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1.
Arq Gastroenterol ; 56(2): 178-183, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31460583

RESUMO

BACKGROUND: Abdominal tuberculosis is an increasing problem in developing world. OBJECTIVE: The objective of the study was to describe the clinical presentations, drug resistance pattern and treatment outcomes of abdominal tuberculosis in Western India. METHODS: All the cases of abdominal tuberculosis from May 2014 to April 2017, diagnosed on the basis of clinical profile and gross morphological findings at endoscopy, imaging, followed by histology and/or GeneXpert and MGIT culture were included. All patients received antitubercular drug (AKT) therapy according to national protocol. Patients were followed from diagnoses till completion of treatment and various parameters were studied. RESULTS: Out of the 176 patients, 48% were males. Abdominal pain was most common complaint in 83.5%. On colonoscopy terminal ileum and ileocaecal valve were most commonly involved segments. Upper gastrointestinal tract was involved in four patients. Overall ulceronodular lesions were most common followed by ulcerative/nodular lesion. Strictures in bowel were seen in 28 (15.9%) patients with ileocaecal valve being most commonly involved, of which 23 had symptomatic relief with AKT and only three required dilatation. Histopathology showed granuloma in 80.8% cases. MGIT was positive in 43 (35.80%) cases and GeneXpert was positive in 35 (26.1%) cases. Eight patients had multi drug resistant tuberculosis. Only two patients required surgical management. CONCLUSION: Abdominal tuberculosis with wide spectrum of presentation, can still be managed with early diagnosis and treatment even in patients with sub acute intestinal obstruction. Weight gain or resolving symptoms were considered early markers of treatment response. Patients with stricture can become asymptomatic with medical treatment alone.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Gastrointestinal/diagnóstico , Tuberculose Gastrointestinal/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Resistência a Medicamentos , Endoscopia Gastrointestinal , Feminino , Seguimentos , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Socioeconômicos , Resultado do Tratamento , Adulto Jovem
3.
Medicine (Baltimore) ; 98(33): e16761, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415374

RESUMO

RATIONALE: Liver transplanted patients have excellent survival rates, but infectious complications are a major cause of morbidity and mortality. Diagnosis and treatment of tuberculosis (TB) in liver recipients are very challenging. Specific recommendations for anti-TB treatment in liver transplanted patients are lacking. PATIENT CONCERNS AND DIAGNOSIS: A 22-year-old male liver transplanted patient because of biliary atresia showed unexpected acute hemoptysis while he was on immunosuppressive therapy with tacrolimus and mycophenolate mofetil. Computed tomography (CT) identified a pulmonary arteriovenous malformation (PAVM) successfully treated with endovascular embolization. A post-embolization thoracic CT revealed pulmonary cavitation and miliary pattern suggesting pulmonary TB causing PAVM. TB diagnosis was confirmed by microbiological assays and genetic amplification techniques. INTERVENTION: Anti-TB 4-drug regimen was started. Following the beginning of treatment, liver enzymes increased. In order to clarify if liver cytolysis was due to hepatotoxicity or hepatic rejection linked to the reduction of immunosuppression or a worsening of pre-existing graft hepatitis, a liver biopsy was performed. A mild graft rejection was found so that tacrolimus doses were increased despite the risk of tubercular dissemination. OUTCOME: The patient completed anti-TB therapy in 8 months with resolution of TB disease and stable liver disease. LESSONS: TB management in liver transplanted patients is challenging and needs to be individualized especially if chronic graft hepatitis is present.


Assuntos
Rejeição de Enxerto , Hospedeiro Imunocomprometido , Transplante de Fígado , Tuberculose Pulmonar/diagnóstico , Antituberculosos/uso terapêutico , Diagnóstico Diferencial , Feminino , Hemoptise/etiologia , Humanos , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/tratamento farmacológico , Adulto Jovem
4.
Pan Afr Med J ; 32: 159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308862

RESUMO

Introduction: Focus has been put on strengthening surveillance systems in high tuberculosis (TB) burden countries, like Zambia, however inadequate information on factors associated with unfavourable TB treatment outcomes is generated from the system. We determined the proportion of tuberculosis treatment outcomes and their associated factors. Methods: We defined unfavourable outcome as death, lost-to-follow-up, treatment-failure, or not-evaluated and favourable outcome as a patient cured or completed-treatment. We purposively selected a 1st level hospital, an urban-clinic and a peri-urban clinic. We abstracted data from TB treatment registers at these three health facilities, for all TB cases on treatment from 1st January to 31st December, 2015. We calculated proportions of treatment outcomes and analysed associations between unfavourable outcome and factors such as age, HIV status, health facility, and patient type, using univariate logistics regression. We used multivariable stepwise logistic regression to control for confounding and reported the adjusted odds ratios (AOR) and 95% confidence intervals (CI). Results: We included a total of 1,724 registered TB patients, from one urban clinic 694 (40%), a 1st Level Hospital 654 (38%), and one peri-urban-clinic 276 (22%). Of the total patients, 43% had unfavourable outcomes. Of the total unfavourable outcomes, were recorded as treatment-failure (0.3%), lost-to-follow-up (5%), death (9%) and not evaluated (29%). The odds of unfavourable outcome were higher among patients > 59 years (AOR=2.9, 95%CI: 1.44-5.79), relapses (AOR=1.65, 95%CI: 1.15-2.38), patients who sought treatment at the urban clinic (AOR=1.76, 95%CI:1.27-2.42) and TB/HIV co-infected patients (AOR=1.56, 95%CI:1.11-2.19). Conclusion: Unfavourable TB treatment outcomes were high in the selected facilities. We recommend special attention to TB patients who are > 59 years old, TB relapses and TB / HIV co-infected. The national TB programme should strengthen close monitoring of health facilities in increasing efforts aimed at evaluating all the outcomes. Studies are required to identify and test interventions aimed at improving treatment outcomes.


Assuntos
Antituberculosos/uso terapêutico , Programas Nacionais de Saúde/organização & administração , Vigilância da População , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Coinfecção/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Resultado do Tratamento , Tuberculose/epidemiologia , Adulto Jovem , Zâmbia/epidemiologia
5.
Pan Afr Med J ; 32: 206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312318

RESUMO

Introduction: Tuberculosis (TB) is currently causing more deaths than Human Immunodeficiency Virus (HIV) globally. Ghana as one of the 30 high burden TB/HIV countries has a high annual TB case-fatality rate of 10%. The study sought to assess the effect of HIV infection on TB treatment outcomes and assess the time to mortality after treatment onset. Methods: We conducted a review of treatment files of TB patients who were treated from January 2013 to December 2015 in two urban hospitals in the Accra Metropolis. Modified Poisson regression analysis was used to measure the association between HIV infection and TB treatment outcomes. Kaplan-Meier survival estimates were used to plot survival curves. Results: Seventy-seven percent (83/107) of HIV infected individuals had successful treatment, compared to 91.2% (382/419) treatment success among HIV non-infected individuals. The proportion of HIV-positive individuals who died was 21.5% (23/107) whilst that of HIV-negative individuals was 5.5% (23/419). Being HIV-positive increased the risk of adverse outcome relative to successful outcome by a factor of 2.89(95% CI 1.76-4.74). The total number of deaths recorded within the treatment period was 46; of which 29(63%) occurred within the first two months of TB treatment. The highest mortality rate observed was among HIV infected persons (38.6/1000 person months). Of the 107 TB/HIV co-infected patients, 4(3.7%) initiated ART during TB treatment. Conclusion: The uptake of ART in co-infected individuals in this study was very low. Measures should be put in place to improve ART coverage among persons with TB/HIV co-infection to help reduce mortality.


Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/epidemiologia , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Estudos de Coortes , Coinfecção , Feminino , Gana/epidemiologia , Infecções por HIV/mortalidade , Soropositividade para HIV/epidemiologia , Hospitais Urbanos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Distribuição de Poisson , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Tuberculose/mortalidade , Adulto Jovem
6.
Epidemiol Health ; 41: e2019028, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31319659

RESUMO

OBJECTIVES: Tuberculosis (TB) is common in children with human immunodeficiency virus (HIV), but its effect on the survival of HIV-infected children is not well understood. Therefore, the aim of this study was to assess the incidence and predictors of active TB among HIV-positive children at Adama Referral Hospital and Medical College, Oromia, Ethiopia. METHODS: A retrospective study was conducted over 5 years using a checklist to gather data from 428 randomly selected pediatric patient charts. The checklist was adapted from the standardized antiretroviral therapy (ART) follow-up form currently used by the institution's ART clinic. Data were analyzed by bivariate and multivariable analysis using Cox regression proportional hazards models, as appropriate. Survival was calculated and compared using the Kaplan-Meier and log-rank tests. RESULTS: Of the 466 charts reviewed, 428 patient records were included in the analysis. A total of 67 new TB cases were observed during the follow-up period. Hence, the incidence rate in this cohort was found to be 6.03 per 100 child-years of observation. A baseline hemoglobin level <10 g/dL (adjusted hazard ratio [aHR], 7.04; 95% confidence interval [CI], 1.03 to 48.15), moderate wasting (aHR, 2.86; 95% CI, 1.02 to 7.99), and not receiving isoniazid preventive therapy (aHR, 8.23; 95% CI, 2.11 to 32.06) were among the independent predictors of TB occurrence. CONCLUSIONS: The incidence of TB was high, particularly in pre-ART patients receiving chronic care for HIV. Close followup of HIV-positive children is crucial to protect them against the development of TB. Initiating isoniazid preventive therapy, averting malnutrition, and managing anemia are also of significant importance.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Tuberculose/epidemiologia , Antirretrovirais/uso terapêutico , Antituberculosos/uso terapêutico , Criança , Pré-Escolar , Etiópia/epidemiologia , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Isoniazida/uso terapêutico , Masculino , Encaminhamento e Consulta , Estudos Retrospectivos , Fatores de Risco , Tuberculose/prevenção & controle
7.
Medicine (Baltimore) ; 98(27): e16280, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277156

RESUMO

RATIONALE: Tuberculous retropharyngeal abscess is rare, but it can be fatal if not treated appropriately. It usually occurs secondary to tuberculosis of the cervical spine. Moreover, tuberculous abscess involving the chest wall is relatively rare in skeletal tuberculosis. Although the optimal treatment is controversial, most clinicians suggest a combination of sufficient antituberculous medication and complete resection to prevent recurrence and increase therapeutic efficacy. Herein, we present an unusual case of retropharyngeal abscess with cervical Pott disease and tuberculous abscess of the chest wall. PATIENT CONCERNS: The patient was a 27-year-old Indonesian woman who had neck pain, dysphagia, and odynophagia, but no neurological deficit. Examination of the oral cavity showed anterior displacement of the posterior pharyngeal wall. The mass over the right anterior chest wall measured approximately 5 × 4 cm in size. DIAGNOSES: Radiography and computed tomography findings were suggestive of retropharyngeal abscess extending to the cervical spine and chest wall abscess. INTERVENTIONS: She was admitted to the hospital for treatment. Drainage of the retropharyngeal and chest wall abscesses with debridement of the chest wall was performed. OUTCOMES: No complications occurred after early surgical treatment and administration of antituberculous medication. The patient recovered well and went back to her own country after discharge. LESSONS: Tuberculous retropharyngeal abscess with Pott disease and tuberculous abscess of the chest wall are both complicated diagnoses that physicians have to consider in similar patient presentations.


Assuntos
Abscesso/etiologia , Antituberculosos/uso terapêutico , Drenagem/métodos , Mycobacterium tuberculosis/imunologia , Abscesso Retrofaríngeo/etiologia , Parede Torácica/microbiologia , Tuberculose da Coluna Vertebral/complicações , Abscesso/diagnóstico , Abscesso/terapia , Adulto , Feminino , Humanos , Mycobacterium tuberculosis/isolamento & purificação , Abscesso Retrofaríngeo/microbiologia , Abscesso Retrofaríngeo/terapia , Parede Torácica/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Tuberculose da Coluna Vertebral/diagnóstico , Tuberculose da Coluna Vertebral/terapia
8.
Pan Afr Med J ; 32: 68, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223360

RESUMO

Primary hepatic tuberculosis is a rare presentation and sporadically reported in the literature, mostly from our part of the world. Sometimes the presentation can be atypical and mimics hepatic tumor and poses diagnostic challenge. We, herein, present a case of a 58-year-old man who presented to us with abdominal pain and weight loss. Raised serum alkaline phosphatase (ALP) and imaging raised a suspicion of gall bladder carcinoma with hepatic invasion. Peroperative frozen section revealed hepatic chronic granulomatous inflammation with caseous necrosis consistent with the diagnosis of hepatic tuberculosis. Surgery was postponed and he was put on antituberculous treatment. It is important to consider tuberculosis in the differential diagnosis of the space occupying lesion of liver in a patient with vague symptoms and abnormal findings on imaging.


Assuntos
Antituberculosos/uso terapêutico , Neoplasias Hepáticas/diagnóstico , Tuberculose Hepática/diagnóstico , Dor Abdominal/etiologia , Diagnóstico Diferencial , Neoplasias da Vesícula Biliar/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose Hepática/tratamento farmacológico , Perda de Peso
9.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(6): 643-647, 2019 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-31238612

RESUMO

Objective: To analyze the epidemiological characteristics, trend and related factors of tuberculosis patients that delayed for care, in Wuhan from 2008 to 2017. Methods: Data regarding tuberculosis (TB) patients was collected from the tuberculosis management information system (TMIS), a part of the China information system for disease control and prevention from 2008 to 2017. A total of 64 208 tuberculosis patients, aged 0 to 95 years were included for the analysis. Unconditional logistic regression method was used to estimate those factors that associated with this study. Results: Days of delay among TB patients appeared as M=10 (P(25)-P(75): 3-28) day, in Wuhan, 2008-2017. The prevalence of the delay was 52.5% (33 703/64 208), presenting a downward trend from 2008 to 2017 (trend χ(2)=10.64, P<0.001), but the proportions of women and ≥65 year-olds were gradually increasing. Results from the multivariate logistic regression analysis showed that factors as: patients living far away from the city vs. near the city (OR=1.29, 95%CI: 1.25-1.35), and age above 45 years vs. younger than 25 years (the age 45-64 years group vs. aged less than 25 years group, OR=1.22, 95%CI: 1.15-1.29; the age 65 or above group vs. aged less than 25 years group, the OR=1.30, 95%CI: 1.22-1.39) were under higher risk on the delay of seeking care. Occupation, way of case-finding and classification of tuberculosis patients also appeared as influencing factors on this issue. Conclusions: Prevalence on the delay of care was 52.5% among tuberculosis patients in Wuhan, 2008-2017, but with an annual decrease. Attention should be paid to female, wrinkly or elderly tuberculosis patients regarding the delay of care on TB, in Wuhan.


Assuntos
Antituberculosos/uso terapêutico , Diagnóstico Tardio , Conhecimentos, Atitudes e Prática em Saúde , Acesso aos Serviços de Saúde , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Características de Residência/estatística & dados numéricos , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Assistência à Saúde/organização & administração , Feminino , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Prevalência , Distribuição por Sexo , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
10.
Infect Dis Poverty ; 8(1): 44, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31182164

RESUMO

BACKGROUND: Tuberculosis (TB) prevalence is closely associated with poverty in China, and poor patients face more barriers to treatment. Using an insurance-based approach, the China-Gates TB program Phase II was implemented between 2012 and 2014 in three cities in China to improve access to TB care and reduce the financial burden on patients, particularly among the poor. This study aims to assess the program effects on service use, and its equity impact across different income groups. METHODS: Data from 788 and 775 patients at baseline and final evaluation were available for analysis respectively. Inpatient and outpatient service utilization, treatment adherence, and patient satisfaction were assessed before and after the program, across different income groups (extreme poverty, moderate poverty and non-poverty), and in various program cities, using descriptive statistics and multi-variate regression models. Key stakeholder interviews were conducted to qualitatively evaluate program implementation and impacts. RESULTS: After program implementation, the hospital admission rate increased more for the extreme poverty group (48.5 to 70.7%) and moderate poverty group (45.0 to 68.1%), compared to the non-poverty group (52.9 to 64.3%). The largest increase in the number of outpatient visits was also for the extreme poverty group (4.6 to 5.7). The proportion of patients with good medication adherence increased by 15 percentage points in the extreme poverty group and by ten percentage points in the other groups. Satisfaction rates were high in all groups. Qualitative feedback from stakeholders also suggested that increased reimbursement rates, easier reimbursement procedures, and allowance improved patients' service utilization. Implementation of case-based payment made service provision more compliant to clinical pathways. CONCLUSION: Patients in extreme or moderate poverty benefited more from the program compared to a non-poverty group, indicating improved equity in TB service access. The pro-poor design of the program provides important lessons to other TB programs in China and other countries to better address TB care for the poor.


Assuntos
Assistência à Saúde/economia , Acesso aos Serviços de Saúde/economia , Aceitação pelo Paciente de Cuidados de Saúde , Satisfação do Paciente , Tuberculose/economia , Tuberculose/psicologia , Adulto , Idoso , Antituberculosos/economia , Antituberculosos/uso terapêutico , China , Estudos Transversais , Feminino , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Reembolso de Seguro de Saúde , Modelos Logísticos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Satisfação do Paciente/economia , Pobreza/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários , Tuberculose/tratamento farmacológico
11.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(5): 559-564, 2019 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-31177738

RESUMO

Objective: To understand the medical expenditure and related household economic burden of pulmonary tuberculosis (TB) patients receiving full course treatment in designated TB hospitals in China and identify the related factors. Method: A cross-sectional study was conducted in 535 consecutive TB patients receiving TB treatment from April 2017 to June 2017 in 5 designated TB hospitals in eastern and western China selected through stratified cluster sampling. A questionnaire was used to collect the information about patients' social economic characteristics and TB diagnosis and treatment expenditure. Results: The average total medical expenditure for TB treatment was 12 635.5 yuan (RMB), in which the direct medical expenditure accounted for 65.3% of the total. Nearly half of the total medical expenditure occurred in pre-treatment period. The expenditure in pre- treatment period was higher in the patients with low education level, newly treated patients, and initial sputum negative patients. The median (quartile) for the ratio of total medical expenditure to annual household income was 22%(10%-57%). Ordinal logistic regression analysis showed that low-level education background, lower household income, hospitalization and suffering from other chronic disease might increase the ratio of medical expenditure to annual household income. Conclusions: Medical expenditure for full course TB treatment is still high in patients in designated TB hospitals. It is suggested to strengthen the capability building of timely found and referral of TB patients in non- designated hospitals and improve fee reduction and exemption policy for some patients.


Assuntos
Antituberculosos/economia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Gastos em Saúde , Hospitais de Doenças Crônicas , Tuberculose Pulmonar/economia , Antituberculosos/uso terapêutico , China/epidemiologia , Estudos Transversais , Humanos , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia
13.
J Physiol Pharmacol ; 70(1)2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31172969

RESUMO

The incidence of tuberculosis (TB) in some countries increases continuously, especially caused by mycobacterial strains resistant to various anti-tuberculotic drugs (AT). The emergence and spread of drug-resistant tuberculosis (multidrug-resistant - MDR-TB, and extensively drug-resistant - XDR-TB) suggest the crucial role of pharmacotherapy protocol tailored to the respective patient with MDR-TB or XDR-TB (a personalized approach) and requirements for fast and precise diagnostics of the degree of resistance. The aim of this study was to characterize a molecular basis of resistance to AT, and to identify the presence of the resistance using conventional susceptibility testing and molecular genetic methods using PCR tests in Slovakia during years 2009 - 2017. Furthermore, we focused on evaluation of the relationship between the level of resistance, the clinical status, and some laboratory markers of patients with drug-resistant TB. Totally 1157 strains isolated from patients in 2009 - 2017 were tested for resistance using classical methods and in resistant strains, the molecular-genetic tests were performed. Increased incidence of recurrence, prolonged time required to culture conversion, increased mortality during treatment, plasma C-reactive protein concentrations and sedimentation rate, broader spectrum of AT used, as well as higher incidence of adverse effects (sufficiently controlled with symptomatic treatment) were observed with higher degree of resistance. Contrary, the number of patients who achieved remission decreased. Rapid and precise identification of MDR-TB or XDR-TB strains using both classical and molecular-genetic testing is an essential tool for personalized drug treatment and prevention of resistance spread and worsening. Both tests should be used for correct diagnosis of resistant TB. Higher level of resistance required more aggressive therapeutic approach, associated with adverse effects and prolongation of the culture conversion time, as well as increased risk of relapse. Effective pharmacotherapy led to significant decrease of CRP levels in all groups of patients. The most frequent adverse effects of ATs - impairment of liver and kidney functions - were effectively managed by symptomatic treatment.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , DNA Bacteriano/análise , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Fenótipo , Eslováquia/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
14.
BMC Infect Dis ; 19(1): 544, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221100

RESUMO

BACKGROUND: Bedaquiline was recently introduced into World Health Organization (WHO)-recommended regimens for treatment of drug resistant tuberculosis. There is limited data on the long-term safety of bedaquiline. Because bedaquiline prolongs the QT interval, there are concerns regarding cardiovascular safety. The Western Cape Province in South Africa has an established pharmacovigilance programme: a targeted spontaneous reporting system which solicits reports of suspected adverse drug reactions (ADRs) in patients with HIV-1 and/or tuberculosis infection. Since 2015, bedaquiline has been included in the treatment regimens recommended for resistant tuberculosis in South Africa. We describe ADRs in patients on bedaquiline-containing tuberculosis treatment that were reported to the Western Cape Pharmacovigilance programme. METHODS: We reviewed reports of suspected ADRs and deaths received between March 2015 and June 2016 involving patients receiving bedaquiline-containing tuberculosis treatment. A multidisciplinary panel assessed causality, and categorised suspected ADRs using World Health Organisation-Uppsala Monitoring Centre system categories. "Confirmed ADRs" included all ADRs categorised as definite, probable or possible. Preventability was assessed using Schumock and Thornton criteria. Where a confirmed ADR occurred in a patient who died, the panel categorised the extent to which the ADR contributed to the patient's death as follows: major contributor, contributor or non-contributor. RESULTS: Thirty-five suspected ADRs were reported in 32 patients, including 13 deaths. There were 30 confirmed ADRs, of which 23 were classified as "possible" and seven as "probable". Bedaquiline was implicated in 22 confirmed ADRs in 22 patients. The most common confirmed ADR in patients receiving bedaquiline was QT prolongation (8 cases, 7 of which were severe). A fatal arrhythmia was suspected in 4 sudden deaths. These 4 patients were all taking bedaquiline together with other QT-prolonging drugs. There were 8 non-bedaquiline-associated ADRs, of which 7 contributed to deaths. CONCLUSIONS: Confirmed ADRs in patients receiving bedaquiline reflect the known safety profile of bedaquiline. Quantifying the incidence and clinical consequences of severe QT-prolongation in patients receiving bedaquiline-containing regimens is a research priority to inform recommendations for patient monitoring in treatment programmes for drug resistant tuberculosis. Pharmacovigilance systems within tuberculosis treatment programmes should be supported and encouraged, to provide ongoing monitoring of treatment-limiting drug toxicity.


Assuntos
Antituberculosos/efeitos adversos , Doenças Cardiovasculares/etiologia , Diarilquinolinas/efeitos adversos , Adulto , Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/etiologia , Masculino , África do Sul , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/patologia , Adulto Jovem
15.
BMC Infect Dis ; 19(1): 553, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234780

RESUMO

BACKGROUND: Kazakhstan remains a high-burden TB prevalence country with a concomitent high-burden of multi-drug resistant tuberculosis. For this reason, we performed an in depth genetic diversity and population structure characterization of Mycobacterium tuberculosis complex (MTC) genetic diversity in Kazakhstan with both patient and community benefit. METHODS: A convenience sample of 700 MTC DNA cultures extracts from 630 tuberculosis patients recruited from 12 out of 14 regions in Kazakhstan, between 2010 and 2015, was independently studied by high-throughput hybridization-based methods, TB-SPRINT (59-Plex, n = 700), TB-SNPID (50-Plex, n = 543). DNA from 391 clinical isolates was successfully typed by two methods. To resolve the population structure of drug-resistant clades in more detail two complementary assays were run on the L2 isolates: an IS6110-NTF insertion site typing assay and a SigE SNP polymorphism assay. RESULTS: Strains belonged to L2/Beijing and L4/Euro-American sublineages; L2/Beijing prevalence totaled almost 80%. 50% of all samples were resistant to RIF and to INH., Subtyping showed that: (1) all L2/Beijing were "modern" Beijing and (2) most of these belonged to the previously described 94-32 sublineage (Central Asian/Russian), (3) at least two populations of the Central Asian/Russian sublineages are circulating in Kazakhstan, with different evolutionary dynamics. CONCLUSIONS: For the first time, the global genetic diversity and population structure of M. tuberculosis genotypes circulating in Kazakhstan was obtained and compared to previous local studies. Results suggest a region-specific spread of a very limited number of L2/Beijing clonal complexes in Kazakhstan many strongly associated with an MDR phenotype.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adulto , Idoso , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Evolução Molecular , Variação Genética , Genótipo , Humanos , Cazaquistão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico/métodos , Fenótipo , Prevalência , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto Jovem
16.
BMC Infect Dis ; 19(1): 564, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253115

RESUMO

BACKGROUND: The increased incidence of drug-resistant TB is a major challenge for effective TB control. Limited therapeutic options and poor treatment outcomes of DR-TB may increase drug-resistance rates. The objective of the study is to retrospectively compare MDR-TB and pre-XDR-TB treatment regimens and outcomes in two large TB reference centres in Italy from January 2000 to January 2015. METHODS: A retrospective, multicentre study was conducted at the Regional TB Reference Centre Villa Marelli Institute (Milan) and at the Reference Center for MDR-TB and HIV-TB, Eugenio Morelli Hospital (Sondalo). The supra-national Reference Laboratory in Milan performed DST. Inclusion criteria were: age ≥ 18 and culture-confirmed diagnosis of MDR- or pre-XDR TB. Chi-square or Fisher exact test was used to detect differences in the comparison between treatment outcomes, therapeutic regimens, and drug-resistances. Computations were performed with STATA 15. RESULTS: A total of 134 patients were selected. Median (IQR) age at admission was 33 (26-41) years and 90 patients (67.2%) were male. Pulmonary TB was diagnosed in 124 (92.5%) patients. MDR- and pre-XDR-TB cases were 91 (67.9%) and 43 (32.1%), respectively. The WHO shorter MDR-TB regimen could have been prescribed in 16/84 (19.1%) patients. Treatment success was not statistically different between MDR- and pre-XDR-TB (81.3% VS. 81.4%; P = 0.99). Mortality in MDR-TB and pre-XDR-TB groups was 4.4 and 9.3%, respectively (P = 0.2). Median duration of treatment was 18 months and a total of 110 different regimens were administered. Exposure to linezolid, meropenem, and amikacin was associated with a better outcome in both groups (P = 0.001, P < 0.001, and P = 0.004, respectively). CONCLUSIONS: Tailored treatment regimens based on DST results can achieve successful outcomes in patients with pre-XDR-TB.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Amicacina/farmacologia , Amicacina/uso terapêutico , Antituberculosos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/mortalidade , Feminino , Humanos , Itália , Laboratórios Hospitalares , Linezolida/farmacologia , Linezolida/uso terapêutico , Masculino , Meropeném/farmacologia , Meropeném/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade
18.
Pan Afr Med J ; 32: 85, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223376

RESUMO

Parotid tuberculosis remains a very rare localization in the Department of Otolaryngology and Cervico-Facial Surgery (ENT) sphere. It is presented in the form of a deceptive clinical picture causing confusion with other pathologies of the parotid gland, including tumor pathology. In addition, its lack of knowledge by practitioners increases the risk of missing the diagnosis. Often, the diagnosis is a histological surprise on a piece of excision after an exploratory parotidectomy. However, its treatment is primarily medical if the positive diagnosis is well established. We report medical observation of two new cases aged 44 and 45 respectively, who consult our center for parotid swelling. Radiological examinations were in favor of intraparotid cystic lesions. Both patients benefited from an excision whose histopathological study was in favor of primary parotid tuberculosis. The subsequent evolution was favorable under antituberculous treatment.


Assuntos
Antituberculosos/uso terapêutico , Doenças Parotídeas/diagnóstico , Tuberculose/diagnóstico , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Parotídeas/tratamento farmacológico , Doenças Parotídeas/microbiologia , Neoplasias Parotídeas/diagnóstico , Tuberculose/tratamento farmacológico
19.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(1): 44-49, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31102357

RESUMO

Rifamycins, a group of bacterial RNA polymerase inhibitors, are the firstline antimicrobial drugs to treat tuberculosis. In light of the emergence of rifamycinresistant bacteria, development of new RNA polymerase inhibitors that kill rifamycinresistant bacteria with high bioavailability is urgent. Structural analysis of bacterial RNA polymerase in complex with inhibitors by crystallography and cryo-EM indicates that RNA polymerase inhibitors function through five distinct molecular mechanisms:inhibition of the extension of short RNA; competition with substrates; inhibition of the conformational change of the'bridge helix'; inhibition of clamp opening;inhibition of clamp closure. This article reviews the research progress of these five groups of RNA polymerase inhibitors to provide references for the modification of existing RNA polymerase inhibitors and the discovery of new RNA polymerase inhibitors.


Assuntos
RNA Polimerases Dirigidas por DNA , Descoberta de Drogas , RNA Bacteriano , Antituberculosos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , RNA Polimerases Dirigidas por DNA/metabolismo , Descoberta de Drogas/tendências , Farmacorresistência Bacteriana , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Humanos , Tuberculose/tratamento farmacológico , Tuberculose/enzimologia
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