Latent Pulmonary Tuberculosis Research Articles

КОВІД-19-АСОЦІЙОВАНІ ЗМІНИ ІМУНИТЕТУ ТА УРАЖЕННЯ ЛЕГЕНЬ

The review of the literature presents basic data on the mechanisms of pathogenesis of a new viral COVID-19 infection: viral damage, immune dysfunction, endothelial lesions. The features of immunological changes in the COVID-19-associated conditions of different severity and genesis of pulmonary lesions have been described. The results of studies on the features of pulmonary pathology in viral lung lesions, acute respiratory distress syndrome, chronic obstructive lung disease, interstitial pulmonary fibrosis, bronchial asthma, active and latent pulmonary tuberculosis have been presented. Additionally, some pathological mechanisms leading to the formation of long-term disease and persistent changes in the lungs after COVID-19 (fibrosis, bronchiectasis, obstructive bronchiolitis, pulmonary thromboembolism) have been outlined. The autoimmune complications due to this viral infection and vaccination against COVID-19, the features of vaccine-induced immunity and the role of crossimmunological reactivity have been reviewed. Key words: COVID-19, SARS-CoV-2 virus, pathogenesis, immunity, lung damage.

Nutritional status and patterns of anemia in sudanese adult patients with active pulmonary tuberculosis: A cross-sectional study.

Malnutrition increases the risk of developing tuberculosis (TB) and causes reactivation of latent pulmonary TB. On the other hand, TB is a recognized cause of malnutrition. Evaluation of the nutritional status and anemia of tuberculous patients with active disease is an important step toward TB management. A. Patients' ages ranged from 16- to 74-year old, with the majority between 20- and 40-year old. Male: female ratio was 2:1. The majority of males and females (91.2% and 84.5%, respectively) had low BF%. Underweight (BMI < 18.5) was 62%, whereas overweight (BMI ≥25.0) was 4%. BMI showed a significant decline with chronicity of the illness (P < 0.001). Eighty participants showed anemia, 90% microcytic hypochromic, and 10% normocytic normochromic. Serum albumin was low in 21%, with no relation to renal disease and insignificant association with proteinuria. Patients with active pulmonary TB are likely to have microcytic hypochromic anemia, low BF%, and low BMI, especially with a long duration of the disease.

Protective Effect of the T1212C Macrophage Mannose Receptor Gene Polymorphism on Pulmonary Tuberculosis

The interaction between the mannose receptor, which is encoded by the macrophage mannose receptor (MMR) gene, and the most virulent antigen (the mannose-capped lipoarabinomannan) cell wall of virulent strains of Mycobacterium tuberculosis trigger an innate and adaptive immune response. It also produces pro and anti-inflammatory cytokines, which play a role in the pathogenesis of tuberculosis (TB) infection. Therefore, MMR gene polymorphism is a risk factor and is associated with the prognosis for active pulmonary TB. This study aimed to determine the correlation between MMR gene polymorphism and active or latent pulmonary tuberculosis. In this phase, MMR gene polymorphism was analyzed using a case-control design consisting of 74 control group subjects (patients with latent TB) and 74 case groups (patients with active pulmonary TB). The subject’s MMR gene DNA sequencing examination. The study was conducted at the Teaching Hospital, Faculty of Medicine, Universitas Padjadjaran Bandung, from February 2014 to January 2015. The statistical analysis used chi-square and odds ratio. The study’s result has shown the MMR gene polymorphism factor that correlated to the incidence of active pulmonary TB was T1212C (OR=0.253; 95% CI=0.111−0.575; p=0.001). There was an MMR gene in one SNP in the control group (C1323T) only and five single nucleotide polymorphisms (SNPs) in both groups (C1303T, C1221, T1212C, G1186A, and G1195A). Therefore, it can be concluded that MMR gene polymorphism on the T1212C site correlated with the incidence of active pulmonary tuberculosis and was protective.

Expression of miRNA-29a-3p and IFN-γ as biomarkers in active and latent pulmonary tuberculosis.

Diagnosis and management of latent tuberculosis (TB) infections are one of the challenges of eradicating pulmonary TB. A critical aspect of controlling pulmonary TB spread is early diagnosis. One TB biological marker type under evaluation is microRNAs (miRNAs). Mycobacterium tuberculosis infection causes epigenetic changes. The upregulation of miRNA-29a-3p suppresses the immune response by post-transcriptionally inhibiting interferon (INF)-γ expression in T cells, increasing susceptibility to pulmonary TB. This study aimed to assess miRNA-29a-3p expression as a biomarker of active and latent pulmonary TB infection. This case-control study included 50 individuals with active TB, 33 household contacts with a positive IFN-γ release assay (IGRA), and 30 healthy controls. An enzyme-linked immunosorbent assay-based IGRA was used to determine latent pulmonary TB infection in household contacts. Quantitative real-time PCR was used to quantify miRNA-29a-3p expression. Data analysis used analyses of variance and receiver operating characteristic (ROC) curves. miRNA-29a-3p expression differed significantly between active TB, latent TB, and healthy participants (controls; p = <0.001. ROC curve analysis showed that miRNA-29a-3p expression had 86% sensitivity and 73% specificity with an area under the ROC curve (AUC) of 0.763 (95% confidence interval [CI]: 0.668-0.858). The miRNA-29a-3p ROC curve had 84.8% sensitivity and 70% specificity with an AUC of 0.808 (95% CI: 0.698-0.919) for latent TB. Additionally, miRNA-29a-3p expression was significantly correlated with active (p<0.0001) and latent (p<0.0001) pulmonary TB. However, miRNA-29a-3p expression was not significantly correlated with INF-γ levels in patients with active (R=0.005; p=0.62) and latent (R=0.010; p=0.38) pulmonary TB or healthy controls (R=0.060; p=0.19). miRNA-29a-3p expression was increased in patients with active and latent pulmonary TB. Therefore, miRNA-29a-3p represents a potential biomarker for latent and active pulmonary TB. However, IFN-γ levels were not correlated with miR-29a-3p expression.

Screening of Latent Pulmonary Tuberculosis infection in Kurdistan regional-Iraq using QuantiFERON-TB gold plus technique

Background and Objective: Pulmonary tuberculosis (PTB) is a serious disease that mainly affects the lungs. The aim of this study was a screening of latent pulmonary tuberculosis (LTBI) in Kurdistan Regional-Iraq, using QuantiFERON-TB Gold Plus technique (QFT-Plus). Methodology: The study analyzed 24close contact persons (11 male and 13 female) their ages ranged from 16 to 66 years. Interferon-gamma had been measured by sandwich ELISA. Results: Our result showed diagnosis of (3\24) contacts Infected with LTBI, (1\24) contact intermediate and (20\24) normal individual persons by QFT-Plus technique. Conclusion: Our study recommends screening for LTBI in populations at increased risk (close contacts persons with active pulmonary tuberculosis patients) and QFT-Plus is important test for diagnosis of PTBI.

Prevalence of latent pulmonary tuberculosis in children with diabetes mellitus attending a Tertiary Care Hospital in Mansoura: a cross-sectional study

Aims Tuberculosis (TB) and diabetes mellitus are closely associated with each other. We conducted a cross-sectional study to assess the prevalence and pattern of latent pulmonary TB in diabetic children using a combined screening tool. Settings and design A cross-sectional study was carried out in a Tertiary Care Hospital, Mansoura, Egypt, during the period from January to December, 2016. Materials and methods The study enrolled all diabetic children with the inclusion criteria who were available during the study period and attending the endocrinology outpatient clinics or admitted in the inpatient ward. A total of 70 diabetic patients completed tuberculin skin test (TST) reading, and their results were compared with those of 70 healthy controls. All patients were subjected to detailed medical history, complete physical examination, and laboratory and radiological evaluation. TB screening was done for both groups using TST, sputum microscopy and culture, and chest radiography. We used TST induration diameter more than 6 mm as the cut-off value to determine test positivity. Results A total of 53 (75.7%) patients of the studied diabetic group were poorly controlled. TST was positive in 30% of the screened diabetic patients. Test positivity was significantly higher among diabetic group when compared with control group. TST positivity was significantly higher in poorly controlled diabetic cases. There was a statistically significant negative correlation between TST induration diameter and HBA1C. Conclusion Diabetic patients are more vulnerable to latent pulmonary TB. The association between poor glycemic control and latent pulmonary TB among diabetic patients was evident. Combining TST with sputum culture and chest radiography did not improve screening results.

Mycobacterium tuberculosis produces small noncoding RNAs during infections to regulate mycobacterial and eukaryotic gene expression

Abstract Mycobacterium tuberculosis (Mtb) presently infects 1/3 of the World’s population, causing both active and latent pulmonary tuberculosis (TB). The pathogenic mechanisms used by Mtb remain poorly defined. We used a small RNA sequencing strategy on RNA extracted from Mtb-infected THP-1 macrophages to characterize the changes in eukaryotic microRNAs (miRs) and identify any mycobacterially-encoded small RNAs. A large number of mammalian microRNAs were differentially regulated during the infection course. Target prediction programs indicated that the mRNAs regulated by the miRs were involved in immune processes, metabolic pathways, cell communication, and developmental events. In addition, 35 Mtb-encoded small RNAs (18–30 nucleotides, mRs) were discovered. Several of the Mtb-encoded mRs were detected in lung tissue biopsies from TB infected monkeys. The 100–150 nucleotides surrounding the 35 Mtb-encoded small RNAs had extensive secondary RNA folding capabilities, including hairpins and antisense stretches more characteristic of eukaryotic pre-microRNAs. Two such small RNAs, Mtb-mR-1 and Mtb-mR-6 were transcribed in Mycobacterium avium complex and Mtb in a hairpin loop and antisense sequence-dependent manner. These mRs were not expressed in Mycobacterium smegmatis, revealing a restricted expression to pathogenic strains. Mtb-encoded mR-1 and mR-6 modulated both prokaryotic and eukaryotic gene expression. Taken together, our findings reveal potentially novel pathogenic processes utilized by Mtb during infections.

Erythrodermic Psoriasis Improved by Ustekinumab: A Report of Two Cases.

Dear Editor: Erythrodermic psoriasis is a severe form of psoriasis, presenting as prominent erythema rather than thick scales, affecting the entirebody including the face, trunk, extremities, and nails. The disease poses a therapeutic challenge, and numerous treatment choices have been examined1. Ustekinumab (Stelara; Jannssen Biotech Inc., Horsham, PA, USA) is a human monoclonal antibody targeting the p40 subunit shared by interleukin (IL)-12 and IL-23. This biological agent has shown good efficacy against plaque-type psoriasis and emerging effectiveness in a variety of inflammatory skin diseases such as atopic dermatitis2. Erythrodermic psoriasis has been an exclusion criterion in studies evaluating the efficacy of ustekinumab for psoriasis, but recently, a few reports have proven its efficacy in treating erythrodermic psoriasis3,4,5. Herein, we report 2 cases of erythrodermic psoriasis that successfully improved following ustekinumab treatment. A 42-year-old man presented with a 7-year history of erythrodermic psoriasis and a 5-year history of psoriatic arthritis. He was previously treated with cyclosporine A, methotrexate, and narrow band ultraviolet B phototherapy. The treatments were interrupted due to liver enzyme elevation and low efficacy. The patient was treated with ustekinumab 45 mg subcutaneously at 0, week 4, and every 12 weeks thereafter. The patient was also diagnosed with latent pulmonary tuberculosis by the QuantiFERON-TB Gold In-Tube test (Cellestis Limited, Carnegie, VIC, Australia). He was concurrently treated with isoniazid 300 mg/day for 6 months and has not experienced a recurrence of tuberculosis to date. At week 28, his Psoriasis Area and Severity Index (PASI) score decreased from 64.8 (baseline) to 9.6 (Fig. 1). The psoriasis aggravated temporarily during discontinuation of the treatment for 5 months and he promptly recovered upon restarting ustekinumab injections. His arthritis symptoms improved slightly, but the improvement was not sufficient for him to stop taking oral sulfasalazine and steroid for the arthralgia. Fig. 1 A 42-year-old man presented with whole body erythema with scanty scales. He responded well to ustekinumab (A: baseline, B: 28 weeks after the treatment, C: 76 weeks after the treatment). The second case is a 26-year-old man suffering from erythrodermic psoriasis for 10 years. Therapies with conventional systemic agents and anti-tumornecrosis factor were discontinued due to lack of efficacy. Four months after the first administration of ustekinumab (45 mg), the patient achieved 75% improvement of the PASI score from 50.9 (baseline) to 4.4 (Fig. 2A, B). Currently, the patient has received treatment for 112 weeks, and is maintaining a PASI 90 improvement (Fig. 2C). Fig. 2 A 26-year-old man. (A) Baseline: normal skin islands are noticeable within the diffuse erythroderma. Clinical improvement was significant and sustained (B) 28 weeks after the treatment and (C) 112 weeks after the treatment, respectively. Both patients are currently on treatment, and show sustained responses without any adverse reactions or exacerbations. Although further studies are needed to evaluate the efficacy and safety of ustekinumab, it is likely that ustekinumab can be an effective therapeutic option for patients affected by erythrodermic psoriasis where other treatments have failed.

Adiponectin Levels as a Marker of Inflammation in Pulmonary Tuberculosis

Background: tuberculosis (TB) is a multisystem disease with myriad presentations and manifestations that may be pulmonary or extra-pulmonary. It is the most common cause of infectious diseases related mortality worldwide. Mechanisms underlying host defense to TB infection are poorly understood. Adiponectin is a protein produced exclusively in adipose tissue; it is lower in obese subjects than their lean counterparts. Another adipocyte hormone is leptin which is higher with fat mass and body mass index (BMI). Wasting is a known feature of TB with a decrease in BMI. Patients with pulmonary TB disease often suffer from weight loss and BMI and leptin are known to be inversely correlated with adiponectin. Thus, increased adiponectin may be a promising marker for severity of the disease independent of the BMI and leptin. Aims of the work: the work aimed to evaluate the levels of serum adiponectin in patients with pulmonary TB in both active and latent TB patients as a diagnostic marker for tuberculous inflammation. Also, levels of serum leptin and measured BMI were evaluated and compared to make a relationship among active TB, latent TB, and healthy control groups. Subjects and Methods: the subjects were divided into 3 equal groups. The 1st group included 25 patients with active pulmonary TB. The 2nd group included 25 patients with latent TB after 6 months of diagnosis. The 3rd group included 25 healthy control volunteers. Serum levels of adiponectin and leptin were measured and BMI values were calculated to all groups. Results: Serum adiponectin levels in patients with active pulmonary TB were very highly significantly increased compared to both latent TB patients and healthy subjects (P<0.0001), while serum adiponectin levels in patients with latent pulmonary TB were only significantly increased compared to the healthy subjects (P<0.05). On the other hand, serum leptin levels in patients with active pulmonary TB were very highly significantly decreased compared to both latent TB patients and healthy subjects (P<0.0001), while serum leptin levels in patients with latent pulmonary TB were only significantly decreased compared to the healthy subjects (P<0.05). Also, BMI in patients with active pulmonary TB were very highly significantly decreased compared to both latent TB patients and healthy subjects (P<0.001), while BMI in patients with latent pulmonary TB were only significantly decreased compared to the healthy subjects (P<0.05). Conclusion: the higher levels of adiponectin with lower levels of leptin in association with lower BMI measurements might indicate activity and severity of the TB disease. On the other hand, the lower levels of adiponectin with higher levels of leptin in association with higher BMI measurements might indicate stability and latency of the TB disease. Thus, increased adiponectin in the serum of pulmonary TB patients may be promising markers for severity of the disease independent of the BMI and leptin levels.

Heterozygosity at the A625C Polymorphic Site of the MyD88 Gene Is Associated with Mycobacterium bovis Infection in Cattle

The study demonstrates that in cattle, animals heterozygous at the MyD88 A625C polymorphic marker have a 5-fold reduced risk for active pulmonary tuberculosis (odds ratio [OR] = 0.19; P = 6 × 10(-12)). The reduced risk, however, does not extend to animals with latent pulmonary tuberculosis (OR = 0.83; P = 0.40). Heterozygosity at the A625C single nucleotide polymorphism is associated with intermediate levels of tumor necrosis factor alpha, gamma interferon, and nitric oxide synthase (NOS). Accordingly, deficiency as well as overexpression of proinflammatory cytokines or NOS favor tuberculosis, while heterozygosity provides the animals with the optimal level of inflammation.

LATENT PULMONARY TUBERCULOSIS

Objective: To assess the prevalence of latent pulmonary tuberculosis (TB) in young adults males on MMR screening. Design: Descriptive study Place and duration of study: The study was carried out at Combined Military Hospital Kohat from January 2004 to August 2005. Material and Methods: A total of 4000 freshly inducted recruits aged between 18-23 years were subjected to MMR using an Odalka camera. Individuals with suspicious findings had a standard chest radiograph taken and on confirmation of findings they were inoculated with tuberculin and readings of Mantoux test were recorded. Results: Out of 4000 MMR films, 2.15% were judged suspicious and standard chest radiographs were taken. 1.2% showedfeatures suggestive of pulmonary TB. 0.175% showed non-tuberculous pulmonary findings and 0.05% showed cardiac lesions. 0.725 % chest radiographs were normal. 1.2 % suspected cases of pulmonary TB were investigated further with Mantoux test. 0.745% had strongly positive Mantoux test and were labeled as latent pulmonary TB. Conclusions: Pulmonary TB is a major health issue in our country. There is a highprevalence of latent pulmonary TB in our asymptomatic adult population. MMR is an effective and cheap method of early detection and should be considered for mass screening of our younger population on a larger scale.

Pulmonary tuberculosis in allogeneic hematopoietic stem cell transplantation.

Pulmonary tuberculosis (TB) is an endemic infectious disease in Taiwan. A retrospective study was conducted to define clinical manifestations and outcomes of patients with pulmonary TB among hematopoietic stem cell transplantation (HSCT) recipients. We identified eight out of 350 HSCT recipients as having pulmonary TB over a 6-year period. The relative risk of having pulmonary TB after HSCT was 13.1-fold higher than in the general population. There was a trend toward increased risk of having pulmonary TB in allogeneic HSCT as compared to autologous HSCT (4.8 +/- 1.8% vs 0, P = 0.067). All the eight patients with pulmonary TB received allogeneic HSCT and most (seven of eight patients) developed the infection during treatment for GVHD. Computed tomography of the chest was normal in one patient, with the rest showing either interstitial (two patients) or alveolar infiltrates (five patients) at the onset of pulmonary TB. The four fatal cases had an obviously shorter duration between HSCT and onset of infection. Our data suggest that pulmonary TB in HSCT recipients is not uncommon in this endemic area. Therefore, an effective strategy of prophylactic treatment for candidates and recipients of allogeneic HSCT, who may have latent pulmonary TB infection, must be developed.