Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.495
Filtrar
1.
Monaldi Arch Chest Dis ; 90(1)2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32231347

RESUMO

Drug-resistant tuberculosis (DR-TB) is a global challenge and a major contributor of death from anti-microbial resistance. With the main aim to determine factors contributing to treatment outcomes observed among DR-TB patients in the countries in Eastern Europe and Central Asia (EECA), a multi-method study was conducted in: Azerbaijan, Belarus, Romania, Tajikistan and Ukraine. Both quantitative and qualitative methodologies were used for data collection and analysis. The quantitative approaches included a desk review of documents related to the DR-TB responses and an analysis of clinical records of DR-TB patients in selected health facilities of the five countries. Qualitative methods included in-depth interviews with national TB programme (NTP) managers, other healthcare providers and non-governmental organizations (NGOs) workers, as well as interviews and Focus Group Discussions (FGDs) with DR-TB patients. The desk review of 38 reports identified as the main challenges to address DR-TB financial and/or management issues and adverse events of the medicines. The most common recommendations related to treatment outcome focussed on general programme management, treatment regimen composition, clinical management and social support for the patients. In all the five countries the NTPs still have a vertical structure. Some integration into the primary health care system (PHC) already exists but further involvement of PHC facilities is feasible and recommended. Interviews with stakeholders indicated that alcoholism and homelessness and a lack of appropriate response to these issues remain as major challenges for a sub-set of patients. Civil society groups, NGOs and communities are substantially engaged in providing different services to DR-TB patients, especially in Ukraine, Romania and Tajikistan. Data from clinical records of 212 patients revealed that independent risk factors for unfavourable treatment outcome (death, loss to follow-up, failure) were culture-positivity at two months of treatment, history of treatment with second-line drugs and homelessness. More powerful, less toxic and shorter oral treatment regimens as well as comprehensive patient support are needed to improve treatment outcome of patients with DR-TB.


Assuntos
Antituberculosos/administração & dosagem , Assistência à Saúde , Tuberculose Resistente a Múltiplos Medicamentos/terapia , Alcoolismo , Ásia/epidemiologia , Europa Oriental/epidemiologia , Pessoas em Situação de Rua , Humanos , Atenção Primária à Saúde , Fatores de Risco , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
2.
N Engl J Med ; 382(10): 893-902, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32130813

RESUMO

BACKGROUND: Patients with highly drug-resistant forms of tuberculosis have limited treatment options and historically have had poor outcomes. METHODS: In an open-label, single-group study in which follow-up is ongoing at three South African sites, we investigated treatment with three oral drugs - bedaquiline, pretomanid, and linezolid - that have bactericidal activity against tuberculosis and to which there is little preexisting resistance. We evaluated the safety and efficacy of the drug combination for 26 weeks in patients with extensively drug-resistant tuberculosis and patients with multidrug-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. The primary end point was the incidence of an unfavorable outcome, defined as treatment failure (bacteriologic or clinical) or relapse during follow-up, which continued until 6 months after the end of treatment. Patients were classified as having a favorable outcome at 6 months if they had resolution of clinical disease, a negative culture status, and had not already been classified as having had an unfavorable outcome. Other efficacy end points and safety were also evaluated. RESULTS: A total of 109 patients were enrolled in the study and were included in the evaluation of efficacy and safety end points. At 6 months after the end of treatment in the intention-to-treat analysis, 11 patients (10%) had an unfavorable outcome and 98 patients (90%; 95% confidence interval, 83 to 95) had a favorable outcome. The 11 unfavorable outcomes were 7 deaths (6 during treatment and 1 from an unknown cause during follow-up), 1 withdrawal of consent during treatment, 2 relapses during follow-up, and 1 loss to follow-up. The expected linezolid toxic effects of peripheral neuropathy (occurring in 81% of patients) and myelosuppression (48%), although common, were manageable, often leading to dose reductions or interruptions in treatment with linezolid. CONCLUSIONS: The combination of bedaquiline, pretomanid, and linezolid led to a favorable outcome at 6 months after the end of therapy in a high percentage of patients with highly drug-resistant forms of tuberculosis; some associated toxic effects were observed. (Funded by the TB Alliance and others; ClinicalTrials.gov number, NCT02333799.).


Assuntos
Antituberculosos/administração & dosagem , Diarilquinolinas/administração & dosagem , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Linezolida/administração & dosagem , Nitroimidazóis/administração & dosagem , Administração Oral , Adolescente , Adulto , Antituberculosos/efeitos adversos , Carga Bacteriana , Diarilquinolinas/efeitos adversos , Quimioterapia Combinada , Tuberculose Extensivamente Resistente a Medicamentos/mortalidade , Feminino , Humanos , Análise de Intenção de Tratamento , Linezolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Nitroimidazóis/efeitos adversos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto Jovem
5.
Artigo em Inglês | MEDLINE | ID: mdl-32049259

RESUMO

Tuberculosis (TB) is still a leading cause of morbidity and mortality among people living with HIV (PLHIV). The diagnosis of latent TB is required for the implementation of prophylactic therapy with isoniazid (PTI). However, low access to diagnosis of latent TB and non-adherence to PTI may hinder potential benefits of this essential intervention. In this study, we addressed the access and adherence to PTI in a cohort of PLHIV with positive tuberculin skin test (TST) in a reference HIV clinic in Sao Paulo, Brazil. We have also analyzed the occurrence of active TB over a median of 131 months after a positive TST among study participants. Our findings revealed that 88.3% of the 238 TST-positive patients had access to PTI, and 196 (93.3%) of those with access adhered to PTI. Active tuberculosis was diagnosed in three of the 196 TST-positive patients who adhered to PTI (1.5%; 95% confidence interval [CI] 0.3-4.4%), whereas seven cases were detected among 42 patients without access or who did not adhere to PTI (16.6%; 95% CI 7.0-31.3%). The apparent beneficial effect of PTI in our cohort is consistent with previous studies including PLHIV, and highlights the importance of reliably delivering each of the steps between screening for latent TB and provision of PTI.


Assuntos
Antituberculosos/administração & dosagem , Infecções por HIV/complicações , Isoniazida/administração & dosagem , Tuberculose/tratamento farmacológico , Adulto , Brasil , Estudos de Coortes , Feminino , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Socioeconômicos , Teste Tuberculínico , Tuberculose/complicações
6.
Am J Trop Med Hyg ; 102(3): 553-561, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31933460

RESUMO

Pulmonary tuberculosis (TB) is a major global public health problem. Thailand is listed as one of the countries with a high burden of pulmonary TB. Various factors are known to contribute to unsuccessful pulmonary TB treatment. However, studies in Thailand remain limited, especially in rural settings. This study aimed to identify the prevalence and associated factors of unsuccessful pulmonary TB treatment in community hospitals. A cross-sectional study was conducted from June-July 2019. We enrolled all patients receiving treatments in four community hospitals in central Thailand. The collected data included baseline characteristics, comorbid illnesses, a history of directly observed treatment-short course (DOTS), sputum acid-fast bacilli smear results, and chest radiography and treatment outcomes. Univariate and multivariate analyses were used to identify factors associated with unsuccessful pulmonary TB treatment. A total of 786 patients were enrolled in the study. Prevalence of unsuccessful treatment was 18.7%. Associated factors of unsuccessful pulmonary TB treatment were previously treated TB (adjusted odds ratio [AOR]: 2.1, 95% CI: 1.2-3.7), existence of comorbid illnesses (AOR: 2.8, 95% CI: 1.5-5.0), DOTS not performed (AOR: 2.5, 95% CI: 1.4-4.5), chest radiography showing multiple lung lesions at first diagnosis (AOR: 3.0, 95% CI: 1.7-5.2), no chest radiography improvement in the first follow-up (AOR: 17.7, 95% CI: 8.2-38.0), and unknown status of chest radiography in the first follow-up (AOR: 48.1, 95% CI: 22.3-103.5). Health promotion and primary care should be implemented in the communities to achieve ultimate successful treatment.


Assuntos
Antituberculosos/uso terapêutico , Hospitais Comunitários/normas , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Antituberculosos/administração & dosagem , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural , Tailândia , Resultado do Tratamento , Adulto Jovem
7.
Medicine (Baltimore) ; 99(2): e18367, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914015

RESUMO

Little is known about the decay kinetics of interferon (IFN)-γ response and its influencing factors in tuberculous pleurisy. We enrolled thirty-two patients with tuberculous pleurisy prospectively and followed up at month 0, 6, and 9, at which time peripheral venous blood was drawn for interferon gamma release assay (IGRA) by means of QuantiFERON-TB Gold In-Tube (QFT-GIT). Demographic and clinical data were captured. To identify significant predictive factors influencing the IFN-γ response, multiple linear regression analyses were performed. Percentage of CD4+, CD8+, Vγ2Vδ2 T cells and Treg cells were measured by flow cytometry. The percentage of QFT-GIT-positive patients at baseline, month 6 and month 9 were 96.9% (30/32), 90.6% (29/32) and 84.4% (27/32), respectively. Quantitative IFN-γ response at baseline were significantly correlated with symptom duration (P = .003, R = 0.261) and age (P = .041, R = 0.132). Besides, the decreases of the IFN-γ response at month 6 and month 9 were positively correlated with the IFN-γ level at baseline. The dynamic tendency of the percentages of Treg cells was similar to the IFN-γ responses at each time-point. Quantitative IFN-γ response could be influenced by host immune status, instead of disease burden and anti-tuberculosis treatment. IGRA is probably not a useful biomarker of treatment efficacy in tuberculous pleurisy.


Assuntos
Testes de Liberação de Interferon-gama/métodos , Interferon gama/imunologia , Tuberculose Pleural/sangue , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Feminino , Citometria de Fluxo/métodos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Linfócitos T/imunologia , Tuberculose Pleural/diagnóstico , Tuberculose Pleural/tratamento farmacológico , Tuberculose Pleural/metabolismo
8.
Am J Med Sci ; 359(1): 42-50, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31902440

RESUMO

We report a case of liver transplant patient who presented with lung masses, found to be Mycobacterium spindle cell pseudotumors. The masses demonstrated hypermetabolic activities on positron emission tomography. Core biopsy revealed sheets of spindle histiocytic cells with abundant acid-fast bacilli identified as Mycobacterium avium-intracellulare complex. This finding is a rare presentation of Mycobacterium infection, mainly nontuberculous Mycobaterium. It is characterized by a benign, spindle cell mass-forming reaction. Most of the reported cases had acquired immune deficiency syndrome or organ transplant. Histopathology illustrating the proliferation of spindle cell shaped histiocytes containing numerous acid-fast bacilli is the gold standard for diagnosis. The standard treatment has not been well established; previously reported cases followed the standard treatment for Mycobacterium based on organ involvement. Our case is the first case to our knowledge that reports pulmonary Mycobacterium spindle cell pseudotumors in a liver transplant recipient.


Assuntos
Transplante de Fígado , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/patologia , Granuloma de Células Plasmáticas Pulmonar/microbiologia , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , Etambutol/administração & dosagem , Etambutol/uso terapêutico , Feminino , Humanos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Granuloma de Células Plasmáticas Pulmonar/diagnóstico , Granuloma de Células Plasmáticas Pulmonar/tratamento farmacológico
9.
BMC Infect Dis ; 20(1): 81, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996142

RESUMO

BACKGROUND: Macrophages play a key role in the infection process, and alternatively activated macrophages (M2 polarization) play important roles in persistent infection via the immune escape of pathogens. This suggests that immune escape of pathogens from host immunity is an important factor to consider in treatment failure and multidrug-resistant tuberculosis (MDR-TB)/extensively drug-resistant tuberculosis (XDR-TB). In this study, we investigated the association between macrophage polarization and MDR-TB/XDR-TB and the association between macrophage polarization and the anti-TB drugs used. METHODS: iNOS and arginase-1, a surface marker of polarized macrophages, were quantified by immunohistochemical staining and imaging analysis of lung tissues of patients who underwent surgical treatment for pulmonary TB. Drug susceptibility/resistance and the type and timing of anti-tuberculosis drugs used were investigated. RESULTS: The M2-like polarization rate and the ratio of the M2-like polarization rate to the M1-like polarization rate were significantly higher in the MDR-TB/XDR-TB group than in the DS-TB group. The association between a high M2-like polarization rate and MDR-TB/XDR-TB was more pronounced in patients with a low M1-like polarization rate. Younger age and a higher M2-like polarization rate were independent associated factors for MDR-TB/XDR-TB. The M2-like polarization rate was significantly higher in patients who received anti-TB drugs containing pyrazinamide continuously for 4 or 6 weeks than in those who received anti-TB drugs not containing pyrazinamide. CONCLUSIONS: The M2-like polarization of macrophages is associated with MDR-TB/XDR-TB and anti-TB drug regimens including pyrazinamide or a combination of pyrazinamide, prothionamide and cycloserine.


Assuntos
Antituberculosos/administração & dosagem , Tuberculose Extensivamente Resistente a Medicamentos/imunologia , Ativação de Macrófagos/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Resistente a Múltiplos Medicamentos/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Ciclosserina/administração & dosagem , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Feminino , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Protionamida/administração & dosagem , Pirazinamida/administração & dosagem , Falha de Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
10.
J Agric Food Chem ; 68(5): 1257-1265, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31927919

RESUMO

Bedaquiline (TMC-207) is a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB). Moreover, there is a present and growing concern for natural-product-mediated drug interaction, as these are inadvertently taken by patients as a dietary supplement, food additive, and medicine. In the present study, we investigated the impact of 20 plant-based natural products, typically phenolics, on in vivo oral bedaquiline pharmacokinetics, as previous studies are lacking. Three natural phenolics were identified that can significantly enhance the oral exposure of bedaquiline upon coadministration. We further investigated the possible role of all of the phytochemicals on in vitro P-glycoprotein (P-gp) induction and inhibition and CYP3A4 inhibition in a single platform as bedaquiline is the substrate for both P-gp and CYP3A4. In conclusion, curcumin, CC-I (3',5-dihydroxyflavone-7-O-ß-d-galacturonide-4'-O-ß-d-glucopyranoside), and 6-gingerol should not be coadministered with bedaquiline to avoid untoward drug interactions and, subsequently, its dose-dependent adverse effects.


Assuntos
Antituberculosos/farmacocinética , Diarilquinolinas/farmacocinética , Suplementos Nutricionais/efeitos adversos , Interações Alimento-Droga , Fenóis/efeitos adversos , Extratos Vegetais/efeitos adversos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antituberculosos/administração & dosagem , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Diarilquinolinas/administração & dosagem , Suplementos Nutricionais/análise , Feminino , Humanos , Fenóis/administração & dosagem , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Resistente a Múltiplos Medicamentos/metabolismo
11.
Expert Opin Drug Saf ; 19(1): 23-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31809218

RESUMO

Introduction: Antiretroviral and anti-tuberculosis (TB) drugs are often co-administered in people living with HIV (PLWH). Early initiation of antiretroviral therapy (ART) during TB treatment improves survival in patients with advanced HIV disease. However, safety concerns related to clinically significant changes in drug exposure resulting from drug-drug interactions, development of overlapping toxicities and specific challenges related to co-administration during pregnancy represent barriers to successful combined treatment for HIV and TB.Areas covered: Pharmacokinetic interactions of different classes of ART when combined with anti-TB drugs used for sensitive-, drug-resistant (DR) and latent TB are discussed. Overlapping drug toxicities, implications of immune reconstitution inflammatory syndrome (IRIS), safety in pregnancy and research gaps are also explored.Expert opinion: New antiretroviral and anti-tuberculosis drugs have been recently introduced and international guidelines updated. A number of effective molecules and clinical data are now available to build treatment regimens for PLWH with latent or active TB. Adopting a systematic approach that also takes into account the need for individualized variations based on the available evidence is the key to successfully integrate ART and TB treatment and improve treatment outcomes.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Antituberculosos/administração & dosagem , Animais , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Antituberculosos/efeitos adversos , Interações Medicamentosas , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose Latente/tratamento farmacológico , Tuberculose/tratamento farmacológico
12.
PLoS One ; 14(12): e0227101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31877199

RESUMO

BACKGROUND: The Ministry of Health in Brazil included ethambutol in the intensive phase of sensible tuberculosis (TB) treatment in March 2010, due to the increasing drug resistance, and implemented the fixed dose combination in the TB treatment guidelines. METHODS: A retrospective cohort study was performed to determine the impact of change from three to four drugs schemes on the TB cure and frequency of adverse drug reactions (ADRs) in TB patients. To answer this question, we used data from 730 randomly selected patients who received anti-TB treatment between January 2007 and December 2014 in a reference center from Salvador, Brazil. FINDINGS: TB patients who received the RHEZ regimen (n = 365) developed ADRs more frequently than those treated with the RHZ (n = 365) (86 [23.6%] vs. 55 [15.1%]; p = 0.01). This difference in ADR incidence was even higher in patients above 30 years-old (64 [74.4%] vs. 36 [65.5%]; p = 0.01). The overall number of ADR episodes was greater in patients from the RHEZ group than in the group that received RHZ (170 [61.4%] vs. 107 [38.6%]; p = 0.03). Multivariable logistic regression analysis adjusted for age, alcohol use and diabetes demonstrated that patients receiving the RHEZ regimen had increased odds of developing ADRs than those undertaking the RHZ scheme (odds ratio [OR]: 1.61, 95% confidence interval [CI]: 1.10-2.35; p = 0.015). The overall cure rate was similar between the distinct treatment groups. CONCLUSION: The patients treated with the four-drug regimen exhibited increased risk of ADRs compared to those who received the three-drug regimen, and especially in patients older than 30 years of age.


Assuntos
Antituberculosos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Tuberculose/tratamento farmacológico , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Brasil/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
Rev Soc Bras Med Trop ; 53: e20190207, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31859946

RESUMO

INTRODUCTION: Adverse drug reactions can develop when using anti-tuberculosis medication, and the effects of the drugs can also significantly hinder the treatment of patients. METHODS: A cross-sectional survey was conducted in 73 patients using two standardized questionnaires and the World Health Organization Quality of Life-Bref. RESULTS: All patients reported the presence of adverse drug reactions, 71.6% of which are minor and 28.3% both major and minor. The global quality of life analysis showed that patients with tuberculosis have a good average (67.3%). CONCLUSIONS: There is an association between quality of life and adverse drug reaction, educational level, and vulnerability.


Assuntos
Antituberculosos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Qualidade de Vida/psicologia , Tuberculose/tratamento farmacológico , Idoso , Antituberculosos/administração & dosagem , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Inquéritos e Questionários , Centros de Atenção Terciária , Tuberculose/psicologia
14.
Pan Afr Med J ; 34: 23, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31762892

RESUMO

Central nervous system tuberculosis is a major cause of morbidity and mortality in developing countries. Intracranial tuberculoma is rare and is one of the most severe cases of tuberculosis. We present two cases. The first one is about a girl of 7 years, followed for 5 months for lymph nodes tuberculosis on anti-TB treatment that presents generalized tonic-clonic seizures associated with progressive intracranial hypertension syndrome. Brain MRI has objectified necrotic nodules in left hemisphere. The surgical approach of the lesions was direct with complete excision. The diagnosis of tuberculoma was confirmed by anatomopathological examination. The second case is about a 6-year-old girl with no particular medical history, which presents for three months progressive and treatment-resistant cervico-occipital headaches associated with walking difficulties. The MRI objectified left cerebellar tumor process interpreted preoperatively as medulloblastoma. The patient was operated on intraoperative, appearance was that of a nodular lesion. Anatomopathological examination confirmed the diagnosis. The intracranial tuberculoma is an unusual variety of the central nervous system tuberculosis and remains a topical issue in Morocco. The prognosis depends on prompt diagnosis, quality of surgical resection and anti-TB treatment. The diagnostic confirmation is histological and should therefore be evoked infront of any intracranial process mimicking a brain tumor.


Assuntos
Antituberculosos/administração & dosagem , Neoplasias Encefálicas/diagnóstico , Tuberculoma Intracraniano/diagnóstico , Criança , Terapia Combinada , Diagnóstico Diferencial , Feminino , Cefaleia/etiologia , Humanos , Imagem por Ressonância Magnética , Meduloblastoma/diagnóstico , Convulsões/etiologia , Tuberculoma Intracraniano/terapia
15.
Crit Rev Ther Drug Carrier Syst ; 36(3): 239-276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679248

RESUMO

Pulmonary tuberculosis (TB) is a leading cause of death worldwide and is caused by the pathogen Mycobacterium tuberculosis (MTb). As treatment for TB, dry powders for inhalation (DPIs) are considered stable compared with nebulizers and metered dose inhalers and are suitable for high-dose formulations. Although extensive research has been done over the last two to three decades on nanocarrier-based DPIs for targeting MTb infection, none of the anti-TB DPI formulations have reached the market. Challenges in the proper assessment of nanocarrier-based DPIs due to the complexity of lungs is one of the reasons. In this review, the details of in vitro evaluation parameters of nanocarriers and nanocarrier-based DPIs along with their need and basic principles are discussed. Further, the thorough in vitro, ex vivo, and in vivo pharmacological evaluations, together with their procedures wherever required, are covered. The different evaluation parameters during process development, release specifications, and stability studies suggested by U.S. Food and Drug Administration Center for Drug Evaluation and Research to apply for new drug applications and abbreviated new drug applications of DPIs are also discussed. Lastly, the evaluation parameters for DPIs provided in European, United States, British, and Indian pharmacopeias are summarized.


Assuntos
Antituberculosos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Nanopartículas/administração & dosagem , Tuberculose Pulmonar/tratamento farmacológico , Administração por Inalação , Animais , Antituberculosos/química , Portadores de Fármacos/química , Inaladores de Pó Seco , Humanos , Nanopartículas/química , Pós/administração & dosagem , Pós/química , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Pan Afr Med J ; 33: 326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692828

RESUMO

Introduction: Human immunodeficiency virus (HIV) and tuberculosis (TB) are the leading causes of death from infectious disease worldwide. The prevalence of HIV among children with TB in moderate to high prevalence countries ranges between 10% and 60%. This study aimed to determine the prevalence of HIV infection among children treated for TB in Directly Observed Treatment Short-Course (DOTS) clinics in Lubumbashi and to identify risk of death during this co-infection. Methods: This is a cross-sectional study of children under-15, treated for tuberculosis from January 1, 2013 to December 31, 2015. Clinical, paraclinical and outcome data were collected in 22 DOTS of Lubumbashi. A statistical comparison was made between dead and survived HIV-infected TB children. We performed the multivariate analyzes and the significance level set at p-value <0.05. Results: A total of 840 children with TB were included. The prevalence of HIV infection was 20.95% (95% CI: 18.34-23.83%). The mortality rate was higher for HIV-infected children (47.73%) compared to HIV-uninfected children (17.02%) (p<0.00001). Age <5 years (aOR=6.50 [1.96-21.50]), a poor nutritional status (aOR=23.55 [8.20-67.64]), and a negative acid-fast bacilli testing (aOR=4.51 [1.08-18.70]) were associated with death during anti-TB treatment. Conclusion: TB and HIV co-infection is a reality in pediatric settings in Lubumbashi. High mortality highlights the importance of early management.


Assuntos
Antituberculosos/administração & dosagem , Infecções por HIV/epidemiologia , Estado Nutricional , Tuberculose/epidemiologia , Criança , Pré-Escolar , Coinfecção , Estudos Transversais , República Democrática do Congo/epidemiologia , Terapia Diretamente Observada , Feminino , Infecções por HIV/mortalidade , Humanos , Masculino , Prevalência , Fatores de Risco , Tuberculose/tratamento farmacológico , Tuberculose/mortalidade
18.
Dis Colon Rectum ; 62(11): 1390-1400, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31596764

RESUMO

BACKGROUND: Few data are published on perianal tuberculosis. OBJECTIVE: This study aimed to determine the best method to diagnose tuberculosis in patients with fistula-in-ano and to conduct a systematic review to determine the incidence and characteristics of tuberculosis fistula-in-ano. DATA SOURCES: The prospective study data and existing literature were derived from PubMed, Google scholar, and Scopus STUDY SELECTION:: Prospective analysis of patients with tuberculous fistula-in-ano treated between 2014 and 2018 was conducted, and a systematic review of studies describing ≥3 patients with tuberculosis fistula-in-ano was completed. INTERVENTION: Testing of tuberculosis was performed by histopathology or polymerase chain reaction of tissue or pus from the fistula tract. MAIN OUTCOME MEASURES: The primary outcomes measured were the detection rate of various tests to detect tuberculosis in fistula-in-ano and the prevalence rate of tuberculosis in simple versus complex fistulas. RESULTS: In 637 samples (410 patients) tested, tuberculosis was detected in 49 samples (43 patients). Additional samples (n = 106) sent in patients with a high index of suspicion tested positive in 14 more patients. Thus, overall, 63 samples tested positive in 57 patients (total: 743 samples in 410 patients were tested). Tuberculosis was detected in 2 of 181 patients (1.1%) in tissue (histopathology), in 28 of 341 patients (8.2%) in tissue (polymerase chain reaction), and in 19 of 115 patients (16.5%) in pus (polymerase chain reaction) samples. To detect tuberculosis, tissue (polymerase chain reaction) was significantly better than tissue (histopathology) (28/341 vs 2/181, p < 0.00001) and pus (polymerase chain reaction) was significantly better than tissue (polymerase chain reaction) (19/115 vs 28/341, p < 0.0009). Tuberculosis was significantly more common in complex fistulas than in simple fistulas (20.3% vs 7.2%, p = 0.0002). The systematic review (n = 199) highlighted that tubercular fistulas are more common in recurrent and complex fistulas and in tuberculosis endemic regions. LIMITATIONS: The true sensitivity and specificity of each testing modality could not be determined because not all patients with tuberculosis fistula-in-ano were tested by every diagnostic modality studied. CONCLUSIONS: The tuberculosis detection rate of polymerase chain reaction was significantly higher than histopathology. Among polymerase chain reaction, pus had higher detection rate than tissue. Tuberculosis was associated with more complex and recurrent fistulas.


Assuntos
Fissura Anal , Mycobacterium tuberculosis , Fístula Retal , Estreptomicina/administração & dosagem , Tuberculose Gastrointestinal , Assistência ao Convalescente/métodos , Antituberculosos/administração & dosagem , Técnicas Bacteriológicas/métodos , Técnicas Bacteriológicas/estatística & dados numéricos , Feminino , Fissura Anal/diagnóstico , Fissura Anal/epidemiologia , Fissura Anal/microbiologia , Fissura Anal/terapia , Humanos , Incidência , Índia/epidemiologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/estatística & dados numéricos , Fístula Retal/diagnóstico , Fístula Retal/epidemiologia , Fístula Retal/microbiologia , Fístula Retal/terapia , Recidiva , Reprodutibilidade dos Testes , Procedimentos Cirúrgicos Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Tuberculose Gastrointestinal/diagnóstico , Tuberculose Gastrointestinal/epidemiologia , Tuberculose Gastrointestinal/fisiopatologia , Tuberculose Gastrointestinal/terapia
19.
N Z Med J ; 132(1503): 46-52, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31581181

RESUMO

This report details the investigation of oncology and haematology patients, as well as cancer centre staff, friends and family who were exposed to an oncology patient with reactivated pulmonary tuberculosis (TB) in a New Zealand cancer centre. A total of 46 patients, seven staff members and 14 family and friends were identified as being exposed to the index case of TB (Mr K). These people were screened for TB infection by the use of a symptom questionnaire, Qiagen QuantiFeron (QFT)® Gold Plus test and, if potentially immunocompromised, a chest x-ray (CXR). There were no confirmed secondary cases of TB in any of the groups screened for infection, but surveillance for signs and symptoms of TB disease in those with significant risk is ongoing. In this article we discuss the public health response to TB in a cancer centre and potential preventative strategies for the future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Antituberculosos/administração & dosagem , Busca de Comunicante/métodos , Controle de Infecções , Mycobacterium tuberculosis/isolamento & purificação , Neoplasias Gástricas/complicações , Tuberculose Pulmonar , Idoso , Broncoscopia/métodos , Progressão da Doença , Evolução Fatal , Gastrectomia/métodos , Humanos , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Masculino , Estadiamento de Neoplasias , Nova Zelândia/epidemiologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/fisiopatologia , Neoplasias Gástricas/terapia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/terapia , Tuberculose Pulmonar/transmissão
20.
PLoS Med ; 16(10): e1002891, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31584944

RESUMO

BACKGROUND: Excellent adherence to tuberculosis (TB) treatment is critical to cure TB and avoid the emergence of resistance. Wirelessly observed therapy (WOT) is a novel patient self-management system consisting of an edible ingestion sensor (IS), external wearable patch, and paired mobile device that can detect and digitally record medication ingestions. Our study determined the accuracy of ingestion detection in clinical and home settings using WOT and subsequently compared, in a randomized control trial (RCT), confirmed daily adherence to medication in persons using WOT or directly observed therapy (DOT) during TB treatment. METHODS AND FINDINGS: We evaluated WOT in persons with active Mycobacterium tuberculosis complex disease using IS-enabled combination isoniazid 150 mg/rifampin 300 mg (IS-Rifamate). Seventy-seven participants with drug-susceptible TB in the continuation phase of treatment, prescribed daily isoniazid 300 mg and rifampin 600 mg, used IS-Rifamate. The primary endpoints of the trial were determination of the positive detection accuracy (PDA) of WOT, defined as the percentage of ingestions detected by WOT administered under direct observation, and subsequently the proportion of prescribed doses confirmed by WOT compared to DOT. Initially participants received DOT and WOT simultaneously for 2-3 weeks to allow calculation of WOT PDA, and the 95% confidence interval (CI) was estimated using the bootstrap method with 10,000 samples. Sixty-one participants subsequently participated in an RCT to compare the proportion of prescribed doses confirmed by WOT and DOT. Participants were randomized 2:1 to receive WOT or maximal in-person DOT. In the WOT arm, if ingestions were not remotely confirmed, the participant was contacted within 24 hours by text or cell phone to provide support. The number of doses confirmed was collected, and nonparametric methods were used for group and individual comparisons to estimate the proportions of confirmed doses in each randomized arm with 95% CIs. Sensitivity analyses, not prespecified in the trial registration, were also performed, removing all nonworking (weekend and public holiday) and held-dose days. Participants, recruited from San Diego (SD) and Orange County (OC) Divisions of TB Control and Refugee Health, were 43.1 (range 18-80) years old, 57% male, 42% Asian, and 39% white with 49% Hispanic ethnicity. The PDA of WOT was 99.3% (CI 98.1; 100). Intent-to-treat (ITT) analysis within the RCT showed WOT confirmed 93% versus 63% DOT (p < 0.001) of daily doses prescribed. Secondary analysis removing all nonworking days (weekends and public holidays) and held doses from each arm showed WOT confirmed 95.6% versus 92.7% (p = 0.31); WOT was non-inferior to DOT (difference 2.8% CI [-1.8%, 9.1%]). One hundred percent of participants preferred using WOT. WOT associated adverse events were <10%, consisting of minor skin rash and pruritus associated with the patch. WOT provided longitudinal digital reporting in near real time, supporting patient self-management and allowing rapid remote identification of those who needed more support to maintain adherence. This study was conducted during the continuation phase of TB treatment, limiting its generalizability to the entire TB treatment course. CONCLUSIONS: In terms of accuracy, WOT was equivalent to DOT. WOT was superior to DOT in supporting confirmed daily adherence to TB medications during the continuation phase of TB treatment and was overwhelmingly preferred by participants. WOT should be tested in high-burden TB settings, where it may substantially support low- and middle-income country (LMIC) TB programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01960257.


Assuntos
Antituberculosos/administração & dosagem , Terapia Diretamente Observada/métodos , Adesão à Medicação , Tuberculose/tratamento farmacológico , Tecnologia sem Fio , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Humanos , Isoniazida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Estudos Prospectivos , Rifampina/administração & dosagem , Autoadministração , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA