-free nucleosomes), and indicators of redox status (malonaldehyde, 8-isoprostane, total oxidants, and antioxidants), as well as a score of radiological abnormalities (SRA) and a QoL questionnaire, in 25 patients with pulmonary TB at the time of diagnosis (t0) and two months after the initiation of treatment (t2).ResultsWe found higher antioxidant levels in the patients with the worst QoL at t0, and all the indicators of the prooxidant state were significantly reduced at t2, while the total antioxidant levels increased. LTB4, a pro-inflammatory eicosanoid, was diminished at t2, while all the pro-resolutory lipids decreased substantially. Significant correlations between the SRA and the QoL scores were observed, the latter showing a substantial reduction at t2, ranking it as a reliable tool for monitoring disease evolution during TB treatment.DiscussionThese results suggest that evaluating a combination of these markers might be a valuable predictor of QoL improvement and a treatment response indicator; in particular, the oxidation metabolites and eicosanoid ratios could also be proposed as a future target for adjuvant therapies to reduce inflammation-associated lung injury in TB disease.

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Section: Discussioncontrasting

confidence: 69%

Serum pro-inflammatory biomarkers associated with improvement in quality of life in pulmonary tuberculosis

Carreto-Binaghi,

Sartillo-Mendoza,

Muñoz-Torrico

et al. 2023

Front. Immunol.

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“…The persistence of inflammation (post-treatment) in subjects with TBDM has been previously reported, suggesting that it could signify a delay in the sterilization process of lesions [ 29 ]. The differences we observed in APTB subjects, with and without DM, may be indicative that comorbidity leads to a greater pulmonary involvement related to persistent inflammation [ 3 , 7 , 82 ]. In addition, the differentiation shown by the panel of inflammation markers between APTB patients who completed treatment and their initial state, unlike those with TBDM, suggests a persistent chronic low-grade inflammation in individuals managing TBDM, despite maintaining good glycemic control.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Systemic Inflammation Before and After Standard Anti-tuberculosis Treatment in Patients With Active Pulmonary Tuberculosis and Diabetes Mellitus

López-González,

Martínez-Soto,

Avila-Cervantes

et al. 2024

Cureus

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Background Diabetes mellitus (DM) is a common comorbidity of active pulmonary tuberculosis (APTB) that increases the risk of treatment failure during anti-tuberculosis chemotherapy. Evaluating systemic inflammatory response could help determine differences in response to treatment between APTB patients and those with APTB and DM. Methodology To explore changes in systemic inflammation, measured by a set of inflammatory mediators in subjects with APTB and TBDM before and after six months of anti-tuberculosis chemotherapy, 30 APTB and nine TBDM subjects underwent cytokine testing, including interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta 1 (TGF-β1) by enzyme-linked immunosorbent assay, C-reactive protein by nephelometry, and sialic acid by colorimetric assay at baseline and following six months of standard anti-tuberculosis treatment. Sputum smear microscopy or molecular biology (Xpert MTB/RIF) was used for diagnosis, and sputum smear microscopy was performed monthly during the treatment of the patient with pulmonary tuberculosis to evaluate his evolution. Principal component analysis examined changes in the inflammatory status. Results Both groups showed negative sputum smear microscopy in the sixth month after starting anti-tuberculosis chemotherapy. TGF-β1 was found to be significantly higher in subjects with TBDM before treatment compared to APTB patients (p<0.001), and systemic inflammation continued only in TBDM subjects after treatment (accumulation and persistence of inflammatory mediators like IL-6, IL-8, IL-10, IFN-γ, TNF-α, TGF-β1, C-reactive protein, and sialic acid in blood). On the other hand, the mediators IFN-γ, C-reactive protein, and total sialic acid were found to be most influential in distinguishing pre- and post-treatment inflammatory response in subjects with APTB without DM. Conclusions Inflammatory mediators analyzed in combination, including IFN-γ, CRP, and total sialic acid, may be useful in evaluating the systemic inflammatory response in subjects with APTB and TBDM before and after anti-tuberculosis treatment. Determining these mediators revealed persistent systemic inflammation in TBDM subjects after six months of standard tuberculosis treatment, despite negative sputum smear microscopy results and good glycemic control. This suggests a need for inflammation-modulating therapies during tuberculosis control. Finally, monitoring sputum smear microscopy results alongside the determination of proposed inflammatory mediators (IFN-γ, CRP, and total sialic acid) are effective in evaluating the response to anti-tuberculosis treatment in APTB subjects without DM, warranting further investigation.

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“…The other limitation of our study is that it did not look into whether undernutrition is a risk factor for TB or not because it was difficult to determine whether undernutrition or TB occurred first in TB patients. Even though diabetes or pre-diabetes increases the risk of TB [51], we left it out of the study because we were unable to collect diabetes or pre-diabetes data for both the cases and the controls. Another limitation of our study was that we ignored PLOS ONE socioeconomic factors such as income level at the time of TB diagnosis since they were not feasible to quantify.…”

Section: Plos Onementioning

confidence: 99%

Determinants of tuberculosis disease development in children in central Ethiopia: A matched case-control study

Burusie,

Enquesilassie,

Salazar-Austin

et al. 2024

PLoS ONE

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Background The risk factors for tuberculosis (TB) disease development in children remained understudied, particularly in low-income countries like Ethiopia. The objective of this study was to identify determinants of TB disease development in general and in relation to BCG vaccination in children in central Ethiopia. Methods We employed a 1:1 age-matched case-control design to compare the characteristics of children who developed TB (cases) with those who did not (controls). Data were collected in healthcare facilities in Addis Ababa city, Adama, and Bishoftu towns between September 25, 2021, and June 24, 2022. Two hundred and fifty-six cases were drawn at random from a list of childhood TB patients entered into SPSS software, and 256 controls were selected sequentially at triage from the same healthcare facilities where the cases were treated. A bivariate conditional logistic regression analysis was performed first to select candidate variables with p-values less than or equal to 0.20 for the multivariable model. Finally, variables with a p-value less than 0.05 for a matched adjusted odds ratio (mORadj) were reported as independent determinants of TB disease development. Results The mean age of the cases was nine years, while that of the controls was 10 years. Males comprised 126 cases (49.2%) and 119 controls (46.5%), with the remainder being females. Ninety-nine (38.7%) of the cases were not BCG-vaccinated, compared to 58 (22.7%) of the controls. Household TB contact was experienced by 43 (16.8%) of the cases and 10 (3.9%) of the controls. Twenty-two (8.6%) of the cases and six (2.3%) of the controls were exposed to a cigarette smoker in their household. Twenty-two (8.6%) of the cases and three (1.2%) of the controls were positive for HIV. Children who were not vaccinated with BCG at birth or within two weeks of birth had more than twice the odds (mORadj = 2.11, 95% CI = 1.28–3.48) of developing TB compared to those who were. Children who ever lived with a TB-sick family member (mORadj = 4.28, 95% CI = 1.95–9.39), smoking family members (mORadj = 3.15, 95% CI = 1.07–9.27), and HIV-infected children (mORadj = 8.71, 95% CI = 1.96–38.66) also had higher odds of developing TB disease than their counterparts. Conclusions Being BCG-unvaccinated, having household TB contact, having a smoker in the household, and being HIV-infected were found to be independent determinants of TB disease development among children.

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Tuberculosis and diabetes mellitus: Relating immune impact of co-morbidity with challenges in disease management in high burden countries

Cited by 13 publications

References 77 publications

Serum pro-inflammatory biomarkers associated with improvement in quality of life in pulmonary tuberculosis

Serum pro-inflammatory biomarkers associated with improvement in quality of life in pulmonary tuberculosis

Evaluation of Systemic Inflammation Before and After Standard Anti-tuberculosis Treatment in Patients With Active Pulmonary Tuberculosis and Diabetes Mellitus

Determinants of tuberculosis disease development in children in central Ethiopia: A matched case-control study

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