Dynamics of Human Anelloviruses in Plasma and Clinical Outcomes Following Kidney Transplantation.

BACKGROUND: Torque teno virus, the major member of the genus Alphatorquevirus , is an emerging biomarker of the net state of immunosuppression after kidney transplantation. Genetic diversity constitutes a main feature of the Anelloviridae family, although its posttransplant dynamics and clinical correlates are largely unknown. METHODS: The relative abundance of Alphatorquevirus , Betatorquevirus , and Gammatorquevirus genera was investigated by high-throughput sequencing in plasma specimens obtained at various points during the first posttransplant year (n = 91 recipients). Total loads of all members of the Anelloviridae family were also quantified by an "in-house" polymerase chain reaction assay targeting conserved DNA sequences (n = 195 recipients). In addition to viral kinetics, clinical study outcomes included serious infection, immunosuppression-related adverse event (opportunistic infection and cancer)' and acute rejection. RESULTS: Alphatorquevirus DNA was detected in all patients at every point, with an increase from pretransplantation to month 1. A variable proportion of recipients had detectable Betatorquevirus and Gammatorquevirus at lower frequencies. At least 1 change in the predominant genus (mainly as early transition to Alphatorquevirus predominance) was shown in 35.6% of evaluable patients. Total anelloviruses DNA levels increased from baseline to month 1, to peak by month 3 and decrease thereafter, and were higher in patients treated with T-cell depleting agents. There was a significant albeit weak-to-moderate correlation between total anelloviruses and TTV DNA levels. No associations were found between the predominant Anelloviridae genus or total anelloviruses DNA levels and clinical outcomes. CONCLUSIONS: Our study provides novel insight into the evolution of the anellome after kidney transplantation.

Genetic polymorphisms in TLR3, IL10 and CD209 influence the risk of BK polyomavirus infection after kidney transplantation.

Genetic determinants of BK polyomavirus infection after kidney transplantation remain poorly investigated. We assessed the potential impact of 13 different single nucleotide polymorphisms within genes mainly involved in innate immune responses on the risk of BKPyV viremia in 204 KT recipients. After a median follow-up of 1121.5 days, the cumulative incidence of any-level BKPyV viremia was 24.5% (50/204). There was a significant association between the minor T allele of TLR3 (rs3775291) SNP and the development of BKPyV viremia (adjusted hazard ratio [aHR]: 2.16; 95% confidence interval [CI]: 1.08-4.30; P value = 0.029), whereas the minor G allele of CD209 (rs4804803) SNP exerted a protective role (aHR: 0.54; 95% CI: 0.29-1.00; P value = 0.050). A higher incidence of BKPyV viremia was also observed for the minor G allele of IL10 (rs1800872) SNP, although the absence of BKPyV events among homozygotes for the reference allele prevented multivariable analysis. The BKPyV viremia-free survival rate decreased with the increasing number of unfavorable genotypes (100% [no unfavorable genotypes], 85.4% [1 genotype], 70.9% [2 genotypes], 52.5% [3 genotypes]; P value = 0.008). In conclusion, SNPs in TLR3, CD209 and IL10 genes play a role in modulating the susceptibility to any-level BKPyV viremia among KT recipients.

Human pegivirus type 1 infection in kidney transplant recipients: Replication kinetics and clinical correlates.

BACKGROUND: Increasing evidence suggests that infection with the nonpathogenic human pegivirus type 1 (HPgV-1) exerts a clinical benefit in human immunodeficiency virus (HIV) patients, which could be attributable to immunomodulatory effects. Whether this impact can be extrapolated to kidney transplantation (KT) remains largely unknown. METHODS: We measured plasma HPgV-1 RNA by real-time polymerase chain reaction targeting the 5' untranslated region at various points (pretransplantation, day 7, months 1, 3, 6, and 12) in 199 KT recipients. Study outcomes included posttransplant serious infection, immunosuppression-related adverse event (opportunistic infection and/or de novo cancer), and acute graft rejection. RESULTS: HPgV-1 infection was demonstrated in 52 (26.1%) patients, with rates increasing from 14.7% at baseline to 19.1% by month 12 (p-value = .071). De novo infection occurred in 13.8% of patients with no detectable HPgV-1 RNA before transplantation. Double-organ (liver-kidney or kidney-pancreas) transplantation (odds ratio [OR]: 5.62; 95% confidence interval [CI]: 1.52-20.82) and donation after brain death (OR: 2.21; 95% CI: 1.00-4.88) were associated with posttransplant HPgV-1 infection, whereas pretransplant hypertension was protective (OR: 0.23; 95% CI: 0.09-0.55). There were no significant differences in the incidence of study outcomes according to HPgV-1 status. Plasma HPgV-1 RNA levels at different points did not significantly differ between patients that subsequently developed outcomes and those remaining free from these events. No correlation between HPgV-1 RNA and immune parameters or torque teno virus DNA load was observed either. CONCLUSION: Unlike patients living with HIV, HPgV-1 infection does not seem to influence patient or graft outcomes after KT.

Gestações na adolescência e adesão à consulta puerperal / Adolescent pregnancies and adherence to puerperal consultation / Embarazos en adolescentes y adherencia a la consulta puerperal

Resumo Objetivo: identificar o perfil das gestações e prevalência de adesão à consulta puerperal entre puérperas adolescentes comparadas a não adolescentes, assistidas em um ambulatório de hospital de ensino do interior de Minas Gerais. Método: estudo transversal aninhado a uma coorte de puérperas; amostra não probabilística, por conveniência; gestação na adolescência - variável dependente; sociodemográficas, clínicas e obstétricas - variáveis independentes. Utilizado instrumento próprio, testado mediante piloto. Calculadas razões de prevalência e intervalos de confiança; aplicados testes qui-quadrado e exato de Fisher, considerando nível de significância de 5%, e regressão de Poisson com variância robusta. Resultados: entrevistadas 121 puérperas, 18,2% (22) adolescentes, verificou-se entre elas baixa escolaridade (p<0,001); menor número de gestações cursando com patologias (p = 0,016); predomínio de primíparas (p<0,001) e maiores índices de parto normal (p = 0,032). A prevalência de adesão à consulta puerperal foi de 34,7% e de 31,8% para adolescentes. Não houve diferenças em relação à adesão e idade das puérperas. Conclusão: adolescentes não apresentaram desfechos obstétricos e neonatais negativos, embora tenha sido observada menor escolaridade. Identificou-se associação entre idade precoce e ausência de doenças na gestação e maiores índices de partos vaginais normais. A adesão ao retorno puerperal apresentou-se pouco inferior, porém sem significância estatística.

Abstract Objective: to determine the profile of pregnancies and prevalence of adherence to puerperal consultation among adolescent puerperal women compared to non-adolescent puerperal women served in an outpatient clinic of a teaching hospital in the rural area of Minas Gerais. Method: cross-sectional study nested in a cohort of puerperal women; non-probabilistic sample, by convenience; adolescent pregnancy - dependent variable; sociodemographic, clinical and obstetric - independent variables. It employed its own instrument, tested by means of a pilot test. Prevalence ratios and confidence intervals were calculated; chi-square and Fisher's exact tests were applied, considering a significance level of 5%, and Poisson regression with robust variance. Results: we interviewed 121 puerperal women, of which 18.2% (22) were adolescents, and observed among them low educational level (p<0.001); fewer pregnancies with pathologies (p=0.016); predominance of primiparous women (p<0.001), and higher rates of normal delivery (p=0.032). The prevalence of adherence to puerperal consultation was 34.7% and 31.8% for adolescents. There were no differences regarding adherence and age of puerperal women. Conclusion: adolescents did not present negative obstetric and neonatal outcomes, although a lower educational level was observed. Association was found between early age and absence of diseases during pregnancy and higher rates of normal vaginal deliveries. Adherence to puerperal return visit was slightly lower, but without statistical significance.

Resumen Objetivo: identificar el perfil de embarazos y la prevalencia de adherencia a las consultas puerperales entre madres adolescentes frente a las no adolescentes, atendidas en un hospital clínico universitario en el interior de Minas Gerais (Brasil). Método: estudio transversal anidado en un grupo de puérperas; muestra no probabilística, por conveniencia; embarazo adolescente - variable dependiente; variables sociodemográficas, clínicas y obstétricas- variables independientes. Se utilizó instrumento propio, prueba piloto. Se calcularon razones de prevalencia e intervalos de confianza; Se aplicaron las pruebas chi-cuadrado y exacta de Fisher, considerando un nivel de significancia del 5%, y regresión de Poisson con varianza robusta. Resultados: se entrevistaron a 121 puérperas, el 18,2% (22) eran adolescentes, siendo confirmado entre ellas una baja escolaridad (p<0,001); menor número de embarazos con patologías (p = 0,016); predominando las primíparas (p<0,001) y mayores tasas de parto normal (p = 0,032). La prevalencia de adherencia a la consulta puerperal fue del 34,7% y de 31,8% en adolescentes. No hubo diferencias en cuanto a la adherencia y la edad de las puérperas. Conclusión: las adolescentes no presentaron resultados obstétricos y neonatales negativos, aunque se observó menor escolaridad. Se identificó una asociación entre la edad precoz y la ausencia de enfermedades durante el embarazo y mayores tasas de partos vaginales normales. La adherencia al retorno puerperal fue ligeramente inferior, pero sin significación estadística.

CMV infection, valganciclovir exposure, and the risk of BK viremia and associated nephropathy after kidney transplantation: Is there a link?

BACKGROUND: Immunomodulatory effects attributable to cytomegalovirus (CMV) would predispose to BK polyomavirus (BKPyV) infection after kidney transplantation (KT), although available evidence is conflicting. It has been suggested that (val)ganciclovir therapy may increase the risk of BKPyV viremia and BKPyV-associated nephropathy (BKPyVAN) as a result of drug-induced T-cell impairment. METHODS: We investigated whether CMV replication and/or (val)ganciclovir exposure (either as prophylaxis or treatment) were associated with the development of BKPyV viremia or BKPyVAN in a prospective cohort of 399 KT recipients. CMV infection (any level or high-level viremia and area under the curve of DNAemia) and (val)ganciclovir exposure (any duration of therapy and cumulative days of treatment) during the first post-transplant year were explored through separate landmark survival analyses. RESULTS: Cumulative incidence of BKPyV viremia and BKPyVAN after a median follow-up of 551 days was 23.1% and 2.5%, respectively. One-year rates of CMV infection and (val)ganciclovir therapy were 47.4% and 54.1%, respectively. No differences were observed in BKPyV viremia- or BKPyVAN-free survival according to previous CMV infection or (val)ganciclovir exposure in any of the landmark analyses. Adjusted Cox models confirmed this lack of association. CONCLUSION: Our findings do not confirm the existence of a relevant impact of CMV infection or (val)ganciclovir therapy on the risk of post-transplant BKPyV events.

Cultural adaptation and assessment of the reliability of the Special Needs Kids Questionnaire for the Brazilian context / Adaptación cultural y evaluación de la fidedignidad del Cuestionario Infantil de Necesidades Especiales para el contexto brasileño / Adaptação cultural e avaliação da fidedignidade do Special Needs Kids Questionnaire para o contexto brasileiro

ABSTRACT Objective To carry out the cultural adaptation of the Special Needs Kids Questionnaire into Brazilian Portuguese and assess its reliability. Methods Methodological study conducted between September 2019 and June 2020 from the stages of translation, back-translation, content validation, semantic validation and pilot test. Content Validation Index, Cronbach's Alpha Coefficient and Intraclass Correlation Coefficient were calculated. Results After the second round, the adapted version had a Content Validation Index greater than 0.80 in all items and was considered understandable by the mothers. The pilot test included 89 mothers of children born prematurely from the Neonatal Intensive Care Unit in the test and 44 in the retest. All items had Cronbach's Alpha greater than 0.70. Of the 20 items, 15 showed moderate reliability, three high and two weak. Conclusion The instrument proved to be reliable and has the potential to identify the fragmentation and discontinuity of the care received.

RESUMEN Objetivo Realizar la adaptación cultural del Cuestionario para niños con necesidades especiales al portugués brasileño y evaluar su fiabilidad. Métodos Estudio metodológico realizado entre septiembre de 2019 y junio de 2020 a partir de las etapas de traducción, retrotraducción, validación de contenido, validación semántica y prueba piloto. Se calcularon el índice de validación de contenido, el coeficiente alfa de Cronbach y el coeficiente de correlación intraclase. Resultados Después de la segunda ronda, la versión adaptada tuvo un Índice de Validación de Contenido superior a 0,80 en todos los ítems y fue considerada comprensible por las madres. La prueba piloto incluyó a 89 madres de niños nacidos prematuramente de la Unidad de Cuidados Intensivos Neonatales en la prueba y 44 en la reprueba. Todos los ítems tenían un Alfa de Cronbach superior a 0,70. De los 20 ítems, 15 mostraron confiabilidad moderada, tres alta y dos débil. Conclusión El instrumento demostró ser confiable y tiene potencial para identificar la fragmentación y discontinuidad de la atención recibida.

RESUMO Objetivo Realizar a adaptação cultural do Special Needs Kids Questionnarie para o português do Brasil e avaliar sua fidedignidade. Métodos Estudo metodológico realizado entre setembro de 2019 e junho de 2020 a partir das etapas de tradução, retrotradução, validação de conteúdo, validação semântica e teste piloto. -Foi calculado Índice de Validação de Conteúdo, Coeficiente Alpha de Cronbach e Coeficiente de Correlação Intraclasse. Resultados Após segunda rodada, a versão adaptada apresentou Índice de Validação de Conteúdo superior a 0,80 em todos os itens e foi considerada compreensível pelas mães. O teste piloto contou com 89 mães de crianças nascidas prematuras egressas da Unidade de Terapia Intensiva Neonatal no teste e 44 no reteste. Todos os itens apresentaram Alpha de Cronbach superior a 0,70. Dos 20 itens, 15 demonstraram moderada confiabilidade, três alta e dois fraca. Conclusão Instrumento mostrou-se fidedigno e tem potencial para identificar a fragmentação e descontinuidade do cuidado recebido.

Intususcepción como causa de obstrucción intestinal en el adulto: un desafío para los cirujanos / Intussusception as cause of intestinal obstruction in the adult: a challenge for surgeons

La intususcepción en adultos es una condición inusual, que corresponde al 5 % de todos los casos de obstrucción intestinal y carece de síntomas específicos. El diagnóstico preoperatorio sigue siendo un desafío para el cirujano y el tratamiento óptimo de esta condición es controvertido. Se presentan dos casos clínicos de intususcepción con diferente etiología. El primero sufrió una intususcepción colocólica por un adenocarcinoma y, el segundo, una intususcepción ileocólica por un tumor del estroma gastrointestinal (GIST). Los casos fueron diagnosticados preoperatoriamente mediante tomografía axial de abdomen. En ambos casos, se practicó una resección quirúrgica oncológica. El estudio de histopatología confirmó el diagnóstico definitivo. Se describen el diagnóstico y el tratamiento de la intususcepción como causa de obstrucción intestinal en los adultos, y se presenta una revisión de la literatura científica

Intestinal intussusception in adults is a rare finding, with non specific symptoms and is responsible for 5% of intestinal obstructions. Pre-operative diagnosis remains a challenge for surgeons and the optimal treatment is still in debate. We present two cases of intestinal intussusception caused by different etiologies; the first is a colon-colonic intussusception caused by an adenocarcinoma, and the second is an ileo-colonic intussusception caused by a gastrointestinal stromal tumor (GIST). Both cases were diagnostic pre-operatively by abdominal CT. Oncologic surgical resection was performed in both cases. Histopathology report confirmed neoplastic tissues. We describe the diagnosis and treatment of intestinal intussusception as a cause of intestinal obstruction in the adult population

Toxin B PCR Amplification Cycle Threshold Adds Little to Clinical Variables for Predicting Outcomes in Clostridium difficile Infection: a Retrospective Cohort Study.

The objective of the present study was to evaluate the value of the PCR cycle threshold (CT ) for predicting the recurrence/severity of infection compared to that of toxin detection plus clinical variables. First episodes of Clostridium difficile infection (CDI) diagnosed during 2015 at our institution were included. Samples were tested for glutamate dehydrogenase (GDH) and toxin A/B by use of a single enzyme immunoassay (EIA). The Xpert C. difficile PCR assay was performed on GDH-positive samples. Medical data were reviewed by investigators blinded to diagnostic results for comparison of patients with and without recurrence or a poor outcome (severe/severe-complicated CDI episodes and all-cause death). We generated two sets of predictive models by incorporating the presence of a positive toxin EIA ("EIA-including model") or the optimal PCR CT cutoff value ("PCR-including model") into the clinical variables. Among 227 episodes of CDI included in the study, the rates of recurrence and poor outcome were 15.8% and 30.8%, respectively. The mean PCR CT was lower for episodes with recurrence (24.00 ± 3.28 versus 26.02 ± 4.54; P = 0.002) or a poor outcome (24.9 ± 4.24 versus 26.05 ± 4.47; P = 0.07). The optimal cutoff value for recurrence was 25.65 (sensitivity, 77.8% [95% confidence interval {CI}, 60.9 to 89.9]; and specificity, 46.6% [95% CI, 39.4 to 53.9]). The area under the receiver operator characteristics curve (auROC) for the "PCR-including model" was similar to that for the "EIA-including model" (0.785 versus 0.775, respectively). The optimal PCR CT value for poor outcome was 27.55 (sensitivity, 78.6% [95% CI, 67.1 to 87.5]; and specificity, 35.7% [95% CI, 28.2 to 43.7]). The auROC of the "PCR-including model" was again similar to that of the "EIA-including model" (0.804 versus 0.801). Despite the inverse correlation between PCR CT and the risk of CDI recurrence/severity, this determination does not meaningfully increase the predictive value of clinical variables plus toxin EIA.

Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression-related complications after kidney transplantation.

The replication kinetics of nonpathogenic anelloviruses belonging to the Alphatorquevirus genus (such as torque teno virus) might reflect the overall state of posttransplant immunosuppression. We analyzed 221 kidney transplant (KT) recipients in whom plasma alphatorquevirus DNA load was quantified by real-time polymerase chain reaction at baseline and regularly through the first 12 posttransplant months. Study outcomes included posttransplant infection and a composite of opportunistic infection and/or de novo malignancy (immunosuppression-related adverse event [iRAE]). Alphatorquevirus DNA loads at month 1 were higher among patients who subsequently developed posttransplant infection (P  = .023) or iRAE (P  = .009). Likewise, those with iRAE beyond months 3 and 6 also exhibited higher peak viral loads over the preceding periods. Areas under the curve for log10 alphatorquevirus DNAemia estimated by months 1 or 6 were significantly higher in patients experiencing study outcomes. Alphatorquevirus DNA loads above 3.15 and 4.56 log10 copies/mL at month 1 predicted the occurrence of posttransplant infection (adjusted hazard ratio [aHR]: 2.88; 95% confidence interval [CI]: 1.13-7.36; P  = .027) and iRAE (aHR: 5.17; 95% CI: 2.01-13.33; P  = .001). In conclusion, posttransplant monitoring of plasma alphatorquevirus DNA kinetics may be useful to identify KT recipients at increased risk of immunosuppression-related complications.

Herpes zoster in kidney transplant recipients: protective effect of anti-cytomegalovirus prophylaxis and natural killer cell count. A single-center cohort study.

Despite its impact on quality of life and potential for complications, specific risk and protective factors for herpes zoster (HZ) after kidney transplantation (KT) remain to be clarified. We included 444 patients undergoing KT between November 2008 and March 2013. Peripheral blood lymphocyte subpopulations were measured at baseline and months 1 and 6. The risk factors for early (first post-transplant year) and late HZ (years 1-5) were separately assessed. We observed 35 episodes of post-transplant HZ after a median follow-up of 48.3 months (incidence rate: 0.057 per 1000 transplant-days). Median interval from transplantation was 18.3 months. Six patients (17.1%) developed disseminated infection. Postherpetic neuralgia occurred in 10 cases (28.6%). The receipt of anti-cytomegalovirus (CMV) prophylaxis with (val)ganciclovir decreased the risk of early HZ [adjusted hazard ratio (aHR): 0.08; 95% CI: 0.01-1.13; P-value = 0.062], whereas the natural killer (NK) cell at month 6 was protective for the occurrence of late HZ [aHR (per 10-cells/µl increase): 0.94; 95% CI: 0.88-1.00; P-value = 0.054]. In conclusion, two easily ascertainable factors (whether the patient is receiving anti-CMV prophylaxis and the NK cell count at month 6) might be potentially useful to tailor preventive strategies according to individual susceptibility to post-transplant HZ.

Association between baseline serum hepcidin levels and infection in kidney transplant recipients: Potential role for iron overload.

BACKGROUND: The liver-synthesized peptide hepcidin is a key regulator of iron metabolism and correlates with total iron stores. We analyzed the association between pre-transplant hepcidin-25 levels and infection after kidney transplantation (KT). METHODS: Serum hepcidin-25 levels were measured at baseline by high-sensitivity ELISA in 91 patients undergoing KT at our institution between December 2011 and March 2013. The impact of this biomarker on the incidence of post-transplant infection (excluding lower urinary tract infection) during the first year was assessed by Cox regression. RESULTS: Mean hepcidin-25 level was 82.3 ± 67.4 ng/mL and strongly correlated with serum ferritin (Spearman's rho = 0.703; P < .001). There were no significant differences in hepcidin-25 levels between patients with or without overall infection (96.4 ± 67.5 vs 72.6 ± 66.7 ng/mL; P = .101). Such difference was evident for opportunistic (128.9 ± 75.0 vs 73.0 ± 62.3 ng/mL; P = .003) and, to a lesser extent, surgical-site infection (107.5 ± 73.3 vs 76.5 ± 65.2 ng/mL; P = .087). Patients with hepcidin-25 levels ≥72.5 ng/mL had higher 12-month cumulative incidence of overall infection (51.2% vs 29.2%; P = .032). After multivariate adjustment, hepcidin-25 ≥72.5 ng/mL acted as an independent risk factor for overall (adjusted hazard ratio [aHR] 3.86; 95% confidence interval [CI] 1.49-9.96; P = .005) and opportunistic infection (aHR 4.32; 95% CI 1.18-15.75; P = .027). CONCLUSION: Elevated baseline serum hepcidin-25 levels were associated with increased risk of infection after KT, suggesting a role for iron overload in the individual susceptibility to post-transplant infection.

Serum sCD30: A promising biomarker for predicting the risk of bacterial infection after kidney transplantation.

BACKGROUND: The transmembrane glycoprotein CD30 contributes to regulate the balance between Th1 and Th2 responses. Previous studies have reported conflicting results on the utility of its soluble form (sCD30) to predict post-transplant infection. METHODS: Serum sCD30 was measured by a commercial ELISA assay at baseline and post-transplant months 1, 3, and 6 in 100 kidney transplant (KT) recipients (279 monitoring points). The impact of sCD30 levels on the incidence of overall, bacterial and opportunistic infection during the first 12 months after transplantation was assessed by Cox regression. RESULTS: There were no differences in serum sCD30 according to the occurrence of overall or opportunistic infection. However, sCD30 levels were higher in patients with bacterial infection compared to those without at baseline (P=.038) and months 1 (P<.0001), 3 (P=.043), and 6 after transplantation (P=.006). Patients with baseline sCD30 levels ≥13.5 ng/mL had lower 12-month bacterial infection-free survival (35.0% vs 80.0%; P<.0001). After adjusting for potential confounders, baseline sCD30 levels ≥13.5 ng/mL remained as an independent risk factor for bacterial infection (adjusted hazard ratio [aHR]: 4.65; 95% confidence interval [CI]: 2.05-10.53; <.001). Analogously, sCD30 levels ≥6.0 ng/mL at month 1 acted as a risk factor for subsequent bacterial infection (aHR: 5.29; 95% CI: 1.11-25.14; P=.036). CONCLUSION: Higher serum sCD30 levels were associated with an increased risk of bacterial infection after KT. We hypothesize that this biomarker reflects a Th2 -polarized T-cell response, which exerts a detrimental effect on the immunity against bacterial pathogens.

Identification and Characterization of the Dermal Panniculus Carnosus Muscle Stem Cells.

The dermal Panniculus carnosus (PC) muscle is important for wound contraction in lower mammals and represents an interesting model of muscle regeneration due to its high cell turnover. The resident satellite cells (the bona fide muscle stem cells) remain poorly characterized. Here we analyzed PC satellite cells with regard to developmental origin and purported function. Lineage tracing shows that they originate in Myf5(+), Pax3/Pax7(+) cell populations. Skin and muscle wounding increased PC myofiber turnover, with the satellite cell progeny being involved in muscle regeneration but with no detectable contribution to the wound-bed myofibroblasts. Since hematopoietic stem cells fuse to PC myofibers in the absence of injury, we also studied the contribution of bone marrow-derived cells to the PC satellite cell compartment, demonstrating that cells of donor origin are capable of repopulating the PC muscle stem cell niche after irradiation and bone marrow transplantation but may not fully acquire the relevant myogenic commitment.

Molecular epidemiology and clinical features of human T cell lymphotropic virus type 1 infection in Spain.

Human T cell lymphotropic virus type 1 (HTLV-1) infection in Spain is rare and mainly affects immigrants from endemic regions and native Spaniards with a prior history of sexual intercourse with persons from endemic countries. Herein, we report the main clinical and virological features of cases reported in Spain. All individuals with HTLV-1 infection recorded at the national registry since 1989 were examined. Phylogenetic analysis was performed based on the long terminal repeat (LTR) region. A total of 229 HTLV-1 cases had been reported up to December 2012. The mean age was 41 years old and 61% were female. Their country of origin was Latin America in 59%, Africa in 15%, and Spain in 20%. Transmission had occurred following sexual contact in 41%, parenteral exposure in 12%, and vertically in 9%. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was diagnosed in 27 cases and adult T cell leukemia/lymphoma (ATLL) in 17 subjects. HTLV-1 subtype could be obtained for 45 patients; all but one belonged to the Cosmopolitan subtype a. One Nigerian pregnant woman harbored HTLV-1 subtype b. Within the Cosmopolitan subtype a, two individuals (from Bolivia and Peru, respectively) belonged to the Japanese subgroup B, another two (from Senegal and Mauritania) to the North African subgroup D, and 39 to the Transcontinental subgroup A. Of note, one divergent HTLV-1 strain from an Ethiopian branched off from all five known Cosmopolitan subtype 1a subgroups. Divergent HTLV-1 strains have been introduced and currently circulate in Spain. The relatively large proportion of symptomatic cases (19%) suggests that HTLV-1 infection is underdiagnosed in Spain.

Association between HLA alleles and HAM/TSP in individuals infected with HTLV-1.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) develops in less than 5 % of HTLV-1 carriers. It is unclear which factors trigger the development of disease. The aim of this study was to explore the influence of HLA alleles on the development of HAM/TSP. A total of 40 HTLV-1-infected individuals belonging to the Spanish HTLV-1 cohort were examined. HTLV-1 proviral load was measured by real-time polymerase chain reaction. HLA class I (A, B, C) and class II (DRB1, DQB1) alleles were genotyped using the bead array technology. Median HTLV-1 proviral load in 12 HAM/TSP patients was greater than in 28 asymptomatic carriers (637 vs. 71 copies per 10(4) peripheral blood mononuclear cells; p = 0.006). Moreover, HAM/TSP was significantly associated with HLA-B 07 and HLA-DRB1 01:01 (p = 0.039). Interestingly, individuals with these HLA alleles had greater HTLV-1 proviral load than asymptomatic carriers (p = 0.036). In summary, HLA testing should be considered in asymptomatic HTLV-1 individuals and close monitoring of HTLV-1 proviral load along with periodic neurological evaluations should be prioritized in HLA-DRB1 01:01 and HLA-B 07 carriers.

Trends in the prevalence and distribution of HTLV-1 and HTLV-2 infections in Spain.

BACKGROUND: Although most HTLV infections in Spain have been found in native intravenous drug users carrying HTLV-2, the large immigration flows from Latin America and Sub-Saharan Africa in recent years may have changed the prevalence and distribution of HTLV-1 and HTLV-2 infections, and hypothetically open the opportunity for introducing HTLV-3 or HTLV-4 in Spain. To assess the current seroprevalence of HTLV infection in Spain a national multicenter, cross-sectional, study was conducted in June 2009. RESULTS: A total of 6,460 consecutive outpatients attending 16 hospitals were examined. Overall, 12% were immigrants, and their main origin was Latin America (4.9%), Africa (3.6%) and other European countries (2.8%). Nine individuals were seroreactive for HTLV antibodies (overall prevalence, 0.14%). Evidence of HTLV-1 infection was confirmed by Western blot in 4 subjects (prevalence 0.06%) while HTLV-2 infection was found in 5 (prevalence 0.08%). Infection with HTLV types 1, 2, 3 and 4 was discarded by Western blot and specific PCR assays in another two specimens initially reactive in the enzyme immunoassay. All but one HTLV-1 cases were Latin-Americans while all persons with HTLV-2 infection were native Spaniards. CONCLUSIONS: The overall prevalence of HTLV infections in Spain remains low, with no evidence of HTLV-3 or HTLV-4 infections so far.

HTLV infection among foreign pregnant women living in Spain.

BACKGROUND: The overall seroprevalence of HTLV infection among pregnant women in Spain is below 0.02% and accordingly universal antenatal screening is not recommended. However, as the number of immigrants has significantly increased during the last decade, this population might warrant specific considerations. OBJECTIVE: To evaluate the seroprevalence of HTLV infection among immigrant pregnant women living in Spain. METHODS: From January 2009 to December 2010 a cross-sectional study was carried out in all foreign pregnant women attended at 14 Spanish clinics. All were tested for HTLV antibodies using a commercial enzyme-immunoassay, being reactive samples confirmed by Western blot or PCR. RESULTS: A total of 3337 foreign pregnant women were examined. Their origin was as follows: Latin America 1579 (47%), North Africa 507 (16%), East Europe 606 (18%), Sub-Saharan Africa 316 (9%), North America and West Europe 116 (3.5%) and Asia and Australia 163 (5%). A total of 7 samples were confirmed as HTLV positive, of which 6 were HTLV-1 and 1 HTLV-2. HTLV-1 infection was found in 5 women coming from Latin America and 1 from Morocco. The only woman with HTLV-2 came from Ghana. The overall HTLV seroprevalence was 0.2%, being 0.3% among Latin Americans and 0.2% among Africans. It was absent among women coming from other regions. CONCLUSIONS: The seroprevalence of HTLV infection among foreign pregnant women in Spain is 0.2%, being all cases found in immigrants from Latin America and Africa. Given the benefit of preventing vertical transmission, antenatal screening should be recommended in pregnant women coming from these regions.