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1.
BMJ Open ; 11(6): e044349, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135033

RESUMO

OBJECTIVE: This study was designed to identify the risk factors for drug-resistant tuberculosis (DR-TB) and the association between comorbidity and drug resistance among retreated pulmonary tuberculosis (PTB). DESIGN: A retrospective study was conducted among all the 36 monitoring sites in Shandong, China, over a 16-year period. Baseline characteristics were collected from the TB Surveillance System. Categorical variables were compared by Fisher's exact or Pearson's χ2 test. The risk factors for drug resistance were identified using univariable analysis and multivariable logistic models. The influence of comorbidity on different types of drug resistance was evaluated by performing multivariable logistic models with the covariates adjusted by age, sex, body mass index, drinking/smoking history and cavity. RESULTS: A total of 10 975 patients with PTB were recorded during 2004-2019, and of these 1924 retreated PTB were finally included. Among retreated PTB, 26.2% were DR-TB and 12.5% had comorbidity. Smoking (adjusted OR (aOR): 1.69, 95% CI 1.19 to 2.39), cavity (aOR: 1.55, 95% CI 1.22 to 1.97) and comorbidity (aOR: 1.44, 95% CI 1.02 to 2.02) were risk factors for DR-TB. Of 504 DR-TB, 9.5% had diabetes mellitus, followed by hypertension (2.0%) and chronic obstructive pulmonary disease (1.8%). Patients with retreated PTB with comorbidity were more likely to be older, have more bad habits (smoking, alcohol abuse) and have clinical symptoms (expectoration, haemoptysis, weight loss). Comorbidity was significantly associated with DR-TB (aOR: 1.44, 95% CI 1.02 to 2.02), overall rifampin resistance (aOR: 2.17, 95% CI 1.41 to 3.36), overall streptomycin resistance (aOR: 1.51, 95% CI 1.00 to 2.27) and multidrug resistance (aOR: 1.96, 95% CI 1.17 to 3.27) compared with pan-susceptible patients (p<0.05). CONCLUSION: Smoking, cavity and comorbidity lead to an increased risk of drug resistance among retreated PTB. Strategies to improve the host's health, including smoking cessation, screening and treatment of comorbidity, might contribute to the control of tuberculosis, especially DR-TB, in China.


Assuntos
Mycobacterium tuberculosis , Preparações Farmacêuticas , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Antituberculosos/uso terapêutico , China/epidemiologia , Comorbidade , Humanos , Estudos Retrospectivos , Fatores de Risco , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia
2.
BMC Infect Dis ; 21(1): 510, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059022

RESUMO

OBJECTIVE: To determine the prevalence of Latent Tuberculosis in patients with hematological neoplasms at the Instituto Nacional de Cancerología in Mexico City using the Tuberculin skin test (TST). METHODS: This retrospective study included all patients with a recent diagnosis of hematological neoplasms who were admitted for treatment from 2017 to 2018 and who were screened for latent tuberculosis with the TST. The prevalence of latent tuberculosis in this group, tolerance and therapeutic adherence in treated patients are described. RESULTS: The files of 446 patients with hematological malignancy who had a TST were reviewed. The prevalence of latent tuberculosis was 31.2% (n = 139). Ninety-three patients received isoniazid, 15.1% had some adverse reactions, but only 4 (4.3%) had to discontinue treatment. Two patients with latent tuberculosis under treatment with Isoniazid reactivated tuberculosis infection. CONCLUSIONS: The prevalence in our study was within the range of other similar Mexican populations. Isoniazid treatment had an adequate tolerance and adherence. Longer follow-up could offer more information on the risk of reactivation in both groups.


Assuntos
Neoplasias Hematológicas/epidemiologia , Tuberculose Latente/epidemiologia , Adulto , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Institutos de Câncer , Feminino , Neoplasias Hematológicas/microbiologia , Humanos , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Prevalência , Estudos Retrospectivos , Teste Tuberculínico , Tuberculose/epidemiologia , Tuberculose/etiologia
3.
BMC Infect Dis ; 21(1): 513, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074248

RESUMO

BACKGROUND: In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB. METHODS: A subset of 138 PLHIV from the 'SOUTH' study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity. RESULTS: A total of 81 patients (58.7%) were males, median age 34 (IQR 29  ̶ 40) years, median CD4 cell count of 180 (IQR 68  ̶ 345) cells/µL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0  ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04  ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03  ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient's colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74  ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79  ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8. CONCLUSION: Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.


Assuntos
Carga Bacteriana/métodos , Infecções por HIV/epidemiologia , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adulto , Antirretrovirais/sangue , Antituberculosos/uso terapêutico , Contagem de Linfócito CD4 , Contagem de Colônia Microbiana , Feminino , Infecções por HIV/sangue , Humanos , Masculino , Técnicas de Amplificação de Ácido Nucleico , Razão de Chances , Estudos Retrospectivos , Sensibilidade e Especificidade , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Uganda/epidemiologia
4.
Medicina (Kaunas) ; 57(6)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34070995

RESUMO

Tuberculosis (TB), a bacterialinfectious disease caused by Mycobacterium tuberculosis (M.tb), which causes significant mortality in humans worldwide. Current treatment regimen involve the administration of multiple antibiotics over the course of several months that contributes to patient non-compliance leading to relapse and the development of drug-resistant M.tb (MDR and XDR) strains. Together, these facts highlight the need for the development of shorter TB treatment regimens. Host-directed therapy (HDT) is a new and emerging concept that aims to augment host immune response using drugs/compounds with or without adjunct antibiotics against M.tb infection. Autophagy is a natural catabolic mechanism of the cell that involves delivering the cytosolic constituents to the lysosomes for degradation and recycling the components; thereby maintaining the cellular and energy homoeostasis of a cell. However, over the past decade, an improved understanding of the role of autophagy in immunity has led to autophagy activation by using drugs or agents. This autophagy manipulation may represent a promising host-directed therapeutic strategy for human TB. However, current clinical knowledge on implementing autophagy activation by drugs or agents, as a stand-alone HDT or as an adjunct with antibiotics to treat human TB is insufficient. In recent years, many reports on high-throughput drug screening and measurement of autophagic flux by fluorescence, high-content microscopy, flow cytometry, microplate reader and immunoblotting have been published for the discovery of drugs that modulate autophagy. In this review, we discuss the commonly used chemical screening approaches in mammalian cells for the discovery of autophagy activating drugs against M.tbinfection. We also summarize the various autophagy-activating agents, both pre-clinical candidates and compounds approved for advanced clinical investigation during mycobacterial infection. Finally, we discuss the opportunities and challenges in using autophagy activation as HDT strategy to improve TB outcome and shorten treatment regimen.


Assuntos
Mycobacterium tuberculosis , Preparações Farmacêuticas , Tuberculose , Animais , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Autofagia , Humanos , Tuberculose/tratamento farmacológico
5.
Front Public Health ; 9: 663974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968888

RESUMO

Setting: Programmatic management of drug-resistant tuberculosis in Ningbo, China. Objective: To assess whether data-driven genetic determinants of drug resistance patterns could outperform phenotypic drug susceptibility testing in predicting clinical meaningful outcomes among patients with multidrug-resistant tuberculosis (MDR-TB). Design: We conducted a prospective cohort study of 104 MDR-TB patients. All MDR-TB isolates underwent drug susceptibility testing and genotyping for mutations that could cause drug resistance. Study outcomes were time to sputum smear conversion and probability of treatment success, as well as time to culture conversion within 6 months. Data were analyzed using latent class analysis, Kaplan-Meier curves, and Cox regression models. Results: We report that latent class analysis of data identified two latent classes that predicted sputum smear conversion with P = 0.001 and area under receiver-operating characteristic curve of 0.73. The predicted latent class memberships were associated with superior capability in predicting sputum culture conversion at 6 months and overall treatment success compared to phenotypic drug susceptibility profiling using boosted logistic regression models. Conclusion: These results suggest that genetic determinants of drug resistance in combination with phenotypic drug-resistant tests could serve as useful biomarkers in predicting treatment prognosis in MDR-TB.


Assuntos
Mycobacterium tuberculosis , Preparações Farmacêuticas , Antituberculosos/uso terapêutico , China/epidemiologia , Resistência a Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Estudos Prospectivos
7.
Int J Tuberc Lung Dis ; 25(5): 367-372, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33977904

RESUMO

BACKGROUND: TB is the leading cause of mortality among people living with HIV (PLHIV), for whom isoniazid preventive therapy (IPT) has a proven mortality benefit. Despite WHO recommendations, countries have been slow in scaling up IPT. This study describes processes, challenges, solutions, outcomes and lessons learned during IPT scale-up in Kenya.METHODS: We conducted a desk review and analyzed aggregated Ministry of Health (MOH) IPT enrollment data from 2014 to 2018 to determine trends and impact of program activities. We further analyzed IPT completion reports for patients initiated from 2015 to 2017 in 745 MOH sites in Nairobi, Central, Eastern and Western Kenya.RESULTS: IPT was scaled up 75-fold from 2014 to 2018: the number of PLHIV covered increased from 9,981 to 749,890. The highest percentage increases in the cumulative number of PLHIV on IPT were seen in the quarters following IPT pilot projects in 2014 (49%), national launch in 2015 (54%), and HIV treatment acceleration in 2016 (158%). Among 250,069 patients initiating IPT from 2015 to 2017, 97.5% completed treatment, 0.2% died, 0.8% were lost to follow-up, 1.0% were not evaluated, and 0.6% discontinued treatment.CONCLUSIONS: IPT can be scaled up rapidly and effectively among PLHIV. Deliberate MOH efforts, strong leadership, service delivery integration, continuous mentorship, stakeholder involvement, and accountability are critical to program success.


Assuntos
Infecções por HIV , Tuberculose , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Isoniazida/uso terapêutico , Quênia/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
8.
Int J Tuberc Lung Dis ; 25(5): 395-399, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33977908

RESUMO

BACKGROUND: Treatment outcomes in multidrug-resistant TB (MDR-TB) patients are suboptimal in several low-incidence countries.METHODS: The primary outcome measure was the proportion of successfully treated patients in Italy during an 18-year period. Secondary outcomes were treatment outcomes in certain drug-containing regimens and the possibility for the WHO shorter MDR-TB regimen.RESULTS: In the 191 patients included (median age at admission: 33 years; 67.5% male, following drug-resistance patterns were found: MDR-TB in 68.6%, pre-extensively drug-resistant TB (pre-XDR-TB) in 30.4% and XDR-TB in 1.1% patients. The most frequently prescribed drugs were fluoroquinolones in 84.6% cases, amikacin in 48.7%, linezolid in 34.6% and meropenem/clavulanic acid in 29.5%. The median duration of treatment was 18 months. Treatment success was achieved in 71.2% patients, of whom, 44% were cured and 27.2% completed treatment. Treatment success rates did not statistically differ between the MDR- (68.8%) and pre-XDR-TB (77.6%) groups (P = 0.26). Treatment success rates had large variability between North and South of Italy (81.3% vs. 53.3%). Only 22.5% of the cases would have been eligible for shorter MDR-TB regimensCONCLUSION: Our study highlights variability in treatment outcomes in MDR- and pre-XDR-TB patients. Study findings confirmed the potential utility of linezolid and, for patients with limited oral options, meropenem/clavulanic acid and amikacin.


Assuntos
Tuberculose Extensivamente Resistente a Medicamentos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
10.
BMC Infect Dis ; 21(1): 449, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006254

RESUMO

BACKGROUND: There is a need for innovative strategies to improve TB testing uptake and patient retention along the continuum of TB care early-on in treatment without burdening under-resourced health systems. We used a mixed methods approach to develop and pilot test a tuberculosis literacy and counselling intervention at an urban clinic in KwaZulu Natal, South Africa, to improve TB testing uptake and retention in tuberculosis care. METHODS: We engaged in discussions with clinic staff to plan and develop the intervention, which was delivered by senior social work students who received one-week training. The intervention included: 1) group health talks with all patients attending the primary clinic; and 2) individual counselling sessions, using motivational interviewing techniques, with newly diagnosed tuberculosis patients. We compared social work students' tuberculosis knowledge, attitudes, and practices before and after their training. We assessed the change in number of tuberculosis diagnostic tests performed after implementation via an interrupted time series analysis with a quasi-Poisson regression model. We compared pre- and post-intervention probabilities of treatment initiation and completion using regression analyses, adjusting for potential baseline confounders. We conducted focus groups with the students, as well as brief surveys and one-on-one interviews with patients, to assess acceptability, feasibility, and implementation. RESULTS: During the study period, 1226 individuals received tuberculosis diagnostic testing and 163 patients started tuberculosis treatment, of whom 84 (51.5%) received individual counselling. The number of diagnostic tuberculosis tests performed increased by 1.36 (95%CI 1.23-1.58) times post-intervention, adjusting for background calendar trend. Probabilities of TB treatment initiation and treatment completion increased by 10.1% (95%CI 1.5-21.3%) and 4.4% (95%CI -7.3-16.0%), respectively. Patients found the counselling sessions alleviated anxiety and increased treatment self-efficacy. Social work students felt the clinic staff were collaborative and highly supportive of the intervention, and that it improved patient engagement and adherence. CONCLUSIONS: Engaging clinic staff in the development of an intervention ensures buy-in and collaboration. Education and counselling before and early-on in tuberculosis treatment can increase tuberculosis testing and treatment uptake. Training junior social workers can enable task-shifting in under-resourced settings, while addressing important service gaps in tuberculosis care.


Assuntos
Aconselhamento , Letramento em Saúde , Tuberculose/diagnóstico , Adulto , Antituberculosos/uso terapêutico , Estudos de Viabilidade , Feminino , Pessoal de Saúde/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes/psicologia , Projetos Piloto , África do Sul , Resultado do Tratamento , Tuberculose/tratamento farmacológico
11.
BMC Infect Dis ; 21(1): 466, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022850

RESUMO

BACKGROUND: Pulmonary tuberculosis (TB) in people living with HIV (PLH) frequently presents as sputum smear-negative. However, clinical trials of TB in adults often use smear-positive individuals to ensure measurable bacterial responses following initiation of treatment, thereby excluding HIV-infected patients from trials. METHODS: In this prospective case cohort study, 118 HIV-seropositive TB patients were assessed prior to initiation of standard four-drug TB therapy and at several time points through 35 days. Sputum bacillary load, as a marker of treatment response, was determined serially by: smear microscopy, Xpert MTB/RIF, liquid culture, and colony counts on agar medium. RESULTS: By all four measures, patients who were baseline smear-positive had higher bacterial loads than those presenting as smear-negative, until day 35. However, most smear-negative PLH had significant bacillary load at enrolment and their mycobacteria were cleared more rapidly than smear-positive patients. Smear-negative patients' decline in bacillary load, determined by colony counts, was linear to day 7 suggesting measurable bactericidal activity. Moreover, the decrease in bacterial counts was comparable to smear-positive individuals. Increasing cycle threshold values (Ct) on the Xpert assay in smear-positive patients to day 14 implied decreasing bacterial load. CONCLUSION: Our data suggest that smear-negative PLH can be included in clinical trials of novel treatment regimens as they contain sufficient viable bacteria, but allowances for late exclusions would have to be made in sample size estimations. We also show that increases in Ct in smear-positive patients to day 14 reflect treatment responses and the Xpert MTB/RIF assay could be used as biomarker for early treatment response.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Antituberculosos/uso terapêutico , Carga Bacteriana/efeitos dos fármacos , Soropositividade para HIV , HIV/imunologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Testes Diagnósticos de Rotina , Feminino , Seguimentos , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/virologia , Humanos , Masculino , Microscopia , Técnicas de Amplificação de Ácido Nucleico , Estudos Prospectivos , Resultado do Tratamento , Tuberculose Pulmonar/virologia
12.
J Int Med Res ; 49(5): 3000605211014999, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33983063

RESUMO

Female genital tuberculosis (FGTB) is an infection caused by Mycobacterium tuberculosis and usually occurs secondary to pulmonary tuberculosis (TB) through the blood circulation, lymph circulation, or direct spreading from abdominal TB. FGTB is an uncommon type of TB that can destroy genital organs, and lead to menstrual disorders and infertility. The diagnosis of FGTB is often made by detection of acid-fast bacilli under microscopy, culture with endometrial biopsy, or histopathological examination of epithelioid granuloma on a biopsy. A multidrug anti-TB regimen is the major management of FGTB, including rifampicin, isoniazid, pyrazinamide, and ethambutol, while surgery is proposed in more deteriorated cases. However, the conception rate in infertile women with FGTB is still low, even after multidrug anti-TB therapy. Additionally, the risk of complications, such as ectopic pregnancy or miscarriage, remains high. In this review, we summarize the characteristics of FGTB, present current epidemiological data, and focus on its early diagnosis and effective management.


Assuntos
Infertilidade Feminina , Mycobacterium tuberculosis , Tuberculose dos Genitais Femininos , Antituberculosos/uso terapêutico , Feminino , Humanos , Infertilidade Feminina/diagnóstico , Isoniazida , Gravidez , Rifampina/uso terapêutico , Tuberculose dos Genitais Femininos/diagnóstico , Tuberculose dos Genitais Femininos/tratamento farmacológico
13.
BMC Public Health ; 21(1): 942, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006238

RESUMO

BACKGROUND: The End Tuberculosis (TB) Strategy aims to achieve 90% reduction of deaths due to TB by 2030, compared with 2015. Mortality due to tuberculosis in Mali was 13 per 100,000 inhabitants in 2014 and 11 per 100,000 inhabitants in 2017. Risk factors for death are not known. The objective of this study was to determine the time and risk factors for death in pulmonary TB patients with positive microscopy. METHODS: We conducted a retrospective cohort study from October to December 2016 in Commune VI of Bamako. Smear positive cases pulmonary tuberculosis from 2011 to 2015 were included. We reviewed the treatment registers and collected sociodemographic, clinical, biological and therapeutic data. Median time to death and hazard ratio (HR) were estimated by the Kaplan-Meier method and a Cox regression model, respectively. RESULTS: In total, we analysed 1362 smear positive cases of pulmonary TB including 104 (8%) HIV positive and 90 (7%) deaths. The mean age was 36 ± 13 years, the sex ratio of males to females was 2:1. Among the deaths, 48 (53%) occurred during the first 2 months of treatment. Age ≥ 45 years (HR 2.09 95% CI [1.35-3.23]), weight <  40 kg (HR 2.20 95% CI [1.89-5.42]), HIV unknown status (HR 1.96, 95% CI [1.04-3.67]) and HIV-positive (HR 7.10 95% CI [3.53-14.26]) were significantly associated with death. CONCLUSIONS: The median time to death was 2 months from the start of treatment. Independent risk factors for death were age ≥ 45 years, weight <  40 kg, unknown and positive HIV status. We recommend close monitoring of patients over 45 years, HIV testing in those with unknown status, an adequate care for positive HIV status, as well as a nutritional support for those with weight below 40 kg during the intensive phase of TB treatment.


Assuntos
Infecções por HIV , Tuberculose Pulmonar , Adulto , Antituberculosos/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Mali/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tuberculose Pulmonar/tratamento farmacológico , Adulto Jovem
14.
BMC Public Health ; 21(1): 964, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020616

RESUMO

BACKGROUND: Prevention of TB is paramount to achieving elimination targets as recommended by the World Health Organization's action framework for low incidence countries striving to eliminate TB. Although the rates of TB in Canada are low, understanding the latent TB infection (LTBI) cascade is paramount to identifying gaps in care and treatment barriers, thereby increasing the effectiveness of preventive strategies. The purpose of this study was to examine the LTBI cascade of care and identify barriers to treatment completion in adults referred from primary care to a regional tertiary care TB clinic in Ottawa, Canada. METHODS: Electronic medical records between January 2010 and December 2016 were reviewed retrospectively and an LTBI cascade of care was constructed from The Ottawa Hospital TB clinic and surrounding primary care clinics. A cohort of 2207 patients with untreated LTBI was used to ascertain the associations between demographic and clinical factors for both treatment non-initiation and non-completion using log-binomial univariable and multivariable regression models. RESULTS: Of 2207 patients with untreated LTBI who were seen in the clinic during the study period, 1771 (80.2%) were offered treatment, 1203 (67.9% of those offered) started treatment, and 795 (66.1% of those started) completed treatment. In multivariable analysis, non-initiation of treatment was associated with older age (adjusted risk ratio [aRR] 1.06 per 5-year increase, 95% CI: 1.03-1.08) and female gender (aRR 1.28, 95% CI: 1.11-1.47). Non completion of treatment was associated with referral from the TB Clinic back to the primary care team following initial consult (aRR 1.62, 95% CI: 1.35-1.94) and treatment with the standard of 9 months of Isoniazid (9H) compared to 4 months of Rifampin (4R) (aRR 1.45, 95% CI:1.20-1.74). CONCLUSIONS: LTBI treatment completion was significantly decreased among patients who were referred back to primary care from the TB clinic. The 4R regimen resulted in more people completing LTBI treatment compared to 9H in keeping with a recently published RCT. Improved education, communication, and collaboration between tertiary care TB clinics and primary care teams may improve treatment completion rates and address the TB burden in low incidence communities in Canada.


Assuntos
Tuberculose Latente , Adulto , Idoso , Antituberculosos/uso terapêutico , Canadá/epidemiologia , Feminino , Humanos , Incidência , Isoniazida , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Estudos Retrospectivos
15.
Nat Commun ; 12(1): 2716, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976135

RESUMO

Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. This has been linked to worse clinical outcomes in tuberculosis, as undetected strains with different antibiotic resistance profiles can lead to treatment failure. Here, we examine the amount of polyclonal infections in sputum and surgical resections from patients with tuberculosis in the country of Georgia. For this purpose, we sequence and analyse the genomes of Mycobacterium tuberculosis isolated from the samples, acquired through an observational clinical study (NCT02715271). Access to the lung enhanced the detection of multiple strains (40% of surgery cases) as opposed to just using a sputum sample (0-5% in the general population). We show that polyclonal infections often involve genetically distant strains and can be associated with reversion of the patient's drug susceptibility profile over time. In addition, we find different patterns of genetic diversity within lesions and across patients, including mutational signatures known to be associated with oxidative damage; this suggests that reactive oxygen species may be acting as a selective pressure in the granuloma environment. Our results support the idea that the magnitude of polyclonal infections in high-burden tuberculosis settings is underestimated when only testing sputum samples.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Genoma Bacteriano , Granuloma/patologia , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/patologia , Antituberculosos/uso terapêutico , Biópsia , Células Clonais , Estudos de Coortes , Variação Genética , República da Geórgia , Granuloma/tratamento farmacológico , Granuloma/microbiologia , Granuloma/cirurgia , Humanos , Pulmão/microbiologia , Pulmão/patologia , Pulmão/cirurgia , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Espécies Reativas de Oxigênio/metabolismo , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/cirurgia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/cirurgia
17.
BMJ Open ; 11(5): e047514, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986067

RESUMO

OBJECTIVE: To assess the cost effectiveness of once weekly rifapentine and isoniazid for 12 weeks (3HP) to the current standard care for latent tuberculosis (TB) infection (LTBI) in Iqaluit, Nunavut. DESIGN: A cost-effectiveness analysis using a Markov model reflecting local practices for LTBI treatment. SETTING: A remote Canadian arctic community with a high incidence of TB. PARTICIPANTS: Hypothetical patients with LTBI. INTERVENTIONS: The cost effectiveness of 3HP was compared with the existing standard of care in the study region which consists of 9 months of twice weekly isoniazid (9H) given by directly observed therapy. OUTCOME MEASURES: Effectiveness was measured in quality-adjusted life years (QALYs) with model parameters were derived from historical programmatic data, a local implementation study of 3HP and published literature. Costs from the perspective of the Nunavut healthcare system were measured in 2019 US dollars and were obtained primarily from local, empirically collected data. Secondary health outcomes included estimated TB cases and TB deaths averted using 3HP versus 9H. One way and probabilistic sensitivity analyses were performed. RESULTS: The 3HP regimen was dominant over 9H: costs were lower (US$628 vs US$924/person) and health outcomes slightly improved (20.14 vs 20.13 QALYs/person). In comparison to 9H, 3HP treatment resulted in fewer TB cases (27.89 vs 30.16/1000 persons) and TB deaths (2.29 vs 2.48/1000 persons). 3HP completion, initiation and risk of fatal adverse events were the primary drivers of cost effectiveness. CONCLUSION: In a remote Canadian arctic setting, using 3HP instead of 9H for LTBI treatment may result in cost savings and similar or improved health outcomes.


Assuntos
Isoniazida , Tuberculose Latente , Antituberculosos/uso terapêutico , Canadá , Análise Custo-Benefício , Humanos , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Rifampina/análogos & derivados
18.
N Engl J Med ; 384(18): 1705-1718, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33951360

RESUMO

BACKGROUND: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. METHODS: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. RESULTS: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. CONCLUSIONS: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.).


Assuntos
Antibióticos Antituberculose/administração & dosagem , Antituberculosos/uso terapêutico , Moxifloxacina/administração & dosagem , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/administração & dosagem , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Antibióticos Antituberculose/efeitos adversos , Antituberculosos/efeitos adversos , Criança , Intervalos de Confiança , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Moxifloxacina/efeitos adversos , Rifampina/efeitos adversos , Adulto Jovem
19.
BMC Public Health ; 21(1): 859, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947361

RESUMO

BACKGROUND: The Ministry of Health Zambia recommends tuberculosis preventive treatment (TPT) with 6 months daily isoniazid for all people living with human immunodeficiency virus (HIV) after ruling out active tuberculosis disease. We sought to estimate the percentage of people living with HIV who progress through each stage of the tuberculosis case-finding and prevention cascade in two provinces with the highest tuberculosis burden in Zambia. METHODS: In this cross-sectional survey, we used a two-stage cluster sampling method. We sampled 12 healthcare facilities with probability proportional to size. Patient volume determined facility cluster size. During October 2018, from each facility we systematically sampled medical records of adults and children living with HIV. Our primary outcome of interest was TPT initiation rate among eligible people living with HIV, weighted for complex survey design. The Rao-Scott adjusted chi-square test was used to test for differences in TPT initiation rate and other indicators from the tuberculosis prevention cascade by age group and province of residence. Additionally, we conducted semi-structured interviews with healthcare workers at each facility to assess TPT knowledge and identify challenges to its implementation. RESULTS: We sampled 482 records of people living with HIV (including 128 children living with HIV). Excluding two people diagnosed with tuberculosis disease before enrollment in HIV care, 93.4% underwent tuberculosis symptom screening. Of those, 4.7% were diagnosed with tuberculosis disease and 95.3% were TPT-eligible, of whom 24.7% initiated TPT. TPT initiation was lower among eligible children (7.7%) compared with adults (25.2%, p = 0.03) and Copperbelt residents (3.1%) compared with Lusaka residents (35.8%, p < 0.01). TPT completion rate was 38.4% among people living with HIV who initiated the 6-month course. Among interviewed healthcare workers, 58.3% (unweighted) incorrectly relayed the number of symptoms needed for a positive tuberculosis symptom screen, 83.3% (unweighted) reported insufficient isoniazid stockpile for completion at the time of TPT initiation, and only 27.3% (unweighted) reported receiving TPT-specific training. CONCLUSIONS: TPT uptake among people living with HIV in Zambia is challenged by inconsistent tuberculosis screening, lack of TPT training for healthcare workers, and supply chain inefficiencies. Addressing these barriers may increase TPT initiations and improve outcomes among people living with HIV.


Assuntos
Infecções por HIV , Tuberculose , Adulto , Antituberculosos/uso terapêutico , Criança , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Zâmbia/epidemiologia
20.
BMC Infect Dis ; 21(1): 394, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926375

RESUMO

BACKGROUND: Whole-genome sequencing has shown that the Mycobacterium tuberculosis infection process can be more heterogeneous than previously thought. Compartmentalized infections, exogenous reinfections, and microevolution are manifestations of this clonal complexity. The analysis of the mechanisms causing the microevolution -the genetic variability of M. tuberculosis at short time scales- of a parental strain into clonal variants with a patient is a relevant issue that has not been yet completely addressed. To our knowledge, a whole genome sequence microevolution analysis in a single patient with inadequate adherence to treatment has not been previously reported. CASE PRESENTATION: In this work, we applied whole genome sequencing analysis for a more in-depth analysis of the microevolution of a parental Mycobacterium tuberculosis strain into clonal variants within a patient with poor treatment compliance in Argentina. We analyzed the whole-genome sequence of 8 consecutive Mycobacterium tuberculosis isolates obtained from a patient within 57-months of intermittent therapy. Nineteen mutations (9 short-term, 10 fixed variants) emerged, most of them associated with drug resistance. The first isolate was already resistant to isoniazid, rifampicin, and streptomycin, thereafter the strain developed resistance to fluoroquinolones and pyrazinamide. Surprisingly, isolates remained susceptible to the pro-drug ethionamide after acquiring a frameshift mutation in ethA, a gene required for its activation. We also found a novel variant, (T-54G), in the 5' untranslated region of whiB7 (T-54G), a region allegedly related to kanamycin resistance. Notably, discrepancies between canonical and phage-based susceptibility testing to kanamycin were previously found for the isolate harboring this mutation. In our patient, microevolution was mainly driven by drug selective pressure. Rare short-term mutations fixed together with resistance-conferring mutations during therapy. CONCLUSIONS: This report highlights the relevance of whole-genome sequencing analysis in the clinic for characterization of pre-XDR and MDR resistance profile, particularly in patients with incomplete and/or intermittent treatment.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Argentina , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Isoniazida/uso terapêutico , Adesão à Medicação , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Estreptomicina/farmacologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Sequenciamento Completo do Genoma
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