Pediatric tuberculosis in a high burden setting: Socio-spatial distribution, blood elements features, and outcomes.

Background: The childhood tuberculosis (TB) epidemic has been long neglected. Data on pediatric tuberculosis is needed to develop effective strategies against TB. Methods: We retrospectively reviewed 200 medical records from children aged 0-15 years who suffered from tuberculosis between 2011 and 2021 in Libreville, Gabon. We collected and analyzed socio-demographic data and clinical data. Results: 141 children files were selected (43 % girls and 57 % boys). The mean age of the patients was 9.2 years (CI: 8.5-10). Sixty per cent (60 %) of cases were from precarious housing areas, 35.34 % from mixed housing areas, and 4.51 % from residential. The cure rate was 75.24 %, 9.52 % relapsed, and 15.24 % died. Deaths were significantly higher in older children (Dunn's post-test p < 0.01). Children who recovered had higher haemoglobin and platelet counts than those who died (Dunn's test: haemoglobin p < 0.0001; thrombocytes p < 0.05). The haemoglobin threshold value of 5.5 g/dL identified children death with up to 80 % sensitivity and 86 % specificity. Thrombocytes count identified children's death with a sensitivity of 80 % and a specificity of 51 %. Conclusion: Precariousness is associated with childhood tuberculosis. The directly observed therapy (DOTS) in older children should be reinforced to limit tuberculosis-associated deaths. Haemoglobin concentration and platelet are vital prognosis markers in pediatric tuberculosis.

Understanding the Spectrum and Management of Post-Tuberculosis Lung Disease: A Comprehensive Review.

Post-tuberculosis lung disease (PTLD) poses a significant clinical challenge in regions with a high burden of tuberculosis (TB). This review provides a comprehensive overview of PTLD, encompassing its pathogenesis, clinical manifestations, diagnostic modalities, management strategies, long-term outcomes, and public health implications. PTLD arises from residual lung damage following TB treatment and is characterized by a spectrum of pathological changes, including fibrosis, bronchiectasis, and cavitation. Clinical presentation varies widely, from chronic cough and hemoptysis to recurrent respiratory infections, which are oftentimes a diagnostic dilemma. Radiological imaging, pulmonary function tests, and careful consideration of patient history play pivotal roles in diagnosis. Management strategies involve pharmacological interventions to alleviate symptoms and prevent disease progression, which are influenced by the extent of lung damage, comorbidities, and access to healthcare. Rehabilitation programs and surgical options are available for select cases. Prognosis is influenced by the extent of lung damage, comorbidities, and access to healthcare. Prevention efforts through a TB control program and early detection are crucial in reducing the burden of PTLD. This review stresses the importance of understanding and addressing PTLD to mitigate its impact on individuals and public health systems worldwide.

Adverse drug reactions due to linezolid in the programmatic management of drug-resistant tuberculosis in India: A retrospective multicenter study.

BACKGROUND: Monitoring and managing adverse drug reactions (ADR) are critical for treating drug-resistant tuberculosis (TB). OBJECTIVE: To study symptomatic, linezolid-attributable ADRs in TB patients initiated on all oral longer bedaquiline-based treatment regime for multidrug-resistant/rifampicin-resistant (MDR/RR)-TB under programmatic conditions. METHODS: It was a multicenter, retrospective study of people with MDR/RR-TB in nine TB units in Nagpur, India, from March 2020 to April 2022. RESULTS: The study consisted of a sample size of 106 individuals with multidrug-resistant and rifampicin-resistant tuberculosis out of a total of 110 individuals with the disease. Of these, 45 (42.45%) experienced linezolid ADRs, with an incidence of 11.37 cases per 1000 person-weeks. These patients were significantly younger (31.24 ± 11.13 years) and more likely to be female (27, 50%) than those without ADRs. ADR severity was mild in 20 (44.45%), moderate in 15 (33.33%), and severe in 10 (22.22%) patients. The most common ADR was peripheral neuropathy (42, 93.33%), followed by lactic acidosis (3, 6.67%), anemia (2, 4.44%), and optic neuritis (2, 4.44%). Dosing was reduced in 17 (37.78%) patients, and linezolid was withdrawn entirely in 19 (42.22%) patients. Only 9 (20%) patients continued linezolid unmodified. For mild to moderate linezolid-associated symptomatic peripheral neuropathy, symptom management with or without dose reduction is an effective strategy; however, immediate linezolid withdrawal is necessary in severe or life-threatening peripheral neuropathy cases. After a mean follow-up of 41 ± 21.33 weeks, ADR symptoms resolved completely in 4 (6.67%) patients and decreased in 42 (93.33%) patients. CONCLUSION: Linezolid ADRs, often neuropathy, frequently occur in patients on an all-oral bedaquiline-based treatment regime for MDR/RR-TB. Women and younger patients are more likely to experience these ADRs, usually mild to moderate in severity. Management of symptomatic linezolid-associated peripheral neuropathy should be based on ADR severity. These ADRs often affect linezolid dosing, so it is important to identify and manage them early.

Effect of Metformin on systemic chemokine responses during anti-tuberculosis chemotherapy.

BACKGROUND: Metformin (MET), by boosting immunity, has been suggested as a host-adjunctive therapy to anti-tuberculosis treatment (ATT). METHODS: We evaluated whether adding MET to the standard ATT can alter the host chemokine response. We investigated the influence of metformin on the plasma levels of a wide panel of chemokines in a group of active tuberculosis patients before treatment, at 2nd month of ATT and at 6-months of ATT as part of our clinical study to examine the effect of metformin on ATT. RESULTS: Our results demonstrated that addition of metformin resulted in diminished CC (CCL1 and CCL3) and CXC (CXCL-2 and CXCL-10) chemokines in MET arm as compared to non-MET arm at the 2nd month and 6th month of ATT. In addition to this, MET arm showed significantly diminished chemokines in individuals with high bacterial burden and cavitary disease. CONCLUSION: Our current data suggest that metformin alters chemokines responses that could potentially curb excessive inflammation during ATT.

A ten-year experience of musculoskeletal tuberculosis at a tertiary care hospital in South India.

Background: The delayed identification and management of musculoskeletal tuberculosis (MSTB) poses substantial health challenges and leads to significant morbidity. This study aimed to collate ten years of hospital data and provide valuable insights into the clinical, diagnostics, and outcomes of the patients diagnosed with MSTB. Methods: A retrospective study was undertaken to review clinic records from 2013 to 2022 for all individuals diagnosed with MSTB in a tertiary care hospital in South India. Results: Over a decade, 400 cases of MSTB were diagnosed, revealing 57 % males and 43 % females with a mean age of 43.2 ± 18.9 years. Spinal TB constituted 72 % of cases, with the most common involvement of thoracic vertebrae (50.9 %). Extra-spinal MSTB accounted for 28 %, prevalent more in the pediatric age group (p < 0.05). Surgical intervention was required for 80 % of spinal TB cases and 58 % of extra-spinal MSTB cases. The average follow-up duration was two years, with 73 % completing treatment. Unfortunately, seven patients died, and three experienced relapse. Conclusion: Spinal TB is the most common type of MSTB and is predominant in young and middle-aged adults, while extra-spinal MSTB is more frequently observed in children. Where use of MRI facilitates early detection of spinal TB; histopathological and microbiological examination confirm the diagnosis. Combining anti-tubercular drugs with modern surgical approaches is essential for obtaining favorable outcomes and improving the quality of life of such patients. It is crucial to have advanced and affordable diagnostic facilities, along with increased public awareness, to reinforce tuberculosis control strategies.

Characterization of peripheral cytokine-secreting cells responses in HIV/TB co-infection.

Background: Currently the responses of peripheral cytokine-secreting cells in the natural course of human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection haven't been fully elucidated. Methods: The function of peripheral proinflammatory, regulatory and cytotoxic cytokine-secreting cells were investigated by direct intracellular cytokine staining (ICS) and flow cytometry, additionally, the absolute numbers of different cytokine-secreting cells were measured among patients with HIV/TB co-infection (HT group), and compared them with the healthy controls (HC group), patients with TB (TB group) and patients with HIV infection (HIV group). After one week's anti-TB treatment, the changes of the percentages of cytokine-secreting cells were further evaluated in TB and HT groups. Results: Totally 26 individuals in the HC group, 51 in the TB group, 26 in the HIV group and 29 in the HT group were enrolled. The HT. HT group exhibited significantly lower absolute numbers of IFN-γ+CD4+, IFN-γ+CD8+, TNF-α+CD4+, IL17A+CD4+ T cells and TNF-α+CD14+ monocytes than the TB and HIV groups. Compared with the TB group, the percentages of CD8+ T cells secreting IFN-γ and perforin (p=0.010; p=0.043) were significantly lower among the HT group. Compared with the HIV group, the percentages of CD4+, CD8+ T cells and CD14+ monocytes secreting TNF-α (p=0.013; p=0.001; p<0.001) were significantly decreased, and the percentage of CD8+ T cells secreting IL-17A (p=0.015) was significantly increased among the HT group. Both the percentages of CD4+ T cells secreting TGF-ß (p<0.001; p=0.001), and CD4+ and CD8+ T cells secreting granzyme A (all p<0.001), were significantly higher among the HT group than among the TB group and HIV group. After one week's anti-TB treatment, an increased percentage of CD4+ T cells secreting TNF-α (p=0.003) was found in the TB group, and an increased percentage of CD8+ T cells secreting TNF-α (p=0.029) was found in the HT group. Conclusion: Significantly different functional profiles of peripheral proinflammatory, regulatory, and cytotoxic cytokine-secreting cells were observed in the natural course of HIV/TB co-infection compared to TB and HIV infection alone, even though the absolute numbers of those cells were significantly lower in HIV/TB co-infection. TNF-α-secreting CD8+ T cells may be a more sensitive marker for early evaluation of anti-TB treatment efficacy in patients with HIV/TB co-infection.

microRNAs associated with the pathogenesis and their role in regulating various signaling pathways during Mycobacterium tuberculosis infection.

Despite more than a decade of active study, tuberculosis (TB) remains a serious health concern across the world, and it is still the biggest cause of mortality in the human population. Pathogenic bacteria recognize host-induced responses and adapt to those hostile circumstances. This high level of adaptability necessitates a strong regulation of bacterial metabolic characteristics. Furthermore, the immune reponse of the host virulence factors such as host invasion, colonization, and survival must be properly coordinated by the pathogen. This can only be accomplished by close synchronization of gene expression. Understanding the molecular characteristics of mycobacterial pathogenesis in order to discover therapies that prevent or resolve illness relies on the bacterial capacity to adjust its metabolism and replication in response to various environmental cues as necessary. An extensive literature details the transcriptional alterations of host in response to in vitro environmental stressors, macrophage infection, and human illness. Various studies have recently revealed the finding of several microRNAs (miRNAs) that are believed to play an important role in the regulatory networks responsible for adaptability and virulence in Mycobacterium tuberculosis. We highlighted the growing data on the existence and quantity of several forms of miRNAs in the pathogenesis of M. tuberculosis, considered their possible relevance to disease etiology, and discussed how the miRNA-based signaling pathways regulate bacterial virulence factors.

Circulating Monocyte-Like Myeloid Derived Suppressor Cells and CD16 Positive Monocytes Correlate With Immunological Responsiveness of Tuberculosis Patients.

Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In this work, we studied the relationship between myeloid-derived suppressor cells (MDSC) and monocytes subsets with the immunological responsiveness of TB patients. Individuals with active TB were classified as low responders (LR-TB) or high responders (HR-TB) according to their T cell responses against a cell lysate of Mycobacterium tuberculosis (Mtb-Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to Mtb compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD16 positive monocytes as compared to HR-TB and healthy donors. Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like (PMN-MDSC) MDSC were increased in patients and the proportion of M-MDSC inversely correlated with IFN-γ levels released after Mtb-Ag stimulation in HR-TB. We also found that LR-TB displayed the highest percentages of circulating M-MDSC. These results demonstrate that CD16 positive monocytes and M-MDSC frequencies could be used as another immunological classification parameter. Interestingly, in LR-TB, frequencies of CD16 positive monocytes and M-MDSC were restored after only three weeks of anti-TB treatment. Together, our findings show a link between the immunological status of TB patients and the levels of different circulating myeloid cell populations.

Insights into the Unique Lung Microbiota Profile of Pulmonary Tuberculosis Patients Using Metagenomic Next-Generation Sequencing.

The microbiota plays an important role in human health and disease development. The lung microbiota profile in pulmonary tuberculosis (TB) patients and the effects of anti-TB treatment on the profile need to be determined thoroughly and comprehensively. This study primarily aimed to determine the lung microbiota profile associated with pulmonary TB and characterize the longitudinal changes during anti-TB treatment. A total of 53 participants, comprising 8 healthy individuals, 12 untreated pulmonary TB patients, 15 treated pulmonary TB patients, 11 cured pulmonary TB patients, and 7 lung cancer patients, were recruited in the present study. Bronchioalveolar lavage fluid (BALF) samples were collected from the above participants, and throat swabs were taken from healthy individuals. Microbiomes in the samples were examined using metagenomic next-generation sequencing (mNGS). Differences in microbiota profiles were determined through a comparison of the indicated groups. Our findings indicated that the BALF samples displayed decreased richness and diversity of the microbiota compared to those of the throat swab samples, and these two kinds of samples exhibited obvious separation on principal-coordinate analysis (PCoA) plots. Untreated pulmonary TB patients displayed a unique lung microbiota signature distinct from that of healthy individuals and lung cancer patients. Our data first demonstrated that anti-TB treatment with first-line drugs increases alpha diversity and significantly affects the beta diversity of the lung microbiota, while it also induces antibiotic resistance genes (ARGs). IMPORTANCE Characterization of the lung microbiota could lead to a better understanding of the pathogenesis of pulmonary TB. Here, we applied the metagenomic shotgun sequencing instead of 16S rRNA sequencing method to characterize the lung microbiota using the BALF samples instead of sputum. We found that alterations in the lung microbiota are associated with TB infection and that anti-TB treatment significantly affects the alpha and beta diversity of the lung microbiota in pulmonary TB patients. These findings could help us better understand TB pathogenesis.

Treatment and pregnancy outcomes of pregnant women exposed to second-line anti-tuberculosis drugs in South Africa.

BACKGROUND: Multi-drug resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) in pregnant women is a cause for concern globally; few data have described the safety of second-line anti-TB medications during pregnancy. We aim to describe TB treatment and pregnancy outcomes among pregnant women receiving second-line anti-tuberculosis treatment for MDR/RR-TB in Johannesburg, South Africa. METHODS: We conducted a retrospective record review of pregnant women (≥ 18 years) who received treatment for MDR/RR-TB between 01/2010-08/2016 at three outpatient treatment sites in Johannesburg, South Africa. Demographic, treatment and pregnancy outcome data were collected from available medical records. Preterm birth (< 37 weeks), and miscarriage were categorized as adverse pregnancy outcomes. RESULTS: Out of 720 women of child-bearing age who received MDR/RR-TB treatment at the three study sites, 35 (4.4%) pregnancies were identified. Overall, 68.7% (24/35) were HIV infected, 83.3% (20/24) were on antiretroviral therapy (ART). Most women, 88.6% (31/35), were pregnant at the time of MDR/RR-TB diagnosis and four women became pregnant during treatment. Pregnancy outcomes were available for 20/35 (57.1%) women, which included 15 live births (11 occurred prior to 37 weeks), 1 neonatal death, 1 miscarriage and 3 pregnancy terminations. Overall, 13/20 (65.0%) women with known pregnancy outcomes had an adverse pregnancy outcome. Of the 28 women with known TB treatment outcomes 17 (60.7%) completed treatment successfully (4 were cured and 13 completed treatment), 3 (10.7%) died and 8 (28.6%) were lost-to-follow-up. CONCLUSIONS: Pregnant women with MDR/RR-TB suffer from high rates of adverse pregnancy outcomes and about 60% achieve a successful TB treatment outcome. These vulnerable patients require close monitoring and coordinated obstetric, HIV and TB care.

Omental tuberculosis (TB) is a rare disease which can mimic Gastrointestinal malignancies: A case report.

INTRODUCTION: Omental tuberculosis is a rare disease which can mimic Gastrointestinal malignancies. It should be considered as one of the differential diagnosis when the patient presents with abdominal mass with vague symptoms. Histological diagnosis is the final conclusion in these patients. PRESENTATION OF CASE: An elderly male patient who presented with epigastric pain with epigastric mass and diagnosed with omental tuberculosis as a result of USS guided tissue biopsy revealed granuloma with central caseous necrosis. The size of the mass completely resolved after completion of anti TB treatment in this patient. DISCUSSION: Presence of caseous necrosis with granulomas in histology and positive culture of tuberculosis from tissue are the definitive diagnosis for omental tuberculosis. And the response to treatment with anti TB drug supports the diagnosis. CONCLUSION: Omental TB is a rare entity which can be misdiagnosed as GI malignancies. Medical management is the treatment of choice for omental TB. Surgery is needed when complications occur in extrapulmonary TB.

[Pseudotumoral ocular tuberculosis: about 2 cases]. / Forme pseudotumorale de tuberculose oculaire: à propos de 2 cas.

Ocular manifestations of tuberculosis are non-specific and polymorphic as they can affect all the tunics of the eye and cause severe visual loss in the absence of early and appropriate treatment. We here report 2 casesof pseudotumoral ocular tuberculosis with favorable outcome under antibacillary treatment; the first patient recently had had spontaneous burst of the eyeball with exit of a burgeoning fleshy and suppurative mass measuring 10cm/6cm, the second patient had granuloma of the ciliary body mimicking melanoma; then we here discuss the clinical and therapeutic particularities of this disease.

Coordinated In Vitro Release of Granulysin, Perforin and IFN-γ in TB and HIV/TB Co-Infection Associated with Clinical Outcomes before and after Anti-TB Treatment.

Granule-associated killing molecules released from cytotoxic T lymphocytes participate as a crucial step in immunity against tuberculosis (TB), but the role of coordinated production remains controversial. Coordinated release of effector molecules in vitro after stimulating peripheral blood mononuclear cells (PBMCs) of active TB or HIV/TB coinfection patients with PPD, purified protein derivative of tuberculin and avirulent Mtb, H37Ra, an attenuated strain were investigated in association with clinical outcomes. Perforin, granzyme-B, granulysin and IFN-γ were measured using ELISA. Before anti-TB treatment, PBMCs of TB stimulated with PPD or H37Ra released higher perforin, granzyme-B, and granulysin levels than in HIV/TB and released significantly higher IFN-γ (p = 0.045, p = 0.022). Granulysin positively correlated with perforin in TB (p = 0.042, r = 0.385), HIV/TB coinfection (p = 0.003, r = 0.941) after PPD stimulation, and after H37Ra stimulation in TB (p = 0.005, r = 0.549), but negatively correlated with granzyme B in TB (p = 0.042, r = -0.386), HIV/TB coinfection (p = 0.042, r = 0.754) were noted. After anti-TB treatment, increased levels of perforin, granulysin and IFN-γ in TB or HIV/TB upon PPD or H37Ra stimulation, and decreased granzyme-B levels after PPD (p = 0.003) or H37Ra (p = 0.028) stimulation in TB were observed. These results suggest that granulysin may act synergistic with perforin and IFN-γ in TB, indicating its crucial function in host immunity to tuberculosis. Future studies with larger numbers of patients ought to be conducted in the future.

Characteristics of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome and its influence on tuberculosis treatment outcomes in persons living with HIV.

OBJECTIVE: The influence of tuberculosis (TB)-immune reconstitution inflammatory syndrome (IRIS) on TB treatment outcomes and its risk factors were investigated among people with human immunodeficiency virus (HIV) and co-infected with TB. METHODS: Newly diagnosed, culture-confirmed, pulmonary TB patients with HIV and enrolled in a clinical trial (NCT00933790) were retrospectively analysed for IRIS occurrence. Risk factors and TB outcomes (up to 18 months after initiation of anti-TB treatment [ATT]) were compared between people who experienced IRIS (IRIS group) and those who did not (non-IRIS group). RESULTS: TB-IRIS occurred in 82 of 292 (28%) participants. Significant baseline risk factors predisposing to TB-IRIS occurrence in univariate analysis were: lower CD4+ T-cell count, CD4/CD8 ratio, haemoglobin levels, presence of extra-pulmonary TB focus, and higher HIV viral load; the last two retained significance in the multivariate analysis. After 2 months of ATT commencement, sputum smear conversion was documented in 45 of 80 (56.2%) vs. 124 of 194 (63.9%) (p=0.23), culture conversion was in 75 of 80 (93.7%) vs. 178 of 194 (91.7%) (p=0.57) and the median decline in viral load (log10copies/mm3) was 2.7 in the IRIS vs. 1.1 in the non-IRIS groups (p<0.0001), respectively. An unfavourable response to TB therapy was detected in 17 of 82 (20.7%) and 28 of 210 (13.3%) in the IRIS and non-IRIS groups, respectively (p=0.14). CONCLUSIONS: TB-IRIS frequently occurred in people with advanced HIV infection and in those who presented with extra-pulmonary TB lesions, without influencing subsequent TB treatment outcomes.

Anti-tuberculosis (TB) chemotherapy dynamically rescues Th1 and CD8+ T effector levels in Han Chinese pulmonary TB patients.

CD4+/CD8+ T cells play a major role in conferring immune protection against tuberculosis (TB), but it remains unknown how the immune responses of CD4+/CD8+ T cells exactly correlate with the clinical variables and disease statuses during anti-TB chemotherapy. To address this, several major immune parameters of CD4+/CD8+ T cells in peripheral blood derived from pulmonary TB patients and healthy volunteers were evaluated. We observed that active TB infection induced lower CD3+ T cell and CD4+ T cell levels but higher CD8+T cell levels, while anti-TB chemotherapy reversed these effects. Also, anti-TB treatment induced enhanced production of IL-2 and IFN-γ but reduced expression of IL-10 and IL-6. Moreover, the dynamic changes of CD3, CD4, and CD8 levels did not show a significant association with sputum smear positivity. However, the frequencies of IL-2+CD4+ or IL-10 + CD4+ T effector subpopulation or IL-1ß production in peripheral blood showed significant difference between patients positive for sputum smear and patients negative for sputum smear after anti-TB treatment. These findings implicated that recovery of Th1/CD8+T cell effector levels might be critical immunological events in pulmonary TB patients after treatment and further suggested the importance of these immunological parameters as potential biomarkers for prediction of TB progress and prognosis.

The serum concentration of vitamin B12 as a biomarker of therapeutic response in tuberculosis patients with and without human immunodeficiency virus (HIV) infection.

BACKGROUND: Prior to clinical trials of new tuberculosis (TB) drugs or therapeutic vaccines, it is necessary to develop monitoring tools to predict treatment outcomes in TB patients. METHODS: Micronutrients concentration level was determined from a total of 262 study participants with five clinical groups: 57 TB patients coinfected with HIV (HIV+TB+), 87 active TB Patients (TB cases), 71 HIV infected without active and latent TB infection (HIV+TST-), 22 latent TB infection (TST+) and 25 healthy controls (TST-). Vitamin A concentration was measured using high-performance liquid chromatography (HPLC), whereas iron and vitamin B12 concentrations were measured using Cobas® 6000 analyzer. RESULT: The serum concentration levels of iron, vitamin A and vitamin B12 had a significant difference between active TB and latent (LTBI) or healthy controls. Six months after treatment, the serum concentration levels of vitamin A, vitamin B12 and iron in tuberculosis became indistinguishable from the levels of LTBIs and healthy control individuals. The concentration levels of iron and vitamin B12 in HIV+TB+patients at the end of TB treatment were normalized to the levels observed in healthy controls (TST-) regardless of HAART treatment. However, the concentration level of vitamin A in HIV+TB+patients HAART untreated at the end of TB treatment was not normalized to the levels observed in healthy controls (TST-) or HAART untreated HIV+TST-. CONCLUSION: Detecting serum concentration levels of vitamin B12 and vitamin A might be used as a biomarker of the diagnostic method of active TB regardless of HIV-infected individuals. Moreover, detecting serum concentration of vitamin B12 might also be used for TB treatment responses monitoring biomarker in TB-HIV-co-infected individuals regardless of HAART (in)eligibility and therapy.

Plasma Eicosanoid Levels in Tuberculosis and Tuberculosis-Diabetes Co-morbidity Are Associated With Lung Pathology and Bacterial Burden.

Host eicosanoids are lipid mediators of inflammation that are commonly accepted as important modulators of the host immune response in Mycobacterium tuberculosis infection. During active tuberculosis (TB), eicosanoids may play an important role in the regulation of inflammatory responses. However, a detailed investigation of the relationship of eicosanoids in TB and TB-diabetes comorbidity (TB-DM) and association to disease pathology or bacterial burdens has not been studied. To study this, we examined the plasma levels of Lipoxin A4 (LXA4), 15-epi-LXA4, Leukotriene B4 (LTB4), and Prostaglandin E2 (PGE2) in individuals with either TB-DM, TB, diabetes mellitus (DM) or healthy controls (HC). Plasma levels of LXA4, 15-epi-LXA4, and PGE2 were significantly increased while the levels of LTB4 were significantly decreased in TB-DM and TB group compared to DM and HC. The ratio of LXA4 to LTB4 and 15-epiLXA4 to LTB4 was significantly enhanced in TB-DM compared to TB. Moreover, the levels of LXA4, 15-epi-LXA4 and the ratios of LXA4 to LTB4 and 15-epiLX4 to LTB4 were significantly increased in TB individuals with bilateral or cavitary disease and these markers also revealed a significant positive relationship with bacterial burden. At the completion of anti-tuberculosis therapy (ATT), levels of LXA4, 15-epi-LXA4, and PGE2 in TB-DM and TB groups were diminished and levels of LTB4 were enhanced in the TB group compared to pre-treatment. Our data imply that alteration and upregulation of eicosanoids are standard characteristics of TB-DM co-morbidity. Our data also demonstrate that modulation in the eicosanoid levels reflect disease severity and extent in TB and TB-DM and are modulated by ATT.

Comparison of Histological, Microbiological, and Molecular Methods in Diagnosis of Patients with TBLN Having Different Anti-TB Treatment Background.

OBJECTIVE: The influence of anti-tuberculosis (TB) treatment history on tuberculous lymphadenitis (TBLN) diagnosis is unclear. Therefore, this study aims to evaluate the diagnostic methods, including histology, microbiology, and molecular tests, used for TBLN. METHODS: In this study, suspected patients with TBLN and having different anti-TB treatment background were enrolled. All the samples were tested simultaneously by histology, Ziehl-Neelsen (ZN) staining, mycobacterial culture (culture), Xpert MTB/RIF (xpert), real-time PCR, and high-resolution melting curve PCR (HRM). Thereafter, the performance of these methods on samples with different anti-TB treatment background was assessed. RESULTS: In our study, 89 patients were prospectively included 82 patients with TBLN and 7 with other diseases. The overall sensitivities of Xpert, real-time PCR, histology, ZN staining, and culture were 86.6%, 69.5%, 58.5%, 43.9%, and 22.0%, respectively. The anti-TB treatment history revealed dramatic influences on the sensitivity of culture (P < 0.0001). In fact, the treatment that lasted over 3 months also influenced the sensitivity of Xpert (P < 0.05). However, the treatment history did not affect the performance of remaining tests (P > 0.05). For rifampicin drug susceptibility test (DST), the anti-TB treatment showed only significant influence on the success rate of culture DST (P = 0.001), but not on those of Xpert and HRM tests (P > 0.05). CONCLUSION: Other tests as well as culture should be considered for patients with TBLN having retreatment history or over 1-month treatment to avoid false negative results.

Comparison of Histological, Microbiological, and Molecular Methods in Diagnosis of Patients with TBLN Having Different Anti-TB Treatment Background / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The influence of anti-tuberculosis (TB) treatment history on tuberculous lymphadenitis (TBLN) diagnosis is unclear. Therefore, this study aims to evaluate the diagnostic methods, including histology, microbiology, and molecular tests, used for TBLN.</p><p><b>METHODS</b>In this study, suspected patients with TBLN and having different anti-TB treatment background were enrolled. All the samples were tested simultaneously by histology, Ziehl-Neelsen (ZN) staining, mycobacterial culture (culture), Xpert MTB/RIF (xpert), real-time PCR, and high-resolution melting curve PCR (HRM). Thereafter, the performance of these methods on samples with different anti-TB treatment background was assessed.</p><p><b>RESULTS</b>In our study, 89 patients were prospectively included 82 patients with TBLN and 7 with other diseases. The overall sensitivities of Xpert, real-time PCR, histology, ZN staining, and culture were 86.6%, 69.5%, 58.5%, 43.9%, and 22.0%, respectively. The anti-TB treatment history revealed dramatic influences on the sensitivity of culture (P < 0.0001). In fact, the treatment that lasted over 3 months also influenced the sensitivity of Xpert (P < 0.05). However, the treatment history did not affect the performance of remaining tests (P > 0.05). For rifampicin drug susceptibility test (DST), the anti-TB treatment showed only significant influence on the success rate of culture DST (P = 0.001), but not on those of Xpert and HRM tests (P > 0.05).</p><p><b>CONCLUSION</b>Other tests as well as culture should be considered for patients with TBLN having retreatment history or over 1-month treatment to avoid false negative results.</p>

Is duration of preoperative anti-tuberculosis treatment a risk factor for postoperative relapse or non-healing of spinal tuberculosis?

PURPOSE: This study evaluated the relationship between spinal TB postoperative recurrence or non-healing and duration of preoperative anti-TB treatment (ATT). METHODS: From January 2004 to January 2013, patients who underwent surgery for spinal TB and met this study's inclusion criteria were retrospectively reviewed. Observed parameters were age, sex, initial ESR, preoperative ESR, degree of ESR change, initial CRP, preoperative CRP, degree of CRP change, duration of preoperative ATT, surgical approach, presence of internal fixation, location of spinal lesion, number of involved segments, duration of operation, and intraoperative blood loss. The data were analyzed by univariate and multivariate analyses for spinal TB recurrence or non-healing to determine related risk factors. RESULTS: A total of 223 patients met the inclusion criteria. There were 84 female and 139 male patients with a mean age of 42.2 years (range 2-85 years). The follow-up period was 18-72 months (average 28.7 months). Among 223 patients observed, 23 patients had postoperative relapse or non-healing (10.3 %) during the follow-up period. Statistical analysis indicated that the location of a spinal lesion was significantly associated with postoperative relapse or non-healing. Risk of postoperative relapse or non-healing in thoracolumbar TB was 2.524-fold (95 % CI 1.026-6.580) that of lumbosacral TB. CONCLUSIONS: Duration of preoperative ATT may not be a risk factor for postoperative recurrence or non-healing of spinal TB. Junctional zones such as the lumbosacral and thoracolumbar junction have a higher recurrence rate than non junctional.