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1.
Expert Opin Drug Saf ; 19(1): 23-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31809218

RESUMO

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


Assuntos
Fármacos Anti-HIV/administração & dosagem , Antituberculosos/administração & dosagem , Animais , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Antituberculosos/efeitos adversos , Interações de Medicamentos , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose Latente/tratamento farmacológico , Tuberculose/tratamento farmacológico
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(11): 1409-1413, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31838813

RESUMO

Objective: To investigate the survival time of multidrug-resistant tuberculosis (MDR-TB) patients and the influential factors in Wuhan. Methods: The relevant information were collected from TB management information system, cause of death reporting system and medical records by trained doctors. The univariate and multivariate Cox proportional hazards model were applied to analyze the factors affecting survival time of patients. Results: A total of 552 patients with MDR-TB were included in the analysis. After the diagnosis of MDR-TB, the cumulative survival rates from the first year to the third year were 0.94, 0.88, and 0.80, respectively. The mortality density of MDR-TB patients was 6.52/100 person-years, and the median survival time was (89.52±1.85) months. Kaplan-Meier analysis showed that the cumulative survival rate of the standardized treatment group was significantly higher than that of the non-standardized treatment group (Log rank=101.070, P<0.001). Compared with the patients aged <30 years, the HR of the patients aged 30-years and ≥60 years were 2.987 (95%CI: 1.268-7.036), 4.957 (95%CI: 1.942-12.653). Compared with the patients with the education level of high school and above, the HR of the patients with education level of junior high school/primary school and below were 1.908 (95%CI: 1.152-3.160), 1.681(95%CI: 1.033-2.735). Compared with the patients without diabetes, the HR of the patients with diabetes was 1.961(95%CI: 1.347-2.854). Compared with the patients without other serious diseases, the HR of the patients with other serious diseases was 2.597 (95%CI: 1.820-3.706). Compared with the patients who had been treated less than one time, the HR of the patients having previous treatment with more than 2 times was 1.611 (95%CI: 1.077-2.409). Compared with patients receiving standard MDR regimen treatment, the HR of the patients receiving no standard MDR regimen treatment was 3.155 (95%CI: 2.132-4.670). Conclusions: The cumulative survival rate of MDR-TB patients without standard treatment was significantly lower than that of patients with standard treatment. Older age, low educational level, diabetes mellitus, other serious diseases, more than two times treatment in the past, and receiving no multi-drug resistance regimen treatment were the risk factors affecting the survival of MDR-TB patients.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Modelos de Riscos Proporcionais , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/mortalidade , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
3.
Rev Soc Bras Med Trop ; 53: e20190207, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31859946

RESUMO

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


Assuntos
Antituberculosos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Qualidade de Vida/psicologia , Tuberculose/tratamento farmacológico , Idoso , Antituberculosos/administração & dosagem , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Inquéritos e Questionários , Centros de Atenção Terciária , Tuberculose/psicologia
4.
Praxis (Bern 1994) ; 108(15): 1019-1026, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31771497

RESUMO

CME: Extrapulmonary Tuberculosis Abstract. While tuberculosis mostly manifests as pulmonary infection, a dissemination in any extrapulmonary organ is possible. Extrapulmonary tuberculosis mostly affects lymph nodes, pleura and bones. Patients with immunosuppressive conditions such as an HIV co-infection or immunosuppressive therapies like TNF-alpha-inhibitors have a higher risk of a dissemination of tuberculosis. Diagnosis of extrapulmonary tuberculosis is difficult, as microbiological testing mostly requires invasive procedures to obtain a sample for direct proof of tuberculosis by microscopy, culture, molecular methods (e.g. Xpert® MTB/RIF) or histology. Treatment follows guidelines of pulmonary tuberculosis with a two-month regimen consisting of four drugs (rifampicin, isoniazide, pyrazinamide and ethambuthol), followed by a four-month therapy with two drugs (rifampicin and isoniazide). Duration of therapy is extended in tuberculous meningitis to one year and in a skeletal dissemination up to six to nine months. Corticosteroids are recommended in cerebral and pericardial tuberculosis.


Assuntos
Antibióticos Antituberculose , Mycobacterium tuberculosis , Tuberculose , Antibióticos Antituberculose/uso terapêutico , Humanos , Rifampina , Sensibilidade e Especificidade , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico
5.
Pan Afr Med J ; 33: 326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692828

RESUMO

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


Assuntos
Antituberculosos/administração & dosagem , Infecções por HIV/epidemiologia , Estado Nutricional , Tuberculose/epidemiologia , Criança , Pré-Escolar , Coinfecção , Estudos Transversais , República Democrática do Congo/epidemiologia , Terapia Diretamente Observada , Feminino , Infecções por HIV/mortalidade , Humanos , Masculino , Prevalência , Fatores de Risco , Tuberculose/tratamento farmacológico , Tuberculose/mortalidade
6.
BMC Infect Dis ; 19(1): 852, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615537

RESUMO

BACKGROUND: The dual challenge of low diagnostic sensitivity of microscopy test and technical challenge of performing a TB culture test poses a problem for case detection and initiation of Tuberculosis (TB) second-line treatment. There is thus need for a rapid, reliable and easily accessible assay. This comparative analysis was performed to assess diagnostic performance characteristics of GeneXpert MTB/RIF and Line Probe Assay (LPA). METHODS: Three hundred twenty nine sputum samples of patients across the 47 counties in Kenya suspected to have drug resistant TB were picked and subjected to GeneXpert, LPA and Culture MGIT at the National TB Reference Laboratory. Sensitivity, specificity and predictive values were then determined to assess the performance characteristics of the various assays. RESULTS: Against culture MGIT as the gold standard for TB diagnosis, GeneXpert had a sensitivity, specificity, positive predictive value, and negative predictive value of 78.5, 64.9, 59.4 and 82.2% respectively while LPA had 98.4, 66.0, 65.4 and 98.4%. For diagnosis of rifampicin mono-resistance GeneXpert had a moderate agreement (Kappa 0.59, P < 0.01) (sensitivity 62.50%, specificity 96.50%) while LPA that had almost perfect agreement (Kappa = 0.89, p < 0.01) with a (sensitivity 90.0% and specificity 99.1%). CONCLUSION: LPA has a better performance characteristic to GeneXpert and an alternative to culture with regards to detection of RIF's mono-resistance.


Assuntos
Farmacorresistência Bacteriana/genética , Mycobacterium tuberculosis/genética , Rifampina/uso terapêutico , Tuberculose/diagnóstico , Proteínas de Bactérias/genética , Feminino , Humanos , Quênia , Masculino , Reação em Cadeia da Polimerase Multiplex/métodos , Mycobacterium tuberculosis/isolamento & purificação , Hibridização de Ácido Nucleico/métodos , Oxirredutases/genética , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose/tratamento farmacológico
7.
Internist (Berl) ; 60(11): 1155-1175, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31641790

RESUMO

Tuberculosis is a bacterial infectious disease that is usually transmitted by inhalation of droplets containing the bacteria. The World Health Organization (WHO) estimates that approximately 10 million patients were newly diagnosed with tuberculosis in 2017. Rapid diagnosis relies on a combination of imaging and microbiological, molecular, and, rarely, immunological tests. Genotypic methods enable early diagnosis and allow highly accurate prediction of drug resistance. Phenotypic (culture-based) methods are the diagnostic gold standard. Standard management of patients with pan drug-susceptible pulmonary tuberculosis includes a combination of rifampicin, isoniazid, ethambutol and pyrazinamide for 2 months followed by rifampicin and isoniazid for additional 4 months, which leads to cure rates of >80%. With individualized treatment schemes, similar cure rates can be achieved for patients with multidrug-resistant tuberculosis.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Etambutol/uso terapêutico , Humanos , Isoniazida/uso terapêutico , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
8.
Pharm Res ; 36(12): 166, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31650321

RESUMO

The discovery of drugs to treat tuberculosis (TB) was a major medical milestone in the twentieth century. However, from the outset, drug resistance was observed. Currently, of the 10 million people that exhibit TB symptoms each year, 450,000 have multidrug or extensively drug resistant (MDR or XDR) TB. While greater understanding of the host and pathogen (Mycobacterium tuberculosis, Mtb) coupled with scientific ingenuity will lead to new drugs and vaccines, in the meantime 4000 people die daily from TB. Thus, efforts to improve existing TB drugs should also be prioritized. Improved efficacy and decreased dose and associated toxicity of existing drugs would translate to greater compliance, life expectancy and quality of life of Mtb infected individuals. One potential strategy to improve existing drugs is to deliver them by inhalation as aerosols to the lung, the primary site of Mtb infection. Inhaled drugs are used for other pulmonary diseases, but they have yet to be utilized for TB. Inhaled therapies for TB represent an untapped opportunity that the pharmaceutical, clinical and regulatory communities should consider.


Assuntos
Antituberculosos/administração & dosagem , Tuberculose/tratamento farmacológico , Administração por Inalação , Aerossóis/química , Antituberculosos/efeitos adversos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Resistência a Múltiplos Medicamentos , Humanos , Pulmão , Mycobacterium tuberculosis/efeitos dos fármacos , Nebulizadores e Vaporizadores
9.
BMC Infect Dis ; 19(1): 859, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623569

RESUMO

BACKGROUND: Tuberculosis (TB) remains one of the infectious diseases with a leading cause of death among adults worldwide. Metformin, a first-line medication for the treatment of type 2 diabetes, may have potential for treating TB. The aims of the present systematic review were to evaluate the impact of metformin prescription on the risk of tuberculosis diseases, the risk of latent TB infection (LTBI) and treatment outcomes of tuberculosis among patients with diabetic mellitus. METHODS: Databases were searched through March 2019. Observational studies reporting the effect of metformin prescription on the risk and treatment outcomes of TB were included in the systematic review. We qualitatively analyzed results of included studies, and then pooled estimate effects with 95% confidence intervals (CIs) of different outcome using random-effect meta-analyses. RESULTS: This systematic review included 6980 cases from 12 observational studies. The meta-analysis suggested that metformin prescription could decrease the risk of TB among diabetics (pooled odds ratio [OR], 0.38; 95%CI, 0.21 to 0.66). Metformin prescription was not related to a lower risk of LTBI (OR, 0.73; 95%CI, 0.30 to 1.79) in patients with diabetes. Metformin medication during the anti-tuberculosis treatment is significantly associated with a smaller TB mortality (OR, 0.47; 95%CI, 0.27 to 0.83), and a higher probability of sputum culture conversion at 2 months of TB disease (OR, 2.72; 95%CI, 1.11 to 6.69) among patients with diabetes. The relapse of TB was not statistically reduced by metformin prescription (OR, 0.55; 95%CI, 0.04 to 8.25) in diabetics. CONCLUSIONS: According to current observational evidence, metformin prescription significantly reduced the risk of TB in patients with diabetes mellitus. Treatment outcomes of TB disease could also be improved by the metformin medication among diabetics.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Tuberculose/patologia , Antituberculosos/uso terapêutico , Humanos , Razão de Chances , Fatores de Risco , Escarro/microbiologia , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/mortalidade
10.
EMBO J ; 38(22): e101876, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31583725

RESUMO

Clonal microbial populations are inherently heterogeneous, and this diversification is often considered as an adaptation strategy. In clinical infections, phenotypic diversity is found to be associated with drug tolerance, which in turn could evolve into genetic resistance. Mycobacterium tuberculosis, which ranks among the top ten causes of mortality with high incidence of drug-resistant infections, exhibits considerable phenotypic diversity. In this study, we quantitatively analyze the cellular dynamics of DNA damage responses in mycobacteria using microfluidics and live-cell fluorescence imaging. We show that individual cells growing under optimal conditions experience sporadic DNA-damaging events manifested by RecA expression pulses. Single-cell responses to these events occur as transient pulses of fluorescence expression, which are dependent on the gene-network structure but are triggered by extrinsic signals. We demonstrate that preexisting subpopulations, with discrete levels of DNA damage response, are associated with differential susceptibility to fluoroquinolones. Our findings reveal that the extent of DNA integrity prior to drug exposure impacts the drug activity against mycobacteria, with conceivable therapeutic implications.


Assuntos
Proteínas de Bactérias/metabolismo , Ciprofloxacino/farmacologia , Dano ao DNA/genética , Mycobacterium tuberculosis/genética , Análise de Célula Única , Estresse Fisiológico , Tuberculose/patologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Dano ao DNA/efeitos dos fármacos , Humanos , Microfluídica , Mycobacterium tuberculosis/efeitos dos fármacos , Recombinases Rec A/genética , Recombinases Rec A/metabolismo , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
11.
BMC Infect Dis ; 19(1): 839, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606032

RESUMO

BACKGROUND: Household contact tracing of index TB cases has been advocated as a key part of TB control for many years, but has not been widely implemented in many low-resource setting because of the current dearth of high quality evidence for effectiveness. Innovative strategies for earlier, more effective treatment are particularly important in contexts with hyper-endemic levels of HIV, where levels of TB infection remain extremely high. METHODS: We present the design of a household cluster-randomised controlled trial of interventions aimed at improving TB-free survival and reducing childhood prevalence of Mycobacterium tuberculosis infection among household contacts of index TB cases diagnosed in two provinces of South Africa. Households of index TB cases will be randomly allocated in a 1:1 ratio to receive either an intensified home screening and linkage for TB and HIV intervention, or enhanced standard of care. The primary outcome will compare between groups the TB-free survival of household contacts over 15 months. All participants, or their next-of-kin, will provide written informed consent to participate. DISCUSSION: Evidence from randomised trials is required to identify cost-effective approaches to TB case-finding that can be applied at scale in sub-Saharan Africa. TRIAL REGISTRATION: ISRCTN16006202 (01/02/2017: retrospectively registered) and NHREC4399 (11/04/2016: prospectively registered). Protocol version: 4.0 (date: 18th January 2018).


Assuntos
Busca de Comunicante/métodos , Tuberculose/prevenção & controle , Adulto , Criança , Análise Custo-Benefício , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Estudos Retrospectivos , Risco , África do Sul/epidemiologia , Padrão de Cuidado , Resultado do Tratamento , Teste Tuberculínico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Carga Viral
12.
Medicine (Baltimore) ; 98(41): e17523, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593125

RESUMO

Therapeutic drug monitoring has been employed in anti-tuberculosis (TB) drugs to assess optimal dose for maximum therapeutic effects and minimal toxicity. But the determinants of serum concentration need further evidences.In a retrospective case-control study, clinical and laboratory data were collected from 717 in-patients with TB at Xi'an Chest Hospital, China. Two hours serum concentrations of isoniazid, rifampicin, pyrazinamide as well as ethambutol were obtained and analyzed by liquid chromatography-tandem mass spectrometry.The month 2 culture conversion group had lower concentration of isoniazid, pyrazinamide, and ethambutol than month 1 group. Statistical analysis showed that serum concentrations of isoniazid, rifampicin, pyrazinamide, and ethambutol revealed a positive relationship with dose (mg/kg) (P < .001, P < .001, P < .001, and P = .003, respectively). Furthermore, isoniazid concentration was related to smoking (P = .009) and prior TB (P = .011), while rifampicin and pyrazinamide concentrations were correlated to sex (P = .004 and 0.025, respectively). Ethambutol concentration was associated with creatinine clearance (Ccr, P = .002).It is necessary to optimize drug doses using therapeutic drug monitoring while considering the following determinants: weight, smoking status, prior TB, sex, and Ccr. Furthermore, low 2 hours serum concentrations can be associated with longer culture conversion.


Assuntos
Etambutol/sangue , Isoniazida/sangue , Pirazinamida/sangue , Rifampina/sangue , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/sangue , Antituberculosos/metabolismo , Antituberculosos/uso terapêutico , Estudos de Casos e Controles , China/epidemiologia , Cromatografia Líquida/instrumentação , Creatinina/metabolismo , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Etambutol/metabolismo , Etambutol/uso terapêutico , Feminino , Humanos , Isoniazida/metabolismo , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pirazinamida/metabolismo , Pirazinamida/uso terapêutico , Estudos Retrospectivos , Rifampina/metabolismo , Rifampina/uso terapêutico , Fatores Sexuais , Fumar/efeitos adversos , Tuberculose/sangue , Adulto Jovem
13.
Eur J Med Chem ; 183: 111713, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31557610

RESUMO

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become the world's leading killer disease due to a single infectious agent which survives in the host macrophage for the indefinite period. Hence, it is necessary to enhance the efficacy of the clinically existing antitubercular agents or to discover new anti antitubercular agents. Here, we report the synthesis, characterization and antimycobacterial evaluation of protein-drug conjugates. A carrier protein, Transferrin (Tf) was covalently conjugated to isoniazid (INH) utilizing hydrazone and amide linkers. The purity of the reactions was confirmed by SDS-PAGE while conjugation was confirmed by UV-visible spectrophotometry, MALDI-TOF analysis, and FTIR spectrophotometry. The in vitro antitubercular assay result showed that the inhibitory activity of the parent drug was conserved in both the conjugates. The conjugates were effective against intracellular Mtb H37Rv and were devoid of cytotoxic effect at therapeutic concentration.


Assuntos
Antituberculosos , Isoniazida , Mycobacterium tuberculosis/efeitos dos fármacos , Transferrina , Tuberculose/tratamento farmacológico , Antituberculosos/síntese química , Antituberculosos/farmacologia , Estabilidade de Medicamentos , Humanos , Isoniazida/síntese química , Isoniazida/química , Isoniazida/farmacologia , Testes de Sensibilidade Microbiana , Transferrina/química , Tuberculose/microbiologia
14.
Int J Mycobacteriol ; 8(3): 244-251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31512600

RESUMO

Background: Tuberculosis (TB) with human immunodeficiency virus (HIV) coinfection is the highest clinical epidemiology and public health issue. Despite many programs established to tackle the epidemic, TB target controls have not been reached. One of the many factors attributed to the failure in TB treatment is HIV coinfection. The aim of this study is to assess the survival rate of HIV infection among TB patients and the risk factors of death among the TB patients with HIV coinfection during the retro of directly observed treatment, short-course (DOTS) program. Methods: This study is a retrospective cohort conducted to compare the survivorship between TB/HIV patients for 8 months DOTS. Death among TB patients was considered as failures and those defaulted or survived were censored. The Cox proportional-hazards regression and log-linear model were used to establish the hazard ratio (HR) of death for each variable at baseline and estimate the risk factors effect among TB patients. Results: The findings revealed that 50% of death from TB/HIV patients were from HIV coinfection (advanced HR = 2.01, 95% confidence interval = 1.13-3.17). The risk of death was significantly higher in HIV-positive TB patients (P = 0.000) during the extension care phase. TB/HIV-positive patients on antiretroviral therapy have decreased survival rate (log-rank test = 14.88, df = 2, P = 0.0001). The probability of TB patients surviving is significantly decreased in HIV positive with some factors such as age, weight, smoking, and alcohol found significant. Conclusion: The probability of survival in HIV-positive TB patients was significantly lower during the TB treatment. Weight loss, age, alcohol, smoking, and pregnancy were showed to affect the survival probability of TB/HIV patients' coinfection significantly.


Assuntos
Antituberculosos/uso terapêutico , Coinfecção/mortalidade , Infecções por HIV/microbiologia , Tuberculose/tratamento farmacológico , Contagem de Linfócito CD4 , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Humanos , Masculino , Gravidez , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , África do Sul , Taxa de Sobrevida , Resultado do Tratamento , Tuberculose/complicações , Tuberculose/mortalidade
15.
Int J Mycobacteriol ; 8(3): 262-266, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31512602

RESUMO

Background: Childhood tuberculosis (TB) is a major health problem worldwide, especially in developing countries. In 2015, there are estimated 950,000 cases of childhood TB. Since most TB in children is paucibacillary, this gives rise not only to problem in diagnosing but also in monitoring the response to anti-TB treatment as well. Soluble urokinase-type plasminogen activator receptor (suPAR), a glycosylphosphatidylinositol-linked membrane protein of various cells of immune system, is one of the potential biomarkers to be used in the management of TB. The objective of this study is to study the decrease of serum suPAR level after anti-TB treatment in children with TB and its association with patient characteristics. Methods: We conducted a prospective study on children suspected of having TB due to a history of contact with active TB case and symptoms such as coughing, fever, and enlarged lymph nodes. The diagnosis of TB is established by history, physical examination including anthropometric examination. Tuberculin skin test using PPD RT-23 and interferon-gamma releasing assay with Quantiferon TB-Gold Plus was performed. Chest X-rays were read by two independent radiologists. Microbiological examination was performed using microscopic examination and Xpert MTB/RIF. The level of suPAR before and after anti-TB treatment was examined with the Elisa method. Results: There was no significant difference of serum suPAR levels before and after anti-TB treatment (mean 0.71 [standard deviation 0.585] ng/mL; P = 0.072). There was no association between ages (P = 0.112), nutritional status (P = 0.228), diagnosis of pulmonary or extrapulmonary TB (P = 0.956), and radiological feature (P = 0.810) with serum suPAR levels decrease. Conclusion: There is no suPAR serum level decrease 2 months after treatment with anti-TB and there is no association with age, nutritional status, pulmonary or extrapulmonary TB diagnosis, and radiological feature.


Assuntos
Antituberculosos/uso terapêutico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Tuberculose/tratamento farmacológico , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Tuberculose/sangue , Tuberculose/diagnóstico
16.
Int J Mycobacteriol ; 8(3): 298-301, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31512609

RESUMO

We report a case of idiopathic pulmonary fibrosis (IPF) treated with pirfenidone who developed tuberculosis (TB) and later had exfoliative dermatitis secondary to an interaction between pirfenidone and rifampicin. This case report highlights the possible risk of developing TB in patients diagnosed with IPF and on antifibrotic therapy like pirfenidone. Furthermore, this case report documents a previously unreported adverse reaction due to the interaction of rifampicin with pirfenidone.


Assuntos
Eritema/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Piridonas/efeitos adversos , Rifampina/efeitos adversos , Tuberculose/tratamento farmacológico , Tuberculose/etiologia , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Antibióticos Antituberculose/efeitos adversos , Interações de Medicamentos , Humanos , Fibrose Pulmonar Idiopática/complicações , Índia , Masculino , Piridonas/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Expert Rev Med Devices ; 16(10): 863-875, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31550943

RESUMO

Introduction: Tuberculosis (TB) remains one of the most alarming worldwide infectious diseases primarily in low-income countries, where the infection shows a higher and unvaried prevalence. In the last years, the emergence and spread of Mycobacterium tuberculosis (Mtb) strains resistant to first-line anti-TB drugs are the cause of major concern and prompted the implementation of new treatments, including the development of new drugs and the repurposing of old ones. Areas covered: In this review, we discuss solutions against TB based on nanomaterials (NMTs), alone or combined with current anti-TB drugs. We will summarize drug delivery platforms tested in in vivo or in vitro models and their activity against mycobacteria. We will describe how the new nanotechnologies based on carbon nanomaterials, like carbon nanotubes and graphene oxide are now facing the panorama of the medical fight against TB. Expert opinion: We foresee that in the next decade carbon nanomaterials will be at the forefront in fighting emerging antibiotic-resistant Mtb strains by shortening treatment periods, reducing adverse effects and mitigating antibiotic use. However, toxicity and biodegradation studies should be done prior to the clinical translation of carbon nanomaterials.


Assuntos
Grafite/uso terapêutico , Nanotubos de Carbono/química , Tuberculose/terapia , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Sistemas de Liberação de Medicamentos , Grafite/química , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
18.
Pan Afr Med J ; 33: 111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489089

RESUMO

Introduction: High mortality among individuals receiving retreatment for tuberculosis (RT-TB) persists, although reasons for these poor outcomes remain unclear. Methods: We retrospectively reviewed 394 RT-TB patients diagnosed between January 2010 and June 2016 in Accra, Ghana. Results: Of RT-TB patients, 161 (40.9%) were treated empirically (negative/absent smear, culture or Xpert), of whom 30.4% (49/161) had only extrapulmonary TB signs or symptoms. Mortality during treatment was 19.4%; 15-day mortality was 10.8%. In multivariable proportional hazards regression, living with HIV (aHR=2.69 [95 CI: 1.51, 4.80], p<0.01) and previous loss-to-follow up (aHR=8.27 (95 CI: 1.10, 62.25), p=0.04) were associated with mortality, while drug susceptibility testing (DST, aHR=0.36 (95 CI: 0.13, 1.01), p=0.052) was protective. Isoniazid resistance was observed in 40% (23/58 tested) and rifampin resistance in 19.1% (12/63 tested). Conclusion: High rates of extrapulmonary TB and smear/culture negative disease highlight the barriers to achieving DST-driven RT-TB regimens and the need for improved diagnostics. Our finding of poly-drug resistance in rifampin-susceptible cases supports access to comprehensive first line DST. Additionally, interventions to reduce mortality, especially in HIV co-infected RT-TB patients, are urgently needed.


Assuntos
Antituberculosos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose/tratamento farmacológico , Adulto , Antituberculosos/farmacologia , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Feminino , Gana , Infecções por HIV/epidemiologia , Humanos , Isoniazida/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Retratamento , Estudos Retrospectivos , Rifampina/farmacologia , Tuberculose/microbiologia , Tuberculose/mortalidade , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade
19.
Pan Afr Med J ; 33: 120, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31489098

RESUMO

Introduction: This study aimed to describe the epidemiological, clinical and evolutionary profile of patients treated for tuberculosis at the Regional Hospital of Maradi. Methods: We conducted a retrospective, descriptive and analytical study of data from the medical records of patients treated for tuberculosis from 1st January 2015 to 31st December 2017. Results: A total of 595 patients were followed (406 men, 68.24%, and 189 women, 31.76%) with a prevalence of 27,71%. The average age of patients was 42.3 ranging from 13 months to 85 years; 70.5% of these patients were from urban areas. Merchants represented 36.9% of the cases. Bacterial test was positive in 64.7% of cases. Functional signs included: coughing (99.5%), fever (79.5%), and chest pain. Pulmonary tuberculosis represented 78.7% of cases. Therapy was effective in 81.28% of cases. HIV prevalence was 13.6%, lethality 10.42% (40.4% of patients died from TB/HIV co-infection). Conclusion: Tuberculosis is a scourge in low-income countries, with 10.42% of deaths. HIV/AIDS infection has negatively contributed to these deaths during the study period. The search for comorbidities in any patient with tuberculosis should be systematic in order to improve their global management.


Assuntos
Antituberculosos/administração & dosagem , Infecções por HIV/epidemiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Coinfecção/epidemiologia , Feminino , Hospitais , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Níger/epidemiologia , Prevalência , Estudos Retrospectivos , Tuberculose/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto Jovem
20.
BMC Infect Dis ; 19(1): 794, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500572

RESUMO

BACKGROUND: Regimens that could treat both rifampin-resistant (RR) and rifampin-susceptible tuberculosis (TB) while shortening the treatment duration have reached late-stage clinical trials. Decisions about whether and how to implement such regimens will require an understanding of their likely clinical impact and how this impact depends on local epidemiology and implementation strategy. METHODS: A Markov state-transition model of 100,000 representative South African adults with TB was used to simulate implementation of the regimen BPaMZ (bedaquiline, pretomanid, moxifloxacin, and pyrazinamide), either for RR-TB only or universally for all patients. Patient outcomes, including cure rates, time with active TB, and time on treatment, were compared to outcomes under current care. Sensitivity analyses varied the drug-resistance epidemiology, rifampin susceptibility testing practices, and regimen efficacy. RESULTS: Using BPaMZ exclusively for RR-TB increased the proportion of all RR-TB that was cured by initial treatment from 60 ± 1% to 67 ± 1%. Expanding use of BPaMZ to all patients increased cure of RR-TB to 89 ± 1% and cure of all TB from 87.3 ± 0.1% to 89.5 ± 0.1%, while shortening treatment by 1.9 months/person. In sensitivity analyses, reducing the coverage of rifampin susceptibility testing resulted in lower projected proportions of patients cured under all regimen scenarios (current care, RR-only BPaMZ, and universal BPaMZ), compared to the proportions projected using South Africa's high coverage; however, this reduced coverage resulted in greater expected incremental benefits of universal BPaMZ implementation, both when compared to RR-only BPaMZ implementation and when compared to to current care under the same low rifampin susceptibility testing coverage. In settings with higher RR-TB prevalence, the benefits of BPaMZ were magnified both for RR-specific and universal BPaMZ implementation. CONCLUSIONS: Novel regimens such as BPaMZ could improve RR-TB outcomes and shorten treatment for all patients, particularly with universal use. Decision-makers weighing early options for implementing such regimens at scale will want to consider the expected impact on patient outcomes and on the burden of treatment in their local context.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose/tratamento farmacológico , Adulto , Diarilquinolinas/uso terapêutico , Humanos , Cadeias de Markov , Nitroimidazóis/uso terapêutico , Prevalência , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , África do Sul/epidemiologia , Resultado do Tratamento , Tuberculose/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
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