Characterization of Latin American migrants at risk for Trypanosoma cruzi infection in a non-endemic setting. Insights into initial evaluation of cardiac and digestive involvement.

BACKGROUND: Trypanosoma cruzi causes Chagas disease (CD), a potentially fatal disease characterized by cardiac disorders and digestive, neurological or mixed alterations. T. cruzi is transmitted to humans by the bite of triatomine vectors; both the parasite and disease are endemic in Latin America and the United States. In the last decades, population migration has changed the classic epidemiology of T. cruzi, contributing to its global spread to traditionally non-endemic countries. Screening is recommended for Latin American populations residing in non-endemic countries. METHODS: The present study analyzes the epidemiological characteristics of 2,820 Latin American individuals who attended the International Health Service (IHS) of the Hospital Clinic de Barcelona between 2002 and 2019. The initial assessment of organ damage among positive cases of T. cruzi infection was analyzed, including the results of electrocardiogram (ECG), echocardiogram, barium enema and esophagogram. RESULTS: Among all the screened individuals attending the clinic, 2,441 (86.6%) were born in Bolivia and 1,993 (70.7%) were female. Of individuals, 1,517 (81.5%) reported previous exposure to the vector, which is a strong risk factor associated with T. cruzi infection; 1,382 individuals were positive for T. cruzi infection. The first evaluation of individuals with confirmed T. cruzi infection, showed 148 (17.1%) individuals with Chagasic cardiomyopathy, the main diagnostic method being an ECG and the right bundle branch block (RBBB) for the most frequent disorder; 16 (10.8%) individuals had a normal ECG and were diagnosed of Chagasic cardiomyopathy by echocardiogram. CONCLUSIONS: We still observe many Latin American individuals who were at risk of T. cruzi infection in highly endemic areas in their countries of origin, and who have not been previously tested for T. cruzi infection. In fact, even in Spain, a country with one of the highest proportion of diagnosis of Latin American populations, T. cruzi infection remains underdiagnosed. The screening of Latin American populations presenting with a similar profile as reported here should be promoted. ECG is considered necessary to assess Chagasic cardiomyopathy in positive individuals, but echocardiograms should also be considered as a diagnostic approach given that it can detect cardiac abnormalities when the ECG is normal.

Enfermedad por citomegalovirus en los pacientes inmunodeprimidos por glomerulonefritis necrosante pauciinmune / Cytomegalovirus disease in immunosuppressed patients with necrotizing pauci-immune glomerulonephritis

Introducción: La afectación renal por glomerulonefritis necrosante pauciinmune (GNPI) asociada a vasculitis de pequeño vaso requiere tratamiento inmunodepresor, cuyos efectos secundarios incluyen un mayor riesgo de procesos infecciosos, como la enfermedad por citomegalovirus (CMV), aunque no hay recomendaciones sobre su manejo en las guías de práctica clínica (GPC).ObjetivoEstudiar la incidencia de enfermedad por CMV y sus determinantes.Pacientes y métodosPacientes con diagnóstico histológico de GNPI en los últimos 10 años, determinando la carga viral de CMV y analizando los determinantes de su concurrencia.ResultadosSe realizaron 44 biopsias durante el periodo de estudio. Del total, 11 pacientes (25%) desarrollaron enfermedad por CMV; todos habían recibido tratamiento inmunodepresor. Cuatro (30,8%) fallecieron durante el ingreso. Los factores determinantes de la enfermedad fueron la edad (por cada 10 años OR: 3,0, IC 95%: 1,0 a 8,9, p = 0,012) y la albúmina (por cada g/L OR: 0,8, IC 95%: 0,6 a 1,0, p = 0,012).ConclusionesLa incidencia de enfermedad por CMV en pacientes inmunodeprimidos por GNPI es alta, con alta mortalidad. Sería necesario incluir estrategias en las GPC para prevenir su desarrollo. (AU)

Introduction: Renal involvement due to necrotizing pauci-immune glomerulonephritis (PIGN) associated with small vessel vasculitis requires the use of immunosuppressive. Associated side effects include an increased risk of infectious processes, such as cytomegalovirus (CMV) disease; therefore, there are no recommendations on its management in the various clinical practice guidelines (CPG).ObjectiveTo study the incidence of CMV disease and its determinants.Patients and methodsPatients with histological diagnosis of necrotizing pauci-immune glomerulonephritis in the last 10 years, who were determined the viral load of CMV, analyzing the determinants of its occurrence.ResultsForty-four biopsies were performed during the study period. Eleven patients (25%) developed CMV disease; all had received immunosuppressive treatment. Four (30.8%) died during admission. The determinants of CMV disease were age (for every 10 years OR: 3.0, 95% CI: 1.0-8.9, p = 0.012), and plasma albumin (for each g/L OR: 0.8, 95% CI: 0.6-1.0, p = 0.012).ConclusionsThe incidence of CMV disease in immunocompromised patients due to PIGN is high, with high mortality. It would be necessary to include strategies in the CPGs to prevent it. (AU)

Efficacy and safety of oral fosfomycin for asymptomatic bacteriuria in kidney transplant recipients: Results from a Spanish multicenter cohort.

Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR]: 1.1 - 10.5). Most episodes (96.4% [132/137]) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum ß-lactamase-producing Enterobacterales [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [95%CI]: 31.9 - 48.9) for the whole cohort and 42.3% (95%CI: 31.2 - 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR]: 2.42; 95%CI: 1.11 - 5.29; P-value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 - 41.35; P-value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.

Risk Factors for Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients: A Multinational Case-Control Study.

BACKGROUND: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors. METHODS: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections. RESULTS: Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40-62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection. CONCLUSIONS: Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.

[Cytomegalovirus disease in immunosuppressed patients with necrotizing pauci-immune glomerulonephritis]. / Enfermedad por citomegalovirus en los pacientes inmunodeprimidos por glomerulonefritis necrosante pauciinmune.

INTRODUCTION: Renal involvement due to necrotizing pauci-immune glomerulonephritis (PIGN) associated with small vessel vasculitis requires the use of immunosuppressive. Associated side effects include an increased risk of infectious processes, such as cytomegalovirus (CMV) disease; therefore, there are no recommendations on its management in the various clinical practice guidelines (CPG). OBJECTIVE: To study the incidence of CMV disease and its determinants. PATIENTS AND METHODS: Patients with histological diagnosis of necrotizing pauci-immune glomerulonephritis in the last 10 years, who were determined the viral load of CMV, analyzing the determinants of its occurrence. RESULTS: Forty-four biopsies were performed during the study period. Eleven patients (25%) developed CMV disease; all had received immunosuppressive treatment. Four (30.8%) died during admission. The determinants of CMV disease were age (for every 10 years OR: 3.0, 95% CI: 1.0-8.9, p = 0.012), and plasma albumin (for each g/L OR: 0.8, 95% CI: 0.6-1.0, p = 0.012). CONCLUSIONS: The incidence of CMV disease in immunocompromised patients due to PIGN is high, with high mortality. It would be necessary to include strategies in the CPGs to prevent it.

Successful treatment of invasive aspergillosis caused by Aspergillus parafelis in a kidney transplant recipient.

Invasive aspergillosis (IA) is associated with a high mortality rate in kidney-transplant recipients. Azole-resistance is increasing in Aspergillus fumigatus. We report a clinical case of a kidney-transplant recipient with cerebellar and pulmonary aspergillosis caused by azole-resistant Aspergillus parafelis (molecular identification through ß-tubulin sequence). The patient experienced an effective resolution after three surgical procedures and associated antifungal therapy. This case highlights that azole-resistant aspergillosis should be considered in every patient with IA as long as susceptibility testing results are not known. Therefore, in selected patients with IA and central nervous system involvement, empirical combination antifungal therapy could be considered.

Endocarditis infecciosa sobre TAVI: la necesidad de trabajar en equipo para mejorar los resultados. Respuesta / Infective endocarditis after transcatheter aortic valve implantation: A call for a joined effort to improve its results. Reply

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Oral fosfomycin for the treatment of lower urinary tract infections among kidney transplant recipients-Results of a Spanish multicenter cohort.

Oral fosfomycin may constitute an alternative for the treatment of lower urinary tract infections (UTIs) in kidney transplant recipients (KTRs), particularly in view of recent safety concerns with fluroquinolones. Specific data on the efficacy and safety of fosfomycin in KTR are scarce. We performed a retrospective study in 14 Spanish hospitals including KTRs treated with oral fosfomycin (calcium and trometamol salts) for posttransplant cystitis between January 2005 and December 2017. A total of 133 KTRs developed 143 episodes of cystitis. Most episodes (131 [91.6%]) were produced by gram-negative bacilli (GNB), and 78 (54.5%) were categorized as multidrug resistant (including extended-spectrum ß-lactamase-producing Enterobacteriaceae [14%] or carbapenem-resistant GNB [3.5%]). A median daily dose of 1.5 g of fosfomycin (interquartile range [IQR]: 1.5-2) was administered for a median of 7 days (IQR: 3-10). Clinical cure (remission of UTI-attributable symptoms at the end of therapy) was achieved in 83.9% (120/143) episodes. Among those episodes with follow-up urine culture, microbiological cure at month 1 was achieved in 70.2% (59/84) episodes. Percutaneous nephrostomy was associated with a lower probability of clinical cure (adjusted odds ratio: 10.50; 95% confidence interval: 0.98-112.29; P = 0.052). In conclusion, fosfomycin is an effective orally available alternative for treating cystitis among KTRs.

Endocarditis infecciosa después de TAVI: aportaciones de la experiencia en un único centro sobre la incidencia y los factores asociados / Infective endocarditis after transcatheter aortic valve implantation: Contributions of a single-centre experience on incidence and associated factors

INTRODUCCIÓN: La endocarditis infecciosa (EI) sobre transcatheter aortic valve implantation (TAVI) es una complicación emergente. Existen datos incompletos y dispares sobre su incidencia. Se aporta la experiencia en nuestro centro sobre incidencia, mortalidad y factores asociados de la EI post-TAVI y se compara con datos de la literatura. MÉTODOS: Estudio retrospectivo observacional de los casos de EI diagnosticados en pacientes que habían recibido TAVI, entre el 1 de junio de 2009 y el 1 de noviembre de 2017, en un centro universitario tras una mediana de seguimiento de 15,3 meses (rango intercuartil [RIC] 9,1-36,2). Se analizaron la incidencia, los datos clínicos, microbiológicos y pronósticos, y los factores asociados a EI post-TAVI. RESULTADOS: Se detectaron 11 pacientes con EI de 200 TAVI. Incidencia global: 5,5% (2,77 casos por 100 años-paciente). La mediana de tiempo hasta la EI post-TAVI fue de 112 días (RIC 36-578), la tasa de mortalidad intrahospitalaria fue del 36,4% y la mortalidad al año, del 54,5%. Todos los microorganismos identificados fueron grampositivos (4 Enterococcus faecalis, 3 Staphylococcus coagulasa negativo). Los pacientes con EI post-TAVI eran significativamente más jóvenes (mediana 78, RIC 73-80, frente a 82, RIC 79-84, p = 0,002), tenían un EuroSCORE mayor (5,1 ± 2,4 frente a 3,2 ± 1,2, p < 0,001) y más frecuentemente antecedentes de neoplasia (18,2% frente al 4,2%, p < 0,03). CONCLUSIONES: En nuestro medio, la incidencia de EI post-TAVI es mayor que la descrita en series multicéntricas, lo que concuerda con la tendencia publicada en la literatura. Conlleva una elevada mortalidad y se asocia con una peor situación clínica basal

INTRODUCTION: Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is an emerging complication. There are incomplete and disparate data on its incidence. We present the experience of a single-centre of incidence, mortality and associated factors of IE after TAVI. METHODS: A retrospective observational study of IE cases in people who received a TAVI, between 06/01/2009 and 11/01/2017, in a university hospital, during a median follow-up period of 15.3months (interquartile range [IQR] 9.1-36.2). Incidence, clinical, microbiological and prognostic data, and factors associated with IE after TAVI were analysed. RESULTS: Eleven patients with IE of 200 TAVI were detected. Global incidence: 5.5% (2.77 cases per 100 patient-year). The median of days from TAVI to IE was 112 (IQR 36-578), the in-hospital mortality rate was 36.4%, and the one-year mortality rate was 54.5%. All the organisms identified were gram-positive (4 Enterococcus faecalis, 3 coagulase-negative Staphylococcus). The patients with IE after TAVI were significantly younger (median 78 years, IQR 73-80, versus 82 years, IQR 79-84, P=.002), they had a higher EuroSCORE (5.1±2.4 versus 3.2 ± 1.2, P < .001), and they more frequently had a history of neoplasia (18.2% versus 4.2%, P < .03). CONCLUSIONS: In our area, IE after TAVI has an incidence greater than that described in multicentre series, this is in line with the trend published in the literature. It leads to high mortality and is associated with a worse baseline clinical situation

Infective endocarditis after transcatheter aortic valve implantation: Contributions of a single-centre experience on incidence and associated factors. / Endocarditis infecciosa después de TAVI: aportaciones de la experiencia en un único centro sobre la incidencia y los factores asociados.

INTRODUCTION: Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is an emerging complication. There are incomplete and disparate data on its incidence. We present the experience of a single-centre of incidence, mortality and associated factors of IE after TAVI. METHODS: A retrospective observational study of IE cases in people who received a TAVI, between 06/01/2009 and 11/01/2017, in a university hospital, during a median follow-up period of 15.3months (interquartile range [IQR] 9.1-36.2). Incidence, clinical, microbiological and prognostic data, and factors associated with IE after TAVI were analysed. RESULTS: Eleven patients with IE of 200 TAVI were detected. Global incidence: 5.5% (2.77 cases per 100 patient-year). The median of days from TAVI to IE was 112 (IQR 36-578), the in-hospital mortality rate was 36.4%, and the one-year mortality rate was 54.5%. All the organisms identified were gram-positive (4 Enterococcus faecalis, 3 coagulase-negative Staphylococcus). The patients with IE after TAVI were significantly younger (median 78years, IQR 73-80, versus 82 years, IQR 79-84, P=.002), they had a higher EuroSCORE (5.1±2.4 versus 3.2±1.2, P<.001), and they more frequently had a history of neoplasia (18.2% versus 4.2%, P<.03) CONCLUSIONS: In our area, IE after TAVI has an incidence greater than that described in multicentre series, this is in line with the trend published in the literature. It leads to high mortality and is associated with a worse baseline clinical situation.

Delayed haemolysis after artesunate therapy in a cohort of patients with severe imported malaria due to Plasmodium falciparum / Hemólisis diferida tras el tratamiento con artesunato en una cohorte de pacientes con malaria grave importada por Plasmodium falciparum

Introduction: Delayed haemolytic anaemia is one of the more frequent events after treatment with intravenous artesunate in patients with severe malaria. Little is known about its frequency and the outcomes of patients with this condition. Methods: A retrospective study was conducted to describe the incidence of delayed haemolysis in a cohort of patients with severe malaria by Plasmodium falciparum treated with artesunate between August 2013 and July 2015. Results: The study included 52 patients with malaria due to Plasmodium falciparum, with 21 having severe malaria. The majority were male (66.7%), and the median age was 43 years. Four patients (19%) presented post-artesunate delayed haemolysis 11-13 days from the initiation of treatment. Two patients required hospital admission and red blood cell transfusion. Conclusion: Post-artesunate delayed haemolysis is frequent in patients with severe malaria treated with intravenous artemisinins. These patients should be monitored for 4 weeks after treatment is started (AU)

Introducción: La anemia hemolítica diferida es uno de los acontecimientos más frecuentes tras el tratamiento con artesunato intravenoso en pacientes con malaria grave. Se desconocen con exactitud la frecuencia y evolución de los pacientes que la presentan. Métodos: Estudio retrospectivo sobre la incidencia de hemólisis diferida en una cohorte de pacientes con malaria grave por Plasmodium falciparum tratados con artesunato intravenoso entre agosto de 2013 y julio de 2015. Resultados: De 52 pacientes con malaria por Plasmodium falciparum, 21 cumplían criterios de gravedad. La mayoría eran hombres (66,7%) y la mediana de edad era de 43 años. Cuatro pacientes (19%) presentaron hemólisis diferida post-artesunato, de 11 a 13 días tras el inicio del tratamiento. Dos pacientes requirieron hospitalización y transfusión de hematíes. Conclusión: La hemólisis diferida post-artesunato es frecuente en los pacientes con malaria grave tratados con artesunato intravenoso. Estos pacientes deben ser monitorizados al menos 4 semanas tras el tratamiento (AU)

Sentinel surveillance of imported dengue via travellers to Europe 2012 to 2014: TropNet data from the DengueTools Research Initiative.

We describe the epidemiological pattern and genetic characteristics of 242 acute dengue infections imported to Europe by returning travellers from 2012 to 2014. The overall geographical pattern of imported dengue (South-east Asia > Americas > western Pacific region > Africa) remained stable compared with 1999 to 2010. We isolated the majority of dengue virus genotypes and epidemic lineages causing outbreaks and epidemics in Asia, America and Africa during the study period. Travellers acted as sentinels for four unusual dengue outbreaks (Madeira, 2012-13; Luanda, 2013; Dar es Salaam, 2014; Tokyo, 2014). We were able to characterise dengue viruses imported from regions where currently no virological surveillance data are available. Up to 36% of travellers infected with dengue while travelling returned during the acute phase of the infection (up to 7 days after symptom onset) or became symptomatic after returning to Europe, and 58% of the patients with acute dengue infection were viraemic when seeking medical care. Epidemiological and virological data from dengue-infected international travellers can add an important layer to global surveillance efforts. A considerable number of dengue-infected travellers are viraemic after arrival back home, which poses a risk for dengue introduction and autochthonous transmission in European regions where suitable mosquito vectors are prevalent.

Delayed haemolysis after artesunate therapy in a cohort of patients with severe imported malaria due to Plasmodium falciparum.

INTRODUCTION: Delayed haemolytic anaemia is one of the more frequent events after treatment with intravenous artesunate in patients with severe malaria. Little is known about its frequency and the outcomes of patients with this condition. METHODS: A retrospective study was conducted to describe the incidence of delayed haemolysis in a cohort of patients with severe malaria by Plasmodium falciparum treated with artesunate between August 2013 and July 2015. RESULTS: The study included 52 patients with malaria due to Plasmodium falciparum, with 21 having severe malaria. The majority were male (66.7%), and the median age was 43 years. Four patients (19%) presented post-artesunate delayed haemolysis 11-13 days from the initiation of treatment. Two patients required hospital admission and red blood cell transfusion. CONCLUSION: Post-artesunate delayed haemolysis is frequent in patients with severe malaria treated with intravenous artemisinins. These patients should be monitored for 4 weeks after treatment is started.

The role of red blood cell exchange for severe imported malaria in the artesunate era: a retrospective cohort study in a referral centre.

BACKGROUND: Intravenous artesunate has replaced quinine as the first-line therapy for severe imported malaria, given its anti-malarial superiority shown in clinical trials conducted in endemic countries. Evidence for red blood cell (RBC) exchange in patients with severe malaria treated with artesunate is lacking. This retrospective cohort study describes the experience at Hospital Clinic of Barcelona with the use of artesunate for severe malaria and the joint use of RBC exchange in selected cases. METHODS: Patients treated for severe malaria at Hospital Clinic of Barcelona between August 2013 and January 2015 were included in this retrospective study. Severe malaria was defined according to WHO criteria. Data were extracted from electronic hospital records. A log-linear mixed model approach was used to estimate parasite clearance times. RESULTS: Within the study period, 42 patients were diagnosed of malaria at this centre, of which 38 had Plasmodium falciparum (90.5 %). Sixteen patients (42 %) had severe malaria cases and were treated with intravenous artesunate. Four patients underwent RBC exchange within a period of 15 h after the first dose of artesunate (range 9-21 h). The procedure lasted a median of 2 h (IQR 1.8-2 h), using a median of 12 (IQR 11-14) units of packed RBCs to replace a median of 3794 ml (IQR 2977-4343). The technique was well-tolerated without haemodynamic complications. There were no deaths. The regression model showed an estimated time to 95 % decay of 21.6 h (95 % CI 17.3-28.8). When assessing effect modification by RBC exchange, there was no difference in the parasite elimination rate (p = 0.286). DISCUSSION AND CONCLUSION: In this study RBC exchange failed to show benefits in terms of parasite clearance probably due to the small number of patients analysed. The evidence for exchange transfusion remains limited.