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1.
Pan Afr Med J ; 38: 66, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33889232

RESUMO

Introduction: tuberculosis (TB) remains a global health issue with high morbidity and mortality rates especially in the developing countries. It is a multi-organ disease and can influence biochemical changes. This study sought to determine the influence of tuberculosis and its drug treatment on serum biochemical parameters in patients in Nigeria. Methods: it was a descriptive observational cohort study on 150 subjects whose blood samples were analyzed for serum albumin, serum sodium, and serum potassium. The subjects were grouped into 3: TB group= 50 new TB subjects not on treatment, F group= 50 TB subjects on treatment for 2/12 or more and C group= 50 non-TB control subjects. These biochemical variables were compared between the 3 groups. Results: male/female ratio was 1: 1.5, mean age 37.1±0.92 years, and range 18-65 years. The differences in mean values of serum albumin, calcium and sodium between the three groups were significant (p<0.001), whereas that of serum potassium was not significant (p=0.056). Those patients with new case TB had a significantly lower serum sodium, serum albumin and serum calcium than the control group and those on treatment, p<0.001. There was significant positive correlation between serum albumin and serum calcium (r=0.0.420, p<0.001) as well as serum sodium (r=0.310, p<0.001) in the study population. Similarly, the correlation between serum calcium and serum sodium was positive and significant (r=0.200, p=0.014). In contrast, the correlation between serum potassium and serum albumin and that between serum potassium and serum calcium was not significant. Conclusion: tuberculosis with or without anti-tuberculous medications was associated with significant reduction in serum albumin, serum sodium and serum calcium in this study.


Assuntos
Cálcio/sangue , Albumina Sérica/análise , Sódio/sangue , Tuberculose/sangue , Adolescente , Adulto , Idoso , Antituberculosos/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Potássio/sangue , Tuberculose/tratamento farmacológico , Adulto Jovem
2.
Lancet Child Adolesc Health ; 5(5): 350-356, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33770510

RESUMO

BACKGROUND: Shorter regimens for tuberculosis prevention can improve completion rates and protection against developing active tuberculosis disease after tuberculosis exposure. We aimed to assess the safety and feasibility of 1 month of daily isoniazid and rifapentine (1HP) in children and adolescents in a low-resource setting in south Asia with low prevalence of HIV. METHODS: This prospective cohort study was done in eight tuberculosis facilities in Karachi, Pakistan. Eligible participants were aged 2-19 years and were household contacts of patients with drug-susceptible tuberculosis infection. After clinical, radiological, and laboratory evaluation to rule out tuberculosis disease, participants were prescribed 1HP as a preventive regimen. Isoniazid was administered as 100 mg or 300 mg oral tablets and rifapentine was administered as 150 mg oral tablets. Dosing was according to participant bodyweight. The primary endpoints were the cumulative probability of a household contact completing all stages of the preventive care cascade, assessed in all eligible participants, and the proportion of household contacts completing 1HP, assessed among all those who initiated the regimen. Safety was assessed in all household contacts who initiated the 1HP regimen. FINDINGS: Between Dec 21, 2019, and March 20, 2020, 1395 household contacts of 253 patients with tuberculosis were identified, including 678 household contacts who were eligible to participate. 628 (93%) completed evaluation, of whom ten (2%) had active tuberculosis disease. Of the 618 individuals eligible for tuberculosis prevention, 408 (66%) initiated 1HP, 385 (94%) of whom completed the regimen. The median duration of 1HP was 31 days (IQR 30-32) in those who completed the regimen. The cumulative probability of completing all steps of the tuberculosis prevention cascade was 58%. A girl aged 11 years developed tuberculosis disease within 6 months of completing 1HP. A boy aged 14 years developed a burning sensation during 1HP therapy and discontinued the regimen. No other adverse events were observed. INTERPRETATION: 1HP can be safely and feasibly implemented as tuberculosis prevention in children and adolescents in programmatic settings. FUNDING: The Global Fund to Fight AIDS, Tuberculosis and Malaria.


Assuntos
Antituberculosos/administração & dosagem , Duração da Terapia , Isoniazida/administração & dosagem , Rifampina/análogos & derivados , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Tuberculose/prevenção & controle , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Paquistão/epidemiologia , Estudos Prospectivos , Rifampina/administração & dosagem , Adulto Jovem
3.
Toxicology ; 455: 152749, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33771660

RESUMO

Isoniazid (INH), a synthetic first-line tuberculosis antibiotic, has been widely used in clinical treatment. It has been reported to cause toxic effects at multiple tissue sites and also increases the incidence of adverse pregnancy outcomes; but the mechanism of action of INH on the reproductive system of female mammals remains unclear. Here, we demonstrate that oral INH (40 mg/kg/day every other day for 28 days) severely affects oocyte maturation and fertilization, late blastocyst development and fertility. We found that INH could disrupt standard spindle assembly, chromosome arrangement, and actin filament dynamics, which compromised meiotic progression of mouse oocytes. INH treatment increased the level of reactive oxygen species (ROS) and activated the oxidative stress response pathway, Keap1-Nrf2. It also caused apoptosis of oocytes and mitochondrial dysfunction. Our findings demonstrate that oral INH reduces fertility and damages the mammalian reproductive system by altering cytoskeletal dynamics and Juno expression, inducing oxidative stress and apoptosis, and activating the Keap1-Nrf2 signaling pathway in mouse oocytes.


Assuntos
Antituberculosos/toxicidade , Isoniazida/toxicidade , Oócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Animais , Antituberculosos/administração & dosagem , Apoptose/efeitos dos fármacos , Feminino , Isoniazida/administração & dosagem , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/metabolismo , Oócitos/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
4.
BMJ Case Rep ; 14(3)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653871

RESUMO

A 30-year-old, multiparous widow, with postpolio residual paralysis, presented with complaints of dull aching abdominal pain for 15 days. Ultrasound showed a mixed echogenic right adnexal mass with free fluid in the pelvis and abdomen. CT abdomen and pelvis revealed partially defined peripherally enhancing collection in lower abdomen and right adnexa suggestive of tubo-ovarian abscess. There was mild ileal wall thickening and few enlarged mesenteric lymph nodes. Ascitic fluid did not show acid fast bacilli and cultures were sterile. Extensive diagnostic laboratory work was done which was inconclusive. Diagnostic laparoscopy could not be performed due to non-availability of elective operation theatre in the COVID-19 pandemic. Presumptive extrapulmonary tuberculosis was clinically and radiologically diagnosed. She was started on daily anti tuberculosis treatment. This case shows us the importance of imaging as a diagnostic tool and as an alternative for laparoscopy in COVID-19 pandemic to diagnose abdomino-pelvic tuberculosis.


Assuntos
Abscesso Abdominal , Doenças dos Anexos , Antituberculosos/administração & dosagem , Tuberculose Urogenital , Abscesso Abdominal/diagnóstico por imagem , Abscesso Abdominal/etiologia , Dor Abdominal/diagnóstico , Doenças dos Anexos/diagnóstico , Doenças dos Anexos/fisiopatologia , Doenças dos Anexos/terapia , Adulto , /terapia , Diagnóstico Diferencial , Feminino , Humanos , Pelve/diagnóstico por imagem , Síndrome Pós-Poliomielite/complicações , Tomografia Computadorizada por Raios X/métodos , Tuberculose Urogenital/complicações , Tuberculose Urogenital/diagnóstico , Tuberculose Urogenital/fisiopatologia , Tuberculose Urogenital/terapia , Ultrassonografia/métodos
6.
BMC Infect Dis ; 21(1): 90, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478428

RESUMO

BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. TRIAL REGISTRATION: The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 ).


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Rifampina/análogos & derivados , Rifampina/uso terapêutico , Adolescente , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Londres , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Autoadministração , Resultado do Tratamento , Adulto Jovem
7.
PLoS Med ; 18(1): e1003502, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33465063

RESUMO

BACKGROUND: Tuberculosis (TB) rates among Tibetan refugee children and adolescents attending boarding schools in India are extremely high. We undertook a comprehensive case finding and TB preventive treatment (TPT) program in 7 schools in the Zero TB Kids project. We aimed to measure the TB infection and disease burden and investigate the risk of TB disease in children and adults who did and did not receive TPT in the schools. METHODS AND FINDINGS: A mobile team annually screened children and staff for TB at the 7 boarding schools in Himachal Pradesh, India, using symptom criteria, radiography, molecular diagnostics, and tuberculin skin tests. TB infection (TBI) was treated with short-course regimens of isoniazid and rifampin or rifampin. TB disease was treated according to Tibetan and Indian guidelines. Between April 2017 and December 2019, 6,582 schoolchildren (median age 14 [IQR 11-16] years) and 807 staff (median age 40 [IQR 33-48] years) were enrolled. Fifty-one percent of the students and 58% of the staff were females. Over 13,161 person-years of follow-up in schoolchildren (median follow-up 2.3 years) and 1,800 person-years of follow-up in staff (median follow-up 2.5 years), 69 TB episodes occurred in schoolchildren and 4 TB episodes occurred in staff, yielding annual incidence rates of 524/100,000 (95% CI 414-663/100,000) person-years and 256/100,000 (95% CI 96-683/100,000) person-years, respectively. Of 1,412 schoolchildren diagnosed with TBI, 1,192 received TPT. Schoolchildren who received TPT had 79% lower risk of TB disease (adjusted hazard ratio [aHR] 0.21; 95% CI 0.07-0.69; p = 0.010) compared to non-recipients, the primary study outcome. Protection was greater in recent contacts (aHR 0.07; 95% CI 0.01-0.42; p = 0.004), the secondary study outcome. The prevalence of recent contacts was 28% (1,843/6,582). Two different TPT regimens were used (3HR and 4R), and both were apparently effective. No staff receiving TPT developed TB. Overall, between 2017 and 2019, TB disease incidence decreased by 87%, from 837/100,000 (95% CI 604-1,129/100,000) person-years to 110/100,000 (95% CI 36-255/100,000) person-years (p < 0.001), and TBI prevalence decreased by 42% from 19% (95% CI 18%-20%) to 11% (95% CI 10%-12%) (p < 0.001). A limitation of our study is that TB incidence could be influenced by secular trends during the study period. CONCLUSIONS: In this study, following implementation of a school-wide TB screening and preventive treatment program, we observed a significant reduction in the burden of TB disease and TBI in children and adolescents. The benefit of TPT was particularly marked for recent TB contacts. This initiative may serve as a model for TB detection and prevention in children and adolescents in other communities affected by TB.


Assuntos
Antituberculosos/administração & dosagem , Programas de Rastreamento/métodos , Refugiados , Tuberculose/diagnóstico , Tuberculose/prevenção & controle , Adolescente , Adulto , Criança , Feminino , Humanos , Incidência , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Instituições Acadêmicas , Tibet/etnologia , Tuberculose/epidemiologia
8.
Lancet HIV ; 8(1): e8-e15, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33387480

RESUMO

BACKGROUND: Isoniazid preventive therapy prevents active tuberculosis in people with HIV, but previous studies have found no evidence of benefit in people with HIV who had a negative tuberculin skin test, and a non-significant effect on mortality. We aimed to estimate the effect of isoniazid preventive therapy given with antiretroviral therapy (ART) for the prevention of tuberculosis and death among people with HIV across population subgroups. METHODS: We searched PubMed, Embase, the Cochrane database, and conference abstracts from database inception to Jan 15, 2019, to identify potentially eligible randomised trials. Eligible studies were trials that enrolled HIV-positive adults (age ≥15 years) taking ART who were randomly assigned to either daily isoniazid preventive therapy plus ART or ART alone and followed up longitudinally for outcomes of incident tuberculosis and mortality. We approached all authors of included trials and requested individual participant data: coprimary outcomes were relative risk of incident tuberculosis and all-cause mortality. We did a single-stage meta-analysis of individual participant data using stratified Cox-proportional hazards models. We did prespecified subgroup analyses by sex, CD4 cell count, and evidence of immune sensitisation to tuberculosis (indicated by tuberculin skin test or interferon-γ release assays [IGRAs]). We also assessed the relative risk of liver injury in an additional prespecified analysis. This study is registered with PROSPERO, CRD42019121400. FINDINGS: Of 838 records, we included three trials with data for 2611 participants and 8584·8 person-years of follow-up for the outcome of incident tuberculosis, and a subset of 2362 participants with 8631·6 person-years of follow-up for the coprimary outcome of all-cause mortality. Risk for tuberculosis was lower in participants given isoniazid preventive therapy and ART than participants given ART alone (hazard ratio [HR] 0·68, 95% CI 0·49-0·95, p=0·02). Risk of all-cause mortality was lower in participants given isoniazid preventive therapy and ART than participants given ART alone, but this difference was non-significant (HR 0·69, 95% CI 0·43-1·10, p=0·12). Participants with baseline CD4 counts of less than 500 cells per µL had increased risk of tuberculosis, but there was no significant difference in the benefit of isoniazid preventive therapy with ART by sex, baseline CD4 count, or results of tuberculin skin test or IGRAs. 65 (2·5%) of 2611 participants had raised alanine aminotransferase, but data were insufficient to calculate an HR. INTERPRETATION: Isoniazid preventive therapy with ART prevents tuberculosis across demographic and HIV-specific and tuberculosis-specific subgroups, which supports efforts to further increase use of isoniazid preventive therapy with ART broadly among people living with HIV. FUNDING: National Institutes of Health and National Institute of Allergy and Infectious Diseases.


Assuntos
Antibioticoprofilaxia , Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controle , Adulto , Antirretrovirais/administração & dosagem , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Contagem de Linfócito CD4 , Coinfecção , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Masculino , Resultado do Tratamento
10.
J Zoo Wildl Med ; 51(4): 1062-1066, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33480591

RESUMO

In 2015, an estimated 17-year-old female Bornean elephant (Elephas maximus borneensis) at Fukuyama Zoo in Japan exhibited anorexia and significant weight loss. Pan-susceptible Mycobacterium tuberculosis complex (MTBC) was isolated from vaginal discharge, oral mucus, urine, and fecal samples by culture. The isolate was identified as Mycobacterium caprae by genetic analysis. Isoniazid, pyrazinamide, and levofloxacin were administered rectally. Body weight increased to normal, but subsequently decreased again. Elevation of liver enzymes occurred, likely related to the increase in isoniazid dosage. After recovery from side effects, the elephant's weight increased further. However, isoniazid-resistant M. caprae was isolated from oral mucus after anti-tuberculosis drug treatment for 9 mo. The regimen was changed to rifampicin, pyrazinamide, ethambutol, and levofloxacin, administered orally or rectally. The 18-mo treatment was completed in October 2018. This elephant has shown no clinical sign since. No MTBC-positive sample had been obtained as of March 2020.


Assuntos
Isoniazida/uso terapêutico , Levofloxacino/uso terapêutico , Infecções por Mycobacterium/veterinária , Mycobacterium/isolamento & purificação , Pirazinamida/uso terapêutico , Administração Retal , Animais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Proteínas de Bactérias , Elefantes , Isoniazida/administração & dosagem , Japão/epidemiologia , Levofloxacino/administração & dosagem , Mycobacterium/efeitos dos fármacos , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium/microbiologia , Pirazinamida/administração & dosagem
11.
Medicine (Baltimore) ; 99(52): e23853, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350777

RESUMO

INTRODUCTION: The association of human immunodeficiency virus (HIV) infection with Burkitt lymphoma is related to the presence of Epstein Barr virus infection and the impact of the HIV antigen on the expansion of B-polyclonal cells. In Southeast Europe, the association is rare, and recognizing this is important in the therapeutic decision to increase patient survival rate. The association of HIV with Burkitt lymphoma and tuberculosis is even more rarely described in the literature. PATIENT CONCERNS: We present the case of a 40-year-old patient who presented with a 3-week history of fever (max. 38.7 °C), painful axillary swelling on the right side, lumbar pain, gait disorders, headache, and night sweats. Clinical manifestations included marked weight loss (about 30 kg in the last 2 months before his admission). DIAGNOSIS: A LyCD4 count of 38/µL and a HIV1 viral load of 384,000/mm3, classified the patient into a C3 stage. A biopsy of the right axillary lymph node was performed for suspected ganglionic tuberculosis due to immunodeficiency. Histopathological examination confirmed the diagnosis of Burkitt lymphoma. Cultures on Löwenstein-Jensen medium from sputum harvested at first admission were positive for Mycobacterium tuberculosis. INTERVENTIONS: Highly active antiretroviral therapy, chemotherapeutic agents for Burkitt lymphoma, anti-tuberculous drug therapy, neurosurgical intervention of spinal cord decompression, and antibiotic therapy of the associated bacterial infection. OUTCOME: Burkitt lymphoma disseminated rapidly, with central nervous system, spinal cord, osteomuscular, adrenal, and spleen involvement. The evolution under treatment was unfavorable, with patient death occurring 6 months after diagnosis. CONCLUSIONS: The association of HIV infection with Burkitt lymphoma and tuberculosis is rare in the highly active antiretroviral therapy (HAART) era, posing prompt and multidisciplinary therapeutic management issues. Similar cases of HIV-TB and Burkitt lymphoma association have been described, but none of the other cases showed the involvement of the central nervous system or of the bilateral adrenal glands.


Assuntos
Antineoplásicos/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Antituberculosos/administração & dosagem , Encéfalo , Linfoma de Burkitt , Infecções por HIV , Medula Espinal , Tuberculose Pulmonar , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Linfoma de Burkitt/complicações , Linfoma de Burkitt/patologia , Linfoma de Burkitt/fisiopatologia , Linfoma de Burkitt/cirurgia , Contagem de Linfócito CD4/métodos , Deterioração Clínica , Descompressão Cirúrgica/métodos , Evolução Fatal , Infecções por HIV/sangue , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Procedimentos Neurocirúrgicos/métodos , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Medula Espinal/cirurgia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/fisiopatologia , Tuberculose Pulmonar/terapia , Carga Viral/métodos
12.
Medicine (Baltimore) ; 99(50): e23649, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327347

RESUMO

The objective is to investigate the time to initial sputum culture conversion (SCC) and its predictors among multidrug-resistant tuberculosis (MDR-TB) patients in Hangzhou, China.A retrospective cohort study was conducted among patients who initiated MDR-TB treatment from 2011 to 2015 in Hangzhou, China. Successful achievement of initial SCC was defined as 2 consecutive negative cultures taken at least 30 days apart after initiation of treatment of MDR-TB. Successful treatment outcomes included being cured and completing treatment, while poor treatment outcomes included treatment failure, loss to follow-up, and death. Time to initial SCC was analyzed using the Kaplan-Meier method, and Cox proportional hazards regression was used to identify predictors of SCC.Among 384 patients enrolled with MDR-TB, 359 (93.5%) successfully achieved initial SCC after a median of 85 days (interquartile range, 40-112 days). A higher rate of SCC was observed in participants with successful treatment outcomes than those with poor treatment outcomes (P<.01). Multivariate analysis showed that age 25 to 64 years (compared with age<25; adjusted odds ratio [AOR], 0.7; 95% confidence interval [CI], 0.5-0.9; P < .01), age ≥65 years (compared with age < 25; AOR, 0.5; 95% CI, 0.3-0.8; P < .01), and household registration in Hangzhou (compared with non-Hangzhou registration; AOR, 1.3; 95% CI, 1.0-1.5; P < .05) were found to be associated with SCC.Although high SCC and treatment success rates were observed among MDR-TB patients in Hangzhou, the prolonged duration to initial SCC underscores the importance of emphasizing measures for infection control. A new policy of shifting outpatient treatment to inpatient treatment in China may reduce the risk of transmission from patients in the time window prior to SCC.


Assuntos
Antituberculosos/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Escarro/citologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Antituberculosos/administração & dosagem , China , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Características de Residência , Estudos Retrospectivos , Fatores Sexuais , Fatores Socioeconômicos , Fatores de Tempo , Adulto Jovem
14.
Int J Nanomedicine ; 15: 7491-7507, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116484

RESUMO

Background: Tuberculosis (TB) is a leading cause of death amongst infectious diseases. The poor response to antitubercular agents necessitates the long-term use of high drug doses, resulting in low patient compliance, which is the main reason for chemotherapy failure and contributes to the development of multidrug-resistant TB. Patient non-compliance has been a major obstacle in the successful management of TB. The aim of this work was to develop and characterise rifapentine (RPT)-loaded PLGA-based nanoparticles (NPs) for reducing dosing frequency. Methods: RPT-loaded PLGA and PLGA-PEG NPs were prepared using premix membrane homogenisation combined with solvent evaporation method. The resulting NPs were characterised in terms of physicochemical characteristics, toxicity, cellular uptake and antitubercular activity. NPs were further evaluated for pharmacokinetic and biodistribution studies in mice. Results: The resulting NPs showed suitable and safe physicochemical characteristics and could be taken up by macrophages. RPT-loaded NPs were more effective against Mycobacterium tuberculosis than free RPT. In vivo studies revealed that NPs could improve pharmacokinetic parameters, particularly for RPT/PLGA-PEG NPs. Moreover, both formulations had no toxicity to the organs of mice and could reduce hepatotoxicity. Conclusion: The application of PLGA-based NPs as sustained-release delivery vehicles for RPT could prolong drug release, modify pharmacokinetics, increase antitubercular activity and diminish toxicity, thereby allowing low dosage and frequency.


Assuntos
Antituberculosos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Nanopartículas/administração & dosagem , Rifampina/análogos & derivados , Administração Oral , Animais , Antituberculosos/farmacocinética , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Hemólise/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química , Prostaglandinas A/química , Rifampina/administração & dosagem , Rifampina/farmacocinética , Distribuição Tecidual
15.
Medicine (Baltimore) ; 99(44): e22258, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126298

RESUMO

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


Assuntos
Antituberculosos/sangue , Ingestão de Alimentos , Jejum/sangue , Fatores de Tempo , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/tratamento farmacológico , Administração Oral , Adulto , Antituberculosos/administração & dosagem , China , Esquema de Medicação , Etambutol/administração & dosagem , Etambutol/sangue , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/sangue , Masculino , Pirazinamida/administração & dosagem , Pirazinamida/sangue , Rifampina/administração & dosagem , Rifampina/sangue , Resultado do Tratamento
16.
Int J Nanomedicine ; 15: 5901-5909, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884258

RESUMO

Background: Tuberculosis (TB) has always been recognized as one of the fatal infectious diseases, which is caused by Mycobacterium tuberculosis (M.tb). Isonicotinic acid hydrazide or isoniazid (INH) is one of the most commonly utilized drugs in the treatment of TB. Patients need to take 300 mg daily of INH for 6 months in combination with another anti-TB drug and tolerate several side effects of INH. On the other hand, the emergence of resistant strains of anti-TB antibiotics is one of the major problems in the treatment of this disease. So, antimicrobial drug delivery by nanofluids could improve the efficacy, and reduce the adverse effects of antimicrobial drugs. The purpose of this study was to perform a novel method to synthesize INH-conjugated multi-wall carbon nanotubes (MWCNTs) for more effective drug delivery, as well as, TB treatment. Methods: INH-conjugated functionalized MWCNTs were prepared, using a reflux system. The characterization of the obtained nano-drug was performed by the elemental analyses of total nitrogen, hydrogen, carbon and sulfur (CHNS), Raman spectroscopy, Fourier transform infrared (FTIR), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) methods. The nanofluid of nano-drug was prepared by the ultrasonic method, and the related antibacterial effect studies were carried out on the two strains of M.tb. Results: The antimicrobial effect of INH-conjugated MWCNTs was found to be much better at low concentrations than the pure drug in all of the strains. Conclusion: Since one of the main antimicrobial mechanisms of MWCNTs is through the destruction of the bacterial cell wall, in addition to its antimicrobial effects, it increased the drug delivery of INH at lower doses compared to drug alone. So, the nanofluid, containing INH-conjugated MWCNTs, had a better lethal effect on a variety of M.tb strains than that of the drug alone.


Assuntos
Antituberculosos/farmacologia , Isoniazida/administração & dosagem , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Nanoestruturas/química , Antituberculosos/administração & dosagem , Antituberculosos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Isoniazida/química , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanoestruturas/administração & dosagem , Nanotubos de Carbono/química , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Tuberculose/microbiologia
17.
PLoS Negl Trop Dis ; 14(8): e0007857, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866170

RESUMO

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is currently treated with a daily combination of rifampin and either injectable streptomycin or oral clarithromycin. An intermittent oral regimen would facilitate treatment supervision. We first evaluated the bactericidal activity of newer antimicrobials against M. ulcerans using a BU animal model. The imidazopyridine amine telacebec (Q203) exhibited high bactericidal activity whereas tedizolid (an oxazolidinone closely related to linezolid), selamectin and ivermectin (two avermectine compounds) and the benzothiazinone PBTZ169 were not active. Consequently, telacebec was evaluated for its bactericidal and sterilizing activities in combined intermittent regimens. Telacebec given twice a week in combination with a long-half-life compound, either rifapentine or bedaquiline, sterilized mouse footpads in 8 weeks, i.e. after a total of only 16 doses, and prevented relapse during a period of 20 weeks after the end of treatment. These results are very promising for future intermittent oral regimens which would greatly simplify BU treatment in the field.


Assuntos
Antituberculosos/administração & dosagem , Úlcera de Buruli/tratamento farmacológico , Imidazóis/administração & dosagem , Mycobacterium ulcerans/efeitos dos fármacos , Piperidinas/administração & dosagem , Piridinas/administração & dosagem , Animais , Antituberculosos/uso terapêutico , Úlcera de Buruli/microbiologia , Diarilquinolinas , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Imidazóis/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Oxazolidinonas , Piperidinas/uso terapêutico , Piridinas/uso terapêutico , Rifampina/análogos & derivados , Tetrazóis
18.
PLoS Comput Biol ; 16(8): e1008107, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32810158

RESUMO

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


Assuntos
Antituberculosos/uso terapêutico , Modelos Teóricos , Tuberculose Pulmonar/tratamento farmacológico , Antituberculosos/administração & dosagem , Antituberculosos/farmacocinética , Quimioterapia Combinada , Humanos , Adesão à Medicação
20.
PLoS One ; 15(8): e0235411, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822368

RESUMO

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


Assuntos
Tempo para o Tratamento/estatística & dados numéricos , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Comorbidade , Etiópia , Feminino , Hospitais Privados/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/estatística & dados numéricos , Tuberculose Pulmonar/epidemiologia
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