Safety and effectiveness of low-dose amikacin in nontuberculous mycobacterial pulmonary disease treated in Toronto, Canada

Amikacin; NTM lung disease; Nontuberculous mycobacteriaAmikacina; Malaltia pulmonar per micobacteri no tuberculós; Micobacteri no tuberculósAmikacina; Enfermedad pulmonar por micobacteria no tuberculosa; Micobacteria no tuberculosaBACKGROUND: Treatment guidelines suggest either a low-dose or high-dose approach when prescribing amikacin for nontuberculous mycobacterial pulmonary disease (NTM PD), but data supporting the low-dose approach are limited. The purpose of this study was to describe the safety and efficacy of the use of a low-dose of intravenous amikacin in a cohort of patients with NTM PD. METHODS: We retrospectively reviewed all patients with NTM PD who received amikacin at our institution between July 1, 2003 and February 28, 2017. Demographics, clinical, microbiological and radiological data, indication and dose of amikacin, and adverse drug effects were recorded. RESULTS: A total of 107 patients received a regimen containing amikacin for a median (IQR) of 7 (4-11) months. Seventy (65.4%) were female and the mean age (SD) was 58.3 (14.9) years. Amikacin was started at a median dose of 9.9 (2.5) mg/kg/day. Ototoxicity was observed in 30/77 (39%) patients and it was related to female sex (OR 4.96, 95%CI 1.24-19.87), and total dose of amikacin per bodyweight (OR 1.62, 95%CI 1.08-2.43). Patients of East Asian ethnicity were less likely to develop ototoxicity (0.24, 95%CI 0.06-0.95). Out of 96 patients who received amikacin for more than 3 months, 65 (67.7%) experienced symptom improvement and 30/62 (49.2%) converted their sputum to culture negative within a year. CONCLUSIONS: Patients with NTM PD treated with low-dose intravenous amikacin frequently developed ototoxicity, which was associated with female sex, and total dose of amikacin per bodyweight. Physicians should carefully consider dose, treatment duration, and long term prognosis in balancing risks and benefits of intravenous amikacin in NTM PD

Impact of the COVID-19 pandemic on tuberculosis management in Spain

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impacte; TuberculosiCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impacto; TuberculosisCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impact; TuberculosisBackground The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. Methods Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. Results A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 ( P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 ( P = 0.001). Conclusions The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures.This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.MLA was supported by a postdoctoral grant “Rio Hortega” and ASM was supported by a postdoctoral grant “Juan Rodés” (JE18/00022) from the Instituto de Salud Carlos III through the Spanish Ministry of economy and competitiveness

Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola

Angola; Rifampicina; Mutaciones rpoBAngola; Rifampicina; Mutacions rpoBAngola; Rifampicin; rpoB mutationsBackground The importance of Mycobacterium tuberculosis strains with disputed rpoB mutations remains to be defined. This study aimed to assess the frequency and types of rpoB mutations in M. tuberculosis isolates from Cubal, Angola, a country with a high incidence of tuberculosis. Methods All isolates included (n = 308) were analyzed using phenotypic drug susceptibility testing and GenoType MTBDRplus assay. DNA sequencing of the rpoB gene and determination of rifampicin MIC by macrodilution method were additionally performed on isolates yielding discordant results (n = 12) and those in which the mutation detected was not characterized (n = 8). Results In total, 85.1% (74/87) of rifampicin-resistant strains had undisputed rpoB mutations -S450L (49), D435V (15), H445D (3), H445Y (2), Q432ins (1), L449M plus S450F (1), S450F (1), S450W (1) and S450Y (1)-; 10.3% (9/87) had disputed rpoB mutations—L430P plus S493L (1), N437del (1), H445L (3), D435Y (2), L452P (2)-, 2.3% (2.3%) showed no rpoB mutations and 2.3% (2/87) showed heteroresistance—D435Y plus L452P and L430P plus S493L-. Conclusion Disputed rpoB mutations were common, occurring in 10.3% of rifampicin resistant isolates. Current phenotyping techniques may be unable to detect this resistance pattern. To increase their sensitivity, a lower concentration of RIF could be used in these tests or alternatively, rpoB mutations could be screened and characterized in all M. tuberculosis strains.This work was supported by Probitas Foundation. Thanks to the financial support received from Probitas Foundation it was possible not only purchase the equipment and reagents to launch the study but to strengthen the capacity of the laboratory and local staff

Evaluation of Two Different Strategies for Schistosomiasis Screening in High-Risk Groups in a Non-Endemic Setting

Diagnosis; Non-endemic; SchistosomiasisDiagnóstico; No endémico; EsquistosomiasisDiagnòstic; No endèmic; EsquistosomiasiA consensus on the recommended screening algorithms for schistosomiasis in asymptomatic high-risk subjects in non-endemic areas is lacking. The objective of this study was to evaluate the real-life performance of direct microscopy and ELISA serology for schistosomiasis screening in a high-risk population in a non-endemic setting. A retrospective cohort study was conducted in two out-patient Tropical Medicine units in Barcelona (Spain) from 2014 to 2017. Asymptomatic adults arriving from the Sub-Saharan region were included. Schistosomiasis screening was conducted according to clinical practice following a different strategy in each setting: (A) feces and urine direct examination plus S. mansoni serology if non-explained eosinophilia was present and (B) S. mansoni serology plus uroparasitological examination as the second step in case of a positive serology. Demographic, clinical and laboratory features were collected. Schistosomiasis cases, clinical management and a 24 month follow-up were recorded for each group. Four-hundred forty individuals were included. The patients were mainly from West African countries. Fifty schistosomiasis cases were detected (11.5% group A vs. 4 % group B, p = 0.733). When both microscopic and serological techniques were performed, discordant results were recorded in 18.4% (16/88). Schistosomiasis cases were younger (p < 0.001) and presented eosinophilia and elevated IgE (p < 0.001) more frequently. Schistosomiasis is a frequent diagnosis among high-risk populations. Serology achieves a similar performance to direct diagnosis for the screening of schistosomiasis in a high-risk population

COVID-19 Clinical Profile in Latin American Migrants Living in Spain: Does the Geographical Origin Matter?

COVID-19; Latin America; SeverityCOVID-19; Amèrica Llatina; GravetatCOVID-19; América Latina; GravedadThe aim of this study was to describe and compare the clinical characteristics of hospitalized patients with COVID-19 pneumonia according to their geographical origin. This is a retrospective case-control study of hospitalized patients with confirmed COVID-19 pneumonia treated at Vall d’Hebron University Hospital (Barcelona) during the first wave of the pandemic. Cases were defined as patients born in Latin America and controls were randomly selected among Spanish patients matched by age and gender. Demographic and clinical variables were collected, including comorbidities, symptoms, vital signs and analytical parameters, intensive care unit admission and outcome at 28 days after admission. Overall, 1080 hospitalized patients were registered: 774 (71.6%) from Spain, 142 (13.1%) from Latin America and the rest from other countries. Patients from Latin America were considered as cases and 558 Spanish patients were randomly selected as controls. Latin American patients had a higher proportion of anosmia, rhinorrhea and odynophagia, as well as higher mean levels of platelets and lower mean levels of ferritin than Spanish patients. No differences were found in oxygen requirement and mortality at 28 days after admission, but there was a higher proportion of ICU admissions (28.2% vs. 20.2%, p = 0.0310). An increased proportion of ICU admissions were found in patients from Latin America compared with native Spanish patients when adjusted by age and gender, with no significant differences in in-hospital mortality.Isabel Campos-Varela’s research activity is funded by grant PI19/00330 from Instituto de Salud Carlos III. CIBERehd is supported by Instituto de Salud Carlos III. The work was independent of all funding. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors

Tuberculosis multirresistente en un área rural de Angola

La Tuberculosis Multirresistente (TB MDR) es una enfermedad causada por el bacilo Mycobacterium tuberculosis (MTB) resistente a la rifampicina (RIF) e isoniazida (INH). En 2017 se notificaron a nivel mundial más de 160.000 casos de TB MDR, de los cuales sólo un 25% inició tratamiento con fármacos de segunda línea. Sin embargo, las estimaciones sugieren que unos 558.000 casos desarrollaron TB resistente a RIF, y que de estos un 82% tenían TB MDR. Existen numerosas barreras que justifican las diferencias entre los casos notificados y los casos estimados, como son la dificultad de acceso a los sistemas de salud, la falta de medios diagnósticos y la falta de notificación de casos. En Angola, se desconocía la prevalencia de TB MDR debido a la falta de métodos apropiados para su diagnóstico. La realización de los proyectos relacionados con la presente tesis puso de manifiesto los primeros casos del país. Los trabajos que componen esta tesis se realizaron a raíz de un primer estudio realizado por nuestro grupo en el que se observó una alta proporción de fracaso entre los pacientes diagnosticados de TB que iniciaban tratamiento con fármacos de primera línea. Estos datos hicieron sospechar la posibilidad de que una de las causas del alto porcentaje de fracasos fuera la existencia de TB MDR. Para corroborar esta hipótesis, se instaló el primer equipo de diagnóstico molecular rápido de detección de MTB y resistencia a RIF (Xpert MTB/RIF) en el país, lo que permitió conocer la prevalencia de esta enfermedad, así como poder iniciar el tratamiento adecuado con fármacos de segunda línea en los pacientes infectados por cepas de TB MDR. El primero de los trabajos que componen esta tesis describe la prevalencia de TB MDR encontrada en Cubal, con cifras mucho más altas a las estimadas por la OMS para Angola (8% en pacientes no tratados previamente para TB y 71,1% en los pacientes que habían recibido tratamiento para TB previamente), así como los factores relacionados con el desarrollo de TB MDR. En el segundo trabajo se describen las características clínicas y la evolución de los pacientes diagnosticados de TB MDR que fueron tratados con un régimen estandarizado de segunda línea, observándose que más del 80% de los pacientes presentaron efectos adversos relacionados con los fármacos de segunda línea y que sólo un 54% de los casos completaron el tratamiento y se curaron. Las conclusiones de esta tesis han sido enormemente valiosas para conocer que la TB MDR es un problema importantísimo en el país. A raíz de los hallazgos observados en los artículos descritos en esta tesis el programa nacional de Angola de lucha contra la TB (PNLT) ha instalado nuevos aparatos Xpert MTB/RIF en el país y las guías de tratamiento se han modificado, contemplando el régimen de segunda línea e iniciándose los trámites para la realización de un estudio epidemiológico para conocer la prevalencia de TB MDR a nivel nacional.Multidrug-resistant TB (MDR TB) is caused by bacillus Mycobacterium tuberculosis (MTB) resistant to rifampin (RIF) and isoniazid (INH). In 2017, more than 160,000 cases of MDR TB were reported, and only 25% of them started treatment with second-line drugs. However, it’s estimated that about 558,000 cases developed RIF-resistant TB, of which 82% had MDR TB. There are numerous barriers that justify the differences between reported cases and estimated cases, such as the difficulty of access to health systems, the lack of diagnostic tools and the poor case notification. In Angola, the prevalence of MDR TB was unknown since there was no appropriate method for diagnosis. The realization of the projects related to this thesis revealed the first cases of the country. The papers that compose this thesis were inspired by the results of a first study carried out by our group in which a high proportion of failure was observed among patients diagnosed with TB who started treatment with first-line drugs. These data suggested that one of the causes of the high percentage of failures was the presence of MDR TB in the area. To corroborate this hypothesis, the first rapid molecular diagnosis equipment for detection of both MTB and resistance to RIF (Xpert MTB / RIF) was installed in the country, which allowed to know the prevalence of this disease, and to initiate the appropriate treatment with second-line drugs in patients infected with MDR TB strains. The first of the studies that compose this thesis describes the prevalence of MDR TB found in Cubal, which is much higher than the estimated by WHO for Angola (8% in patients not previously treated for TB and 71.1% in patients who had received treatment for TB previously), as well as factors related to the development of MDR TB. The second study describes the clinical characteristics and microbiological outcomes of patients diagnosed with MDR TB who were treated with a standardized second-line regimen, observing that more than 80% of the patients experienced adverse effects related to second-line drugs and that only 54% of cases achieved treatment success. The conclusions of this thesis have been enormously valuable to know that MDR TB is a very important problem in the country. Based on the results observed in the articles described in this thesis, Angola's national TB control program (PNLT) has installed new Xpert MTB / RIF devices in the country and the treatment guidelines have been modified, considering the regimen for MDR TB and starting the process for the performance of an epidemiological study to know the prevalence of MDR TB nationwide

Tuberculosis multirresistente en un área rural de Angola

La Tuberculosis Multirresistente (TB MDR) es una enfermedad causada por el bacilo Mycobacterium tuberculosis (MTB) resistente a la rifampicina (RIF) e isoniazida (INH). En 2017 se notificaron a nivel mundial más de 160.000 casos de TB MDR, de los cuales sólo un 25% inició tratamiento con fármacos de segunda línea. Sin embargo, las estimaciones sugieren que unos 558.000 casos desarrollaron TB resistente a RIF, y que de estos un 82% tenían TB MDR. Existen numerosas barreras que justifican las diferencias entre los casos notificados y los casos estimados, como son la dificultad de acceso a los sistemas de salud, la falta de medios diagnósticos y la falta de notificación de casos. En Angola, se desconocía la prevalencia de TB MDR debido a la falta de métodos apropiados para su diagnóstico. La realización de los proyectos relacionados con la presente tesis puso de manifiesto los primeros casos del país. Los trabajos que componen esta tesis se realizaron a raíz de un primer estudio realizado por nuestro grupo en el que se observó una alta proporción de fracaso entre los pacientes diagnosticados de TB que iniciaban tratamiento con fármacos de primera línea. Estos datos hicieron sospechar la posibilidad de que una de las causas del alto porcentaje de fracasos fuera la existencia de TB MDR. Para corroborar esta hipótesis, se instaló el primer equipo de diagnóstico molecular rápido de detección de MTB y resistencia a RIF (Xpert MTB/RIF) en el país, lo que permitió conocer la prevalencia de esta enfermedad, así como poder iniciar el tratamiento adecuado con fármacos de segunda línea en los pacientes infectados por cepas de TB MDR. El primero de los trabajos que componen esta tesis describe la prevalencia de TB MDR encontrada en Cubal, con cifras mucho más altas a las estimadas por la OMS para Angola (8% en pacientes no tratados previamente para TB y 71,1% en los pacientes que habían recibido tratamiento para TB previamente), así como los factores relacionados con el desarrollo de TB MDR. En el segundo trabajo se describen las características clínicas y la evolución de los pacientes diagnosticados de TB MDR que fueron tratados con un régimen estandarizado de segunda línea, observándose que más del 80% de los pacientes presentaron efectos adversos relacionados con los fármacos de segunda línea y que sólo un 54% de los casos completaron el tratamiento y se curaron. Las conclusiones de esta tesis han sido enormemente valiosas para conocer que la TB MDR es un problema importantísimo en el país. A raíz de los hallazgos observados en los artículos descritos en esta tesis el programa nacional de Angola de lucha contra la TB (PNLT) ha instalado nuevos aparatos Xpert MTB/RIF en el país y las guías de tratamiento se han modificado, contemplando el régimen de segunda línea e iniciándose los trámites para la realización de un estudio epidemiológico para conocer la prevalencia de TB MDR a nivel nacional.Multidrug-resistant TB (MDR TB) is caused by bacillus Mycobacterium tuberculosis (MTB) resistant to rifampin (RIF) and isoniazid (INH). In 2017, more than 160,000 cases of MDR TB were reported, and only 25% of them started treatment with second-line drugs. However, it’s estimated that about 558,000 cases developed RIF-resistant TB, of which 82% had MDR TB. There are numerous barriers that justify the differences between reported cases and estimated cases, such as the difficulty of access to health systems, the lack of diagnostic tools and the poor case notification. In Angola, the prevalence of MDR TB was unknown since there was no appropriate method for diagnosis. The realization of the projects related to this thesis revealed the first cases of the country. The papers that compose this thesis were inspired by the results of a first study carried out by our group in which a high proportion of failure was observed among patients diagnosed with TB who started treatment with first-line drugs. These data suggested that one of the causes of the high percentage of failures was the presence of MDR TB in the area. To corroborate this hypothesis, the first rapid molecular diagnosis equipment for detection of both MTB and resistance to RIF (Xpert MTB / RIF) was installed in the country, which allowed to know the prevalence of this disease, and to initiate the appropriate treatment with second-line drugs in patients infected with MDR TB strains. The first of the studies that compose this thesis describes the prevalence of MDR TB found in Cubal, which is much higher than the estimated by WHO for Angola (8% in patients not previously treated for TB and 71.1% in patients who had received treatment for TB previously), as well as factors related to the development of MDR TB. The second study describes the clinical characteristics and microbiological outcomes of patients diagnosed with MDR TB who were treated with a standardized second-line regimen, observing that more than 80% of the patients experienced adverse effects related to second-line drugs and that only 54% of cases achieved treatment success. The conclusions of this thesis have been enormously valuable to know that MDR TB is a very important problem in the country. Based on the results observed in the articles described in this thesis, Angola's national TB control program (PNLT) has installed new Xpert MTB / RIF devices in the country and the treatment guidelines have been modified, considering the regimen for MDR TB and starting the process for the performance of an epidemiological study to know the prevalence of MDR TB nationwide

Tuberculosis multirresistente en un área rural de Angola

La Tuberculosis Multirresistente (TB MDR) es una enfermedad causada por el bacilo Mycobacterium tuberculosis (MTB) resistente a la rifampicina (RIF) e isoniazida (INH). En 2017 se notificaron a nivel mundial más de 160.000 casos de TB MDR, de los cuales sólo un 25% inició tratamiento con fármacos de segunda línea. Sin embargo, las estimaciones sugieren que unos 558.000 casos desarrollaron TB resistente a RIF, y que de estos un 82% tenían TB MDR. Existen numerosas barreras que justifican las diferencias entre los casos notificados y los casos estimados, como son la dificultad de acceso a los sistemas de salud, la falta de medios diagnósticos y la falta de notificación de casos. En Angola, se desconocía la prevalencia de TB MDR debido a la falta de métodos apropiados para su diagnóstico. La realización de los proyectos relacionados con la presente tesis puso de manifiesto los primeros casos del país. Los trabajos que componen esta tesis se realizaron a raíz de un primer estudio realizado por nuestro grupo en el que se observó una alta proporción de fracaso entre los pacientes diagnosticados de TB que iniciaban tratamiento con fármacos de primera línea. Estos datos hicieron sospechar la posibilidad de que una de las causas del alto porcentaje de fracasos fuera la existencia de TB MDR. Para corroborar esta hipótesis, se instaló el primer equipo de diagnóstico molecular rápido de detección de MTB y resistencia a RIF (Xpert MTB/RIF) en el país, lo que permitió conocer la prevalencia de esta enfermedad, así como poder iniciar el tratamiento adecuado con fármacos de segunda línea en los pacientes infectados por cepas de TB MDR. El primero de los trabajos que componen esta tesis describe la prevalencia de TB MDR encontrada en Cubal, con cifras mucho más altas a las estimadas por la OMS para Angola (8% en pacientes no tratados previamente para TB y 71,1% en los pacientes que habían recibido tratamiento para TB previamente), así como los factores relacionados con el desarrollo de TB MDR. En el segundo trabajo se describen las características clínicas y la evolución de los pacientes diagnosticados de TB MDR que fueron tratados con un régimen estandarizado de segunda línea, observándose que más del 80% de los pacientes presentaron efectos adversos relacionados con los fármacos de segunda línea y que sólo un 54% de los casos completaron el tratamiento y se curaron. Las conclusiones de esta tesis han sido enormemente valiosas para conocer que la TB MDR es un problema importantísimo en el país. A raíz de los hallazgos observados en los artículos descritos en esta tesis el programa nacional de Angola de lucha contra la TB (PNLT) ha instalado nuevos aparatos Xpert MTB/RIF en el país y las guías de tratamiento se han modificado, contemplando el régimen de segunda línea e iniciándose los trámites para la realización de un estudio epidemiológico para conocer la prevalencia de TB MDR a nivel nacional.Multidrug-resistant TB (MDR TB) is caused by bacillus Mycobacterium tuberculosis (MTB) resistant to rifampin (RIF) and isoniazid (INH). In 2017, more than 160,000 cases of MDR TB were reported, and only 25% of them started treatment with second-line drugs. However, it's estimated that about 558,000 cases developed RIF-resistant TB, of which 82% had MDR TB. There are numerous barriers that justify the differences between reported cases and estimated cases, such as the difficulty of access to health systems, the lack of diagnostic tools and the poor case notification. In Angola, the prevalence of MDR TB was unknown since there was no appropriate method for diagnosis. The realization of the projects related to this thesis revealed the first cases of the country. The papers that compose this thesis were inspired by the results of a first study carried out by our group in which a high proportion of failure was observed among patients diagnosed with TB who started treatment with first-line drugs. These data suggested that one of the causes of the high percentage of failures was the presence of MDR TB in the area. To corroborate this hypothesis, the first rapid molecular diagnosis equipment for detection of both MTB and resistance to RIF (Xpert MTB / RIF) was installed in the country, which allowed to know the prevalence of this disease, and to initiate the appropriate treatment with second-line drugs in patients infected with MDR TB strains. The first of the studies that compose this thesis describes the prevalence of MDR TB found in Cubal, which is much higher than the estimated by WHO for Angola (8% in patients not previously treated for TB and 71.1% in patients who had received treatment for TB previously), as well as factors related to the development of MDR TB. The second study describes the clinical characteristics and microbiological outcomes of patients diagnosed with MDR TB who were treated with a standardized second-line regimen, observing that more than 80% of the patients experienced adverse effects related to second-line drugs and that only 54% of cases achieved treatment success. The conclusions of this thesis have been enormously valuable to know that MDR TB is a very important problem in the country. Based on the results observed in the articles described in this thesis, Angola's national TB control program (PNLT) has installed new Xpert MTB / RIF devices in the country and the treatment guidelines have been modified, considering the regimen for MDR TB and starting the process for the performance of an epidemiological study to know the prevalence of MDR TB nationwide