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3.
Sci Rep ; 14(1): 7695, 2024 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565912

RESUMEN

Tuberculosis (TB) remains a significant public health concern, particularly in low-resource settings. The treatment outcome is a crucial indicator of the effectiveness of TB treatment programs. Assessing the current treatment outcome and its associated factors is essential for improving patient care and reducing the spread of TB. Therefore, this study aimed to assess TB treatment outcomes and their associated factors among TB patients who received treatment at public healthcare facilities in Motta Town, Northwest Ethiopia. A facility-based retrospective cross-sectional study design was employed in two TB treatment centers in Motta town from January 2017 to December 2021. The study participants were all patients diagnosed with TB who received treatment. A p-value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 362 TB patients were included in the study. The overall treatment success rate was 88.4% (95% CI 85.1, 91.7). Male gender (AOR = 2.40, 95% CI 1.16, 4.98), normal nutritional status (AOR = 3.11, 95% CI 1.33, 7.25), HIV negative status (AOR = 3.35, 95% CI 1.31, 8.60), and non-presumptive drug resistance to TB (AOR = 3.72, 95% CI 1.74, 7.98) were significantly associated with successful TB treatment outcomes (p < 0.05). In the current study, nine out of ten study participants had successful TB treatment outcome rates. Male gender, normal nutritional status, non-presumed drug resistance to TB, and HIV-negative status were significantly associated with successful TB treatment outcomes. By taking risk factors associated with poor treatment outcomes like those found in this study into account, patient management and treatment can be optimized. Sufficient TB control measures for populations are imperative and could significantly reduce the nation's total TB burden.


Asunto(s)
Infecciones por VIH , Tuberculosis , Humanos , Masculino , Estudios Retrospectivos , Etiopía/epidemiología , Estudios Transversales , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis/complicaciones , Resultado del Tratamiento , Infecciones por VIH/tratamiento farmacológico , Atención a la Salud , Antituberculosos/uso terapéutico
4.
Front Cell Infect Microbiol ; 14: 1361326, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38572322

RESUMEN

Spinal tuberculosis is a common extrapulmonary type that is often secondary to pulmonary or systemic infections. Mycobacterium tuberculosis infection often leads to the balance of immune control and bacterial persistence. In this study, 64 patients were enrolled and the clinicopathological and immunological characteristics of different age groups were analyzed. Anatomically, spinal tuberculosis in each group mostly occurred in the thoracic and lumbar vertebrae. Imaging before preoperative anti-tuberculosis therapy showed that the proportion of abscesses in the older group was significantly lower than that in the younger and middle-aged groups. However, pathological examination of surgical specimens showed that the proportion of abscesses in the older group was significantly higher than that in the other groups, and there was no difference in the granulomatous inflammation, caseous necrosis, inflammatory necrosis, acute inflammation, exudation, granulation tissue formation, and fibrous tissue hyperplasia. B cell number was significantly lower in the middle-aged and older groups compared to the younger group, while the number of T cells, CD4+ T cells, CD8+ T cells, macrophages, lymphocytes, plasma cells, and NK cells did not differ. Meaningfully, we found that the proportion of IL-10 high expression and TGF-ß1 positive in the older group was significantly higher than that in the younger group. TNF-α, CD66b, IFN-γ, and IL-6 expressions were not different among the three groups. In conclusion, there are some differences in imaging, pathological, and immune features of spinal tuberculosis in different age groups. The high expression of IL-10 and TGF-ß1 in older patients may weaken their anti-tuberculosis immunity and treatment effectiveness.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis de la Columna Vertebral , Persona de Mediana Edad , Humanos , Anciano , Interleucina-10/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Tuberculosis de la Columna Vertebral/tratamiento farmacológico , Tuberculosis de la Columna Vertebral/metabolismo , Linfocitos T CD8-positivos/metabolismo , Absceso/tratamiento farmacológico , Absceso/metabolismo , Antituberculosos/uso terapéutico , Necrosis/tratamiento farmacológico , Necrosis/metabolismo , Linfocitos T CD4-Positivos , Citocinas/metabolismo
6.
Indian J Tuberc ; 71(2): 153-162, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38589119

RESUMEN

BACKGROUND: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis is one of the top ten causes of death worldwide. Isoniazid (INH) is an important component of anti-tuberculosis therapy (ATT). Low isoniazid levels can serve as a risk factor for the development of treatment failure, relapse of disease and acquired secondary resistance. Hence, serum level of isoniazid becomes a critical factor in determining the treatment outcome of patients on ATT. This study aimed to evaluate the correlation between serum isoniazid concentration and therapeutic response in patients of pulmonary tuberculosis in Central India. METHODS: This was a prospective single cohort observational study conducted at a tertiary care hospital. Therapeutic response in newly diagnosed patients of pulmonary TB was determined based the microbiological, clinical and radiological parameters. Serum INH levels were estimated based on a spectrophotometric method using nano-spectrophotometer. RESULTS: In this study, patients had a significant improvement in treatment outcome as evident by a significant decrease in the TB score I at end of IP (p = 0.001) and a significant decline in the Timika score at end of CP (p = 0.001). Although all patients converted to sputum negative at end of CP, 20% remained positive at end of IP. Lower INH levels were seen in 13.3% of the study population. Higher INH levels were observed in sputum converters, patients with low TB score I and low Timika score, although no statistically significant difference was noted (p > 0.05). CONCLUSION: In this study, we could not find any statistically significant association between serum INH levels and therapeutic outcome of the patients. Further studies on a larger population could provide better understanding about the prevalence of low serum isoniazid levels among the Indian population and establish its relationship with therapeutic outcome. Also, the usage of a comparatively less expensive spectrophotometric method of analysis makes this feasible in almost every district hospital without the need of high-performance liquid chromatography which is costlier and needs more expertise.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Humanos , Isoniazida/uso terapéutico , Antituberculosos/uso terapéutico , Estudios Prospectivos , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis/tratamiento farmacológico , India
7.
Indian J Tuberc ; 71(2): 163-169, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38589120

RESUMEN

BACKGROUND: The management of choice for granulomatous mastitis (GM) has yet to be determined but few studies have demonstrated that anti-tubercular treatment (ATT) could be an effective alternative therapeutic option. Hence, the objective of the current study is to determine the clinical feature, radiological imaging findings, and histopathological examination results exhibited by GM and tuberculosis (TB)-proven GM as well as to evaluate the ATT clinical outcome in GM patients. METHODS: The study was performed on 68 GM patients who were referred to the department of pulmonology by the breast clinic (from January 2018 to August 2021). Study populations were categorized into two groups GM and TB-proven GM patients and all were prescribed with standard ATT regimen and were continuously followed up. SPSS version 25 was employed for statistical assessment. RESULTS: Our study showed that 6 patients from GM and 4 patients from the TB-proven GM group got relapsed. For patients who displayed partial remission, ATT treatment was started after assessing the side effects potential. 14.6% (n = 6) and 7.4% (n = 2) patients who initially demonstrated partial remission were also completely cured. ATT treatment curable rate was determined to be 90% (n = 37) and 81.5% (n = 22) for GM and TB-proven GM patients correspondingly. Therefore, the current study demonstrated nil significant differences between groups. CONCLUSION: The current study warrants that ATT therapy could be an effective and better treatment of choice for GM patients irrespective of their clinical condition.


Asunto(s)
Mastitis Granulomatosa , Tuberculosis , Femenino , Humanos , Mastitis Granulomatosa/diagnóstico por imagen , Mastitis Granulomatosa/tratamiento farmacológico , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Resultado del Tratamiento , Mamografía , Antituberculosos/uso terapéutico
9.
J Korean Med Sci ; 39(13): e104, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38599596

RESUMEN

BACKGROUND: The hollow-fiber infection model (HFIM) is a valuable tool for evaluating pharmacokinetics/pharmacodynamics relationships and determining the optimal antibiotic dose in monotherapy or combination therapy, but the application for personalized precision medicine in tuberculosis treatment remains limited. This study aimed to evaluate the efficacy of adjusted antibiotic doses for a tuberculosis patient using HFIM. METHODS: Model-based Bayesian forecasting was utilized to assess the proposed reduction of the isoniazid dose from 300 mg daily to 150 mg daily in a patient with an ultra-slow-acetylation phenotype. The efficacy of the adjusted 150-mg dose was evaluated in a time-to-kill assay performed using the bacterial isolate Mycobacterium tuberculosis (Mtb) H37Ra in a HFIM that mimicked the individual pharmacokinetic profile of the patient. RESULTS: The isoniazid concentration observed in the HFIM adequately reflected the target drug exposures simulated by the model. After 7 days of repeated dose administration, isoniazid killed 4 log10 Mtb CFU/mL in the treatment arm, while the control arm without isoniazid increased 1.6 log10 CFU/mL. CONCLUSION: Our results provide an example of the utility of the HFIM for predicting the efficacy of specific recommended doses of anti-tuberculosis drugs in real clinical setting.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Isoniazida/farmacología , Isoniazida/uso terapéutico , Teorema de Bayes , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(4): 371-375, 2024 Apr 12.
Artículo en Chino | MEDLINE | ID: mdl-38599815

RESUMEN

As a chronic infectious disease, tuberculosis (TB) is closely related to immune regulation and immune effect. Immunotherapy which can improve the curative effect of tuberculosis and control the spread of tuberculosis, is one of the important means for the comprehensive treatment of tuberculosis. From October 2022 to September 2023, research on the immunotherapy of tuberculosis at home and abroad continues to increase, providing new opportunities for the treatment of multidrug-resistant and extensively drug-resistant tuberculosis. Host-targeted therapy and therapeutic vaccines are new directions for research into TB adjuvant therapy.


Asunto(s)
Mycobacterium tuberculosis , Vacunas contra la Tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Humanos , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Tuberculosis/prevención & control , Vacunas contra la Tuberculosis/uso terapéutico , Inmunoterapia , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico
11.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(4): 376-382, 2024 Apr 12.
Artículo en Chino | MEDLINE | ID: mdl-38599816

RESUMEN

Tuberculosis, caused by infection with Mycobacterium tuberculosis (MTB), remains a global public health challenge. Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains make tuberculosis more difficult to control. New tools to study the biology of MTB can identify novel targets for drug discovery. Recently, the Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) combined with next-generation sequencing has provided many novel insights into the physiology and genetics of MTB. This review summarizes the application and optimization of CRISPRi in MTB biology.


Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/uso terapéutico , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Biología , Pruebas de Sensibilidad Microbiana
12.
BMC Infect Dis ; 24(1): 364, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38556907

RESUMEN

BACKGROUND: The emergence of Drug Resistant Tuberculosis (DR-TB) is one of the main public health and economic problems facing the world today. DR-TB affects mostly those in economically productive years and prevents them from being part of the workforce needed for economic growth. The aim of this study was to determine the Clinical Profile and Outcomes of DR-TB in Central Province of Zambia. METHODS: This was a retrospective cross sectional study that involved a review of records of patients with confirmed DR-TB who were managed at Kabwe Central Hospital's Multi-Drug Resistant TB (MDR-TB) Ward from the year 2017 to 2021. 183 patients were managed during this period and all were recruited in the study. Data was collected from DR-TB registers and patient files and then entered in SPSS version 22 where all statistical analyses were performed. RESULTS: The study revealed that the prevalence of DR-TB among registered TB patients in Central Province was 1.4%. Majority of those affected were adults between the ages of 26 and 45 years (63.9%). The study also found that more than half of the patients were from Kabwe District (60.7%). Other districts with significant number of cases included Kapiri Mposhi 19 (10.4%), Chibombo 12 (6.6%), Chisamba 10 (5.5%), Mumbwa 7 (3.8%) and Mkushi 7 (3.8%). Furthermore, the analysis established that most of the patients had RR-TB (89.6%). 9.3% had MDR-TB, 0.5% had IR-TB and 0.5% had XDR-TB. RR-TB was present in 93.8% of new cases and 88.9% of relapse cases. MDR-TB was present in 6.2% of new cases and 10% of relapse cases. With regard to outcomes of DR-TB, the investigation revealed that 16.9% of the patients had been declared cured, 45.9% had completed treatment, 6% were lost to follow up and 21.3% had died. Risk factors for mortality on multivariate analysis included age 36-45 years (adjusted odds ratio [aOR] 0.253, 95% CI [0.70-0.908] p = 0.035) and male gender (aOR 0.261, 95% CI [0.107-0.638] p = 0.003). CONCLUSION: The research has shown beyond doubt that the burden of DR-TB in Central Province is high. The study recommends putting measures in place that will help improve surveillance, early detection, early initiation of treatment and proper follow up of patients.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Adulto , Humanos , Masculino , Persona de Mediana Edad , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Estudios Transversales , Prevalencia , Recurrencia , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Zambia/epidemiología , Femenino
13.
Int J Tuberc Lung Dis ; 28(4): 195-201, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38563340

RESUMEN

In Togo, the COVID-19 pandemic paved the way for decentralising directly observed treatment (DOT) to the community level through the evaluation of two innovative community-based DOT approaches-a community health worker-based (CHW-DOT) and family-based (FB-DOT). METHODS We conducted an observational prospective study from April 2021 to January 2022. Sputum conversion at Month 2 and favourable treatment outcomes at Month 6 were assessed and compared between the two groups. Sociodemographic and clinical factors related to these outcomes were identified. RESULTS A total of 182 TB patients were enrolled. The CHW-DOT group had significantly increased odds of sputum conversion (aOR 2.95, 95% CI 1.09-7.98) and lower odds of unsuccessful treatment outcomes (aOR 0.37, 95% CI 0.13-1.1). Non-smokers had 4.85 higher odds of converting than smokers (aOR 4.85, 95% CI 1.76-13.42) and lower odds of an unsuccessful treatment than smokers (aOR 0.11, 95% CI 0.04-0.32). CONCLUSION CHW-DOT is associated with higher sputum smear conversion rates and a more favourable treatment outcome. The use of tobacco, significantly associated with outcomes, also suggests that a smoking cessation component may be a valuable adjunct to a CHW-DOT approach during TB treatment..


Asunto(s)
Tuberculosis , Humanos , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Estudios Prospectivos , Togo/epidemiología , Pandemias , Resultado del Tratamiento , Instituciones de Salud , Antituberculosos/uso terapéutico
14.
Front Public Health ; 12: 1356826, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38566794

RESUMEN

Purpose: This study examined the patterns and frequency of genetic changes responsible for resistance to first-line (rifampicin and isoniazid), fluoroquinolones, and second-line injectable drugs in drug-resistant Mycobacterium tuberculosis (MTB) isolated from culture-positive pulmonary tuberculosis (PTB) symptomatic attendees of spiritual holy water sites (HWSs) in the Amhara region. Patients and methods: From June 2019 to March 2020, a cross-sectional study was carried out. A total of 122 culture-positive MTB isolates from PTB-suspected attendees of HWSs in the Amhara region were evaluated for their drug resistance profiles, and characterized gene mutations conferring resistance to rifampicin (RIF), isoniazid (INH), fluoroquinolones (FLQs), and second-line injectable drugs (SLIDs) using GenoType®MTBDRplus VER2.0 and GenoType®MTBDRsl VER2.0. Drug-resistant MTB isolates were Spoligotyped following the manufacturer's protocol. Results: Genetic changes (mutations) responsible for resistance to RIF, INH, and FLQs were identified in 15/122 (12.3%), 20/122 (16.4%), and 5/20 (25%) of MTB isolates, respectively. In RIF-resistant, rpoB/Ser531Lue (n = 12, 80%) was most frequent followed by His526Tyr (6.7%). Amongst INH-resistant isolates, katG/Ser315Thr1 (n = 19, 95%) was the most frequent. Of 15 MDR-TB, the majority (n = 12, 80%) isolates had mutations at both rpoB/Ser531Leu and katG/Ser315Thr1. All 20 INH and/or RIF-resistant isolates were tested with the MTBDRsl VER 2.0, yielding 5 FLQs-resistant isolates with gene mutations at rpoB/Ser531Lue, katG/Ser315Thr1, and gyrA/Asp94Ala genes. Of 20 Spoligotyped drug-resistant MTB isolates, the majority (n = 11, 55%) and 6 (30%) were SIT149/T3-ETH and SIT21/CAS1-Kili sublineages, respectively; and they were any INH-resistant (mono-hetero/multi-). Of 15 RIF-resistant (RR/MDR-TB) isolates, 7 were SIT149/T3-ETH, while 6 were SIT21/CAS1-Kili sublineages. FLQ resistance was detected in four SIT21/CAS1-Kili lineages. Conclusion: In the current study, the most common gene mutations responsible for resistance to INH, RIF, and FLQs were identified. SIT149/T3-ETH and SIT21/CAS1-Kili constitute the majority of drug-resistant TB (DR-TB) isolates. To further understand the complete spectrum of genetic changes/mutations and related genotypes, a sequencing technology is warranted.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Isoniazida/farmacología , Rifampin/farmacología , Etiopía , Estudios Transversales , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Mutación , Genotipo , Fluoroquinolonas
15.
PLoS One ; 19(4): e0301507, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38564589

RESUMEN

BACKGROUND: We compared the cost-consequence of a home-based multidrug-resistant tuberculosis (MDR-TB) model of care, based on task-shifting of directly observed therapy (DOT) and MDR-TB injection administration to lay health workers, to a routine clinic-based strategy within an established national TB programme in Eswatini. METHODS: Data on costs and effects of the two ambulatory models of MDR-TB care was collected using documentary data and interviews in the Lubombo and Shiselweni regions of Eswatini. Health system, patient and caregiver costs were assessed in 2014 in US$ using standard methods. Cost-consequence was calculated as the cost per patient successfully treated. RESULTS: In the clinic-based and home-based models of care, respectively, a total of 96 and 106 MDR-TB patients were enrolled in 2014, with treatment success rates of 67.8% and 82.1%. Health system costs per patient treated were slightly lower in the home-based strategy (US$19 598) compared to the clinic-based model (US$20 007). The largest costs in both models were for inpatient care, administration of DOT and injectable treatment, and drugs. Costs incurred by patients and caregivers were considerably higher in the clinic-based model of care due to the higher direct travel costs to the nearest clinic to receive DOT and injections daily. In total, MDR patients in the clinic-based strategy incurred average costs of US$670 compared to US$275 for MDR-TB patients in the home-based model. MDR-TB patients in the home-based programme, where DOT and injections was provided in their homes, only incurred out-of-pocket travel expenses for monthly outpatient treatment monitoring visits averaging US$100. The cost per successfully treated patient was US$31 106 and US$24 157 in the clinic-based and home-based models of care, respectively. The analysis showed that, in addition to the health benefits, direct and indirect costs for patients and their caregivers were lower in the home-based care model. CONCLUSION: The home-based strategy used less resources and generated substantial health and economic benefits, particularly for patients and their caregivers, and decision makers can consider this approach as an alternative to expand and optimise MDR-TB control in resource-limited settings. Further research to understand the appropriate mix of treatment support components that are most important for optimal clinical and public health outcomes in the ambulatory home-based model of MDR-TB care is necessary.


Asunto(s)
Servicios de Atención de Salud a Domicilio , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Esuatini , Análisis Costo-Beneficio , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Atención Ambulatoria , Antituberculosos/uso terapéutico , Costos de la Atención en Salud
16.
Nat Commun ; 15(1): 2962, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580642

RESUMEN

The projected trajectory of multidrug resistant tuberculosis (MDR-TB) epidemics depends on the reproductive fitness of circulating strains of MDR M. tuberculosis (Mtb). Previous efforts to characterize the fitness of MDR Mtb have found that Mtb strains of the Beijing sublineage (Lineage 2.2.1) may be more prone to develop resistance and retain fitness in the presence of resistance-conferring mutations than other lineages. Using Mtb genome sequences from all culture-positive cases collected over two years in Moldova, we estimate the fitness of Ural (Lineage 4.2) and Beijing strains, the two lineages in which MDR is concentrated in the country. We estimate that the fitness of MDR Ural strains substantially exceeds that of other susceptible and MDR strains, and we identify several mutations specific to these MDR Ural strains. Our findings suggest that MDR Ural Mtb has been transmitting efficiently in Moldova and poses a substantial risk of spreading further in the region.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Moldavia/epidemiología , Genotipo , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Farmacorresistencia Bacteriana Múltiple/genética
17.
Ann Clin Microbiol Antimicrob ; 23(1): 29, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38581051

RESUMEN

BACKGROUND: The prevalence of multidrug-resistant tuberculosis (MDR-TB) among Korean tuberculosis patients is about 4.1%, which is higher than the OECD average of 2.6%. Inadequate drug use and poor patient compliance increase MDR-TB prevalence through selective pressure. Therefore, prompt detection of drug resistance in tuberculosis patients at the time of diagnosis and quantitative monitoring of these resistant strains during treatment are crucial. METHODS: A multiplex droplet digital PCR (ddPCR) assay was developed and assessed using DNA material of nine Mycobacterium tuberculosis strains with known mutation status that were purchased from the Korean National Tuberculosis Association. We collected a total of 18 MDR-TB residual samples referred for PCR analysis. Total DNA was extracted from the samples and subjected to the quadruplex ddPCR assay. Their results were compared to those of known resistance phenotypes. RESULTS: The analytical sensitivity and specificity of the multiplex ddPCR assay for detecting INH, RIF, EMB, FQ, and SM resistance-causing mutations ranged from 71.43 to 100% and 94.12-100%, respectively. Follow-up sample results showed that the quadruplex ddPCR assay was sensitive enough to detect IS6110 and other mutations even after onset of treatment. CONCLUSIONS: We developed a sensitive and accurate multiplex ddPCR assay that can detect the presence of tuberculosis quantitatively and resistance-conveying mutations concurrently. This tool could aid clinicians in the diagnosis and treatment monitoring of tuberculosis.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Isoniazida/uso terapéutico , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Reacción en Cadena de la Polimerasa , Mutación , Sensibilidad y Especificidad , Pruebas de Sensibilidad Microbiana , ADN/uso terapéutico
18.
Biomed Environ Sci ; 37(2): 157-169, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38582978

RESUMEN

Objective: China is among the 30 countries with a high burden of tuberculosis (TB) worldwide, and TB remains a public health concern. Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China. However, molecular epidemiological studies of Kashgar are lacking. Methods: A population-based retrospective study was conducted using whole-genome sequencing (WGS) to determine the characteristics of drug resistance and the transmission patterns. Results: A total of 1,668 isolates collected in 2020 were classified into lineages 2 (46.0%), 3 (27.5%), and 4 (26.5%). The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid (7.4%, 124/1,668), streptomycin (6.0%, 100/1,668), and rifampicin (3.3%, 55/1,668). The rate of rifampicin resistance was 1.8% (23/1,290) in the new cases and 9.4% (32/340) in the previously treated cases. Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains, respectively: 18.6% vs. 8.7 or 9%, P < 0.001. The estimated proportion of recent transmissions was 25.9% (432/1,668). Multivariate logistic analyses indicated that sex, age, occupation, lineage, and drug resistance were the risk factors for recent transmission. Despite the low rate of drug resistance, drug-resistant strains had a higher risk of recent transmission than the susceptible strains (adjusted odds ratio, 1.414; 95% CI, 1.023-1.954; P = 0.036). Among all patients with drug-resistant tuberculosis (DR-TB), 78.4% (171/218) were attributed to the transmission of DR-TB strains. Conclusion: Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Rifampin/farmacología , Estudios Retrospectivos , Farmacorresistencia Bacteriana Múltiple/genética , Pruebas de Sensibilidad Microbiana , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Mutación
19.
BMC Genomics ; 25(1): 387, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643090

RESUMEN

BACKGROUND: Drug-resistant tuberculosis (TB) is a major threat to global public health. Whole-genome sequencing (WGS) is a useful tool for species identification and drug resistance prediction, and many clinical laboratories are transitioning to WGS as a routine diagnostic tool. However, user-friendly and high-confidence automated bioinformatics tools are needed to rapidly identify M. tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM), detect drug resistance, and further guide treatment options. RESULTS: We developed GenoMycAnalyzer, a web-based software that integrates functions for identifying MTBC and NTM species, lineage and spoligotype prediction, variant calling, annotation, drug-resistance determination, and data visualization. The accuracy of GenoMycAnalyzer for genotypic drug susceptibility testing (gDST) was evaluated using 5,473 MTBC isolates that underwent phenotypic DST (pDST). The GenoMycAnalyzer database was built to predict the gDST for 15 antituberculosis drugs using the World Health Organization mutational catalogue. Compared to pDST, the sensitivity of drug susceptibilities by the GenoMycAnalyzer for first-line drugs ranged from 95.9% for rifampicin (95% CI 94.8-96.7%) to 79.6% for pyrazinamide (95% CI 76.9-82.2%), whereas those for second-line drugs ranged from 98.2% for levofloxacin (95% CI 90.1-100.0%) to 74.9% for capreomycin (95% CI 69.3-80.0%). Notably, the integration of large deletions of the four resistance-conferring genes increased gDST sensitivity. The specificity of drug susceptibilities by the GenoMycAnalyzer ranged from 98.7% for amikacin (95% CI 97.8-99.3%) to 79.5% for ethionamide (95% CI 76.4-82.3%). The incorporated Kraken2 software identified 1,284 mycobacterial species with an accuracy of 98.8%. GenoMycAnalyzer also perfectly predicted lineages for 1,935 MTBC and spoligotypes for 54 MTBC. CONCLUSIONS: GenoMycAnalyzer offers both web-based and graphical user interfaces, which can help biologists with limited access to high-performance computing systems or limited bioinformatics skills. By streamlining the interpretation of WGS data, the GenoMycAnalyzer has the potential to significantly impact TB management and contribute to global efforts to combat this infectious disease. GenoMycAnalyzer is available at http://www.mycochase.org .


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/genética , Pruebas de Sensibilidad Microbiana , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Micobacterias no Tuberculosas , Resistencia a Medicamentos , Internet
20.
Rev Gaucha Enferm ; 45: e20230127, 2024.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-38655930

RESUMEN

OBJECTIVE: To analyze the association between the provision of tuberculosis treatment actions and the sociodemographic and clinical characteristics of cases during the COVID-19 pandemic. METHOD: Cross-sectional study conducted with data from secondary sources of 134 tuberculosis cases that underwent treatment in 2020 in the city of Pelotas, RS, Brazil. Data were analyzed using descriptive statistics, Chi-square test, and Fisher's exact test. RESULTS: The least frequently offered actions in the period were: three or more control smear microscopies (12.7%), smear microscopy at the end of treatment (16.7%), chest X-ray at sixth month (48.5%) and sputum culture (49%). The number of medical and nursing consultations did not reach six in 52.9% and 83.3% of cases, respectively. The lower offer of treatment actions was associated with: retreatment (p<0.001); comorbidities (p=0.023); HIV infection (p<0.001); mental disorder (p=0.013); illicit substance use (p=0.018); normal chest X-ray (p=0.024); and special treatment regimen (p=0.009). CONCLUSION: After the COVID-19 pandemic, it is essential to invest in cases follow-up, especially those undergoing retreatment, with comorbidities, drug use, normal chest X-ray results, and special treatment regimens.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Estudios Transversales , Masculino , Femenino , Brasil/epidemiología , Adulto , Persona de Mediana Edad , Pandemias , Adulto Joven , Anciano , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis/tratamiento farmacológico , Comorbilidad , Adolescente , Antituberculosos/uso terapéutico
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