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1.
Ann Glob Health ; 88(1): 26, 2022.
Article in English | MEDLINE | ID: covidwho-1847566

ABSTRACT

Background: The COVID-19 pandemic has undone years of progress in providing essential TB services and controlling the TB burden. Italy, a low TB burden country, has an incidence of 7.1 cases per 100,000 people. To control the TB spreading in Italy is critical to investigate the characteristics of patients with the worst outcomes and the highest risk of adverse events related to antituberculosis therapy. Therefore, we conducted a large retrospective study in TB patients admitted to the Clinic of Infectious Diseases University of Bari, Italy, in order to describe the clinical presentation and the factors associated with adverse events and outcomes. Methods: We retrospectively evaluated the patients admitted to the Clinic of Infectious Diseases from January 2013 to 15 December 2021. We stratified our cohort into two groups: <65 years of age and ≥65 years in order to assess any differences between the two groups. Two logistic regression models were implemented considering the dependent variables as: (I) the adverse events; and (II) the unsuccessful treatments. Results: In total, 206 consecutive patients [60% (n = 124) M, median age 39 years, range 16-92] were diagnosed and admitted with TB at Clinic of Infectious Diseases. Of the whole sample, 151 (74%) were <65 years and 55 (26%) were ≥65. Statistically significant differences between the two groups were detected (p-value < 0.05) for nationality (p-value = 0.01), previous contact with TB patient (p-value = 0.00), type of TB (p-value = 0.00), unsuccessful treatment (p-value = 0.00), length of hospitalization (p-value = 0.02) and diagnostic delay (p-value = 0.01). Adverse events related to TB drug regimen were reported in 24% (n = 49). Age < 65 years (O.R. = 3.91; 95% CI 1.72-4.21), non-Italian nationality (O.R. = 4.45; 95% CI 2.22-4.98.), homeless (O.R. = 3.23; 95% CI 2.58-4.54), presence of respiratory symptoms (O.R. = 1.23; 95% CI 1.10-1.90), diagnostic delay (O.R = 2.55; 95% CI 1.98-3.77) resulted associated with unsuccessful treatment outcome (death, failure or lost to follow up). Finally, age < 65 years (O.R. = 1.73; 95% CI 1.31-2.49), presence of pulmonary TB (O.R. = 1.15; 95% CI 1.02-1.35), length of hospitalization (O.R. = 1.82; 95% CI 1.35-2.57) and TB culture positive (O.R. = 1.35; 95% CI 1.12-1.82) were associated with adverse events in our populations. Conclusions: The pharmacological approach alone seems insufficient to treat and cure a disease whose ethiopathogenesis is not only due to the Mycobacterium tuberculosis, but also to the poverty or the social fragility. Our data suggest that young foreigners, the homeless, and the people with low social and economic status are at higher risk of an unfavorable outcome in low incidence TB countries. Targeted actions to support this highly vulnerable population both in terms of outcome and occurrence of adverse events are needed.


Subject(s)
COVID-19 , Tuberculosis, Pulmonary , Adolescent , Adult , Aged , Aged, 80 and over , Antitubercular Agents/adverse effects , Delayed Diagnosis , Hospitals , Humans , Middle Aged , Pandemics , Referral and Consultation , Retrospective Studies , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology , Young Adult
2.
Lancet Infect Dis ; 22(4): 507-518, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1839425

ABSTRACT

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.


Subject(s)
Antibiotics, Antitubercular , HIV Infections , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Adolescent , Adult , Antibiotics, Antitubercular/therapeutic use , Child , Cross-Sectional Studies , HIV Infections/complications , HIV Infections/drug therapy , Humans , Prospective Studies , Rifampin , Sensitivity and Specificity , Tuberculosis/diagnosis , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy
3.
J Bras Pneumol ; 48(2): e20210515, 2022.
Article in English, Portuguese | MEDLINE | ID: covidwho-1836603

ABSTRACT

OBJECTIVE: To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. METHODS: The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. RESULTS: The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. CONCLUSIONS: This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.


Subject(s)
Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , Tuberculosis , Brazil/epidemiology , Humans , Lung , Mexico/epidemiology , Oxygen , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology
4.
Comput Intell Neurosci ; 2022: 1708133, 2022.
Article in English | MEDLINE | ID: covidwho-1816843

ABSTRACT

Objective: To explore the effect of big data analysis-based remote management combined with Yangyin Runfei decoction on coagulation function, pulmonary function, and quality of life (QOL) of pulmonary tuberculosis (PTB) patients. Methods: A total of 90 PTB patients treated in our hospital from May 2019 to May 2020 were selected as the subjects and divided into the experimental group (EG) and control group (CG) according to their admission order, with 45 cases each. Patients in CG accepted routine management and treatments and those in EG received big data analysis-based remote management combined with Yangyin Runfei decoction, so as to compare the clinical indicators between the two groups. Results: Compared with CG after treatment, EG presented an obviously higher total clinical effective rate, various pulmonary function indicators, and GQOLI-74 score (P < 0.001) and significantly lower various coagulation indicators and inflammatory factor indicators (P < 0.001). Conclusion: Performing big data analysis-based remote management combined with Yangyin Runfei decoction to PTB patients can effectively improve their QOL and pulmonary function and present a higher application value compared to routine management and treatments. Further research will be conducive to establishing a better solution for patients. This trial is registered with Clinical Study Registration Number: https://clinicaltrials.gov/ct2/show/ChiCTR2200057257.


Subject(s)
Quality of Life , Tuberculosis, Pulmonary , Data Analysis , Humans , Treatment Outcome , Tuberculosis, Pulmonary/drug therapy
5.
BMC Infect Dis ; 22(1): 204, 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1779608

ABSTRACT

BACKGROUND: There was a lack of information about prognostic accuracy of time to sputum culture conversion (SCC) in forecasting cure among extensively drug-resistant tuberculosis (XDR-TB) patients. Therefore, this study evaluated the prognostic accuracy of SCC at various time points in forecasting cure among XDR-TB patients. METHODS: This retrospective observational study included 355 eligible pulmonary XDR-TB patients treated at 27 centers in Pakistan between 01-05-2010 and 30-06-2017. The baseline and follow-up information of patients from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. Time to SCC was analyzed by Kaplan-Meier method, and differences between groups were compared through log-rank test. Predictors of time to SCC and cure were respectively evaluated by multivariate Cox proportional hazards and binary logistic regression analyses. A p-value < 0.05 was considered statistically significant. RESULTS: A total of 226 (63.6%) and 146 (41.1%) patients respectively achieved SCC and cure. Median time to SCC was significantly shorter in patients who achieved cure, 3 months (95% confidence interval [CI]: 2.47-3.53), than those who did not (median: 10 months, 95% CI: 5.24-14.76) (p-value < 0.001, Log-rank test). Patient's age > 40 years (hazards ratio [HR] = 0.632, p-value = 0.004), baseline sputum grading of scanty, + 1 (HR = 0.511, p-value = 0.002), + 2, + 3 (HR = 0.523, p-value = 0.001) and use of high dose isoniazid (HR = 0.463, p-value = 0.004) were significantly associated with early SCC. Only SCC at 6 month of treatment had statistically significant association with cure (odds ratio = 15.603, p-value < 0.001). In predicting cure, the sensitivities of SCC at 2, 4 and 6 months were respectively 41.8% (95%CI: 33.7-50.2), 69.9% (95%CI: 61.7-77.2) and 84.9% (95%CI: 78.1-90.3), specificities were respectively, 82.8% (95%CI: 76.9-87.6), 74.6% (95%CI: 68.2-80.4) and 69.4% (95%CI: 62.6-75.5) and prognostic accuracies were respectively 65.9% (95%CI: 60.7-70.8), 72.7% (95%CI: 67.7-77.2) and 75.8% (95%CI: 71.0-80.1). CONCLUSION: In forecasting cure, SCC at month 6 of treatment performed better than SCC at 2 and 4 months. However, it would be too long for clinicians to wait for 6 months to decide about the regimen efficacy. Therefore, with somewhat comparable prognostic accuracy to that SCC at 6 month, using SCC at 4 month of treatment as a prognostic marker in predicting cure among XDR-TB patients can decrease the clinicians waiting time to decide about the regimen efficacy.


Subject(s)
Extensively Drug-Resistant Tuberculosis , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , Adult , Antitubercular Agents/therapeutic use , Extensively Drug-Resistant Tuberculosis/diagnosis , Extensively Drug-Resistant Tuberculosis/drug therapy , Humans , Prognosis , Retrospective Studies , Sputum , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy
8.
Int J Mol Sci ; 23(4)2022 Feb 10.
Article in English | MEDLINE | ID: covidwho-1715394

ABSTRACT

Tuberculosis (TB) is one of the ten leading causes of death worldwide. Patients with TB have been observed to suffer from depression and anxiety linked to social variables. Previous experiments found that the substantial pulmonary inflammation associated with TB causes neuroinflammation, neuronal death, and behavioral impairments in the absence of brain infection. Curcumin (CUR) is a natural product with antioxidant, anti-inflammatory and antibacterial activities. In this work, we evaluated the CUR effect on the growth control of mycobacteria in the lungs and the anti-inflammatory effect in the brain using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive mycobacteria (strain H37Rv). The results have shown that CUR decreased lung bacilli load and pneumonia of infected animals. Finally, CUR significantly decreased neuroinflammation (expression of TNFα, IFNγ and IL12) and slightly increased the levels of nuclear factor erythroid 2-related to factor 2 (Nrf2) and the brain-derived neurotrophic factor (BDNF) levels, improving behavioral status. These results suggest that CUR has a bactericidal effect and can control pulmonary mycobacterial infection and reduce neuroinflammation. It seems that CUR has a promising potential as adjuvant therapy in TB treatment.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antitubercular Agents/pharmacology , Brain/microbiology , Curcumin/pharmacology , Lung/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis/drug therapy , Animals , Brain/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Disease Models, Animal , Inflammation/drug therapy , Inflammation/metabolism , Lung/metabolism , Male , Mice , Mice, Inbred BALB C , Mycobacterium tuberculosis/drug effects , Tuberculosis/metabolism , Tuberculosis, Pulmonary/metabolism
9.
Epidemiol Infect ; 150: e41, 2022 02 22.
Article in English | MEDLINE | ID: covidwho-1709007

ABSTRACT

Mycobacterium tuberculosis is the cause of tuberculosis (TB), a granulomatous illness that mostly affects the lungs. Pakistan is one of the eight nations that accounts for two-thirds of all new cases of developing TB. TB has long been an endemic disease in Pakistan. According to the World Health Organization (WHO) estimates, the nation has over 500 000 incident TB infections per year, with a rising number of drug-resistant cases. Recently, the coexistence of COVID-19 and TB in Pakistan has provided doctors with a problem. Fever or chills, cough, shortness of breath or difficulty breathing are all signs of COVID-19. After SARS-CoV-2 infection, cough might persist for weeks or months and it is frequently accompanied by persistent tiredness, cognitive impairment, dyspnoea or pain - a group of long-term consequences known as post-COVID syndrome or protracted COVID. Coughing with mucus or blood, and coughing that continues over 2 months are indications of TB. The same clinical presentation features make it difficult for healthcare personnel to effectively evaluate the illness and prevent the spread of these fatal diseases. Pakistan lacks the necessary healthcare resources to tackle two contagious diseases at the same time. To counteract the sudden increase in TB cases, appropriate management and effective policies must be implemented. Thus, in order to prevent the spread of these infectious diseases, it is critical to recognise and address the problems that the healthcare sector faces, as well as to create an atmosphere in which the healthcare sector can function at its full potential.


Subject(s)
COVID-19/epidemiology , Delivery of Health Care , Tuberculosis, Pulmonary/epidemiology , Humans , Pakistan/epidemiology , SARS-CoV-2 , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy
10.
BMJ Glob Health ; 7(2)2022 02.
Article in English | MEDLINE | ID: covidwho-1685569

ABSTRACT

INTRODUCTION: Active case finding (ACF) of individuals with tuberculosis (TB) is a key intervention to find the 30% of people missed every year. However, ACF requires screening large numbers of individuals who have a low probability of positive results, typically <5%, which makes using the recommended molecular tests expensive. METHODS: We conducted two ACF surveys (in 2020 and 2021) in high TB burden areas of Lao PDR. Participants were screened for TB symptoms and received a chest X-ray. Sputum samples of four consecutive individuals were pooled and tested with Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) (Xpert-MTB/RIF) (2020) or Xpert-Ultra (2021). The agreement of the individual and pooled samples was compared and the reasons for discrepant results and potential cartridge savings were assessed. RESULTS: Each survey included 436 participants, which were tested in 109 pools. In the Xpert-MTB/RIF survey, 25 (sensitivity 89%, 95% CI 72.8% to 96.3%) of 28 pools containing MTB-positive samples tested positive and 81 pools containing only MTB-negative samples tested negative (specificity 100%, 95% CI 95.5% to 100%). In the Xpert-Ultra survey, all 32 (sensitivity 100%, 95% CI 89.3% to 100%) pools containing MTB-positive samples tested positive and all 77 (specificity 100%, 95% CI 95.3% to 100%) containing only MTB-negative samples tested negative. Pooling with Xpert-MTB/RIF and Xpert-Ultra saved 52% and 46% (227/436 and 199/436, respectively) of cartridge costs alone. CONCLUSION: Testing single and pooled specimens had a high level of agreement, with complete concordance when using Xpert-Ultra. Pooling samples could generate significant cartridge savings during ACF campaigns.


Subject(s)
Antibiotics, Antitubercular , Tuberculosis, Pulmonary , Tuberculosis , Antibiotics, Antitubercular/pharmacology , Antibiotics, Antitubercular/therapeutic use , Drug Resistance, Bacterial , Humans , Laos , Rifampin , Sensitivity and Specificity , Sputum/microbiology , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology
11.
PLoS One ; 16(12): e0261442, 2021.
Article in English | MEDLINE | ID: covidwho-1593549

ABSTRACT

A laboratory validation study was conducted to assess the equivalence of Xpert MTB/RIF Ultra testing on the GeneXpert System and the GeneXpert Omni System ('Omni') for tuberculosis and rifampicin resistance. High concordance of the two devices was demonstrated for well-characterized clinical samples as well as control materials, with controls tested on Omni at normal and challenging environmental conditions (i.e. 35°C, 90% relative humidity). Equivalence of the Cts for all probes was also shown. Equivalence was demonstrated for the Omni and GeneXpert devices for tuberculosis and rifampicin resistance detection for a diverse range of clinical specimens and environmental conditions.


Subject(s)
Antibiotics, Antitubercular/pharmacology , Mycobacterium tuberculosis/drug effects , Point-of-Care Testing , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Pulmonary/diagnosis , Bacterial Proteins/genetics , DNA-Directed RNA Polymerases/genetics , Drug Resistance, Multiple, Bacterial/genetics , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Rifampin/pharmacology , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy
12.
Molecules ; 26(21)2021 Oct 23.
Article in English | MEDLINE | ID: covidwho-1512507

ABSTRACT

Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years). While this regimen is normally effective when taken as prescribed, many people with TB experience difficulties in complying with their medication schedule. Furthermore, the oral administration of standard anti-TB drugs causes severe side effects and widespread resistances. Recently, we proposed an original platform for pulmonary TB treatment consisting of mannitol microspheres (Ma MS) containing iron (III) trimesate metal-organic framework (MOF) MIL-100 nanoparticles (NPs). In the present work, we loaded this system with the first-line anti-TB drug isoniazid (INH) and evaluated both the viability and safety of the drug vehicle components, as well as the cell internalization of the formulation in alveolar A549 cells. Results show that INH-loaded MOF (INH@MIL-100) NPs were efficiently microencapsulated in Ma MS, which displayed suitable aerodynamic characteristics for pulmonary administration and non-toxicity. MIL-100 and INH@MIL-100 NPs were efficiently internalized by A549 cells, mainly localized in the cytoplasm. In conclusion, the proposed micro-nanosystem is a good candidate for the pulmonary administration of anti-TB drugs.


Subject(s)
Antitubercular Agents/pharmacology , Isoniazid/pharmacology , Metal-Organic Frameworks/pharmacology , Tuberculosis, Pulmonary/drug therapy , A549 Cells , Administration, Inhalation , Antitubercular Agents/administration & dosage , Antitubercular Agents/chemistry , Capsules/administration & dosage , Capsules/chemistry , Capsules/pharmacology , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Isoniazid/administration & dosage , Isoniazid/chemistry , Metal-Organic Frameworks/administration & dosage , Metal-Organic Frameworks/chemistry , Particle Size
13.
Front Immunol ; 12: 656419, 2021.
Article in English | MEDLINE | ID: covidwho-1506563

ABSTRACT

Tuberculosis (TB) is the global health problem with the second highest number of deaths from a communicable disease after COVID-19. Although TB is curable, poor health infrastructure, long and grueling TB treatments have led to the spread of TB pandemic with alarmingly increasing multidrug-resistant (MDR)-TB prevalence. Alternative host modulating therapies can be employed to improve TB drug efficacies or dampen the exaggerated inflammatory responses to improve lung function. Here, we investigated the adjunct therapy of natural immune-modulatory compound berberine in C57BL/6 mouse model of pulmonary TB. Berberine treatment did not affect Mtb growth in axenic cultures; however, it showed increased bacterial killing in primary murine bone marrow-derived macrophages and human monocyte-derived macrophages. Ad libitum berberine administration was beneficial to the host in combination with rifampicin and isoniazid. Berberine adjunctive treatment resulted in decreased lung pathology with no additive or synergistic effects on bacterial burdens in mice. Lung immune cell flow cytometry analysis showed that adjunctive berberine treatment decreased neutrophil, CD11b+ dendritic cell and recruited interstitial macrophage numbers. Late onset of adjunctive berberine treatment resulted in a similar phenotype with consistently reduced numbers of neutrophils both in lungs and the spleen. Together, our results suggest that berberine can be supplemented as an immunomodulatory agent depending on the disease stage and inflammatory status of the host.


Subject(s)
Antitubercular Agents/therapeutic use , Berberine/therapeutic use , Immunologic Factors/therapeutic use , Isoniazid/therapeutic use , Rifampin/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Animals , Antitubercular Agents/pharmacology , Berberine/pharmacology , Cytokines/immunology , Dendritic Cells/drug effects , Drug Therapy, Combination , Female , Humans , Immunologic Factors/pharmacology , Isoniazid/pharmacology , Lung/drug effects , Lung/immunology , Lung/microbiology , Lung/pathology , Macrophages/drug effects , Macrophages/immunology , Male , Mice, Inbred C3H , Mice, Inbred C57BL , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Neutrophils/drug effects , Neutrophils/immunology , Rifampin/pharmacology , Spleen/drug effects , Spleen/immunology , Spleen/microbiology , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/pathology
14.
J Mother Child ; 25(2): 127-134, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1498444

ABSTRACT

Various guidelines are in place for management for COVID-19 and pulmonary tuberculosis (PTB) in pregnancy. However, to the best of our knowledge, there are no significant guidelines for the management of COVID-19 and PTB co-infection in pregnancy. Pregnancy being an altered physiological state, the use of various drugs and their outcomes are altered. Here we present two cases of COVID-19 and PTB co-infection in pregnancy which were managed successfully.


Subject(s)
COVID-19 , Coinfection , Latent Tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , COVID-19/complications , Coinfection/diagnosis , Female , Humans , Pregnancy , Tuberculosis/complications , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy
15.
PLoS One ; 16(9): e0257647, 2021.
Article in English | MEDLINE | ID: covidwho-1430547

ABSTRACT

INTRODUCTION: Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment. MATERIALS AND METHOD: We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application. RESULTS: Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01-1.44), 1.73 (95% CI: 1.05-2.84) and 2.68 (95% CI: 1.4-5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81-4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33-8.00) and 1.92 (95% CI: 0.80-4.60) while for >2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement <2, and a smear grade less than 2+ had a better prognosis and constituted minimal disease. CONCLUSION: Baseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.


Subject(s)
Mycobacterium tuberculosis/physiology , Rifampin/therapeutic use , Sputum/microbiology , Tuberculosis, Pulmonary/diagnostic imaging , Tuberculosis, Pulmonary/drug therapy , Adult , Female , Humans , Kaplan-Meier Estimate , Male , Multivariate Analysis , Proportional Hazards Models , Rifampin/pharmacology , Treatment Outcome , Tuberculosis, Pulmonary/microbiology , Young Adult
16.
Sci Rep ; 11(1): 18023, 2021 09 09.
Article in English | MEDLINE | ID: covidwho-1402127

ABSTRACT

Similar to global trends, the incidence rate of tuberculosis (TB) in China declined from 2000 to 2018. In this study, we aimed to evaluate TB trends in northern Guizhou Province and identify risk factors associated with rifampicin-resistant (RR) and concurrent extrapulmonary TB (EPTB). We analyzed data of TB patients hospitalized in Affiliated Hospital of Zunyi Medical University from 2011 to 2018, and assessed correlations between demographic characteristics of patients and RR-TB as well as concurrent EPTB. Our results showed that numbers of new, retreated, RR-TB and concurrent EPTB cases increased gradually from 2011 to 2018. Retreated patients had the highest odds of RR-TB but a lower likelihood of concurrent EPTB compared to new patients. Patients between 21 and 40 years of age had a higher likelihood of RR-TB compared to those 20 years and younger. Female patients and patients from Bijie city as well as the Miao ethnic minority had higher odds of concurrent EPTB. In summary, our data demonstrate upward trends in new, rifampicin-resistant and concurrent extrapulmonary TB cases in northern Guizhou Province of China, which should not be overlooked especially during and post the COVID-19 pandemic because TB is a greater long-term global health threat than COVID-19.


Subject(s)
Antibiotics, Antitubercular/therapeutic use , Mycobacterium tuberculosis/drug effects , Rifampin/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , China/epidemiology , Drug Resistance, Multiple, Bacterial/physiology , Expert Systems , Female , Humans , Incidence , Male , Middle Aged , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Retrospective Studies , Risk Factors , Young Adult
18.
Med Sci Monit ; 27: e934292, 2021 Aug 09.
Article in English | MEDLINE | ID: covidwho-1348802

ABSTRACT

The World Health Organization (WHO) estimated that in 2019, 10.0 million people worldwide developed tuberculosis (TB), with 1.4 million deaths from TB in that year. Infection with Mycobacterium tuberculosis that is resistant to at least isoniazid and rifampin and an additional chemotherapeutic agent is known as multidrug-resistant TB (MDR TB). Until recently, the prevalence of drug resistance in patients with TB has been poorly understood due to a lack of infection surveillance and molecular testing. Countries with the highest prevalence of TB, including MDR TB, are also those most affected by the COVID-19 pandemic. The identification of MDR TB requires careful monitoring and resources for molecular testing. Previous treatment regimens have required intravenous treatments of long duration and high cost. The 2020 and 2021 recommendations from the WHO for the management of drug-susceptible TB and MDR TB have included oral treatment regimens and reduced treatment duration. This Editorial aims to present the rationale for the 2020 and 2021 recommendations from the WHO for the management of drug-susceptible TB and MDR TB.


Subject(s)
Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Tuberculosis/drug therapy , Antitubercular Agents/therapeutic use , Clinical Protocols/standards , Global Health , Humans , Mycobacterium tuberculosis/isolation & purification , Tuberculosis/epidemiology , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Pulmonary/epidemiology , World Health Organization
20.
BMJ Case Rep ; 14(7)2021 Jul 13.
Article in English | MEDLINE | ID: covidwho-1309821

ABSTRACT

Scarce data exist about the coinfection of SARS-CoV-2 and Mycobacterium tuberculosis (MTB). A young woman who was undergoing treatment for multiple sclerosis was brought to our hospital with a COVID-19 positive status. On further evaluation, her chest X-ray showed right upper and mid-zone opacity, which lead to the suspicion of MTB. Her sputum came positive for acid-fast bacilli (AFB) staining and cartridge-based nucleic acid amplification test (CBNAAT) confirmed it, and rifampicin resistance was not detected. She was started on an antitubercular regimen. She was discharged, and by the end of the intensive phase of treatment, her symptoms subsided, but her sputum CBNAAT still showed the presence of TB bacillus.


Subject(s)
COVID-19 , Coinfection , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Female , Humans , SARS-CoV-2 , Sensitivity and Specificity , Sputum , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy
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