anti-TB Treatment Research Articles

Tuberculous Meningitis: Is the Fixed Dose Anti-TB treatment strategy effective? Case report from Sri Lanka (P3-10.002)

Tuberculous Meningitis: Is the Fixed Dose Anti-TB treatment strategy effective? Case report from Sri Lanka (P3-10.002)

Anemia and anti-tuberculosis treatment outcome in persons with pulmonary tuberculosis: A multi-center prospective cohort study

BackgroundTuberculosis (TB) remains a major plague of humanity. People with TB (PWTB) are commonly anemic. Here, we assessed whether the severity of anemia in PWTB prior to anti-TB treatment (ATT) was a risk factor for an unfavorable outcome. MethodsPatients ≥ 18 years old with culture-confirmed drug-susceptible pulmonary TB enrolled between 2015 and 2019 in a multi-center Brazilian cohort were followed for up to 24 months and classified according to anemia severity (mild, moderate, and severe), based on hemoglobin levels. A multinomial logistic regression model was employed to assess whether anemia was associated with unfavorable outcome (death, failure, loss to follow-up, regimen modification or relapse), compared to treatment success (cure or treatment completion). ResultsAmong 786 participants who met inclusion criteria, 441 (56 %) were anemic at baseline. Patients with moderate/severe anemia were more HIV-seropositive, as well as more symptomatic and had higher frequencies of unfavorable outcomes compared to the other groups. Moderate/severe anemia (adjusted OR [aOR]: 7.80, 95 %CI:1.34–45.4, p = 0.022) was associated with death independent of sex, age, BMI, HIV and glycemic status. ConclusionModerate/severe anemia prior to ATT was a significant risk factor for death. Such patients should be closely monitored given the high risk of unfavorable ATT outcomes.

Observation Study among Cured Cases of Pulmonary Tuberculosis: A Long-Term Study under the Revised National Tuberculosis Control Program

Background: Tuberculosis is one of the leading causes of mortality in India. The Revised National Tuberculosis Control Program (RNTCP) is a robust public health system to deal with Tuberculosis (TB) in India. Unless the treated patient comes back to the system with signs and symptoms of TB due to relapse or reinfection, there is no mechanism of follow-up or any method to know the relapse rate in the population. This study aimed to analysed trends in relapse tuberculosis cases and describe their associations with socio-demographic and clinical factors.Subjects dan Method: In this prospective cohort study, 750 selected sample size who were declared “Cured” in four randomly selected TB units of Gwalior district were followed up for 1–5 years through home visits by trained staff with structured data collection forms. Data Collection was done between January 2022 to June 2022 and afterwards analyzed using Microsoft excel spreadsheet.Results: The mean age of the index cases was Mean= 30.53; SD= 14.24 years, and there were 39 females and 64 males. At early stage (1-to-2-year posttreatment follow-up of 248 index cases) 199 (80.2%) were healthy and working without any symptoms of TB. Symptoms of TB were present in 49 (19.8%) cases. The after 2-year posttreatment TB Symptoms were present in 54 (19.3%) cases.Conclusion: Long-term follow-up of cured, new smear-positive TB cases reinforce the effectiveness of anti-TB treatment under the RNTCP as assessed by improved health outcomes in more than two-thirds of cases and posttreatment survival of 80.72% of index cases. Further investigation needed to continue such follow-up for all TB cases treated under the RNTCP for effective end-TB strategy. Keywords: tuberculosis treatment, follow-up, relapses, RNTCP Correspondence: Ramniwas Mahore. Department Of Community Medicine. G R Medical College Gwalior 474009 Madhya Pradesh, India. Email: Drmahore@gmail.com. Mobile: 9425334365.

Simultaneous Determination of Rifamycin Antibiotics and Their Active Metabolites in Human Plasma Using UHPLC-MS/MS to Evaluate Their Impact on Target Peak Concentrations: A Short Communication.

Standard and proper antituberculosis (anti-TB) treatment is essential for patients with TB, and rifamycin antibiotics are key components of anti-TB therapy. Therapeutic drug monitoring (TDM) of rifamycin antibiotics can shorten the time to response and complete treatment of TB. Notably, antimicrobial activities of the major active metabolites of rifamycin are similar to those of their parent compounds. Thus, a rapid and simple assay was developed for simultaneous determination of rifamycin antibiotics and their major active metabolites in plasma to evaluate their impact on target peak concentrations. Here, the authors have developed and validated a method for simultaneous determination of rifamycin antibiotics and their active metabolites in human plasma using ultrahigh-performance liquid chromatography tandem mass spectrometry. Analytical validation of the assay was performed in accordance with the bioanalytical method validation guidance for industry described by the US Food and Drug Administration and the guidelines for bioanalytical method validation described by the European Medicines Agency. The drug concentration quantification method for rifamycin antibiotics, including rifampicin, rifabutin, and rifapentine, and their major active metabolites was validated. Significant differences in the proportions of active metabolites in rifamycin antibiotics may affect the redefinition of their effective concentration ranges in the plasma. The method developed herein is expected to redefine the ranges of "true" effective concentrations of rifamycin antibiotics (including parent compounds and their active metabolites). The validated method can be successfully applied for high-throughput analysis of rifamycin antibiotics and their active metabolites for TDM in patients receiving anti-TB treatment regimens containing these antibiotics. Proportions of active metabolites in rifamycin antibiotics markedly varied among individuals. Depending on the clinical indications of patients, the therapeutic ranges for rifamycin antibiotics may be redefined.

A challenging high-risk surgery for necrotizing pneumonia in a right bilobed lung

BackgroundNecrotizing pneumonia is rare in children and is one of the most serious complications of a lung infection caused by antibiotic failure. We present a 12-year-old leukopenic child with a long-lasting lung infection, presenting as having a lung hydatid cyst, but diagnosing with necrotizing pneumonia in the right bilobed lung. Failure to medical treatment and ongoing leukopenia justified surgical intervention with positive results.Case presentationThe patient was referred to our teaching hospital’s pediatric surgery department. He had previously been diagnosed with intestinal tuberculosis (TB) and received anti-TB treatment. On referral to our hospital, the patient was suffering from restlessness, frequent coughing, fever, vomiting, and diarrhea. Following the completion of the clinical work-up, a blood test revealed leukopenia (white blood cell count of 2100/microliter), a normal platelet count, and a lesion in the right lung. Computerized tomography scanning (CT-Scan) image reported a lung hydatid cyst. In the pediatrics ward, a broad-spectrum antibiotics regimen with triple-antibiotic therapy (linezolid, vancomycin, and metronidazole) was instituted and continued for a week with no response, but worsening of the condition. In the pediatric surgery ward, our decision for surgical intervention was due to the failure of medical treatment because of a pulmonary lesion. Our team performed right lung upper lobe anterior segment wedge resection due to necrotizing pneumonia and followed the patient 45 days post-operation with a reasonable result.ConclusionLiving in remote rural areas with low resources and inaccessibility to proper and specialized diagnostic and treatment centers will all contribute to an improper diagnosis and treatment of lung infection. In total, all of these will increase the morbidity and mortality due to lung necrosis in the pediatric population, regardless of their age. In low-resource facilities, high-risk patients can benefit from surgical intervention to control the ongoing infection process.

Detection of antigen Ag85B expression is useful for the diagnosis of tuberculosis, especially for those with an antituberculosis treatment history.

The present study used immunohistochemistry (IHC) to detect antigen Ag85B in tissue sections and aimed to evaluate its validity in histopathologic diagnosis of tuberculosis (TB). In total, 204 patients with confirmed TB and 40 other diseases were included in the present study. Ziehl-Neelsen (Z-N) stains, IHC (anti-Ag85B), and quantitative fluorescence polymerase chain reaction were used to detect acid-fast bacilli, Mycobacterium tuberculosis (MTB) antigen, and MTB DNA. Immunohistochemistry was significantly more sensitive than Z-N stains (93.1% vs 67.2%; P < .001). The sensitivity of Z-N stains significantly correlated with anti-TB treatment history. The sensitivity of Z-N stains was lower in rifampicin (RIF)-resistant TB compared with RIF-sensitive TB (52.8% vs 69.0%; P = .091) and those without treatment history (52.8% vs 84.0%; P = .015). However, IHC was not significantly affected by treatment history (P = .410). Moreover, expression patterns of Ag85B were dependent on treatment history and commonly showed weak scattered spots in RIF-susceptible TB. Conversely, strong brown rods were often found in those with RIF-resistant TB. Immunohistochemistry is a simple, sensitive technique for the diagnosis of TB, especially for those patients with treatment history. The expression pattern of Ag85B is a potential marker for evaluating anti-TB treatment response.

Factors Associated with the Effectiveness of Regimens for the Treatment of Tuberculosis in Patients Coinfected with HIV/AIDS: Cohort 2015 to 2019.

(1) Background: Infection with the Human Immunodeficiency Virus (HIV) is a significant challenge for tuberculosis (TB) control, with increasing mortality rates worldwide. Moreover, the loss to follow-up is very high, with low adherence to treatment, resulting in unfavorable endpoints. This study aimed to analyze the effectiveness of TB treatment in patients coinfected with HIV/AIDS and its associated factors. (2) Methods: Patients coinfected with TB and HIV/AIDS at a Reference Hospital for infectious diseases were followed up for a maximum of one year from the start of TB treatment until cure or censorship (death, abandonment, and transfer) from 2015 to 2019. The Cox proportional model was used to identify risk factors for effectiveness. (3) Results: Of the 244 patients included in the cohort, 58.2% (142/244) had no treatment effectiveness, 12.3% (30/244) died, and 11.1% (27/244) abandoned treatment. Viral suppression at the onset of TB treatment (HR = 1.961, CI = 1.123-3.422), previous use of Antiretroviral Therapy (HR = 1.676, CI = 1.060-2.651), new cases (HR = 2.407, CI = 1.197-3.501), not using illicit drugs (HR = 1.763, CI = 1.141-2.723), and using the basic TB regimen (HR = 1.864, CI = 1.084-3.205) were significant variables per the multivariate Cox regression analysis. (4) Conclusion: TB treatment for most TB patients coinfected with HIV/AIDS was not effective. This study identified that an undetectable viral load at the beginning of the disease, previous use of ART, not using illicit drugs and not having previously taken anti-TB treatment are factors associated with successful TB treatment.

CeRNA network identified hsa-miR-17-5p, hsa-miR-106a-5p and hsa-miR-2355-5p as potential diagnostic biomarkers for tuberculosis.

This study aims to analyze the regulatory non-coding RNAs in the pathological process of tuberculosis (TB), and identify novel diagnostic biomarkers. A longitudinal study was conducted in 5 newly diagnosed pulmonary tuberculosis patients, peripheral blood samples were collected before and after anti-TB treatment for 6 months, separately. After whole transcriptome sequencing, the differentially expressed RNAs (DE RNAs) were filtrated with |log2 (fold change) | > log2(1.5) and P value < .05 as screening criteria. Then functional annotation was actualized by gene ontology enrichment analysis, and enrichment pathway analysis was conducted by Kyoto Encyclopedia of Genes and Genomes database. And finally, the competitive endogenous RNA (ceRNA) regulatory network was established according to the interaction of ceRNA pairs and miRNA-mRNA pairs. Five young women were recruited and completed this study. Based on the differential expression analysis, a total of 1469 mRNAs, 996 long non-coding RNAs, 468 circular RNAs, and 86 miRNAs were filtrated as DE RNAs. Functional annotation demonstrated that those DE-mRNAs were strongly involved in the cellular process (n = 624), metabolic process (n = 513), single-organism process (n = 505), cell (n = 651), cell part (n = 650), organelle (n = 569), and binding (n = 629). Enrichment pathway analysis revealed that the differentially expressed genes were mainly enriched in HTLV-l infection, T cell receptor signaling pathway, glycosaminoglycan biosynthesis-heparan sulfate/heparin, and Hippo signaling pathway. CeRNA networks revealed that hsa-miR-17-5p, hsa-miR-106a-5p and hsa-miR-2355-5p might be regarded as potential diagnostic biomarkers for TB. Immunomodulation-related genes are differentially expressed in TB patients, and hsa-miR-106a-5p, hsa-miR-17-5p, hsa-miR-2355-5p might serve as potential diagnostic biomarkers.

Gut microbiota characteristics of Mongolian and Han populations in anti-tuberculosis drug-induced liver injury: a population-based case–control study

BackgroundThe pathogenesis of anti-tuberculosis (TB) drug-induced liver injury (ADLI) is complicated and remains unclear. We aimed to analyse the relationship between the characteristics of gut microbiota and ADLI in Mongolian and Han patients with pulmonary TB and identify the most notable bacteria related to the occurrence of liver injury in those populations.MethodsPatients with concurrent liver injury (LI) and no liver injury (ULI) before receiving first-line anti-TB drug treatment (T1) from the Han population in Tangshan and the Mongolian population in Inner Mongolia were selected as research subjects. At the time of liver injury (T2), stool samples were measured by bacterial 16S rRNA gene high-throughput sequencing to analyse and compare the differences in the gut microbiota of the LI and ULI Mongolian and Han patients at T1 and T2 and identify the differences between those patients.ResultsA total of 45 Mongolian and 37 Han patients were enrolled in our study. A dynamic comparison from T1 to T2 showed that the microbiota of the LI and ULI groups changed significantly from T1 to T2 in both the Mongolian and Han populations. However, there were commonalities and personality changes in the microbiota of the two ethnic groups.ConclusionDifferences in gut microbes in ADLI were found among the Han and Mongolian patients in our study. Ekmania and Stenotrophomonas were related to the occurrence of ADLI in Mongolian patients, while Ekmania and Ruminococcus__gnavus_group were related to the occurrence of ADLI in the Han population.

Gut microbiome variation in pulmonary TB patients with diabetes or HIV comorbidities

BackgroundThe gut microbiota is known to play a critical role in shaping the host immunity, and metabolism and influences the onset and progression of both communicable and non-communicable diseases. This study assessed the gut microbiome of tuberculosis (TB) cases with diabetes mellitus (DM) or HIV comorbidities before anti-TB therapy and after the intensive phase anti-TB therapy.MethodsNinety cases comprising 60 TB-only, 23 TB-DM, 7 TB-HIV were recruited, among which 35 TB-only, 10 TB-DM, 5 TB-HIV were also sampled after 2 months of anti-TB treatment. Total gut microbiome was detected by 16S rRNA gene sequencing of DNA extracted from collected stool specimen. The taxonomic and functional diversity of the different groups were compared in addition to changes that could occur after 2 months antibiotics use.ResultsCompared to the healthy controls, the gut microbiome of all the TB cohorts was characterized by a significant decreased alpha diversity and significant compositional changes. All the three TB cohorts were enriched with inflammatory related microorganisms of the genera Escherichia-shigella, Streptococcus, Enterococcus and Erysipelatoclostridium with depletion in beneficial taxa of the genera Faecalibacterium, Bifidobacterium and Clostridium. In pairwise comparison with the healthy controls, the TB-only cohort were enriched with Streptococcus and Erysipelatoclostridium, the TB-DM enriched with Bacteroides, and TB-HIV enriched with Escherichia-shigella, Dialister and Erysipelatoclostridium. After the intensive phase anti-TB therapy, there was general enrichment of the genera Erysipelotrichaceae_UCG 003, Veillonella and Fusobacterium.ConclusionOur findings show a dysbiotic gut microbiome and associated upregulation of inflammation related microorganism in gut microbiome of TB individuals with or without comorbidity.

Abdominal Tuberculosis in Children: A Case Series of Five Patients

Tuberculosis remains (TB) to be one of the most common causes of child morbidity and mortality. Abdominal TB is not frequently diagnosed and, although its incidence is not definitively established, there are data that seem to indicate that it accounts for approximately 1-3% of all pediatric TB cases and for no more than 10% of those with extrapulmonary manifestations. It seems, however, that abdominal TB is significantly more common than usually thought as signs and symptoms are non-specific and may mimic other diseases. The delayed or wrong diagnosis of pediatric abdominal TB can have dramatic consequences as they can lead to untreated TB with miliary dissemination, unnecessary surgery, or dangerous drug therapies. This report describes five cases of abdominal TB diagnosed among 216 pediatric patients admitted for TB in Italy from 2011 to 2021. Our cases evidence that abdominal TB is a complex and potentially very severe disease that, when not appropriately diagnosed, may be associated with severe complications and prolonged anti-TB therapy. Discussion among specialists is crucial to achieve an early diagnosis and to promptly start the anti-TB treatment. Further studies are needed to clarify the appropriate duration of therapy as well as management of MDR abdominal TB cases.

Analysis of a Combined HBHA and ESAT-6-Interferon-γ-Release Assay for the Diagnosis of Tuberculous Lymphadenopathies

The incidence of tuberculosis lymphadenopathy (TBLA) is increasing, and diagnostic procedures lack sensitivity and are often highly invasive. TBLA may be asymptomatic, and differential diagnosis with other adenopathies (ADPs) is difficult. We evaluated a blood-cell interferon-γ release assay (IGRA) with two different stage-specific mycobacterial antigens for the differential diagnosis of ADP suspected of mycobacterial origin. Twenty-one patients were included and divided into three groups: (1) cervical/axillar ADP (n = 8), (2) mediastinal ADP (n = 10), and (3) disseminated ADP (n = 3). The mycobacterial antigens used for the IGRA were the heparin-binding haemagglutinin (HBHA) and the early-secreted antigenic target-6 (ESAT-6), a latency-associated antigen and a bacterial replication-related antigen, respectively. Diagnosis of TBLA based on microbiological results and/or response to anti-TB treatment was obtained for 15 patients. An IGRA profile highly suggestive of active TB (higher IFN-γ response to ESAT-6 compared to HBHA) was found for 3/6 TBLA patients from group 1, and for all the TBLA patients from groups 2 and 3, whereas this profile was not noticed in patients with a final alternative diagnosis. These results highlight the potential value of this combined HBHA/ESAT-6 IGRA as a triage test for the differential diagnosis of ADP.

Changes in Notified Incidence of Pulmonary Tuberculosis in China, 2005–2020

ObjectiveTo evaluate the trend of notified incidence of pulmonary tuberculosis (PTB) in China at different periods by population and region and to explore the effect of TB prevention and control in recent years. MethodsUsing pooled data on TB cases reported by the TB Information Management Reporting System (TBIMS) from 2005 to 2020, we calculated the annual percentage change (APC) using the Joinpoint regression model. ResultsFrom 2005 to 2020, a total of 16.2 million cases of PTB were reported in China, with an average notified incidence of 75.5 per 100,000 population. The age standardization rate (ASR) continued to decline from 116.9 (/100,000) in 2005 to 47.6 (/100,000) in 2020, with an average annual decrease of 5.6% [APC = –5.6, 95% confidence interval (CI): –7.0 to –4.2]. The smallest decline occurred in 2011–2018 (APC = –3.4, 95% CI: –4.6 to –2.3) and the largest decrease in 2018–2020 (APC = –9.2, 95% CI: –16.4 to –1.3). From 2005 to 2020, the ASR in males (159.8 per 100,000 in 2005, 72.0 per 100,000 in 2020) was higher than that in females (62.2 per 100,000 in 2005, 32.3 per 100,000 in 2020), with an average annual decline of 6.0% for male and 4.9% for female. The average notified incidence was the highest among older adults (65 years and over) (182.3/100,000), with an average annual decline of 6.4%; children (0–14 years) were the lowest (4.8/100,000), with an average annual decline of 7.3%, but a significant increase of 3.3% between 2014 and 2020 (APC = 3.3, 95% CI: 1.4 to 5.2); middle-aged (35–64 years) decreased by 5.8%; and youth (15–34 years) decreased by an average annual rate of 4.2%. The average ASR in rural areas (81.3/100,000) is higher than that in urban areas (76.1/100,000). The average annual decline in rural areas was 4.5% and 6.3% in urban areas. South China had the highest average ASR (103.2/100,000), with an average annual decline of 5.9%, while North China had the lowest (56.5/100,000), with an average annual decline of 5.9%. The average ASR in the southwest was 95.3 (/100,000), with the smallest annual decline (APC = –4.5, 95% CI: –5.5 to –3.5); the average ASR in the Northwest China was 100.1 (/100,000), with the largest annual decline (APC = –6.4, 95% CI: –10.0 to –2.7); Central, Northeastern, and Eastern China declined by an average of 5.2%, 6.2%, and 6.1% per year, respectively. ConclusionsFrom 2005 to 2020, the notified incidence of PTB in China continued to decline, falling by 55%. For high-risk groups such as males, older adults, high-burden areas in South, Southwest, and Northwest China, and rural regions, proactive screening should be strengthened to provide timely and effective anti-TB treatment and patient management services for confirmed cases. There is also a necessity to be vigilant about the upward trend of children in recent years, the specific reasons for which need to be further studied.

Hepatocyte ferroptosis contributes to anti-tuberculosis drug-induced liver injury: Involvement of the HIF-1α/SLC7A11/GPx4 axis

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common serious adverse event observed during the clinical treatment of tuberculosis. However, the molecular mechanisms underlying ATB-DILI remain unclear. A recent study has indicated that ferroptosis and lipid peroxidation may be involved in liver injury. Therefore, this study aimed to investigate the role of ferroptosis in the molecular mechanisms underlying ATB-DILI. Our results showed that anti-TB drugs induced hepatocyte damage in vivo and in vitro and inhibited BRL-3A cell activity in a dose-dependent manner, accompanied by increased lipid peroxidation and reduced antioxidant levels. Moreover, ACSL4 expression and Fe2+ concentration significantly increased following anti-TB drug treatment. Interestingly, anti-TB drug-induced hepatocyte damage was reversed by ferrostatin-1 (Fer-1, a specific ferroptosis inhibitor). In contrast, treatment with erastin (a ferroptosis inducer) resulted in further elevation of ferroptosis indicators. Additionally, we also found that anti-TB drug treatment inhibited HIF-1α/SLC7A11/GPx4 signaling in vivo and in vitro. Notably, HIF-1α knockdown significantly enhanced anti-TB drug-induced ferroptotic events and the subsequent exacerbation of hepatocyte damage. In conclusion, our findings indicated that ferroptosis plays a crucial role in the development of ATB-DILI. Furthermore, anti-TB drug-induced hepatocyte ferroptosis was shown to be regulated by HIF-1α/SLC7A11/GPx4 signaling. These findings shed new light on the mechanisms underlying ATB-DILI and suggest novel therapeutic strategies for this disease.

Diagnostic Dilemma of Chest Wall Tuberculosis Masquerading Breast Lump and Sarcoma

Chest wall tuberculosis (TB) is rare and can often masquerade as a tumour. Diagnostic confirmation is made by bacteriological findings of acid-fast bacilli and culture of Mycobacterium tuberculosis or histopathological findings. This is a 37-year-old immunocompetent lady who presented with a 3-month history of gradually increasing right breast lump with suspicious characteristics during clinical examinations. Ultrasound of the breast showed normal breast tissue with a well-defined hypoechoic lesion within the anterior inferior pectoralis muscle. CT scan of the thorax revealed a right anterior chest wall lesion with multiple lung nodules and consolidations. Thus, there was a high suspicion of chest wall tumour and an initial diagnosis of soft tissue sarcoma was made. Biopsy of the lesion showed necrotising granulomatous inflammation but no acid-fast bacilli. A revised diagnosis of chest wall tuberculosis was made. She attended follow-up complaining of shortness of breath and pleuritic chest pain with signs of right pleural effusion. Her symptoms improved after the initiation of anti-TB treatment. This case demonstrated the challenge in making an early diagnosis of chest wall TB and commencement of anti-TB treatment.

ЭФФЕКТИВНОСТЬ ЛЕЧЕНИЯ РИФАМПИЦИН-УСТОЙЧИВОГО ТУБЕРКУЛЕЗА В СОЧЕТАНИИ С СИНДРОМОМ ЗАВИСИМОСТИ ОТ АЛКОГОЛЯ

Rifampicin-resistant tuberculosis (RR-TB) – multi-drug and extensively drug-resistant tuberculosis (MDR and XDR) – is a global problem. Purpose of the work. To study the features of RR-TB combined with alcohol dependence syndrome (ADS). Material and Methods. A total of 420 patients with active pulmonary TB were examined. All patients were divided into groups depending on the presence or absence of ADS. The patients with ADS were referred to the main groups (MG), those without ADS – to the comparison groups (CG). Results. When evaluating the outcome of the main course of treatment in patients with MDR-TB without ADS, the indicator of "successful treatment" was achieved in 88.6% of patients, and in those with MDR-TB combined with ADS – in 58.0% (&lt;0.05). The indicator "successful treatment" was confirmed only in 26.8% of patients with MBT XDR. When XDR-TB was combined with ADS the indicator of "successful treatment" was obtained in 20.4% of patients, the outcome "death" was present in 52.3%, all cases due to TB. In the treatment of XDR-TB without ADS, "successful treatment" was achieved in 65.4% cases, the outcome "death" was in 11.5%. Conclusions. RR-TB in combination with alcohol dependence syndrome is a serious problem. It has been established that the absence of alcohol dependence syndrome in patients with MDR-TB allows for effective anti-TB treatment and good results.

Mortality among persons receiving tuberculosis treatment in Itezhi-Tezhi District of Zambia: A retrospective cohort study.

Itezhi-Tezhi District in southern Zambia has been reporting tuberculosis (TB) mortality rates that are fourfold higher than the national average of six percent. We conducted a retrospective cohort study to establish the demographic and clinical characteristics associated with mortality among persons under treatment for TB in Itezhi-Tezhi District, as well as the likely causes and time to death. We reviewed medical records for persons with TB registered in 19 public health facilities in Itezhi-Tezhi District between January 2015 and December 2018. Of the 506 persons with TB registered in the study period, 426 were included in the analysis. Of these, 71 (16.7%) died before completing treatment. The overall mortality rate was 31.8 per 1,000 person-months of observation. Most of the deaths (53 [74.7%]) occurred in the first month of treatment (median: 16 days; interquartile range: 5-52 days). In a multivariate Cox regression model, type of TB was found to be an independent predictor of mortality while on TB treatment. The risk of dying was more than twice higher for persons with clinically diagnosed PTB compared to those with bacteriologically confirmed PTB (adjusted hazard ratio = 2.2, 95% CI: 1.4-3.6). In a sub-analysis of persons with clinically diagnosed PTB, persons with TB who were on a community-based DOT plan were more than twice more likely to die compared to those on facility-based DOT plan (adjusted hazard ratio = 2.21, 95% CI: 1.1-4.8). Common likely causes of death were pulmonary TB disease (66.0%), anemia (12.8%), cardiac failure (4.3%), pneumocystis jiroveci pneumonia (4.3%), and gastroenteritis (4.2%). These findings show that most deaths occurred during the first month of treatment. Clinical evaluation at initiation of anti-TB treatment and during follow-up care, especially in persons with clinically diagnosed PTB, should include screening and treatment of other conditions.

Evaluation of the Toxic Activity of the Graphene Oxide in the Ex Vivo Model of Human PBMC Infection with Mycobacterium tuberculosis.

Graphene Oxide has been proposed as a potential adjuvant to develop improved anti-TB treatment, thanks to its activity in entrapping mycobacteria in the extracellular compartment limiting their entry in macrophages. Indeed, when administered together with linezolid, Graphene Oxide significantly enhanced bacterial killing due to the increased production of Reactive Oxygen Species. In this work, we evaluated Graphene Oxide toxicity and its anti-mycobacterial activity on human peripheral blood mononuclear cells. Our data show that Graphene Oxide, different to what is observed in macrophages, does not support the clearance of Mycobacterium tuberculosis in human immune primary cells, probably due to the toxic effects of the nano-material on monocytes and CD4+ lymphocytes, which we measured by cytometry. These findings highlight the need to test GO and other carbon-based nanomaterials in relevant in vitro models to assess the cytotoxic activity while measuring antimicrobial potential.

A Case Report on Pulmonary Tuberculosis Associated with Deep Vein Thrombosis

Public health problems such as tuberculosis remain a major concern, especially in developing countries. According to WHO (World Health Organization), for every second someone gets infected with tuberculosis. India is the second most populated nation in the world contributes to 23% of TB incident cases annually out of 9.6 million worldwide. The overall morbidity and mortality associated with TB are reduced with early initiation of anti-TB treatment. In India, most antituberculosis regimens are Rifampicin-based under the Revised National Tuberculosis Control Program (RNTCP). Despite its rarity, deep venous thrombosis (DVT) should be considered especially in those with severe disseminated or pulmonary tuberculosis. This case report describes a 31-year-old female with pulmonary tuberculosis initiated on rifampicin-based antituberculosis treatment presented with deep vein thrombosis.&#x0D; Keywords: Tuberculosis, Deep vein thrombosis, pulmonary tuberculosis

Incidence of and Risk Factors for Acute Kidney Injury During Antituberculosis Treatment: A Prospective Cohort Study and Literature Review.

Acute kidney injury (AKI) is occasionally detected in patients receiving anti-tuberculosis (TB) treatment. This prospective cohort study is the first to investigate the incidence, risk factors, and renal outcomes of AKI during anti-TB treatment. This study was conducted from January 1, 2016, to May 31, 2018. Patients with a new diagnosis of TB and on standard anti-TB treatment were enrolled, and the patients received regular laboratory monitoring. AKI was defined according to the Kidney Disease: Improving Global Outcome (KDIGO) criteria. Urinalysis, renal ultrasonography, blood erythrocyte morphology, and fractional excretion of sodium were performed at AKI onset. The TB treatment regimen was adjusted by the primary physician if necessary. Risk factors for AKI were identified through Cox regression. In total, 106 patients were recruited (mean age 52.6years, 71.7% men). Eleven (10.3%) patients experienced AKI. Increased serum uric acid and hemoglobin levels were noted at AKI onset. All patients with AKI achieved renal recovery and completed anti-TB treatment containing rifampin. Age [hazard ratio (HR) 1.06 (1.02-1.11)], a higher baseline estimated glomerular filtration rate [eGFR; HR 1.04 (1.02-1.06)], and a blood eosinophil count>350 (109/L) [HR 10.99 (2.28-53.02)] were associated with a higher risk of AKI during TB treatment. Regular pharmacovigilant monitoring revealed an incidence of renal impairment during anti-TB treatment that was higher than expected. AKI was more common in older patients with a higher eGFR and blood eosinophil count. However, the complications had no influence on TB treatment completion, and no permanent renal impairment occurred.