HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

COVID-19 vaccine failure

COVID-19 affects the population unequally with a higher impact on aged and immunosuppressed people. Hence, we assessed the effect of SARS-CoV-2 vaccination in immune compromised patients (older adults and oncohematologic patients), compared with healthy counterparts. While the acquired humoral and cellular memory did not predict subsequent infection 18 months after full immunization, spectral and computational cytometry revealed several subsets within the CD8+ T-cells, B-cells, NK cells, monocytes and CD45RA+ CCR7- Tγδ cells differentially expressed in further infected and non-infected individuals not just following immunization, but also prior to that. Of note, up to 7 subsets were found within the CD45RA+ CCR7- Tγδ population with some of them being expanded and other decreased in subsequently infected individuals. Moreover, some of these subsets also predicted COVID-induced hospitalization in oncohematologic patients. Therefore, we hereby have identified several cellular subsets that, even before vaccination, strongly related to COVID-19 vulnerability as opposed to the acquisition of cellular and/or humoral memory following vaccination with SARS-CoV2 mRNA vaccines.This study has been funded through Programa Estratégico Instituto de Biología y Genética Molecular (IBGM Junta de Castilla y León. Ref. CCVC8485), Junta de Castilla y León (Proyectos COVID 07.04.467B04.74011.0) and the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global; SGL21-03-026 and SGL2021-03-038)N

Considerations on HTLV-1 infection in Spain

Consideraciones sobre la infección por HTLV-1 en España

Hospital admissions in individuals with HTLV-1 infection in Spain

OBJECTIVE: To examine the clinical burden and disease spectrum, as well as time trends for human T-cell leukemia virus type 1 (HTLV-1) and HTLV type 2 (HTLV-2) hospital admissions. DESIGN: Retrospective, observational study using the Spanish National Hospital Discharge Database. METHODS: Information for the diagnostic codes HTLV-1 and HTLV-2 using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) was retrieved from the national public registry since 1997--2015. RESULTS: From a total of 66 462 136 nationwide hospital admissions recorded during the study period, 135 included HTLV diagnosis, being HTLV-1 in 115 (85.2%) and HTLV-2 in 20 (14.8%). The overall hospital admission rate because of HTLV was 2.03 per million, without significant yearly changes. First admissions represented 104 (77%) whereas 31 (23%) were re-admissions. The median in-hospital stay for HTLV patients was 9 days. In-hospital death occurred in 11 (8.1%). The median age of individuals with HTLV admission was 48 years and 60 (44.4%) were women. HTLV was recorded as the main diagnosis in 20%. The most frequent clinical conditions recorded alongside HTLV diagnosis were myelopathy (61; 45.2%), leukemia/lymphoma (30; 22.2%), solid organ transplantation (14; 10.4%) and child delivery (7; 5.2%). CONCLUSION: The rate of HTLV diagnosis in hospitalized patients in Spain is low, roughly of two per million admissions. Despite continuous large immigrant flows from HTLV-1 endemic areas, no significant rising in hospitalizations because of HTLV-1 associated illnesses were noticed during the last two decades. Classical clinical complications of HTLV-1 infection, such as myelopathy and lymphoma account for more than two-thirds of cases

Manual de Enfermedades Infecciosas y Terapia Antimicrobiana

Este Manual va dirigido a los alumnos del Máster en Enfermedades Infecciosas & Terapia Antimicrobiana de la Universidad Internacional de La Rioja (UNIR). El temario se adapta al programa del título universitario y complementa las clases online emitidas en directo (‘streaming’) con otros recursos docentes, en forma de vídeos, páginas web y foros virtuales. Es nuestro deseo que este texto sea una referencia en lengua española para los numerosos graduados en Medicina, Farmacia, Biología y Enfermería que están formándose o ya trabajan en unidades de enfermedades infecciosas y salud pública. En España no está reconocida de forma oficial la especialidad de enfermedades infecciosas, de modo que no existe un MIR de infectología. Aspiramos a que este texto actualizado y al que han contribuido expertos de toda la geografía española, sea el libro de consulta para todos los profesionales sanitarios interesados en la patología infecciosa. Los autores son todos profesores universitarios y gozan de una amplia experiencia docente. Por otro lado, el Manual tiene un marcado carácter clínico y está orientado al tratamiento antimicrobiano. El temario comprende 80 temas, que abordan de forma exhaustiva y actualizada los principales síndromes clínicos infecciosos. A continuación se abordan por separado las patologías más frecuentes causadas por bacterias, hongos, virus y parásitos. En una sección aparte, se describen las infecciones características de grupos de población especiales (viajeros, gestantes, inmunodeprimidos, etc.). Por último, se actualizan los tratamientos antimicrobianos y las vacunas. Agradeceremos los comentarios que puedan hacernos llegar los lectores. Los tendremos en cuenta para futuras ediciones. Pretendemos que este Manual sea un pilar fundamental para la formación de especialistas en enfermedades infecciosas en lengua española. El buen manejo de las personas infectadas es el mejor reconocimiento al esfuerzo que supone la edición de esta obra. Vicente Soriano, en nombre de los autore

Manual de Enfermedades Infecciosas y Terapia Antimicrobiana II

Tomo II Infecciones fúngicas Infecciones víricas Infecciones por protozoos y helmintos Infecciones emergentes y olvidadas Infecciones en poblaciones especiales Tratamiento antimicrobiano Salud PúblicaEste Manual va dirigido a los alumnos del Máster en Enfermedades Infecciosas & Terapia Antimicrobiana de la Universidad Internacional de La Rioja (UNIR). El temario se adapta al programa del título universitario y complementa las clases online emitidas en directo (‘streaming’) con otros recursos docentes, en forma de vídeos, páginas web y foros virtuales. Es nuestro deseo que este texto sea una referencia en lengua española para los numerosos graduados en Medicina, Farmacia, Biología y Enfermería que están formándose o ya trabajan en unidades de enfermedades infecciosas y salud pública. En España no está reconocida de forma oficial la especialidad de enfermedades infecciosas, de modo que no existe un MIR de infectología. Aspiramos a que este texto actualizado y al que han contribuido expertos de toda la geografía española, sea el libro de consulta para todos los profesionales sanitarios interesados en la patología infecciosa. Los autores son todos profesores universitarios y gozan de una amplia experiencia docente. Por otro lado, el Manual tiene un marcado carácter clínico y está orientado al tratamiento antimicrobiano. El temario comprende 80 temas, que abordan de forma exhaustiva y actualizada los principales síndromes clínicos infecciosos. A continuación se abordan por separado las patologías más frecuentes causadas por bacterias, hongos, virus y parásitos. En una sección aparte, se describen las infecciones características de grupos de población especiales (viajeros, gestantes, inmunodeprimidos, etc.). Por último, se actualizan los tratamientos antimicrobianos y las vacunas. Agradeceremos los comentarios que puedan hacernos llegar los lectores. Los tendremos en cuenta para futuras ediciones. Pretendemos que este Manual sea un pilar fundamental para la formación de especialistas en enfermedades infecciosas en lengua española. El buen manejo de las personas infectadas es el mejor reconocimiento al esfuerzo que supone la edición de esta obra. Vicente Soriano, en nombre de los autore

Manual de Enfermedades Infecciosas y Terapia Antimicrobiana I

Tomo I Introducción a las infecciones Síndromes infecciosos Infecciones bacterianasEste Manual va dirigido a los alumnos del Máster en Enfermedades Infecciosas & Terapia Antimicrobiana de la Universidad Internacional de La Rioja (UNIR). El temario se adapta al programa del título universitario y complementa las clases online emitidas en directo (‘streaming’) con otros recursos docentes, en forma de vídeos, páginas web y foros virtuales. Es nuestro deseo que este texto sea una referencia en lengua española para los numerosos graduados en Medicina, Farmacia, Biología y Enfermería que están formándose o ya trabajan en unidades de enfermedades infecciosas y salud pública. En España no está reconocida de forma oficial la especialidad de enfermedades infecciosas, de modo que no existe un MIR de infectología. Aspiramos a que este texto actualizado y al que han contribuido expertos de toda la geografía española, sea el libro de consulta para todos los profesionales sanitarios interesados en la patología infecciosa. Los autores son todos profesores universitarios y gozan de una amplia experiencia docente. Por otro lado, el Manual tiene un marcado carácter clínico y está orientado al tratamiento antimicrobiano. El temario comprende 80 temas, que abordan de forma exhaustiva y actualizada los principales síndromes clínicos infecciosos. A continuación se abordan por separado las patologías más frecuentes causadas por bacterias, hongos, virus y parásitos. En una sección aparte, se describen las infecciones características de grupos de población especiales (viajeros, gestantes, inmunodeprimidos, etc.). Por último, se actualizan los tratamientos antimicrobianos y las vacunas. Agradeceremos los comentarios que puedan hacernos llegar los lectores. Los tendremos en cuenta para futuras ediciones. Pretendemos que este Manual sea un pilar fundamental para la formación de especialistas en enfermedades infecciosas en lengua española. El buen manejo de las personas infectadas es el mejor reconocimiento al esfuerzo que supone la edición de esta obra. Vicente Soriano, en nombre de los autore

Crispr/casrx proof-of-concept for rna degradation: A future tool against rna viruses?

Influenza viruses provide a great threat for the human population, causing highly contagious respiratory infections that can lead to serious clinical complications. There are a limited variety of influenza antivirals, and these antivirals are subjected to the constant emergence of resistances. Therefore, the development of new antiviral strategies to combat influenza viruses and other RNA viruses must be promoted. In this work, we design a proof-of-concept of a recently described CRISPR/Cas tool that has been proposed as a possible future RNA virus antiviral, named CRISPR/CasRx. For this, we verified the efficiency of the CasRx endonuclease in the degradation of the eGFP mRNA reporter gene and we established the best conditions for, and the efficient performance of, the CRISPR/CasRx system. The results were measured by fluorescence microscopy, flow cytometry, and qRT-PCR. The analyses demonstrated a reduction in fluorescence, regardless of the amount of eGFP reporter plasmid transfected. The analyses showed an 86–90% reduction in fluorescence by flow cytometry and a 51–80% reduction in mRNA expression by qRT-PCR. Our results demonstrate that the CasRx endonuclease is an efficient tool for eGFP mRNA knockdown. Therefore, subsequent experiments could be useful for the development of a new antiviral tool

Human T-lymphotropic virus type 1 infection and disease in Spain

Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected disease despite roughly 15 million people are chronically infected worldwide. Lifelong less than 10% of carriers develop life-threatening diseases, mostly a subacute myelopathy known as tropical spastic paraparesis (TSP) and a lymphoproliferative disorder named adult T-cell leukemia (ATL). HTLV-1 is efficiently transmitted perinatally (breastfeeding), sexually (more from men to women) and parenterally (transfusions, injection drug user (IDU), and transplants). To date there is neither prophylactic vaccine nor effective antiviral therapy. A total of 327 cases of HTLV-1 infection had been reported at the HTLV-1 Spanish registry until December 2016, of whom 34 had been diagnosed with TSP and 25 with ATL. Overall 62% were Latin American immigrants and 13% were persons of African origin. The incidence of HTLV-1 in Spain has remained stable for nearly a decade with 20–25 new cases yearly. Of the 21 newly diagnosed HTLV-1 cases during year 2016, one was a native Spaniard pregnant woman, and four presented with symptomatic disease, including three with ATL and one with TSP. Underdiagnosis of HTLV-1 in Spain must be high (iceberg model), which may account for the disproportionate high rate of symptomatic cases (almost 20%) and the late recognition of preventable HTLV-1 transmissions in special populations, such as newborns and transplant recipients. Our current estimate is of 10 000 persons living with HTLV-1 infection in Spain. Given the large flux of immigrants and visitors from HTLV-1 endemic regions to Spain, the expansion of HTLV-1 screening policies is warranted. At this time, it seems worth recommending HTLV testing to all donor/recipient organ transplants and pregnant women regardless place of birth. Although current leukoreduction procedures largely prevent HTLV-1 transmission by blood transfusions, HTLV testing of all first-time donors should be cost-effective contributing to unveil asymptomatic unaware HTLV-1 carriers.The work was funded in part by grants from F-IES and ISCIII-Fondos Feder (PI13/01574; ICI14/00372; CD14/0243; FI14/0264; CM13/0309; CES12/003).Peer reviewe

Adult T-cell leukemia/lymphoma in HTLV-1 non-endemic regions

Background HTLV-1 infection is a neglected disease, despite producing neurological and lymphoproliferative severe illnesses and affect over 10 million people worldwide. Roughly 5% of HTLV-1 carriers develop Adult T-cell leukemia/lymphoma (ATLL), one of the most aggressive hematological malignancies. Methods A national HTLV-1 register exists since 1989 in Spain, a non-endemic country with a large migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic. The main features of all patients diagnosed with ATLL in Spain up to date are reported. Results A total of 451 cases of HTLV-1 infection had been reported in Spain until the end of year 2022. ATLL had been diagnosed in 35 (7.8%). The current average incidence of ATLL in Spain is of two cases per year. Women represent 57% of ATLL patients. Mean age at diagnosis was 47 years-old. Roughly 57% were Latin Americans and 26% Africans. At diagnosis, the majority presented with acute or lymphoma clinical forms. Survival was shorter than one year in most of them. Mean HTLV-1 proviral load was significantly greater in ATLL patients than in asymptomatic HTLV-1 carriers (2,305 vs 104 copies/104 PBMC). HTLV-1 subtyping in 6 ATLL patients found the 1a transcontinental variant (n = 4) and the Japanese variant (n = 2). All ATLL patients were negative for HIV-1, did not develop HTLV-1-associated myelopathy and were not transplant recipients. Conclusion The rate of ATLL is very low in Spain and mostly associated to migrants from HTLV-1 endemic regions. Given the poor clinical outcome of ATLL, HTLV-1 testing should be performed at least once in all migrants coming from HTLV-1 endemic countries and in natives who have lived in or had sex partners from such regions