Bridging the gap between molecular and genomic epidemiology in tuberculosis: inferring MIRU-VNTR patterns from genomic data.

The transition from MIRU-VNTR-based epidemiology studies in tuberculosis (TB) to genomic epidemiology has transformed how we track transmission. However, short-read sequencing is poor at analyzing repetitive regions such as the MIRU-VNTR loci. This causes a gap between the new genomic data and the large amount of information stored in historical databases. Long-read sequencing could bridge this knowledge gap by allowing analysis of repetitive regions. However, the feasibility of extracting MIRU-VNTRs from long reads and linking them to historical data has not been evaluated. In our study, an in silico arm, consisting of inference of MIRU patterns from long-read sequences (using MIRUReader program), was compared with an experimental arm, involving standard amplification and fragment sizing. We analyzed overall performance on 39 isolates from South Africa and confirmed reproducibility in a sample enriched with 62 clustered cases from Spain. Finally, we ran 25 consecutive incident cases, demonstrating the feasibility of correctly assigning new clustered/orphan cases by linking data inferred from genomic analysis to MIRU-VNTR databases. Of the 3,024 loci analyzed, only 11 discrepancies (0.36%) were found between the two arms: three attributed to experimental error and eight to misassigned alleles from long-read sequencing. A second round of analysis of these discrepancies resulted in agreement between the experimental and in silico arms in all but one locus. Adjusting the MIRUReader program code allowed us to flag potential in silico misassignments due to suboptimal coverage or unfixed double alleles. Our study indicates that long-read sequencing could help address potential chronological and geographical gaps arising from the transition from molecular to genomic epidemiology of tuberculosis. IMPORTANCE: The transition from molecular epidemiology in tuberculosis (TB), based on the analysis of repetitive regions (VNTR-based genotyping), to genomic epidemiology transforms in the precision with which we track transmission. However, short-read sequencing, the most common method for performing genomic analysis, is poor at analyzing repetitive regions. This means that we face a gap between the new genomic data and the large amount of information stored in historical databases, which is also an obstacle to cross-national surveillance involving settings where only molecular data are available. Long-read sequencing could help bridge this knowledge gap by allowing analysis of repetitive regions. Our study demonstrates that MIRU-VNTR patterns can be successfully inferred from long-read sequences, allowing the correct assignment of new cases as clustered/orphan by linking new data extracted from genomic analysis to historical MIRU-VNTR databases. Our data may provide a starting point for bridging the knowledge gap between the molecular and genomic eras in tuberculosis epidemiology.

Accelerating SARS-CoV-2 genomic surveillance in a routine clinical setting with nanopore sequencing.

BACKGROUND: SARS-CoV-2 genomic analysis has been key to the provision of valuable data to meet both epidemiological and clinical demands. High-throughput sequencing, generally Illumina-based, has been necessary to ensure the widest coverage in global variant tracking. However, a speedier response is needed for nosocomial outbreak analyses and rapid identification of patients infected by emerging VOCs. An alternative based on nanopore sequencing may be better suited to delivering a faster response when required; however, although there are several studies offering side-by-side comparisons of Illumina and nanopore sequencing, evaluations of the usefulness in the hospital routine of the faster availability of data provided by nanopore are still lacking. RESULTS: We performed a prospective 10-week nanopore-based sequencing in MinION in a routine laboratory setting, including 83 specimens where a faster response time was necessary. The specimens analyzed corresponded to i) international travellers in which lineages were assigned to determine the proper management/special isolation of the patients; ii) nosocomial infections and health-care-worker infections, where SNP-based comparisons were required to rule in/out epidemiological relationships and tailor specific interventions iii) sentinel cases and breakthrough infections to timely report to the Public Health authorities. MinION-based sequencing was compared with the standard procedures, supported on Illumina sequencing; MinION accelerated the delivery of results (anticipating results 1-12 days) and reduced costs per sample by 28€ compared to Illumina, without reducing accuracy in SNP calling. CONCLUSIONS: Parallel integration of Illumina and nanopore sequencing strategies is a suitable solution to ensure both high-throughput and rapid response to cope with accelerating the surveillance demands of SARS-CoV-2 while also maintaining accuracy.

First importations of SARS-CoV-2 P.1 and P.2 variants from Brazil to Spain and early community transmission / Primeras importaciones de las variantes SARS-CoV-2 P.1 y P.2 de Brasil a Madrid y transmisión comunitaria

Introduction: SARS-CoV-2variants of concern (VOC) have been described in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Among them, the most scarce information has been obtained from the P.1 variant and more data on its global presence and about its spreading dynamics are needed.Methods: Whole genome sequencing was performed prospectively on travellers arriving from Brazil and on a random selection of SARS-CoV-2 positive cases from our population.Results: In this study we report the first SARS-CoV-2 P.1 and P.2 variants exported from Brazil to Spain. The case infected with the P.1 variant, who had only stayed in Rio de Janeiro, required hospitalisation. The two P.2 cases remained asymptomatic. A wider distribution for P.1 variant beyond the Brazilian Amazonia should be considered. The exportation of the P.2 variant, carrying the E484K mutation, deserves attention. One month after the first description of P.1 and P.2 importations from Brazil to Madrid, these variants were identified circulating in the community, in cases without a travel history, and involved in household transmissionsConclusion: Whole genome sequencing of SARS-CoV-2 positive travellers arriving from Brazil allowed us to identify the first importations of P.1 and P.2 variants to Spain and their early community transmission.

Introducción: Se han descrito «variantes de preocupación» (VOC) de SARS-CoV-2 en el Reino Unido (B.1.1.7), Sudáfrica (B.1.351) y Brasil (P.1). Entre ellas, se dispone de información más escasa para la variante P.1 y se necesitan más datos sobre su presencia global y sobre su dinámica de expansión.Métodos: Se realizó secuenciación del genoma completo de forma prospectiva de SARS-CoV-2 en viajeros procedentes de Brasil y en una selección aleatoria de casos positivos de SARS-CoV-2 de nuestra población.Resultados: En este estudio reportamos las primeras variantes de SARS-CoV-2 P.1 y P.2 exportadas desde Brasil a España. El caso infectado por la variante P.1, que solo había permanecido en Río de Janeiro, requirió hospitalización. Los 2 casos de la variante P.2 permanecieron asintomáticos. Se debe considerar una distribución más amplia para la variante P.1 más allá de la Amazonía brasileña. La exportación de la variante P.2, que porta la mutación E484K, merece asimismo atención adicional. Un mes después de la primera descripción de las importaciones de P.1 y P.2 de Brasil a Madrid, se identificaron estas variantes circulando en la comunidad, en casos sin antecedentes de viaje, e implicadas en transmisiones domiciliarias.Conclusión: La secuenciación de genoma completo de viajeros positivos para SARS-CoV-2 procedentes de Brasil nos permitió identificar las primeras importaciones de variantes P.1 y P.2 a España y su transmisión comunitaria precoz.

Composición corporal y concentraciones de adipocitoquinas en hemodiálisis: la ganancia de grasa abdominal como factor de riesgo cardiovascular añadido / Body composition analysis and adipocytokine concentrations in haemodialysis patients: abdominal fat gain as an additional cardiovascular risk factor

Introducción: La grasa abdominal y, sobre todo, su ganancia a lo largo del tiempo, se ha consolidado como un factor de riesgo cardiovascular en pacientes urémicos. Objetivos: Analizar los cambios en la grasa abdominal en los pacientes de hemodiálisis (HD) a lo largo de un año y estudiar sus posibles relaciones con los cambios en los niveles circulantes de adipocitocinas. Como objetivo secundario intentamos validar los datos obtenidos por bioimpedancia eléctrica (BIA) con los obtenidos por absorciometría dual de rayos X (DXA). Material y métodos: Se realizó un estudio prospectivo de un año de duración en 18 pacientes en HD. En cada paciente se cuantificó, basalmente y al cabo de un año, la composición corporal por BIA y DXA y se determinaron varios parámetros bioquímicos incluyendo adipocitocinas. Resultados: Se evidenció un aumento significativo del ángulo de fase [4,8° (4,1-5,6) frente a 5,2° (4,4-5,8); p<0,05], del agua intracelular por BIA [48,3% (43,1-52,3) frente a 50,3% (45,7-53,4); p<0,05] y del cociente entre el porcentaje de grasa de distribución androide/ginecoide (A/G) medido por DXA [1,00 (0,80-1,26) frente a 1,02 (0,91; 1,30); p<0,05]. Se encontró una relación estadísticamente significativa entre las concentraciones de leptina y adiponectina tanto con el porcentaje de masa grasa medida por BIA como con la grasa abdominal estimada mediante DXA (p<0,01). Conclusión: Los pacientes en HD experimentan una ganancia de grasa con el tiempo, especialmente en localización abdominal, evidenciada por un aumento del cociente A/G, lo que podría explicar el aumento del riesgo cardiovascular que presentan (AU)

Introduction: Abdominal fat and its increment over time in particular has become a cardiovascular risk factor in uraemic patients. Objectives: To analyse changes in abdominal fat in haemodialysis patients over one year and study their possible correlation with the variation in adipocytokine serum levels. As a secondary objective, we tried to validate the data obtained by bioelectrical impedance analysis (BIA) with data obtained by dual X-ray absorptiometry (DXA). Material and methods: A prospective one-year study was performed in 18 patients on haemodialysis (HD). In each patient, body composition by BIA and DXA was estimated at baseline and after one year. Several adipocytokine and biochemical parameters were determined. Results: A significant increase in phase angle [4.8° (4.1-5.6) vs. 5.2° (4.4-5.8), P<.05], BIA intracellular water [48.3% (43.1-52.3) vs. 50.3% (45.7-53.4), P<.05] and the ratio between the percentage of android/gynecoid (A/G) distribution of fat measured by DXA [1.00 (0.80-1.26) vs. 1.02 (0.91-1.30), P<.05] was observed. A statistically significant relationship between leptin and adiponectin concentrations and the percentage of fat mass measured by BIA, as well as the abdominal fat percentage estimated by DXA, was found (P<.01). Conclusion: HD patients exhibit a gain in fat mass over time, especially in the abdomen, evidenced by an increased A/G ratio. These findings might explain the increased cardiovascular risk in these patients (AU)

Quiste parameniscal gigante complicado con disección distal e infección regional / Complicated parameniscal giant cyst with distal dissection and regional infection

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Análisis repetido de la resistencia insulínica estimada mediante índice HOMAIR en pacientes no diabéticos en diálisis peritoneal y su relación con la enfermedad cardiovascular y mortalidad / Repeated analysis of estimated insulin resistance using the HOMAIR index in nondiabetic patients on peritoneal dialysis and its relationship with cardiovascular disease and mortality

Los pacientes con enfermedad renal crónica terminal muestran precozmente resistencia insulínica (RI), caracterizada por alteraciones en el metabolismo hidrocarbonado e hiperinsulinemia generalmente asociada a dislipemia y a un patrón pro inflamatorio. La enfermedad cardiovascular (CV) constituye la principal causa de mortalidad en los pacientes en diálisis. Existe una fuerte asociación entre RI, hiperinsulinismo y enfermedad CV. El objetivo del presente estudio fue evaluar el efecto de la diálisis peritoneal (DP) sobre la RI y sus efectos sobre la morbimortalidad CV subsiguiente en pacientes urémicos no diabéticos. Se incluyeron 69 pacientes no diabéticos en DP, 35 incidentes (< 3 meses en DP) y 34 prevalentes (> 3 meses en DP), con 2 mediciones de resistencia insulínica estimada mediante el índice de resistencia a la insulina (HOMAIR), separadas entre sí por 12 meses. El valor medio de HOMAIR en pacientes incidentes fue 1,8 ± 1,3 y 2,2 ± 2,1 en situación basal y a los 12 meses, respectivamente (no significativa [ns]). En pacientes prevalentes estos valores fueron 2,3 ± 1,3 y 2,5 ± 2,2 (ns). En nuestro estudio, las concentraciones medias de glucosa, insulina y RI medida por el HOMAIR y QUICKI (índice cuantitativo de control de la sensibilidad a la insulina) fueron similares en situación basal y al año de seguimiento, tanto en incidentes como en prevalentes. No objetivamos diferencias significativas en relación con la comorbilidad CV, cardiopatía isquémica, insuficiencia cardíaca o comorbilidad vascular cerebral o periférica, ni en función del índice HOMAIR, ni en el de los niveles de insulina. En conclusión, los pacientes no diabéticos en DP no presentan elevación significativa de los niveles de HOMAIR, ni se modifica con paso del tiempo en diálisis, lo que sugiere que la DP no es un factor de riesgo de RI. El hecho de que los índices de RI no se asocien a morbilidad o mortalidad CV parece sugerir el menor peso de este factor en el ámbito de la DP (AU)

Terminal chronic renal failure patients show early insulin resistance (IR), characterised by alterations in the hydrocarbon metabolism and hyperinsulinaemia generally associated with dyslipidaemia and a proinflammatory condition. Cardiovascular disease (CVD) is the main cause of mortality in patients on dialysis. There is a strong association between IR, hyperinsulinism and CV disease. The objective of this study was to evaluate the effect of peritoneal dialysis (PD) on IR and its effects on the subsequent CVD morbidity and mortality in nondiabetic uraemic patients. It involved 69 nondiabetic patients on PD, 35 incident patients (<3 months on PD) and 34 prevalent patients (>3 months on PD), with 2 estimated insulin resistance measurements 12 months apart using the insulin resistance index (HOMAIR). The mean HOMAIR value in incident patients was 1.8±1.3 and 2.2±2.1 at baseline situation and at 12 months respectively (not significant [NS]). In prevalent patients these values were 2.3±1.3 and 2.5±2.2 (NS). In our study, the mean glucose, insulin and IR concentrations measured by the HOMAIR and QUICKI indexes (the latter being a quantitative control for insulin sensitivity control) were similar at baseline situation and the following year, in both incident and prevalent patients. We did not find any significant differences in relation to CVD comorbidity, ischaemic heart disease, heart failure or cerebrovascular or peripheral comorbidity neither in the HOMAIR index or insulin levels. To conclude, nondiabetic patients on PD do not display a significant increase in HOMAIR levels and this remains the case over time when on dialysis (AU)

Hipoadiponectinemia un factor de riesgo cardiovascular con limitaciones en la uremia. Una visión desde la evidencia / Hypoadiponectinemia: a cardiovascular risk factor in uremia

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