Active Pulmonary Tuberculosis Patients Research Articles

Delayed diagnosis and isolation of active pulmonary tuberculosis patients in the largest tertiary care academic hospital in Riyadh, Saudi Arabia; what are we missing?

Delayed diagnosis and isolation of active pulmonary tuberculosis patients in the largest tertiary care academic hospital in Riyadh, Saudi Arabia; what are we missing?

Delayed inpatient diagnosis and isolation of active pulmonary tuberculosis patients, a large tertiary care academic hospital experience in Riyadh, Saudi Arabia. What are we missing?

Objectives:To identify pulmonary tuberculosis (PTB) delayed inpatient diagnosis duration and contributing factors in an academic center in Saudi Arabia (SA).Methods:Retrospective review of all culture-confirmed PTB cases between May 2015 and April 2019. The outcomes were the timing between admission and suspicion of PTB or isolation to either early group (within 24 hours of admission) and late group (24 hours after admission).Results:Forty-nine cases were included with a median age of 49 years; a third of them were above 65 years of age. Most patients were of Saudi nationality and male. Approximately 38% of the cases were in the delayed group, half of them were smear-positive, with an average delay of 5.5 days. This was significant with age above 65 years (odds ratio [OR]=8.93, 95% confidence interval [CI]=2.22-35.95) presence of non-respiratory symptoms (OR=5.6, 95% CI=1.56-19.98), malignancy (OR=13.38, 95% CI=1.46-122.71), chronic medical problems (OR=4.90, 95% CI=1.31-18.32), missed chest x-ray findings (OR= 48, 95% CI=8.63-266.88) or procalcitonin level above 0.5 ng/mL (OR=12, 95% CI=1.58-91.08).Conclusion:Physicians in SA need to have a low threshold for PTB consideration in elderly patients or those with a history of malignancy. A careful review of the initial chest x-ray might help to overcome missing cases of PTB.

Inverse correlation between serum complement component C1q levels and whole blood type-1 interferon signature in active tuberculosis and QuantiFERON-positive uveitis: implications for diagnosis.

ObjectivesTo examine the relation between serum C1q levels and blood type‐1 interferon signature (type‐1 IFN signature) in active pulmonary tuberculosis (APTB) and to determine whether combined measurement of serum C1q and type‐1 IFN signature may add to the diagnosis of QuantiFERON‐positive (QFT+) patients with uveitis of unknown cause.MethodsC1q was determined (ELISA) in serum from two distinct Indonesian cohorts, and in total, APTB (n = 72), QFT+ uveitis of unknown aetiology (n = 58), QFT− uveitis (n = 51) patients and healthy controls (HC; n = 73) were included. The type‐1 IFN signature scores were previously determined.ResultsSerum C1q was higher in APTB than HC (P < 0.001). APTB patients with uveitis had higher serum C1q than APTB patients without uveitis (P = 0.0207). Serum C1q correlated inversely with type‐1 IFN signature scores in APTB (P = 0.0036, r 2 = 0.3526), revealing that these biomarkers for active TB disease can be mutually exclusive. Stratification of QFT+ patients with uveitis of unknown cause, by serum C1q and type‐1 IFN signature, yielded four groups with different likelihood of suffering from active TB uveitis.ConclusionSerum C1q is elevated in APTB, especially in those cases with uveitis. We propose that combined measurement of blood type‐1 IFN signature and serum C1q may provide added value in the diagnosis of active TB disease. Combined measurement of type‐1 IFN signature and serum C1q in QFT+ patients without signs of active TB disease, but suffering from uveitis of unknown cause, may be of help to identify cases with low or high likelihood of having active TB uveitis, which may facilitate clinical management decisions.

Non-nutritional anemia: Malaria, thalassemia, G6PD deficiency and tuberculosis in Indonesia.

Anemia affects people worldwide and results in increased morbidity and mortality, particularly in children and reproductive-age women. Anemia is caused by an imbalance between red blood cell (RBC) loss and production (erythropoiesis), which can be caused by not only nutritional factors but also non-nutritional factors, such as inflammation and genetics. Understanding the complex and varied etiology of anemia is crucial for developing effective interventions and monitoring anemia control programs. This review focusses on two interrelated nonnutritional causes of anemia: malaria infection and RBC disorders (thalassemia and G6PD deficiency), as well as tuberculosis. According to the Haldane hypothesis, thalassemia occurs as a protective trait toward malaria infection, whereas G6PDd arises in malaria-endemic regions because of positive selection. Indonesia is a malariaendemic region; thus, the frequency of thalassemia and G6PD deficiency is high, which contributes to a greater risk for non-nutritional anemia. As Indonesia is the second global contributor to the newly diagnosed tuberculosis, and active pulmonary tuberculosis patients are more anemic, tuberculosis is also contributes to the increasing risk of anemia. Therefore, to reduce anemia rates in Indonesia, authorities must consider non-nutritional causes that might influence the local incidence of anemia, and apply co-management of endemic infectious disease such as malaria and tuberculosis, and of genetic disease i.e. thalassemia and G6PDd.

Non-nutritional anemia: Malaria, thalassemia, G6PD deficiency and tuberculosis in Indonesia.

Anemia affects people worldwide and results in increased morbidity and mortality, particularly in children and reproductive-age women. Anemia is caused by an imbalance between red blood cell (RBC) loss and production (erythropoiesis), which can be caused by not only nutritional factors but also non-nutritional factors, such as inflammation and genetics. Understanding the complex and varied etiology of anemia is crucial for developing effective interventions and monitoring anemia control programs. This review focusses on two interrelated nonnutritional causes of anemia: malaria infection and RBC disorders (thalassemia and G6PD deficiency), as well as tuberculosis. According to the Haldane hypothesis, thalassemia occurs as a protective trait toward malaria infection, whereas G6PDd arises in malaria-endemic regions because of positive selection. Indonesia is a malariaendemic region; thus, the frequency of thalassemia and G6PD deficiency is high, which contributes to a greater risk for non-nutritional anemia. As Indonesia is the second global contributor to the newly diagnosed tuberculosis, and active pulmonary tuberculosis patients are more anemic, tuberculosis is also contributes to the increasing risk of anemia. Therefore, to reduce anemia rates in Indonesia, authorities must consider non-nutritional causes that might influence the local incidence of anemia, and apply co-management of endemic infectious disease such as malaria and tuberculosis, and of genetic disease i.e. thalassemia and G6PDd.

Prevalence of invasive aspergillosis in suspected pulmonary tuberculosis at a referral tuberculosis hospital in Shandong, China.

AbstractAlthough the progression of invasive aspergillosis (IA) shares some risk factors in the development of active pulmonary tuberculosis (PTB), however, the prevalence of IA in suspected PTB remains unclear. During a period of 1 year (from January 2016 to December 2016), consecutive patients with suspected PTB were included in a referral TB hospital. Data, including demographic information and underlying diseases, were collected from medical records. PTB were all confirmed by mycobacterial culture (Lowenstein–Jensen medium). IA were diagnosed as proven or probable according to the criteria of the 2008 EORTC/MSG definitions. A descriptive analysis was performed to estimate the corresponding prevalence. During the study year, 1507 patients have a positive mycobacterial culture, with a mean age of 45.6 (s.d.19.9) years old and a female:male ratio of 1:4. Among the 82 patients with non-tuberculous mycobacterial diseases, two patients (2.44%, 95% CI 0.67–8.46%) were diagnosed as IA (one proven and one probable); two probable IA patients (0.15%, 95% CI 0.04–0.55%) were diagnosed in PTB patients (n= 1315), and all were retreatment cases. In addition, all four IA patients (100%) exhibited cavities in both lobes on radiograph. In China, the prevalence of IA is low in active PTB patients. However, when high-risk factors for IA are encountered in PTB patients, further investigations are required and empirically treatment for IA might be warranted.

Poor Vitamin D Status in Active Pulmonary Tuberculosis Patients and Its Correlation with Leptin and TNF-α.

Vitamin D deficiency (VDD) is common in tuberculosis (TB) and may be implicated in the etiology of the disease and in its clinical course. The aim of this study was to investigate the association between leptin, inflammatory markers and VD status in TB patients, stratified for presence or absence of diabetes mellitus (DM). Two hundred ninety-nine TB patients were recruited from October 2015 to August 2016. Also, 91 normal controls were included. The information including socio-demographics, dietary intake and living habits was obtained by face-to-face interview. Serum concentrations of leptin and TNF-α, CRP and IL-6 were compared between TB patients with and without severe VDD (SVDD). Pearson's correlation was used to analyze the association between TNF-α, leptin and 25-hydroxyvitamin D (25(OH)D). A significantly higher prevalence of VDD and SVDD was observed in TB patients compared with normal controls (93.0% vs 70.3%, 65.9% vs 3.3% respectively). Concentration of leptin was significantly lower, while TNF-α higher in TB patients with SVDD compared to those without (p<0.05). After adjustment for confounders, leptin was positively associated with 25(OH)D (r=0.210, p=0.002) with similar correlation in TB patients with DM (r=0.240, p=0.020). A negative association between TNF-α and 25(OH)D was observed (r=-0.197, p=0.003), which was significant only in the subgroup without DM (r=-0.304, p=0.001). Our findings indicate that a higher VD status in TB patients may be related to higher immune activity and less serious tissue damage, and that this relation is different according to presence or absence of DM co-morbidity.

Frequencies of Regulatory Subsets of CD4+ TH Cells in Peripheral Blood in Mycobacterium Tuberculosis-Infected Individuals and Healthy Contacts in a High-Burden Setting from Assam, Northeast India

AbstractBackground:Mycobacterium tuberculosis (Mtb) adapts many strategies to persist and replicate inside human tissue. One such strategy is the manipulation of CD4+ TH cells for subset interconversion to regulatory subsets. The aim of the present study is to get an insight of dynamic changes of CD4+ TH cells to regulatory subsets, CD4+ CD25+ forkhead box P3 (Foxp3)+ T-cells and CD4+ CD25+ Foxp3+ programmed death molecule-1 (Foxp3+) T-cells, in peripheral blood in Mtb-infected individuals and healthy contacts in a high-burden setting from Assam, Northeast India. Materials and Methods: A case–control study was conducted in newly diagnosed active pulmonary tuberculosis (APTBs) patients and 2 sets of controls: (i) individuals infected with latent tuberculosis infection (LTBI) and (ii) healthy close tuberculosis healthy contacts (HCs). The frequencies of different subsets of CD4+ cells with regulatory markers were measured in peripheral blood in 3 groups of study participants. Results and Observations: Frequencies of CD4+ CD25+ Foxp3+ T-cells (1.84 ± 1.40 vs. 4.32 ± 1.82 vs. 11.30 ± 3.66), CD4+ CD25+ Foxp3+ PD1+ T-cells (0.37 ± 1.28 vs. 2.99 ± 3.69 vs. 14.54 ± 5.10) and ligand (PD-L1)-positive CD4+ TH cells (0.80 ± 0.45 vs. 2.28 ± 0.95 vs. 7.13 ± 2.02) were significantly increased from HCs to LTBIs to APTB patients, respectively (P < 0.0001). No significant changes in frequencies of total CD4+ cells were observed between APTBs (29.51 ± 11.93), LTBIs (29.23 ± 8.16) and HCs (28.16 ± 9.73) whereas the mean ratios of CD4+ to CD4+ CD25+ FoxP3+ were significantly decreased from 34.34 ± 47.56 in HCs to 7.96 ± 5.8 in LTBIs to 3.12 ± 2.58 in APTBs (P < 0.0001). Significant decrease in mean ratios of CD4+ CD25+ FoxP3+ to CD4+ CD25+ FoxP3+ PD1+ were also observed from 4.97 ± 1.09 in HCs to 1.44 ± 0.49 in LTBIs to 0.78 ± 0.72 in APTBs. Conclusion: CD4+ TH cells change dynamically to regulatory subsets depending on the status of infection and a shift of response towards excessive regulatory T-cells, and PD-1/PD-L1 production may help in the development of active infection in latently infected individuals. These immunological parameters may be used, as potential biomarkers to see the changing dynamics of Mtb infection.

ACID-FAST BACILLI CONVERSION OF BEIJING AND NON-BEIJING STRAIN OF PULMONARY TUBERCULOSIS IN SOUTH SULAWESI

Beijing strains are a major part of the Mycobacterium tuberculosis Asian phylogenetic lineage. Beijing strains represent about 50% of all TB strains in East Asia and at least 13% of strains worldwide. Beijing strain of Mycobacterium tuberculosis is presumed as the factor of the increase in bacteria virulence and drug resistance, and the contributor in treatment failure. The aim of this study was to analyze the association between acid-fast bacilli conversion with strain genotipe Beijing and non-Beijing of pulmonary tuberculosis in South Sulawesi. The design of research was observational analytic with prospective approach. The sampling technique used consecutive sampling. Data were taken from active pulmonary tuberculosis patients’ medical record in Balai Besar Kesehatan Paru Masyarakat Makassar (Pulmonary Health Center of Makassar) and Community Health Center in Gowa Regency, South Sulawesi from March to June 2018. Collected sputum samples were screened for AFB and identified as Beijing strain and non Beijing strains using Multiplex PCR in Tropical Disease Institute of Universitas Airlangga. The results is showed that the characteristics of the respondents consisted of 12 respondents (33.3%) aged 56-65 years, 25 respondents (69.4%) men and 28 respondents (77.8%) had low category gradation of AFB smear. Univariate analysis showed 6 respondents (16.7%) with Beijing strains, 30 respondents (83.3%) with non-Beijing strains, 32 respondents (88.9%) conversion sputum AFB and 4 respondents (11.1%) non conversion sputum AFB. Bivariate analysis with Chi-Square statistical test shows that p value 0.022 &lt; 0,05, that means there was association of Beijing strains with BTA conversion. Microscopic examination of BTA can be used to monitor and evaluate the treatment of new pulmonary TB patients undergoing treatment and the Beijing Mycobacterium tuberculosis strain has a significant correlation with the treatment failure of anti-tuberculosis drugs in South Sulawesi.

Intestinal parasites co-infection and associated factors among active pulmonary tuberculosis patients in selected health centers, Addis Ababa, Ethiopia: unmatched case control study

BackgroundIn co-endemic areas, rate of intestinal parasites and tuberculosis (TB) co-infection thought to be high. However, there are limited studies on the epidemiology of this co-infection in Ethiopia. Therefore, the present study aimed to generate evidence on intestinal parasites co-infection rate and associated factors among pulmonary tuberculosis patients (PTB) and their household contacts in Addis Ababa, Ethiopia.MethodsUnmatched case-control study was conducted. Data were collected from 91 PTB patients (cases) and 89 household contacts (controls). Socio-demographic characteristics and associated factors were collected using structured questionnaire. Sputum, stool and blood specimens were collected, processed and examined for PTB, intestinal parasites and Human Immunodeficiency virus anti-body test, respectively. Data were entered and analyzed by Statistical Packages for Social Sciences (SPSS) Version 20. Descriptive statistics, Fisher’s exact test, binary logistic regression, and odds ratio were used. P-value of < 0.05 was considered as statistically significant.ResultsThe infection rate of intestinal parasites based on one stool samples in PTB patients and controls was 22 and 9%, respectively. The difference was statistically significant (COR = 2.85;95% CI = 1.18–6.87). The most prevalent intestinal parasite in PTB patients was Gardia lamblia (8.8%, 8), followed equally by Ascaris lumbricoides, Haymenolopsis nana and Entamoeba histolytica/dispar (4.4%, 4). Co-infection in PTB patients was associated with body mass index (BMI) < 18.5 (AOR = 6.71;95% CI = 1.65–27.25) and dirty material in finger nails (AOR = 8.99;95% CI = 2.46–32.78). There was no variable associated with parasitic infections in controls in our analysis, which might be due to the low prevalence of intestinal parasites’.ConclusionsThere was a statistical significant difference in the infection rate of intestinal parasites in PTB patients compared to healthy household contacts. The consequence of co-infection on developing an active disease, disease severity and treatment efficacy needs to be investigated in future.

Mycobacteriumtuberculosis antigens repress Th1 immune response suppression and promotes lung cancer metastasis through PD-1/PDl-1 signaling pathway

Given one-third of the world’s population is infected with Mycobacteriumtuberculosis (MTB), it is important to identify the underling molecular mechanism between development of TB and lung cancer. This study investigated the immune response to MTB infection on lung metastasis in lung cancer cells via T cell-mediated immune response. To clarify this problem, we analyzed the expression levels of PD-1, PD-L1, and PD-L2 and immune function in antigen-specific T cell as derived from MTB patients or spleen lymphocytes derived from wild-type and PD-1 knockout mice with MTB antigen stimulation and Lewis lung cancer cells injection. Our data indicate that the expression levels of PD-1, PD-L1, and PD-L2 were elevated in active pulmonary TB patients, as well as in mice received MTB and lung cancer cells treatment. We also observed the T cell-mediated cellular immune response were inhibited by MTB while MTB significantly promote tumor metastasis in lung. In conclusion, the PD-1/PD-L pathway is required MTB repressed T-cell immune response and promotes tumor metastasis. This study provides evidence that blockade of PD-1/PD-L1 signaling pathway may benefit patients with MTB or other chronic infection and even prevent them from development of cancer.

Diagnostic utility of urinary lipoarabinomannan in pulmonary tuberculosis

Background Urinary lipoarabinomannan (LAM) detection is a promising approach for the rapid diagnosis of active tuberculosis (TB). Objective to assess the diagnostic accuracy of quantitative urine Lipoarabinomannan (LAM) test in the diagnosis of pulmonary tuberculosis and evaluate its efficacy as a follow up test after 3 months of the first line of antituberculous therapy. Methods This study was carried out on 40 patients (32 male and 8 female) with active tubercular infection LAM level was measured in urine by enzyme-linked immunosorbant assay (ELISA). Results Patients with smear positive specimens had higher urine LAM level: grade 1+ (mean ± SD of 1.47 ± 0.85 ng/ml), grade 2+ (1.63 ± 1.05 ng/ml), grade 3+ (4.32 ± 2.56 ng/ml) than that of smear negative (1.42 ± 0.50 ng/ml) (P Conclusion Our finding showed that the urine LAM test is simple, rapid, and reliable diagnostic modality for active pulmonary tuberculosis. Quantitative LAM detection results increased progressively with bacillary burden. Urine LAM testing may be an accessible method to monitor response to anti-TB therapy among active pulmonary tuberculosis patients.

Blood cytokine responses to early secreted protein antigen-6/culture filtrate protein-10 tuberculosis antigens 2 months after antituberculosis treatment among patients with drug-susceptible pulmonary tuberculosis.

Human tuberculosis is a chronic inflammatory disease caused by mycobacterium tuberculosis. Pulmonary tuberculosis is the result of the failure of host immune system to control mycobacterium tuberculosis. The aim of the study was to asses the changes of the cytokines in active pulmonary tuberculosis patients before and after the use of anti-TB therapy. Multiple cytokine responses in active tuberculosis (TB) patients were investigated in this study following anti-TB drug therapy after 2 months. Ninety-six participants with pulmonary TB were engaged in the study between May 2018 and October 2018. Samples of blood were taken early before treatment at 0 and 2 months after using anti-TB therapy. The levels of interferon-gamma (IFN)-γ, interleukin-4 (IL-4), IL-6, IL-10, and tumor necrosis factor (TNF)-α in whole blood plasma collected from the QuantiFERON-TB Gold Plus were measured. Compared with baseline levels, TNF-α, IL6 and IL10 were significantly lower following treatment whereas the IFN-γ and IL-4 increased significantly after treatment. The responses of five cytokines varied significantly after treatment (P < 0.0001) where IFN-γ was highest compared to other cytokines with 123.6%, AUC=0.757 and P < 0001, TNF-α AUC: 0.529 and P = 0.743, IL-4 AUC:0.557 and P = 0.514, IL-6 AUC:0.629 and P = 0.047, IL-10 AUC:0.549 and P = 0.581. It is concluded that changes of cytokines that observed during the treatment of TB patients play a very important role in monitoring pulmonary TB and can be suitable biomarkers to assess the effectiveness of anti-TB therapy in patients with TB.

The blood transcriptional signature for active and latent tuberculosis.

BackgroundAlthough the incidence of tuberculosis (TB) has dropped substantially, it still is a serious threat to human health. And in recent years, the emergence of resistant bacilli and inadequate disease control and prevention has led to a significant rise in the global TB epidemic. It is known that the cause of TB is Mycobacterium tuberculosis infection. But it is not clear why some infected patients are active while others are latent.MethodsWe analyzed the blood gene expression profiles of 69 latent TB patients and 54 active pulmonary TB patients from GEO (Transcript Expression Omnibus) database.ResultsBy applying minimal redundancy maximal relevance and incremental feature selection, we identified 24 signature genes which can predict the TB activation. The support vector machine predictor based on these 24 genes had a sensitivity of 0.907, specificity of 0.913, and accuracy of 0.911, respectively. Although they need to be validated in a large independent dataset, the biological analysis of these 24 genes showed great promise.ConclusionWe found that cytokine production was a key process during TB activation and genes like CYBB, TSPO, CD36, and STAT1 worth further investigation.

Immunophenotyping of circulating mononuclear cells in active pulmonary tuberculosis.

Interpreting the interactions between M. tuberculosis and the host innate and adaptive immune defense mechanisms is mandatory for understanding the pathogenesis of active pulmonary TB (APTB). The aim was to describe the distribution of mononuclear cells in APTB and their relation to disease severity. A case-control study of peripheral blood CD4+ T cells, CD8+ T cells, B-lymphocytes, NK cells, T regulatory lymphocytes (Tregs) and monocytes by flow cytometry. The patients had clinical presentations of APTB, positive tuberculin skin tests, acid-fast bacilli smears and sputum cultures using BACTEC 960. There was a significant decrease in the haemoglobin level and the absolute lymphocytic count (p < 0.01), while both the neutrophil count and erythrocyte sedimentation rate showed significant increase in the APTB patients compared to HC with p-values < 0.001 and < 0.0001 respectively. Both the CD4+/CD8+ ratio and the percentages of CD3-CD19+ cells were significantly lower in APTB patients (p = 0.03 and p = 0.005 respectively). The percentages of CD4+, CD8+, CD3-CD19+, CD14+, and CD3-CD (16+56)+ cells showed no significant differences, when comparing either disease severity groups, or cavitated and non-cavitated groups of APTB patients. There was significant increase in the CD4+25+ lymphocytes in the advanced APTB patients than in the mild disease group (p < 0.05). B-lymphocytes and CD4/CD8 ratios were significantly lower in the APTB patients than controls with no association with disease severity. CD4+ CD25+hi Tregs were significantly higher in the advanced versus mild groups.

The utility and validity of immunological, inflammatory, and nutritional-based scores and indices in active Pulmonary Tuberculosis

Purpose: The host immune/inflammatory cells play an important role in Mycobacterium tuberculosis (TB) evolution. We aimed to validate the utility of immunological, inflammatory, and nutritional-based indices in active pulmonary TB (APTB). Patients and methods: fifty PTB patients with fifty healthy subjects were included. Sputum examined for acid-fast bacilli and peripheral blood samples collected to assess inflammatory indices as [neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), neutrophil-platelet score (NPS), body mass index (BMI), ESR, C-reactive protein (CRP) and/or albumin-based as advanced lung cancer inflammation index (ALI), prognostic nutritional index (PNI). Results: Patients had a significantly lower BMI, Hb, lymphocyte, MPV, WBC/MPV, MLR, LMR, albumin, PNI, ALI, (P =0.00001) and significantly higher neutrophil, monocyte, RDW, NLR, PLR, ESR, CRP (P =0.00001). The increase in mycobacterial load significantly associated with decreased BMI, albumin, PNI, ALI and increased ESR, neutrophil count, CRP, CRP/albumin ratio, GPS, mGPS, and PLR. ROC curve analysis revealed that ESR, RDW, BMI, MLR, ALI, Hb, MPV, monocyte, NLR, PLR, albumin, and lymphocyte, had great decision power that could differentiate APTB patients from controls. The best cutoff value MPV (8.08 fL), albumin (3.99 g/dl), BMI (23.67 kg/m2), Hb (12.3 g/dl), and lymphocyte (2600×109/l) RDW (14.8%), monocyte (550×109/l), and ALI (53%) (P =0.0001). Regression analysis approved that MPV, albumin level; BMI, Hb, lymphocyte, and ALI had the highest odds ratio as the prognostic value of APTB Conclusion: the immunological, inflammatory, and nutritional-based scores are valuable prognostic tools that reflect the degree of host inflammatory activity that promotes disease progression.

Association of TLR8 and TLR9 polymorphisms with tuberculosis in a Chinese Han population: a case-control study

BackgroundToll-like receptor (TLR) single nucleotide polymorphisms (SNPs) have been associated with regulation of TLR expression and development of active tuberculosis (TB). The objectives of this study were to determine whether TLR8 and TLR9 SNPs were associated with the development of latent TB infection (LTBI) and the subsequent pulmonary TB (PTB) in a Chinese Han population.MethodsTwo independent samples were enrolled. The first sample contained 584 TB cases and 608 controls; the second sample included 204 healthy controls, 201 LTBI subjects and 209 bacteria-confirmed active PTB patients. Three SNPs (rs3764880, rs187084 and rs5743836) were genotyped. The associations between the SNPs and risk of LTBI or PTB were investigated using unconditional logistic regression analysis.ResultsThe A-allele of TLR8 rs3764880 SNP was protective against the development of TB in males (A vs G, OR = 0.58, 95%CI = 0.37–0.91). The AA genotype of rs3764880 SNP was found to increase the risk of PTB among females with an OR of 4.81 (1.11–20.85). The G allele of TLR9 SNP rs187084 was found to increase the risk of PTB (G vs A, P = 0.01, OR = 1.48, 95% CI = 1.10–2.00), the significance was also observed under dominant genetic models. The GA-genotype of TLR9 rs187084 SNP was found to increase the risk of PTB with an OR of 1.68 (1.07–2.65), but was found to decrease the risk of MTB infection with an OR = 0.64 (0.41–0.98). TLR9_rs5743836 SNP was excluded from the data analyses, because the minimum allele frequency was< 1%.ConclusionsOur findings in two independent samples indicated that SNPs in TLR8 and TLR9 were associated with the development of TB, and highlight that SNPs may have different effects on disease pathogenesis and progression.

Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis?

QuantiFERON-Gold TB (QFT)-positive patients with undetermined cause of uveitis are problematic in terms of whether to diagnose and treat them for tuberculosis (TB). Here, we investigated whether peripheral blood expression of type 1 interferon (IFN)-inducible genes may be of use to stratify QFT-positive patients with uveitis into groups of high versus low risk of having active TB-associated uveitis. We recruited all new uveitis patients in Cipto Mangunkusumo Hospital, Jakarta, Indonesia for one year. We included 12 patients with uveitis and clinically diagnosed active pulmonary TB, 58 QFT-positive patients with uveitis of unknown cause, 10 newly diagnosed sputum-positive active pulmonary TB patients without uveitis and 23 QFT-negative healthy controls. Expression of 35 type 1 IFN-inducible genes was measured in peripheral blood cells from active pulmonary TB patients without uveitis and healthy controls. Differentially expressed genes were identified and used for further clustering analyses of the uveitis groups. A type-1 IFN gene signature score was calculated and the optimal cut-off value for this score to differentiate active pulmonary TB from healthy controls was determined and applied to QFT-positive patients with uveitis of unknown cause. Ten type 1 IFN-inducible genes were differentially expressed between active pulmonary TB and healthy controls. Expression of these 10 genes in QFT-positive patients with uveitis of unknown cause revealed three groups: 1); patients resembling active pulmonary TB, 2); patients resembling healthy controls, and 3); patients displaying an in-between gene expression pattern. A type 1 IFN gene signature score ≥5.61 displayed high sensitivity (100%) and specificity (91%) for identification of active TB. Application of this score to QFT-positive patients with uveitis of unknown cause yielded two groups with expected different likelihood (high vs. low) of having active-TB uveitis, and therefore may be useful in clinical management decisions.

Prevalence of Diabetes Mellitus Among Active Pulmonary Tuberculosis Patients in Addis Ababa, Ethiopia

Prevalence of Diabetes Mellitus Among Active Pulmonary Tuberculosis Patients in Addis Ababa, Ethiopia

Clinical value of the plasma circular RNA hsa_circ_0009024 in the diagnosis and treatment of pulmonary tuberculosis

Objective Detecting plasma level of circular RNA (circRNA) hsa_circ_0009024 in pulmonary tuberculosis (TB) patients, and evaluating its diagnostic value for TB. Methods From January 2016 to December 2016, a hosptial-based, case-control study was performed, which include 90 untreated active pulmonary tuberculosis patients (TB group), 75 healthy people (healthy control)and 84 patient with other diseases (other disease group). Plasma level of circRNA hsa_circ_0009024 was detected by real-time quantitative polymerase chain reaction. Furthermore, the 90 patients with TB were divided into different subgroups according to cavity formation and the lung fields involvement: patients without lung cavity (55 cases) vs those with lung cavity (35 cases), patients with involvement of <2 lung fields (49 cases) vs ≥2 lung fields (41 cases). Plasma levels of hsa_circ_0009024 of 41 TB patientswere monitored andcomparedbefore and after 3 months anti-TB therapy. The sensitivity and specificity of plasma hsa_circ_0009024 were analyzed by using the receiver operating characteristic (ROC) curve. The comparison between two groups was performed with Mann-Whitney U test and the comparison among multigroupswas conducted with Kruskal-Wallis H test. Results Plasma levels of hsa_circ_0009024 in TB patients [1.98 (1.42, 2.71)] were significantly higher than healthy controls [1.03 (0.78, 1.33)] and other disease groups [1.13 (0.77, 1.51)] (H=76.58, P<0.0001). Plasma levels of hsa_circ_0009024 in cavity pulmonary TB patients were higher than pulmonary TB patients without cavity (U=392.50, P<0.0001). Plasma levels of hsa_circ_0009024 in TB patients with involvement of ≥2 lung fields were higher than <2 lung fields (U=590.50, P=0.0008). As compared to pre-treatment [2.01 (1.41, 2.71)], the plasma hsa_circ_0009024 levels decreased significantly in 3 months [1.22 (0.85, 1.47)] (U=292.50, P<0.0001) after anti-TB therapy. The area under the receiver operating characteristics curve (AUC) of plasma hsa_circ_0009024 in discriminating the patients with TB from normal controls, pneumonia patients and lung cancer patients were 0.841 and 0.811, respectively. Conclusion The hsa_circ_0009024 can be used as a potential biomarker in TB diagnosis and monitoring.(Chin J Lab Med, 2018, 41: 399-404) Key words: Tuberculosis, pulmonary; RNA; Biomarkers