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1.
Yonsei Med J ; 64(6): 366-374, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37226563

RESUMO

PURPOSE: The strategy of latent tuberculosis infection (LTBI) treatment in household tuberculosis (TB) contacts has been expanding in South Korea. However, there is little evidence of the cost-effectiveness of LTBI treatment in patients over 35 years of age. This study aimed to evaluate the cost-effectiveness of LTBI treatment among household TB contacts in different age groups in South Korea. MATERIALS AND METHODS: An age-structured model of TB was developed based on the reports from the Korea Disease Control and Prevention Agency and the National Health Insurance Service. Quality-adjusted life-years (QALY) and the averted number of TB-related deaths were estimated along with discounted costs for a measure of incremental cost-effectiveness ratios. RESULTS: The number of cumulative active TB cases would decrease by 1564 and 7450 under the scenario of LTBI treatment for those aged <35 years and <70 years, respectively, relative to the no-treatment scenario. The treatment strategies for patients aged 0 to <35 years, <55 years, <65 years, and <70 years would add 397, 1482, 3782, and 8491 QALYs at a cost of $660, $5930, $4560, and $2530, respectively, per QALY. For the averted TB-related deaths, LTBI treatment targeting those aged 0 to <35 years, <55 years, <65 years, and <70 years would avert 7, 89, 155, and 186 deaths at a cost of $35900, $99200, $111100, and $115700 per deaths, respectively, in 20 years. CONCLUSION: The age-specific expansion policy of LTBI treatment not only for those under 35 years of age but also for those under 65 years of age among household contacts was cost-effective in terms of QALYs and averted TB deaths.


Assuntos
Tuberculose Latente , Humanos , Adulto , Idoso , Tuberculose Latente/tratamento farmacológico , Análise Custo-Benefício , República da Coreia , Programas Nacionais de Saúde
2.
Int J Infect Dis ; 134: 63-70, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37211272

RESUMO

OBJECTIVES: To determine whether weekly oral supplementation with 10,000 IU vitamin D3 for 3 years reduces the risk of sensitization to M. tuberculosis in South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline. METHODS: We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect. RESULTS: 829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D3 vs. placebo, respectively. Mean end-study 25(OH)D concentrations in participants randomized to vitamin D vs. placebo were 104.3 vs 64.7 nmol/l, respectively (95% confidence interval for difference, 37.6 to 41.9 nmol/l). A total of 76/667 (11.4%) participants allocated to vitamin D vs. 89/687 (13.0%) participants allocated to placebo tested QFT-Plus positive at 3-year follow-up (adjusted odds ratio 0.86, 95% confidence interval 0.62-1.19, P = 0.35). CONCLUSION: Weekly oral supplementation with 10,000 IU vitamin D3 for 3 years elevated serum 25(OH)D concentrations among QFT-Plus-negative Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion.


Assuntos
Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Criança , Humanos , África do Sul/epidemiologia , Suplementos Nutricionais , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controle , Vitamina D , Colecalciferol/uso terapêutico , Vitaminas/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Método Duplo-Cego
3.
J Public Health Manag Pract ; 29(3): 345-352, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36867508

RESUMO

OBJECTIVE: More than 80% of active tuberculosis in the United States is due to reactivation of latent tuberculosis infection (LTBI), which can be prevented via screening and treatment. Treatment initiation and completion rates are low for patients with LTBI in the United States, and the barriers to successful treatment are poorly understood. DESIGN: We conducted semistructured qualitative interviews with 38 patients who were prescribed LTBI treatment (9 months isoniazid, 6 months rifampin, or 3 months rifamycin-isoniazid short-course combinations). We used purposeful sampling employing a maximum variation approach to obtain diverse perspectives of patients who did not initiate treatment, who did not complete treatment, and who completed treatment (n = 14, n = 16, and n = 8, respectively). Patients were asked about LTBI knowledge, experience regarding treatment, interactions with providers, and barriers they faced. Using a team coding model (2 coders/analysts), we developed deductively derived (a priori) codes based on our central research questions and inductively derived codes that emerged directly from the data. Analysis of our coding categories and relationships generated a hierarchy of key themes and subthemes. SETTING: Kaiser Permanente Southern California. PARTICIPANTS: Individuals 18 years or older who received a diagnosis of LTBI and prescribed treatment. MAIN OUTCOME MEASURES: LTBI knowledge, attitudes toward LTBI, attitudes toward LTBI treatment, attitudes toward providers, and explanation of barriers. RESULTS: Most patients reported having limited knowledge of LTBI. In addition to the duration of treatment, barriers to initiation and completion included perceived lack of support, uncomfortable side effects, and pervasive minimization of the positive impact of treatment on their health. Many patients felt there was little incentive to overcome barriers. CONCLUSIONS: Overall, patient experience with LTBI treatment initiation and completion could be improved with patient-centered treatment and more frequent follow-ups.


Assuntos
Prestação Integrada de Cuidados de Saúde , Tuberculose Latente , Humanos , Estados Unidos , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/diagnóstico , California , Medidas de Resultados Relatados pelo Paciente , Antituberculosos/uso terapêutico
5.
J Dermatol ; 49(9): 887-894, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35619545

RESUMO

Elderly patients constitute a significant proportion of patients with psoriasis. Nonetheless, treatment for older patients is more challenging than that for younger ones. Biologic agents are preferable to other systemic drugs for elderly patients with moderate-to-severe psoriasis owing to their high efficacy and favorable tolerability. However, there are limited data on tuberculosis infection risk in elderly patients with psoriasis receiving biologic therapy. This study aimed to evaluate the risk of active tuberculosis and latent tuberculosis infection, assess the serial interferon-gamma release assay results, and evaluate treatment compliance and adverse effects of latent tuberculosis infection treatment in elderly patients with psoriasis on biologic therapy. In this single-center retrospective study, medical charts of elderly patients (age ≥ 65 years) with psoriasis who were treated with a biologic agent (guselkumab, adalimumab, secukinumab, or ustekinumab) between January 2015 and December 2020 were reviewed. We analyzed the results of chest X-rays and those of whole-blood interferon-gamma release assays performed for latent tuberculosis infection screening at baseline (IGRA0) and subsequently at follow-up after initiating biologic therapy (IGRA1). In total, 90 patients underwent IGRA0; 46 (51.11%) of them had latent tuberculosis infection before starting biologic therapy. Overall, four and two patients experienced seroconversion and active tuberculosis during biologic therapy, respectively. The interferon-gamma release assay reversion rate was 29.1%, and the interferon-gamma level significantly decreased in all patients after latent tuberculosis infection treatment (p = 0.004). Latent tuberculosis infection treatment was well tolerated in elderly patients (completion rate, 100%). The risk of latent tuberculosis infection in elderly patients with psoriasis on biologic therapy was comparable to that previously reported for all age groups. However, the active tuberculosis rate was relatively higher.


Assuntos
Tuberculose Latente , Psoríase , Tuberculose , Idoso , Terapia Biológica , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Teste Tuberculínico , Tuberculose/diagnóstico , Tuberculose/epidemiologia
6.
Drug Discov Today ; 27(1): 326-336, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34537334

RESUMO

Tuberculosis (TB), an airborne infectious disease mainly caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of human morbidity and mortality worldwide. Given the alarming rise of resistance to anti-TB drugs and latent TB infection (LTBI), new targets and novel bioactive compounds are urgently needed for the treatment of this disease. We provide an overview of the recent advances in anti-TB drug discovery, emphasizing several newly validated targets for which an inhibitor has been reported in the past five years. Our review presents several attractive directions that have potential for the development of next-generation therapies.


Assuntos
Antituberculosos/farmacologia , Desenho de Fármacos/métodos , Desenvolvimento de Medicamentos/tendências , Mycobacterium tuberculosis , Tuberculose , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Tuberculose Latente/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
8.
Rev. chil. enferm. respir ; 36(3): 215-222, set. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1138555

RESUMO

INTRODUCCIÓN: La prevención de la tuberculosis activa en los grupos de riesgo es clave para el control y eliminación de la tuberculosis. El tratamiento de la infección tuberculosa latente (TITL) con rifapentina e isoniazida en dosis semanales por 12 semanas es más corto que con otros esquemas, tiene menor hepatotoxicidad, mejor adherencia y es costo-efectivo. El OBJETIVO del estudio es evaluar la factibilidad de implementar este esquema a nivel programático en Chile. MÉTODOS: Se hizo una intervención piloto en territorios seleccionados entre mayo de 2018 y marzo de 2019. En esos territorios se reemplazó el esquema normado de TITL con isoniazida 6 meses por el esquema rifapentina-isoniazida 12 semanas. Además, se amplió la población objetivo, incluyendo a contactos mayores de 14 años. El tratamiento consistió en la administración conjunta de isoniazida y rifapentina por vía oral con frecuencia semanal, por 12 semanas, de forma supervisada por personal de salud. RESULTADOS: Ingresaron 238 pacientes al piloto, de los cuales 53% fueron mujeres y 54,2% fueron mayores de 14 años. Del total de pacientes, 203 (85,3%) completaron el tratamiento, 22 (9,2%) lo abandonaron, 8 (3,4%) presentaron reacciones adversas y 5 tuvieron otros motivos de egreso. CONCLUSIÓN: Tanto el TITL con rifapentinaisoniazida por 3 meses en dosis semanales supervisadas, como la incorporación de contactos adultos a TITL, son factibles de implementar a nivel programático en Chile.


INTRODUCTION: Prevention of active tuberculosis in risk groups is crucial in tuberculosis control and elimination. Treatment of latent tuberculosis (TITL) with rifapentine and isoniazid in weekly doses for 12 weeks is shorter than other pharmacological treatments, with less liver toxicity, better patient compliance and it is cost-effective. The OBJECTIVE of this study is to evaluate the feasibility to implement this treatment at a programmatic level in Chile. METHODS: A pilot intervention was conducted in selected territories between May 2018 and March 2019. Within these territories, the regulated treatment with isoniazid 6 months was replaced by the 12 weeks treatment with weekly rifapentine-isoniazide. Additionally, the target population was expanded to include contacts over 14 years old, currently not included in the national guidelines. Treatment consisted in oral administration of rifapentine and isoniazide together once a week for 12 weeks, under supervision of trained health workers. RESULTS: From 238 patients entered to the protocol, 53% of them were women and 54.2% were older than 14 years-old. Out of the total number of patients, 203 (85.3%) completed treatment, 22 (9.2%) abandoned, 8 (3.4%) had adverse drug reactions, and 5 ended treatment for different causes. CONCLUSION: Both TITL with rifapentine-isoniazide in 12 supervised weekly doses, and the inclusion of adult contacts in TITL, are feasible to implement at a programmatic level in Chile.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Adulto Jovem , Rifampina/análogos & derivados , Tuberculose Latente/tratamento farmacológico , Isoniazida/uso terapêutico , Antituberculosos/uso terapêutico , Rifampina/uso terapêutico , Fatores de Tempo , Esquema de Medicação , Chile , Projetos Piloto , Administração Oral , Cooperação do Paciente , Terapia Diretamente Observada , Quimioterapia Combinada , Cooperação e Adesão ao Tratamento , Programas Nacionais de Saúde
9.
BMC Infect Dis ; 20(1): 294, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32664847

RESUMO

BACKGROUND: Tuberculosis (TB) is the most common opportunistic infection and the leading cause of death in people living with HIV (PLHIV). HIV-infected children are at a higher risk of TB infection and disease compared to those without HIV. Isoniazid preventive therapy (IPT) is an effective intervention in preventing progression of latent TB infection to active TB. The World Health Organization (WHO) currently recommends that all children aged > 12 months and adults living with HIV in whom active TB has been excluded should receive a 6-months course of IPT as part of a comprehensive package of HIV care. Despite this recommendation, the uptake of IPT among PLHIV has been suboptimal globally. This study sought to determine the factors affecting IPT uptake and completion among HIV-infected children in a large HIV care centre in Nairobi, Kenya. METHOD: This was a cross-sectional mixed methods study comprising of quantitative and qualitative study designs. Medical records of 225 HIV-infected children aged 1 to < 10 years, in care in the Kenyatta National Hospital Comprehensive Care Centre (KNH CCC) were retrospectively reviewed, and 8 purposively selected healthcare providers and 18 consecutively selected caregivers of children were interviewed. RESULTS: IPT uptake among CLHIV in care in the KNH CCC was 68% (152/225) while the treatment completion rate was 82% (94/115). IPT-related health education and counselling were the main facilitators of IPT uptake and completion, while fear of adverse drug reaction, pill burden and lack of an integrated monitoring and evaluation system for IPT were the major barriers. CONCLUSION: The IPT uptake in this study was low and fell short of the set global target of > 90%. The completion rate was however acceptable. There is an urgent need to address the identified barriers.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/prevenção & controle , Adulto , Antituberculosos/efeitos adversos , Criança , Pré-Escolar , Aconselhamento , Estudos Transversais , Feminino , Pessoal de Saúde , Humanos , Lactente , Isoniazida/efeitos adversos , Quênia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Pesquisa Qualitativa , Encaminhamento e Consulta , Estudos Retrospectivos , Resultado do Tratamento , Recusa do Paciente ao Tratamento
10.
AIDS Res Ther ; 17(1): 28, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460788

RESUMO

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection constitute a deadly infectious disease synergy disease and major public health problem throughout the world. The risk of developing active TB in people living with HIV (PLHIV) is 21 times higher than the rest of the world population. The overlap of latent TB infection and HIV infection has resulted in marked increases in TB incidence in countries with dual epidemics. Although antiretroviral therapy (ART) is the single most significant way to reduce incident TB in PLHIV, besides early ART initiation, isoniazid preventive therapy (IPT) is the key intervention to prevent TB among PLHIV. This prospective cohort and longitudinal study aimed to document; retention, adherence, development of active TB disease, possible adverse drug reactions and completion among patients initiated on IPT in Jan 2019. METHODS: This was both a prospective cohort and longitudinal study nested within a national quality improvement collaborative in which multiple quality improvement teams tested changes in care delivery to improve the delivery of IPT. The prospective cohort were HIV patients without TB disease initiated on a dosage of Isoniazid 300 mg/day for adults and 150 mg/day for children for a period of 6 months. Association statistics were used to describe patient characteristics and outcomes. Variables with p-value < 0.05 were used to determine linear by linear associations between patient characteristics assumed to influence both primary and secondary outcomes. Variables with a p-value < 0.05 were included in the logistical regression model. The final model included those factors that retained statistical significance. The odds ratios (OR) and adjusted OR (AOR) along with its 95% confidence interval were used to determine the power of relationship in determining the outcomes of interest. The model was tested for fitness using goodness-of-fit Hosmer-Lemeshow tests. RESULTS: The completion of IPT was at 89%. A significant proportion of patients adhered to treatment (89%) and kept their appointment schedules-retention (89%). All patients (100%) received IPT at each appointment visit. Only 4% of patients experienced side effects of isoniazid (INH) but none of them developed active TB at the end of the 6 month INH dose. Multivariate logistic regression analysis of covariates of IPT completion revealed a strong and statistical association between IPT completion and age, gender, retention and side effects of INH. Our multivariate model found that children below 15 years were less likely to complete INH than patients ≥ 15 years (AOR = 0.416, p = 0.230, df = 1). Female patients were 2 times more likely to complete INH dose than male patients (AOR = 1.598, p = 0.018). Patients who kept all their appointment schedules were 10 times more likely to complete IPT than those who missed one or more schedules (AOR = 10.726, p = 0.000, df = 1). We also found that patients who did not report any side effects associated with INH were 2 times more likely to complete INH (AOR = 1.958, p = 0.016, df = 1) than patients who reported one or more side effects. CONCLUSION: Treatment completion is the end-point of the IPT initiation strategy in Uganda. With a completion rate of 89%, our results seem re-assuring and suggest that improvement collaborative is an effective approach to achieving results through combined efforts. The high rates of completion are encouraging indicators of progress in the implementation of collaborative activities in the study setting. However, such collaboratives would require periodic evaluation to prevent possible relapses in progress attained.


Assuntos
Antituberculosos/administração & dosagem , Isoniazida/administração & dosagem , Tuberculose Latente/prevenção & controle , Tuberculose/prevenção & controle , Adolescente , Adulto , Antituberculosos/uso terapêutico , Criança , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Humanos , Incidência , Colaboração Intersetorial , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Uganda/epidemiologia , Adulto Jovem
12.
BMJ Case Rep ; 12(11)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690687

RESUMO

A previously healthy 54-year-old ethnically Danish man was referred to the Department of Infectious Diseases at Aarhus University Hospital after an unexpected detection of Mycobacterium tuberculosis DNA in his lungs. Further examination revealed widespread dissemination of the tuberculosis (TB) to brain, mastoid, urinary and gastrointestinal tract. Thirteen months earlier, the patient was orchiectomised due to recurring inflammation of the right testicle. Three and a half months prior to admission to our department the patient started immunosuppressive therapy with steroids due to radiological and histological findings in the lungs that were interpreted as sarcoidosis (SA). This treatment is likely to be co-responsible for the pronounced dissemination of the TB. The patient was Bacillus Calmette-Guérin (BCG)-vaccinated as a child and had no apparent risk factors for TB apart from travelling in TB-endemic countries until 10 years before falling ill. Screening for latent TB was not performed prior to starting steroid treatment.


Assuntos
Antimaláricos/uso terapêutico , Tuberculose Latente/patologia , Prednisolona/uso terapêutico , Sarcoidose/patologia , Diagnóstico Diferencial , Humanos , Tuberculose Latente/diagnóstico por imagem , Tuberculose Latente/tratamento farmacológico , Masculino , Anamnese , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Sarcoidose/diagnóstico por imagem , Sarcoidose/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia
13.
Rev Esp Quimioter ; 32 Suppl 2: 63-68, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31475814

RESUMO

The use of biological (or targeted) therapies constitutes a major advance in the management of autoinflammatory and malignant diseases. However, due to the selective effect of these agents on the host's immune response, reactivation of certain pathogens that cause latent infection is to be expected. The most relevant concern is the risk of reactivation of latent tuberculosis infection (LTBI) and progression to active tuberculosis among patients treated with agents targeting tumor necrosis factor (TNF)-α. Systematic screening for LTBI at base-line with appropriate initiation of antituberculous treatment, if needed, is mandatory in this patient population as risk minimization strategy. In addition, reactivation of hepatitis B virus induced by B-cell-depleting (anti-CD20) and anti-TNF-α agents should be also prevented among HBsAg-positive patients and those with isolated anti-HBc IgG positivity (risk of "occult HBV infection"). The present review summarizes available evidence regarding the risk of reactivation of these latent infections induced by newer biological agents, as well as the recommendations included in the most recent guidelines.


Assuntos
Terapia Biológica/métodos , Infecções/terapia , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Animais , Humanos , Hospedeiro Imunocomprometido
14.
Mar Drugs ; 17(10)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561525

RESUMO

Pyrazinamide (PZA) is the only drug for the elimination of latent Mycobacterium tuberculosis (MTB) isolates. However, due to the increased number of PZA-resistance, the chances of the success of global TB elimination seems to be more prolonged. Recently, marine natural products (MNPs) as an anti-TB agent have received much attention, where some compounds extracted from marine sponge, Haliclona sp. exhibited strong activity under aerobic and hypoxic conditions. In this study, we screened articles from 1994 to 2019 related to marine natural products (MNPs) active against latent MTB isolates. The literature was also mined for the major regulators to map them in the form of a pathway under the dormant stage. Five compounds were found to be more suitable that may be applied as an alternative to PZA for the better management of resistance under latent stage. However, the mechanism of actions behind these compounds is largely unknown. Here, we also applied synthetic biology to analyze the major regulatory pathway under latent TB that might be used for the screening of selective inhibitors among marine natural products (MNPs). We identified key regulators of MTB under latent TB through extensive literature mining and mapped them in the form of regulatory pathway, where SigH is negatively regulated by RshA. PknB, RshA, SigH, and RNA polymerase (RNA-pol) are the major regulators involved in MTB survival under latent stage. Further studies are needed to screen MNPs active against the main regulators of dormant MTB isolates. To reduce the PZA resistance burden, understanding the regulatory pathways may help in selective targets of MNPs from marine natural sources.


Assuntos
Antituberculosos/uso terapêutico , Produtos Biológicos/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Tuberculose Latente/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana/métodos , Mutação/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Pirazinamida/uso terapêutico
15.
World J Gastroenterol ; 25(26): 3291-3298, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341356

RESUMO

Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection, particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis. Active tuberculosis (TB) after SOT is a significant cause of morbidity and mortality. Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection (LTBI) due to the effects of long-term immunosuppressive therapy. Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation. Isoniazid with vitamin B6 supplementation is the treatment of choice. However, liver transplantation (LT) candidates and recipients have an increased risk of isoniazid-induced liver toxicity, leading to lower treatment completion rates than in other SOT populations. Fluoroquinolones (FQs) exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid. In the present review, we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.


Assuntos
Antituberculosos/administração & dosagem , Fluoroquinolonas/administração & dosagem , Tuberculose Latente/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Aloenxertos , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Incidência , Isoniazida/efeitos adversos , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Fígado , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/microbiologia , Fatores de Risco , Resultado do Tratamento
16.
Ann Glob Health ; 85(1)2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30741506

RESUMO

Tuberculosis (TB) presents new challenges as a global public health problem, especially at a time of increasing threats to some particular patients due to Human Immunodeficiency Virus (HIV) infection and multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. The World Health Assembly strives to reduce TB deaths by 95% and to decrease TB incidence by 95% by 2035. However, new approaches are necessary in order to attain these objectives. Such approaches include active ascertainment of cases in high risk populations, increasing the availability of accurate point-of-care testing, rapid detection of drug resistance, novel vaccines, and new prophylaxis and treatment regimens (particularly for MDR and XDR TB). The ultimate objective of those programs is to develop highly effective drug regimens that can achieve high cure rates regardless of strains' resistance patterns.


Assuntos
Antituberculosos/uso terapêutico , Necessidades e Demandas de Serviços de Saúde , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Coinfecção , Cultura , Desenvolvimento de Medicamentos , Quimioterapia Combinada , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Testes de Sensibilidade Microbiana , Técnicas de Amplificação de Ácido Nucleico , Testes Imediatos , Radiografia Torácica , Escarro , Teste Tuberculínico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Vacinas contra a Tuberculose/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
17.
J Infect ; 77(6): 469-478, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30339803

RESUMO

OBJECTIVES: Since the risk of multidrug-resistant tuberculosis (MDR-TB) may depend on the setting, we aimed to determine the associations of risk factors of MDR-TB across different regions. METHODS: A systematic review and meta-analysis was performed with Pubmed and Embase databases. Information was retrieved on 37 pre-defined risk factors of MDR-TB. We estimated overall Mantel-Haenszel odds ratio as a measure of the association. RESULTS: Factors of previous TB disease and treatment are the most important risk factors associated with MDR-TB. There was also a trend towards increased risk of MDR-TB for patients 40 years and older, unemployed, lacking health insurance, smear positive, with non-completion and failure of TB treatment, showing adverse drug reaction, non-adherent, HIV positive, with COPD and with M. Tuberculosis Beijing infection. Effect modification by geographical area was identified for several risk factors such as male gender, married patients, urban domicile, homelessness and history of imprisonment. CONCLUSIONS: Assessment of risk factors of MDR-TB should be conducted regionally to develop the most effective strategy for MDR-TB control. Across all regions, factors associated with previous TB disease and treatment are essential risk factors, indicating the appropriateness of diagnosis, treatment and monitoring are an important requirements.


Assuntos
Antituberculosos/uso terapêutico , Saúde Global , Tuberculose Latente/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Interações entre Hospedeiro e Microrganismos , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Razão de Chances , Medição de Risco , Fatores de Risco , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico
18.
Actas Dermosifiliogr (Engl Ed) ; 109(7): 584-601, 2018 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29871738

RESUMO

Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents.


Assuntos
Antituberculosos/uso terapêutico , Terapia Biológica/efeitos adversos , Tuberculose Latente/tratamento farmacológico , Tuberculose/prevenção & controle , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antituberculosos/administração & dosagem , Monitoramento de Medicamentos , Hidradenite Supurativa/tratamento farmacológico , Humanos , Imunidade Celular , Tuberculose Latente/diagnóstico , Seleção de Pacientes , Psoríase/tratamento farmacológico , Risco , Subpopulações de Linfócitos T/imunologia , Tuberculose/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
19.
Inflamm Bowel Dis ; 24(10): 2272-2277, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29718223

RESUMO

Background: Treatment for latent tuberculosis infection (LTBI) is of particular concern in patients with inflammatory bowel disease (IBD) initiating biologic therapies to prevent tuberculosis (TB) reactivation. This study aimed to evaluate the effectiveness of LTBI treatment in IBD patients receiving biologic therapy. Methods: There was a retrospective review of all IBD patients diagnosed with LTBI following a tuberculin skin test (TST) and/or interferon gamma release assay (IGRA) and who received biologic therapy between 2002 and 2016. The primary outcome was tuberculosis reactivation after completion of LTBI treatment. Results: Three-hundred twenty-nine IBD patients were identified, and 35 (27 Crohn's disease; 8 ulcerative colitis) met the study inclusion criteria. The mean age was 38.3 years, and 68.6% were male. The most common LTBI treatment regimen was isoniazid (INH) for 9 months (74%). Biologic therapies used were infliximab (40%), adalimumab (29%), vedolizumab (20%), and certolizumab pegol (11%). Combination therapy with an immunomodulator was administered in 57% of cases. The median time from initiation of LTBI treatment to biologics was 43 days. The mean duration of follow-up was 2.9 years. The estimated median annual risk of TB reactivation without treatment was 0.52% by a prediction formula. Only 1 patient taking adalimumab monotherapy developed reactivation of TB several years after completing 6 months of isoniazid therapy. The estimated TB reactivation rate was 0.98 cases per 100 patient-years of follow-up in our cohort. Conclusions: Treatment for LTBI in patients with IBD treated with biologics is effective but does not eliminate the risk of reactivation. 10.1093/ibd/izy133_video1izy133.video15776720675001.


Assuntos
Antituberculosos/uso terapêutico , Terapia Biológica/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Tuberculose Latente/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Adulto , Feminino , Seguimentos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/induzido quimicamente , Tuberculose Latente/diagnóstico , Tuberculose Latente/microbiologia , Masculino , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Teste Tuberculínico
20.
J Crohns Colitis ; 12(8): 954-962, 2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-29757355

RESUMO

BACKGROUND: Biologic therapies have revolutionised the treatment of immune-mediated diseases including inflammatory bowel disease [IBD] and rheumatological disorders. However, biologic treatments are associated with an increased risk of reactivation of latent tuberculosis. Data from regular monitoring for latent tuberculosis infection [LTBI] during biologic treatment are lacking. METHODS: Consecutive patients eligible for biologic therapies were screened for LTBI and prospectively followed up for 3 years. Incidence and risk factors of latent tuberculosis tests conversion (interferon gamma release assays [IGRA], tuberculin skin tests [TST], and chest radiography [CXR]) with clinical outcomes were studied. RESULTS: A total of 108 patients [83 IBD; 25 rheumatological disorders] were included. At baseline, 18/108 [16.7%] patients [five IBD; 13 rheumatological disorders] were tested positive for LTBI. Of these, 14/18 [77.8%] patients received isoniazid monotherapy for 9 months. Of the remainder, 17/90 [18.9%] patients had LTBI test conversion while on biologic therapies and of these 14/17 [82.4%] received isoniazid monotherapy for 9 months. Age, sex, smoking status, alcohol use, travel history, disease type, and immunosuppressive therapy were not associated with LTBI test conversion. In subjects with IGRA conversion, serial IGRA levels normalised after completion of isoniazid except in one patient whose IGRA remained persistently elevated despite isoniazid and who subsequently developed active TB. CONCLUSIONS: Conversion of LTBI is common and occurred early during biologic therapy in an area with intermediate TB burden. Subjects with latent TB tests conversion and persistently high IGRA levels may have an increased risk of TB reactivation or development of active TB, and they require close observation or intensive workup for active TB.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antirreumáticos/uso terapêutico , Antituberculosos/uso terapêutico , Terapia Biológica , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Testes de Liberação de Interferon-gama , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia Torácica , Doenças Reumáticas/imunologia , Fatores de Risco , Teste Tuberculínico , Adulto Jovem
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