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1.
BMC Infect Dis ; 20(1): 570, 2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32758165

RESUMEN

BACKGROUND: In sub-Saharan Africa (SSA), most prisons are overcrowded with poor ventilation and put prisoners disproportionally at risk of exposure to Mycobacterium tuberculosis (TB) and developing TB infection but are mostly missed due to poor access to healthcare. Active case-finding (ACF) of TB in prisons facilitates early diagnosis and treatment of inmates and prevent the spread. We explored literature and described evidence on TB ACF interventions and approaches for prisoners in SSA prisons. METHODS: Guided by the Arksey and O'Malley framework, we searched PubMed, Google Scholar, SCOPUS, Academic search complete, CINAHL and MEDLINE with full text via EBSCOhost for articles on prisoners and ACF from 2000 to May 2019 with no language restriction. Two investigators independently screened the articles at the abstract and full-text stages in parallel guided by the eligibility criteria as well as performed the methodological quality appraisal of the included studies using the latest mixed-method appraisal tool. We extracted all relevant data, organized them into themes and sub-themes, and presented a narrative summary of the results. RESULTS: Of the 391 eligible articles found, 31 met the inclusion criteria. All 31 articles were published between 2006 and 2019 with the highest six (19.4%) in 2015. We found evidence in 11 countries. That is, Burkina Faso, Cameroon, Coˆte d'Ivoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Malawi, Nigeria, South Africa, Uganda, and Zambia with most 41.9% (13/31) recorded in Ethiopia. These intervention studies were conducted in 134 prisons between 2001 and 2018 using either a single or combination of mass, facility-led, entry, peer educators for routine screening, and exit ACF approaches. The majority (74%) of the studies utilized only a mass screening approach. The most (68%) reported study outcome was smear-positive TB cases only (68%). We found no evidence in 16 SSA countries although they are classified among the three high-burden country lists for TB TB/HIV and Multidrug resistant-TB group. CONCLUSION: Our review highlights a dearth of evidence on TB ACF interventions in most SSA countries prisons. Hence, there is the need to scaling-up ACF interventions in SSA prisons, particularly countries included in the three high-burden country lists for TB, TB/HIV, and MDR-TB.


Asunto(s)
Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/inmunología , Prisioneros , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , África del Sur del Sahara/epidemiología , Antibióticos Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico , Prevalencia , Rifampin/uso terapéutico , Esputo/microbiología , Prueba de Tuberculina , Tuberculosis Resistente a Múltiples Medicamentos/microbiología
2.
BMC Infect Dis ; 20(1): 594, 2020 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-32787869

RESUMEN

BACKGROUND: Implementation of an effective Tuberculosis Routine Surveillance System in low-income countries like Tanzania is problematic, despite being an essential tool for the detection and effective monitoring of drug resistant tuberculosis. Long delays in specimen transportation from the facilities to reference laboratory and results dissemination back to the health facilities, result in poor patient management, particularly where multidrug-resistant tuberculosis disease is present. METHODS: Following a detailed qualitative study, a pilot intervention of a revised Tuberculosis Routine Surveillance System was implemented in Mwanza region, Tanzania. This included the use of rapid molecular methods for the detection of both tuberculosis and drug resistance using Xpert MTB/RIF in some Mwanza sites, the use of Xpert MTB/RIF and Line Probe Assay at the Central Tuberculosis Reference Laboratory, a revised communication strategy and interventions to address the issue of poor form completion. A before and after comparison of the intervention on the number of drug resistant tuberculosis cases identified and the time taken for results feedback to the requesting site was reported. RESULTS: The revised system for previously treated cases tested at the Central Reference Laboratory was able to obtain the following findings; the number of cases tested increased from 75 in 2016 to 185 in 2017. The times for specimen transportation from health facilities to the reference laboratory were reduced by 22% (from 9 to 7 days). The median time for the district to receive results was reduced by 36% (from 11 to 7 days). Overall the number of drug resistant tuberculosis cases starting treatment increased by 67% (from 12 to 20). CONCLUSION: Detection of drug resistance could significantly be enhanced, and delays reduced by introduction of new technologies and improved routine surveillance system, including better communication using mobile applications such as 'WhatsApp' and close follow-ups. A larger scale study is now merited to ascertain if these benefits are robust across different contexts.


Asunto(s)
Diagnóstico Tardío/prevención & control , Pruebas Diagnósticas de Rutina/métodos , Monitoreo Epidemiológico , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Antibióticos Antituberculosos/uso terapéutico , Comunicación , Farmacorresistencia Bacteriana Múltiple , Instituciones de Salud , Humanos , Laboratorios , Mycobacterium tuberculosis/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Proyectos Piloto , Estudios Prospectivos , Investigación Cualitativa , Rifampin/uso terapéutico , Manejo de Especímenes/métodos , Tanzanía/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico
3.
BMC Infect Dis ; 20(1): 543, 2020 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-32711457

RESUMEN

BACKGROUND: The main advantage of GeneXpert MTB/RIF® (Xpert) molecular diagnostic technology is the rapid detection of M.tuberculosis DNA and mutations associated with rifampicin (RIF) resistance for timely initiation of appropriate treatment and, consequently, preventing further transmission of the disease. We assessed time to treatment initiation and treatment outcomes of RIF-resistant and RIF-susceptible TB patients diagnosed and treated in Vladimir TB Dispensary, Russia in 2012, before and after implementation of GeneXpert MTB/RIF® diagnostic technology. METHODS: All adult patients suspected of having TB during February-December 2012 underwent a clinical examination, chest x-ray, microscopy, culture, and phenotypic drug susceptibility testing (DST). Starting August 2012 Xpert diagnostic technology became available in the facility. We used logistic regression to compare treatment outcomes in pre-Xpert and post-Xpert periods. Kaplan-Meier curves and log-rank test were used to compare the time to treatment initiation between the groups. RESULTS: Of 402 patients screened for TB during February-December 2012, 338 were diagnosed with TB (280 RIF-susceptible, 58 RIF-resistant). RIF-resistant patients in the post-Xpert group started treatment with second-line drugs (SLD) earlier than those in pre-Xpert group (median 11 vs. 37 days, Log-rank p = 0.02). The hazard ratio for time to SLD treatment initiation was significantly higher in post-Xpert group (HR:2.06; 95%CI:1.09,3.89) compared to pre-Xpert group. Among the 53/58 RIF-resistant TB patients with available treatment outcome, 28 (53%) had successful outcomes (cured/completed treatment) including 15/26 (58%) in post-Xpert group versus 13/27 (48%) in pre-Xpert group. The observed difference, however, was not statistically significant (OR:0.69; 95%CI:0.23,2.06). Among RIF-susceptible TB cases time to treatment initiation was not significantly different between the groups (2 vs. 3 days, Log-rank p = 0.73). Of 252/280 RIF-susceptible TB cases with treatment outcome, 199 (79%) cases had successful outcome including 94/114 (82%) in post-Xpert group versus 105/138 (76%) in pre-Xpert group (OR:0.68; 95%CI:0.36,1.26). CONCLUSION: We observed that availability of Xpert for initial diagnosis significantly reduced the time to SLD treatment for RIF-resistant patients in the Vladimir TB Dispensary. Although implementation of rapid diagnostics did not improve treatment outcomes, early diagnosis of MDR-TB is important for selection of appropriate treatment regimen and prevention of transmission of drug-resistant strains of TB.


Asunto(s)
Antibióticos Antituberculosos/uso terapéutico , Pruebas de Sensibilidad Microbiana/métodos , Mycobacterium tuberculosis/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Rifampin/uso terapéutico , Tiempo de Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adolescente , Adulto , Anciano , ADN Bacteriano/genética , Farmacorresistencia Bacteriana/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Estudios Prospectivos , Federación de Rusia , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto Joven
4.
BMC Infect Dis ; 20(1): 501, 2020 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-32652944

RESUMEN

BACKGROUND: Tuberculosis (TB) still causes high economic burden on patients in China, especially for rural patients. Our study aims to explore the risk factors associated with the high costs for TB inpatients in rural China from the aspects of inpatients' socio-demographic and institutional attributes. METHODS: Generalized linear models were utilized to investigate the factors associated with TB inpatients' total costs and out-of-pocket (OOP) expenditures. Quantile regression (QR) models were applied to explore the effect of each factor across the different costs range and identify the risk factors of high costs. RESULTS: TB inpatients with long length of stay and who receive hospitalization services cross provincially, in tertiary and specialized hospitals were likely to face high total costs and OOP expenditures. QR models showed that high total costs occurred in Dingyuan and Funan Counties, but they were not accompanied by high OOP expenditures. CONCLUSIONS: Early diagnosis, standard treatment and control of drug-resistant TB are still awaiting for more efforts from the government. TB inpatients should obtain medical services from appropriate hospitals. The diagnosis and treatment process of TB should be standardized across all designated medical institutions. Furthermore, the reimbursement policy for migrant workers who suffered from TB should be ameliorated.


Asunto(s)
Tuberculosis/economía , Adolescente , Adulto , Anciano , China , Femenino , Costos de la Atención en Salud , Gastos en Salud , Humanos , Pacientes Internos , Tiempo de Internación/economía , Masculino , Persona de Mediana Edad , Análisis de Regresión , Población Rural , Centros de Atención Terciaria/economía , Tuberculosis/diagnóstico , Tuberculosis/terapia , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/economía , Tuberculosis Resistente a Múltiples Medicamentos/terapia , Adulto Joven
5.
Int J Infect Dis ; 96: 390-397, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32353546

RESUMEN

OBJECTIVES: Numerous studies investigate the advantages of rapid molecular drug susceptibility testing (DST) in comparison to phenotypic DST, but the clinical impact on treating multi/extensively drug resistant TB(M/XDR-TB) is less studied. Therefore, we examined how molecular DST testing may improve MDR-TB treatment management and outcome in Chinese settings. METHODS: We performed a comparative study of patient cohorts before and after the implementation of molecular DST diagnosis with Genotype MTBDRsl/MTBDRplus assay in two Chinese hospitals. We collected clinical information including time to sputum culture conversion and final treatment outcome. RESULTS: In total, 242 MDR-TB patients were studied including 114 before (pre-implementation group) and 128 after the implementation (post-implementation group) of molecular DST. Time to MDR-TB diagnosis was significantly reduced for patients in the post-implementation group, as compared to the pre-implementation group (median,16 vs 62 days; P < 0.001). Patients with early available molecular DST results had a more rapid culture conversion (aHR1.94 95% CI: 1.37-2.73; median,12 vs 24 months, respectively; P < 0.001) and higher rate of treatment success (68% vs 47%, P < 0.01). CONCLUSIONS: The use of molecular DST in routine care for MDR-TB diagnosis as compared to phenotypic DST was associated with a decreased time to culture conversion and improved treatment outcome, highlighting its important clinical value.


Asunto(s)
Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Anciano , China , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular/métodos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Esputo/microbiología , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología
7.
PLoS One ; 15(5): e0232632, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32365116

RESUMEN

The MDR/MTB ELITe MGB® Kit on the ELITe InGenius® platform (ELITechGroup SpA, Italy) is the first system for simultaneous detection of the Mycobacterium tuberculosis complex (MTBc) genome and the main mutations responsible for resistance to Isoniazid (inhA, katG) and Rifampicin (rpoB), from decontaminated and heat inactivated samples. In this study we compared the performance of the MDR/MTB ELITe MGB® Kit (ELITe) with culture in 100 pulmonary and 160 extra-pulmonary samples. The sensitivity and specificity of ELITe compared to culture for pulmonary samples were 98.0% and 98.0% respectively; for extra-pulmonary samples the overall sensitivity was 86.3% (80% for urine, 85% for biopsy and gastric aspirate and 95% for cavitary fluid) and specificity was 100%. Genotypic Isoniazid and Rifampicin susceptibility typing was feasible in 96% of sputum MTBc-positive samples and 43% of extra-pulmonary samples; all samples were found to be drug susceptible by phenotypic and ELITe (100% agreement). Detection of mutations in the rpoB, kat G or inhA genes was evaluated on 300 spiked samples (60 per biological matrix) and all resistance profiles were correctly identified by ELITe. Molecular agreement between ELITe and Xpert was 98.0% and 93.3% for pulmonary and extra-pulmonary samples, respectively. In conclusion, our results provide evidence to support the use of MDR/MTB ELITe MGB® Kit in combination with ELITe InGenius® for the diagnosis of MTBc and the detection of Rifampicin and Isoniazid resistance-related mutations in both pulmonary and extra-pulmonary samples. This system simplifies the laboratory workflow, shortens report time and is an aid in choosing appropriate therapeutic treatment and patient management.


Asunto(s)
Farmacorresistencia Bacteriana , Isoniazida/farmacología , Juego de Reactivos para Diagnóstico , Rifampin/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Antibióticos Antituberculosos/uso terapéutico , Biopsia , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Temperatura , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico
9.
BMC Infect Dis ; 20(1): 315, 2020 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-32345228

RESUMEN

BACKGROUND: Despite the predictive role of body weight variation in treatment outcome in multidrug-resistant tuberculosis (MDR-TB), few corroborating data are available. We studied weight variation in patients with MDR-TB to identify groups of weight change and to determine factors that influence these changes. METHODS: We analyzed patients with rifampicin resistance who were treated with an MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 at three major drug-resistant TB centers in Guinea. Patients were seen monthly until the end of treatment. Clinical outcome was the body mass index (BMI). We used a linear mixed model to analyze trajectories of BMI and a latent class mixed model to identify groups of BMI trajectories. RESULTS: Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3-8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m2. Factors associated with faster BMI progression were success of MDR-TB treatment (0.24 [SE 0.09] per kg/m2; p = 0.0205) and absence of lung cavities on X-ray (0.18 [0.06] per kg/m2; p = 0.0068). Two groups of BMI change were identified: rapid BMI increase (n = 121; 85%) and slow BMI increase (n = 22; 15%). Patients in the slow BMI increase group were mostly female (68%) had no history of TB treatment (41%), had a positive HIV infection (59%), and had a more severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelet count, and higher SGOT. These patients also had a longer time to initial culture conversion (log-rank test: p = 0.0218). CONCLUSION: Quantitative BMI data on patients with MDR-TB treated with a short regimen allowed the identification of subgroups of patients with different trajectories of BMI and emphasized the usefulness of BMI as a biomarker for the monitoring of MDR-TB treatment outcome.


Asunto(s)
Antibióticos Antituberculosos/uso terapéutico , Índice de Masa Corporal , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Estudios de Cohortes , Depresión/etiología , Disnea/etiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Adulto Joven
10.
BMC Infect Dis ; 20(1): 298, 2020 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-32321429

RESUMEN

BACKGROUND: There are unique challenges in the diagnosis and management of multi drug resistant tuberculosis (MDR-TB) in children. It is difficult to obtain confirmatory microbiological diagnosis in TB pericarditis. It is essential to differentiate between drug sensitive and drug resistant forms of TB as it has a major bearing on the regimen used, and inappropriate TB treatment combined with steroid use for pericarditis can lead to deterioration. With lack of samples, the treatment decision relies on the drug resistance pattern of the close contact if available. Therapeutic challenges of MDR-TB management in a child involve use of toxic drugs that need to be judiciously handled. We report a 2 years 4 months old male child who was diagnosed with TB pericarditis and treated based on the resistance pattern of his mother who was on treatment for pulmonary MDR-TB. CASE PRESENTATION: This 2 years 4 months old male child was diagnosed with TB involving his pericardium. Getting him started on an appropriate regimen was delayed due to the difficulty in establishing microbiological confirmation and drug susceptibility. He was commenced on a regimen based on his mother's drug resistance pattern and required surgery due to cardiac failure during the course of his treatment. He successfully completed 2 years of therapy. CONCLUSIONS: This child's case demonstrates that despite unique challenges in diagnosis and management of drug resistant extra pulmonary tuberculosis in children, treatment of even complex forms can be successful. The need for high suspicion of MDR-TB, especially when there is close contact with pulmonary TB, careful design of an effective regimen that is tolerated by the child, indications for invasive surgical management of pericarditis, appropriate follow-up and management of adverse effects are emphasised.


Asunto(s)
Antituberculosos/uso terapéutico , Pericarditis Tuberculosa/diagnóstico , Pericarditis Tuberculosa/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos , Preescolar , Estudios de Seguimiento , Humanos , Masculino , Mycobacterium tuberculosis/efectos de los fármacos , Pericarditis Tuberculosa/cirugía , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/terapia
11.
PLoS One ; 15(4): e0230504, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32255811

RESUMEN

Multidrug-resistant (MDR) TB is more difficult to diagnose and treat compared with drug-susceptible TB. Young children are at greater risk of severe TB disease and death when treatment is delayed compared to adults. We sought to describe characteristics of children (<13 years) diagnosed with MDR TB between 2008-2010 in three South African provinces and assess factors associated with pre-treatment loss to follow-up. We matched laboratory and medical records at treatment facilities to identify pre-treatment loss and examined demographic and clinical characteristics for association with loss. Categorical variables were examined for association using Pearson's x2 or Fisher's exact test, employing Bonferroni correction for multiple pairwise comparisons. Between 2008-2010, 156 children were diagnosed with laboratory-confirmed MDR TB. Only 44% (n = 69) were documented as having received treatment. Young children (<2 years) (47/59, 80%), children with extrapulmonary (EP) TB (27/34, 79%), and children diagnosed at general hospitals (60/97, 62%) were most likely to be lost before treatment. Children most vulnerable to death from TB are most likely to be lost before treatment, possibly leading to underestimates of disease burden, case notifications, and poor outcomes among this population. Point-of-care diagnosis and robust follow-up may reduce pre-treatment loss in this population.


Asunto(s)
Insuficiencia del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Antituberculosos/uso terapéutico , Niño , Preescolar , Bases de Datos Factuales , Hospitales Generales , Humanos , Lactante , Sudáfrica , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico
12.
APMIS ; 128(5): 406-413, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32202675

RESUMEN

In areas of low tuberculosis (TB) prevalence, laboratory diagnosis of TB may essentially cover non-tuberculous mycobacteria (NTM) in addition to Mycobacterium tuberculosis (MTB). In this study, a semi-automated PCR workflow distinguishing MTB and NTM (Anyplex™ MTB/NTMe, Seegene) and subsequently detecting MTB isoniazid/rifampicin resistance (Allplex™ MTB/MDRe, Seegene) was evaluated for replacing smear microscopy of acid-fast bacilli as the rapid screening method for TB. With 279 clinical samples, 47 cultures positive for MTB and 76 for NTM, the Anyplex™ MTB/NTMe assay and smear microscopy showed equal sensitivities (49.6% vs 50.8%, respectively) but Anyplex™ MTB/NTMe was more sensitive for MTB (63.8% vs 25.6%) than for NTM (40.8% vs 64.5%). Allplex™ MTB/MDRe showed a slightly higher sensitivity of 68.1% for MTB (32/47 positive, n = 222). Antibiotic resistance profiles were correctly identified for all MTB isolates (one MDR isolate). Specificity was 100% for both assays. Anyplex™ MTB/NTMe detected all the 18 NTM species present in the study. The analytical performance of the evaluated high-throughput workflow was relatively weak compared to culture but potentially adequate as a rapid screening method analogous to smear microscopy with additional differentiation between TB, MDR-TB, and NTM.


Asunto(s)
Automatización de Laboratorios , Farmacorresistencia Bacteriana Múltiple , Mycobacterium tuberculosis/aislamiento & purificación , Micobacterias no Tuberculosas/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Técnicas Bacteriológicas , Humanos , Técnicas de Diagnóstico Molecular , Mycobacterium tuberculosis/genética , Micobacterias no Tuberculosas/genética , Valor Predictivo de las Pruebas , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad
13.
J Bras Pneumol ; 46(2): e20180386, 2020.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-32130331

RESUMEN

OBJECTIVE: To evaluate the risk factors for the development of tuberculosis and multidrug-resistant tuberculosis (MDR-TB) in patients treated at a tertiary referral hospital. METHODS: This was a cross-sectional study based on data obtained from patients treated at the Júlia Kubitschek Hospital, located in the city of Belo Horizonte, Brazil, between October of 2012 and October of 2014. We evaluated sociodemographic, behavioral, clinical, and radiological variables. The outcome considered to identify associations between tuberculosis and the explanatory variables was the treatment prescribed. To evaluate the associations between MDR-TB and the same explanatory variables, the change in MDR-TB treatment was considered. RESULTS: The factors associated with tuberculosis were alcoholism, comorbidities, pulmonary cavitations, and a radiological pattern suggestive of tuberculosis. Cavitation and previous treatment for tuberculosis were associated with MDR-TB. CONCLUSIONS: Despite the significant progress made in the fight against tuberculosis, there is a need for coordinated actions that include social protection measures and patient support.


Asunto(s)
Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Antituberculosos/uso terapéutico , Brasil/epidemiología , Estudios Transversales , Humanos , Pruebas de Sensibilidad Microbiana , Centros de Atención Terciaria , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/microbiología
14.
Rev Soc Bras Med Trop ; 53: e20190175, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32049199

RESUMEN

INTRODUCTION: The present study sought to assess the mean and activity based cost (ABC) of the laboratory diagnosis for tuberculosis through the application of conventional and molecular techniques-Xpert®MTB/RIF and Genotype®MTBDRplus-in a tertiary referral hospital in Brazil. METHODS: The mean cost and ABC formed the basis for the cost analysis of the TB laboratory diagnosis. RESULTS: The mean cost and ABC were US$ 4.00 and US$ 3.24, respectively, for a bacilloscopy; US$ 6.73 and US$ 5.27 for a Lowenstein-Jensen (LJ) culture; US$ 105.42 and US$ 76.56 for a drug sensitivity test (DST)-proportions method (PM) in LJ; US$ 148.45 and US$ 136.80 for a DST-BACTECTM MGITTM 960 system; US$ 11.53 and US$ 9.89 for an Xpert®MTB/RIF; and US$ 84.21 and US$ 48.38 for a Genotype®MTBDRplus. CONCLUSIONS: The mean cost and ABC proved to be good decision-making parameters in the diagnosis of TB and MDR-TB. The effective implementation of algorithms will depend on the conditions at each location.


Asunto(s)
Costos y Análisis de Costo/estadística & datos numéricos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/economía , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/economía , Brasil , Genotipo , Humanos , Mycobacterium tuberculosis/aislamiento & purificación , Sensibilidad y Especificidad , Centros de Atención Terciaria
15.
Int J Infect Dis ; 92S: S15-S25, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32032752

RESUMEN

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.


Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Niño , Preescolar , Trazado de Contacto , Humanos , Control de Infecciones , Tuberculosis Latente/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Factores de Riesgo , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/prevención & control
16.
BMC Infect Dis ; 20(1): 19, 2020 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-31910878

RESUMEN

BACKGROUND: Pyrazinamide still may be a useful drug for treatment of rifampin-resistant (RR-TB) or multidrug-resistant tuberculosis (MDR-TB) in China while awaiting scale up of new drugs and regimens including bedaquiline and linezolid. The level of pyrazinamide resistance among MDR-TB patients in China is not well established. Therefore, we assessed pyrazinamide resistance in a representative sample and explored determinants and patterns of pncA mutations. METHODS: MDR-TB isolates from the 2007 national drug resistance survey of China were sub-cultured and examined for pyrazinamide susceptibility by BACTEC MGIT 960 method. pncA mutations were identified by sequencing. Characteristics associated with pyrazinamide resistance were analyzed using univariable and multivariable log-binominal regression. RESULTS: Of 401 MDR-TB isolates, 324 were successfully sub-cultured and underwent drug susceptibility testing. Pyrazinamide resistance was prevalent in 40.7% of samples, similarly among new and previously treated MDR-TB patients. Pyrazinamide resistance in MDR-TB patients was associated with lower age (adjusted OR 0.54; 95% CI, 0.34-0.87 for those aged ≧60 years compared to < 40 years). Pyrazinamide resistance was not associated with gender, residential area, previous treatment history and Beijing genotype. Of 132 patients with pyrazinamide resistant MDR-TB, 97 (73.5%) had a mutation in the pncA gene; with 61 different point mutations causing amino acid change, and 11 frameshifts in the pncA gene. The mutations were scattered throughout the whole pncA gene and no hot spot region was identified. CONCLUSIONS: Pyrazinamide resistance among MDR-TB patients in China is common, although less so in elderly patients. Therefore, pyrazinamide should only be used for treatment of RR/MDR-TB in China if susceptibility is confirmed. Molecular testing for detection of pyrazinamide resistance only based on pncA mutations has certain value for the rapid detection of pyrazinamide resistance in MDR-TB strains but other gene mutations conferring to pyrazinamide resistance still need to be explored to increase its predictive ability .


Asunto(s)
Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Pirazinamida/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Adulto , Factores de Edad , Amidohidrolasas/genética , Antituberculosos/efectos adversos , Secuencia de Bases/genética , China/epidemiología , Diarilquinolinas/uso terapéutico , Genes Bacterianos/genética , Genotipo , Humanos , Linezolid/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Mutación Puntual/genética , Polimorfismo de Nucleótido Simple/genética , Prevalencia , Pirazinamida/efectos adversos , Rifampin/efectos adversos , Rifampin/uso terapéutico , Factores de Riesgo , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico
17.
PLoS One ; 15(1): e0227215, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31910223

RESUMEN

Rapid diagnosis of tuberculosis (TB) and antibiotic resistances are imperative to initiate effective treatment and to stop transmission of the disease. A new generation of more sensitive, automated molecular TB diagnostic tests has been recently launched giving microbiologists more choice between several assays with the potential to detect resistance markers for rifampicin and isoniazid. In this study, we determined analytical sensitivities as 95% limits of detection (LoD95) for Xpert MTB/Rif Ultra (XP-Ultra) and BD-MAX MDR-TB (BD-MAX) as two representatives of the new test generation, in comparison to the conventional FluoroType MTB (FT-MTB). Test matrices used were physiological saline solution, human and a mucin-based artificial sputum (MUCAS) each spiked with Mycobacterium tuberculosis in declining culture- and qPCR-controlled concentrations. With BD-MAX, XP-Ultra, and FT-MTB, we measured LoD95TB values of 2.1 cfu/ml (CI95%: 0.9-23.3), 3.1 cfu/ml (CI95%: 1.2-88.9), and 52.1 cfu/ml (CI95%: 16.7-664.4) in human sputum; of 6.3 cfu/ml (CI95%: 2.9-31.8), 1.5 cfu/ml (CI95%: 0.7-5.0), and 30.4 cfu/ml (CI95%: 17.4-60.7) in MUCAS; and of 2.3 cfu/ml (CI95%: 1.1-12.0), 11.5 cfu/ml (CI95%: 5.6-47.3), and 129.1 cfu/ml (CI95%: 82.8-273.8) in saline solution, respectively. LoD95 of resistance markers were 9 to 48 times higher compared to LoD95TB. BD-MAX and XP-Ultra have an equal and significantly increased analytical sensitivity compared to conventional tests. MUCAS resembled human sputum, while both yielded significantly different results than normal saline. MUCAS proved to be suitable for quality control of PCR assays for TB diagnostics.


Asunto(s)
Técnicas de Diagnóstico Molecular/instrumentación , Mycobacterium tuberculosis/aislamiento & purificación , Juego de Reactivos para Diagnóstico/normas , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Antibióticos Antituberculosos/farmacología , Antibióticos Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Humanos , Límite de Detección , Pruebas de Sensibilidad Microbiana/instrumentación , Pruebas de Sensibilidad Microbiana/métodos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Mycobacterium tuberculosis/fisiología , Control de Calidad , Reacción en Cadena en Tiempo Real de la Polimerasa , Esputo/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología
18.
PLoS One ; 15(1): e0227100, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31899769

RESUMEN

BACKGROUND: Treatment outcomes among patients treated for multidrug-resistant tuberculosis (MDR-TB) are often sub-optimal. Therefore, the early prediction of poor treatment outcomes may be useful in patient care, especially for clinicians when they have the ability to make treatment decisions or offer counselling or additional support to patients. The aim of this study was to develop a simple clinical risk score to predict poor treatment outcomes in patients with MDR-TB, using routinely collected data from two large countries in geographically distinct regions. METHODS: We used MDR-TB data collected from Hunan Chest Hospital, China and Gondar University Hospital, Ethiopia. The data were divided into derivation (n = 343; 60%) and validation groups (n = 227; 40%). A poor treatment outcome was defined as treatment failure, lost to follow up or death. A risk score for poor treatment outcomes was derived using a Cox proportional hazard model in the derivation group. The model was then validated in the validation group. RESULTS: The overall rate of poor treatment outcome was 39.5% (n = 225); 37.9% (n = 86) in the derivation group and 40.5% (n = 139) in the validation group. Three variables were identified as predictors of poor treatment outcomes, and each was assigned a number of points proportional to its regression coefficient. These predictors and their points were: 1) history of taking second-line TB treatment (2 points), 2) resistance to any fluoroquinolones (3 points), and 3) smear did not convert from positive to negative at two months (4 points). We summed these points to calculate the risk score for each patient; three risk groups were defined: low risk (0 to 2 points), medium risk (3 to 5 points), and high risk (6 to 9 points). In the derivation group, poor treatment outcomes were reported for these three groups as 14%, 27%, and 71%, respectively. The area under the receiver operating characteristic curve for the point system in the derivation group was 0.69 (95% CI 0.60 to 0.77) and was similar to that in the validation group (0.67; 95% CI 0.56 to 0.78; p = 0.82). CONCLUSION: History of second-line TB treatment, resistance to any fluoroquinolones, and smear non-conversion at two months can be used to estimate the risk of poor treatment outcome in patients with MDR-TB with a moderate degree of accuracy (AUROC = 0.69).


Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Adulto , Anciano , Antibacterianos/uso terapéutico , Femenino , Fluoroquinolonas/uso terapéutico , Humanos , Masculino , Anamnesis , Persona de Mediana Edad , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología
19.
Lancet Infect Dis ; 20(3): 308-317, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31924549

RESUMEN

INTRODUCTION: Tuberculous meningitis accounts for 1-5% of tuberculosis cases. Diagnostic delay contributes to poor outcomes. We evaluated the performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis diagnosis. METHODS: In this prospective validation study, we tested the cerebrospinal fluid (CSF) of adults presenting with suspected meningitis (ie, headache or altered mental status with clinical signs of meningism) to the Mulago National Referral Hospital and Mbarara Regional Referral Hospital in Uganda. We centrifuged the CSF, resuspended the cell pellet in 2 mL CSF, and tested 0·5 mL aliquots with Xpert Ultra, Xpert MTB/RIF (Xpert), and mycobacterial growth indicator tube (MGIT) culture. We quantified diagnostic performance against the uniform case definition of probable or definite tuberculous meningitis and a composite microbiological reference standard. FINDINGS: From Nov 25, 2016, to Jan 24, 2019, we screened 466 adults with suspected meningitis and tested 204 for tuberculous meningitis. Uniform clinical case definition classified 51 participants as having probable or definite tuberculous meningitis. Against this uniform case definition, Xpert Ultra had 76·5% sensitivity (95% CI 62·5-87·2; 39 of 51 patients) and a negative predictive value of 92·7% (87·6-96·2; 153 of 165), compared with 55·6% sensitivity (44·0-70·4; 25 of 45; p=0·0010) and a negative predictive value of 85·8% (78·9-91·1; 121 of 141) for Xpert and 61·4% sensitivity (45·5-75·6; 27 of 44; p=0·020) and negative predictive value of 85·2% (77·4-91·1; 98 of 115) for MGIT culture. Against the composite microbiological reference standard, Xpert Ultra had sensitivity of 92·9% (80·5-98·5; 39 of 42), higher than Xpert at 65·8% (48·6-80·4; 25 of 38; p=0·0063) and MGIT culture at 72·2% (55·9-86·2; 27 of 37; p=0·092). Xpert Ultra detected nine tuberculous meningitis cases missed by Xpert and MGIT culture. INTERPRETATION: Xpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required. FUNDING: Wellcome Trust, National Institute of Health, National Institute of Neurologic Diseases and Stroke, Fogarty International Center, and National Institute of Allergy and Infectious Diseases.


Asunto(s)
Infecciones por VIH/complicaciones , Técnicas de Diagnóstico Molecular/métodos , Tuberculosis Meníngea/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Líquido Cefalorraquídeo/microbiología , Hospitales , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Uganda
20.
Lancet Infect Dis ; 20(3): 299-307, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31924551

RESUMEN

BACKGROUND: Xpert MTB/RIF Ultra (Xpert Ultra) might have higher sensitivity than its predecessor, Xpert MTB/RIF (Xpert), but its role in tuberculous meningitis diagnosis is uncertain. We aimed to compare Xpert Ultra with Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. METHODS: In this prospective, randomised, diagnostic accuracy study, adults (≥16 years) with suspected tuberculous meningitis from a single centre in Vietnam were randomly assigned to cerebrospinal fluid testing by either Xpert Ultra or Xpert at baseline and, if treated for tuberculous meningitis, after 3-4 weeks of treatment. Test performance (sensitivity, specificity, and positive and negative predictive values) was calculated for Xpert Ultra and Xpert and compared against clinical and mycobacterial culture reference standards. Analyses were done for all patients and by HIV status. FINDINGS: Between Oct 16, 2017, and Feb 10, 2019, 205 patients were randomly assigned to Xpert Ultra (n=103) or Xpert (n=102). The sensitivities of Xpert Ultra and Xpert for tuberculous meningitis diagnosis against a reference standard of definite, probable, and possible tuberculous meningitis were 47·2% (95% CI 34·4-60·3; 25 of 53 patients) for Xpert Ultra and 39·6% (27·6-53·1; 21 of 53) for Xpert (p=0·56); specificities were 100·0% (95% CI 92·0-100·0; 44 of 44) and 100·0% (92·6-100·0; 48 of 48), respectively. In HIV-negative patients, the sensitivity of Xpert Ultra was 38·9% (24·8-55·1; 14 of 36) versus 22·9% (12·1-39·0; eight of 35) by Xpert (p=0·23). In HIV co-infected patients, the sensitivities were 64·3% (38·8-83·7; nine of 14) for Xpert Ultra and 76·9% (49·7-91·8; ten of 13) for Xpert (p=0·77). Negative predictive values were 61·1% (49·6-71·5) for Xpert Ultra and 60·0% (49·0-70·0) for Xpert. Against a reference standard of mycobacterial culture, sensitivities were 90·9% (72·2-97·5; 20 of 22 patients) for Xpert Ultra and 81·8% (61·5-92·7; 18 of 22) for Xpert (p=0·66); specificities were 93·9% (85·4-97·6; 62 of 66) and 96·9% (89·5-91·2; 63 of 65), respectively. Six (22%) of 27 patients had a positive test by Xpert Ultra after 4 weeks of treatment versus two (9%) of 22 patients by Xpert. INTERPRETATION: Xpert Ultra was not statistically superior to Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. A negative Xpert Ultra or Xpert test does not rule out tuberculous meningitis. New diagnostic strategies are urgently required. FUNDING: Wellcome Trust and the Foundation for Innovative New Diagnostics.


Asunto(s)
Técnicas de Diagnóstico Molecular/métodos , Tuberculosis Meníngea/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Infecciones por VIH/complicaciones , Humanos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Distribución Aleatoria , Sensibilidad y Especificidad , Vietnam
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