Extrapulmonary Tuberculosis Patients Research Articles

Diagnostic accuracy of truenat MTB plus for the detection of pulmonary and extrapulmonary tuberculosis

BackgroundThe diagnosis of Tuberculosis (TB) has been a challenge till the advent of rapid molecular diagnostic tests. The traditional diagnostic tests have its own limitations with regard to its performance or the turnaround time. Truenat MTB Plus assay, a battery-operated molecular assay developed in India has been introduced for its use in pulmonary TB (PTB). However, the diagnostic accuracy of the assay is not well studied in comparison with Mycobacterial culture, especially for extrapulmonary TB (EPTB). AimWe aimed at evaluating the diagnostic accuracy of Truenat MTB Plus assay for both PTB and EPTB comparing with culture for adult population. MethodsThe specimens from presumptive PTB and EPTB patients were processed for Truenat MTB Plus assay, solid or liquid culture and AFB staining. The electronic data of all the specimen reports collected retrospectively were analysed for the sensitivity and specificity. ResultsOut of the 736 samples which had valid culture reports, 364 (49.4 %) were respiratory and 372 (50.6 %) were extrapulmonary specimens. The test positivity rate for smear microscopy, Truenat MTB Plus assay and culture was 3.7 % (27), 8.2 % (60), 7.1 % (52) respectively. Of the 60 Truenat MTB Plus positive patients with TB, 33 (55 %) were PTB and 27 (45 %) were EPTB. We estimated overall sensitivity and specificity of Truenat MTB Plus as 90 % (95 % CI: 73.4–97.8) and 98. 2 (95 % CI:96–99.3) respectively for the detection of PTB. The overall sensitivity and specificity for EPTB was 81.8 % (95 % CI: 59.7–94.8) and 97.4 % (95 % CI: 95.1–98.8) respectively. ConclusionsTruenat MTB Plus assay has comparable diagnostic accuracy with other molecular assays. The Truenat MTB Plus assay can be used for the diagnosis of PTB and EPTB, especially in resource limited settings.

Factors associated with hospitalization and mortality in adult and pediatric extrapulmonary tuberculosis at a tertiary care hospital in Central India

Background Comorbidities complicate the management of tuberculosis (TB) and have become an essential part of the end TB strategy to eradicate TB. However, pulmonary TB has received the most attention, and little is known about the impact of comorbidities and other factors on outcomes in patients with extrapulmonary tuberculosis (EPTB). Objectives Our aim was to analyze the factors associated with hospitalization and mortality in EPTB at a hospital in Central India, using non-TB patients with similar clinical presentations as a comparison. Methods Patients with presumptive EPTB were prospectively enrolled and followed up until the end of treatment or for at least 6 months. Detailed demographic and clinical information was collected for all participants, and patients were categorized as TB or non-TB using a composite reference standard. Multivariate logistic regression was used to analyze the impact of various clinical findings and risk factors on hospitalization and mortality. Results A total of 276 patients were categorized as TB cases and 175 as non-TB cases. Factors associated with hospitalization in children were younger age and non-adenitis site of disease. In adults, factors associated with mortality were older age, non-adenitis site of disease and HIV infection regardless of TB diagnosis, while diabetes mellitus increased the odds of mortality in EPTB patients. Conclusion Our results show that comorbidities increase the odds of death in both TB and non-TB patients in low-resource settings. This argues for a shift away from the traditional vertical management of diseases in these areas and supports a continued focus on building robust healthcare systems.

Role of GeneXpert in the diagnosis of extrapulmonary tuberculosis.

The World Health Organization endorsed the cartridge-based nucleic acid amplification test Xpert MTB/RIF (GXP) for the diagnosis of tuberculosis (TB). Studies about GXP efficiency in extrapulmonary TB (EPTB) are scarce. Hence, we decided to study the role of GXP in EPTB. This prospective observational study, conducted in the pulmonary medicine department of a tertiary care hospital after ethics committee permission, recruited 200 EPTB patients. The diagnosis of TB was achieved with the help of clinico-radiological correlation with microbiological test positivity. Acid-fast bacilli (AFB) culture was treated as the comparative gold standard. Patients who had no or incomplete data were excluded from the study. Data was analyzed to calculate the sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of TB and the detection of rifampicin resistance. The majority of cases were women (126 patients: 63%). The mean age was 23.71 years. On GXP, 130 (65%) had detected mycobacterium tuberculosis (MTB), and 70 (35%) did not. Adding AFB culture data, 168 (81.5%) showed microbiological evidence of TB, and 32 (18.5%) were negative. On the drug susceptibility test, 131 cases were rifampicin-sensitive, 32 were rifampicin-resistant TB, and in 5 cases, data was unavailable. The most common extrapulmonary site of involvement was the lymph node, with 94 patients (47%). The most common lymph node involved was the cervical lymph node, with 70 patients (74.5%). The sensitivity, specificity, positive predictive value, and negative predictive value of GXP in EPTB collectively were 76.68%, 86.48%, 96%, and 45.7%, respectively. GXP is useful for the rapid detection of EPTB and the identification of rifampicin resistance, especially in a high-prevalence country like India.

Analysis of epidemiological characteristics of extrapulmonary tuberculosis from South-Central China.

This study aimed to investigate the epidemiological and drug resistance (DR) characteristics of extrapulmonary tuberculosis (EPTB) in South-Central China. EPTB inpatients who were culture-positive for Mycobacterium tuberculosis were retrospectively included in a study at a provincial TB hospital in Hunan, a province in South-Central China, from January 2013 to December 2021. Demographic, clinical, and drug susceptibility data were retrieved from TB treatment records. Descriptive statistical methods and a Chi-squared test were used to analyze the epidemiological and DR characteristics of EPTB patients. A logistic regression model was used to explore the risk factors of rifampicin-resistant/multidrug-resistant (RR/MDR)-EPTB. A total of 1,324 cases were included. The majority of EPTB patients were in the age range of 20-29 years, were predominantly men (male-to-female ratio: 2.03), and were farmers (65.63%). Most EPTB cases were found in 2013 and 2017 from 2013 to 2021. The most prevalent subtypes of EPTB were lymphatic TB (29.83%, 395/1,324), multiple EPTB (20.85%, 276/1,324), and musculoskeletal TB (14.65%, 194/1,324). Musculoskeletal TB and genitourinary TB predominantly presented as exclusive EPTB forms, while lymphatic TB and pharyngeal/laryngeal TB often co-occurred with pulmonary TB (PTB). Drug susceptibility testing results showed that total DR rates (resistance to any of RFP, isoniazid [INH], streptomycin [STR], and/or ethambutol [EMB]) and RR/MDR rates in EPTB were 25.23% and 12.39%, respectively. Musculoskeletal TB exhibited the highest rates of total DR (31.40%), INH resistance (28.90%), STR resistance (20.10%), EMB resistance (6.20%), MDR (13.90%), and poly-DR (6.70%). The multivariable logistic regression model showed that patients aged from 20 to 59 years (compared to those aged 10 years), workers (compared to retirees), and EPTB patients from the south and west of Hunan (compared to those from the east of Hunan) were at an increased risk of developing RR/MDR EPTB (all OR values > 1). Our study provided a detailed account of the epidemiological and DR characteristics of EPTB in Hunan province, China. The significant DR rates, particularly in musculoskeletal TB cases, highlight the need for timely diagnosis, effective drug susceptibility testing, and the development of more effective treatment regimens for EPTB, especially targeting musculoskeletal TB treatments.

Prevalence of vitamin D deficiency and the effect of vitamin D3 supplementation on response to anti-tuberculosis therapy in patients with extrapulmonary tuberculosis

BackgroundWe aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course.MethodsSerum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment.ResultsSerum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group.ConclusionsVitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course.

Isoniazid-Induced Cerebellitis in a Chronic Kidney Disease Patient

Abstract The bacterial disease tuberculosis (TB), when it affects organs of the body other than the lungs, is called extrapulmonary TB. The treatment regimen includes the drugs isoniazid, rifampicin, pyrazinamide, and ethambutol, of which isoniazid is known to be the most active drug. Adverse drug reactions commonly include immunological as well as drug toxicity effects, with the latter being particularly important in renally impaired patients because of high risk of drug accumulation. Cerebellitis, which is an inflammatory condition that results in cerebellar dysfunction, is a rare complication of isoniazid use. Diagnosis is made after excluding all other possibilities. In the case described here, the extrapulmonary TB patient was a known case of chronic kidney disease (G4). He presented with slurred speech and sedation; magnetic resonance imaging scan showed bilateral fluid-attenuated inversion recovery hyperintensities in the dentate nuclei, indicative of cerebellitis. Dramatic improvement was seen upon replacing Isoniazid with levofloxacin and administration of antioxidants and pyridoxine supplements, which confirmed the diagnosis of isoniazid-induced cerebellitis.

Mortality among extrapulmonary tuberculosis patients in the HIV endemic setting: lessons from a tertiary level hospital in Mbeya, Tanzania

Extrapulmonary tuberculosis (EPTB) has received less attention than pulmonary tuberculosis due to its non-contagious nature. EPTB can affect any organ and is more prevalent in people living with HIV. Low- and middle-income countries are now facing the double burden of non-communicable diseases (NCDs) and HIV, complicating the management of patients with symptoms that could be compatible with both EPTB and NCDs. Little is known about the risk of death of patients presenting with symptoms compatible with EPTB. We included patients with a clinical suspicion of EPTB from a tertiary level hospital in Mbeya, Tanzania, to assess their risk of dying. A total of 113 (61%) patients were classified as having EPTB, and 72 (39%) as having non-TB, with corresponding mortality rates of 40% and 41%. Associated factors for mortality in the TB groups was hospitalization and male sex. Risk factors for hospitalization was having disease manifestation at any site other than lymph nodes, and comorbidities. Our results imply that NCDs serve as significant comorbidities amplifying the mortality risk in EPTB. To strive towards universal health coverage, focus should be on building robust health systems that can tackle both infectious diseases, such as EPTB, and NCDs.

Extra-pulmonary tuberculosis frequency and the risk factors influence (case of the PHE-Batna regional unit) (2017-2022)

Context: Tuberculosis is an infectious disease that is endemic in developing countries. The causal agent is Mycobacterium tuberculosis. Extra-pulmonary tuberculosis (EPTB) is receiving renewed attention due to an unexplained increase in its relative frequency. The aim of this study was to carry out a retrospective descriptive survey to assess the frequency of extra-pulmonary tuberculosis in an eastern Algeria population range. Methods: this study took place at the regional tuberculosis Batna’s Public hospitalian establishment unit; over a period of 64 months (2017-2022). 2405 files were studied through the collection of information recorded at laboratory level. Results: Out of 2405 samples, 102 were positive (4.24%). There was a clear predominance of females (64.70%) and males (35.29%), giving a sex ratio of 1.8. The age group most affected was 11 to 49. Pus was the most common specimen with a percentage of 44.12%, followed by urine (28.43%), CSF (14.70%). The incidence of extra pulmonary tuberculosis in patients in Batna’s Department and neighbouring Departments is 4.24%, with adult women being the most affected. Conclusion: Extrapulmonary tuberculosis is common and should not be neglected; it is no longer a pathology of the past but still remains relevant today.

Dynamics of Matricellular Protein Levels in Blood Predict Recovery in Patients with Human Immunodeficiency Virus-Tuberculosis Coinfection.

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6-18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection.

Change in psychological parameters and quality of life among individuals with pulmonary and extrapulmonary tuberculosis following the intensive phase of therapy: A longitudinal observational study from central India

BackgroundTuberculosis (TB) is a global health concern, impacting millions annually, with limited attention to the psychological distress it inflicts. Psychological comorbidities, such as depression, anxiety, and stress, significantly affect the quality of life (QoL) of TB patients. Available literature on this topic is restricted to the pulmonary TB (PTB) patients; while psychological issues of the extrapulmonary TB (EPTB) patients who comprise a significant proportion of this disease entity remains unexplored. Additionally, the impact of anti-TB treatment on psychological parameters has received limited attention and vice-versa. This study aimed to assess depression, anxiety, stress, and QoL of TB patients at diagnosis and to understand how these parameters change after the intensive phase of treatment. MethodsA longitudinal observational study involving 40 TB patients (31 EPTB and 9 TB) was conducted to assess depression, anxiety, stress and QoL among them. Participants were followed up after the intensive treatment phase. ResultsAt baseline, 32.5% (n = 13) and 65% (n = 26) participants experienced moderate-severe depression, and moderate-severe anxiety, and stress, respectively. QoL was notably compromised, especially in the psychological domain. Post-intensive treatment, anxiety and depression showed significant improvement (Z = −2.271, p = 0.023 and Z = −2.093, p = 0.036), but QoL and stress levels remained largely unchanged (p > 0.05). ConclusionThis study highlights the high prevalence of psychological distress and poor QoL among TB patients. Following intensive phase of therapy, severity of depression and anxiety reduced significantly; however, change in stress-level and QoL was non-significant. Although study is limited by in terms for small sample size, the need of holistic, multidisciplinary treatment approach (including mental health professionals) for such patients can't be overemphasized. Implementing baseline psychological screenings and providing mental health support if required, are critical to improve the overall health and QoL of these individuals.

Concomitant bedaquiline and delamanid therapy in patients with drug-resistant extra-pulmonary tuberculosis in Mumbai, India

BackgroundWorld Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India. MethodsRetrospective cohort study based on routinely collected programmatic data. Individualised regimens were based on drug-susceptibility testing and previous drug exposure. Drug-resistant EPTB patients initiated on regimens containing concurrent BDQ and DLM from April 2016 to October 2019 were included.Patients who completed treatment were followed up at 12 months. ResultsOf 17 patients, median age was 23 years (IQR = 21–30 years) and 12/17 (71 %) were female. Pre-extensively drug-resistant tuberculosis and extensively drug-resistant TB was reported in 13/17 (76.4 %) and 2/17 (11.7 %) patients respectively. Microbiological reports were unavailable for two patients with central nervous system TB. Lymph node TB was the commonest form of EPTB in 9/17 (53 %) of patients. Median duration of treatment was 18.9 months. At least one grade three or four severe adverse event (SAE) was reported by 13/17 (76.4 %) patients. Thirteen (76.4 %) patients had favourable outcomes. None of the patients relapsed or died in the one-year period of post-treatment follow-up. ConclusionConcurrent BDQ-DLM-based regimens in drug-resistant EPTB were effective and associated with manageable adverse events.

Frequency and Structure of Drug Resistance of M. tuberculosis in Pulmonary and Extrapulmonary Tuberculosis

The objective: to assess changes in the data on drug resistance of M. tuberculosis for 2015-2021 and compare it with data for 2012-2014.Subjects and Methods. Using continuous sampling, the frequency of drug resistance of Mycobacterium tuberculosis (MTB DR) was studied in isolates from 151 pulmonary tuberculosis (PTB) patients and isolates from 805 extrapulmonary tuberculosis (EPTB) patients, who were treated at the clinic of St. Petersburg Research Institute of Phthisiopulmonology in 2015-2021. The results were compared with similar data for 2012-2014 which was published in 2016.Results. In 2015-2021 versus 2012-2014, the overall frequency of MTB DR decreased by 4.2% in pulmonary tuberculosis patients (from 90.1 to 85.9%) and by 2.9% in extrapulmonary tuberculosis patients (from 80.2 to 77.4%). The structure of MTB DR in pulmonary tuberculosis changed insignificantly, the frequency of MDR decreased from 42.5 to 36.5%, and XDR (as per the definitions before 2022) remained the same – 39.5%. In extrapulmonary tuberculosis, the structure of MTB DR deteriorated due to lower frequency of MDR (from 66.3 to 48.3%) and higher frequency of XDR (from 3.2 to 19.0%, p<0.01).

Clinical manifestations and prognosis of tuberculous spondylitis in an adolescent with disseminated tuberculosis: a case report

Indonesia is one of the countries with the highest number of tuberculosis (TB) cases globally. Around 10-20% of adolescents with TB infection progress to pulmonary TB, and less than 0.5% develop miliary or central nervous system TB. TB spondylitis occurs in only 5.6% of extrapulmonary TB patients. The clinical manifestations of disseminated and TB spondylitis are heterogeneous and insidious, with several potential risk- and prognostic factors. We report the case of a 16-year-old male admitted with abdominal distension, paraplegia, and urinary retention. He was diagnosed with disseminated TB with TB spondylitis. This case was unique because the patient had no classic symptoms of pulmonary TB. This report focuses on the diagnosis, comprehensive management, and prognosis of TB spondylitis, as well as the risk factors for disseminated TB. The management consisted of antituberculous agents and surgery. The prognosis is influenced by the patient’s age, severity of kyphosis deformity, number of vertebrae involved, lesion site, and patient’s health status, including nutritional status.

Effect of Combined HAART Plus ATT in Patients of Extrapulmonary Tuberculosis in HIV Patients and Effect on Quality of Life.

HIV is a disease which reduces human resistant to fight. When our immunity becomes so weak that we are not able to fight even the common commensals of our body, this leads to what is called as an opportunistic infection. Tuberculosis is one of those most common type of opportunistic infection and in this pulmonary tuberculosis is more common. Extrapulmonary tuberculosis with HIV is the area of lesser research. In this study we tried to prove the Prevalence of extrapulmonary tuberculosis in AIDS patients and also the effect of combined HAART and ATT on prevalence of extrapulmonary tuberculosis and also its effect on Quality of life of the patient. This is a retrospective study conducted in a tertiary centre in the Department of Otorhinolaryngology & head and neck surgery from January 2020 to December 2020. A total of 80 patients were studied for 1year. Confirmed cases of AIDS with extra pulmonary tuberculosis in head and neck region were studied, keeping all ethical issues in mind and after complete treatment of ATT along with HAART. After treatment, a significant number of patients got resolved with EPTB and gave positive response on their quality of life. Not only pulmonary tuberculosis, extrapulmonary tuberculosis with HIV is on the rise nowadays. Combined treatment of both can help in decreasing prevalence of extrapulmonary tuberculosis and improves quality of life.

Prevalence of extra-pulmonary tuberculosis in Africa: A systematic review and meta-analysis.

The burden of extra-pulmonary tuberculosis (EPTB) is not well quantified in TB endemic countries such as those in sub-Saharan Africa. This study aimed to quantify that burden via a systematic review of the prevalence of EPTB in African countries. Studies were retrieved by searching five databases; 105 studies published between 1990 and 2023 were included. The studies described the prevalence of EPTB among the general population (4 studies), TB patients (68) and patients with other conditions, including HIV (15), meningitis (3), renal failure (3) and other comorbidities, some of which are cancer (12). Due to the low number of studies reporting EPTB in patients with conditions other than TB, the meta-analysis was performed on studies reporting on EPTB among TB patients (68 studies). Meta-analysis was performed on the 68 studies (271,073 participants) using a random-effects model to estimate the pooled prevalence of EPTB. Meta-regression was used to explore possible explanations for heterogeneity according to regions and time periods. The pooled prevalence of EPTB among TB patients was 26% (95% CI 23-29%). There was substantial heterogeneity of prevalence for the five African regions. The Eastern region had the highest prevalence of 32% (95% CI 28-37%) and the lowest in Western Africa, 16% (95% CI 10-24%). There was no significant difference in the prevalence of EPTB between the 3 eleven-year time periods. Our systematic review and meta-analysis give insight into the burden of EPTB in Africa. This review could inform clinical and programmatic practices-a higher suspicion index for clinicians and more effort for better services. This could contribute to efforts aiming to end TB, which have historically been focused on PTB.Coordinated efforts that target both EPTB and PTB are needed.

Xpert MTB/RIF Ultra for the rapid diagnosis of extrapulmonary tuberculosis in a clinical setting of high tuberculosis prevalence country and interpretation of ‘trace’ results

To evaluate the diagnostic performance of Xpert MTB/RIF Ultra (Ultra) for the diagnosis of extrapulmonary tuberculosis (EPTB) from different types of extrapulmonary specimens in comparison with culture and composite microbiological reference standard (CRS). A total of 240 specimens were prospectively collected from presumptive EPTB patients between July 2021–January 2022 and tested by Ultra, Xpert, culture and acid-fast bacilli (AFB) smear microscopy. Out of 240 specimens, 35.8 %, 20.8 %, 11.3 %, and 7.1 % were detected as Mycobacterium tuberculosis complex by Ultra, Xpert, culture and AFB microscopy, respectively. An additional 15.0 % cases were detected by Ultra compared to Xpert MTB/RIF (Xpert) assay. A total of 28 (11.7 %) cases were identified as ‘trace’ category by Ultra with indeterminate rifampicin resistance result; of which 36.4 % were clinically confirmed as EPTB. Compared to culture, the sensitivity and specificity of Ultra and Xpert were 100 % and 72.3 %; 92.6 % and 88.3 %, respectively. In comparison with CRS, these were respectively: 98.9 % and 100 %; 57.5 % and 100 %. For individual category of specimens, sensitivity of Ultra was 100 % with varying specificity. We found that Ultra was highly sensitive for the rapid diagnosis of EPTB and has extensive potential over current diagnostics in high TB burden countries, but ‘trace’ results should be interpreted with caution.

Pangenome and genomic signatures linked to the dominance of the lineage-4 of Mycobacterium tuberculosis isolated from extrapulmonary tuberculosis patients in western Ethiopia.

The lineage 4 (L4) of Mycobacterium tuberculosis (MTB) is not only globally prevalent but also locally dominant, surpassing other lineages, with lineage 2 (L2) following in prevalence. Despite its widespread occurrence, factors influencing the expansion of L4 and its sub-lineages remain poorly understood both at local and global levels. Therefore, this study aimed to conduct a pan-genome and identify genomic signatures linked to the elevated prevalence of L4 sublineages among extrapulmonary TB (EPTB) patients in western Ethiopia. A cross-sectional study was conducted at an institutional level involving confirmed cases of extrapulmonary tuberculosis (EPTB) patients from August 5, 2018, to December 30, 2019. A total of 75 MTB genomes, classified under lineage 4 (L4), were used for conducting pan-genome and genome-wide association study (GWAS) analyses. After a quality check, variants were identified using MTBseq, and genomes were de novo assembled using SPAdes. Gene prediction and annotation were performed using Prokka. The pan-genome was constructed using GET_HOMOLOGUES, and its functional analysis was carried out with the Bacterial Pan-Genome Analysis tool (BPGA). For GWAS analysis, Scoary was employed with Benjamini-Hochberg correction, with a significance threshold set at p-value ≤ 0.05. The analysis revealed a total of 3,270 core genes, predominantly associated with orthologous groups (COG) functions, notably in the categories of '[R] General function prediction only' and '[I] Lipid transport and metabolism'. Conversely, functions related to '[N] Cell motility' and '[Q] Secondary metabolites biosynthesis, transport, and catabolism' were primarily linked to unique and accessory genes. The pan-genome of MTB L4 was found to be open. Furthermore, the GWAS study identified genomic signatures linked to the prevalence of sublineages L4.6.3 and L4.2.2.2. Apart from host and environmental factors, the sublineage of L4 employs distinct virulence factors for successful dissemination in western Ethiopia. Given that the functions of these newly identified genes are not well understood, it is advisable to experimentally validate their roles, particularly in the successful transmission of specific L4 sublineages over others.

Possible depression in new tuberculosis patients in the Free State province, South Africa.

Despite compelling evidence of comorbidity between tuberculosis (TB) and depression, little is known about the prevalence and determinants of depression among TB patients in the Free State province in South Africa. This study assessed the prevalence and factors associated with possible depression among new drug susceptible TB patients attending primary health care facilities. The study followed a cross-sectional design. Trained fieldworkers conducted face-to-face interviews with conveniently selected patients. Depression was assessed using the Patient Health Questionnaire-9. Data were subjected to descriptive and binomial logistic regression analyses. Out of 208 patients, 46.2% screened positive for possible depression - 22.6%, 18.8%, and 4.8% presenting with mild, moderate, and severe symptoms, respectively. Possible depression odds were three times higher among females than males (adjusted odds ratio [AOR]: 3.0; 95% confidence interval [CI]: 1.25-7.32) and 2.7 times higher among extrapulmonary TB (EPTB) than pulmonary TB patients (95% CI: 1.03-7.21). Longer TB treatment duration was protective (AOR: 0.8; 95% CI: 0.70-0.95) against depression. Among human immunodeficiency virus-positive patients, those on antiretroviral therapy (ART) had 2.5 times higher odds of depression (95% CI: 1.13-5.46) than those who were not. The results highlight a significant burden of possible depression among new TB patients, particularly among females, EPTB patients, and ART recipients. Longer TB treatment duration may offer some protection against depression symptoms, suggesting a need for enhanced adherence support. The results suggest that strengthening TB and mental health service integration is critical to improving treatment outcomes, overall well-being of TB patients, and the performance of the Free State TB programme.

Whole-genome sequencing-based genetic diversity, transmission dynamics, and drug-resistant mutations in Mycobacterium tuberculosis isolated from extrapulmonary tuberculosis patients in western Ethiopia.

Extrapulmonary tuberculosis (EPTB) refers to a form of Tuberculosis (TB) where the infection occurs outside the lungs. Despite EPTB being a devastating disease of public health concern, it is frequently overlooked as a public health problem. This study aimed to investigate genetic diversity, identify drug-resistance mutations, and trace ongoing transmission chains. A cross-sectional study was undertaken on individuals with EPTB in western Ethiopia. In this study, whole-genome sequencing (WGS) was employed to analyze Mycobacterium tuberculosis (MTB) samples obtained from EPTB patients. Out of the 96 genomes initially sequenced, 89 met the required quality standards for genetic diversity, and drug-resistant mutations analysis. The data were processed using robust bioinformatics tools. Our analysis reveals that the majority (87.64%) of the isolates can be attributed to Lineage-4 (L4), with L4.6.3 and L4.2.2.2 emerging as the predominant sub-lineages, constituting 34.62% and 26.92%, respectively. The overall clustering rate and recent transmission index (RTI) were 30 and 17.24%, respectively. Notably, 7.87% of the isolates demonstrated resistance to at least one anti-TB drug, although multi-drug resistance (MDR) was observed in only 1.12% of the isolates. The genetic diversity of MTBC strains in western Ethiopia was found to have low inter-lineage diversity, with L4 predominating and exhibiting high intra-lineage diversity. The notably high clustering rate in the region implies a pressing need for enhanced TB infection control measures to effectively disrupt the transmission chain. It's noteworthy that 68.75% of resistance-conferring mutations went undetected by both GeneXpert MTB/RIF and the line probe assay (LPA) in western Ethiopia. The identification of resistance mutations undetected by both GeneXpert and LPA, along with the detection of mixed infections through WGS, emphasizes the value of adopting WGS as a high-resolution approach for TB diagnosis and molecular epidemiological surveillance.

A Comparative Study of Interleukin 1beta (IL-1 β) Levels in Pulmonary and Extra-Pulmonary Tuberculosis Patients among Iraqi Population

A Comparative Study of Interleukin 1beta (IL-1 β) Levels in Pulmonary and Extra-Pulmonary Tuberculosis Patients among Iraqi Population