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1.
Georgian Med News ; (306): 81-87, 2020 Sep.
Artigo em Russo | MEDLINE | ID: mdl-33130652

RESUMO

The study of the clinical and laboratory dynamics after an intensive phase of treatment in patients with firstly diagnosed pulmonary tuberculosis (FDTB) with alcohol consumption, and the development of a method for predicting the effectiveness of treatment. Examined 109 men with FDTB aged 20 to 50 years. Depending on the level of alcohol consumption, 3 groups of patients were formed. Patients of each group divided into two subgroups depending on the treatment regimen. The highest response to antioxidant therapy had indicators of phagocytic and enzymatic activity of neutrophils and endogenous intoxication. The dynamics of a decrease in all indicators of oxidative stress in groups 1 and 2 was higher in patients who additionally received antioxidants. The positive effects of group 3 was less. The models of prediction the positive dynamics level in the treatment of patients depending on the scheme therapy received have been developed. Predictors of treatment efficacy for patients with FDTB and alcohol intake with standard therapy are baseline alcohol consumption level, phagocytic index, and blood lymphocyte count. When prescribing antioxidants to a standard therapy regimen - initial level of alcohol consumption and phagocytic number. The degree of alcohol consumption is a common determinant of treatment effectiveness, regardless of treatment regimen.


Assuntos
Tuberculose Pulmonar , Adulto , Consumo de Bebidas Alcoólicas , Antioxidantes/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Adulto Jovem
2.
Medicine (Baltimore) ; 99(43): e22076, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120729

RESUMO

INTRODUCTION: Individuals with tuberculosis (TB) who are being treated with anti-tumor necrosis factor α (anti-TNFα) for coexisting conditions may experience unexpected exacerbations of TB after the initiation of antituberculous therapy, so-called anti-TNFα-induced TB-immune reconstitution inflammatory syndrome (anti-TNFα-induced TB-IRIS). Anti-TNFα-induced TB-IRIS is often treated empirically with corticosteroids; however, the evidence of the effectiveness of corticosteroids is lacking and the management can be a challenge. PATIENT CONCERNS: A 32-year-old man on long-term infliximab therapy for Crohn disease visited a clinic complaining of persistent fever and cough that had started 1 week previously. His most recent infliximab injection had been administered 14 days before the visit. A chest X-ray revealed a left pleural effusion, and he was admitted to a local hospital. DIAGNOSIS: A chest computed tomography (CT) scan revealed miliary pulmonary nodules; acid-fast bacilli were found in a sputum smear and a urine sediment sample; and polymerase chain reaction confirmed the presence of Mycobacterium tuberculosis in both his sputum and the pleural effusion. He was diagnosed with miliary TB. INTERVENTIONS: Antituberculous therapy was started and he was transferred to our hospital for further management. His symptoms initially improved after the initiation of antituberculous therapy, but 2 weeks later, his symptoms recurred and shadows on chest X-ray worsened. A repeat chest CT scan revealed enlarged miliary pulmonary nodules, extensive ground-glass opacities, and an increased volume of his pleural effusion. This paradoxical exacerbation was diagnosed as TB-IRIS associated with infliximab. A moderate-dose of systemic corticosteroid was initiated [prednisolone 25 mg/day (0.5 mg/kg/day)]. OUTCOMES: After starting corticosteroid treatment, his radiological findings improved immediately, and his fever and cough disappeared within a few days. After discharge, prednisolone was tapered off over the course of 10 weeks, and he completed a 9-month course of antituberculous therapy uneventfully. He had not restarted infliximab at his most recent follow-up 14 months later. CONCLUSION: We successfully managed a patient with anti-TNFα-induced TB-IRIS using moderate-dose corticosteroids. Due to the limited evidence currently available, physicians should consider the necessity, dosage, and duration of corticosteroids for each case of anti-TNFα-induced TB-IRIS on an individual patient-by-patient basis.


Assuntos
Glucocorticoides/uso terapêutico , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Infliximab/efeitos adversos , Prednisolona/uso terapêutico , Tuberculose Miliar/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Humanos , Masculino , Tomografia Computadorizada por Raios X , Tuberculose Miliar/diagnóstico por imagem , Tuberculose Miliar/etiologia , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/etiologia
3.
BMC Infect Dis ; 20(1): 720, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004004

RESUMO

BACKGROUND: Children living with sputum smear-positive adult tuberculosis (TB) patients are vulnerable to acquire tubercular infection. Contact tracing is an important strategy to control tubercular infection in the community. This study was done to find out prevalence of tuberculosis and tubercular infection in children living with sputum smear-positive adult patients receiving DOTS at recruitment and to find out incidence of tubercular infection and disease in these children on follow up. METHOD: Children (< 15 years) living in contact with adults on DOTS were grouped as < 6 years and 6-14 years. They were further sub grouped as being - uninfected, infected, diseased and on prophylaxis and were followed at 3, 6 and 9 months. Tuberculin skin test (TST) and chest X-ray were done. RESULTS: At recruitment 152 children were enrolled and 21.1% (n = 32) had TB. On follow up, 4.3% (n = 5), 5.8% (n = 6) and 11.6% (n = 11) children developed TB after 3, 6 and 9 months respectively.9 children did not come for the last follow up so the overall prevalence of TB disease at 9 months was 37.7% (n = 54). Out of the 128 children with TST reading 23.4% (n = 30) child contacts were found to be infected already at recruitment. The incidence of TST conversion was 20.7% (n = 18), 26.9% (n = 18) and 16.3% (n = 7) respectively. The overall prevalence of tubercular infection in the children, who were in contact with TB patients for 9 months was 74.5% (n = 73). CONCLUSION: About half the children were either suffering from TB or tubercular infection on recruitment. During 9 months follow up 22 unaffected children developed disease and 43acquired infection.


Assuntos
Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Características da Família , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Escarro/microbiologia , Teste Tuberculínico , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adulto Jovem
4.
Medicine (Baltimore) ; 99(40): e22583, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019474

RESUMO

INTRODUCTION: Henoch-Schönlein purpura (HSP) is an extremely rare condition in patients with pulmonary tuberculosis, with only a few reported cases. Compared to patients with typical clinical symptoms, it is difficult to make a definitive diagnosis when HSP presents as an initial manifestation in pulmonary tuberculosis patients. Herein, a case of pulmonary tuberculosis that showed HSP at first was reported, and the related literatures were reviewed. PATIENT CONCERNS: A 24-year-old man presented with palpable purpura on the extremities, accompanied by abdominal pain, bloody stools, and knee pain. DIAGNOSES: The patient was diagnosed with pulmonary tuberculosis based on the results of interferon gamma release assays, purified protein derivative test, and computed tomography. INTERVENTIONS: The patient was treated with vitamin C and chlorpheniramine for 2 weeks, and the above-mentioned symptoms were relieved. However, 3 weeks later, the purpura recurred with high-grade fever and chest pain during the inspiratory phase. The patient was then treated with anti-tuberculosis drugs, and the purpura as well as the high fever disappeared. OUTCOMES: The patient recovered well and remained free of symptoms during the follow-up examination. CONCLUSION: Pulmonary tuberculosis presenting with HSP as an initial manifestation is not common. Therefore, it is difficult to clinically diagnose and treat this disease. When an adult patient shows HSP, it is important to consider the possibility of tuberculosis to avoid misdiagnosis and delayed treatment.


Assuntos
Antituberculosos/uso terapêutico , Púrpura de Schoenlein-Henoch/etiologia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológico , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Assistência ao Convalescente , Ácido Ascórbico/uso terapêutico , Clorfeniramina/uso terapêutico , Diagnóstico Diferencial , Febre/diagnóstico , Febre/etiologia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Testes de Liberação de Interferon-gama/métodos , Masculino , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Resultado do Tratamento , Tuberculina , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/diagnóstico por imagem , Vitaminas/uso terapêutico , Adulto Jovem
5.
Medicine (Baltimore) ; 99(40): e22639, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019487

RESUMO

INTRODUCTION: Tuberculous meningitis (TBM) is the most fatal type of tuberculosis in which corticosteroids are added with antitubercular therapy to prevent permanent brain damage. However, this treatment may produce paradoxical reactions. In such cases, thalidomide use might reduce central nervous system inflammation and improve the outcome. We present the case of a human immunodeficiency virus-negative patient with TBM who developed paradoxical reactions manifesting as multiple intracranial tuberculomas that were resistant to standard care (antitubercular drugs and corticosteroids) but responded well to thalidomide. PATIENT'S MAIN CONCERN AND CLINICAL FINDINGS: The patient was a 40-year-old Chinese female, who was admitted with a 10-day history of headaches, night sweats, and cough. She was healthy before contracting the infection and had no history of contact with tuberculosis patients. DIAGNOSES, INTERVENTION, AND OUTCOME: We diagnosed the patient with TBM complicated by the occurrence of pulmonary tuberculosis. Positive results were obtained from Gram and Ziehl-Neelsen staining of the sputum and acid-fast bacilli sputum culture. Standard treatment was initiated with antitubercular drugs (daily isoniazid, rifampicin, ethionamide, and pyrazinamide) and corticosteroids (dexamethasone). However, 3 months later the magnetic resonance imaging of the head revealed some new tuberculoma lesion. Thus, a specific therapy of antitubercular drugs and thalidomide was introduced. On completion of a 12-month course of antitubercular drugs with 2 months of thalidomide, the patient showed favorable outcomes without neurologic sequelae. Moreover, thalidomide appeared safe and well tolerated in the patient. CONCLUSION: In addition to the specific anti-tubercular and adjuvant corticosteroid therapies for TBM, thalidomide can be used as a "salvage" antitubercular drug in cases that are unresponsive to corticosteroids.


Assuntos
HIV/imunologia , Imunossupressores/uso terapêutico , Talidomida/uso terapêutico , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Pulmonar/complicações , Corticosteroides/uso terapêutico , Adulto , Antituberculosos/uso terapêutico , Grupo com Ancestrais do Continente Asiático/etnologia , Encéfalo/patologia , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Imagem por Ressonância Magnética/métodos , Terapia de Salvação , Resultado do Tratamento , Tuberculoma/diagnóstico por imagem , Tuberculose Meníngea/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico
6.
Medicine (Baltimore) ; 99(44): e22258, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126298

RESUMO

We aimed to investigate the effect of interval between food intake and drug administration at fasting condition on the plasma concentrations of first-line anti- tuberculosis (TB) drugs in Chinese population. Newly diagnosed TB patients administered the anti-TB drugs under fasting conditions orally, and then had prepared breakfast at 30 minutes and 120 min after dosing, respectively. Blood sampling was also performed 120  minutes after dosing for the detection of Cmax purpose. Overall, twenty-five participants were included in our analysis. The Cmaxs of 30  minutes interval and 120  minutes interval were 21.8 ±â€Š2.0 and 19.2 ±â€Š2.0 µg/mL for rifampin, 1.6 ±â€Š0.2 and 2.1 ±â€Š0.2 µg/mL for isoniazid (INH), 1.5 ±â€Š0.1and 1.5 ±â€Š0.2 µg/mL for ethambutol (EMB), and 49.2 ±â€Š3.7 and 41.5 ±â€Š3.9 µg/mL for pyrazinamide, respectively. Statistical analysis revealed that there was no statistical difference between 2 groups. Additionally, 88.0% and 72.0% of the 25 participants at 2-hour interval group had peak concentrations less than the lower limit of the reference range for INH and EMB, respectively. The Cmaxs of INH were 0.9 ±â€Š0.4 µg/ml for rapid acetylator, which was significantly lower than those of intermediate (1.4 ±â€Š1.0 µg/mL), and slow acetylator (2.5 ±â€Š1.0 µg/mL), respectively (P < .01). In conclusion, our data demonstrate that early food intake at 30 minutes after drug administration had no significant influence on the plasma concentrations. In addition, a high proportion of patients receiving first-line anti-TB regimen fail to achieve the expected plasma drug ranges of INH and EMB (P > .05).


Assuntos
Antituberculosos/sangue , Ingestão de Alimentos , Jejum/sangue , Fatores de Tempo , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/tratamento farmacológico , Administração Oral , Adulto , Antituberculosos/administração & dosagem , China , Esquema de Medicação , Etambutol/administração & dosagem , Etambutol/sangue , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/sangue , Masculino , Pirazinamida/administração & dosagem , Pirazinamida/sangue , Rifampina/administração & dosagem , Rifampina/sangue , Resultado do Tratamento
7.
BMC Infect Dis ; 20(1): 789, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097000

RESUMO

BACKGROUND: People successfully completing treatment for tuberculosis remain at elevated risk for recurrent disease, either from relapse or reinfection. Identifying risk factors for recurrent tuberculosis may help target post-tuberculosis screening and care. METHODS: We enrolled 500 patients with smear-positive pulmonary tuberculosis in South Africa and collected baseline data on demographics, clinical presentation and sputum mycobacterial cultures for 24-loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. We used routinely-collected administrative data to identify recurrent episodes of tuberculosis occurring over a median of six years after successful treatment completion. RESULTS: Of 500 patients initially enrolled, 333 (79%) successfully completed treatment for tuberculosis. During the follow-up period 35 patients with successful treatment (11%) experienced a bacteriologically confirmed tuberculosis recurrence. In our Cox proportional hazards model, a 3+ AFB sputum smear grade was significantly associated with recurrent tuberculosis with a hazard ratio of 3.33 (95% CI 1.44-7.7). The presence of polyclonal M. tuberculosis infection at baseline had a hazard ratio for recurrence of 1.96 (95% CI 0.86-4.48). CONCLUSION: Our results indicate that AFB smear grade is independently associated with tuberculosis recurrence after successful treatment for an initial episode while the association between polyclonal M. tuberculosis infection and increased risk of recurrence appears possible.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/genética , Escarro/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adulto , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Recidiva , Fatores de Risco , África do Sul/epidemiologia , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Adulto Jovem
9.
BMC Infect Dis ; 20(1): 678, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942990

RESUMO

BACKGROUND: Tuberculosis (TB) control is a primary global health priority but the goal to eliminate TB is being threatened by the increase in incidence of multidrug-resistant tuberculosis (MDR-TB). With this series of seven MDR-TB cases in migrant patients with identical Mycobacterium tuberculosis strains we aim to illustrate the challenges encountered during therapy and follow-up: language barriers, access to care for migrant patients, depression due to isolation, adverse reactions to the treatment, management of pediatric TB, further contact tracing. We also discuss best practices for the management of complex MDR-TB cases in settings with low overall TB incidence focusing on modern diagnostic assays and an individualized and an interdisciplinary therapeutic approach. METHODS: We describe a case series of seven consecutively diagnosed MDR-TB patients, six of them treated at our tertiary care hospital between May 2018 and March 2020. Epidemiologic data was gained by semi-structured patient interviews and reconstruction of the migration route. The origin of the cluster was confirmed by genotyping of the TB-strains. RESULTS: Six related patients were diagnosed with pulmonary MDR-TB between May and August 2018. All had a positive Interferon-Gamma-Release Assay (IGRA), in five patients sputum microscopy was positive for acid-fast bacilli (AFB). The genetic and phenotypical drug susceptibility test did not match with MDR-TB strains from an East-African origin. The index patient was identified through genetical fingerprinting. By changing the therapy to a modern MDR-TB regime and using an interdisciplinary and culture-sensitive approach, all patients improved clinically and radiologically. CONCLUSION: Human migration plays an important role for the global spread of MDR-TB in low incidence countries. Early case detection and adequate treatment are key to prevention of outbreaks. Especially language barriers and complex migration routes make genotyping of TB-strains a crucial tool to identify cases clusters, the potential index patient and transmission dynamics. We are fortunate enough to experience times in which new TB-antibiotics were made available and in which molecular assays revolutionized TB-diagnostics. We need to take advantage of that and develop personalized therapies for patients suffering from drug resistant TB.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Antituberculosos/efeitos adversos , Pré-Escolar , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Fenótipo , Gravidez , Escarro/microbiologia , Sudão , Migrantes , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Adulto Jovem
10.
BMC Infect Dis ; 20(1): 686, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948149

RESUMO

BACKGROUND: There is limited research to guide TB treatment specifically in pregnant women and few studies have described the presentation of TB in pregnant women. We aimed to understand TB presentation and treatment outcomes in pregnant women in a low HIV burden setting. We describe a cohort of women of childbearing age treated for TB disease in Lima, Peru, and compare clinical presentation and treatment outcomes among pregnant and non-pregnant women between 2009 and 2012, including 36 pregnant women. METHODS: This is a prospective cohort study. Subjects were recruited from across 106 public health centers in Lima, Peru. Baseline demographic, medical history, and drug-susceptibility test results were collected. We used descriptive statistics to describe demographic and clinical characteristics of the women using Pearson chi-squared, Fisher's exact tests, or Kruskal-Wallis. RESULTS: Among 4500 individuals with pulmonary TB disease, 1334 women were included in analysis with 36 (2.69%) pregnant women. Pregnant women had similar demographics, past medical histories, and clinical presentation to non-pregnant women, except being more likely to be married (p = 0.01) and have cardiac disease (p = 0.04) and less likely to have weight loss (p = 0.05). Twenty (71.4%) pregnant women had pan-susceptible TB compared with 616 (63.1%) non-pregnant women; four (14.3%) pregnant women had mono-resistant TB compared with 154 (15.8%) non-pregnant women; and four (14.3%) pregnant women had multi-drug-resistant TB compared with 140 (14.3%) of non-pregnant women (p = 0.53). Twenty-eight (96.6%) pregnant women had a successful outcome (cure, completed treatment, treatment ended early by clinical team) while one (3.4%) had an unsuccessful outcome (treatment failed) and 1074 (97.3%) non-pregnant women had a successful outcome while 30 (2.7%) had an unsuccessful outcome (p = 0.56). CONCLUSION: In this cohort with low HIV co-infection, we found high TB treatment success rates in both pregnant and non-pregnant women, irrespective of drug-susceptibility profiles. If treated appropriately, pregnant women with TB disease can have successful outcomes.


Assuntos
Complicações Infecciosas na Gravidez/tratamento farmacológico , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Antituberculosos/uso terapêutico , Coinfecção/tratamento farmacológico , Feminino , Infecções por HIV , Humanos , Pessoa de Meia-Idade , Peru , Gravidez , Estudos Prospectivos , Resultado do Tratamento , Tuberculose Pulmonar/tratamento farmacológico , Adulto Jovem
11.
PLoS One ; 15(9): e0238007, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32870914

RESUMO

Tuberculosis (TB) is a serious disease of public health concern, mainly in low- and middle-income countries. Most of these countries have challenges in diagnosis and treatment of TB in people with smear-negative pulmonary tuberculosis (SNPTB), which remains a significant public health challenge because of the global burden of the disease. We evaluated the epidemiology and clinical presentation of SNPTB in a cohort of patients with high HIV burden. The study was a cross-sectional study among patients with SNPTB in four major hospitals that care for TB/HIV patients in north-central Nigeria. All patients 18 years and above who were newly diagnosed as SNPTB, or patients with SNPTB who had not taken TB drugs for up to 2 weeks irrespective of their HIV status were recruited. Demographic data (sex, age), smoking status, and medical history (clinical form of TB, symptoms at admission, diagnostic methods, presence of comorbidities, prior TB treatment) were obtained using a semi-structured questionnaire. Detailed clinical examination was also done on all the study subjects. Baseline results of packed cell volume, HIV test and sputum acid fast bacilli done during TB screening were retrieved from the patients' case notes and recorded. Also, the base line Chest X-ray films taken during TB screening were reviewed and reported by two radiologists blinded to each other's reports. The Xpert MTB/RIF tests and sputum culture (using LJ medium) were done in a TB reference laboratory. A total of 150 patients with SNPTB were studied. Majority of the patients were female 93 (62%). The median age of the patients was 36.5 years with greater percentage of the patients within the ages of 25-44 years 92 (61.3%). Twenty-two (14.7%) of the patients had previous TB treatment. History of cigarette smoking was obtained in only 7(4.7%) of the patients while 82 (64.1%) were HIV positive. All the patients had a history of cough for over a period of at least three weeks, while, 27 (18%) reported having hemoptysis. About 87 (58%) had fever and 110 (73.7%) had anemia, while weight loss and night sweat were reported in 98(65.3%) and 82 (54.7%) of the patients respectively. Chest x rays were reported as typical of TB in only 24 (16%) of the patients. Of the 150 sputa sample analyzed, 21/150 (14.0%) and 22/150 (14.7%) where Gene Xpert and sputum culture positive respectively. The sensitivity and specificity of Gene Xpert assay were 81.8% (18/22; 95% CI 61.5 to 92.7%) and 97.4% (112/115; 95% CI 92.6 to 99.1%), respectively. The study found cough, fever and anemia to be the commonest presentation in patient with SNPTB in a high HIV burden patient's population. There is also relatively high culture positivity among the patients. This underscores the need to expand the facilities for culture and confirmation in TB centers across the country.


Assuntos
Infecções por HIV/complicações , HIV/isolamento & purificação , Programas de Rastreamento , Mycobacterium tuberculosis/fisiologia , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adulto , Antibióticos Antituberculose/uso terapêutico , Estudos Transversais , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Nigéria/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/etiologia
13.
BMC Infect Dis ; 20(1): 612, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811479

RESUMO

BACKGROUND: Pulmonary tuberculosis (PTB) is one of the serious infectious diseases worldwide; however, the gene network involved in the host response remain largely unclear. METHODS: This study integrated two cohorts profile datasets GSE34608 and GSE83456 to elucidate the potential gene network and signaling pathways in PTB. Differentially expressed genes (DEGs) were obtained for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using Metascape database. Protein-Protein Interaction (PPI) network of DEGs was constructed by the online database the Search Tool for the Retrieval of Interacting Genes (STRING). Modules were identified by the plug-in APP Molecular Complex Detection (MCODE) in Cytoscape. GO and KEGG pathway of Module 1 were further analyzed by STRING. Hub genes were selected for further expression validation in dataset GSE19439. The gene expression level was also investigated in the dataset GSE31348 to display the change pattern during the PTB treatment. RESULTS: Totally, 180 shared DEGs were identified from two datasets. Gene function and KEGG pathway enrichment revealed that DEGs mainly enriched in defense response to other organism, response to bacterium, myeloid leukocyte activation, cytokine production, etc. Seven modules were clustered based on PPI network. Module 1 contained 35 genes related to cytokine associated functions, among which 14 genes, including chemokine receptors, interferon-induced proteins and Toll-like receptors, were identified as hub genes. Expression levels of the hub genes were validated with a third dataset GSE19439. The signature of this core gene network showed significant response to Mycobacterium tuberculosis (Mtb) infection, and correlated with the gene network pattern during anti-PTB therapy. CONCLUSIONS: Our study unveils the coordination of causal genes during PTB infection, and provides a promising gene panel for PTB diagnosis. As major regulators of the host immune response to Mtb infection, the 14 hub genes are also potential molecular targets for developing PTB drugs.


Assuntos
Biologia Computacional/métodos , Redes Reguladoras de Genes , Mycobacterium tuberculosis , Mapas de Interação de Proteínas/genética , Transcriptoma , Tuberculose Pulmonar/genética , Biomarcadores , Estudos de Coortes , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Transdução de Sinais/genética , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
14.
PLoS One ; 15(8): e0237062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760105

RESUMO

Nutritional status contributes to the regulation of immune responses against pathogens, and malnutrition has been considered as a risk factor for tuberculosis (TB). Mycobacterium tuberculosis (Mtb), the causative agent of TB, can modulate host lipid metabolism and induce lipid accumulation in macrophages, where the bacilli adopt a dormant phenotype. In addition, serum lipid components play dual roles in the regulation of and protection from Mtb infection. We analyzed the relationship between nutritional status and the humoral immune response in TB patients. We found that serum HDL levels are positively correlated with the serum IgA specific for Mtb antigens. Analysis of the relationship between serum nutritional parameters and clinical parameters in TB patients showed that serum albumin and CRP levels were negatively correlated before treatment. We also observed reduced serum LDL levels in TB patients following treatment. These findings may provide insight into the role of serum lipids in host immune responses against Mtb infection. Furthermore, improving the nutritional status may enhance vaccination efficacy.


Assuntos
Imunidade Humoral , Mycobacterium tuberculosis/imunologia , Estado Nutricional/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Proteína C-Reativa/metabolismo , Progressão da Doença , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Albumina Sérica Humana/metabolismo , Vacinas contra a Tuberculose/imunologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/tratamento farmacológico
15.
Am J Trop Med Hyg ; 103(4): 1593-1596, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32815515

RESUMO

Coinfection of SARS-CoV-2/Mycobacterium tuberculosis (MTB) in patients with HIV/AIDS has not been previously reported. Here, we present two cases of coinfection of SARS-CoV-2 and MTB in patients with HIV. The first case is a 39-year-old patient who was admitted with a 7-day history of fever, myalgia, headache, and cough. The second patient is a 43-year-old man who had a 1-month history of cough with hemoptoic sputum, evolving to mild respiratory distress in the last 7 days. Both patients already had pulmonary tuberculosis and subsequently developed SARS-CoV-2 infection during the 2020 pandemic. Nonadherence to antiretroviral treatment may have been a factor in the clinical worsening of the patients.


Assuntos
Infecções por Coronavirus/microbiologia , Tosse/microbiologia , Infecções por HIV/microbiologia , Cooperação do Paciente/psicologia , Pneumonia Viral/microbiologia , Síndrome do Desconforto Respiratório do Adulto/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Betacoronavirus/patogenicidade , Coinfecção , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Tosse/tratamento farmacológico , Tosse/imunologia , Tosse/virologia , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Mycobacterium tuberculosis/patogenicidade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/imunologia , Síndrome do Desconforto Respiratório do Adulto/virologia , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/virologia
16.
PLoS Comput Biol ; 16(8): e1008107, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32810158

RESUMO

Standard treatment for active tuberculosis (TB) requires drug treatment with at least four drugs over six months. Shorter-duration therapy would mean less need for strict adherence, and reduced risk of bacterial resistance. A system pharmacology model of TB infection, and drug therapy was developed and used to simulate the outcome of different drug therapy scenarios. The model incorporated human immune response, granuloma lesions, multi-drug antimicrobial chemotherapy, and bacterial resistance. A dynamic population pharmacokinetic/pharmacodynamic (PK/PD) simulation model including rifampin, isoniazid, pyrazinamide, and ethambutol was developed and parameters aligned with previous experimental data. Population therapy outcomes for simulations were found to be generally consistent with summary results from previous clinical trials, for a range of drug dose and duration scenarios. An online tool developed from this model is released as open source software. The TB simulation tool could support analysis of new therapy options, novel drug types, and combinations, incorporating factors such as patient adherence behavior.


Assuntos
Antituberculosos/uso terapêutico , Modelos Teóricos , Tuberculose Pulmonar/tratamento farmacológico , Antituberculosos/administração & dosagem , Antituberculosos/farmacocinética , Quimioterapia Combinada , Humanos , Adesão à Medicação
17.
PLoS One ; 15(8): e0235411, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822368

RESUMO

BACKGROUND: Delayed treatment initiation of Tuberculosis patients results in increased infectivity, poor treatment outcome, and increased mortality. However, there is a paucity of evidence on the delay in new adult pulmonary Tuberculosis patients to initiate treatment in Tigray, Northern Ethiopia. OBJECTIVE: To assess the factors associated with treatment initiation delay among new adult pulmonary tuberculosis patients in Tigray, Northern Ethiopia. METHODS: The study design was cross-sectional. A total of 875 new adult pulmonary tuberculosis patients were recruited from 21 health facilities from October 2018 to October 2019. Health facilities were selected by simple random sampling technique and tuberculosis cases from the health facilities were consecutively enrolled. Data were collected using structured questionnaire within the first 2 weeks of treatment initiation. Delay was categorized as patient, health system and total delays. Data were analyzed using SPSS version 21 and logistic regression was used to identify factors associated with the odds of delays to initiate treatment. A p-value of less than 0.05 was reported as statistically significant. RESULTS: The median patient, health system and total delays were 30, 18 and 62 days, respectively. Rural residence, being poor, visiting non-formal medication sources, being primary health care and the private clinic had higher odds of patient delay whereas being HIV positive had lower odds of patient delay. Illiteracy, first visit to primary health care and private clinic had higher odds of health system delay whereas a visit to health facility one time and have no patient delay had lower odds of health system delay. CONCLUSION: The median patient delay was higher than the median health system delay before initiating treatment. Hence, improved awareness of the community and involving the informal medication sources in the tuberculosis pathways would reduce patient delay. Similarly, improved cough screening and diagnostic efficiency of the lower health facilities would shorten health system delay.


Assuntos
Tempo para o Tratamento/estatística & dados numéricos , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Comorbidade , Etiópia , Feminino , Hospitais Privados/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/estatística & dados numéricos , Tuberculose Pulmonar/epidemiologia
18.
PLoS One ; 15(8): e0236362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797053

RESUMO

BACKGROUND: Tuberculosis (TB) is among the top 10 causes of mortality and the first killer among infectious diseases worldwide. One of the factors fuelling the TB epidemic is the global rise of multidrug resistant TB (MDR-TB). The aim of this study was to determine the magnitude and factors associated with MDR-TB in the Tigray Region, Ethiopia. METHOD: This study employed a facility-based cross-sectional study design, which was conducted between July 2018 and August 2019. The inclusion criteria for the study participants were GeneXpert-positive who were not under treatment for TB, PTB patients' ≥15 years of age and who provided written informed consent. A total of 300 participants were enrolled in the study, with a structured questionnaire used to collect data on clinical, sociodemographic and behavioral factors. Sputum samples were collected and processed for acid-fast bacilli staining, culture and drug susceptibility testing. Drug susceptibility testing was performed using a line probe assay. Logistic regression was used to analyze associations between outcome and predictor variables. RESULTS: The overall proportion of MDR-TB was 16.7% (11.6% and 32.7% for new and previously treated patients, respectively). Of the total MDR-TB isolates, 5.3% were pre-XDR-TB. The proportion of MDR-TB/HIV co-infection was 21.1%. A previous history of TB treatment AOR 3.75; 95% CI (0.7-2.24), cigarette smoking AOR 6.09; CI (1.65-2.50) and patients who had an intermittent fever (AOR = 2.54, 95% CI = 1.21-5.4) were strongly associated with MDR-TB development. CONCLUSIONS: The magnitude of MDR-TB observed among new and previously treated patients is very alarming, which calls for an urgent need for intervention. The high proportion of MDR-TB among newly diagnosed cases indicates ongoing transmission, which suggests the need for enhanced TB control program performance to interrupt transmission. The increased proportion of MDR-TB among previously treated cases indicates a need for better patient management to prevent the evolution of drug resistance. Assessing the TB control program performance gaps and an optimal implementation of the WHO recommended priority actions for the management of drug-resistant TB, is imperative to help reduce the current high MDR-TB burden in the study region.


Assuntos
Infecções por HIV/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Estudos Transversais , Etiópia/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Infecções por HIV/patologia , Humanos , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Rifampina/uso terapêutico , Fatores de Risco , Escarro/efeitos dos fármacos , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Adulto Jovem
19.
PLoS One ; 15(8): e0237345, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813724

RESUMO

BACKGROUND: Mixed/polyclonal infections due to different genotypes are reported in Tuberculosis. The current study was designed to understand the fate of mixed infections during the course of treatment and follow-up and its role in disease pathogenesis. METHODS: Sputum samples were collected on 0,1,2,3,6,12 and 24 months from 157 treatment-naïve patients, cultures subjected to Drug-Susceptibility-testing (MGIT 960), spoligotyping, MIRU-VNTR and SNP genotyping. All isolated colonies on thin layer agar (7H11) were subjected to spoligotyping. FINDINGS: One thirty three baseline cultures were positive (133/157, 84.7%), 43(32.3%) had mixture of genotypes. Twenty-four of these patients (55.8%) showed change in genotype while six showed different drug-susceptibility patterns while on treatment. Twenty-three (53.5%) patients with polyclonal infections showed resistance to at least one drug compared to 10/90 (11.1%) monoclonal infections (P<0.0001). Eight patients had recurrent TB, two with a new genotype and two with altered phenotypic DST. CONCLUSIONS: The coexistence of different genotypes and change of genotypes during the same disease episode, while on treatment, confirms constancy of polyclonal infections. The composition of the mixture of genotypes and the relative predominance may be missed by culture due to its limit of detection. Polyclonal infections in TB could be a rule rather than exception and challenges the age-old dogma of reactivation/reinfection.


Assuntos
Antituberculosos/farmacologia , Coinfecção/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/microbiologia , Adolescente , Adulto , Antituberculosos/uso terapêutico , Técnicas de Tipagem Bacteriana , Evolução Clonal , Coinfecção/epidemiologia , Coinfecção/microbiologia , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Feminino , Seguimentos , Técnicas de Genotipagem , Humanos , Limite de Detecção , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium tuberculosis/patogenicidade , Filogenia , Polimorfismo de Nucleotídeo Único , Prevalência , Recidiva , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adulto Jovem
20.
Cochrane Database Syst Rev ; 8: CD013359, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853411

RESUMO

BACKGROUND: Every year, at least one million children become ill with tuberculosis and around 200,000 children die. Xpert MTB/RIF and Xpert Ultra are World Health Organization (WHO)-recommended rapid molecular tests that simultaneously detect tuberculosis and rifampicin resistance in adults and children with signs and symptoms of tuberculosis, at lower health system levels. To inform updated WHO guidelines on molecular assays, we performed a systematic review on the diagnostic accuracy of these tests in children presumed to have active tuberculosis. OBJECTIVES: Primary objectives • To determine the diagnostic accuracy of Xpert MTB/RIF and Xpert Ultra for (a) pulmonary tuberculosis in children presumed to have tuberculosis; (b) tuberculous meningitis in children presumed to have tuberculosis; (c) lymph node tuberculosis in children presumed to have tuberculosis; and (d) rifampicin resistance in children presumed to have tuberculosis - For tuberculosis detection, index tests were used as the initial test, replacing standard practice (i.e. smear microscopy or culture) - For detection of rifampicin resistance, index tests replaced culture-based drug susceptibility testing as the initial test Secondary objectives • To compare the accuracy of Xpert MTB/RIF and Xpert Ultra for each of the four target conditions • To investigate potential sources of heterogeneity in accuracy estimates - For tuberculosis detection, we considered age, disease severity, smear-test status, HIV status, clinical setting, specimen type, high tuberculosis burden, and high tuberculosis/HIV burden - For detection of rifampicin resistance, we considered multi-drug-resistant tuberculosis burden • To compare multiple Xpert MTB/RIF or Xpert Ultra results (repeated testing) with the initial Xpert MTB/RIF or Xpert Ultra result SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the International Standard Randomized Controlled Trials Number (ISRCTN) Registry up to 29 April 2019, without language restrictions. SELECTION CRITERIA: Randomized trials, cross-sectional trials, and cohort studies evaluating Xpert MTB/RIF or Xpert Ultra in HIV-positive and HIV-negative children younger than 15 years. Reference standards comprised culture or a composite reference standard for tuberculosis and drug susceptibility testing or MTBDRplus (molecular assay for detection of Mycobacterium tuberculosis and drug resistance) for rifampicin resistance. We included studies evaluating sputum, gastric aspirate, stool, nasopharyngeal or bronchial lavage specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), fine needle aspirates, or surgical biopsy tissue (lymph node tuberculosis). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study quality using the Quality Assessment of Studies of Diagnostic Accuracy - Revised (QUADAS-2). For each target condition, we used the bivariate model to estimate pooled sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We assessed certainty of evidence using the GRADE approach. MAIN RESULTS: For pulmonary tuberculosis, 299 data sets (68,544 participants) were available for analysis; for tuberculous meningitis, 10 data sets (423 participants) were available; for lymph node tuberculosis, 10 data sets (318 participants) were available; and for rifampicin resistance, 14 data sets (326 participants) were available. Thirty-nine studies (80%) took place in countries with high tuberculosis burden. Risk of bias was low except for the reference standard domain, for which risk of bias was unclear because many studies collected only one specimen for culture. Detection of pulmonary tuberculosis For sputum specimens, Xpert MTB/RIF pooled sensitivity (95% CI) and specificity (95% CI) verified by culture were 64.6% (55.3% to 72.9%) (23 studies, 493 participants; moderate-certainty evidence) and 99.0% (98.1% to 99.5%) (23 studies, 6119 participants; moderate-certainty evidence). For other specimen types (nasopharyngeal aspirate, 4 studies; gastric aspirate, 14 studies; stool, 11 studies), Xpert MTB/RIF pooled sensitivity ranged between 45.7% and 73.0%, and pooled specificity ranged between 98.1% and 99.6%. For sputum specimens, Xpert Ultra pooled sensitivity (95% CI) and specificity (95% CI) verified by culture were 72.8% (64.7% to 79.6%) (3 studies, 136 participants; low-certainty evidence) and 97.5% (95.8% to 98.5%) (3 studies, 551 participants; high-certainty evidence). For nasopharyngeal specimens, Xpert Ultra sensitivity (95% CI) and specificity (95% CI) were 45.7% (28.9% to 63.3%) and 97.5% (93.7% to 99.3%) (1 study, 195 participants). For all specimen types, Xpert MTB/RIF and Xpert Ultra sensitivity were lower against a composite reference standard than against culture. Detection of tuberculous meningitis For cerebrospinal fluid, Xpert MTB/RIF pooled sensitivity and specificity, verified by culture, were 54.0% (95% CI 27.8% to 78.2%) (6 studies, 28 participants; very low-certainty evidence) and 93.8% (95% CI 84.5% to 97.6%) (6 studies, 213 participants; low-certainty evidence). Detection of lymph node tuberculosis For lymph node aspirates or biopsies, Xpert MTB/RIF pooled sensitivity and specificity, verified by culture, were 90.4% (95% CI 55.7% to 98.6%) (6 studies, 68 participants; very low-certainty evidence) and 89.8% (95% CI 71.5% to 96.8%) (6 studies, 142 participants; low-certainty evidence). Detection of rifampicin resistance Xpert MTB/RIF pooled sensitivity and specificity were 90.0% (67.6% to 97.5%) (6 studies, 20 participants; low-certainty evidence) and 98.3% (87.7% to 99.8%) (6 studies, 203 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: We found Xpert MTB/RIF sensitivity to vary by specimen type, with gastric aspirate specimens having the highest sensitivity followed by sputum and stool, and nasopharyngeal specimens the lowest; specificity in all specimens was > 98%. Compared with Xpert MTB/RIF, Xpert Ultra sensitivity in sputum was higher and specificity slightly lower. Xpert MTB/RIF was accurate for detection of rifampicin resistance. Xpert MTB/RIF was sensitive for diagnosing lymph node tuberculosis. For children with presumed tuberculous meningitis, treatment decisions should be based on the entirety of clinical information and treatment should not be withheld based solely on an Xpert MTB/RIF result. The small numbers of studies and participants, particularly for Xpert Ultra, limits our confidence in the precision of these estimates.


Assuntos
Tipagem Molecular/métodos , Tuberculose dos Linfonodos/diagnóstico , Tuberculose Meníngea/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adolescente , Antibióticos Antituberculose/uso terapêutico , Viés , Criança , Fezes/microbiologia , Conteúdo Gastrointestinal/microbiologia , Humanos , Tipagem Molecular/normas , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/uso terapêutico , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose dos Linfonodos/tratamento farmacológico , Tuberculose dos Linfonodos/microbiologia , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Meníngea/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
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