Correlation between serum isoniazid concentration and therapeutic response in patients of pulmonary tuberculosis in Central India: A prospective observational study.

BACKGROUND: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis is one of the top ten causes of death worldwide. Isoniazid (INH) is an important component of anti-tuberculosis therapy (ATT). Low isoniazid levels can serve as a risk factor for the development of treatment failure, relapse of disease and acquired secondary resistance. Hence, serum level of isoniazid becomes a critical factor in determining the treatment outcome of patients on ATT. This study aimed to evaluate the correlation between serum isoniazid concentration and therapeutic response in patients of pulmonary tuberculosis in Central India. METHODS: This was a prospective single cohort observational study conducted at a tertiary care hospital. Therapeutic response in newly diagnosed patients of pulmonary TB was determined based the microbiological, clinical and radiological parameters. Serum INH levels were estimated based on a spectrophotometric method using nano-spectrophotometer. RESULTS: In this study, patients had a significant improvement in treatment outcome as evident by a significant decrease in the TB score I at end of IP (p = 0.001) and a significant decline in the Timika score at end of CP (p = 0.001). Although all patients converted to sputum negative at end of CP, 20% remained positive at end of IP. Lower INH levels were seen in 13.3% of the study population. Higher INH levels were observed in sputum converters, patients with low TB score I and low Timika score, although no statistically significant difference was noted (p > 0.05). CONCLUSION: In this study, we could not find any statistically significant association between serum INH levels and therapeutic outcome of the patients. Further studies on a larger population could provide better understanding about the prevalence of low serum isoniazid levels among the Indian population and establish its relationship with therapeutic outcome. Also, the usage of a comparatively less expensive spectrophotometric method of analysis makes this feasible in almost every district hospital without the need of high-performance liquid chromatography which is costlier and needs more expertise.

Automated Pulmonary Tuberculosis Severity Assessment on Chest X-rays.

According to the 2022 World Health Organization's Global Tuberculosis (TB) report, an estimated 10.6 million people fell ill with TB, and 1.6 million died from the disease in 2021. In addition, 2021 saw a reversal of a decades-long trend of declining TB infections and deaths, with an estimated increase of 4.5% in the number of people who fell ill with TB compared to 2020, and an estimated yearly increase of 450,000 cases of drug resistant TB. Estimating the severity of pulmonary TB using frontal chest X-rays (CXR) can enable better resource allocation in resource constrained settings and monitoring of treatment response, enabling prompt treatment modifications if disease severity does not decrease over time. The Timika score is a clinically used TB severity score based on a CXR reading. This work proposes and evaluates three deep learning-based approaches for predicting the Timika score with varying levels of explainability. The first approach uses two deep learning-based models, one to explicitly detect lesion regions using YOLOV5n and another to predict the presence of cavitation using DenseNet121, which are then utilized in score calculation. The second approach uses a DenseNet121-based regression model to directly predict the affected lung percentage and another to predict cavitation presence using a DenseNet121-based classification model. Finally, the third approach directly predicts the Timika score using a DenseNet121-based regression model. The best performance is achieved by the second approach with a mean absolute error of 13-14% and a Pearson correlation of 0.7-0.84 using three held-out datasets for evaluating generalization.

Patterns and profiles of drug resistance-conferring mutations in Mycobacterium tuberculosis genotypes isolated from tuberculosis-suspected attendees of spiritual holy water sites in Northwest Ethiopia.

Purpose: This study examined the patterns and frequency of genetic changes responsible for resistance to first-line (rifampicin and isoniazid), fluoroquinolones, and second-line injectable drugs in drug-resistant Mycobacterium tuberculosis (MTB) isolated from culture-positive pulmonary tuberculosis (PTB) symptomatic attendees of spiritual holy water sites (HWSs) in the Amhara region. Patients and methods: From June 2019 to March 2020, a cross-sectional study was carried out. A total of 122 culture-positive MTB isolates from PTB-suspected attendees of HWSs in the Amhara region were evaluated for their drug resistance profiles, and characterized gene mutations conferring resistance to rifampicin (RIF), isoniazid (INH), fluoroquinolones (FLQs), and second-line injectable drugs (SLIDs) using GenoType®MTBDRplus VER2.0 and GenoType®MTBDRsl VER2.0. Drug-resistant MTB isolates were Spoligotyped following the manufacturer's protocol. Results: Genetic changes (mutations) responsible for resistance to RIF, INH, and FLQs were identified in 15/122 (12.3%), 20/122 (16.4%), and 5/20 (25%) of MTB isolates, respectively. In RIF-resistant, rpoB/Ser531Lue (n = 12, 80%) was most frequent followed by His526Tyr (6.7%). Amongst INH-resistant isolates, katG/Ser315Thr1 (n = 19, 95%) was the most frequent. Of 15 MDR-TB, the majority (n = 12, 80%) isolates had mutations at both rpoB/Ser531Leu and katG/Ser315Thr1. All 20 INH and/or RIF-resistant isolates were tested with the MTBDRsl VER 2.0, yielding 5 FLQs-resistant isolates with gene mutations at rpoB/Ser531Lue, katG/Ser315Thr1, and gyrA/Asp94Ala genes. Of 20 Spoligotyped drug-resistant MTB isolates, the majority (n = 11, 55%) and 6 (30%) were SIT149/T3-ETH and SIT21/CAS1-Kili sublineages, respectively; and they were any INH-resistant (mono-hetero/multi-). Of 15 RIF-resistant (RR/MDR-TB) isolates, 7 were SIT149/T3-ETH, while 6 were SIT21/CAS1-Kili sublineages. FLQ resistance was detected in four SIT21/CAS1-Kili lineages. Conclusion: In the current study, the most common gene mutations responsible for resistance to INH, RIF, and FLQs were identified. SIT149/T3-ETH and SIT21/CAS1-Kili constitute the majority of drug-resistant TB (DR-TB) isolates. To further understand the complete spectrum of genetic changes/mutations and related genotypes, a sequencing technology is warranted.

Prevalence of Chronic Pulmonary Aspergillosis in Two (2) Tuberculosis Treatment Clinics in Lagos, Nigeria: A Prospective Longitudinal Study.

Background: Chronic pulmonary aspergillosis (CPA) is an underrecognized but common complication of pulmonary tuberculosis. In Nigeria, a tuberculosis-endemic country, there is currently no provision to monitor the development of CPA in patients treated for tuberculosis. This study determined the prevalence and incidence of CPA in Lagos, Nigeria. Methods: A prospective longitudinal study of patients with previously managed tuberculosis was conducted between June 2021 and May 2022. The study cohorts were assessed at 3-month intervals, and the following were collected: sociodemographic data, chest radiographic findings, sputum samples for fungal culture, and venous blood samples for Aspergillus immunoglobulin G estimation. CPA cases were determined using the case definition for resource-constrained countries. Descriptive and inferential statistics were used, and significance was set at a probability of 5% (P < .05). Results: Of the 141 patients recruited, 79 (56.0%) were in the retreatment and 62 (44.0%) in the posttreatment tuberculosis group. The median age (interquartile range) was 40 (30-52) years, with a male-to-female ratio of 1.1:1. Ninety-seven patients (69%) had a GeneXpert test done, of whom 63 (64.9%) were GeneXpert negative. Cough was the most common symptom, with 15 (11%) patients having hemoptysis. The rate of CPA increased steadily as the study progressed: 44 (31.2%) at commencement, 45 (34.9%) at 3 months, 49 (42.6%) at 6 months, and 51 (54.3%) at 9 months. Thus, the overall prevalence of CPA was 49.7%, and the incidence was 6.1%. Conclusions: CPA is common in Nigeria and its true burden may still be underestimated. Increased awareness of CPA as a posttuberculosis lung disease is advocated. Evaluation for CPA should be incorporated in patients' work-up for tuberculosis.

The characteristics of the gut microbiota in patients with pulmonary tuberculosis: A systematic review.

Increasing evidence has indicated dysbiosis of the gut microbiota in patients with pulmonary tuberculosis (PTB). However, the change in the intestinal microbiota varies between different studies. This systematic review was conducted to investigate the characteristics of the gut microbiota in PTB patients. The MBASE, MEDLINE, Web of Science, and Cochrane Library electronic databases were systematically searched, and the quality of the retrieved studies was evaluated using the Newcastle-Ottawa scale. A total of 12 studies were finally included in the systematic review. Compared with healthy controls, the index reflecting α-diversity including the richness and/or diversity index decreased in 6 studies, while ß-diversity presented significant differences in PTB patients in 10 studies. Although the specific gut microbiota alterations were inconsistent, short-chain fatty acid-producing bacteria (including Lachnospiraceae, Ruminococcus, Blautia, Dorea, and Faecalibacterium), bacteria associated with an inflammatory state (e.g., Prevotellaceae and Prevotella), and beneficial bacteria (e.g., Bifidobacteriaceae and Bifidobacterium) were commonly noted. Our systematic review identifies key evidence for gut microbiota alterations in PTB patients, in comparison with healthy controls; however, no consistent conclusion could be drawn, due to the inconsistent results and heterogeneous methodologies of the enrolled studies. Therefore, more well-designed research with standard methodologies and large sample sizes is required.

The burden and natural history of cardiac pathology at TB diagnosis in a high-HIV prevalence district in Zambia: protocol for the TB-Heart study.

BACKGROUND: Tuberculosis (TB) continues to be a major cause of death across sub-Saharan Africa (SSA). In parallel, non-communicable disease and especially cardiovascular disease (CVD) burden has increased substantially in the region. Cardiac manifestations of TB are well-recognised but the extent to which they co-exist with pulmonary TB (PTB) has not been systematically evaluated. The aim of this study is to improve understanding of the burden of cardiac pathology in PTB in those living with and without HIV in a high-burden setting. METHODS: This is a cross-sectional and natural history study to evaluate the burden and natural history of cardiac pathology in participants with PTB in Lusaka, Zambia, a high burden setting for TB and HIV. Participants with PTB, with and without HIV will be consecutively recruited alongside age- and sex-matched TB-uninfected comparators on a 2:1 basis. Participants will undergo baseline assessments to collect clinical, socio-demographic, functional, laboratory and TB disease impact data followed by point-of-care and standard echocardiography. Participants with PTB will undergo further repeat clinical and functional examination at two- and six months follow-up. Those with cardiac pathology at baseline will undergo repeat echocardiography at six months. DISCUSSION: The outcomes of the study are to a) determine the burden of cardiac pathology at TB diagnosis, b) describe its association with patient-defining risk factors and biochemical markers of cardiac injury and stretch and c) describe the natural history of cardiac pathology during the course of TB treatment.

Timely Pulmonary Tuberculosis Diagnosis Based on the Epidemiological Disease Spectrum: Population-Based Prospective Cohort Study in the Republic of Korea.

BACKGROUND: Timely pulmonary tuberculosis (PTB) diagnosis is a global health priority for interrupting transmission and optimizing treatment outcomes. The traditional dichotomous time-divided approach for addressing time delays in diagnosis has limited clinical application because the time delay significantly varies depending on each community in question. OBJECTIVE: We aimed to reevaluate the diagnosis time delay based on the PTB disease spectrum using a novel scoring system that was applied at the national level in the Republic of Korea. METHODS: The Pulmonary Tuberculosis Spectrum Score (PTBSS) was developed based on previously published proposals related to the disease spectrum, and its validity was assessed by examining both all-cause and PTB-related mortality. In our analysis, we integrated the PTBSS into the Korea Tuberculosis Cohort Registry. We evaluated various time delays, including patient, health care, and overall delays, and their system-associated variables in line with each PTBSS. Furthermore, we reclassified the scores into distinct categories of mild (PTBSS=0-1), moderate (PBTBSS=2-3), and severe (PBTBSS=4-6) using a multivariate regression approach. RESULTS: Among the 14,031 Korean patients with active PTB whose data were analyzed from 2018 to 2020, 37% (n=5191), 38% (n=5328), and 25% (n=3512) were classified as having a mild, moderate, and severe disease status, respectively, according to the PTBSS. This classification can therefore reflect the disease spectrum of PTB by considering the correlation of the score with mortality. The time delay patterns differed according to the PTBSS. In health care delays according to the PTBSS, greater PTB disease progression was associated with a shorter diagnosis period, since the condition is microbiologically easy to diagnose. However, with respect to patient delays, the change in elapsed time showed a U-shaped pattern as PTB progressed. This means that a remarkable patient delay in the real-world setting might occur at both apical ends of the spectrum (ie, in both mild and severe cases of PTB). Independent risk factors for a severe PTB pattern were age (adjusted odds ratio 1.014) and male sex (adjusted odds ratio 1.422), whereas no significant risk factor was found for mild PTB. CONCLUSIONS: Timely PTB diagnosis should be accomplished. This can be improved with use of the PTBSS, a simple and intuitive scoring system, which can be more helpful in clinical and public health applications compared to the traditional dichotomous time-only approach.

Case Report on Mycobacterium tuberculosis Presenting As Lemierre's Syndrome: A Reemerging Catastrophe.

Lemierre's syndrome is characterized by internal jugular vein thrombophlebitis and bacteremia, primarily from anaerobic organisms. The condition usually arises after a recent oropharyngeal infection. Young, healthy people with prolonged pharyngitis that progresses into septicemia, pneumonia, or lateral neck stiffness should be suspected of having Lemierre's syndrome. Identifying internal jugular vein thrombophlebitis and developing anaerobic bacterial growth on blood culture are frequently used to confirm the diagnosis. Treatment consists of long-term antibiotic treatment, sometimes in conjunction with anticoagulant medication. In this case report, we describe the unique case of a 29-year-old male with Mycobacterium tuberculosis with pulmonary tuberculosis, tubercular meningitis, tuberculosis-related acute ischemic stroke with septic thrombophlebitis. The patient presented with sudden onset altered sensorium for 4 hours. Magnetic resonance imaging of the brain was done, which suggested obstructive hydrocephalus with periventricular ooze. The patient was started on antibacillary treatment, antibiotics, anticoagulants, and systemic steroids. The patient was vitally stable when he was discharged. Therefore, it is crucial to consider the likelihood of such atypical tuberculosis presentations while providing a prompt and relevant diagnosis and recommending the right course of therapy.

Left-Sided Destroyed Lung With Severe Pulmonary Arterial Hypertension as a Consequence of Recurrent Pulmonary Tuberculosis.

Pulmonary tuberculosis is an infection caused by Mycobacterium tuberculosis, which is an obligate aerobic microbe. Tuberculosis is a multisystemic disease that can attack the respiratory system, genitourinary system, central nervous system, gastrointestinal system, and the skeletal framework of the body. However, the most commonly affected system is the respiratory system (pulmonary tuberculosis). Tuberculosis is an ancient infection that affects millions of people every year, and even after adequate treatment, it is associated with significant morbidity and mortality, which can be attributed to reinfections, complications, extrapulmonary spread, and the long-term effects of tuberculosis on the lungs, leading to various restrictive and obstructive diseases. One of the most hazardous sequelae of pulmonary tuberculosis is the destroyed lung, which is predominately seen in the culminating stage of progressive disease or after reactivation of the disease. Here we present the case of a 46-year-old female patient who presented with complaints of breathlessness, cough with expectoration, and chest pain. With a history of recurrent tuberculosis infections and appropriate antituberculosis treatment for 30 years, the primary infection was recognized at 16 years of age. On examination, the patient was suspected to have developed fibrosis of the left lung, which, on radiological investigation, was confirmed to be a case of a destroyed left lung because of a recurrent tuberculosis infection. The patient was given symptomatic treatment along with broad-spectrum antibiotic therapy.

Pre-extensively Drug-Resistant Pulmonary Tuberculosis With a Giant Primary Splenic Hydatid Cyst With Multiple Adverse Drug Reactions.

Drug-resistant tuberculosis is a noteworthy threat to public health, especially in high-burden countries. Management of these types of tuberculosis is lengthy and associated with a number of adverse drug reactions. Pre-extensively drug-resistant tuberculosis is a serious type of disease that is caused by the strains of Mycobacterium tuberculosis that are resistant to either rifampicin or both, i.e., rifampicin and isoniazid, and resistant to any fluoroquinolones. A splenic hydatid cyst is relatively rare and has never been reported in a case of pre-extensively drug-resistant pulmonary tuberculosis. The present case is a rare case of a young Indian male who was diagnosed with pre-extensively drug-resistant pulmonary tuberculosis through a cartridge-based nucleic acid amplification test and second-line drug susceptibility testing. Further, a diagnostic radiometric investigation showed a giant hydatid cyst in the spleen. He was started on an all-oral longer treatment regimen per the existing protocols. However, his treatment was associated with multiple adverse drug reactions.

Association between STAT4 gene polymorphism and susceptibility to pulmonary tuberculosis in the Moldavian population.

Signal transducer and activator of transcription 4 (STAT4) plays a crucial role in the host immune response against Mycobacterium tuberculosis. This study investigates the association between STAT4 gene polymorphisms and pulmonary tuberculosis (TB) risk in the Moldavian population. A total of 272 TB patients and 251 community-matched controls underwent screening for functional single-nucleotide polymorphisms (SNPs) rs897200 and rs7574865 in the STAT4 gene. The minor T allele and the TT/CT genotype of rs897200 demonstrated a significant association with reduced pulmonary TB risk (allelic model: adjusted OR = .74, p = .025; log-additive model: adjusted OR = .72, p = .02; and dominant model: adjusted OR = .65, p = .023), indicating a protective effect. Similar associations, characterized by an even more pronounced reduction in risk, were observed among females and late-onset TB patients (>44 years). No significant associations were found for rs7574865. In addition, a combined genotype analysis incorporating 43 SNPs from our previous studies revealed potential associations, such as STAT4 rs897200 CT with IFNG rs2430561 AA (adjusted OR = .36, p = .0025) and STAT4 rs897200 CT with TNFA rs1800629 GA (adjusted OR = .33, p = .0012). This study emphasizes the significant association of STAT4 rs897200 with pulmonary TB risk in the Moldavian population, underscoring its role in the disease development.

Prediction of Tuberculosis From Lung Tissue Images of Diversity Outbred Mice Using Jump Knowledge Based Cell Graph Neural Network.

Tuberculosis (TB), primarily affecting the lungs, is caused by the bacterium Mycobacterium tuberculosis and poses a significant health risk. Detecting acid-fast bacilli (AFB) in stained samples is critical for TB diagnosis. Whole Slide (WS) Imaging allows for digitally examining these stained samples. However, current deep-learning approaches to analyzing large-sized whole slide images (WSIs) often employ patch-wise analysis, potentially missing the complex spatial patterns observed in the granuloma essential for accurate TB classification. To address this limitation, we propose an approach that models cell characteristics and interactions as a graph, capturing both cell-level information and the overall tissue micro-architecture. This method differs from the strategies in related cell graph-based works that rely on edge thresholds based on sparsity/density in cell graph construction, emphasizing a biologically informed threshold determination instead. We introduce a cell graph-based jumping knowledge neural network (CG-JKNN) that operates on the cell graphs where the edge thresholds are selected based on the length of the mycobacteria's cords and the activated macrophage nucleus's size to reflect the actual biological interactions observed in the tissue. The primary process involves training a Convolutional Neural Network (CNN) to segment AFBs and macrophage nuclei, followed by converting large (42831*41159 pixels) lung histology images into cell graphs where an activated macrophage nucleus/AFB represents each node within the graph and their interactions are denoted as edges. To enhance the interpretability of our model, we employ Integrated Gradients and Shapely Additive Explanations (SHAP). Our analysis incorporated a combination of 33 graph metrics and 20 cell morphology features. In terms of traditional machine learning models, Extreme Gradient Boosting (XGBoost) was the best performer, achieving an F1 score of 0.9813 and an Area under the Precision-Recall Curve (AUPRC) of 0.9848 on the test set. Among graph-based models, our CG-JKNN was the top performer, attaining an F1 score of 0.9549 and an AUPRC of 0.9846 on the held-out test set. The integration of graph-based and morphological features proved highly effective, with CG-JKNN and XGBoost showing promising results in classifying instances into AFB and activated macrophage nucleus. The features identified as significant by our models closely align with the criteria used by pathologists in practice, highlighting the clinical applicability of our approach. Future work will explore knowledge distillation techniques and graph-level classification into distinct TB progression categories.

Coexistence of ovarian cancer and peritoneal tuberculosis: a case report.

Peritoneal tuberculosis (TB) is known to mimic advanced ovarian cancer. In this case report, we describe a unique case of ovarian cancer (endometrioid carcinoma grade 3) at the International Federation of Gynecology and Obstetrics (FIGO) stage IC1 with pulmonary and peritoneal TB, which was suspected preoperatively to be a coexistence of advanced ovarian cancer and pulmonary TB. A 68-year-old woman presented with a prominent abdominal mass and fever. Laboratory investigations, imaging, and sputum analysis indicated a probable diagnosis of ovarian cancer at FIGO stage IIIC, characterized by peritoneal dissemination and para-aortic lymph node metastasis, which was further complicated by coexisting pulmonary TB. Surgical management included total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy. Intraoperatively, the tumor was localized to the right ovary with significant peritoneal thickening and adhesions indicative of peritoneal TB. The surgery was completed without apparent complications. Postoperative histopathological evaluation confirmed grade 3 endometrioid carcinoma in the right ovary along with evidence of peritoneal TB. Given the extent of adhesions attributed to TB, lymph node dissection for staging was deemed challenging and was thus not pursued. Initiation of anti-TB treatment on postoperative day 2 resulted in marked regression of the preoperatively identified pulmonary nodules and para-aortic lymph node enlargement, suggesting their inflammatory origin from TB. Although postoperative chemotherapy is typically advocated for patients with stage IC1 endometrioid carcinoma grade 3, the patient opted against it. Consequently, no adjuvant therapy was administered and the patient remained under close observation.

Epidemiology of tuberculosis among children in Beijing, China, 2012-2021.

Data on epidemiology trends of paediatric tuberculosis (TB) are limited in China. So, we investigated the clinical and epidemiological profiles in diagnosed TB disease and TB infection patients at Beijing Children's Hospital. Of 3 193 patients, 51.05% had pulmonary TB (PTB) and 15.16% had extrapulmonary TB (EPTB). The most frequent forms of EPTB were TB meningitis (39.05%), pleural TB (29.75%), and disseminated TB (10.33%). PTB patients were significantly younger and associated with higher hospitalization frequency. Children aged 1-4 years exhibited higher risk of PTB and TB meningitis, and children aged 5-12 years had higher risk of EPTB. The proportion of PTB patients increased slightly from 40.9% in 2012 to 65% in 2019, and then decreased to 17.8% in 2021. The percentage of EPTB cases decreased from 18.3% in 2012 to 15.2% in 2019, but increased to 16.4% in 2021. Among EPTB cases, the largest increase was seen in TB meningitis. In conclusion, female and young children had higher risk of PTB in children. TB meningitis was the most frequent forms of EPTB among children, and young children were at high risk of TB meningitis. The distribution of different types of EPTB differed by age.

Increased Risk of Incident Chronic Obstructive Pulmonary Disease and Related Hospitalizations in Tuberculosis Survivors: A Population-Based Matched Cohort Study.

BACKGROUND: Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls. METHODS: We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls. RESULTS: Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs. 4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54-1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81-2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17-2.92). CONCLUSION: TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization.

Immuno-Hematological and Biochemical Changes in Patients with Tuberculosis in Dessie Comprehensive Specialized Hospital, Dessie, Ethiopia.

Background: Tuberculosis (TB) is a serious worldwide health issue, particularly in developing nations like Ethiopia. Patients with tuberculosis experience a range of hematological, immunological, and biochemical alterations. The purpose of this study was to evaluate immunological, hematological, and biochemical alterations of newly diagnosed TB patients at Dessie comprehensive specialized hospital, Dessie, Ethiopia. Methods: A comparative, cross-sectional study was carried out to evaluate the immuno-hematological and biochemical changes in patients with tuberculosis at Dessie comprehensive specialized hospital from January to July 2018. One hundred sixty-four (164) newly diagnosed TB patients, and 80 apparently healthy controls were included consecutively. The variables were expressed in frequency, percentage, and mean ± SD. To compare mean ± SD of the groups or within the groups, we used an independent sample t-test. Statistical significance was defined as a P value less than 0.05. Results: Male TB patients had significantly high mean absolute WBC count, neutrophil count, lymphocyte, platelet count, and systemic immune-inflammation compared with male healthy controls (P=0.001, P=0.011 P=0.021, P=0.001, and P=0.018, respectively). The mean platelet count of female TB patients was significantly higher than that of the female control group (P=0.015). However, mean RBC counts, Hgb, HCT, and MPV of TB patients were significantly lower than those of male (p<0.001) and female healthy controls (P=0.022, 0.015, and 0.001, respectively). The TB patients had developed anemia (23.8%), WBC abnormalities (29.3%), thrombocytosis (11.6%), and thrombocytopenia (9.8%). The cases had significantly higher mean alanine amino transferase, total bilirubin, and glucose level, but the mean total protein, alkaline phosphatase, and total cholesterol of cases were significantly lower than healthy control groups. Conclusion: TB patients in this study showed significant alterations in a number of hematological and biochemical profiles. This indicates that hematological and biochemical profiles should be monitored and properly interpreted for the differential diagnosis of tuberculosis and evaluation of response to treatment.

A Cross-Sectional Study on Awareness of Tuberculosis Control Among Post-Treatment Tuberculosis Patients in a City in China.

Purpose: This study aimed to investigate awareness of tuberculosis control among post-treatment tuberculosis patients, in order to provide a basis for future preventive and control work in this population. Patients and Methods: A cross-sectional descriptive study was conducted on post-treatment patients with tuberculosis in seven districts of Jinan City between July 2021 and December 2022. A face-to-face or telephone interviews using structured questionnaires for the research subjects were conducted by data collectors. Analyses were carried out first for all subjects, and then separately for male and female subjects. Results: A total of 837 valid questionnaires were collected, of which 495 were males and 342 were females. The awareness rate of the core TB knowledge was 82.46%. The ≥65 year group in the total group (OR=0.43, 95% CI: (0.28, 0.68)), male (OR=0.47, 95% CI: (0.27, 0.83)) and female group (OR=0.40, 95% CI: (0.19, 0.86)) was lower than that of the control group. Educational level and monthly income are the main factors of TB cognition in total group. People with university or higher education (OR=2.05, 95% CI: (1.38, 3.05)) and with a monthly income of ≥6,000 (OR=1.89, 95% CI: (1.10, 3.25)) had a higher awareness rate. The group with current residence in the city was more aware than the reference group. Conclusion: In the future, the communication of the main transmission route, suspicious symptoms, and cure of TB needs to be strengthened for the post-treatment TB patients. The elderly, those with secondary school education or below, agricultural workers and low-income people are the groups with weak knowledge of TB, and they are also the groups that need to be focused on health education. The above information should be focused on the above groups of people in order to educate them in a way that is easily acceptable to them.

Associations of prior pulmonary tuberculosis with the incident COPD: a prospective cohort study.

BACKGROUND: Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk of incident COPD has not been studied in a large prospective cohort study of the European population. OBJECTIVES: This study aimed to investigate the association of prior PTB with the risk of COPD. DESIGN: Prospective cohort study. METHODS: A multivariable Cox proportional model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association of prior PTB with COPD. Subgroup analyses were further conducted among individuals stratified by age, sex, body mass index, smoking status, drinking status, physical activity, and polygenic risk score (PRS). RESULTS: The study involved a total of 216,130 participants, with a median follow-up period of 12.6 years and 2788 incident cases of COPD. Individuals with a prior history of PTB at baseline had an 87% higher risk of developing incident COPD compared to those without such history [adjusted hazard ratio (aHR) = 1.87; 95% confidence interval (CI): 1.26-2.77; p = 0.002]. Subgroup analysis revealed that individuals having prior PTB history presented a higher risk of incident COPD among individuals who were aged from 50 to 59 years with aHR of 2.47 (1.02-5.95, p = 0.044), older than 59 years with aHR of 1.81 (1.16-2.81, p = 0.008), male with aHR of 2.37 (1.47-3.83, p < 0.001), obesity with aHR of 3.35 (2.16-5.82, p < 0.001), previous smoking with aHR of 2.27 (1.39-3.72, p < 0.001), current drinking with aHR of 1.98 (1.47-3.83, p < 0.001), low physical activity with aHR of 2.62 (1.30-5.26, p = 0.007), and low PRS with aHR of 3.24 (1.61-6.53, p < 0.001), as well as high PRS with aHR of 2.43 (1.15-5.14, p = 0.019). CONCLUSION: A history of PTB is an important independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

Associations of prior pulmonary tuberculosis with the incident COPDPrior pulmonary tuberculosis (PTB) indicates that an individual has a history of PTB. The impact of prior PTB on the risk of incident chronic obstructive pulmonary disease (COPD) has not been studied in a large prospective cohort study of European population. Here, we investigated the association between prior PTB and risk of COPD in 216,130 participants from the UK biobank (a large biomedical database). After a median follow up of more than 12 years, 2,788 incident COPD cases were recorded. Individuals with prior PTB at baseline had an 87% higher risk of developing incident COPD compared to those without history of PTB. Specifically, individuals with prior PTB presented with a higher risk of incident COPD among those who were older than 50 years, male, obese, had a previous history of smoking, are currently drinking, have low physical activity, and have a low and high genetic predicted lung function. This study suggested prior PTB as an important and independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay.

Introduction: New diagnostic tools are needed to rapidly assess the efficacy of pulmonary tuberculosis (PTB) treatment. The aim of this study was to evaluate several immune biomarkers in an observational and cross-sectional cohort study conducted in Paraguay. Methods: Thirty-two patients with clinically and microbiologically confirmed PTB were evaluated before starting treatment (T0), after 2 months of treatment (T1) and at the end of treatment (T2). At each timepoint plasma levels of IFN-y, 17 pro- and anti-inflammatory cytokines/chemokines and complement factors C1q, C3 and C4 were assessed in unstimulated and Mtb-specific stimulated whole blood samples using QuantiFERON-TB gold plus and recombinant Mycobacterium smegmatis heparin binding hemagglutinin (rmsHBHA) as stimulation antigen. Complete blood counts and liver enzyme assays were also evaluated and correlated with biomarker levels in plasma. Results: In unstimulated plasma, C1q (P<0.001), C4 (P<0.001), hemoglobin (P<0.001), lymphocyte proportion (P<0.001) and absolute white blood cell count (P=0.01) were significantly higher in PTB patients at baseline than in cured patients. C1q and C4 levels were found to be related to Mycobacterium tuberculosis load in sputum. Finally, a combinatorial analysis identified a plasma host signature comprising the detection of C1q and IL-13 levels in response to rmsHBHA as a tool differentiating PTB patients from cured TB profiles, with an AUC of 0.92 (sensitivity 94% and specificity 79%). Conclusion: This observational study provides new insights on host immune responses throughout anti-TB treatment and emphasizes the role of host C1q and HBHA-specific IL-13 response as surrogate plasma biomarkers for monitoring TB treatment efficacy.

Development of a self-microemulsifying drug delivery system to deliver delamanid via a pressurized metered dose inhaler for treatment of multi-drug resistant pulmonary tuberculosis.

Tuberculosis (TB) is a serious health issue that contributes to millions of deaths throughout the world and increases the threat of serious pulmonary infections in patients with respiratory illness. Delamanid is a novel drug approved in 2014 to deal with multi-drug resistant TB (MDR-TB). Despite its high efficiency in TB treatment, delamanid poses delivery challenges due to poor water solubility leading to inadequate absorption upon oral administration. This study involves the development of novel formulation-based pressurized metered dose inhalers (pMDIs) containing self-microemulsifying mixtures of delamanid for efficient delivery to the lungs. To identify the appropriate self-microemulsifying formulations, ternary diagrams were plotted using different combinations of surfactant to co-surfactant ratios (1:1, 2:1, and 3:1). The combinations used Cremophor RH40, Poly Ethylene Glycol 400 (PEG 400), and peppermint oil, and those that showed the maximum microemulsion region and rapid and stable emulsification were selected for further characterization. The diluted self-microemulsifying mixtures underwent evaluation of dose uniformity, droplet size, zeta potential, and transmission electron microscopy. The selected formulations exhibited uniform delivery of the dose throughout the canister life, along with droplet sizes and zeta potentials that ranged from 24.74 to 88.99 nm and - 19.27 to - 10.00 mV, respectively. The aerosol performance of each self-microemulsifying drug delivery system (SMEDDS)-pMDI was assessed using the Next Generation Impactor, which indicated their capability to deliver the drug to the deeper areas of the lungs. In vitro cytotoxicity testing on A549 and NCI-H358 cells revealed no significant signs of toxicity up to a concentration of 1.56 µg/mL. The antimycobacterial activity of the formulations was evaluated against Mycobacterium bovis using flow cytometry analysis, which showed complete inhibition by day 5 with a minimum bactericidal concentration of 0.313 µg/mL. Moreover, the cellular uptake studies showed efficient delivery of the formulations inside macrophage cells, which indicated the potential for intracellular antimycobacterial activity. These findings demonstrated the potential of the Delamanid-SMEDDS-pMDI for efficient pulmonary delivery of delamanid to improve its effectiveness in the treatment of multi-drug resistant pulmonary TB.