Pulmonary Multidrug-resistant Tuberculosis Research Articles

A Study on Pulmonary Tuberculosis and Risk Factors in New and Re-Treated Presumptive Patients at Wad Madani Tuberculosis Center, Sudan (2018-2019): A Cross-Sectional Study

Introduction: The increase in cases of drug-resistant pulmonary tuberculosis, especially in endemic areas, is mainly associated with re-treatment, although resistant tubercle bacilli can be easily transmitted between all susceptible persons. Objective: The study aimed to describe pulmonary tuberculosis, risk factors and MDR in new and re-treated suspected patients attending Wad Madani Tuberculosis Center that provides service in central Sudan. Methods: Cross-sectional laboratory based study among 300 presumptive pulmonary tuberculosis patients during 2018 and 2019 was conducted. Cases were divided into new and re-treated. Mycobacterium tuberculosis DNA and rpoB gene of multi-drug resistance (MDR) were detected in sputum samples by GeneXpert assay as manufacturer instructions. Results: Out of 300 suspected participants, 34% (103/300) were diagnosed as pulmonary tuberculosis using GeneXpert method. The frequency of males, the age group from 21 to 40 and rural housing were the most with percentage reach 68% (70/103), 51% (53/103) and 58.3% (60/103) respectively. All observed symptoms were significantly associated with pulmonary tuberculosis. New cases represented 59.2% (61/103) while re-treated was 40.8% (39/103). The overall frequency of MDR patients was 9.7% (10/103) of which 50% (5/103) had relapse situation. Conclusion: It appeared that the cases of MDR pulmonary tuberculosis are on the increase compared to previous findings, recommended measures must be taken to control the spread of tuberculosis and the causes of re-treatment and relapse must be studied.

Cycloserine Induced Neurotoxicity: A Rare Case Report

Cycloserine is one of the many drugs used in treatment of Multidrug Resistant Tuberculosis (MDR-TB). Neuropsychiatric complaints are common after cycloserine administration. Reports of neuroimaging in cycloserine neurotoxicity are rare. Authors hereby reports a case of 17-year-old female, who presented with hallucination and delirium since 2 weeks. She was a known case of pulmonary MDR-TB and was on Anti-Koch’s Treatment category IV (AKT) for the same since last 12 months. On clinical examination, the patient was conscious and co-operative but disoriented. Magnetic Resonance Imaging (MRI) revealed, symmetric hyperintensities on T2 weighted images in bilateral dentate nuclei with restriction of diffusion, on diffusion weighted images. In addition, two well- defined T2 hypointense ring enhancing lesions were seen in right parietal and occipital regions. Patient’s symptoms improved on stoppage of cycloserine. On follow-up MRI, 4 weeks after withdrawing the durg, there was complete reversal of MRI findings.

Diligence needed on treatment of primary multidrug-resistant pulmonary tuberculosis with concomitant COVID-19 infection.

Diligence needed on treatment of primary multidrug-resistant pulmonary tuberculosis with concomitant COVID-19 infection.

Development of Scoring and Stratification of Severe Lung Involvement in Multidrug-Resistant Pulmonary Tuberculosis Patients

Development of Scoring and Stratification of Severe Lung Involvement in Multidrug-Resistant Pulmonary Tuberculosis Patients

The comparative analysis of the drug resistance of mbtin children, adolescents and the sources of infection in the multidrug resistant tuberculosis focies

145 patients (67 children and 78 adolescents) from the multidrug-resistant tuberculosis infection focies took part in the complex microbiological study. The children and adolescents had undergone treatment for the pulmonary multidrugresistant tuberculosis. The study showed that MDR TB was by 1.7 times more often revealed in the adolescents as compared to the children, while the risk of MDR TB was by 3.7 times higher for the children than for the adolescents. The drug resistance profile of the children and the sources of infection almost completely coincided. The resistance to HRSE (66.1%) and HRESZ (13.6%) developed in the adolescents more often than in the children and adults. The study proves the importance of defining the drug resistance profile in the exposed children and adolescents from the multidrugresistant tuberculosis focies.

Laboratory evaluation of the efficacy of Liastene application in complex therapy of multiresistant pulmonary tuberculosis

OBJECTIVE. Evaluating according to laboratory tests the effectiveness of Liasten in the treatment of patients with multidrug-resistant pulmonary tuberculosis (MDR-TB).
 MATERIALS AND METHODS. Evaluation of the effectiveness of etiotropic and etiopathogenetic therapy in 57 patients with MDR-TB was performed. According to the treatment schemes, patients were divided into groups. The control group (n=22) received individualized antimycobacterial therapy (AMBT) regimens. The experimental group (n=35) received AMBT in combination with Liasten. Evaluation of the effectiveness of treatment regimens was performed on the basis of indicators of general clinical blood tests, immunological and bacteriological studies.
 RESULTS AND DISCUSSION. In patients of the experimental group, compared with the control in 1.5 times more often found positive changes in the hemogram of blood and ESR (p<0.05-0.001), the establishment of a dynamic balance between the pools of lymphocyte cells CD4+ and СD8+ (immunoregulatory index, p<0.05), an increase in the number of phagocytosis active cells (phagocytic index, p<0.05), the content of cationic lysosomal proteins of granulocyte leukocytes (p<0.05), a 1.4-fold decrease in the cytochemical coefficient of neutrophils (p<0.05), the number of proliferated under the action of PPD-L lymphocytes (p<0.05), normalization of phagocytic counts and total redox activity of neutrophils (p<0.05), increase in frequency and reduction of anesthesia was stated.
 CONCLUSIONS. Restoration of the body’s immune status, blood hemogram, increase in frequency and reduction of the time of decontamination were more active and occurred 1.5 times more often in patients receiving a complex combination of AMBT with Liasten.

A Retrospective Comparative Study on Median Time to Sputum Culture Conversion in Multi-Drug Resistant Pulmonary Tuberculosis Patients in Pastoral and Non-Pastoral Settings in Southeast Oromia, Ethiopia.

PurposeSputum culture conversion to negative is an indicator of good interim treatment outcome. Pastoralist community has lesser access to healthcare services. This study aimed to compare the time to culture conversion (TTSCC) between the pastoral and non-pastoral settings and identify its determinants among drug-resistant pulmonary TB patients.Patients and MethodsFour hundred forty-seven drug-resistant pulmonary TB patients were included from selected hospitals of southeastern Oromia, Ethiopia. Kaplan–Meier model using the Log rank test was fit to compute and compare median TTSCC between study participants from the pastoral and non-pastoral settings. The Cox proportional hazard model was fit to identify factors associated with the TTSCC. Adjusted hazard ratio (AHR) with a 95% confidence interval (CI) was used to report the strength of association. Statistical significance was declared at p < 0.05.ResultsThe study participants’ median age (interquartile range) was 29 (24–36) years. The overall median TTSCC among the current study participants was 67 (95% CI, 64–70) days. It was significantly different for patients from the pastoral and non-pastoral settings (p-value <0.001). The median TTSCC for patients from pastoral and non-pastoral settings was 101 (95% CI, 81–121) and 63 (95% CI, 61–64) days. To mention few determinants, patients from the pastoral setting had a 69% lower chance [HR = 0.31 (95% CI 0.24–0.41)] of shorter TTSCC than patients from the non-pastoral setting. Furthermore, patients with baseline body mass index greater than 18.5Kg/M2 had a 35% higher chance of shorter TTSCC [HR = 1.35 (95% CI 1.07–1.71)] compared to their counterparts.ConclusionThe median TTSCC among the study participants from pastoral was longer than those from non-pastoral setting. The pastoral setting, under-nutrition, previous exposure to anti-TB drugs and drug regimen categories were among the notable determinants of the TTSCC among our study participants. Hence, due attention should be given to patients with these determinants during the treatment.

Efficacy of integrating short-course chemotherapy with Chinese herbs to treat multi-drug resistant pulmonary tuberculosis in China: a study protocol

BackgroundTuberculosis (TB) caused Mycobacterium tuberculosis (M.tb) is one of infectious disease that lead a large number of morbidity and mortality all over the world. Although no reliable evidence has been found, it is considered that combining chemotherapeutic drugs with Chinese herbs can significantly improves the cure rate and the clinical therapeutic effect.MethodsMulti-drug resistant pulmonary tuberculosis (MDR-PTB, n = 258) patients with Qi-yin deficiency syndrome will be randomly assigned into a treatment group (n = 172) or control/placebo group (n = 86). The treatment group will receive the chemotherapeutic drugs combined with Chinese herbs granules (1 + 3 granules), while the control group will receive the chemotherapeutic drugs combined with Chinese herbs placebo (1 + 3 placebo granules). In addition, MDR-PTB (n = 312) patients with Yin deficiency lung heat syndrome will be randomly assigned to a treatment (n = 208) or control/placebo (n = 104) group. The treatment group will receive the chemotherapeutic regimen combined with Chinese herbs granules (2 + 4 granules), while the control group will receive the chemotherapeutic drugs and Chinese herbs placebo (2 + 4 placebo granules). The primary outcome is cure rate, the secondary outcomes included time to sputum culture conversion, lesion absorption rate and cavity closure rate. BACTEC™ MGIT™ automated mycobacterial detection system will be used to evaluate the M.tb infection and drug resistance. Chi-square test and Cox regression will be conducted with SAS 9.4 Statistical software to analyze the data.DiscussionThe treatment cycle for MDR-PTB using standardized modern medicine could cause lengthy substantial side effects. Chinese herbs have been used for many years to treat MDR-PTB, but are without high-quality evidence. Hence, it is unknown whether Chinese herbs enhances the clinical therapeutic effect of synthetic drugs for treating MDR-PTB. Therefore, this study will be conducted to evaluate the clinical therapeutic effect of combining Chinese herbs and chemotherapeutic drugs to treat MDR-PTB cases. It will assist in screening new therapeutic drugs and establishing treatment plan that aims to improve the clinical therapeutic effect for MDR-PTB patients.Trial registrationThis trial was registered at ClinicalTrials.gov (ChiCTR1900027720) on 24 November 2019 (prospective registered).Graphical

Culture conversion and six months interim outcomes in retreatment cases of pulmonary MDRTB - a six month interim analysis.

To estimate the time to culture conversion and factors associated with failure to culture conversion, six-month interim outcomes and associated risk factors with poor interim outcomes in multi-drug resistant tuberculosis patients previously treated with second-line drugs. The prospective clinical case series study was conducted from March 2016 to January 2017 at the Indus Hospital Tuberculosis Clinic and seven other sites that are part of the hospital's Programmatic Management of Drug Resistant Tuberculosis initiative. All bacteriologically confirmed multi-drug resistant tuberculosis retreatment patients were enrolled. Data was collected on age, gender, site of enrollment, detailed history of previous treatment with anti-tuberculosis drugs, medical history, history of first-line drugs, history of second-line drugs, treatment outcomes, baseline sputum smear microscopy and monthly follow-up sputum smear microscopy and culture results. Data was subjected to univariate and multiple logistic regression analyses, and risk factors for failure to culture conversion were assessed using Cox Proportional Hazards Model. Out of 266 patients, 143(53.8%) were males, the overall largest age group was 5-24 years 97(36.5%), and 250 (94%) patients had previous history of treatment with first-line drugs. Overall, 101(40.1%) patients experienced poor interim outcome. Poor interim outcomes were significantly associated with higher number of drugs on the regimen, (odds ratio: 1.27; 95% confidence interval: 1.03-1.58) and high sputum smear grading (odds ratio: 4.56; 95% confidence interval: 3.30-18.71). Besides, 186(70.3%) patients experienced culture conversion within the initial six months of treatment. The success rate of re-treatment of multi-drug resistant tuberculosis with conventional regimen was found to be unacceptably low.

New Approaches in the Classification and Prognosis of Sign Clusters on Pulmonary CT Images in Patients With Multidrug-Resistant Tuberculosis.

Background: To date, radiographic sign clusters of multidrug-resistant pulmonary tuberculosis (MDR-TB) patients have not been reported. We conducted a study to investigate the classification and prognosis of sign clusters in pulmonary Computed Tomography (CT) images from patients with MDR-TB for the first time by using principal component analysis (PCA).Methods: The clinical data and pulmonary CT findings of 108 patients with MDR-TB in the Liupanshui Third Hospital were collected (from January 2018 to December 2020). PCA was used to analyze the sign clusters on pulmonary CT, and receiver operating characteristic (ROC) analysis was used to analyze the predictive value of the treatment outcome of MDR-TB patients.Results: Six cluster signs of MDR-TB were determined by PCA: nodules, infiltration, consolidation, cavities, destroyed lung and non-active lesions. Nine months after treatment, the area under the ROC curve (AUC) of MDR-TB patients with a cavity sign cluster was 0.818 (95% CI: 0.733–0.886), and the positive predictive value (PPV) and negative predictive value (NPV) of the treatment outcome were 79.6% (95% CI: 65.7–89.8%) and 72.9% (95% CI: 59.7–83.6%), respectively.Conclusion: PCA plays an important role in the classification of sign groups on pulmonary CT images of MDR-TB patients, and the sign clusters obtained from PCA are of great significance in predicting the treatment outcome.

Peculiarities of the immune status of patients with multidrug­resistant pulmonary tuberculosis after application of treatment regimens with bedaquiline and linezolid

Objective — to investigate immuno-metabolic homeostasis in patients with new and recurrent cases of destructive forms of multidrug-resistant pulmonary tuberculosis (MDR-PTB) after treatment with bedaquiline and linezolid. Materials and methods. A clinical and laboratory examination of 175 people with MDR-PTB (89 patients with new cases and 86 patients with recurrent cases of destructive forms of MDR-PTB). The study was performed before and after treatment with bedaquiline and linezolid. The total leukocytes count (L), the leukocyte differential count (leukocyte formula), was determined in all subjects, The content of populations and subpopulations of lymphocytes were calculated using monoclonal antibodies to CD3+, CD4+, CD8+, CD19+, CD23+, CD56+ lymphocytes antigen in the reaction of indirect immunofluorescence. Quantitative determination of serum immunoglobulins was performed by Manchini radial immunodif­fusion in a gel. The level of circulating immune complexes (CIC) was determined by the spectrophoto­metric method by precipitation in polyethylene glycol. Results and discussion. In patients with new cases of destructive forms of MDR-PTB to treatment revealed hypersensitivity reactions of the first and the fourth type. Expressed activation of humoral and killer parts of immunity detected. In patients with recurrent cases of destructive forms of MDR-PTB before treatment, there are pronounced hypersensitivity reactions of the fourth type and activation of the humoral and killer parts of the immune system.Patients with new cases of destructive forms of MDR-PTB after application of treatment regimens with bedaquiline and linezolid have hypersensitivity reactions of the first and fourth types. Activation of humo­ral and killer parts of immunity detected. In patients with recurrent cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed a pronounced hypersensitivity reaction of the first type and activation of the killer and humoral parts of the immune system. Conclusions. In patients with new cases of destructive forms of MDR-PTB before treatment revealed T-cell immunodeficiency, which is expressed by a decrease in the level of T-lymphocytes (1.7 times relative to normal) and T-helpers (twice below normal). In patients with recurrent cases of destructive forms of MDR-PTB before treatment revealed T-cell immunodeficiency with a marked decrease in the level of T-lymphocytes (1.8 times normal) and T-helpers (1.8 times below normal). In patients with new cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed activation of the T-cell immune system due to increased levels of T-suppressors. In patients with recurrent cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed T-cell immunodeficiency due to the reduced content of T-lymphocytes (1.5 times below normal), namely T-helpers (1.9 times lower than normal).

Clinical characteristics and treatment outcome of multidrug-resistant pulmonary tuberculosis complicated with diabetes mellitus

Objective To compare the clinical characteristics and treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients with and without diabetes melitus (DM), and we improve clinicians’ understanding of drug-resistant pulmonary tuberculosis complicated with diabetes. Methods A total of 322 patients with MDR-TB in Xi’an Chest Hospital were selected as the research subjects, including 60 patients (18.6%) in the DM+ group, 262 patients (81.4%) were in the DM– group without diabetes. Age, gender, body mass index (BMI), complicated liver disease, previous treatment history, cumulative number of lung fields in imaging lesions (<3 or ≥3), clinical data such as cavity, drug resistance characteristics, treatment outcome, adverse reactions and so on were analyzed and compared between the two groups. Results 91.7% of males in DM+ group were higher than 70.2% in DM– group, and there was a statistical difference between the two groups ( P=0.001). The average age of DM+ group was (48.6±11.8) years higher than that of DM– group (34.3±14.8) years. The difference was statistically significant ( P<0.001). BMI of DM+ group was higher than that of DM– group, and there were statistically significant differences between the two groups ( P=0.003). The probability of cavities in DM+ group was higher than DM– group, and the difference between the two groups was statistically significant ( P<0.001). The probability of complicated extrapulmonary tuberculosis in DM+ group was higher than DM– group, and the difference between the two groups was statistically significant ( P=0.024). There were no significant differences between the two groups in initial retreatment, cumulative number of lung fields in imaging lesions (<3 or ≥3), and whether liver disease was complicated ( P>0.05). There was no statistical difference in the drug resistance rates of fluoroquinolones (FQS), AM (CM) and fluoroquinolones + AM (CM) between the two groups ( P>0.05). Univariate analysis of treatment outcome indicated that age, gender, initial retreatment, and the cumulative number of lung fields in the lesions had influence on the prognosis ( P<0.05). When multivariate analysis found that age and the cumulative number of lung fields in the lesions were closely related to the treatment outcome ( P<0.05). The incidence of ADR was 39.2% (85/217) in DM– group and 56.6% (30/53) in the DM+ group, and the ADR rate was higher in the DM+ group, with statistical significance between the two groups ( P=0.029). The sputum negative conversion rate of 3 months in DM+ group was 80.0% (32/40); The negative conversion rate of DM– group was 85.6%(149/174), and there was no statistical significance between the two groups ( P>0.465). Conclusion DM+ patients are mainly middle-aged and elderly males, body mass index (BMI) of DM+ patients is relatively large, and sufficient dosage of tuberculosis drugs should be given according to the body weight of patients to avoid poor therapeutic effect caused by decreased blood drug concentration. At the same time, it was found that DM+ patients were more prone to lung cavity in imaging and increased extrapulmonary tuberculosis. In clinical practice, we should be alert to the possibility of massive hemoptysis at any time and pay attention to the screening of multi-organ tuberculosis in the body. 摘要： 目的 通过对合并与不合并糖尿病(diabetes mellitus, DM)的耐多药肺结核(multi-drug resistance tuberculosis, MDR-TB)患者临床特点及治疗结局进行比较, 提髙临床医生对耐药肺结核合并糖尿病的认识。 方法 以西安市 胸科医院322例耐多药肺结核患者为研究对象, 其中合并糖尿病(DM+)组60例(18.6%);不合并糖尿病(DM–)组262例 (81.4%)。分析比较两组患者的年龄、性别、体质量指数(BMI)、合并肝病、既往治疗史、影像学病灶累计肺野数(<3或≥ 3)、有无空洞、耐药特征、治疗结局、不良反应等临床资料。 结果 DM+组男性占91.7%, 髙于DM–组70.2%, 两组间比 较差异有统计学意义( P=0.001)。DM+组平均年龄(48.6±11.8)岁髙于DM–组(34.3±14.8)岁, 两组间比较差异有统计学 意义( P<0.001)。DM+组BMI髙于DM–组, 两组间差异有统计学意义( P=0.003)。DM+组出现空洞的概率髙于DM–组, 两组间差异有统计学意义( P<0.001)。DM+组合并肺外结核的概率髙于DM–组, 两组间比较差异有统计学意义( P= 0.024)。两组在初复治、影像学病灶累积肺野数(<3或≥3)、是否合并肝病等差异均无统计学意义( P>0.05)。两组在对 氣座诺丽(Fluoroquinolones, FQs)、阿米卡星(Amikacin, Am)[卷曲霉素 Capreomycin, Cm)]、FQs+ Am(Cm)耐药率差异均 无统计学意义( P>0.05)。治疗结局单因素分析提示年龄、性别、初复治、病灶累计肺野数等因素对预后有影响( P<0.05), 多因素分析发现年龄及病灶累计肺野数与治疗结局密切相关( P<0.05)。DM–组不良反应发生率39.2%(85/217);DM+组不良反应发生率56.6%(30/53), DM+组发生不良反应率更髙, 两组间差异有统计学意义( P=0.029)。DM+组3个月痰菌阴转率80.0%(32/40), DM–组阴转率85.6%(149/174), 两组间差异无统计学意义( P>0.465)。 结论 DM+患者以中老年男性为主, 体质量指数(body mass index, BMI)相对较大, 要根据患者体重给与足量结核药以避免出现血 药浓度降低引起治疗效果不佳。DM+患者更容易出现影像学肺部空洞, 肺外结核病增多情况, 在临床上要警惕随时出 现大咯血可能, 注意周身多器官结核的排査。

Prevalence and Correlates of Anxiety and Depressive Symptoms in Patients With and Without Multi-Drug Resistant Pulmonary Tuberculosis in China.

China is still among the 30 high-burden tuberculosis (TB) countries in the world and TB remains a public health concern. TB can be a cause of mental illness, with prolonged treatment and several anti-TB drugs leading to extreme mental health problems such as depression and anxiety in TB patients. To investigate the prevalence of anxiety and depressive symptoms among TB patients, and to explore whether drug resistance is a covariate for depressive and anxiety symptoms, a total of 167 pulmonary tuberculosis patients were enrolled in this study, which was conducted from January 1 to September 30, 2020. Data were collected, using a structured questionnaire with a demographic component, the Hospital Anxiety and Depression Scale (HADS), General Health Questionnaire 20 (GHQ-20), the Tuberculosis-related Stigma Scale (TSS) and the Social Support Rating Scale (SSRS). Association between demographics, disease/treatment characteristics, stigma, social support, and anxiety/depression symptoms were investigated either based on Pearson's correlation coefficient or group comparisons based on independent t-test (or Mann-Whitney U-test) Multiple linear stepwise regression analysis was used for determining the predictors of anxiety and depression. The results showed that multi-drug resistance pulmonary tuberculosis patients were associated with anxiety challenges. Multiple linear regression analysis indicated that self-esteem accounted for 33.5 and 38% of the variation in anxiety and depression, respectively. This shows that among tuberculosis patients, self-esteem is the factor that could most explains the depression and anxiety symptoms of patients, suggesting that we may could through improving the environment, society, and family respect and tolerance of tuberculosis patients, thereby improving the mental health of tuberculosis patients.

Delayed fracture union in a case of vitamin D dependent rickets associated with pulmonary tuberculosis - a case report

&lt;p&gt;Rickets is a defect of bone mineralization caused by vitamin D deficiency, seen most significantly at growth plates that result in radiological bony abnormalities like metaphyseal flaring and cupping, physeal widening with focal and generalised osteomalacia.&lt;strong&gt; &lt;/strong&gt;Here we present a rare case of 7 years old male, a case of vitamin D3 deficiency rickets in a known case of multi drug resistant pulmonary tuberculosis. The patient had suffered left proximal fibular fracture following trivial fall 1.5 month back and had delayed bony union leading to difficulty in walking and pain. The patient was treated with oral vitamin D supplementation. In vitamin D deficiency rickets, there is decreased bone mineralization leading to weak bones and delayed fracture healing in children. Low serum vitamin D levels also caused decreased immunity with increased susceptibility to respiratory infections like pulmonary tuberculosis. Appropriate treatment with injectable or oral vitamin D3 with adequate exposure of sunlight and proper nutrition is the best modality of treatment.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;

Factors Associated with Medical Follow-Up Adherence for Patients on All-Oral Regimen for Multidrug-Resistant Tuberculosis in Shenzhen, China

PurposeThe aim of this study is to identify factors affecting medical follow-up adherence of pulmonary multidrug-resistant tuberculosis (MDR-TB) patients on an all-oral regimen in Shenzhen, China to enhance intervention measures for increased treatment success.MethodsA cohort study was conducted in The Third People’s Hospital of Shenzhen on MDR-TB patients switched to an all-oral regimen to evaluate effectiveness following the WHO’s recommendation in late 2018. We recruited patients in the group for an opinion survey on medical follow-up adherence from May 2019 to June 2020. The survey was designed with socio-demographic questions in collecting baseline characteristics and importance and Likert closed-ended questions for measuring opinions and relevance of different factors to adherence. Linear regression model was used to analyze data collected.ResultsThe findings revealed that gender difference (P = 0.828) had no correlation with adherence. Marital status (P = 0.014), financial situation (P <0.001) and difficulties encountered with medical appointment booking procedures (P = 0.001) were significantly associated with medical follow-up adherence. Single (including widowed and divorced) patients, those with low household income and patients having difficulties making online medical appointment booking, were at higher risk of defaulting from routine MDR-TB medical follow-up.ConclusionOur survey revealed that financial burden, being single and a non-user friendly medical appointment booking system are the main barriers to patients’ medical follow-up compliance. More financial assistance, better patient support and simplifying medical appointment booking procedures are facilitators of better treatment adherence.

Comparison of Chest X-Ray Findings Between Primary and Secondary Multidrug Resistant Pulmonary Tuberculosis

Introduction: Radiological imaging has a key role in multidrug-resistant (MDR) pulmonary tuberculosis (TB) screening and diagnosis. However, new cases of MDR pulmonary TB are often overlooked; therefore, its transmission might continue before its diagnosis. The most widely used and affordable radiological modality is a chest radiograph. This study aims to describe the characteristics of primary and secondary MDR pulmonary TB chest x-ray findings for differential diagnosis.&#x0D; Methods: This study was an analytic observational study with a retrospective design. Researchers evaluated medical record data of primary and secondary MDR pulmonary TB patients who underwent chest x-ray examinations. The patient's chest x-rays were then evaluated. Evaluated variables were lung, pleural, and mediastinal abnormalities and severity category.&#x0D; Results: The most common chest x-ray finding in primary MDR pulmonary TB was consolidation (96.2%), which was mostly unilateral (52.0%), accompanied by cavities (71.2%), most of which were multiple (83.8%) with a moderate category of severity. The most common chest x-ray finding in secondary MDR pulmonary TB was consolidation (100%), which was mostly bilateral (60.4%), accompanied by cavities (80.2%), most of which were multiple (90.1%) with severe category of severity. Pleural thickening (47.5%) was also found.&#x0D; Conclusion: There was a significant difference between primary and secondary MDR pulmonary TB in terms of mild severity category, and pleural thickening. Mild severity category is mostly found in primary MDR-TB and pleural thickening is mostly found in secondary TB.

Comparison of Chest X-Ray Findings Between Primary and Secondary Multidrug Resistant Pulmonary Tuberculosis

Introduction: Radiological imaging has a key role in multidrug-resistant (MDR) pulmonary tuberculosis (TB) screening and diagnosis. However, new cases of MDR pulmonary TB are often overlooked; therefore, its transmission might continue before its diagnosis. The most widely used and affordable radiological modality is a chest radiograph. This study aims to describe the characteristics of primary and secondary MDR pulmonary TB chest x-ray findings for differential diagnosis.&#x0D; Methods: This study was an analytic observational study with a retrospective design. Researchers evaluated medical record data of primary and secondary MDR pulmonary TB patients who underwent chest x-ray examinations. The patient's chest x-rays were then evaluated. Evaluated variables were lung, pleural, and mediastinal abnormalities and severity category.&#x0D; Results: The most common chest x-ray finding in primary MDR pulmonary TB was consolidation (96.2%), which was mostly unilateral (52.0%), accompanied by cavities (71.2%), most of which were multiple (83.8%) with a moderate category of severity. The most common chest x-ray finding in secondary MDR pulmonary TB was consolidation (100%), which was mostly bilateral (60.4%), accompanied by cavities (80.2%), most of which were multiple (90.1%) with severe category of severity. Pleural thickening (47.5%) was also found.&#x0D; Conclusion: There was a significant difference between primary and secondary MDR pulmonary TB in terms of mild severity category, and pleural thickening. Mild severity category is mostly found in primary MDR-TB and pleural thickening is mostly found in secondary TB.

Prediction of Human Pharmacokinetic Profiles of the Antituberculosis Drug Delamanid from Nonclinical Data: Potential Therapeutic Value against Extrapulmonary Tuberculosis.

Delamanid has been studied extensively and approved for the treatment of pulmonary multidrug-resistant tuberculosis; however, its potential in the treatment of extrapulmonary tuberculosis remains unknown. We previously reported that, in rats, delamanid was broadly distributed to various tissues in addition to the lungs. In this study, we simulated human plasma concentration-time courses (pharmacokinetic profile) of delamanid, which has a unique property of metabolism by albumin, using two different approaches (steady-state concentration of plasma-mean residence time [Css-MRT] and physiologically based pharmacokinetic [PBPK] modeling). In Css-MRT, allometric scaling predicted the distribution volume at steady state based on data from mice, rats, and dogs. Total clearance was predicted by in vitro-in vivo extrapolation using a scaled albumin amount. A simulated human pharmacokinetic profile using a combination of human-predicted Css and MRT was almost identical to the observed profile after single oral administration, which suggests that the pharmacokinetic profile of delamanid could be predicted by allometric scaling from these animals and metabolic capacity in vitro. The PBPK model was constructed on the assumption that delamanid was metabolized by albumin in circulating plasma and tissues, to which the simulated pharmacokinetic profile was consistent. Moreover, the PBPK modeling approach demonstrated that the simulated concentrations of delamanid at steady state in the lung, brain, liver, and heart were higher than the in vivo effective concentration for Mycobacterium tuberculosis. These results indicate that delamanid may achieve similar concentrations in various organs to that of the lung and may have the potential to treat extrapulmonary tuberculosis.

Extracellular matrix-inspired inhalable aerogels for rapid clearance of pulmonary tuberculosis

Tuberculosis (TB) remains a leading cause of death from a single infectious agent, and limiting the spread of multidrug-resistant TB (MDR-TB) is now an urgent global health priority. Essential to the persistence of this disease is the ability of Mycobacterium tuberculosis (Mtb) to circumvent host defenses by infecting lung macrophages to create a cellular niche for its survival and proliferation. This has urged the development of new therapeutic strategies that act through mechanisms distinct from conventional antibiotics, and thus are effective against MDR bacteria, while being able to efficiently kill persister Mtb cells in infected host macrophages. Here, we report a new class of gel-like microparticle aerosols, or ‘aerogels’, designed to exploit metabolic vulnerabilities of Mtb pathogens and TB-infected macrophages to enable preferential delivery of synergistic peptide-antibiotic combinations for potent and rapid antitubercular therapy. This is achieved by formulating aerogels through the supramolecular assembly of a de novo designed anti-TB peptide and the extracellular matrix (ECM)-derived polysaccharide, hyaluronic acid (HA). Importantly, HA serves as a nutrient source for Mtb cells during tissue invasion and proliferation, and is recognized by CD44 receptors highly expressed on lung macrophages during TB infection. By exploiting this metabolic substrate for pathogen targeting, HA aerogels are shown to avidly bind and kill both drug-sensitive and drug-resistant mycobacteria, while being efficiently internalized into macrophage host cells in vitro and in vivo to clear Mtb persisters. This multifaceted bioactivity suggests aerogels may serve as a versatile inhalable platform upon which novel biomaterials-enabled therapeutics can be developed to rapidly clear pulmonary MDR-TB.

Optimal methods of psychological support in patientswith multidrug-­resistant pulmonary tuberculosis and their effect on adherence to treatment

Tuberculosis is a severe infectious disease that negatively affects not only the physical condition of patients, but also the psychological condition of patients. The first thing — the shock of the first diagnosis of tuberculosis for the patient. The second thing — when the patient realizes that he must be treated for an unusually long time.&#x0D; Objective — to learn the impact of providing psychological support for the patients with tuberculosis in a phthisiatric hospital in the form of individual counseling and group classes for patients.&#x0D; Materials and methods. A prospective surgical study was provided to establish the level of knowledge, level of adherence to treatment of patients with tuberculosis and the degree of violation of their psycho-emotional state at the beginning of treatment, and individual counseling and group classes for patients. The study included 335 patients with multidrug-resistant pulmonary tuberculosis, who received treatment at the clinic of the National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine on short-term and individualized regimens of antimycobacterial therapy in the framework of scientific developments. Patients received questionnaires before treatment and before discharge, counseling on tuberculosis and their psychological state, various group classes.&#x0D; Results and discussion. A comprehensive approach of treatment using different methods of psychological support allowed increasing the level of adherence to treatment by 32% in the group of patients who received a group classes, compared with those patients who didn’t; reduce the level of stigma by 40.5%, halve the severity anxiety disorders.&#x0D; Conclusions. Comprehensive psychological support should be a mandatory component in the treatment of patients with multidrug-resistant tuberculosis, which can significantly reduce stigma, improve the psychological state of patients and their adaptation in society.