Mutational analysis in drug resistant Mycobacterium tuberculosis in Western Uttar Pradesh.

BACKGROUND: Multi-drug resistant tuberculosis (MDR-TB) results in treatment failure and poor clinical outcomes. This study was carried out with the aim to determine the pattern of drug resistance against Mycobacterium tuberculosis towards first line ATT (anti-tubercular treatment) in sputum smear-positive patients using Line Probe Assay (LPA). METHODS: A cross sectional prospective study was carried out in a tertiary care Hospital of Meerut. A total of 898 sputum samples (on spot and early morning) collected from 449 suspected pulmonary tuberculosis patients as per RNTCP guidelines were screened by microscopy. Decontamination was done by N-acetyl-l-cysteine and sodium hydroxide. Then smear positive samples were subjected to 1st line drug susceptibility testing (DST) using LPA GenoType® MTBDRplus (HAIN Life Science) assay, a molecular method which allows rapid detection of Rifampicin (Rif) and Isoniazid (INH) resistance. RESULTS: The overall burden of MDR TB in this geographical area was 7.9 %. Mono-resistance with Rif alone was around 2.8 %. However, the mono-resistance with INH (inhA gene) and INH (katG gene) was 2.8 % and 1.1 % respectively. Drug resistance of Rif was due to mutations in rpoB gene while resistances to INH were more commonly due to mutation in inhA gene followed by katG gene. TB was more commonly seen in the age group of 30-59 years (43.8 %) and predominantly in males. CONCLUSION: Tuberculosis positivity rate is high in Western Uttar Pradesh. Burden of MDR TB in Western Uttar Pradesh was similar to National data. Line probe assay can be used as a primary method to diagnose multi drug resistant TB as done in present study which can help in earlier initiation of correct therapy.

The Longer the Therapy, the Worse the Severity of the Adverse Drug Reactions that Occur in Drug-Resistant Pulmonary Tuberculosis Patients.

BACKGROUND: It is estimated that drug-resistant (DR) Tuberculosis (TB) (DR-TB) patients in Indonesia are 2.40% of all new TB patients and 13% of previously treated TB patients with a total incidence of DR-TB cases of 24,000 people. The adverse drug reactions (ADRs) of DR-TB are still a problem that can certainly affect the success of therapy. The aim of this study was to determine the correlation between the length of therapy and regimen therapy of DR-TB with the severity of ADRs. METHODS: Data collection was carried out retrospectively on the medical records of DR-TB patients in 2020-2021 and sampling used a purposive sampling technique that complied with the inclusion criteria. RESULTS: Of the 86 patients, the majority of DR-TB patients in X Hospital were 26-45 years old 35 (40.7%), 52 (60.5%) male, the most common comorbid was type II DM, 19 (22.1%), and the most nutritional status was malnutrition as much as 39 (45.3%). The most common type of ADR was hyperuricemia in 31 (36.0%). The results of the correlation analysis showed that there was a relationship between the length of therapy and the severity of ADRs (ρ = 0.002) and there was no relationship between the type of therapy regimen and the severity of ADRs (ρ = 0.184). CONCLUSION: The longer DR-TB therapy, the higher the severity of ADRs and there is no relationship between the type of therapy regimen and the severity of ADRs.

Primary Tuberculosis of Tonsils: Interesting Case Detected During the Histopathological Examination.

Despite being a preventable and curable disease, tuberculosis, which mainly affects the lungs, is still a major cause of illness and death worldwide, with more than one million people dying from it each year. The affliction of the tonsils is uncommon, and isolated tonsillar tuberculosis in the absence of active pulmonary disease is an extremely rare condition that requires early and accurate diagnosis to provide proper management. Microscopic examination is one of the gold-standard tools for diagnosing tuberculosis. However, routine histopathological investigation for tonsillectomy specimens is not justified except in cases of unusual clinical or postoperative presentations. A 20-year-old female patient who experienced recurrent episodes of infections with enlarged tonsils and adenoids and showed a slightly unusual presentation was sent for a histopathology examination. Upon microscopic examination, a caseating granulomatous reaction was found, and staining for acid-fast bacilli tested positive. The patient was treated for tuberculosis of the tonsils, and their condition improved.

Increased tuberculosis case detection in Tanzanian children and adults using African giant pouched rats.

BACKGROUND: African giant pouched rats, trained by Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling (APOPO), have demonstrated their ability to detect tuberculosis (TB) from sputum. We assessed rat-based case detection and compared the mycobacterium bacillary load (MTB-load) in children versus adults. METHODS: From January-December 2022, samples were collected prospectively from 69 Directly Observed Therapy (DOT) facilities' presumed TB patients. Using an average of five rats, APOPO re-evaluated patients with bacteriologically negative (sputum-smear microscopy or Xpert MTB/RIF) results. Rat-positive samples were tested using concentrated smear light-emitting diode microscopy to confirm TB detection before treatment initiation. The rats' identification of pulmonary TB is based on smelling TB-specific volatile organic compounds (VOCs) in sputum. Using STATA, Chi-square for odds ratio and confidence interval was calculated and evaluated: (1) the yield of rat-based TB detection compared to that of the health facilities; (2) rat-based TB detection in children versus adults; and (3) rats' ability to detect TB across MTB-loads and between children and adults. RESULTS: From 35,766 patients, 5.3% (1900/35,766) were smear-positive and 94.7% (33,866/35,766) were smear or Xpert-negatives at DOTS facility. Of those with negative results, 2029 TB cases were detected using rats, contributing to 52% (2029/3929 of total TB identified), which otherwise would have been missed. Compared to DOT facilities, rats were six-fold more likely to detect TB among Acid Fast Bacilli (AFB) 1+/scanty [90% (1829/2029) versus 60% (1139/1900), odds ratio, OR = 6.11, 95% confidence interval, CI: 5.14-7.26]; twice more likely to identify TB cases among children [71% (91/129) versus 51% (1795/3542), OR = 2.3, 95% CI: 1.59-3.42]; and twice more likely to identify TB cases among children with AFB 1+/scanty than adults with the same MTB-load [5% (86/1703) versus 3% (28/1067), OR = 2.0, 95% CI: 1.28-3.03]. CONCLUSIONS: Rats contributed over half of the TB cases identified in program settings, and children, especially those with a lower MTB-load, were more likely to be diagnosed with TB by rats. The chemical signatures, VOCs, were only available for adults, and further research describing the characteristics of VOCs in children versus adults may pave the way to enhance TB diagnosis in children.

Readiness, acceptability, and feasibility of differentiated TB care for COVID-positive pulmonary tuberculosis patients diagnosed in a district in South India: Mixed methods study.

Background: Differentiated tuberculosis care (DTC) approach is the need of the hour to mitigate those risks and provide better treatment outcomes to reduce both mortality and morbidity. Before implementing such an approach, there should be adequate literature on healthcare facility assessment along with qualitative exploration on readiness and acceptability among various stakeholders that are currently needed to fill the gaps in National Tuberculosis Elimination Program. Objectives: Our study objectives were to assess the availability of equipment, treatment, and investigations for managing patients under the DTC approach, to explore the readiness, acceptability, and feasibility of the DTC approach among healthcare providers involved in TB care provision, and to determine the knowledge regarding DTC approach among healthcare providers delivering TB care for COVID-positive pulmonary TB patients. Materials and Methods: All Peripheral Health Institutes (PHIs) in two randomly chosen blocks within the Tiruchirappalli district's health units were selected for the healthcare facilities assessment. By the universal sampling method, all the stakeholders were included. The study population was assessed for their knowledge regarding DTC. Checklist-based assessment of the feasibility of healthcare services followed by a questionnaire-based knowledge assessment was done. An in-depth interview-based exploration of readiness and acceptability of the DTC approach was conducted. This study was conducted among various stakeholders involved in TB care in selected PHIs of Tiruchirappalli from July 2022 to October 2022. Results: The majority of healthcare workers (HCWs) are unaware of bidirectional screening (89.0%) and lack training in providing TB care to COVID-co-infected patients (87.8%), although the majority were aware of risk stratification for TB patients (90.2%) and are linking TB with other co-morbidities (82.9%). About 62.2% of HCWs claimed they are not using information communication technology-based services to receive lab findings from public scans and laboratory centers, and more than one-third were unaware of these facilities. Based on the qualitative assessment, most of them were willing to undergo periodic training to improvise their approach and treatment. Also, most of the HCWs felt manpower can be increased for the specific care of the patients. Conclusion: The research suggests that with sufficient training and upskilling of the HCWs, DTC is almost feasible and that HCWs will accept it if specific strategies are used. More studies like these in assessing the feasibility and acceptability of this DTC approach and exploring the challenges and solutions will help the policymakers in finding the lacunae before implementing this DTC model in various states across India.

Uncovering the Bronchoalveolar Single-Cell Landscape of Patients With Pulmonary Tuberculosis With Human Immunodeficiency Virus Type 1 Coinfection.

BACKGROUND: Coinfection of human immunodeficiency virus type 1 (HIV-1) is the most significant risk factor for tuberculosis (TB). The immune responses of the lung are essential to restrict the growth of Mycobacterium tuberculosis and avoid the emergence of the disease. Nevertheless, there is still limited knowledge about the local immune response in people with HIV-1-TB coinfection. METHODS: We employed single-cell RNA sequencing (scRNA-seq) on bronchoalveolar lavage fluid from 9 individuals with HIV-1-TB coinfection and 10 with pulmonary TB. RESULTS: A total of 19 058 cells were grouped into 4 major cell types: myeloid cells, T/natural killer (NK) cells, B cells, and epithelial cells. The myeloid cells and T/NK cells were further divided into 10 and 11 subsets, respectively. The proportions of dendritic cell subsets, CD4+ T cells, and NK cells were lower in the HIV-1-TB coinfection group compared to the TB group, while the frequency of CD8+ T cells was higher. Additionally, we identified numerous differentially expressed genes between the CD4+ and CD8+ T-cell subsets between the 2 groups. CONCLUSIONS: HIV-1 infection not only affects the abundance of immune cells in the lungs but also alters their functions in patients with pulmonary TB.

Comparative analysis of cartridge-based nucleic acid amplification test (CBNAAT) with conventional methods in the diagnosis of pediatric tuberculosis at a tertiary care center.

BACKGROUND: Tuberculosis is an important cause of morbidity and mortality among children. Early diagnosis and treatment in children are challenging, more so in resource-limited, tuberculosis-endemic countries. In 2017, the WHO endorsed the use of CBNAAT for tuberculosis diagnosis. We have undertaken this study to evaluate the diagnostic value of CBNAAT in pediatric tuberculosis in comparison to other methods like microscopic detection of acid-fast bacilli and detection of mycobacteria-by-mycobacteria growth indicator tube (MGIT). MATERIAL AND METHODS: This hospital-based, cross-sectional, observational prospective study was conducted in the department of pediatrics, at a tertiary care center. A detailed history, general physical examination, and relevant physical examination were performed systematically and the findings were noted in the proforma. All necessary basic investigations like CBC, ESR, X-Ray, etc., and advanced investigations like MRI, CT, and FNAC were done as per the requirement of the subjects and the results were mentioned in the study proforma. Sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were calculated for various methods. A comparison between the two methods was done using the Mc Nemar test. p-value ≤0.05 was taken as statistically significant. All statistical analyses were done using Epi info version 7.2.1.0 statistical software. RESULTS: Among 102 children suspected to be suffering from tuberculosis, the maximum number of TB cases were found in the age group of 11-16 years (43.2%), there were 58.2% of females, 58.8% belonged to the rural population, fever (78.4%) was the most common presenting symptom and 35.3% had a history of contact. In the present study, CBNAAT and ZN staining had equal sensitivity (60.8%) and specificity (100%) while the yield for MGIT culture was quite low (sensitivity 37.3%, specificity 100%). CONCLUSIONS: CBNAAT as a test was found to be useful, especially for early diagnosis and detection of rifampicin resistance in pediatric tuberculosis against MGIT culture. Since MGIT results become available only after 42 days and have a relatively lower yield so they can be utilized only in a selected clinical situation or in patients with high suspicion of tuberculosis where another test is not able to detect the organisms.

How We Treat Drug-Susceptible Pulmonary Tuberculosis: A Practical Guide for Clinicians.

Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis-resistant strains. In this narrative review, through a fictional suggestive case of DS PTB, we guide the reader in a step-by-step commentary to provide an updated review of current evidence in the management of TB, from diagnosis to post-treatment follow-up. World Health Organization and Centre for Diseases Control (CDC) guidelines for TB, as well as the updated literature, were used to support this manuscript.

Ocular manifestations and diagnosis of tuberculosis involving the uvea: a case series.

BACKGROUND: Ocular tuberculosis (TB) affects 1-2% of patients with TB, with TB uveitis being the most common. This series aims to look at different manifestations of tuberculosis associated uveitis and the different tests used to make a presumptive or definitive diagnosis. METHODS: Patients diagnosed with TB related uveitis in Hong Kong SAR between 2017 and 2020 were reviewed. Demographics, clinical features, investigations and treatments of patients were collected. RESULTS: Fifteen eyes in 10 patients with a mean age 57.30 ± 10.17 years were included. The ocular manifestations on presentation included anterior uveitis (50%), posterior uveitis (40%) and panuveitis (10%), where 70% of them were unilateral and 30% were bilaterally infected; on subsequent visits the manifestations further developed into posterior uveitis (40%), panuveitis (40%) and anterior uveitis (20%), where 50% of them were unilateral and 50% bilateral infected. Tuberculosis tests were positive in 5 out of 7 Mantoux tests, 4 out of 4 T-SPOT TB tests, 3 out of 4 QuantiFERON-TB gold tests, 1 out of 1 lymph node biopsy, 0 out of 9 chest x-rays, and no aqueous fluid polymerase chain reaction (PCR) was tested. Vision impairing complications were seen in 6 patients where retinal vasculitis was most commonly seen. With anti-TB treatment prescribed in 9 patients, side effects occurred in 5 patients, including ocular hypertension, disc swelling, and hepatitis. CONCLUSIONS: Ocular TB infections may manifest in various forms, and can involve different parts of the eye. Bilateral involvement of TB is commonly presented, and both eyes should be evaluated at every follow up. When TB is suspected in a patient, diagnostic confirmation requires multimodal investigations where a negative chest x-ray is not useful in ruling out ocular TB infections, especially in an endemic region like Hong Kong. In these patients, it is crucial to have a high index of suspicion for TB, even when they do not demonstrate classical respiratory signs and symptoms of TB.

Identifying the Interaction Between Tuberculosis and SARS-CoV-2 Infections via Bioinformatics Analysis and Machine Learning.

The number of patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2 is still increasing. In the case of COVID-19 and tuberculosis (TB), the presence of one disease affects the infectious status of the other. Meanwhile, coinfection may result in complications that make treatment more difficult. However, the molecular mechanisms underpinning the interaction between TB and COVID-19 are unclear. Accordingly, transcriptome analysis was used to detect the shared pathways and molecular biomarkers in TB and COVID-19, allowing us to determine the complex relationship between COVID-19 and TB. Two RNA-seq datasets (GSE114192 and GSE163151) from the Gene Expression Omnibus were used to find concerted differentially expressed genes (DEGs) between TB and COVID-19 to identify the common pathogenic mechanisms. A total of 124 common DEGs were detected and used to find shared pathways and drug targets. Several enterprising bioinformatics tools were applied to perform pathway analysis, enrichment analysis and networks analysis. Protein-protein interaction analysis and machine learning was used to identify hub genes (GAS6, OAS3 and PDCD1LG2) and datasets GSE171110, GSE54992 and GSE79362 were used for verification. The mechanism of protein-drug interactions may have reference value in the treatment of coinfection of COVID-19 and TB.

Assessment of Knowledge, Attitude, and Practice towards Tuberculosis among Taif University Students.

Tuberculosis (TB) remains a significant public health concern worldwide. Given the dense living and interactive nature of university environments, students may be at higher risk. This cross-sectional study assessed tuberculosis-related knowledge, attitudes, and practices (KAP) among students at Taif University (TU) from November 2022 to May 2023. Using a self-administered online questionnaire with 40 items, 1155 students participated. Key demographics: 68.2% females, 96.9% Saudi citizens, 94.5% unmarried, and 87.5% non-smokers. Of the respondents, 26.5% had no knowledge of TB. The TB-related KAP scores among the aware students were 64.9%, 74.8%, and 81%, respectively. Medical college students exhibited significantly higher TB-related knowledge and attitudes than their non-medical peers (p < 0.001). The findings indicate a commendable level of TB-awareness among TU students, but there remains a substantial uninformed segment. Campaigns to enhance TB knowledge among TU students are suggested.

Pulmonary Tuberculosis with Concomitant Aspergillus Fungal Ball in a Diabetic Indian Male: A Rare Case Report.

Pulmonary tuberculosis is rampant in some countries. The disease is an outcome of infection by Mycobacterium tuberculosis and is more common in immunocompromised individuals. Furthermore, mycetoma or a fungal ball can develop in cavitary lesions of tuberculosis. The present case is a rare presentation of pulmonary tuberculosis with concomitant Aspergillus fungal ball in a diabetic Indian male. A clinical examination with a strong laboratory and radiological workup helped establish the final diagnosis. The patient was initiated on anti-tubercular chemotherapy and advised lobectomy.

Quality of Electronic TB Register Data Compared with Paper-Based Records in the Kyrgyz Republic.

This study evaluated the effectiveness of an electronic system for managing individuals with drug-sensitive pulmonary tuberculosis in the Kyrgyz Republic. This cohort study used programmatic data. The study included people registered on the paper-based system in 2019 and 302 people registered on both the electronic and the paper-based systems between June 2021 and May 2022. The data from the 302 individuals were used to assess the completeness of each form of record and the concordance of the electronic record with the paper-based system. This study showed that for most variables, the completeness and concordance were 85.3-93.0% and were lowest for nonmandatory fields such as medication side effects (26.8% vs. 13.6%). No significant difference was observed in the time taken from symptom onset to diagnosis and treatment initiation between the two systems. However, the electronic system had a significantly higher percentage of subjects who initiated treatment on the day of diagnosis (80.3% vs. 57.1%). The proportion with successful outcomes was similar in both groups, but the electronic system had a significantly lower proportion of individuals with outcomes that were not evaluated or recorded (4.8% vs. 14.3%, p < 0.001). This study highlights the potential advantages and gaps associated with implementing an electronic TB register system for improving records.

Clinical features, resistance patterns and treatment outcomes of drug-resistant extra-pulmonary tuberculosis: A scoping review.

Background: Drug-resistant tuberculosis (DR-TB) is a threat to tuberculosis (TB) control. Extra-pulmonary forms of DR-TB (DR-epTB) are not well characterized. This review summarizes the clinical features, resistance patterns and treatment outcomes of DR-epTB. Methods: We searched EMBASE to identify studies that reported drug-resistance among extra-pulmonary TB sites. All age groups were included in this review. Studies which did not describe drug-resistance patterns at extra-pulmonary TB sites were excluded. We summarized the proportion of resistance to individual anti-TB drugs as well as multi-drug resistant (MDR), pre-extensively drug resistant (pre-XDR) and extensively drug-resistant (XDR) TB. Results: Eighteen studies with a total of 10,222 patients with extra-pulmonary TB of whom 1,236 (12.0%) had DR-epTB, were included in this review. DR-epTB was mostly reported in young people aged 28 to 46 years. While TB meningitis is the most commonly studied form, adenitis is the commonest form of DR-epTB reported in 21% to 47%. Central nervous system TB (3.8% to 51.6%), pleural TB (11.3% to 25.9%), skeletal TB (9.4% to 18.1%), abdominal TB (4.3% to 6.5%), and disseminated TB (3.8%) are also encountered. The HIV co-infection rate is reported to be 5.0% to 81.3% while 2.6% to 25.4 % have diabetes mellitus. Clinical symptoms of DR-epTB are consistent with morbidity in the affected body system. Among patients with DR-epTB, the proportion of MDR TB was 5% to 53% while that for pre-XDR TB and XDR TB was 3% to 40% and 4% to 33%, respectively. Treatment success is achieved in 26% to 83% of patients with DR-epTB while death, treatment loss-to-follow up, and treatment failure occur in 2% to 76%, 7% to 15%, and 0% to 4% respectively. Patients with DR-epTB were reported to have poorer outcomes than those with pulmonary DR-TB and extra-pulmonary drug-susceptible TB. Conclusion: Clinical features of DR-epTB are similar to those observed among people with drug-susceptible EPTB but patients with DR-epTB post worse treatment outcomes.

Assessment of Family Tuberculosis Contact Screening Practice and its Associated Factors Among Pulmonary Tuberculosis Positive Patients in South Wollo Zone, Amhara Region, Ethiopia.

Objectives: The objective of this study was to assess the prevalence and the associated factors of family contact screening practice. Methods: An institution-based cross-sectional study was conducted among 403 randomly selected pulmonary tuberculosis index cases from 1st May to 30th June 2020. Data were collected through a face-to-face interviewer-administered questionnaire. Multivariable logistic regression was performed. Results: The prevalence of family contact screening was 55.3%, (CI: 60-50). Having family support for care and treatment (AOR = 2.21, 95% CI: 1.16-4.21), waiting time of less than 60 min (AOR = 2.03, 95% CI: 1.28-3.21), receiving health education on TB prevention and treatment (AOR = 1.86), 95% CI: 1.05-3.29), and having good knowledge about TB prevention (AOR = 2.76, 95% CI: 1.77-4.294) were factors associated with family TB contact screening practice. Conclusion: This study revealed that the prevalence of family contact screening was low as compared to national and global targets. Factors associated with family contact screening practice were: the presence of family support, shorter waiting time, health education offered by healthcare workers, and a good level of knowledge of the index cases.

Active Screening for Pulmonary Tuberculosis Among Jail Inmates: A Mixed Method Study From Puducherry, South India.

BACKGROUND: Sustainable Development Goal 3 (SDG) aims to end the epidemic of TB by 2030. To achieve this goal, active screening should be initiated in the target populations. These target populations are those without access to proper healthcare like jail inmates. With pulmonary tuberculosis (PTB) being cosmopolitan in India, passive case finding alone cannot suffice to achieve the above-mentioned goal. Thus, active case finding (ACF) becomes the need of the hour. So, we aimed to conduct a mixed methods study that has a quantitative component, i.e., to actively screen the prison inmates for PTB, and a qualitative component, i.e., to know the perceptions of jail inmates towards PTB and the stigmas associated with it. METHODOLOGY: This was a mixed-method study conducted in the Central Jail, Puducherry. The quantitative component involved a facility-based cross-sectional study design and the qualitative component involved a focused group discussion (FGD). Participants were screened for PTB and diabetes mellitus (DM) and their anthropometry (weight, height, body mass index {BMI}, waist-to-hip ratio {WHR}) was noted. Presumptive cases were identified as those with symptoms of cough for more than two weeks with or without other concomitant symptoms. They were subjected to cartridge-based nucleic acid amplification test (CB-NAAT) assay. Data were entered in MS Excel 2017 and analyzed using SPSS version 16 (Armonk, NY: IBM Corp). For the qualitative exercise, purposive sampling with maximum variation technique was done to enroll a diverse subset of population for the FGD. Iterative analysis of the content was performed by the team to generate codes and themes. RESULTS: Out of all the 187 inmates screened, 10.7% were symptomatic. On CB-NAAT examination of the symptomatic inmates, none turned positive. The inmates with presumptive TB were older by age and had a higher proportion of illiteracy and existing co-morbidity (p≤0.05). While random blood sugar (RBS) levels of >140 mg/dL were recorded in 19.7% of inmates, RBS levels of >200 mg/dL considered diagnostic were noted in 5.34% of inmates. A total of 2.67% of the inmates were newly diagnosed with diabetes mellitus. The further management of the newly diagnosed inmates was taken over by the medical supervision team of the Central Jail. From the FGD, thematic manual content analysis was performed. A total of 24 codes were generated. After merging similar codes and removing duplications, the remaining 16 codes were grouped into six broad themes. Conclusions were drawn by interpretation of these themes. CONCLUSION: ACF is important as it is associated with early detection and treatment. It must be done periodically. During the FGD, we came across negative ideologies and stigmas associated with PTB among jail inmates. We used the same platform to clear those ideologies and recommend frequent health education exercises even in socially ostracized communities like jail inmates.

No impact of helminth coinfection in patients with smear positive tuberculosis on immunoglobulin levels using a novel method measuring Mycobacterium tuberculosis-specific antibodies.

Helminth/tuberculosis (TB)-coinfection can reduce cell-mediated immunity against Mycobacterium tuberculosis (Mtb) and increase disease severity, although the effects are highly helminth species dependent. Mtb have long been ranked as the number one single infectious agent claiming the most lives. The only licensed vaccine for TB (BCG) offers highly variable protection against TB, and almost no protection against transmission of Mtb. In recent few years the identification of naturally occurring antibodies in humans that are protective during Mtb infection has reignited the interest in adaptive humoral immunity against TB and its possible implementation in novel TB vaccine design. The effects of helminth/TB coinfection on the humoral response against Mtb during active pulmonary TB are however still unclear, and specifically the effect by globally prevalent helminth species such as Ascaris lumbricoides, Strongyloides stercoralis, Ancylostoma duodenale, Trichuris trichiura. Plasma samples from smear positive TB patients were used to measure both total and Mtb-specific antibody responses in a Peruvian endemic setting where these helminths are dominating. Mtb-specific antibodies were detected by a novel approach coating ELISA-plates with a Mtb cell-membrane fraction (CDC1551) that contains a broad range of Mtb surface proteins. Compared to controls without helminths or TB, helminth/TB coinfected patients had high levels of Mtb-specific IgG (including an IgG1 and IgG2 subclass response) and IgM, which were similarly increased in TB patients without helminth infection. These data, indicate that helminth/TB coinfected have a sustained humoral response against Mtb at the level of active TB only. More studies on the species-specific impact of helminths on the adaptive humoral response against Mtb using a larger sample size, and in relation to TB disease severity, are needed.

Unraveling the Secrets Behind the Multidrug-Resistant Tuberculosis Treatment Outcome in Chronic Renal Failure Patients Requiring Hemodialysis: A Systematic Review.

Multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR TB) is a global concern, with 450,000 new cases and 191,000 deaths in 2021. TB and chronic kidney disease (CKD) have been associated since 1974, with suggested explanations such as oxidative stress, malnutrition, dysfunction in vitamin D metabolism, and a compromised cell-mediated immune response. End-stage renal failure patients are more likely to acquire drug resistance due to poor adherence, adverse drug reactions, and inappropriate dose adjustment. We then aim to evaluate the therapeutic outcome of multidrug-resistant TB of the lungs in patients who require hemodialysis in terms of successful treatment (cured and treatment completed) and the associated factors for a favorable outcome. Our secondary goal is to identify unfavorable treatment outcomes (treatment failed, patient died, or patient lost to follow-up) and the underlying associated factors. We conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Guidelines for this systematic review. We included adults (>19 years old) with chronic kidney disease who needed hemodialysis and had microbiologically confirmed multidrug-resistant pulmonary TB, excluding patients who had a renal allograft transplant, were on peritoneal dialysis, had extrapulmonary TB, were children and pregnant patients. We searched PubMed, MEDLINE, PubMed Central, ScienceDirect, Public Library of Science (PLOS), and Google Scholar. Keywords were combined with the Boolean "AND" operator to gather results as well as the medical subject heading (MeSH) search strategy. After screening study articles by reading their titles and abstracts, the following tools were used to assess the risk of bias: the Newcastle-Ottawa scale for observational studies, the Assessment of Multiple Systematic Reviews (AMSTAR) checklist for systematic reviews, and the Joanna Briggs Institute (JBI) assessment tool for case reports. Primary and secondary outcomes were assessed, and a conclusion was made. We gathered 21,570 studies from the databases between 2013 and 2023, with 30,062 total participants. There were eight eligible studies for review. Patients with CKD, particularly those on dialysis, are at increased risk of TB due to a combination of factors that contribute to immunosuppression. TB reactivation is common in chronic renal failure patients. Diagnostic samples such as sputum and pleural fluid had lower sensitivity rates compared to tissue samples, which led to delays in diagnosis and treatment and, most importantly, contributed to drug resistance. All new dialysis patients should undergo interferon-gamma release assay testing. TB-infected patients with severe renal disease (eGFR 30 ml/min) had increased morbidity and mortality; however, the use of directly observed treatment, short-course (DOTS), and renal-dose adjustment of anti-TB medications significantly reduced these risks. Drug-induced hepatitis and cutaneous reactions were common adverse effects of anti-TB medications. A therapeutic drug monitoring guideline is required to reduce these adverse events and even mortality. Additional research is required to assess the safety and efficacy of therapeutic regimens, as well as their outcomes, in this population with multidrug-resistant TB.

Status of Universal Drug Susceptibility Testing in Pulmonary Tuberculosis Patients Initiated on Treatment in an Urban Setting, South India.

Introduction: Early initiation of drug susceptibility testing (DST) guided anti-tuberculosis treatment benefits the patient in terms of better treatment outcomes and possibly reduces the transmission of tuberculosis (TB) disease in the community. To determine the status of universal DST (UDST) coverage in smear-positive pulmonary TB patients (PTB) initiated on treatment under the TB program in Greater Chennai Corporation. In addition, the barriers and facilitators for UDST were explored. Material and Methods: The data of PTB patients who were initiated on anti-TB treatment from July to December 2019 was abstracted from the NI-KSHAY database of TB Program. The barriers and facilitators for UDST were explored in 5 focus group discussions (FGDs) among the TB program healthcare workers (HCW). UDST coverage was based on the availability of Cartridge-based Nucleic Acid Amplification test (CBNAAT) results in the NI-KSHAY database. Results: The CBNAAT result was available for 1628 (82.6%) of the 1970 smear-positive PTB patients. Non-availability of CBNAAT results was significantly higher among the older age group (>50 years), in female PTB patients, and the Private Sector. Issues with sputum collection, transport of specimens, and receipt of results were highlighted by the HCWs for the non-availability of UDST results. Conclusion: Universal DST coverage in smear-positive PTB patients initiated on treatment in 2019 in Chennai was optimal as per National Strategic Plan for TB elimination UDST target of 80% for the year 2020 but with scope for improvement. The low UDST coverage in the private sector, among female patients and older age groups, needs to be addressed.

Risk for multidrug-resistant tuberculosis in patients treated with anti-tumor necrosis factor agents.

Background: There are few studies on medical conditions associated with the development of drug-resistant TB. Objective: We investigated the risk factors for the occurrence of multidrug-resistant (MDR) tuberculosis (TB) in patients with pulmonary TB. Materials and methods: Based on claims data from the Health Insurance Review and Assessment service in South Korea, we retrospectively investigated patients aged 18 years or older with active pulmonary TB who were treated with anti-TB therapy between January 1, 2008, and February 28, 2021. Results: Among 248,176 patients with pulmonary TB who underwent anti-TB therapy, 2.0% were identified as having MDR-TB. MDR-TB showed male predominance compared to patients without MDR-TB, and patients with MDR-TB were younger. The risk for MDR-TB in patients treated with anti-TB therapy was 3.26 times higher in patients who received anti-tumor necrosis factor (TNF) agents before prescription of anti-TB medications than in those who had never been exposed to anti-TNF agents after adjusting for other TB risk factors (age, sex, inhaled corticosteroid, diabetes mellitus, liver disease, pneumoconiosis, and organ or blood recipients). The risk for MDR-TB was also increased in males and younger patients. Conclusion: Treatment with an anti-TNF agent could be a driver of MDR-TB in patients with pulmonary TB.