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1.
Int J Pharm ; 655: 124031, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38521375

ABSTRACT

Tuberculosis (TB) is a serious health issue that contributes to millions of deaths throughout the world and increases the threat of serious pulmonary infections in patients with respiratory illness. Delamanid is a novel drug approved in 2014 to deal with multi-drug resistant TB (MDR-TB). Despite its high efficiency in TB treatment, delamanid poses delivery challenges due to poor water solubility leading to inadequate absorption upon oral administration. This study involves the development of novel formulation-based pressurized metered dose inhalers (pMDIs) containing self-microemulsifying mixtures of delamanid for efficient delivery to the lungs. To identify the appropriate self-microemulsifying formulations, ternary diagrams were plotted using different combinations of surfactant to co-surfactant ratios (1:1, 2:1, and 3:1). The combinations used Cremophor RH40, Poly Ethylene Glycol 400 (PEG 400), and peppermint oil, and those that showed the maximum microemulsion region and rapid and stable emulsification were selected for further characterization. The diluted self-microemulsifying mixtures underwent evaluation of dose uniformity, droplet size, zeta potential, and transmission electron microscopy. The selected formulations exhibited uniform delivery of the dose throughout the canister life, along with droplet sizes and zeta potentials that ranged from 24.74 to 88.99 nm and - 19.27 to - 10.00 mV, respectively. The aerosol performance of each self-microemulsifying drug delivery system (SMEDDS)-pMDI was assessed using the Next Generation Impactor, which indicated their capability to deliver the drug to the deeper areas of the lungs. In vitro cytotoxicity testing on A549 and NCI-H358 cells revealed no significant signs of toxicity up to a concentration of 1.56 µg/mL. The antimycobacterial activity of the formulations was evaluated against Mycobacterium bovis using flow cytometry analysis, which showed complete inhibition by day 5 with a minimum bactericidal concentration of 0.313 µg/mL. Moreover, the cellular uptake studies showed efficient delivery of the formulations inside macrophage cells, which indicated the potential for intracellular antimycobacterial activity. These findings demonstrated the potential of the Delamanid-SMEDDS-pMDI for efficient pulmonary delivery of delamanid to improve its effectiveness in the treatment of multi-drug resistant pulmonary TB.


Subject(s)
Nitroimidazoles , Oxazoles , Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , Humans , Lung , Metered Dose Inhalers , Tuberculosis, Multidrug-Resistant/drug therapy , Surface-Active Agents , Solubility , Drug Delivery Systems , Emulsions , Biological Availability
2.
Altern Ther Health Med ; 30(10): 139-145, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38330559

ABSTRACT

Context: Early intervention and treatment are key measures for tuberculosis (TB) prevention and control, making early, rapid, and accurate diagnostic methods crucial. The Liquid-solid (Biphasic) rapid cultures is a novel tool for the differential diagnosis of tuberculosis. Objective: The study intended to evaluate the value of the biphasic cultures by comparing it to the acid-fast staining and liquid cultures, which have been the traditional gold-standard technology, to determine its value in the diagnosis of TB. Design: The research team conducted an experimental study. Setting: The study took place at the Affiliated Wuxi Fifth Hospital of Jiangnan University in Wuxi, China. Participants: Participants were 221 patients with suspected pulmonary tuberculosis who had been admitted to the hospital between July 2020 and December 2021. Outcome Measures: Using three methods-liquid-solid (biphasic) culture, acid-fast staining, and mycobacterial growth indicator tube (MGIT) 960 liquid culture, the research team tested participants' sputum samples: (1) for sensitivity; (2) for time to positive culture results, and (3) for differential diagnosis. Results: The biphasic culture's sensitivity was significantly higher than that of acid-fast staining, (P = .0003), and no significant difference existed between it and the MGIT 960 liquid cultures. The biphasic cultures's mean time to positivity was significantly shorter than that of the MGIT 960 liquid culture at the intervals 11-20 d (P < .0001) and 21-35 days (P = .0001). Moreover, the biphasic cultures could preliminarily differentiate nontuberculous mycobacteria (NTM) from mycobacterium tuberculosis (MTB), which is a significant advantage in tuberculosis diagnosis. Conclusions: This study highlights the potential of a biphasic culture as a reliable tool for the rapid differential diagnosis of tuberculosis, with a faster detection cycle and a higher sensitivity than conventional methods. The biphasic cultures is a valuable addition to the tuberculosis diagnostic armamentarium and can help improve patients' outcomes by enabling earlier diagnosis and treatments.


Subject(s)
Mycobacterium tuberculosis , Sputum , Tuberculosis, Pulmonary , Humans , Diagnosis, Differential , Female , Male , Adult , Middle Aged , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/microbiology , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , China , Bacteriological Techniques/methods , Sensitivity and Specificity , Aged
3.
Altern Ther Health Med ; 30(11): 142-147, 2024 Nov.
Article in English | MEDLINE | ID: mdl-38401110

ABSTRACT

Objective: To explore the application effect of comprehensive nursing based on medical-care integration in diabetic patients with pulmonary tuberculosis. Methods: 80 diabetic patients with pulmonary tuberculosis who were treated at Affiliated Hospital of Hebei University from March 2022 to March 2023 were randomly divided into the routine nursing group and the comprehensive nursing group. The routine nursing group received conventional nursing care, while the comprehensive nursing group received comprehensive nursing based on medical-care integration and routine care. The blood glucose levels, tuberculosis cure rate, negative emotions, quality of life, and satisfaction with nursing care were compared before and after nursing in both groups. Results: After receiving comprehensive nursing care, participants had lower fasting blood glucose, 2-hour postprandial blood glucose, and glycated hemoglobin levels than those who received routine nursing care. Compared to patients receiving standard care, patients under comprehensive care demonstrated increased rates of tuberculosis lesion resolution and tuberculosis bacilli conversion. The assessments of patients' negative emotions using SAS and SDS scores showed lower levels, while their scores for physiological, psychological, and social functions were higher. Additionally, they reported heightened levels of satisfaction with nursing care. Conclusion: The provision of comprehensive nursing based on medical-care integration for patients suffering from diabetes complicated by pulmonary tuberculosis by medical and nursing personnel is advantageous for fostering amelioration in the clinical manifestations of individuals afflicted with this condition. Additionally, it facilitates patients' recuperation while significantly enhancing their emotional well-being, quality of life, and nursing satisfaction.


Subject(s)
Holistic Nursing , Tuberculosis, Pulmonary , Humans , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/nursing , Tuberculosis, Pulmonary/psychology , Male , Female , Middle Aged , Holistic Nursing/methods , Adult , Quality of Life/psychology , Aged , Diabetes Mellitus/psychology
4.
PLoS One ; 19(2): e0298244, 2024.
Article in English | MEDLINE | ID: mdl-38359007

ABSTRACT

BACKGROUND: Public health problems related to tuberculosis (TB) remain substantial globally, particularly in resource-limited countries. Determining TB treatment outcomes and identifying contributing factors are the basic components of the TB control strategy. In Ethiopia, different studies have been done on treatment outcomes and multiple associated factors, and there is also a little information on the effect of nutritional status on TB treatment outcomes. So there is a need for comprehensive research that examines the combined effects of multiple factors along with nutritional status. METHODS: A five-year institution-based retrospective cross-sectional study was conducted at Mizan Tepi University Teaching Hospital, South West Ethiopia. This study included all tuberculosis patients who were documented in the TB registration and had known treatment outcomes at the treatment facility between January 1, 2016, and December 31, 2020. Data was collected through a pretested structured data extraction checklist. Data were entered into Epidata version 3.1 and analyzed through SPSS version 22. Multiple logistic regression was employed to assess the association between dependent and independent variables. A p-value of less than 0.05 was considered statistically significant. RESULT: Of the total 625 TB patients, 283 (45.3%), 175 (28%), and 167 (26.7%) had smear-positive, extra-pulmonary, and smear-negative tuberculosis, respectively. The majority of study participants had normal weight (62.2%), were in the age group of 15-44 (67.4%), were new cases (73.8%), and were from urban areas (69.4%). About 32.2% of cases were HIV-positive. The overall unsuccessful treatment rate was 25%. From the total unsuccessful treatment rates, the highest proportion was a death rate of 90 (14.4%), followed by a treatment failure of 56 (9%). Being female (AOR = 1.7, 95% CI: 1.2-2.5), HIV positive (AOR = 2.7, 95% CI: 1.9-4.1), undernutrition (BMI<18.5kg/m2) (AOR = 1.9, 95% CI: 1.3-2.9), and smear-negative pulmonary TB (AOR = 1.6, 95% CI: 1-2.5) were independent predictors of unsuccessful treatment outcomes. CONCLUSION: The treatment success rate in the study area is very poor. Poor treatment outcomes were associated with undernutrition, female gender, HIV positivity and smear-negative pulmonary TB. So, continuous and serious supervision and monitoring of directly observed treatment short course (DOTS) program accomplishment, early detection of HIV and TB, prompt anti TB and antiretroviral treatment initiation and adherence, enhanced nutritional assessment, and counseling services need to be strengthened to improve treatment outcomes.


Subject(s)
HIV Infections , Malnutrition , Tuberculosis, Pulmonary , Tuberculosis , Humans , Female , Adolescent , Young Adult , Adult , Male , Retrospective Studies , Nutritional Status , Cross-Sectional Studies , Universities , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Treatment Outcome , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology , Hospitals, University , Hospitals, Teaching , Ethiopia/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology
5.
Altern Ther Health Med ; 30(1): 83-87, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37820672

ABSTRACT

Objective: Pulmonary tuberculosis (PTB) and chronic pulmonary aspergillosis (CPA) have many similarities in clinical symptoms. In patients with etiology-positive pulmonary tuberculosis (EPTB), Aspergillus infection is easily overlooked, and missed diagnosis occurs. We attempted to analyze the clinical characteristics and risk factors of EPTB combined with CPA (EPTB-CPA), and to suggest to clinicians the possibility of CPA in EPTB patients. Methods: 58 patients with EPTB-CPA diagnosed and treated in Wuhan Pulmonary Hospital from April 2021 to March 2022 were retrospectively collected as the case group. According to the age group of the case group, 174 patients with EPTB were randomly selected as the control group at a ratio of 1:3. Multivariate logistic regression analysis was utilized to analyze the risk factors. Results: Multivariate Logistic regression analysis was performed on the pulmonary cavity, chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, lung damage, anemia, and hypoproteinemia. Among them, pulmonary cavity (P = .001), COPD (P = .006), and bronchiectasis (P = .020) were statistically significant. Conclusion: Our findings suggest that when EPTB patients present with pulmonary cavities and comorbidities such as COPD or bronchiectasis, clinicians should consider the possibility of CPA. Identifying these risk factors can help improve the accuracy of diagnosis and facilitate early detection and management of EPTB-CPA.


Subject(s)
Bronchiectasis , Pulmonary Aspergillosis , Pulmonary Disease, Chronic Obstructive , Tuberculosis, Pulmonary , Humans , Case-Control Studies , Pulmonary Aspergillosis/complications , Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/epidemiology , Retrospective Studies , Risk Factors , Tuberculosis, Pulmonary/complications
6.
Ann Med ; 55(2): 2291554, 2023.
Article in English | MEDLINE | ID: mdl-38079515

ABSTRACT

Background: Tuberculosis (TB) and malnutrition are major global health problems, with multidrug-resistant (MDR) TB complicating international efforts. The role of vitamin D in susceptibility to and as an adjunctive treatment for TB is being studied extensively, although no study has included MDR-TB patients in context to dietary profile with vitamin D levels and sunlight exposure.Objective: This study aimed to estimate vitamin D serum levels and examine their association with dietary intake of vitamin D and sun exposure in patients with MDR-TB.Methods: North Indian participants were enrolled in three groups: MDR-TB, drug-susceptible pulmonary TB (DS-PTB), and healthy controls. All consenting participants underwent the estimation of macro- and micronutrient intake and sunlight exposure using structured questionnaires. Serum biochemistry, including 25-hydroxyvitamin D and calcium levels, was measured, and the correlation between variables was determined.Results: 747 participants were enrolled. Significant differences among the three groups were found in mean serum 25-hydroxyvitamin D levels, body mass index, macronutrient intake, dietary vitamin D and calcium content, and sun exposure index (SEI). All except sun exposure (SEI was highest in DS-PTB patients) were found to follow the trend: MDR-TB < DS-PTB < healthy controls. The mean serum vitamin D levels of all groups were deficient and correlated positively with dietary intake and SEI.Conclusion: In this study's we found significant association of serum vitamin D concentrations, dietary intake and sunlight exposure in MDR-TB, DS-PTB patients and healthy controls. Dietary intake may be more important than sun exposure in determining serum levels. However, the significance of this finding is uncertain. Further studies are required to confirm the association, direction, and potential for vitamin D supplementation to treat or prevent MDR-TB infection.


Subject(s)
Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , Vitamin D Deficiency , Humans , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/epidemiology , Calcium/therapeutic use , Vitamin D , Diet , Vitamins , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/complications , Sunlight , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology
8.
Lancet Microbe ; 4(11): e913-e922, 2023 11.
Article in English | MEDLINE | ID: mdl-37832571

ABSTRACT

BACKGROUND: Respiratory tract microbiota has been described as the gatekeeper for respiratory health. We aimed to assess the impact of standard-of-care and experimental anti-tuberculosis treatment regimens on the respiratory microbiome and implications for treatment outcomes. METHODS: In this retrospective study, we analysed the sputum microbiome of participants with tuberculosis treated with six experimental regimens versus standard-of-care who were part of the HIGHRIF study 2 (NCT00760149) and PanACEA MAMS-TB (NCT01785186) clinical trials across a 3-month treatment follow-up period. Samples were from participants in Mbeya, Kilimanjaro, Bagamoyo, and Dar es Salaam, Tanzania. Experimental regimens were composed of different combinations of rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), moxifloxacin (M), and a new drug, SQ109 (Q). Reverse transcription was used to create complementary DNA for each participant's total sputum RNA and the V3-V4 region of the 16S rRNA gene was sequenced using the Illumina metagenomic technique. Qiime was used to analyse the amplicon sequence variants and estimate alpha diversity. Descriptive statistics were applied to assess differences in alpha diversity pre-treatment and post-treatment initiation and the effect of each treatment regimen. FINDINGS: Sequence data were obtained from 397 pre-treatment and post-treatment samples taken between Sept 26, 2008, and June 30, 2015, across seven treatment regimens. Pre-treatment microbiome (206 genera) was dominated by Firmicutes (2860 [44%] of 6500 amplicon sequence variants [ASVs]) at the phylum level and Streptococcus (2340 [36%] ASVs) at the genus level. Two regimens had a significant depressing effect on the microbiome after 2 weeks of treatment, HR20mg/kgZM (Shannon diversity index p=0·0041) and HR35mg/kgZE (p=0·027). Gram-negative bacteria were the most sensitive to bactericidal activity of treatment with the highest number of species suppressed being under the moxifloxacin regimen. By week 12 after treatment initiation, microbiomes had recovered to pre-treatment level except for the HR35mg/kgZE regimen and for genus Mycobacterium, which did not show recovery across all regimens. Tuberculosis culture conversion to negative by week 8 of treatment was associated with clearance of genus Neisseria, with a 98% reduction of the pre-treatment level. INTERPRETATION: HR20mg/kgZM was effective against tuberculosis without limiting microbiome recovery, which implies a shorter efficacious anti-tuberculosis regimen with improved treatment outcomes might be achieved without harming the commensal microbiota. FUNDING: European and Developing Countries Clinical Trials Partnership and German Ministry of Education and Research.


Subject(s)
Microbiota , Tuberculosis, Pulmonary , Tuberculosis , Humans , Antitubercular Agents/pharmacology , Drug Therapy, Combination , Moxifloxacin/pharmacology , Retrospective Studies , RNA, Ribosomal, 16S , Sputum/microbiology , Tanzania , Tuberculosis/drug therapy , Tuberculosis, Pulmonary/drug therapy , Clinical Trials as Topic
9.
Mymensingh Med J ; 32(4): 1064-1072, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37777903

ABSTRACT

Approximately 10.0% of tuberculosis (TB) Infected individuals develop clinical disease in the absence of immune suppression suggests that individual factors may play a role in the response to infection. Body's immune function is boosted by micronutrient and also plays a major role in response to tubercular infection. Someone, may argue that cell mediated immunity is compromised in iron deficiency before anemia becomes apparent. This descriptive observational study intended to assess serum iron profile in patients suffering from pulmonary tuberculosis. This study included 56 newly diagnosed sputum smear positive and negative pulmonary tuberculosis patients as per inclusion and exclusion criteria and was conducted at the department of the Internal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh with the collaboration of the Biochemistry department, BSMMU, Bangladesh from February 2017 to January 2018. Collected data were recorded in a structured questionnaire and compiled and appropriate analyses were done by using computer-based software Statistical Package for Social Sciences (SPSS) version 23.0. Out of 56 patients, majority was young and at reproductive age, male was predominant (78.6%) with a male to female ratio of 3.7:1. More than three fourth 43(81.0%) patients were found to have low serum iron concentration. Majority 45(80.4%) patients had normal serum TIBC, 6(10.7%) had low serum total iron binding capacity (TIBC) and 5(8.9%) had high serum TIBC. Almost two third 36(64.3%) patients had low serum transferrin saturation and 20(35.7%) had normal serum transferrin saturation. Majority 31(55.4%) patients had normal serum ferritin, 2(3.6%) had low serum ferritin and 23(41.1%) had high serum ferritin. Serum iron concentration and serum ferritin were significantly associated with chest x-ray abnormalities (p<0.01). Half of the patients were smear positive for acid fast bacilli (AFB) (50.0%). No significant association was found between sputum positive for AFB with iron profile status. In smear positive pulmonary tuberculosis patients, more than three fourth (78.6%) patients had low serum iron concentration at baseline and majority 20(80.0%) patients had normal serum iron concentration after 2(two) months. Mean serum iron concentration was 41.8±17.6mcg/l in baseline and 70.4±29.7mcg/l in at 2(two) month. More than sixty percent (60.7%) patients had low serum transferrin saturation at baseline and 20(80.0%) patients had normal serum transferrin saturation after 2(two) months. Mean serum transferrin saturation was 18.1±7.6% at baseline and 31.2±19.4% in at 2(two) months. After 2(two) months follow up serum iron concentration and serum transferrin saturation had significant improvement (p<0.05). Significant iron deficiency status occurred in pulpmonary tuberculosis and which improved after anti-tubercular treatment without iron supplementation.


Subject(s)
Iron Deficiencies , Tuberculosis, Pulmonary , Tuberculosis , Humans , Male , Female , Ferritins , Iron , Tuberculosis, Pulmonary/diagnosis , Transferrins , Transferrin/metabolism
10.
Dtsch Med Wochenschr ; 148(19): 1227-1235, 2023 09.
Article in German | MEDLINE | ID: mdl-37793615

ABSTRACT

Molecular diagnostic tools have changed the approach to the detection of Mycobacterium tuberculosis and associated drug-resistance substantially. PCR-based technologies allow a more rapid detection with higher diagnostic sensitivity in pulmonary and extrapulmonary specimens. However, a real point of care test, which needs minimal technical resources remains missing. Genome sequencing technologies are currently changing tuberculosis drug resistance testing, and for some questions are replacing phenotypic drug resistance testing, based on culture.New evidence on treatment for drug-sensitive tuberculosis allows shortening of treatment to 4 months, or in selected cases even to 2 months based on the use of fluoroquinolones, high dose rifamycins and newly developed TB medicines.Such developments will very likely simplify the management of tuberculosis, although prevention remains the most important pillar of any tuberculosis related public health strategy.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , Tuberculosis , Humans , Sensitivity and Specificity , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Mycobacterium tuberculosis/genetics , Tuberculosis/drug therapy , Polymerase Chain Reaction , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Antitubercular Agents/therapeutic use , Microbial Sensitivity Tests
11.
Antimicrob Agents Chemother ; 67(10): e0068323, 2023 10 18.
Article in English | MEDLINE | ID: mdl-37768317

ABSTRACT

Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1-15), followed by RIF40 (days 16-30). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%-115%); tolbutamide, 80% (74%-86%); omeprazole, 55% (47%-65%); dextromethorphan, 77% (68%-86%); midazolam, 62% (49%-78%), and 117% (105%-130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number NCT04525235.


Subject(s)
Cytochrome P-450 CYP1A2 , Tuberculosis, Pulmonary , Adult , Humans , Midazolam/therapeutic use , Cytochrome P-450 CYP2D6/metabolism , Caffeine , Rifampin/therapeutic use , Cytochrome P-450 CYP2C19 , Cytochrome P-450 CYP3A/metabolism , Dextromethorphan/therapeutic use , Tolbutamide , Cytochrome P-450 CYP2C9/metabolism , Cytochrome P-450 Enzyme System/metabolism , Omeprazole , Drug Interactions , Tuberculosis, Pulmonary/drug therapy , Digoxin/therapeutic use
12.
J Infect Dev Ctries ; 17(8): 1114-1124, 2023 08 31.
Article in English | MEDLINE | ID: mdl-37699092

ABSTRACT

INTRODUCTION: To get a comprehensive idea about the transmission and epidemiology of TB globally and locally, the use of molecular typing methods has become imperative not only for understanding genetic diversity but also the population structure of Mycobacterium tuberculosis complex (MTBC). We aimed to investigate the drug resistance pattern and genetic diversity of MTBC among previously treated patients with sputum smear-positive pulmonary tuberculosis in a South Indian population. METHODOLOGY: 104 patients with sputum smear positivity and who had previously undergone treatment were selected. Drug susceptibility testing, Spoligotyping, MIRU-VNTR, and SNP typing were performed. RESULTS: Mono-resistance to isoniazid 16 (15.38%) was the highest among all drugs. Out of 104 isolates, 24 (23%) isolates were classified as MDR strains. The distributions of most common lineages were: EAI3-Ind-20 (19.23%), EAI5-13 (12.50%), Beijing-12 (11.54%), CAS1-Delhi- 9 (8.65%), and 7 (6.73%) each of T-H37rv, Unknown and Orphan types. MIRU-VNTR-based analysis revealed that there are two major groups: CAS1-Delhi and Beijing groups. Out of 104 isolates, 82 belonged to well-defined lineages and 6 clusters, and the remaining 22 were singletons. SNP analysis showed no mutations associated with five sets of genes in 33 strains. CONCLUSIONS: The occurrence of 11.54% Beijing strains in South India is an important finding. High frequency of Isoniazid mono resistance noticed. Spoligotyping along with MIRU-VNTR and SNP typing is the best approach to the identification of strain lineages. No mutation with Antigen85C gene represents, can be used for vaccine candidates.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Humans , Mycobacterium tuberculosis/genetics , Isoniazid/pharmacology , Isoniazid/therapeutic use , Microbial Sensitivity Tests , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology , India/epidemiology
13.
Lancet ; 402(10402): 627-640, 2023 08 19.
Article in English | MEDLINE | ID: mdl-37567200

ABSTRACT

BACKGROUND: In India, tuberculosis and undernutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of undernutrition in patients and in the population. The aim of this study was to determine the effect of nutritional supplementation on tuberculosis incidence in household contacts of adults with microbiologically confirmed pulmonary tuberculosis. METHODS: In this field-based, open-label, cluster-randomised controlled trial, we enrolled household contacts of 2800 patients with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units of the National Tuberculosis Elimination Programme in four districts of Jharkhand, India. The tuberculosis units were randomly allocated 1:1 by block randomisation to the control group or the intervention group, by a statistician using computer-generated random numbers. Although microbiologically confirmed pulmonary tuberculosis patients in both groups received food rations (1200 kcal, 52 grams of protein per day with micronutrients) for 6 months, only household contacts in the intervention group received monthly food rations and micronutrients (750 kcal, 23 grams of protein per day with micronutrients). After screening all household contacts for co-prevalent tuberculosis at baseline, all participants were followed up actively until July 31, 2022, for the primary outcome of incident tuberculosis (all forms). The ascertainment of the outcome was by independent medical staff in health services. We used Cox proportional hazards model and Poisson regression via the generalised estimating equation approach to estimate unadjusted hazard ratios, adjusted hazard ratios (aHRs), and incidence rate ratios (IRRs). This study is registered with CTRI-India, CTRI/2019/08/020490. FINDINGS: Between Aug 16, 2019, and Jan 31, 2021, there were 10 345 household contacts, of whom 5328 (94·8%) of 5621 household contacts in the intervention group and 4283 (90·7%) of 4724 household contacts in the control group completed the primary outcome assessment. Almost two-thirds of the population belonged to Indigenous communities (eg, Santhals, Ho, Munda, Oraon, and Bhumij) and 34% (3543 of 10 345) had undernutrition. We detected 31 (0·3%) of 10 345 household contact patients with co-prevalent tuberculosis disease in both groups at baseline and 218 (2·1%) people were diagnosed with incident tuberculosis (all forms) over 21 869 person-years of follow-up, with 122 of 218 incident cases in the control group (2·6% [122 of 4712 contacts at risk], 95% CI 2·2-3·1; incidence rate 1·27 per 100 person-years) and 96 incident cases in the intervention group (1·7% [96 of 5602], 1·4-2·1; 0·78 per 100 person-years), of whom 152 (69·7%) of 218 were patients with microbiologically confirmed pulmonary tuberculosis. Tuberculosis incidence (all forms) in the intervention group had an adjusted IRR of 0·61 (95% CI 0·43-0·85; aHR 0·59 [0·42-0·83]), with an even greater decline in incidence of microbiologically confirmed pulmonary tuberculosis (0·52 [0·35-0·79]; 0·51 [0·34-0·78]). This translates into a relative reduction of tuberculosis incidence of 39% (all forms) to 48% (microbiologically confirmed pulmonary tuberculosis) in the intervention group. An estimated 30 households (111 household contacts) would need to be provided nutritional supplementation to prevent one incident tuberculosis. INTERPRETATION: To our knowledge, this is the first randomised trial looking at the effect of nutritional support on tuberculosis incidence in household contacts, whereby the nutritional intervention was associated with substantial (39-48%) reduction in tuberculosis incidence in the household during 2 years of follow-up. This biosocial intervention can accelerate reduction in tuberculosis incidence in countries or communities with a tuberculosis and undernutrition syndemic. FUNDING: Indian Council of Medical Research-India TB Research Consortium.


Subject(s)
Tuberculosis, Pulmonary , Tuberculosis , Adult , Humans , Incidence , India/epidemiology , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/prevention & control , Tuberculosis, Pulmonary/diagnosis , Dietary Supplements
14.
BMC Pulm Med ; 23(1): 264, 2023 Jul 18.
Article in English | MEDLINE | ID: mdl-37464373

ABSTRACT

OBJECTIVE: The purpose of this study was to collect data on the current state of patient delay by patients with tuberculosis (TB) in Lishui City, Zhejiang Province who were under the care of a TB-designated hospital from 2011 to 2021 and to analyze the factors that contribute to this problem in order to provide a scientific basis for the prevention and control of TB. METHODS: In this observational study, we collected data on patients with pulmonary TB that were reported to the Chinese government's disease prevention and control information system by the Traditional Chinese Medicine Hospital in Lishui City between 2011 and 2021. The data included demographics like age, gender, occupation, household registration, current address, date of symptoms, date of first visit, and etiology results. Multivariate logistic regression analysis was used to analyze the factors influencing patient delay by patients with pulmonary TB. RESULTS: There were 3,190 cases of pulmonary TB treated in a TB-designated hospital in Lishui City, Zhejiang Province, between 2011 and 2021. Of these, 2,268 involved patient delay, with the delay rate of 71.10% and the median (Q25, Q75) days of patient delay being 36 (25, 72) days. Results of multivariate logistic regression analysis indicated the presence of risk factors-age > 60 years old (OR = 1.367, 95% CI: 1.144 ~ 1.632), pathogen positive (OR = 1.211, 95% CI: 1.033 ~ 1.419), and employed as peasants (OR = 1.353, 95% CI:1.144 ~ 1.601) for patient delay in patients with pulmonary TB. Patients with diabetes mellitus made up 64.94% of the pulmonary TB population, which was lower than the 71.58% of patients without diabetes mellitus (χ2 = 4.602, P = 0.032). Additionally, the presence of diabetes mellitus may be a protective factor in patient delay in patients with pulmonary TB (OR = 0.641, 95% CI: 0.481 ~ 0.856). CONCLUSION: High rates of patient delay, age > 60 years old, a positive etiology, and being employed as peasants are all possible risk factors for pulmonary TB in Lishui City, Zhejiang Province.


Subject(s)
Tuberculosis, Pulmonary , Tuberculosis , Humans , Middle Aged , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis/epidemiology , Delivery of Health Care , Risk Factors , Cities
15.
Trials ; 24(1): 435, 2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37370174

ABSTRACT

BACKGROUND: The duration and regimen of tuberculosis (TB) treatment is currently based predominantly on whether the M. tuberculosis (Mtb) strain is drug-sensitive (DS) or multidrug-resistant (MDR) with doses adjusted by patients' weight only. The systematic stratification of patients for personalized treatment does not exist for TB. As each TB case is different, individualized treatment regimens should be applied to obtain better outcomes. In this scenario, novel therapeutic approaches are urgently needed to (1) improve outcomes and (2) shorten treatment duration, and host-directed therapies (HDT) might be the best solution. Within HDT, repurposed drugs represent a shortcut in drug development and can be implemented at the short term. As hyperinflammation is associated with worse outcomes, HDT with an anti-inflammatory effect might improve outcomes by reducing tissue damage and thus the risk of permanent sequelae. METHODS: SMA-TB is a multicentre randomized, phase IIB, placebo-controlled, three-arm, double-blinded clinical trial (CT) that has been designed in the context of the EC-funded SMA-TB Project ( www.smatb.eu ) in which we propose to use 2 common non-steroidal anti-inflammatory drugs (NSAID), acetylsalicylic acid (ASA) and ibuprofen (Ibu), as an HDT for use as adjunct therapy added to, and compared with, the standard of care (SoC) World Health Organization (WHO)-recommended TB regimen in TB patients. A total of 354 South African and Georgian adults diagnosed with confirmed pulmonary TB will be randomized into SoC TB treatment + placebo, SoC + acetylsalicylic acid or SoC + ibuprofen. DISCUSSION: SMA-TB will provide proof of concept of the HDT as a co-adjuvant treatment and identify the suitability of the intervention for different population groups (different epidemiological settings and drug susceptibility) in the reduction of tissue damage and risk of bad outcomes for TB patients. This regimen potentially will be more effective and targeted: organ saving, reducing tissue damage and thereby decreasing the length of treatment and sequelae, increasing cure rates and pathogen clearance and decreasing transmission rates. It will result in better clinical practice, care management and increased well-being of TB patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT04575519. Registered on October 5, 2020.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Adult , Humans , Anti-Inflammatory Agents/therapeutic use , Antitubercular Agents/adverse effects , Aspirin/adverse effects , Ibuprofen/adverse effects , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Treatment Outcome , Tuberculosis, Pulmonary/diagnosis , World Health Organization , Clinical Trials, Phase II as Topic
16.
Int J Mycobacteriol ; 12(2): 117-121, 2023.
Article in English | MEDLINE | ID: mdl-37338470

ABSTRACT

Background: Tuberculosis (TB) is a leading cause of mortality worldwide. The higher prevalence of anemia among TB patients is concerning due to its association with delayed sputum conversion and poor treatment outcomes. The present study aimed to evaluate the association of anemia with sputum smear conversion and treatment outcomes among TB patients. Methods: In a prospective community-based cohort study, TB patients were recruited from 63 primary health centers in the district. Blood samples were collected at baseline, at 2 months, and at the end of 6 months. Data were analyzed using SPSS software version 15. Results: Out of 661 patients recruited, anemia was observed among 503 (76.1%) participants. Prevalence of anemia was more among males 387 (76.9%) than 116 (23.1%) females. Out of 503 anemic patients, 334 (66.4%) had mild, 166 (33.0%) had moderate, and 3 (0.6%) had severe anemia at baseline. At 6-month treatment completion, 16 (6.3%) were still anemic. Among 503 anemic patients, 445 (88.4%) were given iron supplements and remaining 58 (11.6%) were managed with diet modifications. After completion of TB treatment, 495 (98.4%) patients had favorable treatment outcomes, whereas 8 (1.6%) patients had died. Severe anemia was not associated with poor outcomes. Conclusions: The presence of anemia among newly diagnosed TB patients, especially pulmonary TB was high. Increased risk of anemia was noted among males who were alcohol and tobacco consumers. There was no significant association between the presence of anemia and sputum conversion from baseline to 6 months of treatment completion.


Subject(s)
Anemia , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Male , Female , Humans , Cohort Studies , Antitubercular Agents/therapeutic use , Prospective Studies , Sputum , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology , Treatment Outcome , Anemia/epidemiology , India/epidemiology
17.
Front Cell Infect Microbiol ; 13: 1105872, 2023.
Article in English | MEDLINE | ID: mdl-37284503

ABSTRACT

Tuberculosis (TB) caused by the complex Mycobacterium tuberculosis (Mtb) is the main cause of death by a single bacterial agent. Last year, TB was the second leading infectious killer after SARS-CoV-2. Nevertheless, many biological and immunological aspects of TB are not completely elucidated, such as the complex process of immunoregulation mediated by regulatory T cells (Treg cells) and the enzymes indoleamine 2,3-dioxygenase (IDO) and heme oxygenase 1 (HO-1). In this study, the contribution of these immunoregulatory factors was compared in mice infected with Mtb strains with different levels of virulence. First Balb/c mice were infected by intratracheal route, with a high dose of mild virulence reference strain H37Rv or with a highly virulent clinical isolate (strain 5186). In the lungs of infected mice, the kinetics of Treg cells during the infection were determined by cytofluorometry and the expression of IDO and HO-1 by RT-PCR and immunohistochemistry. Then, the contribution of immune-regulation mediated by Treg cells, IDO and HO-1, was evaluated by treating infected animals with specific cytotoxic monoclonal antibodies for Treg cells depletion anti-CD25 (PC61 clone) or by blocking IDO and HO-1 activity using specific inhibitors (1-methyl-D,L-tryptophan or zinc protoporphyrin-IX, respectively). Mice infected with the mild virulent strain showed a progressive increment of Treg cells, showing this highest number at the beginning of the late phase of the infection (28 days), the same trend was observed in the expression of both enzymes being macrophages the cells that showed the highest immunostaining. Animals infected with the highly virulent strain showed lower survival (34 days) and higher amounts of Treg cells, as well as higher expression of IDO and HO-1 one week before. In comparison with non-treated animals, mice infected with strain H37Rv with depletion of Treg cells or treated with the enzymes blockers during late infection showed a significant decrease of bacilli loads, higher expression of IFN-g and lower IL-4 but with a similar extension of inflammatory lung consolidation determined by automated morphometry. In contrast, the depletion of Treg cells in infected mice with the highly virulent strain 5186 produced diffuse alveolar damage that was similar to severe acute viral pneumonia, lesser survival and increase of bacillary loads, while blocking of both IDO and HO-1 produced high bacillary loads and extensive pneumonia with necrosis. Thus, it seems that Treg cells, IDO and HO-1 activities are detrimental during late pulmonary TB induced by mild virulence Mtb, probably because these factors decrease immune protection mediated by the Th1 response. In contrast, Treg cells, IDO and HO-1 are beneficial when the infection is produced by a highly virulent strain, by regulation of excessive inflammation that produced alveolar damage, pulmonary necrosis, acute respiratory insufficiency, and rapid death.


Subject(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Mice , Animals , Heme Oxygenase-1 , Mycobacterium tuberculosis/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , T-Lymphocytes, Regulatory , Virulence , COVID-19/metabolism , SARS-CoV-2/metabolism , Lung/microbiology , Necrosis/metabolism
18.
BMJ Case Rep ; 16(3)2023 Mar 02.
Article in English | MEDLINE | ID: mdl-36863757

ABSTRACT

A man in his 20s who had previously experienced multiple episodes of transient loss of consciousness, majorly attributable to the seizures, presented with a 1-month history of increased seizure frequency, high-grade fever and weight loss. Clinically, he had postural instability, bradykinesia and symmetrical cogwheel rigidity. His investigations revealed hypocalcaemia, hyperphosphataemia, inappropriately normal intact parathyroid hormone, metabolic alkalosis, normomagnesemic magnesium depletion, and increased plasma renin activity and serum aldosterone concentration. CT scan of the brain revealed symmetrical calcification of the basal ganglia. The patient had primary hypoparathyroidism (HP). A similar presentation of his brother indicated a genetic cause, most likely autosomal dominant hypocalcaemia with Bartter's syndrome type 5. The patient's fever was caused by underlying haemophagocytic lymphohistiocytosis secondary to pulmonary tuberculosis, which triggered acute episodes of hypocalcaemia. This case represents a complex interplay of a multifaceted relationship between primary HP, vitamin D deficiency and an acute stressor.


Subject(s)
Hypocalcemia , Hypoparathyroidism , Lymphohistiocytosis, Hemophagocytic , Tuberculosis, Pulmonary , Male , Humans , Hypocalcemia/complications , Lymphohistiocytosis, Hemophagocytic/complications , Patients , Tuberculosis, Pulmonary/complications , Fever , Hypoparathyroidism/complications
19.
PLoS One ; 18(3): e0272682, 2023.
Article in English | MEDLINE | ID: mdl-36996065

ABSTRACT

BACKGROUND: The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. METHODS: This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. RESULTS: A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. CONCLUSIONS: The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. TRIAL REGISTRATION: CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).


Subject(s)
Cholecalciferol , Tuberculosis, Pulmonary , Humans , Cholecalciferol/therapeutic use , Dietary Supplements/adverse effects , Treatment Outcome , Vitamin D , Vitamins/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/prevention & control , Double-Blind Method , Recurrence
20.
Int J Prison Health ; 2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36622107

ABSTRACT

PURPOSE: This intensified case finding study aimed to evaluate the prevalence of tuberculosis (TB) disease among people with HIV entering the largest prison in Malaysia. DESIGN/METHODOLOGY/APPROACH: The study was conducted in Kajang prison, starting in July 2013 in the men's prison and June 2015 in the women's prison. Individuals tested positive for HIV infection, during the mandatory HIV testing at the prison entry, were consecutively recruited over five months at each prison. Consented participants were interviewed using a structured questionnaire and asked to submit two sputum samples that were assessed using GeneXpert MTB/RIF (Xpert) and culture, irrespective of clinical presentation. Factors associated with active TB (defined as a positive result on either Xpert or culture) were assessed using regression analyses. FINDINGS: Overall, 214 incarcerated people with HIV were recruited. Most were men (84.6%), Malaysians (84.1%) and people who inject drugs (67.8%). The mean age was 37.5 (SD 8.2) years, and median CD4 lymphocyte count was 376 cells/mL (IQR 232-526). Overall, 27 (12.6%) TB cases were identified, which was independently associated with scores of five or more on the World Health Organization clinical scoring system for prisons (ARR 2.90 [95% CI 1.48-5.68]). ORIGINALITY/VALUE: Limited data exists about the prevalence of TB disease at prison entry, globally and none from Malaysia. The reported high prevalence of TB disease in the study adds an important and highly needed information to design comprehensive TB control programmes in prisons.


Subject(s)
Coinfection , HIV Infections , Prisons , Southeast Asian People , Tuberculosis, Pulmonary , Adult , Female , Humans , Male , HIV Infections/complications , HIV Infections/diagnosis , HIV Infections/epidemiology , Malaysia/epidemiology , Prisons/statistics & numerical data , Southeast Asian People/statistics & numerical data , Tuberculosis/epidemiology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Coinfection/diagnosis , Coinfection/epidemiology , Sputum/microbiology
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