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1.
PLoS One ; 17(5): e0267661, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35511771

RESUMO

BACKGROUND: Diagnosis of tuberculosis (TB) in children is challenging mainly due to the difficulty of obtaining respiratory specimen and lack of sensitive diagnostic tests. The objective of this study was to evaluate the diagnostic performance of Xpert MTB/RIF (Xpert here after) for the diagnosis of pulmonary TB (PTB) from stool specimen in children. METHODS: A cross-sectional study was conducted among consecutively recruited children (less than 15 years old) with presumptive PTB at Jimma Medical Center, Ethiopia. One pulmonary specimen (expectorated sputum or gastric aspirate) was collected from each participant and tested for TB by Xpert and Lowenstein-Jensen (LJ) culture. In addition, one stool specimen per child was collected and tested by Xpert after a single step, centrifuge-free stool processing method adapted from KNCV TB Foundation. Diagnostic performance of Xpert was calculated with reference to LJ culture and to a composite reference standards (CRS) comprising of confirmed TB (positive by Xpert and/or culture) and unconfirmed TB (clinical diagnosis with improvement after anti-TB treatment). RESULTS: A total of 178 children were enrolled; 152 of whom had complete microbiological results. Overall, TB was diagnosed in 13.2% (20/152) of the children with presumptive TB. Of these, only ten had microbiologically confirmed TB (positive Xpert and/or culture) and the remaining ten were clinically diagnosed with positive response to anti-TB treatment and were classified as unconfirmed TB. Stool Xpert had sensitivity of 100% (95%CI: 66.4-100) and specificity of 99.3% (95%CI: 96.2-100) compared to culture; however, the sensitivity was decreased to 50% (95%CI: 27.2-72.8) when compared to CRS. The Xpert on gastric aspirate had sensitivity of 77.8% (95%CI: 40-97.2) compared to culture and 40% (95%CI: 19.1-64) compared to CRS. CONCLUSIONS: The sensitivity of Xpert for stool sample is comparable to that for gastric aspirate. Stool sample is a potential alternative to pulmonary specimen in the diagnosis of pulmonary TB in children using Xpert.


Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Adolescente , Criança , Estudos Transversais , Etiópia/epidemiologia , Hospitais , Humanos , Mycobacterium tuberculosis/genética , Encaminhamento e Consulta , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose/diagnóstico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia
2.
Front Cell Infect Microbiol ; 12: 836987, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35425720

RESUMO

Objective: There is evidence that the gut microbiota play a regulatory role in the occurrence and progression of tuberculosis. The purpose of the current study was to explore the alterations in gut microbiome under different tuberculosis disease stages in the Uyghur population, clarify the composition of microbial taxonomy, search for microbial biomarkers and provide innovative ideas for individual immune prevention and for control strategies. Design: A case-control study of Uyghur individuals was performed using 56 cases of pulmonary tuberculosis (PTB), 36 cases of latent tuberculosis infection (LTBI) and 50 healthy controls (HC), from which stool samples were collected for 16S rRNA gene sequencing. Results: The results showed that the alpha diversity indexes of the PTB group were lower than those of the other two groups (P <0.001), while only observed species were different between LTBI and HC (P <0.05). Beta diversity showed differences among the three groups (P = 0.001). At the genus level, the relative abundance of Bifidobacterium and Bacteroides increased, while Roseburia and Faecalibacterium decreased in the PTB group, when compared with the other two groups, but the changes between the LTBI and HC groups were not significant. The classifier in the test set showed that the ability of the combined genus to distinguish between each two groups was 81.73, 87.26, and 86.88%, respectively, and the validation efficiency was higher than that of a single screened genus. Conclusion: The gut microbiota of PTB patients was significantly disordered compared with LTBI and HC, while the changes of LTBI and HC were not significant. In the future, gut microbiota could be used as a non-invasive biomarker to assess disease activity.


Assuntos
Microbioma Gastrointestinal , Tuberculose Latente , Tuberculose Pulmonar , Tuberculose , Biomarcadores , Estudos de Casos e Controles , Fezes/microbiologia , Humanos , RNA Ribossômico 16S/genética , Tuberculose Pulmonar/microbiologia
3.
Indian J Tuberc ; 69(2): 178-183, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35379399

RESUMO

BACKGROUND: India houses 27% of the tuberculosis cases worldwide. Pediatric tuberculosis accounts for 11% cases worldwide. Microbiological confirmation of diagnosis is difficult in children. We aimed to study the proportion of Stool CBNAAT (Cartridge Based Nucleic Acid Amplification Test) and GA CBNAAT positive cases among the presumptive cases of tuberculosis in children and assess diagnostic utility of the Stool CBNAAT in comparison to GA CBNAAT and culture. METHODS: Ours was a cross sectional study. 75 children, aged 6 months to 12 years who were presumptive cases of pulmonary tuberculosis and who were unable to expectorate, were enrolled. Gastric aspirate and stool samples were obtained and CBNAAT and culture was done. Results of stool CBNAAT were compared with GA CBNAAT and culture. RESULTS: Of the 75 children enrolled, 28 were started on antitubercular therapy, 12 of whom were microbiologically confirmed and 16 were started on clinical grounds. Overall, 10 (13.3%) and 11 (14.6%) were positive by Stool CBNAAT and GA CBNAAT respectively. GA CBNAAT and Stool CBNAAT were found to have near perfect agreement (Cohen's kappa 0.834). Stool CBNAAT had sensitivity and specificity of 73% and 97% as compared to culture. CONCLUSIONS: Stool CBNAAT may be used for bacteriological confirmation of pediatric pulmonary tuberculosis. It was found to have a high degree of concordance with the conventionally used GA CBNAAT. This test would be helpful in endemic countries where there is a dearth of trained staff, especially in the periphery, to obtain gastric aspirate. Discomfort associated with sampling would be avoided.


Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Criança , Estudos Transversais , Humanos , Mycobacterium tuberculosis/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia
4.
Front Public Health ; 10: 808626, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372211

RESUMO

Background: Tuberculosis (TB) is a leading cause of morbidity and mortality in Ethiopia. Investigation of the Mycobacterium tuberculosis complex (MTBC) species circulating in the Ethiopian population would contribute to the efforts made to control TB in the country. Therefore, this study was conducted to investigate the MTBC species and spoligo patterns in the Oromia region (central) of Ethiopia. Methods: A cross-sectional study design was used to recruit 450 smear positive pulmonary TB (PTB) cases from the Oromia region between September 2017 and August 2018. Mycobacteria were isolated from sputum samples on the Lowenstein Jensen (LJ) medium. Molecular identification of the isolates was performed by spoligotyping. The results of spoligotyping were transferred into a query box in the SITVIT2 database and Run TB-Lineage in the TB Insight website for the identification of spoligo international type (SIT) number and linages of the isolates, respectively. Statistical Product and Service Solutions (SPSS) 20 was applied for statistical analysis. Results: Three hundred and fifteen isolates were grouped under 181 different spoligotype patterns. The most dominantly isolated spoligotype pattern was SIT149 and it consisted of 23 isolates. The majority of the isolates were grouped under Euro-American (EA), East-African-Indian (EAI), and Indo-Oceanic (IO) lineages. These lineages consisted of 79.4, 9.8, and 9.8% of the isolates, respectively. One hundred and sixty-five of the isolates were classified under 31 clustered spoligotypes whereas the remaining 150 were singleton types. Furthermore, 91.1% of the total isolates were classified as orphan types. Clustering of spoligotypes was associated (p < 0.001) with EAI lineage. Conclusion: SIT149 and EA lineage were predominantly isolated from the Oromia region substantiating the findings of the similar studies conducted in other regions of Ethiopia. The observation of significant number of singleton and orphan spoligotypes warrants for additional genetic typing of the isolates using method(s) with a better discriminatory power than spoligotyping.


Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Técnicas de Tipagem Bacteriana , Estudos Transversais , Etiópia/epidemiologia , Humanos , Mycobacterium tuberculosis/classificação , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia
5.
J Infect Chemother ; 28(7): 1041-1044, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35450783

RESUMO

INTRODUCTION: Gastric aspirate can be useful for the diagnosis of pulmonary tuberculosis (TB) in patients with smear-negative pulmonary TB or without sputum production. The gastric aspirate smear technique has low sensitivity, and a previous report demonstrated that no patient was diagnosed by only gastric aspirate analysis. However, some patients with TB have been negative on sputum examination but positive on gastric aspirate examination, and the incidence of such cases is uncertain. Therefore, this study investigated the usefulness of gastric aspirate in the diagnosis of pulmonary TB. METHODS: To analyze the diagnostic accuracy of gastric aspirate examination, the data of 513 patients with negative sputum smears or a lack of sputum production, including 203 patients with pulmonary TB (39.6%) and 93 patients with nontuberculous mycobacteriosis who underwent gastric aspiration at Fukujuji Hospital from January 2016 to March 2021, were collected retrospectively. RESULTS: The accuracy rates of gastric aspirate examination for the diagnosis of pulmonary TB were as follows: 21.2% sensitivity and 91.9% specificity for smear positivity, 55.8% sensitivity and 99.6% specificity for nucleic acid amplification test positivity, and 71.4% sensitivity and 100% specificity for culture positivity. Twenty-three patients (11.2%) were diagnosed by gastric aspirate examination alone. Among the 356 patients who underwent three repeated sputum examinations in addition to gastric aspirate examination, the cumulative diagnostic rate for the 3 mycobacterial examinations plus gastric aspirate examination was higher than that for only three sputum examinations. CONCLUSIONS: Gastric aspirate is useful for the diagnosis of TB in patients with smear-negative pulmonary TB or without sputum production.


Assuntos
Mycobacterium tuberculosis , Mycobacterium , Tuberculose Pulmonar , Humanos , Mycobacterium tuberculosis/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia
6.
EBioMedicine ; 78: 103949, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35325781

RESUMO

BACKGROUND: Despite being highly prevalent in hospitalised patients with severe HIV-associated tuberculosis (TB) and sepsis, little is known about the mycobacteriology of Mycobacterium tuberculosis bloodstream infection (MTBBSI). We developed methods to serially measure bacillary load in blood and used these to characterise MTBBSI response to anti-TB therapy (ATT) and relationship with mortality. METHODS: We established a microscopy method for direct visualisation of M. tuberculosis bacilli in blood using a novel lysis-concentration protocol and the fluorescent probe, 4-N,N-dimethylaminonaphthalimide-trehalose (DMN-Tre). We tested blood using GeneXpert® MTB/RIF-Ultra (Xpert-ultra) and Myco/F lytic culture after processing blood through lysis-wash steps to remove PCR inhibitors and anti-microbial drug carry-over. HIV-positive patients predicted to have MTBBSI gave blood samples 0, 4, 24, 48 and 72 h after ATT initiation. Bacillary loads were quantified using microscopy, Xpert-ultra cycle threshold, and culture time-to-positivity. Pharmacodynamics were modelled using these measures combined on an ordinal scale, including association with 12-week mortality. FINDINGS: M. tuberculosis was detected in 27 of 28 recruited participants; 25 (89%) by blood Xpert-ultra, 22 (79%) by DMN-Tre microscopy, and 21 (75%) by Myco/F lytic blood culture. Eight (29%) participants died by 12-week follow-up. In a combined pharmacodynamic model, predicted probabilities of negative DMN-Tre microscopy, blood Xpert-ultra, or blood culture after 72 h treatment were 0·64, 0·27, and 0·94, respectively, in those who survived, compared with 0·23, 0·06, and 0·71 in those who died (posterior probability of slower clearance of MTBBSI in those that died >0·99). DMN-Tre microscopy of blood demonstrated heterogenous bacillary morphologies, including microcolonies and clumps. Bacillary cell-length varied significantly with ATT exposure (mean cell-length increase 0·13 log-µm/day; 95%CrI 0·10-0·16). INTERPRETATION: Pharmacodynamics of MTBBSI treatment can be captured using DMN-Tre microscopy, blood Xpert-ultra and culture. This could facilitate interventional trials in severe HIV-associated TB. FUNDING: Wellcome Trust, NIH Fogarty International Center, South African MRC, NIHR(UK), National Research Foundation of South Africa.


Assuntos
Infecções por HIV , Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Estado Terminal , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
7.
Int J Tuberc Lung Dis ; 26(4): 341-347, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35351239

RESUMO

BACKGROUND: Microbiologic screening of extrapulmonary TB (EPTB) patients could inform recommendations for aerosol precautions and close contact prophylaxis. However, this is currently not routinely recommended in India. Therefore, we estimated the proportion of Indian patients with EPTB with microbiologic evidence of pulmonary TB (PTB).METHODS: We characterized baseline clinical, radiological and sputum microbiologic data of 885 adult and pediatric TB patients in Chennai and Pune, India, between March 2014 and November 2018.RESULTS: Of 277 patients with EPTB, enhanced screening led to the identification of 124 (45%) with concomitant PTB, including 53 (19%) who reported a cough >2 weeks; 158 (63%) had an abnormal CXR and 51 (19%) had a positive sputum for TB. Of 70 participants with a normal CXR and without any cough, 14 (20%) had a positive sputum for TB. Overall, the incremental yield of enhanced screening of patients with EPTB to identify concomitant PTB disease was 14% (95% CI 12-16).CONCLUSIONS: A high proportion of patients classified as EPTB in India have concomitant PTB. Our results support the need for improved symptom and CXR screening, and recommends routine sputum TB microbiology screening of all Indian patients with EPTB.


Assuntos
Tuberculose Pulmonar , Tuberculose , Adulto , Criança , Tosse , Humanos , Índia/epidemiologia , Escarro/microbiologia , Tuberculose/diagnóstico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia
8.
BMC Microbiol ; 22(1): 50, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35135478

RESUMO

BACKGROUND: Mycobacterium tuberculosis population in Russia is dominated by the notorious Beijing genotype whose major variants are characterized by contrasting resistance and virulence properties. Here we studied how these strain features could impact the progression of pulmonary tuberculosis (TB) concerning clinical manifestation and lethal outcome. RESULTS: The study sample included 548 M. tuberculosis isolates from 548 patients with newly diagnosed pulmonary TB in Omsk, West Siberia, Russia. Strains were subjected to drug susceptibility testing and genotyping to detect lineages, sublineages, and subtypes (within Beijing genotype). The Beijing genotype was detected in 370 (67.5%) of the studied strains. The strongest association with multidrug resistance (MDR) was found for epidemic cluster Beijing B0/W148 (modern sublineage) and two recently discovered MDR clusters 1071-32 and 14717-15 of the ancient Beijing sublineage. The group of patients infected with hypervirulent and highly lethal (in a mouse model) Beijing 14717-15 showed the highest rate of lethal outcome (58.3%) compared to Beijing B0/W148 (31.4%; P = 0.06), Beijing Central Asian/Russian (29.7%, P = 0.037), and non-Beijing (15.2%, P = 0.001). The 14717-15 cluster mostly included isolates from patients with infiltrative but not with fibrous-cavernous and disseminated TB. In contrast, a group infected with low virulent 1071-32-cluster had the highest rate of fibrous-cavernous TB, possibly reflecting the capacity of these strains for prolonged survival and chronicity of the TB process. CONCLUSIONS: The group of patients infected with hypervirulent and highly lethal in murine model 14717-15 cluster had the highest proportion of the lethal outcome (58.3%) compared to the groups infected with Beijing B0/W148 (31.4%) and non-Beijing (15.2%) isolates. This study carried out in the TB high-burden area highlights that not only drug resistance but also strain virulence should be considered in the implementation of personalized TB treatment.


Assuntos
Variação Genética , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/mortalidade , Adolescente , Adulto , Antituberculosos/farmacologia , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Federação Russa/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Virulência , Adulto Jovem
9.
PLoS One ; 17(2): e0263967, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35171959

RESUMO

INTRODUCTION: In line with the WHO recommendation, Nepal has started implementing Tuberculosis prevention therapy (TBPT) for under five children exposed to Sputum Smear Positive Pulmonary Tuberculosis, as one of the strategies for prevention, care and control of TB. Implementation fidelity study is important to assess on what extent preventive program is being implemented. The objective of the study measured the implementation fidelity of TBPT program Kaski district, Nepal. METHODS: We used a mixed-method explanatory sequential design study. Quantitative data were collected through retrospective review of records from April 2018 to May 2019 and level of adherence was established. Moderating factors influencing the implementation of TBPT were TBPT were assessed qualitatively. Sixteen in-depth interviews and a focus group discussion was conducted purposively with responsible stakeholders. The study was guided by the Conceptual Framework for Implementation Fidelity (CFIR) developed by Carroll. RESULTS: The majority of the components of the TBPT program were found to be implemented with a moderate level of fidelity. The proportion of under five years children initiate and complete the full course of TBPT was 72.5% and 75.86% respectively. The proportion of index cases traced for household contact, contact tracing within two months and timely initiation of therapy within two months were 54.19%, 82.73% and 86.20%. Moderating factors identified in the implementation of the program were contact tracing and enrollment, partnership and ownership, training resources, medication, awareness and information dissemination. CONCLUSION: The TBPT program is being moderately implemented in Kaski districts. Addressing the key challenges identified in contact tracing, partnership/ownership, incentives, training and knowledge of health workers results in more identification of children eligible for TBPT.


Assuntos
Antibioticoprofilaxia/métodos , Busca de Comunicante/métodos , Implementação de Plano de Saúde , Mycobacterium/isolamento & purificação , Escarro/efeitos dos fármacos , Tuberculose Pulmonar/prevenção & controle , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nepal/epidemiologia , Prognóstico , Estudos Retrospectivos , Escarro/microbiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
10.
Microbiol Spectr ; 10(1): e0045921, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35138161

RESUMO

The prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV) coinfection in Nigeria is currently around 19.1%. This indicates that the two diseases are still a burden on the nation"s health. The aim of this study was to evaluate the diagnostic microbiology capacity and the barriers in performing assay for TB and HIV at peripheral district-level hospital-based laboratories in Oyo State, Nigeria. Diagnostic microbiology capacity was estimated using a scale of 100-point where scores ≤ 49% were categorized as low, 50-79% fair and ≥80% good. Barriers to diagnosis were summarized in proportions. The diagnostic microbiology capacity revealed that 6 (35.3%) and 11 (64.7%) of the laboratories had "fair" and "low" capacity, respectively, to detect TB in cerebrospinal fluid/sputum. In testing for HIV, 3 (17.6%) of the laboratories had "fair capacity" and 14 (82.4%) had "low capacity" to detect CD4 count and HIV antibodies in blood serum. The major diagnostic barriers in almost all (94.1%) the laboratories were lack of culture supplies and nonavailability of reagents/testing kits. There was no diagnostic microbiology service with good capacity to facilitate case detection of HIV and TB at the peripheral hospitals. Hence there is a need to improve the supply of reagents, culture stock and testing kits. This will facilitate the detection of TB and HIV cases in peripheral communities. IMPORTANCE This study provided a snapshot knowledge of testing capabilities and commodity availability at state laboratories. The findings should inform the action of stakeholders to improve diagnostic microbiology capacity, consequently enhancing diagnostic measures in detecting human immunodeficiency virus and Mycobacterium tuberculosis.


Assuntos
Coinfecção/diagnóstico , Infecções por HIV/diagnóstico , Laboratórios Hospitalares/normas , Tuberculose Pulmonar/diagnóstico , Adulto , Anticorpos Antivirais/sangue , Coinfecção/epidemiologia , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Laboratórios Hospitalares/estatística & dados numéricos , Pessoal de Laboratório/normas , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Nigéria/epidemiologia , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia
11.
Sci Rep ; 12(1): 2210, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35140255

RESUMO

Lung cancer (LC) and pulmonary tuberculosis (TB) are the deadliest neoplastic and bacterial infectious diseases worldwide, respectively. Clinicians and pathologists have long discussed the co-existence of LC and TB, and several epidemiologic studies have presented evidence indicating that TB could be associated with the development of LC, particularly adenocarcinoma. Nonetheless, this data remains controversial, and the mechanism which could underlie the association remains largely unexplored. Some bioinformatic studies have shown that human cancer biopsies have a very high frequency of bacterial DNA integration; since Mycobacterium Tuberculosis (MTb) is an intracellular pathogen, it could play an active role in the cellular transformation. Our group performed an exploratory study in a cohort of 88 LC patients treated at the Instituto Nacional de Cancelorogía (INCan) of Mexico City to evaluate the presence of MTb DNA in LC tissue specimens. For the first time, our results show the presence of the MTb IS6110 transposon in 40.9% (n = 36/88) of patients with lung adenocarcinomas. Additionally, through in-situ PCR we identified the presence of IS6110 in the nuclei of tumor cells. Furthermore, shotgun sequencing from two samples identified traces of MTb genomes present in tumor tissue, suggesting that similar Mtb strains could be infecting both patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/microbiologia , Elementos de DNA Transponíveis/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/microbiologia , Mycobacterium tuberculosis/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , DNA Bacteriano/genética , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Masculino , México , Pessoa de Meia-Idade , Análise de Sobrevida , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/microbiologia
12.
Sci Rep ; 12(1): 1656, 2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35102181

RESUMO

Infections with multiple strains of Mycobacterium tuberculosis are now widely recognized as a common occurrence. Identification of patients infected with multiple strains provides both insight into the disease dynamics and the epidemiology of tuberculosis. Analysis of Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeats (MIRU-VNTR) has been shown to be highly sensitive in detecting multiple M. tuberculosis strains even in sputum. The goal of this study was to identify cases of multiple M. tuberculosis strain infections among patients diagnosed with pulmonary tuberculosis in Southwestern Uganda and assessment of factors associated with multiple strain infections. DNA extracted directly from 78 sputum samples, each from an individual patient, was analyzed using the standard 24 loci MIRU-VNTR typing. Five (6.4%) of the 78 patients were infected with multiple strains of M. tuberculosis with all of them being the newly diagnosed cases while two-thirds of them were co-infected with HIV. Exact regression analysis projected that the natives were more likely to harbor multiple strains (OR; 0.981, 95% CI 0-7.926) as well as those with a high microbial load (OR; 0.390, 95% CI 0-3.8167). Despite these findings being not statistically significant due to the small sample size, this points to a critical component of disease dynamics that has clinical implications and emphasizes a need for a study using a larger cohort. It is also essential to study the potential factors associated with higher risk of exposure to newly diagnosed and HIV positive patients at the community level. In addition, our ability to detect multiple M. tuberculosis strains using the standard 24 loci MIRU-VNTR typing especially with allelic diversity in loci 2059 and 3171, which are excluded from the 15-locus MIRU-VNTR, lead us to recommend the use of this genotyping technique, especially in areas with tuberculosis endemicity similar to this study.


Assuntos
Técnicas Bacteriológicas , DNA Bacteriano/genética , Técnicas de Genotipagem , Sequências Repetitivas Dispersas , Repetições Minissatélites , Mycobacterium tuberculosis/genética , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia , Adolescente , Adulto , Coinfecção , DNA Bacteriano/isolamento & purificação , Feminino , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Valor Preditivo dos Testes , Prevalência , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Uganda/epidemiologia , Adulto Jovem
13.
Int J Mol Sci ; 23(3)2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-35163542

RESUMO

The PD-1/PD-L1 pathway is critical in T cell biology; however, the role of the PD-1/PD-L1 pathway in clinical characteristics and treatment outcomes in pulmonary tuberculosis (PTB) patients is unclear. We prospectively enrolled PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects. The expression of PD-1/PD-L1 on peripheral blood mononuclear cells (PBMCs) was measured and correlated with clinical characteristics and treatment outcomes in PTB patients. Immunohistochemistry and immunofluorescence were used to visualize PD-1/PD-L1-expressing cells in lung tissues from PTB patients and from murine with heat-killed MTB (HK-MTB) treatment. A total of 76 PTB, 40 LTBI, and 28 non-TB, non-LTBI subjects were enrolled. The expression of PD-1 on CD4+ T cells and PD-L1 on CD14+ monocytes was significantly higher in PTB cases than non-TB subjects. PTB patients with sputum smear/culture unconversion displayed higher PD-L1 expression on monocytes. PD-L1-expressing macrophages were identified in lung tissue from PTB patients, and co-localized with macrophages in murine lung tissues. Mycobacterium tuberculosis (MTB) whole cell lysate/EsxA stimulation of human and mouse macrophages demonstrated increased PD-L1 expression. In conclusion, increased expression of PD-L1 on monocytes in PTB patients correlated with higher bacterial burden and worse treatment outcomes. The findings suggest the involvement of the PD-1/PD-L1 pathway in MTB-related immune responses.


Assuntos
Antituberculosos/farmacologia , Antígeno B7-H1/metabolismo , Tuberculose Latente/metabolismo , Leucócitos Mononucleares/metabolismo , Mycobacterium tuberculosis/patogenicidade , Receptor de Morte Celular Programada 1/metabolismo , Tuberculose Pulmonar/metabolismo , Regulação para Cima , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antituberculosos/uso terapêutico , Estudos de Casos e Controles , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Tuberculose Latente/microbiologia , Masculino , Camundongos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Células THP-1 , Resultado do Tratamento , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Adulto Jovem
14.
Microbiol Spectr ; 10(1): e0155721, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35196822

RESUMO

Interest in host-directed therapies as alternatives/adjuncts to antibiotic treatment has resurged with the increasing prevalence of antibiotic-resistant tuberculosis (TB). Immunotherapies that reinvigorate immune responses by targeting immune checkpoints like PD-1/PD-L1 have proved successful in cancer therapy. Immune cell inhibitory receptors that trigger Mycobacterium tuberculosis-specific immunosuppression, however, are unknown. Here, we show that the levels of CD84, a SLAM family receptor, increase in T and B cells in lung tissues from M. tuberculosis-infected C57BL/6 mice and in peripheral blood mononuclear cells (PBMCs) from pulmonary TB patients. M. tuberculosis challenge experiments using CD84-deficient C57BL/6 mice suggest that CD84 expression likely leads to T and B cell immunosuppression during M. tuberculosis pathogenesis and also plays an inhibitory role in B cell activation. Importantly, CD84-deficient mice showed improved M. tuberculosis clearance and longer survival than M. tuberculosis-infected wild-type (WT) mice. That CD84 is a putative M. tuberculosis infection-specific inhibitory receptor suggests it may be a suitable target for the development of TB-specific checkpoint immunotherapies. IMPORTANCE Immune checkpoint therapies, such as targeting checkpoints like PD-1/PD-L1, have proved successful in cancer therapy and can reinvigorate immune responses. The potential of this approach for treating chronic infectious diseases like TB has been recognized, but a lack of suitable immunotherapeutic targets, i.e., immune cell inhibitory receptors that trigger immunosuppression specifically during Mycobacterium tuberculosis pathogenesis, has limited the application of this strategy in the development of new TB therapies. Our focus in this study was to address this gap and search for an M. tuberculosis-specific checkpoint target. Our results suggest that CD84 is a putative inhibitory receptor that may be a suitable target for the development of TB-specific checkpoint immunotherapies.


Assuntos
Linfócitos B/imunologia , Mycobacterium tuberculosis/fisiologia , Família de Moléculas de Sinalização da Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Tuberculose Pulmonar/imunologia , Animais , Feminino , Humanos , Pulmão/imunologia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mycobacterium tuberculosis/genética , Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/microbiologia
15.
Eur J Med Res ; 27(1): 24, 2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35151350

RESUMO

BACKGROUND: Tuberculosis (TB) is a communicable disease remains a major global health problem and the leading cause of death from a single infectious agent. Even though many of the WHO recommended TB control strategies were implemented; there is still a major gap in TB case detection and treatment. This study aimed to determine the prevalence of Mycobacterium tuberculosis among presumptive TB patients in Gedeo Zone, Southern Ethiopia. METHODS: A cross-sectional study was conducted on 384 TB suspected patients in Gedeo Zone from February to July 2021. Data were collected using a pretested structured questionnaire. Laboratory examination was processed using Xpert-MTB/RIF assay. Data entry was made using Epi info version 7 and analyzed by SPSS version 24. Logistic regression models were used to determine the risk factors. RESULTS: Out of 384 study participants suspected with TB, M. tuberculosis was isolated from 103 giving an overall prevalence of 26.8%. Males (AOR) = 1.95; 95% CI 1.56-2.65, P = 0.01) were more likely to develop TB than females. Study participants who were illiterate (AOR 2.10; 95% CI 1.17-2.51, P = 0.014) were more likely to develop TB than the educated ones. Cigarette smokers (AOR 2.89; 95% CI 2.10-3.84, P = 0.01), khat chewers (AOR 2.86; 95% CI 1.28-3.79, P = 0.01), vaccination (AOR 0.52; 95% CI 0.21-0.88, P = 0.02), close contact (AOR 3.42; 95% CI 2.24-4.50, P = 0.01) and being positive for HIV (AOR 2.01; 95% CI 1.07-3.52, 0.01) were more likely to develop TB. CONCLUSION: Despite implementation of national and international TB control strategies, TB still remains one of the major public health problems in the country especially in the study area. The high prevalence of MTB was reported different risk groups. Early case detection and management of TB should be given special attention to strengthen and an appropriate control and prevention methods to reduce the emergence and increasing of MTB cases.


Assuntos
Testes Genéticos/métodos , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Adulto Jovem
16.
PLoS One ; 17(1): e0262929, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35085337

RESUMO

BACKGROUND: Rapid diagnosis of tuberculosis (TB) and detection of drug resistance are very important for timely and appropriate management of patients. Xpert MTB/RIF assay is approved for use in TB and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert MTB/RIF assay under routine clinical settings with a heterogeneous group of patients and sample types in Ethiopia. METHODS: A retrospective study was carried out in 2220 presumptive TB cases at Jimma University Medical Center. Data were gathered from the registration logbook using formatted data extraction tools and double entered to epidata version 3.1 and further transported to SPSS version 20 for analysis. Associations were determined using the Chi-square test and P-value <0.05 was considered statistically significant. RESULTS: Of 2220 cases enrolled, 1665 (75%) were adults and the remaining 555 (25%) were children aged less than 14 years. The majority, 1964 (88.46%), had pulmonary manifestation and 256 (11.54%) had extrapulmonary involvements. The overall, frequency of Mycobacterium tuberculosis (MTB) was 9.3% (206/2220), among this 10.27% (171/1665) and 6.3% (35/555) were adults and children, respectively. M. tuberculosis was detected from 171 (8.75%) of pulmonary patients and 35 (13.28%) of extrapulmonary manifested patients. Out of 206 M. tuberculosis positive cases, 7(3.4%) were rifampicin-resistant: four from pulmonary tuberculosis (PTB) patients and three from EPTB patients. In the Chi-square test, the age group of 15-24 years, previous history of TB, pus/lymph node sample, and being HIV positive were significantly associated with TB positivity by Xpert MTB/RIF (P-value <0.001). CONCLUSION: These data suggest that the overall frequency of M. tuberculosis and rifampicin resistance was found to be relatively low compared to the previous reports in Ethiopia. Nevertheless, better diagnostic tools and approaches are still vital to halt the burden of TB and drug-resistant TB in the country.


Assuntos
Farmacorresistência Bacteriana , Soropositividade para HIV , HIV-1 , Mycobacterium tuberculosis , Rifampina , Tuberculose Pulmonar , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Etiópia , Feminino , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/epidemiologia , Soropositividade para HIV/microbiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia
17.
Anal Methods ; 14(4): 438-448, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35022623

RESUMO

Tuberculosis (TB) remains a public health problem that cannot be ignored. The portable and efficient detection of Mycobacterium tuberculosis (MTB) is important for the effective control of this disease. However, current detection techniques do not meet the requirements for MTB detection in the actual environment and often require cumbersome detection steps that are time consuming and inflexible. In this study, a portable immunosensor to detect MTB in sputum was prepared and then subjected to interface characterizations, such as scanning electron microscopy, hydrophilic angle test, and fluorescence characterization. The source and gate voltage of the device were optimized and tested using a non-contact photoresponse. The results showed that the sensitivity of the sensor to luminance increases with the decrease in source voltage. The gate voltage can substantially improve the response of the immunosensor to the normalized current of protein and amplify the signal at least 1.6 times. The optimal voltage detection conditions of source voltage (0.3 V) and gate voltage (0.1 V) were also determined. Several common proteins present in simulated saliva were used for anti-interference tests, and the sensor exhibited good specificity. Finally, the dilution gradient of an actual TB sputum sample was optimized. In the absence of preconditioning, a double-blind experiment was used to distinguish between the sputum from patients with TB and healthy individuals to shorten the TB detection time to a few minutes. Compared with the hospital's conventional detection method using cultures, the proposed method can complete the detection in a shorter time. This study provides a new strategy for the portable diagnosis of TB.


Assuntos
Técnicas Biossensoriais , Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Pulmonar , Método Duplo-Cego , Humanos , Imunoensaio , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia
18.
Bioorg Med Chem ; 53: 116506, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34890996

RESUMO

Tuberculosis (TB) remains a serious public health problem and one of the main concern is the emergence of multidrug-resistant and extensively resistant TB. Hyper-reactive patients develop inflammatory necrotic lung lesions that aggravate the pathology and facilitate transmission of mycobacteria. Treatment of severe TB is a major clinical challenge that has few effective solutions and patients face a poor prognosis, years of treatment and different adverse drug reactions. In this work, fifteen novel and thirty-one unusual thiourea derivatives were synthesized and evaluated in vitro for their antimycobacterial and anti-inflammatory potential and, in silico for ADMET parameters and for structure-activity relationship (SAR). Thioureas derivatives 10, 15, 16, 28 and 29 that had shown low cytotoxicity and high activities were selected for further investigation, after SAR study. These five thioureas derivatives inhibited Mtb H37Rv growth in bacterial culture and in infected macrophages, highlighting thiourea derivative 28 (MIC50 2.0 ± 1.1 and 2.3 ± 1.1 µM, respectively). Moreover, these compounds were active against the hypervirulent clinical Mtb strain M299, in bacterial culture, especially 16, 28 and 29, and in extracellular clumps, highlighting 29, with MIC50 5.6 ± 1.2 µM. Regarding inflammation, they inhibited NO through the suppression of iNOS expression, and also inhibited the production of TNF-α and IL-1ß. In silico studies were carried out suggesting that these five compounds could be administered by oral route and have low toxicological effects when compared to rifampicin. In conclusion, our data show that, at least, thiourea derivatives 16, 28 and 29 are promising antimycobacterial and anti-inflammatory agents, and candidates for further prospective studies aiming new anti-TB drugs, that can be used on a dual approach for the treatment of severe TB cases associated with exacerbated inflammation.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tioureia/farmacologia , Tuberculose Pulmonar/tratamento farmacológico , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antituberculosos/síntese química , Antituberculosos/química , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Índice de Gravidade de Doença , Relação Estrutura-Atividade , Tioureia/síntese química , Tioureia/química , Tuberculose Pulmonar/microbiologia
19.
J Clin Lab Anal ; 36(1): e24154, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34850984

RESUMO

BACKGROUND: There is limited research assessing the utility of the Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) assay for the analysis of bronchoalveolar lavage fluid (BALF) in Chinese patients with suspected pulmonary tuberculosis (PTB). Thus, our objective was to determine the diagnostic accuracy of the Xpert MTB/RIF assay and evaluate its utility for the determination of rifampicin resistance. METHODS: We retrospectively analyzed BALF from 214 patients with suspected PTB between January 2018 and March 2019. Using mycobacterial culture or final clinical diagnosis as the reference standard, the diagnostic accuracy of the smear microscopy (SM), tuberculosis bacillus DNA (TB-DNA), Xpert MTB/RIF assay, and the determination of rifampicin resistance based on the Xpert MTB/RIF assay were compared. RESULTS: As compared to mycobacterial culture, the sensitivity of the Xpert MTB/RIF assay, SM, and TB-DNA were 85.5% (74.2%-93.1%), 38.7% (26.6%-51.9%), and 67.7% (54.7%-79.1%), respectively. As compared to the final diagnosis, the specificity of the Xpert MTB/RIF assay, SM, and TB-DNA were 100.0% (95.9%-100.0%), 94.3% (87.1%-98.1%), and 98.9% (93.8%-100.0%), respectively. The sensitivity and specificity of the rifampicin resistance detection using the Xpert MTB/RIF assay were 100% and 98.0%, respectively, with liquid culture as the reference. CONCLUSIONS: This study demonstrates that the analysis of BALF with the Xpert MTB/RIF assay provides a rapid and accurate tool for the early diagnosis of PTB. The accuracy of diagnosis was superior compared with the SM and TB-DNA. Moreover, Xpert is a quick and accurate method for the diagnosis of rifampicin-resistant tuberculosis and can also provide more effective guidance for the treatment of PTB or multidrug-resistant tuberculosis (MDR-TB).


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Tipagem Molecular/métodos , Mycobacterium tuberculosis , Tuberculose Pulmonar/diagnóstico , Adulto , Antibióticos Antituberculose/farmacologia , Líquido da Lavagem Broncoalveolar/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Estudos Retrospectivos , Rifampina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/microbiologia
20.
Clin Infect Dis ; 74(8): 1390-1400, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-34286831

RESUMO

BACKGROUND: Automated radiologic analysis using computer-aided detection software (CAD) could facilitate chest X-ray (CXR) use in tuberculosis diagnosis. There is little to no evidence on the accuracy of commercially available deep learning-based CAD in different populations, including patients with smear-negative tuberculosis and people living with human immunodeficiency virus (HIV, PLWH). METHODS: We collected CXRs and individual patient data (IPD) from studies evaluating CAD in patients self-referring for tuberculosis symptoms with culture or nucleic acid amplification testing as the reference. We reanalyzed CXRs with three CAD programs (CAD4TB version (v) 6, Lunit v3.1.0.0, and qXR v2). We estimated sensitivity and specificity within each study and pooled using IPD meta-analysis. We used multivariable meta-regression to identify characteristics modifying accuracy. RESULTS: We included CXRs and IPD of 3727/3967 participants from 4/7 eligible studies. 17% (621/3727) were PLWH. 17% (645/3727) had microbiologically confirmed tuberculosis. Despite using the same threshold score for classifying CXR in every study, sensitivity and specificity varied from study to study. The software had similar unadjusted accuracy (at 90% pooled sensitivity, pooled specificities were: CAD4TBv6, 56.9% [95% confidence interval {CI}: 51.7-61.9]; Lunit, 54.1% [95% CI: 44.6-63.3]; qXRv2, 60.5% [95% CI: 51.7-68.6]). Adjusted absolute differences in pooled sensitivity between PLWH and HIV-uninfected participants were: CAD4TBv6, -13.4% [-21.1, -6.9]; Lunit, +2.2% [-3.6, +6.3]; qXRv2: -13.4% [-21.5, -6.6]; between smear-negative and smear-positive tuberculosis was: were CAD4TBv6, -12.3% [-19.5, -6.1]; Lunit, -17.2% [-24.6, -10.5]; qXRv2, -16.6% [-24.4, -9.9]. Accuracy was similar to human readers. CONCLUSIONS: For CAD CXR analysis to be implemented as a high-sensitivity tuberculosis rule-out test, users will need threshold scores identified from their own patient populations and stratified by HIV and smear status.


Assuntos
Aprendizado Profundo , Infecções por HIV , Tuberculose Pulmonar , Tuberculose , Infecções por HIV/complicações , Humanos , Sensibilidade e Especificidade , Software , Triagem , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/microbiologia , Raios X
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