Groups Of Tuberculosis Patients Research Articles

Gut bacterial and fungal dysbiosis in tuberculosis patients

BackgroundRecent studies have more focused on gut microbial alteration in tuberculosis (TB) patients. However, no detailed study on gut fungi modification has been reported till now. So, current research explores the characteristics of gut microbiota (bacteria)- and mycobiota (fungi)-dysbiosis in TB patients and also assesses the correlation between the gut microbiome and serum cytokines. It may help to screen the potential diagnostic biomarker for TB.ResultsThe results show that the alpha diversity of the gut microbiome (including bacteria and fungi) decreased and altered the gut microbiome composition of TB patients. The bacterial genera Bacteroides and Prevotella were significantly increased, and Blautia and Bifidobacterium decreased in the TB patients group. The fungi genus Saccharomyces was increased while decreased levels of Aspergillus in TB patients. It indicates that gut microbial equilibrium between bacteria and fungi has been altered in TB patients. The fungal-to-bacterial species ratio was significantly decreased, and the bacterial-fungal trans-kingdom interactions have been reduced in TB patients. A set model including Bacteroides, Blautia, Eubacterium_hallii_group, Apiotrichum, Penicillium, and Saccharomyces may provide a better TB diagnostics option than using single bacterial or fungi sets. Also, gut microbial dysbiosis has a strong correlation with the alteration of IL-17 and IFN-γ.ConclusionsOur results demonstrate that TB patients exhibit the gut bacterial and fungal dysbiosis. In the clinics, some gut microbes may be considered as potential biomarkers for auxiliary TB diagnosis.

ВОЗРАСТНЫЕ ОСОБЕННОСТИ ФОРМИРОВАНИЯ ВНЕКЛЕТОЧНЫХ ЛОВУШЕК НЕЙТРОФИЛОВ У ЗДОРОВЫХ ЛИЦ И БОЛЬНЫХ ТУБЕРКУЛЁЗОМ

Abstracts. Introduction. Forming a neutrophil extracellular trap (NET) from DNA (NETosis) is considered as a potentially significant marker in the diagnosis of tuberculosis. However, there is practically a lack of data regarding the age-related differences in forming extracellular traps in research publications. Aim. To determine the age-related differences of NETosis in healthy individuals and in tuberculosis (TB) patients. Materials and Methods. The ability of neutrophils to form extracellular traps was investigated in 4 groups: 1) 4-7-year-old children diagnosed with the primary tuberculosis complex, who fell ill within Omsk region; 2) healthy and uninfected children at the same age; 3) adults with tuberculosis, and 4) adults without tuberculosis. For this purpose, isolated fractions of neutrophils from peripheral blood of the groups under research were stimulated with a mixture of bacteria (probiotic) for 30 minutes. In the hanging-drop preparation, we analyzed the proportion of neutrophil extracellular traps and cells in the state of various motility degrees. Results and Discussion. Age-related differences in the ability of neutrophils to form extracellular traps were characterized by a more pronounced response of neutrophils to the NETosis stimulant in children in the control group in comparison with neutrophils isolated from blood in the group of healthy adult volunteers: Neutrophils of children (Me=16.1; Q1=12.8; Q3=18.3) were statistically significantly more intense (p=0.0002) than those of adults (Me=8.6; Q1=7.1; Q3=10.5) and formed filamentous NETs. In the groups of pediatric and adult pulmonary TB patients, the response of neutrophils to the NETosis stimulant was diametrically opposite. Neutrophils of children with primary tuberculosis complex, as of those in the control group, predominantly formed filamentous NETs, but in greater amounts, while neutrophils of adults with infiltrative or focal form and with at most 2 segments involved mainly formed cloudy NETs, whereas filamentous NETs prevailed for the adults in the control group after stimulation. At the same time, proportion of cloudy NETs did not exceed 5% in healthy children and healthy adults. Comparing the findings of our study with literature data, we hypothesized that, most likely, there is a greater increase in PAD4 expression and more pronounced histone H3 citrullination in children’s neutrophils than in those of adults. Conclusions. Our findings indicate more pronounced ex vivo processes induced by NETosis stimulator in both groups of children (healthy individuals and TB patients) as compared to adults in the respective groups, which should be considered by the researchers interpreting the findings of the ability of neutrophils to form extracellular traps in tuberculosis.

Otoprotective and antioxidant activity of cytoflavin in pulmonary tuberculosis patients receiving amikacin

The objective: to study the potential otoprotective and antioxidant activity of cytoflavin in new pulmonary tuberculosis patients receiving aminoglycoside amikacin.Subjects and Methods. A randomized controlled trial was conducted and included 90 patients with new infiltrative pulmonary tuberculosis with decay, of both genders aged from 20 to 50 years old. Clinical, paraclinical and statistical methods were used in the study. Audiometric screening was carried out by Diagnostic Audiometer AD 226. The degree of antioxidant protection was determined by the oxidation reaction of ABTS in blood serum and plasma.Results. The study included 4 groups of tuberculosis patients and 1 group of healthy donors. Dissemination of pulmonary tuberculosis in 4 groups was approximately the same and was measured by scores. Prior to the start of treatment in all 4 groups (the group receiving standard chemotherapy (CTX) without amikacin, the group receiving «CTX+amikacin», the group receiving «CTX+cytofl avin», the group receiving «CTX+amikacin+cytofl avin») there was a decrease in blood antioxidant activity compared to Control Group. After 3 months of tuberculosis treatment in all 4 groups, the results improved, while in «CTX+Cytofl avin» Group they were similar to Control Group, and «CTX+Amikacin+Cytofl avin Group», they were only 4.8% less. The elevated level of leukocytes decreased by 10.6% in CTX Group, 16.9% in «CTX+Amikacin» Group, 38.3% in «CTX+Cytofl avin» Group, and 72.3% in «CTX+Amikacin+Cytofl avin» Group. In the study, manifestations of oto- and vestibulotoxicity were found only in the «CTX+Amikacin» Group (in 4/20 (5%)). There were no such cases in «Amikacin+Cytofl avin» Group consisting of 23 patients.

The significance of notch signaling in the regulation of Тreg-lymphocyte differentiation in patients with infiltrative pulmonary tuberculosis

Data on the role of regulatory T lymphocytes (Treg) in the immunopathogenesis of tuberculosis are actively accumulating in the current literature. The overwhelming effect of Treg cells on the proliferation, functional activity of Th1 lymphocytes and antigen-presenting cells allows to consider this population as a possible target of modulation of the immune response in patients with tuberculosis. The Notch signaling pathway participates in the regulation of FoxP3 transcription factor expression and, therefore, is capable of supporting suppressor activity of Treg lymphocytes. A key role in the functioning of the Notch signaling cascade belongs to the enzyme γ-secretase that cleaves the intracellular domain of the receptor (Notch ICD), with the subsequent formation of a complex that regulates cell differentiation. The actively studied inhibitor of γ-secretase is DAPT – N-[N-(3.5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester). Mononuclear leukocytes isolated from the blood of patients with drug-sensitive and drug-resistant pulmonary tuberculosis by gradient centrifugation before the start of anti-tuberculosis therapy were used as the material for the study. The cells were cultured under conditions of stimulation with Mycobacterium tuberculosis antigens CFP10-ESAT6 or with the addition of γ-secretase inhibitor (DAPT) at doses of 5 μM/L and 10 μM/L in combination with CFP10-ESAT6 at 37 °C and 5% CO2 for 72 h to the incubation medium. The number of Treg lymphocytes was assessed by flow cytofluorimetry by determining the expression of the CD4 surface receptor (FITC) and the intracellular transcription factor FoxP3 (PE). In intact cell cultures of pulmonary tuberculosis patients, the relative number of Treg lymphocytes was statistically significantly (p < 0.001) higher than that of healthy donors. Stimulation of cells with CFP10-ESAT6 antigens was accompanied by an increase in the proportion of CD4+FoxP3+ cells in both groups of tuberculosis patients. Addition of γ-secretase inhibitor at a concentration of 5 μM/L to the incubation medium did not lead to statistically significant changes in the number of Treg lymphocytes. The increase in DAPT concentration up to 10 μM/L was accompanied by a decrease in the number of Treg lymphocytes in comparison with the corresponding indices upon stimulation with CFP10-ESAT6 antigens in all groups of the subjects. Regardless of cultivation conditions, the number of CD4+FoxP3+ cells in patients with drug-resistant mycobacteria exceeded their number in patients with drug-sensitive pulmonary tuberculosis. Inhibition of the Notch signaling pathway by a γ-secretase inhibitor (DAPT) at a concentration of 10 μM/L contributed to a decrease in the number of Treg lymphocytes in patients with drug-sensitive and drug-resistant pulmonary tuberculosis. Reduction of Treg lymphocyte number by γ-secretase inhibitor confirms the importance of Notch signaling cascade as a potential target for correction of Treg lymphocytes immunosuppressive activity and pathogenetic therapy of tuberculosis.

The Magnitude of Anxiety and Depressive Symptoms Among Tuberculosis Patients in Community Health Centers Setting During the Peak of COVID-19 Pandemic.

BackgroundMental health problems can occur in patients with chronic diseases such as tuberculosis, and the stress of a pandemic exacerbates the condition. The study aims to explore the magnitude of anxiety and depressive symptoms in tuberculosis (TB) patients in community health centers (CHCs) settings during the COVID-19 pandemic.MethodsThe study design was quantitative and cross-sectional. Subjects were TB patients who were recruited from TB services by doctors in CHCs. TB patients (n=74) were screened for anxiety and depressive symptoms over 4 months. Screening results are uploaded on a cloud-based digital platform and analyzed. Non-TB patients, as a comparison, were recruited and screened from the same cloud-based digital platform (n=245) during the same period. Analysis was carried out using Rasch modeling for data transformation. Data was analyzed then for frequency distribution for both groups and the logistic binaries to measure the burden of the mixed anxiety and depressive symptoms among the TB patient age’s sub-group.ResultsIn both groups, there were 48.9% of mild, moderate, and severe categories of anxiety and 63.9% of depressive symptoms. In the TB-patients group, anxiety occurred at 48.7%, of which 23% were in the moderate and severe categories, compared to 13.4% for non-TB patients. Depressive symptoms were present in 71.6% of the TB patient group, of which 28.4% were in the moderate and severe categories, compared to 15.5% of non-TB patients. TB patients aged less than 20 years experienced moderate–severe anxiety with depressive symptoms simultaneously (mixed) as much as 16.3% or 4.6 times more than those aged over 20 years (p<0.05).ConclusionModerate and severe anxiety and depressive symptoms were shown higher in the TB patients’ group. Adolescents with TB are more susceptible to mental and emotional disorders.

Vitamin C Supplementation Improves Pulmonary Tuberculosis Patients' Sputum Conversion During Intensive Phase Category I Treatment in Medan

Background: Many factors influence the success of the acceleration of Acid-Fast Bacilli (AFB) sputum conversion in the treatment of the intensive phase of pulmonary tuberculosis (TB). One of these factors is the nutritional status or nutrition of pulmonary TB patients. Through a fenton reaction, Vitamin C is known to be able to sterilize Mycobacterium tuberculosis. This study aims to determine the effect of giving vitamin C on the conversion of AFB sputum in the intensive phase of pulmonary TB treatment. Method: This study was an inferential, quasi-experimental evaluation of the acceleration of AFB sputum conversion following vitamin C supplementation in patients with category I pulmonary TB. The study group was separated into two groups: 40 TB patients getting Anti Tuberculosis Treatment (ATT) with vitamin C, and 40 TB patients receiving ATT with placebo. Every two weeks, AFB sputum was examined, and vitamin C levels were measured before and after two months of therapy. Results: Conversion of AFB occurred sooner in the vitamin C group of pulmonary TB patients, with as many as 29 patients (72.5%) experiencing conversion of AFB sputum at the end of the second week of therapy, whereas there was no conversion in the placebo group. At the end of the fourth week, all patients (100%) given vitamin C showed AFB sputum conversion, whereas only eight patients (20%) in the placebo group had conversion at the end of the fourth week of treatment. Vitamin C levels increased significantly in the group of pulmonary tuberculosis patients who received vitamin C supplementation. Conclusion: Vitamin C supplementation in the treatment of pulmonary TB can accelerate the conversion of AFB sputum, which is statistically significant.

Особливості цитокінової регуляції при мультирезистентному туберкульозі залежно від ступеня ендогенної інтоксикації

Актуальність. Туберкульоз (ТБ) відноситься до інтерлейкінзалежних імунодефіцитів із вираженими змінами в цитокіновій системі. Незважаючи на значні успіхи в досягненні контролю над ТБ, залишається невизначеною роль окремих цитокінів у формуванні резистентних його форм, не вирішені питання ідентифікації інтегральних маркерів прогресування патологічного процесу при мультирезистентному туберкульозі легень (МРТБ), а також відсутнє прогностичне визначення їх ролі в забезпеченні ефективності стандартних програм протитуберкульозної хіміотерапії. У зв’язку із вищезазначеним закономірно виникає необхідність аналізу показників окремих цитокінів у сироватці крові пацієнтів із МРТБ залежно від профілю резистентності, що може відображати ступінь вираженості місцевого та системного характеру специфічного запалення, особливості імуноцитокінової регуляції з метою удосконалення програми лікування. ТБ відноситься до захворювань, які супроводжуються ендогенною інтоксикацією, тобто накопиченням в організмі кінцевих та проміжних продуктів метаболізму при порушеному обміні внаслідок запальної реакції. Шляхами формування ендогенної інтоксикації при ТБ є цитотоксична гіпоксія, порушення внутрішньоклітинного гомеостазу, масивне утворення та подальша резорбція продуктів тканинного розпаду, імуноцитокіновий та гормональний дисбаланс тощо. Мета дослідження — оцінити показники ендогенної інтоксикації, встановити особливості цитокінової регуляції у хворих на мультирезистетний туберкульоз легень залежно від профілю резистентності мікобактерій та визначити їх роль у формуванні системної запальної реакції. Матеріали та методи. Об’єктом дослідження стали 116 пацієнтів із діагнозом вперше діагностованого туберкульозу легень із збереженою чутливістю до антимікобактеріальних препаратів; із МРТБ із діагностованою стійкістю як мінімум до двох препаратів I ряду; хворі на туберкульоз із розширеною резистентністю. Використано клінічні, рентгенологічні, біохімічні, мікроскопічні, мікробіологічні, імуноферментні та статистичні методи дослідження. Результати. Проведений кореляційний аналіз за Пірсоном між про- і протизапальними цитокінами показав, що у хворих на МРТБ коефіцієнт кореляції негативний, слабкої сили між показниками інтерлейкіну (ІЛ)-6 та ІЛ-10, між ІЛ-18 та ІЛ-10 (–0,22, р &lt; 0,001; –0,16, р &lt; 0,001). Продукція ІЛ-6 та ІЛ-10 у групах хворих на ТБ незалежно від резистентності зростає у відповідь на підвищення синтезу ендотоксинів мікобактерій туберкульозу, наростання ендогенної інтоксикації та цитотоксичної гіпоксії створює передумови для розвитку їх резистентності. Дисбаланс співвідношення ІЛ-18 та ІЛ-10 у цих хворих характеризує збільшення ступеня тяжкості стану пацієнта, поширеність запального процесу в легенях і формування резистентності; відзначається істотна перевага лімфоцитів Тх 2-го типу (гуморального), що вказує на розвиток дефекту клітинно-опосередкованого імунного захисту та перевагу неефективної протизапальної імунної активації. Висновки. Комплексна оцінка показників інтегральних індексів ендогенної інтоксикації та рівня окремих про- та протизапальних цитокінів у плазмі крові хворих на МРТБ свідчить про помірно виражену ендогенну інтоксикацію, виснажені клітинні ланки імунної реактивності за рахунок формування умов розвитку резистентності мікобактерій туберкульозу із подальшим наростанням цитотоксичної гіпоксії та активації синдрому системної запальної відповіді. Аналіз вмісту ІЛ-6, ІЛ-10 і ІЛ-18 у плазмі крові хворих із мультирезистентністю довів, що їх рівень залежить від характеру резистентності мікобактерій туберкульозу.

Comparison of clustering in tuberculosis using fuzzy c-means and k-means methods

Tuberculosis (TB) is a health problem that has yet to be resolved in Indonesia. Based on WHO data, in 2021 Indonesia will still be in the third rank of the highest TB cases in the world. This study aims to determine how many groups of TB patients are based on age, gender, HIV status, history of diabetes mellitus, chest X-ray, and the results of the Molecular Rapid Test (TCM). The data used in this study were 985 from 2017 to 2020. The method used in this research is K-Nearest Neighbor (KNN) in carrying out the imputation process, as well as comparing the k-means and Fuzzy C-Means (FCM) methods in classifying TB data. Before doing the grouping, the data cleaning process is carried out by an imputation process which is useful for filling in the missing data in this case, using the KNN method. To produce maximum results of data grouping or clustering, it is necessary to determine the right number of clusters. For this reason, this study tries to compare the elbow, silhouette coefficient, and Davies Bouldin Index (DBI) methods. The application of the KNN method in the data imputation process in this study is to use k=5. The application of the K-Means algorithm is to form groups of TB patients based on six features. Determination of the optimal number of clusters using the K-means and FCM methods shows the optimal number of clusters, namely K = 2 but with different values. The results of the clustering test using the elbow method with the K-means and FCM methods are 93288.49. The DBI value for the K-means and FCM methods is 0.4937. Meanwhile, the clustering trial with the silhouette coefficient on K-means yields a value of 0.6318 which is better than the FCM which produces a value of 0.6321. This shows that the results of clustering k-means with silhouette coefficients produce better cluster quality because they have a lower silhouette coefficient value than FCM.

A decrease in PPD specific CD4 T cell CD38 and HLA-DR expression in pulmonary tuberculosis patients after 8 weeks of therapy correlates with successful anti-tuberculosis treatment

Tuberculosis (TB) is a major health problem in Indonesia with a million new cases each year. The CD4 T cell adaptive immune response against Mycobacterium tuberculosis (MTB) is central to the control of this disease. We investigated whether standard therapy of TB causes changes to these cells in the early stages of treatment. To do this we took blood samples from 2 groups of TB patients in Banda Aceh, Indonesia; one from a group of patients before treatment, and the other from a group who become smear negative after 8 weeks treatment. MTB specific CD4 T cells were identified by ex vivo stimulation with PPD and flow cytometric measurement of intracellular cytokines and surface markers. We found no difference in total PPD specific CD4 T cells between the groups, but that the proportion of these cells CD38 + HLA-DR+ was significantly lower in the treatment group. This decrease was not specific to Interferon gamma (IFNg), Interleukin-2 (IL-2) or Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) producing cells. Our findings show that anti-MTB treatment affects the adaptive immune response, and that measuring the decrease of the PPD specific CD4 T cell CD38+HLA-DR+ phenotype could be a useful parameter for determination of treatment success.

Association of gene polymorphisms and environmental factors in tuberculosis patients and their household contacts.

Tuberculosis (TB) is an important public health problem in China and environmental and genetic factors have an impact on its occurrence and development. We explored the relationship between environmental factors, genetic susceptibility genes and gene-environment interactions and the incidence of TB, as well as their high-risk combination, which can provide a scientific basis for prevention of the disease. The 242 individuals, which included 82 TB patients, 67 family genetically related patients and 93 healthy controls, all of whom were of the Han population in Guangdong Province. The basic information of subjects was collected, including general conditions, behaviour habits, family environmental factors and blood samples. Two single nucleotides with potential functions (interleukin-10 [IL-10] rs1800896, interferon-γ [IFN-γ] rs2430561) were screened by bioinformatics tools and identified by polymerase chain reaction-restriction fragment length polymorphism. We found that gender, education, TB exposure history, fitness activities, residential areas and indoor hygiene conditions were all associated with the occurrence of TB. In the dominant model, AG+GG of IL-10 and AA of IFN-γ are high-risk genotypes. Multifactor dimensionality reduction (MDR) analysis of TB-prone families shows that a combination of male sex, IL-10 AA and AG genotypes and smoking history are elements of high risk for TB infection (prediction accuracy 62.45%, cross-validation consistency 10/10). The MDR analysis of the TB patients group and the healthy control group showed that the combination of low education level, history of TB exposure, and IFN-γ AA genotype represented a higher risk of TB infection (prediction accuracy 80.34%, cross-validation consistency 10/10). The occurrence of TB in TB-prone families in the Han population of Guangdong Province is related to environmental factors as well as cytokines IL-10 and IFN-γ. We also found high-risk combinations of genes and environmental factors, providing clues for the timely detection of high-risk groups.

Diagnostic Value of Leukocyte Count Abnormalities in Newly Diagnosed Tuberculosis Patients

Background: The diagnosis of tuberculosis (TB) is frequently challenging given that the clinical and radiographic features of TB are often nonspecific. Altered leukocyte count ratios could serve as new tools of diagnostic orientation of tuberculosis. The aim of this study was to assess the diagnostic value of the leukocyte count ratios for the diagnosis of TB. Methods: This was a cross-sectional study including cases of newly diagnosed TB patients from registers of the TB treatment center of the Douala General Hospital. Control subjects were healthy volunteers, age and sex matched, recruited at the blood bank. Sociodemographic, clinical data and peripheral blood parameters were collected. The diagnostic value of leukocyte counts was determined using receiver operating characteristics curve analysis. Results: In total, 204 TB patients and 204 control subjects were included in the study. The gender of the participants was equitably distributed in the 2 study groups (male 61.8%; female 38.2%). The median age of TB patients was 33 years while that of control patients was 32 years. The monocyte-lymphocyte count ratio (MLR) and neutrophil-lymphocyte count ratio (NLR) were significantly higher in the TB patients group compared to control group. A NLR >1.19 and MLR >0.29 were identified as cut-off values for discriminating TB patients. The areas under the curves (AUC) were 0.77 and 0.84 for the MLR and NLR respectively. Conclusion: A raised NLR > 1.19 and MLR > 0.29 are predictive of tuberculosis. The NLR has greater diagnostic ability as evidenced by its higher AUC. Further research is needed to confirm or refute our findings.

Nutritional status evaluation and nutrient intake in adult patients with pulmonary tuberculosis and their contacts.

Malnutrition is a common status in patients with tuberculosis (TB). Because TB is disseminated through the sputum of infected persons, individuals who maintain relations with a TB patient are at high risk of infection; this risk is greater when contacts present an inadequate nutritional status. The aim of this work was to analyse and compare the nutritional status and macro and micronutrient intake of TB patients and their household contacts. A cross-sectional study was carried out in TB patients from Nuevo Leon, México, and their household contacts. Thirty-nine patients diagnosed with TB and 62 contacts were evaluated. Anthropometric evaluation was performed considering weight, height, body mass index (BMI) and waist-hip ratio (WHR); nutrient intake was evaluated by applying 24-hour dietary recalls. According to anthropometric assessment, the study population showed a greater trend towards being overweight and obese; 62% of TB patients and contacts had this type of malnutrition, while only 8% of individuals were undernourished. A greater tendency towards malnutrition was observed in the TB patient group. TB patients and their contacts presented as overweight and obese. Both groups showed similar patterns in macro and micronutrient intake. Implications of deficiencies in the intake of these nutrients are discussed on the basis of their effects on individual health.

GENETIC POLYMORPHISM OF TUBERCULOSIS MYCOBACTERIA IN THE CITY WITH LIMITED POPULATION MIGRATION AND HIGH INCIDENCE OF HIV INFECTION

87 isolates of M. tuberculosis isolated from tuberculosis patients in the Novouralsk municipality in 2013-2016 were studied. It was found out that a high percentage of isolates had multiple drug resistance: 66 and 85.3% among newly diagnosed and previously treated patients, respectively. Genotyping allowed revealing the dominance of isolates of the Beijing family, both among newly diagnosed (75.5%) and previously treated patients (85.3%), with 52.8 and 67.6% of isolates, respectively, belonging to the Beijing B0/W148 variant. MIRU-VNTR-typing detected nine isolates of the Beijing B0/W148 family with an atypical number of repeats in the QUB26 locus (two). A high rate of tuberculosis with concurrent HIV (39.1%) was noted, while in groups of tuberculosis patients with various HIV statuses, no difference was detected in the ratio of multiple drug resistant pathogens and belonging to the Beijing genotype (BeijingB0/W148). The article demonstrates the possibility of using genotyping technologies to confirm/deny the epidemiological relationship between patients and search for previously unknown mechanisms of tuberculosis infection transmission.

Stigma against tuberculosis may hinder non-household contact investigation: a qualitative study in Thailand.

A northern province in Thailand. To explore experiences and perspectives on tuberculosis (TB) contact investigations in non-household contacts. Focus group discussions and in-depth interviews with eight groups: three groups of former TB patients (teachers, students and hospital staff) and five groups of representatives from congregate settings such as schools and workplaces. Data were analysed using the modified grounded theory. Annual health check-ups at the workplace contributed to the early detection of active TB in teachers. Former TB patients were highly exposed to non-household contacts, but contact investigations were limited to household contacts only. Barriers and facilitators for non-household contact investigations are associated with five factors, including information, awareness and knowledge about TB; stigma; empathy; health system response and informing non-household contacts about TB exposure. Stigma may be the main barrier to investigations among non-household contacts because TB patients tend to withhold information about their diagnosis from colleagues. Lack of knowledge and misperceptions regarding TB transmission contributed to stigma. Empathy with other people encouraged TB patients to inform non-household contacts. Non-household contact investigations are not performed despite the risk of TB transmission. To promote contact investigations in congregate settings, interventions to overcome TB stigma and improve public knowledge about TB transmission are required.

Exploration of some new secretory proteins to be employed for companion diagnosis of Mycobacterium tuberculosis

Tuberculosis (TB) is a highly infectious disease and its early and precise diagnosis is essential to reduce morbidity and mortality of patients. Since the routine diagnostic tests (like Monteux, AFB smear microscopy, chest X-Ray) do not give infallible results, additional tests are always recommended. Therefore to address the concerns about non-specificity of the present battery of diagnostic tests, we have attempted to analyze some unique secretory antigens which could be able to identify the stage specific infection of MTB. In this study, we have used recombinant proteins CFP-10, ESAT-6, Ag85 A, Ag85B, Ag85C, PE3, PE4 and Mycp1 to eliminate heterogeneity and cross reactivity in clinical diagnosis. Amplified genes were cloned and over-expressed in Escherichia coli BL21 (DE3). The recombinantly purified proteins were used as antigens against 158 sera samples of TB patients. Secretory proteins showed better response than the PPD control. Among all the used antigens PE3 and PE4 proteins showed better reactivity levels among all the groups of TB patients. The secretions of CFP-10 and ESAT-6 were also higher as compared to other secretory proteins like Ag85 A, Ag85B, Ag85C and MycP1.The clinical use of these newly identified secretory antigens could be of significant value for the confirmatory, rapid, simple and low-cost diagnosis of TB patients.

Usefulness of Adenosine Deaminase Assay in Diagnosis of Patients with HIV Infection and Pleural Tuberculosis.

The utility of the adenosine deaminase (ADA) assay in the diagnosis of patients with pleural tuberculosis (TB) and human immunodeficiency virus (HIV) infection is controversial. Forty-eight HIV positive patients with pleural effusion were evaluated; ADA assay was obtained in forty-three of them. Twenty-five patients presented diagnosis of TB. Patients with diagnosis of TB showed a median value of ADA of 70 IU/L (interquartile range (IQR) 41–89) and the non-TB group a median of 27.5 IU/L (IQR 13.5–52). Patients with diagnosis of TB had a median cluster of differentiation 4 (CD4) count of 174 (IQR 86–274) and the non-TB group had a median of 134 (IQR 71–371). Receiver operating characteristic curve was performed with an area under the curve of 0.79. The best cut-off obtained was 35 IU/L with a sensibility of 80% and a specificity of 66%. There was no correlation between CD4 lymphocytes count and the value of ADA in the TB patient group.

ЭФФЕКТИВНОСТЬ КЛАПАННОЙ БРОНХОБЛОКАЦИИ В КОМПЛЕКСНОМ ЛЕЧЕНИИ БОЛЬНЫХ ДЕСТРУКТИВНЫМ ТУБЕРКУЛЕЗОМ ЛЕГКИХ, СОЧЕТАННЫМ С ВИЧ-ИНФЕКЦИЕЙ

Goal of the study : to enhance the efficiency of the comprehensive treatment of destructive pulmonary tuberculosis in HIV patients using bronchial valve block. Materials and methods . A study was conducted enrolling two groups of tuberculosis patients with destructive drug resistant pulmonary forms and concurrent HIV infection having comparable clinical and laboratory characteristics. Treatment of the patients in the main group (n = 68) included valve bronchial block. Patients from the comparison group (n = 57) received the same treatment but without valve bronchial block. Results of the study . Adding valve bronchial block to the treatment of tuberculosis is a positive factor confidently promoting sputum conversion (OR = 4.13; 95% CI 3.50-4.75) and healing of cavities (OR = 3.89; 95% CI 3.30-4.48). When using valve bronchial block the healing of cavities made 55.9%, while in the comparison group it made only 24.6%; (p = 0.0004, χ2 ). Sputum conversion was achieved in 75.0%, and in the comparison group, this rate was 42.1% (p = 0.0002, χ2 ). The above rates varied respectively the degree of immunosuppression in the patients.

Identification of Tuberculosis Patient Characteristics Using K-Means Clustering

In Indonesia, tuberculosis remains one of the major health problems unresolved. Indonesia is second ranked in the world as the country with the most tuberculosis cases. The purpose of this research is to study how K-means clustering applied to the treatment of tuberculosis patients data in order to identify the characteristics of tuberculosis patients. The results of K-means clustering validated by gene shaving and silhoutte coefficient. The experiment results indicate the optimum clusters value obtained from the K-mean clustering that has been validated by gene shaving and silhouette coefficient. K-means clustering divided four groups of tuberculosis patients based on their characteristics. There were divided at a category of disease (pulmonary TB, Extra Pulmonary TB and both), the age of the patient and the results of treatment of tuberculosis.

生活困難者を対象とした啓発冊子「結核のしおり」の効果の検証

Delay in seeking care is one of the critical issues in tuberculosis (TB) control among homeless persons in Japan. Yet knowledge of and attitude towards TB among homeless persons have remained unclear and limited efforts have been made to disseminate information related to TB among homeless persons. To evaluate the effect of TB leaflets, produced and distributed to homeless persons by a group of ex-homeless TB patients, and to understand what homeless persons know about TB. Self-administered questionnaire was conducted among homeless persons before and after distribution of the TB leaflets. Changes in the responses to each question were also subjected to principal component analysis to group questions into types according to response patterns and identify constructs of TB-related knowledge. Results of 88 participants were analyzed. TB knowledge score related to risks and symptoms significantly improved after the intervention (from 54.3% to 70.6%, p < 0.05), while knowledge on treatment cost did not. Two components were identified, namely, the "improvement in TB impression" and "improvement in TB knowledge". TB leaflets were effective in improving certain aspects of TB knowledge. However, its effect on knowledge regarding treatment cost, which may be crucial in improving delay, was limited and thus the messages need to be revised.

An adverse immune-endocrine profile in patients with tuberculosis and type 2 diabetes

Diabetes is a risk factor for the development of pulmonary tuberculosis (TB) and both diseases present endocrine alterations likely to play a role in certain immuno-endocrine-metabolic associated disorders. Patients with TB, or with TB and type 2 diabetes (TB+T2DM) and healthy controls (HCo) were assessed for plasma levels of cortisol, dehydroepiandrosterone (DHEA), estradiol, testosterone, growth hormone (GH), prolactin, insulin-like growth factor-1 (IGF-1), cytokines (IL-6, IL-10, IFN-γ) and the specific lymphoproliferative capacity of peripheral blood mononuclear cells. All patients had higher levels of cortisol with a reduction in DHEA, thus resulting in an increased cortisol/DHEA ratio (Cort/DHEA). Increased prolactin and particularly GH levels were found in both groups of TB patients. This was not paralleled by increased concentrations of IGF, which remained within the levels of HCo. Estradiol levels were significantly augmented in patients TB, and significantly more in TB+T2DM, whereas testosterone levels were decreased in both groups of patients. IFN- γ and IL-6 concentrations were significantly increased in all TB, even further in TB+T2DM; while IL-10 was equally increased in both groups of TB patients. The invitro specific proliferative capacity was decreased in both groups of patients as compared to that of HCo. The adverse immune-endocrine profile of TB seems to be slightly more pronounced in patients who also have T2DM.