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1.
PLoS Negl Trop Dis ; 18(2): e0011968, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38359088

RESUMO

BACKGROUND: Patients with recurrent TB have an increased risk of higher mortality, lower success rate, and a relatively feeble likelihood of treatment completion than those with new-onset TB. This study aimed to assess the epidemiology of recurrent TB in Tanzania; specifically, we aim to determine the prevalence of TB recurrence and factors associated with unfavourable treatment outcomes among patients with recurrent TB in Tanzania from 2018 to 2021. METHODS: In this cross-sectional study, we utilized Tanzania's routinely collected national TB program data. The study involved a cohort of TB patients over a fixed treatment period registered in the TB and Leprosy case-based District Health Information System (DHIS2-ETL) database from 2018 to 2021 in Tanzania. We included patients' sociodemographic and clinical factors, facility characteristics, and TB treatment outcomes. We conducted bivariate analysis and multivariable multi-level mixed effects logistic regression of factors associated with TB recurrence and TB treatment outcomes to account for the correlations at the facility level. A purposeful selection method was used; the multivariable model included apriori selected variables (Age, Sex, and HIV status) and variables with a p-value <0.2 on bivariate analysis. The adjusted odds ratio and 95% confidence interval were recorded, and a p-value of less than 0.05 was considered statistically significant. FINDINGS: A total of 319,717 participants were included in the study; the majority were adults aged 25-49 (44.2%, n = 141,193) and above 50 years (31.6%, n = 101,039). About two-thirds were male (60.4%, n = 192,986), and more than one-fifth of participants (22.8%, n = 72,396) were HIV positive. Nearly two in every hundred TB patients had a recurrent TB episode (2.0%, n = 6,723). About 10% of patients with recurrent TB had unfavourable treatment outcomes (9.6%, n = 519). The odds of poor treatment outcomes were two-fold higher for participants receiving treatment at the central (aOR = 2.24; 95% CI 1.33-3.78) and coastal zones (aOR = 2.20; 95% CI 1.40-3.47) than the northern zone. HIV-positive participants had 62% extra odds of unfavourable treatment outcomes compared to their HIV-negative counterparts (aOR = 1.62; 95% CI 1.25-2.11). Bacteriological TB diagnosis (aOR = 1.39; 95% CI 1.02-1.90) was associated with a 39% additional risk of unfavourable treatment outcomes as compared to clinical TB diagnosis. Compared to community-based DOT, patients who received DOT at the facility had 1.39 times the odds of poor treatment outcomes (aOR = 1.39; 95%CI 1.04-1.85). CONCLUSION: TB recurrence in Tanzania accounts for 2% of all TB cases, and it is associated with poor treatment outcomes. Unfavourable treatment outcomes were recorded in 10% of patients with recurrent TB. Poor TB treatment outcome was associated with HIV-positive status, facility-based DOT, bacteriologically confirmed TB and receiving treatment at the hospital level, differing among regions. We recommend post-treatment follow-up for patients with recurrent TB, especially those coinfected with HIV. We also propose close follow-up for patients treated at the hospital facility level and strengthening primary health facilities in TB detection and management to facilitate early treatment initiation.


Assuntos
Infecções por HIV , Tuberculose , Adulto , Humanos , Masculino , Feminino , Antituberculosos/uso terapêutico , Tanzânia/epidemiologia , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose/complicações , Resultado do Tratamento , Estudos Retrospectivos
2.
Biomed Pharmacother ; 167: 115539, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37742606

RESUMO

Among different strategies to develop novel therapies, drug repositioning (aka repurposing) aims at identifying new uses of an already approved or investigational drug. This approach has the advantages of availability of the extensive pre-existing knowledge of the drug's safety, pharmacology and toxicology, manufacturing and formulation. It provides advantages to the risk-versus-rewards trade-off as compared to the costly and time-consuming de novo drug discovery process. Clofazimine, a red-colored synthetic derivative of riminophenazines initially isolated from lichens, was first synthesized in the 1950 s, and passed through several phases of repositioning in its history as a drug. Being initially developed as an anti-tuberculosis treatment, it was repurposed for the treatment of leprosy, prior to re-repositioning for the treatment of multidrug-resistant tuberculosis and other infections. Since 1990 s, reports on the anticancer properties of clofazimine, both in vitro and in vivo, started to appear. Among the diverse mechanisms of action proposed, the activity of clofazimine as a specific inhibitor of the oncogenic Wnt signaling pathway has recently emerged as the promising targeting mechanism of the drug against breast, colon, liver, and other forms of cancer. Seventy years after the initial discovery, clofazimine's journey as a drug finding new applications continues, serving as a colorful illustration of drug repurposing in modern pharmacology.


Assuntos
Clofazimina , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Clofazimina/farmacologia , Clofazimina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Descoberta de Drogas , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico
3.
Trop Med Int Health ; 28(5): 357-366, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36864011

RESUMO

OBJECTIVE: In 2018, shorter treatment regimens (STR) for people with drug-resistant tuberculosis (DR-TB) were introduced in Tanzania and included kanamycin, high-dose moxifloxacin, prothionamide, high-dose isoniazid, clofazimine, ethambutol and pyrazinamide. We describe treatment outcomes of people diagnosed with DR-TB in a cohort initiating treatment in 2018 in Tanzania. METHODS: This was a retrospective cohort study conducted at the National Centre of Excellence and decentralised DR-TB treatment sites for the 2018 cohort followed from January 2018 to August 2020. We reviewed data from the National Tuberculosis and Leprosy Program DR-TB database to assess clinical and demographic information. The association between different DR-TB regimens and treatment outcome was assessed using logistic regression analysis. Treatment outcomes were described as treatment complete, cure, death, failure or lost to follow-up. A successful treatment outcome was assigned when the patient achieved treatment completion or cure. RESULTS: A total of 449 people were diagnosed with DR-TB of whom 382 had final treatment outcomes: 268 (70%) cured; 36 (9%) treatment completed; 16 (4%) lost to follow-up; 62 (16%) died. There was no treatment failure. The treatment success rate was 79% (304 patients). The 2018 DR-TB treatment cohort was initiated on the following regimens: 140 (46%) received STR, 90 (30%) received the standard longer regimen (SLR), 74 (24%) received a new drug regimen. Normal nutritional status at baseline [adjusted odds ratio (aOR) = 6.57, 95% CI (3.33-12.94), p < 0.001] and the STR [aOR = 2.67, 95% CI (1.38-5.18), p = 0.004] were independently associated with successful DR-TB treatment outcome. CONCLUSION: The majority of DR-TB patients on STR in Tanzania achieved a better treatment outcome than on SLR. The acceptance and implementation of STR at decentralised sites promises greater treatment success. Assessing and improving nutritional status at baseline and introducing new shorter DR-TB treatment regimens may strengthen favourable treatment outcomes.


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/uso terapêutico , Estudos Retrospectivos , Tanzânia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Resultado do Tratamento
4.
Front Cell Infect Microbiol ; 12: 997283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325467

RESUMO

Tuberculosis (TB) is among the most difficult infections to treat, requiring several months of multidrug therapy to produce a durable cure. The reasons necessitating long treatment times are complex and multifactorial. However, one major difficulty of treating TB is the resistance of the infecting bacterium, Mycobacterium tuberculosis (Mtb), to many distinct classes of antimicrobials. This review will focus on the major gaps in our understanding of intrinsic drug resistance in Mtb and how functional and chemical-genetics can help close those gaps. A better understanding of intrinsic drug resistance will help lay the foundation for strategies to disarm and circumvent these mechanisms to develop more potent antitubercular therapies.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , Mycobacterium tuberculosis/genética , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Resistência a Medicamentos
5.
Afr Health Sci ; 22(2): 169-177, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36407334

RESUMO

Introduction: The objective of this study is to observe the trend in treatment outcomes and identify determinants of treatment success among patients recruited into care through the DOTS strategy. Methodology: A retrospective record review of tuberculosis patients (2012-2016) was carried out at the Tuberculosis and Leprosy Referral Centre, Eku, Delta State, Nigeria. Results: Records of four hundred and twenty five (425) tuberculosis patients under DOTS were reviewed over five years. The highest number of cases under treatment, 102 (24.0%), was recorded in 2013. The mean age (SD) of patients was 37.3 (±16.5) years, majority of the patients were male (62.4%) and 18% had TB/HIV co-infection. Treatment outcomes of patients were cured (53.4%), completed (27.8%), died (6.8%), failed (2.4%), lost to follow up (4.9%), transferred out (1.2%) and not evaluated (3.5%). Over all, treatment success rate was 81.2% with a trend of 88.7% (2012), 87.3% (2013), 85.9% (2014), 65.0% (2015) and 65.8% (2016) respectively. Patient characteristics were not associated with treatment success. Conclusion: The treatment success rate was high and in line with the national recommendation of 80% and above. The trend showed a reduction in number of new cases enrolled into the DOTS programme, reduction in success rate with a concomitant increase in loss to follow up. There was no association between patient characteristics and TB treatment success. System strengthening on patient follow up, community health education and treatment adherence is recommended.


Assuntos
Infecções por HIV , Tuberculose , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Terapia Diretamente Observada , Antituberculosos/uso terapêutico , Estudos Retrospectivos , Nigéria/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Resultado do Tratamento , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Encaminhamento e Consulta
6.
Tuberculosis (Edinb) ; 136: 102247, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35977438

RESUMO

Non-tuberculous mycobacteria are a heterogeneous group of environmental bacteria and other than the well-known Mycobacterium tuberculosis complex and Mycobacterium leprae. They could cause localized or disseminated infections. Mycobacterium chelonae and Mycobacterium fortuitum are among the most clinically relevant non-tuberculous mycobacteria species. The infections treatment is complex since they are resistant to antituberculosis drugs and the biofilm formation makes them impermeable to several antibiotics. Antimicrobial photodynamic therapy (aPDT) constitutes an alternative to eliminate pathogens, principally those antimicrobials resistant. Among explored photosensitizers, phthalocyanines are considered excellent, but with a disadvantage: a lack solubility in aqueous media. Consequently, several nanocarriers have been studied in the last years. In this work, a Zn-phthalocyanine into liposomes was evaluated to photoinactivate M. fortuitum and M. chelonae. The results show a higher photodynamic activity of ZnPc into liposomes respect to solution. Furthermore, M. fortuitum was more sensible to aPDT than M. chelonae.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium chelonae , Mycobacterium tuberculosis , Antituberculosos/uso terapêutico , Humanos , Isoindóis , Lipossomos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Compostos Organometálicos , Fármacos Fotossensibilizantes/farmacologia , Compostos de Zinco
7.
BMJ Open ; 12(5): e054434, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35613774

RESUMO

INTRODUCTION: Tanzania is adapting a shortened injectable-free multidrug resistant tuberculosis (MDR-TB) regimen, comprising new drugs such as bedaquiline and delamanid and repurposed drugs such as clofazimine and linezolid. The regimen is implemented using a pragmatic prospective cohort study within the National TB and Leprosy Programme and is accompanied by a process evaluation. The process evaluation aims to unpack the implementation processes, their outcomes and the moderating factors in order to understand the clinical effectiveness of the regimen. This protocol describes the methods employed in understanding the implementation processes of the new MDR-TB regimen in 15 regions of Tanzania. METHODS: This study adopts a concurrent mixed-methods design. Using multiple data collection tools, we capture information on: implementation outcomes, stakeholder response to the intervention and the influence of contextual factors. Data will be collected from the 22 health facilities categorised as dispensaries, health centres, district hospitals and referral hospitals. Health workers (n=132) and patients (n=220) will fill a structured questionnaire. For each category of health facility, we will conduct five focus group discussions and in-depth interviews (n=45) for health workers. Participant observations (n=9) and review documents (n=22) will be conducted using structured checklists. Data will be collected at two points over a period of 1 year. We will analyse quantitative data using descriptive and inferential statistical methods. Thematic analysis will be used for qualitative data. ETHICS AND DISSEMINATION: This study received ethical approval from National Institute of Medical research (NIMR), Ref. NIMR/HQ/R.8a/Vol.IX/3269 and from the Mbeya Medical Research and Ethics Review Committee, Ref. SZEC-2439/R.A/V.I/38. Our findings are expected to inform the wider implementation of the new MDR-TB regimen as it is rolled out countrywide. Dissemination of findings will be through publications, conferences, workshops and implementation manuals for scaling up MDR-TB treatments.


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/uso terapêutico , Protocolos Clínicos , Humanos , Estudos Prospectivos , Tanzânia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
8.
Expert Opin Investig Drugs ; 31(2): 139-144, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35034512

RESUMO

INTRODUCTION: Tuberculosis is an infectious disease that affected more than 50 million people and killed 6.7 million patients in the past 5 years alone. Additionally, rising incidence of treatment resistance threatens the global effort to eradicate this disease. With limited options available, additional novel antibiotics are needed for the treatment of multidrug-resistant tuberculosis (MDR-TB). Telacebec is a first-in-class antibiotic that targets the pathogen's energy metabolism. AREAS COVERED: This paper provides an overview of the recent progress in the development and testing of telacebec. We discuss published clinical data and examine the design and setup of its clinical trials. We also offer insights on the therapeutic potential of telacebec and aspects of which should be evaluated in the future. EXPERT OPINION: The first phase 2a trial showed a correlation between dosage and bacterial load in patient sputum, which should be confirmed using a direct measurement method such as colony-forming unit counting. Its clinical efficacy, favorable pharmacokinetic properties, low arrhythmogenic risk, and activity against MDR-TB strains make telacebec a suitable candidate for further development. Future clinical testing in combination with approved second-line drugs will reveal its full potential against MDR-TB. Considering recent preclinical studies, we also recommend initiating clinical trials for Buruli ulcer and leprosy.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Humanos , Imidazóis , Piperidinas/uso terapêutico , Piridinas/uso terapêutico , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
9.
Front Cell Infect Microbiol ; 12: 1085946, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36733851

RESUMO

Combination therapy is necessary to treat tuberculosis to decrease the rate of disease relapse and prevent the acquisition of drug resistance, and shorter regimens are urgently needed. The adaptation of Mycobacterium tuberculosis to various lesion microenvironments in infection induces various states of slow replication and non-replication and subsequent antibiotic tolerance. This non-heritable tolerance to treatment necessitates lengthy combination therapy. Therefore, it is critical to develop combination therapies that specifically target the different types of drug-tolerant cells in infection. As new tools to study drug combinations earlier in the drug development pipeline are being actively developed, we must consider how to best model the drug-tolerant cells to use these tools to design the best antibiotic combinations that target those cells and shorten tuberculosis therapy. In this review, we discuss the factors underlying types of drug tolerance, how combination therapy targets these populations of bacteria, and how drug tolerance is currently modeled for the development of tuberculosis multidrug therapy. We highlight areas for future studies to develop new tools that better model drug tolerance in tuberculosis infection specifically for combination therapy testing to bring the best drug regimens forward to the clinic.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Antituberculosos/uso terapêutico , Quimioterapia Combinada , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Tolerância a Medicamentos
11.
Curr Pharm Des ; 27(17): 2026-2040, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33634753

RESUMO

Mycobacterium tuberculosis, because of its unique biochemical behavior and a complex host relationship, successfully evades the host immune system. Therefore, chemotherapy appears to be the first-line option for patients with tuberculosis. However, poor patient compliance with anti-tubercular treatment and variability in anti-tubercular drug pharmacokinetics are among the major driving factors for the emergence of drug resistance. The rising cases of extrapulmonary TB, cross-resistance patterns, high prevalence of tuberculosis and HIV co-infections make tuberculosis treatment more complicated than conventional multidrug therapy. Due to their distinct advantages like higher solubility, increased payload, controlled release profiles, tissue-specific accumulation, and lack of toxicity, nanoscale materials have immense potential for drug delivery applications. An appropriate selection of polymer and careful particle engineering further improves therapeutic outcomes with opportunities to overcome conventional anti-tubercular drugs' challenges. The present review introduces the prospect of using nanotechnology in tuberculosis (TB) chemotherapy and provides a comprehensive overview of recent advances in nanocarriers implied for delivering anti-tubercular drugs.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Antituberculosos/uso terapêutico , Quimioterapia Combinada , Humanos , Hansenostáticos/uso terapêutico , Nanotecnologia , Tuberculose/tratamento farmacológico
12.
PLoS One ; 16(1): e0244581, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33471851

RESUMO

BACKGROUND: The Lagos State Tuberculosis, Buruli Ulcer, and Leprosy Control Program (LSTBLCP) started engaging private hospitals under the Public-Private Mix (PPM) Program in 2008. The study aimed to evaluate the trend and predictors of successful Tuberculosis (TB) treatment outcomes of patients managed across these private health facilities between 2010-2016 in Lagos, Nigeria. METHODS: Retrospective review of TB treatment register and treatment cards of patients commenced on TB treatment between January 2010 and December 2016 in 36 private health facilities engaged by the LSTBLCP. Between December 2016 and February 2017, data were collected and entered into Microsoft Excel by trained data entry clerks. The analysis was done using SPSS software. Independent predictors of successful treatment outcomes were determined using multivariate analysis at the statistical significance of p<0.05 and 95% confidence interval. RESULTS: A total of 1660 records of TB patients were reviewed. 1535 (92.47%) commenced treatment, while 1337 (87.10%) of all records had documented treatment outcomes. Of the 1337 patients with outcomes, 1044 (78.09%) had a successful treatment outcome, and 293 (21.91%) had an unsuccessful outcome. Majority were male, 980 (59.04%), Human Immunodeficiency Virus (HIV) negative status, 1295 (80.24%), diagnosed with smear, 1141 (73.14%), treated in private not-for-profit (PNFP) hospital, 1097 (66.08%), treated for TB between 2014-2016 (18.96%-19.52%). In multivariate analysis, age>20years (aOR = 0.26, p = 0.001), receiving TB treatment in 2013 (aOR = 0.39, p = 0.001), having genexpert for TB diagnosis (aOR = 0.26, p = 0.031) and being HIV positive (aOR = 0.37, p = 0.001) significantly reduced likelihood of successful treatment outcome. The site of TB, being on ART or CPT, were confounding determinants of successful treatment outcomes as they became non-significant at the multivariate analysis level. CONCLUSION: Treatment outcome among Lagos private hospitals was low compared with NTBLCP and World Health Organization (WHO) target. We urge the government and TB stakeholders to strengthen the PPM interventions to improve adherence, particularly among People Living with HIV (PLHIV) and older TB patients. Hence, promotion of early care-seeking, improving diagnostic and case holding efficiencies of health facilities, and TB/HIV collaborative interventions can reduce the risk of an unsuccessful outcome.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose/tratamento farmacológico , Adulto , Terapia Diretamente Observada , Feminino , Hospitais Privados , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Nigéria/epidemiologia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adulto Jovem
13.
Int J Dermatol ; 60(3): 363-367, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33251595

RESUMO

BACKGROUND: Cutaneous tuberculosis (CTB) rarely involves the ear as the primary site, but while diagnosing and treating ear infections, it should be considered a differential diagnosis in a tropical country such as India. The present study reports the incidence and clinical presentation of auricular tuberculosis (TB) in a tertiary care hospital in New Delhi. METHODS: A retrospective, observational study was conducted from 2005 to 2019 whereby all cases of CTB confirmed by biopsy were retrieved from the database. The demographic details, clinical details, Mantoux results, and photographs were extracted and studied. The data were entered into MS Excel and analyzed. RESULTS: In a retrospective analysis of 886 cases of CTB over a period of 15 years, we found 20 cases (2.26%) of ear involvement (1 case with bilateral involvement). The median age of the patients with ear involvement was 29 years with 42.11% men and 57.89% women. Morphological variants seen over pinna were predominantly classic plaque type (31.58%) and nodular (31.58%), with few ulcerative (21.05%) and tumoral forms (15.79%). CTB of the pinna showed predominant involvement of either helix or ear lobule (7 cases each). All cases were strongly positive to tuberculin and showed response to the empirical antitubercular treatment. CONCLUSION: CTB can exclusively affect the pinna in varied presentations. The ear lobules and the helix are the usual sites of affection. It is rare for both ears to be affected with CTB, unlike bacilliferous leprosy. Regression following institution of antitubercular treatment is a reasonable way to confirm CTB.


Assuntos
Tuberculose Cutânea , Adulto , Antituberculosos/uso terapêutico , Feminino , Humanos , Índia/epidemiologia , Masculino , Estudos Retrospectivos , Teste Tuberculínico , Tuberculose Cutânea/diagnóstico , Tuberculose Cutânea/tratamento farmacológico , Tuberculose Cutânea/epidemiologia
14.
PLoS One ; 15(12): e0244451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33373997

RESUMO

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013-2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.


Assuntos
Coinfecção/tratamento farmacológico , Atenção à Saúde/organização & administração , Infecções por HIV/tratamento farmacológico , Implementação de Plano de Saúde , Hanseníase/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Assistência ao Convalescente/organização & administração , Assistência ao Convalescente/estatística & dados numéricos , Antirretrovirais/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Quimioprevenção/métodos , Estudos de Coortes , Coinfecção/microbiologia , Atenção à Saúde/métodos , Atenção à Saúde/estatística & dados numéricos , Farmacorresistência Bacteriana Múltipla , Feminino , Infecções por HIV/virologia , Humanos , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Modelos Organizacionais , Mycobacterium leprae/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Equipe de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/estatística & dados numéricos , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Uganda , Adulto Jovem
15.
Afr Health Sci ; 20(2): 625-632, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33163023

RESUMO

BACKGROUND: Following initiation of MDR-TB treatment, patients have a choice to receive follow up DOT supervision at either the central initiating facility or at a peripheral facility. OBJECTIVES: We describe the adherence patterns of MDR-TB patients undergoing DOT supervision at the two health facility categories during intensive phase of treatment. METHODS: We used a retrospective cohort of patients initiated on MDR TB treatment at Mulago National Referral Hospital between 2014 and 2016. We extracted data from the National Tuberculosis and Leprosy Program records and analysed these using STATA V14. RESULT: Majority (84.01%) of the patients received their DOT supervision from the peripheral facilities. Males made up 62.1% of patients, and 91.2% had had their household contacts screened for MDR-TB. 26.5% of the patients on peripheral DOT supervision had good adherence to treatment protocol compared to 0% among patients on central initiating health facility DOT supervision. Among the patients with good adherence, 24.1% had contacts screened for MDR-TB as compared to 3.6% with poor adherence. CONCLUSION: More patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settingsMore patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settings.


Assuntos
Antituberculosos/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Estudos de Coortes , Busca de Comunicante/métodos , Feminino , Seguimentos , Instalações de Saúde , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose/epidemiologia , Tuberculose/psicologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Uganda/epidemiologia , Adulto Jovem
16.
Antimicrob Agents Chemother ; 64(11)2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32900682

RESUMO

Multidrug therapy is often required. Examples include antiviral therapy, nosocomial infections, and, most commonly, anti-Mycobacterium tuberculosis therapy. Our laboratory previously identified a mathematical approach to identify 2-drug regimens with a synergistic or additive interaction using a full factorial study design. Our objective here was to generate a method to identify an optimal 3-drug therapy. We studied M. tuberculosis isolate H37Rv in log-phase growth in flasks. Pretomanid and moxifloxacin were chosen as the base 2-drug regimen. Bedaquiline (plus M2 metabolite) was chosen as the third drug for evaluation. Total bacterial burden and bacterial burden less-susceptible to study drugs were enumerated. A large mathematical model was fit to all the data. This allowed extension to evaluation of the 3-drug regimen by employing a Monte Carlo simulation. Pretomanid plus moxifloxacin demonstrated excellent bacterial kill and suppressed amplification of less-susceptible pathogens. Total bacterial burden was driven to extinction in 3 weeks in 6 of 9 combination therapy evaluations. Only the lowest pretomanid/moxifloxacin exposures in combination did not extinguish the bacterial burden. No combination regimen allowed resistance amplification. Generation of 95% credible intervals about estimates of the interaction parameters α (αs, αr-p, and αr-m) by bootstrapping showed the interaction was near synergistic. The addition of bedaquiline/M2 metabolite was evaluated by forming a 95% confidence interval regarding the decline in bacterial burden. The addition of bedaquiline/M2 metabolite shortened the time to eradication by 1 week and was significantly different. A model-based system approach to evaluating combinations of 3 agents shows promise to rapidly identify the most promising combinations that can then be trialed.


Assuntos
Mycobacterium tuberculosis , Preparações Farmacêuticas , Antituberculosos/uso terapêutico , Quimioterapia Combinada , Hansenostáticos
18.
Int J Mycobacteriol ; 9(1): 103-106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474499

RESUMO

Hansen's disease is a chronic infectious granulomatous disease with varied clinical presentation. In the postelimination era, histoid Hansen's disease is an important emerging lepromatous subset known to mimic varied dermatoses, thereby making clinical diagnosis difficult and often delayed. We report two cases of histoid Hansen's disease bereft of clinical cardinal signs of leprosy.


Assuntos
Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/microbiologia , Hanseníase/microbiologia , Abdome/microbiologia , Abdome/patologia , Adulto , Antituberculosos/uso terapêutico , Doença Granulomatosa Crônica/tratamento farmacológico , Humanos , Hanseníase/classificação , Masculino
20.
Emerg Infect Dis ; 25(8): 1604-1607, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31310204

RESUMO

Whether Mycobacterium leprae transmits from placenta to fetus remains unknown. We describe the case of a pregnant woman with untreated histoid leproma. Although her newborn was healthy, laboratory examination revealed intact M. leprae present in the placenta, suggesting that the placental barrier might prevent vertical dissemination of M. leprae.


Assuntos
Hanseníase/diagnóstico , Hanseníase/microbiologia , Mycobacterium leprae/isolamento & purificação , Placenta/microbiologia , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/microbiologia , Antituberculosos/uso terapêutico , Biópsia , China/epidemiologia , Feminino , Humanos , Hanseníase/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Pele/patologia , Resultado do Tratamento , Ultrassonografia
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