Resistant Tuberculosis Research Articles

Estimating the survival function Maximum Likelihood and Cramér-Von Mises Method use of amixture distribution weibull and ailamujia with apractical application

Tow failure distributions were mixed ,weibull distribution and ailamujia distribution it's called weibull –ailamujia distribution which consists of four features, the two distributions were mixed by adding a mixing parameter ,the mixture of two distributions would be more efficient ,and representative of the data than the single distributions. A group of statistical properties of the mixture distribution were studied , such as the probability function ,the survival function and the failure rate function .classical estimation method were used to estimate the parameters of the mixture distribution, which are maximum likelihood of method ,the cramer –von mises method ,The method were compared using monte carlo simulations real data were taken regarding drug –resistant tuberculosis (TB) Multi Drug Resistance(MDR) methods were compared using the MSE statistical criterion ,and the result should a preference for the method cramer-von mises for having the lowest MSE

Highlighting the Importance of Matrix Metalloproteinase 1, 8, and 9 Expression during the Progression of Mycobacterium tuberculosis Infection

Tuberculosis (TB) is one of the major threats to public health; annually it kills more than 1.5 million people around the globe. Tuberculosis is caused by an intracellular pathogen named Mycobacterium tuberculosis (Mtb). This Mtb enters the lung through the respiratory passage by inhalation in healthy individuals. Infection of this disease starts from the settlement of Mtb to the lung alveoli of the host from the external bacilli air droplets. After settlement, the multiplication of Mtb results in the induction of innate immunity through the alveolar macrophages. Compared to other infectious diseases, tuberculosis infection was transmitted rapidly by the infected aerosols released from infected persons to healthy persons through the air. After infection, disease development results in the formation of drug-resistance TB (DR-TB) with four subcategories, i.e. Single-drug resistant TB (SDR-TB), multi-drug resistant TB (MDR-TB), extensive drug-resistant TB (XDR-TB), and total-drug resistant TB (TDR-TB). As a result, this DR-TB may act as a major source of TB death due to spontaneous antimicrobial resistance (AMR). This AMR makes the anti-TB drugs ineffective. In the current scenario, researchers are trying to find the drug target to decrease tuberculosis progression instead of drug resistance. The present review reports that the outcome of research studies showed that matrix metalloproteinase (MMP) may act as a suitable target for treating Mtb infection with the help of specific proteinase inhibitors. Recent reports have shown the specific role of matrix metalloproteinases 1, 8, and 9 in the disease progression and its role in normal homeostasis mechanism with the help of specific animal models/In vitro models.

Rifampicin resistant Mycobacterium tuberculosis in Vietnam, 2020–2022

ObjectiveWe conducted a descriptive analysis of multi-drug resistant tuberculosis (MDR-TB) in Vietnam’s two largest cities, Hanoi and Ho Chi Minh city. MethodsAll patients with rifampicin resistant tuberculosis were recruited from Hanoi and surrounding provinces between 2020 and 2022. Additional patients were recruited from Ho Chi Minh city over the same time period. Demographic data were recorded from all patients, and samples collected, cultured, whole genome sequenced and analysed for drug resistance mutations. Genomic susceptibility predictions were made on the basis of the World Health Organization’s catalogue of mutations in Mycobacterium tuberculosis associated with drug resistance, version 2. Comparisons were made against phenotypic drug susceptibility test results where these were available. Multivariable logistic regression was used to assess risk factors for previous episodes of tuberculosis. Results233/265 sequenced isolates were of sufficient quality for analysis, 146 (63 %) from Ho Chi Minh City and 87 (37 %) from Hanoi. 198 (85 %) were lineage 2, 20 (9 %) were lineage 4, and 15 (6 %) were lineage 1. 17/211 (8 %) for whom HIV status was known were infected, and 109/214 (51 %) patients had had a previous episode of tuberculosis. The main risk factor for a previous episode was HIV infection (odds ratio 5.1 (95 % confidence interval 1.3–20.0); p = 0.021). Sensitivity for predicting first-line drug resistance from whole genome sequencing data was over 90 %, with the exception of pyrazinamide (85 %). For moxifloxacin and amikacin it was 50 % or less. Among rifampicin-resistant isolates, prevalence of resistance to each non-first-line drug was < 20 %. ConclusionsDrug resistance among most MDR-TB strains in Vietnam’s two largest cities is confined largely to first-line drugs. Living with HIV is the main risk factor among patients with MDR-TB for having had a previous episode of tuberculosis.

Acquired rifamycin resistance among patients with tuberculosis and HIV in new York City, 2001–2023

IntroductionAcquired rifamycin resistance (ARR) in tuberculosis (TB) has been associated with HIV infection and can necessitate complicated TB treatment regimens, particularly in people living with HIV (PLWH). This work examines clinical characteristics and treatment outcomes of PLWH who developed ARR from 2001 to 2023 in New York City (NYC) to inform best practices for treating these patients. MethodsPLWH who developed ARR 2001–2023 were identified from the NYC TB registry. ResultsSixteen PLWH developed ARR; 15 were diagnosed 2001–2009 and the 16th was diagnosed in 2017. Median CD4 count was 48/mm3. On initial presentation, 14 had positive sputum cultures; of these, 12 culture-converted prior to developing ARR. Ten patients completed a course of TB treatment but subsequently relapsed; in six of these cases, ARR was discovered upon relapse, triggering treatment with a non-rifamycin-containing regimen, while in the other four, ARR was discovered during a second round of rifamycin-containing treatment. Three patients were lost to follow-up during their initial course of TB treatment and later returned to care; after being restarted on a rifamycin-containing regimen, ARR was discovered. Finally, three patients culture-converted during their first course of treatment but subsequently had cultures that grew rifamycin-resistant Mycobacterium tuberculosis prior to treatment completion, leading to changes in their treatment regimens. Among the 16 patients, eight died before being cured of TB, seven successfully completed treatment, and one was lost to follow-up. ConclusionsPLWH should be monitored closely for the development of ARR during treatment for TB, and sputum culture conversion should be interpreted cautiously in this group. Collecting a final sputum sample may be especially important for PLWH, as treatment failure and relapse were common in this population. The decrease in the number of cases of ARR among PLWH during the study period may reflect the decrease in the total number of PLWH diagnosed with TB in NYC in recent years, improved immune status of PLWH due to increased uptake of antiretroviral drugs, and improvements in the way anti-TB regimens are designed for PLWH (such as recommending daily rather than intermittent rifamycin dosing).

To study the profile of multi-drug resistant tuberculosis (MDR) TB patients on shorter regimen at a tertiary care Centre of North India

The effectiveness of shorter regimen for the treatment of MDR-TB patients was found in the study done by Damien Foundation in Bangladesh, therefore we planned to study the profile MDR-TB patients who were taking shorter regimen so that various factors can be explored related to this regimen in Indian scenario.This was a prospective longitudinal study done in respiratory medicine department between January 2020 to December 2021. There were 177 patients of MDR/ RR pulmonary TB were identified and as per inclusion criteria and based on exclusion criteria 84 patients were excluded therefore our study population comprised of 93 remaining patients those who filled the study protocol, their treatment (Injectable shorter regimen ) and follow up investigations done as per programmatic management of drug resistant TB guideline of National TB elimination programme. There were 55(59%) males and 38(41%) were females and mean age of patient was 31±15.11 years (range 4-82 years). Out of 93 patients 27(29%) were smokers and 25(27%) were alcoholics and the most common symptom was fever 92(98.9%). The most common comorbidity was diabetes mellitus 11(11.9%). The most common minor side effect seen was GI intolerance in 41(44.1%) patients.Out of 93 patients 76.3% (71) were cured and 23.7% (22) patients were failed to cure. The association between smoking and treatment outcome was statistically significant (p value=0.013). The association between treatment outcome and previous history of adequate treatment was found to be significant (p=0.016).

Rifampicin Resistant Tuberculosis Among Presumptive Pulmonary Tuberculosis in Province Referral Hospital, Indonesia: Dynamic Cases of a 7-Year Report.

Indonesia has the second highest tuberculosis (TB) cases globally. This study aimed to determine the sociodemographic factors associated with TB and rifampicin-resistant tuberculosis (RR-TB) cases among presumptive pulmonary TB patients in Aceh Referral Hospital. Study Design: A retrospective cross-sectional study. A retrospective cross-sectional review of presumptive pulmonary TB patients having a sputum test at the clinical microbiology laboratory was conducted from January 2015 to December 2021. Patient characteristics and drug susceptibility data were abstracted from the hospital information system of TB (SITB) and analyzed by univariate and bivariate analysis. The Mycobacterium tuberculosis (MTB) was detected in 32.8% sample (1,521/4,637). Of the TB-confirmed cases, 14.1% (215/1,521) were resistant to rifampicin (RR-TB). Most of them were male patients (71.63%), were in the age range of 35-54 years (48.7%), lived in rural areas of the country (56.3%), and were previously TB-treated cases (65.5%). Overall, 35-44-year-old patients (adjusted odds ratio [AOR]=2.11, 95% CI=1.25, 3.5, P<0.05) were more likely to have RR-TB compared to>65-year-old patients. Gender and residence were not associated with RR-TB (P>0.05). Case detection decreased in pandemic conditions (19.5% in 2019 to 13.9% and 7.91% in 2020 and 2021, respectively). The findings revealed the dynamic cases and sociodemographic factors of TB and RR-TB in a province referral hospital in Indonesia for 7 years. The cases of TB and RR-TB among presumptive TB patients were 32.8% and 14.1%, respectively. The cases were found to be more noticeable in males, adults (45-54 years old), and patients residing in rural areas.

Knowledge, attitudes, and practices towards childhood tuberculosis among healthcare workers at two primary health facilities in Lusaka, Zambia.

Zambia is among the 30 high-burden countries for tuberculosis (TB), Human Immunodeficiency Virus (HIV)-associated TB, and multi-drug resistant/rifampicin resistant TB with over 5000 children developing TB every year. However, at least 32% of the estimated children remain undiagnosed. We assessed healthcare workers' (HCWs) knowledge, attitudes, and practices (KAP) towards childhood TB and the factors associated with good KAP towards childhood TB. Data was collected at two primary healthcare facilities in Lusaka, Zambia from July to August 2020. Structured questionnaires were administered to HCWs that were selected through stratified random sampling. Descriptive analysis was done to determine KAP. A maximum knowledge, attitude, and practice scores for a participant were 44, 10, and 8 points respectively. The categorization as either "poor" or "good" KAP was determined based on the mean/ median. Logistic regression analysis was performed to assess the associations between participant characteristics and KAP at statistically significant level of 0.05%. Among the 237 respondents, majority were under 30 years old (63.7%) and were female (72.6%). Half of the participants (50.6%) were from the outpatient department (OPD) and antiretroviral therapy (ART) clinic, 109 (46.0) had been working at the facility for less than 1 year, 134 (56.5%) reported no previous training in TB. The median/mean KAP scores were 28 (IQR 24.0-31.0), 7 (IQR = 6.0-8.0) and 5 points (SD = 1.9) respectively. Of the participants, 43.5% (103/237) had good knowledge, 48.1% (114/237) had a good attitude, and 54.4% (129/237) had good practice scores on childhood TB. In the multivariate analysis, clinical officers and individuals with 1-5 years' work experience at the facility had higher odds, 2.61 (95% CI = 1.18-5.80, p = 0.018) and 3.09 (95% CI = 1.69-5.65, p = 0.001) of having good attitude respectively, and medical doctors had 0.17 lower odds (95% CI = 0.18-5.80, p = 0.018) of good childhood TB practice. Other participant characteristics didn't show a significant association with the scores. The study found suboptimal levels of knowledge, attitude, and practices regarding childhood TB among HCWs. Targeted programmatic support needs to be provided to address the above gaps.

Genetic mechanisms of co-emergence of INH-resistant Mycobacterium tuberculosis strains during the standard course of antituberculosis therapy.

The incidence of isoniazid (INH) resistant Mycobacterium tuberculosis is increasing globally. This study aimed to identify the molecular mechanisms behind the development of INH resistance in M. tuberculosis strains collected from the same patients during the standard course of treatment. Three M. tuberculosis strains were collected from a patient before and during antituberculosis (anti-TB) therapy. The strains were characterized using phenotypic drug susceptibility tests, Mycobacterial Interspersed Repeated Unit-Variable-Number Tandem Repeats (MIRU-VNTR), and whole-genome sequencing (WGS) to identify mutations associated with INH resistance. To validate the role of the novel mutations in INH resistance, the mutated katG genes were electroporated into a KatG-deleted M. tuberculosis strain (GA03). Three-dimensional structures of mutated KatG were modeled to predict their impact on INH binding. The pre-treatment strain was susceptible to INH. However, two INH-resistant strains were isolated from the patient after anti-TB therapy. MIRU-VNTR and WGS revealed that the three strains were clonally identical. A missense mutation (P232L) and a nonsense mutation (Q461Stop) were identified in the katG of the two post-treatment strains, respectively. Transformation experiments showed that katG of the pre-treatment strain restored INH susceptibility in GA03, whereas the mutated katG genes from the post-treatment strains rendered negative catalase activity and INH resistance. The protein model indicated that P232L reduced INH-KatG binding affinity while Q461Stop truncated gene transcription. Our results showed that the two katG mutations, P232L and Q461Stop, accounted for the co-emergence of INH-resistant clones during anti-TB therapy. The inclusion of these mutations in the design of molecular assays could increase the diagnostic performance.IMPORTANCEThe evolution of drug-resistant strains of Mycobacterium tuberculosis within the lung lesions of a patient has a detrimental impact on treatment outcomes. This is particularly concerning for isoniazid (INH), which is the most potent first-line antimycobacterial drug. However, the precise genetic factors responsible for drug resistance in patients have not been fully elucidated, with approximately 15% of INH-resistant strains harboring unknown genetic factors. This raises concerns about the emergence of drug-resistant clones within patients, further contributing to the global epidemic of resistance. In this study, we revealed the presence of two novel katG mutations, which emerged independently due to the stress exerted by antituberculosis (anti-TB) treatment on a parental strain. Importantly, we experimentally demonstrated the functional significance of both mutations in conferring resistance to INH. Overall, this research sheds light on the genetic mechanisms underlying the evolution of INH resistance within patients and provides valuable insights for improving diagnostic performance by targeting specific mutations.

Bacteriophage therapy for the treatment of Mycobacterium tuberculosis infections in humanized mice

The continuing emergence of new strains of antibiotic-resistant bacteria has renewed interest in phage therapy; however, there has been limited progress in applying phage therapy to multi-drug resistant Mycobacterium tuberculosis (Mtb) infections. In this study, we show that bacteriophage strains D29 and DS6A can efficiently lyse Mtb H37Rv in 7H10 agar plates. However, only phage DS6A efficiently kills H37Rv in liquid culture and in Mtb-infected human primary macrophages. We further show in subsequent experiments that, after the humanized mice were infected with aerosolized H37Rv, then treated with DS6A intravenously, the DS6A treated mice showed increased body weight and improved pulmonary function relative to control mice. Furthermore, DS6A reduces Mtb load in mouse organs with greater efficacy in the spleen. These results demonstrate the feasibility of developing phage therapy as an effective therapeutic against Mtb infection.

Direct TAMRA-dUTP labeling of M. tuberculosis genes using loop-mediated isothermal amplification (LAMP)

Fluorescent molecule-based direct labeling of amplified DNA is a sensitive method employed across diverse DNA detection and diagnostics systems. However, using pre-labeled primers only allows for the attachment of a single fluorophore to each DNA strand and any modifications of the system are less flexible, requiring new sets of primers. As an alternative, direct labeling of amplified products with modified nucleotides is available, but still poorly characterized. To address these limitations, we sought a direct and adaptable approach to label amplicons produced through Loop-mediated isothermal amplification (LAMP), using labeled nucleotides (dUTPs) rather than primers. The focus of this study was the development and examination of a direct labeling technique of specific genes, including those associated with drug resistance in Mycobacterium tuberculosis. We used 5-(3-Aminoallyl)-2′-deoxyuridine-5′triphosphate, tagged with 5/6-TAMRA (TAMRA-dUTP) for labeling LAMP amplicons during the amplification process and characterized amplification and incorporation efficiency. The optimal TAMRA-dUTP concentration was first determined based on amplification efficiency (0.5% to total dNTPs). Higher concentrations of modified nucleotides reduced or completely inhibited the amplification yield. Target size also showed to be determinant to the success of amplification, as longer sequences showed lower amplification rates, thus less TAMRA incorporated amplicons. Finally, we were able to successfully amplify all four M. tuberculosis target genes using LAMP and TAMRA-modified dUTPs.

Prediction of pyrazinamide resistance in Mycobacterium tuberculosis using structure-based machine-learning approaches.

Pyrazinamide is one of four first-line antibiotics used to treat tuberculosis; however, antibiotic susceptibility testing for pyrazinamide is challenging. Resistance to pyrazinamide is primarily driven by genetic variation in pncA, encoding an enzyme that converts pyrazinamide into its active form. We curated a dataset of 664 non-redundant, missense amino acid mutations in PncA with associated high-confidence phenotypes from published studies and then trained three different machine-learning models to predict pyrazinamide resistance. All models had access to a range of protein structural-, chemical- and sequence-based features. The best model, a gradient-boosted decision tree, achieved a sensitivity of 80.2% and a specificity of 76.9% on the hold-out test dataset. The clinical performance of the models was then estimated by predicting the binary pyrazinamide resistance phenotype of 4027 samples harbouring 367 unique missense mutations in pncA derived from 24 231 clinical isolates. This work demonstrates how machine learning can enhance the sensitivity/specificity of pyrazinamide resistance prediction in genetics-based clinical microbiology workflows, highlights novel mutations for future biochemical investigation, and is a proof of concept for using this approach in other drugs.

Synergistic combination of antimicrobial peptide and isoniazid as inhalable dry powder formulation against multi-drug resistant tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) has posed a serious threat to global public health, and antimicrobial peptides (AMPs) have emerged to be promising candidates to tackle this deadly infectious disease. Previous study has suggested that two AMPs, namely D-LAK120-A and D-LAK120-HP13, can potentiate the effect of isoniazid (INH) against mycobacteria. In this study, the strategy of combining INH and D-LAK peptide as a dry powder formulation for inhalation was explored. The antibacterial effect of INH and D-LAK combination was first evaluated on three MDR clinical isolates of Mycobacteria tuberculosis (Mtb). The minimum inhibitory concentrations (MICs) and fractional inhibitory concentration indexes (FICIs) were determined. The combination was synergistic against Mtb with FICIs ranged from 0.25 to 0.38. The INH and D-LAK peptide at 2:1 mole ratio (equivalent to 1: 10 mass ratio) was identified to be optimal. This ratio was adopted for the preparation of dry powder formulation for pulmonary delivery, with mannitol used as bulking excipient. Spherical particles with mass median aerodynamic diameter (MMAD) of around 5 µm were produced by spray drying. The aerosol performance of the spray dried powder was moderate, as evaluated by the Next Generation Impactor (NGI), with emitted fraction and fine particle fraction of above 70 % and 45 %, respectively. The circular dichroism spectra revealed that both D-LAK peptides retained their secondary structure after spray drying, and the antibacterial effect of the combination against the MDR Mtb clinical isolates was successfully preserved. The combination was found to be effective against MDR Mtb isolates with KatG or InhA mutations. Overall, the synergistic combination of INH with D-LAK peptide formulated as inhaled dry powder offers a new therapeutic approach against MDR-TB.

Exploring the Therapeutic Benefits of Silymarin Herbal Extract as a Supplement to Pulmonary Tuberculosis Treatment: A Comprehensive Review from Laboratory to Clinical Trials

Abstract: Indonesia is ranked second in the number of tuberculosis (TB) cases with an incidence rate of 300 per 1000 population. A combination of antibiotics with a minimum six-month-administration regimen is an effective first line of TB treatment. Silymarin (Sm) is a plant extract which is known to have hepatoprotective and anti-microbial effects. This literature review aimed to discuss the potential of Sm in pulmonary TB treatment, starting from laboratory studies to clinical trials in humans. Studies on the use of Sm in tuberculosis literatures were obtained from a rapid systematic search in Pubmed and ScienceDirect databases. Supporting articles were searched based on specific keywords with inclusion criteria. The in vitro test showed immunomodulatory and bactericidal capacities of Sm against Mycobacterium tuberculosis. The in vivo test of Sm administration showed that Sm was able to increase the percentage of macrophage cells expressing the cytokines NF-κB and IFN-β. Sm had a bactericidal effect at levels &gt;50 μM. The hepatoprotective character of Sm could prevent the increase in liver enzymes in mice receiving anti-TB drugs. Clinical trials showed that administration of Sm could prevent anti-tuberculosis drug hepatoxicity. In conclusion, silymarin has the potential to be an adjuvant therapy for the treatment of anti-TB drug-sensitive or resistant tuberculosis, as well as protection against the hepatotoxic properties of anti-TB drugs. Keywords: tuberculosis; silymarin; supplementation therapy; antituberculosis therapy

Rapid detection of multidrug resistance in tuberculosis using nanopore-based targeted next-generation sequencing: a multicenter, double-blind study.

Resistance to anti-tuberculous drugs is a major challenge in the treatment of tuberculosis (TB). We aimed to evaluate the clinical availability of nanopore-based targeted next-generation sequencing (NanoTNGS) for the diagnosis of drug-resistant tuberculosis (DR-TB). This study enrolled 253 patients with suspected DR-TB from six hospitals. The diagnostic efficacy of NanoTNGS for detecting Mycobacterium tuberculosis and its susceptibility or resistance to first- and second-line anti-tuberculosis drugs was assessed by comparing conventional phenotypic drug susceptibility testing (pDST) and Xpert MTB/RIF assays. NanoTNGS can be performed within 12 hours from DNA extraction to the result delivery. NanoTNGS showed a remarkable concordance rate of 99.44% (179/180) with the culture assay for identifying the Mycobacterium tuberculosis complex. The sensitivity of NanoTNGS for detecting drug resistance was 93.53% for rifampicin, 89.72% for isoniazid, 85.45% for ethambutol, 74.00% for streptomycin, and 88.89% for fluoroquinolones. Specificities ranged from 83.33% to 100% for all drugs tested. Sensitivity for rifampicin-resistant tuberculosis using NanoTNGS increased by 9.73% compared to Xpert MTB/RIF. The most common mutations were S531L (codon in E. coli) in the rpoB gene, S315T in the katG gene, and M306V in the embB gene, conferring resistance to rifampicin, isoniazid, and ethambutol, respectively. In addition, mutations in the pncA gene, potentially contributing to pyrazinamide resistance, were detected in 32 patients. Other prevalent variants, including D94G in the gyrA gene and K43R in the rpsL gene, conferred resistance to fluoroquinolones and streptomycin, respectively. Furthermore, the rv0678 R94Q mutation was detected in one sample, indicating potential resistance to bedaquiline. NanoTNGS rapidly and accurately identifies resistance or susceptibility to anti-TB drugs, outperforming traditional methods. Clinical implementation of the technique can recognize DR-TB in time and provide guidance for choosing appropriate antituberculosis agents.

Empowering care: Unleashing pharmaceutical care to confront MDR-TB transmission risks-A prospective interventional study

IntroductionAccording to recent NTEP report it was estimated that in India the MDR-TB cases were 9.1/lakh population. Patients undergoing the pulmonary TB are known to cause MDR-TB due to multi drug resistance. Early identification of risk elements in Multidrug resistant-TB patients is crucial to managing and preventing the disease. ObjectiveTo evaluate risk variables that contribute to cause Multidrug resistant tuberculosis and to providing patient counselling to TB patients regarding risk factors. Methodology: A Prospective interventional study to assess the various Risk factors involved in cause of Multi drug resistance tuberculosis. This study was conducted for period of 09 months. The study is conducted with standard validated questionnaires which are prepared to assess the risk factors among Multidrug resistant-TB patients. Study site includes the tertiary care hospitals in Belagavi. ResultOverall, 120 Multidrug resistant tuberculosis patients were recruited from the district tuberculosis centre, Belagavi District, Karnataka. India. Most patients (47.50%) were aged 25–44 years. Of the 120 MDR-TB patients, 67.50% are male and 32.5% are female. Of 120 MDR-TB patients, 7.50% are HIV positive. As part of the study, smoking (26.67%), chewing tobacco (50%), and alcohol consumption (33.33%) were found to be other major risk factors. 24.17% of patients had a family history of tuberculosis, of which 5% had contact with an infected person as a source of infection. ConclusionThis study documented various risk variables involved in the emergence of Multidrug resistant TB. This research also highlighted the significance of pharmaceutical care in the effective management of multidrug-resistant tuberculosis (MDR-TB). This study identified risk variables that contribute to MDR-TB and helped educate tuberculosis patients about these risk factors.

Estimation of country-specific tuberculosis resistance antibiograms using pathogen genomics and machine learning

BackgroundGlobal tuberculosis (TB) drug resistance (DR) surveillance focuses on rifampicin. We examined the potential of public and surveillance Mycobacterium tuberculosis (Mtb) whole-genome sequencing (WGS) data, to generate expanded country-level resistance...

Diagnostic Accuracy of The TrueNat MTB/RIF Assay And Comparison With The Reference Standards To Detect Pulmonary Tuberculosis And Rifampicin Resistance in Sputum Samples From Patients Attending A Tertiary Care Hospital in Bhubaneswar, India

Background: A rapid and accurate diagnostic tool is necessary for correct diagnosis and treatment of TB. This study evaluated and compared the sensitivity, specificity and concordance of TrueNAT MTB/RIF assay with smear microscopy, Xpert MTB/RIF and MGIT culture. Methods: In all, 4500 patients (1500 each of patients with Diabetes, elderly and HIV-positive patients) attending the Chest and TB department of Capital Hospital, Bhubaneswar were screened. 392 sputum samples were collected from presumptive TB patients. Standard diagnostic procedures (Smear Microscopy, Xpert MTB/RIF, TrueNAT MTB tests and MGIT culture) were performed. Results: This diagnostic efficiency of rapid molecular TrueNAT MTB/RIF assays have similar properties as Xpert MTB/RIF and may be used for the diagnosis of TB and Rifampicin resistance. Among participants, the TrueNAT MTB shows the sensitivity of 80%, 100% and 78.26% while the specificity was 97.9%, 95.83% and 100%. The concordance rates between all tests were calculated and the TrueNAT MTB showed good agreement with the culture method among study participants (κ = 0.793, 0.554, and 0.862, respectively). Conclusion: The TrueNAT assays are sensitive for diagnosis of TB patients with faster turnabout time from testing to treatment and economical.

Tuberculosis prevalence and rifampicin resistance among presumptive patients in Nasarawa State: A three-year retrospective study

Objective: To investigate the prevalence and rifampicin resistance of tuberculosis among presumptive patients in Nasarawa state, Nigeria. Methods: Patient data collected from January 2019 to December 2021 were retrospectively computed from the register at the tuberculosis laboratory of Dalhatu Araf Specialist Hospital, Lafia. A total of 91884 patient records were analyzed to determine tuberculosis prevalence, rifampicin resistance, and patients’ characteristics using Chi-squared test. Results: An overall prevalence of 8.0% was recorded among presumptive patients over the three-year period with a decreasing trend in prevalence from 10.0% (2019) to 6.5% (2021), though the number of samples progressively increased each year and more than doubled in 2021. Most of the patients tested for tuberculosis were females (52.6%) and were mostly older than 15 years (84.1%). Conversely, a higher resistance to rifampicin was observed among tuberculosis positive male patients (55.6%) than in females (44.4%). Similarly, tuberculosis positive patients older than 15 years (84.6%) showed greater resistance to rifampicin than those younger than 15 years (15.4%). Statistically, no relationship was established among age, sex, year of sampling and tuberculosis prevalence or rifampicin resistance rate. Conclusions: Despite the downward trends in tuberculosis prevalence and rifampicin resistance rate observed in this study, measures at maintaining the gains achieved in the fight against tuberculosis must remain paramount as the race towards reducing tuberculosis incidence and mortality by 2025 continues.

Factors Associated with Non-Adherence to Treatment Among Migrants with MDR-TB in Wuhan, China: A Cross-Sectional Study.

Multidrug resistant tuberculosis (MDR-TB) has attracted increasing attention in achieving the global goal of tuberculosis (TB) control. China has the second largest TB burden worldwide and has been experiencing large-scale domestic migration. This study aims to explore the effect of migrants on non-adherence to MDR-TB treatment. A cross-sectional study was carried out in Wuhan, China. The exposure cases were migrants who were not locally registered in the residence registration system. The control cases were local residents. Non-adherence cases were patients who were lost follow-up or refused treatment. Chi-square and t-test were used to compare variables between migrants and local residents. Logistic regression models using enter method were used to determine the relationship between migration and non-adherence to treatment. Moderation and medication effects on the association between migrant status and non-adherence were also explored. We studied 73 migrants and 219 local residents. The migrants, who did not to adhere to treatment (55, 75.3%), was far higher than that of local residents (89, 40.6%). Migrants with MDR-TB had 10.38-times higher difficulty in adhering to treatment (adjusted OR = 10.38, 95% CI 4.62-25.28) than local residents. This additional likelihood was moderated by age and treatment registration group. Migration had an indirect association with non-adherence to treatment via social medial insurance (adjusted OR = 1.05, 95% CI 1.01-1.13). There a significant increased likelihood of non-adherence to treatment among migrants with MDR-TB, highlighting the importance of improving treatment adherence in this population. Migration prevented migrants from gaining access to social medical insurance and indirectly reduced their likelihood of adherence to treatment.

Association between biomarkers of inflammation and dyslipidemia in drug resistant tuberculosis in Uganda

BackgroundActive tuberculosis (TB) significantly increases the risk of cardiovascular disease, but the underlying mechanisms remain unclear. This study aimed to investigate the association between inflammation biomarkers and dyslipidemia in patients with drug-resistant TB (DR-TB).MethodsThis was a secondary analysis of data from a cross-sectional multi-center study in Uganda conducted 2021. Participants underwent anthropometric measurements and laboratory tests included a lipid profile, full haemogram and serology for HIV infection. Dyslipidemia was defined as total cholesterol > 5.0 mmol/l and/or low-density lipoprotein cholesterol > 4.14 mmol/l, and/or triglycerides (TG) ≥ 1.7 mmol/l, and/or high density lipoprotein cholesterol (HDL-c) < 1.03 mmol/l for men and < 1.29 mmol/l for women. Biomarkers of inflammation were leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil/lymphocyte (NLR), platelet/lymphocyte, and lymphocyte/monocyte (LMR) ratios, mean corpuscular volume (MCV), and the systemic immune inflammation index (SII) (neutrophil × platelet/lymphocyte). Modified Poisson Regression analysis was used for determining the association of the biomarkers and dyslipidemia.ResultsOf 171 participants, 118 (69.0%) were co-infected with HIV. The prevalence of dyslipidemia was 70.2% (120/171) with low HDL-c (40.4%, 69/171) and hypertriglyceridemia (22.5%, 38/169) being the most common components. Patients with dyslipidemia had significantly higher lymphocyte (P = 0.008), monocyte (P < 0.001), and platelet counts (P = 0.014) in addition to a lower MCV (P < 0.001) than those without dyslipidemia. Further, patients with dyslipidemia had lower leucocyte (P < 0.001) and neutrophil (P = 0.001) counts, NLR (P = 0.008), LMR (P = 0.006), and SII (P = 0.049). The MCV was inversely associated with low HDL-C (adjusted prevalence ratio (aPR) = 0.97, 95% CI 0.94–0.99, P = 0.023) but was positively associated with hypertriglyceridemia (aPR = 1.04, 95% CI 1.00-1.08, P = 0.052).ConclusionsIndividuals with dyslipidemia exhibited elevated lymphocyte, monocyte, and platelet counts compared to those without. However, only MCV demonstrated an independent association with specific components of dyslipidemia. There is need for further scientific inquiry into the potential impact of dyslipidemia on red cell morphology and a pro-thrombotic state among patients with TB.