Hybrid capture shotgun sequencing detected unexpected viruses in the cerebrospinal fluid of children with acute meningitis and encephalitis.

PURPOSE: Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS). METHODS: A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines. RESULTS: Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections. CONCLUSION: This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings.

[Epidemiology of hepatitis E virus infection in Spain]. / Epidemiología de la infección por el virus de la hepatitis E en España.

The general features of the epidemiology and ecology of hepatitis E virus in Spain are already known after 20 years of investigations. Genotype 3 strains, mainly from sub-genotype 3f, circulated among swine livestock and certain wild mammals, and would be sporadically transmitted to humans through direct contact with the reservoirs or by consumption of foods derived from them. Bivalve shellfish contaminated by hepatitis E virus from sewage could also play a role in transmission. Although the interpretation of results from seroprevalence studies in low endemic settings is still controversial, antibody to hepatitis E virus displays an overall prevalence less than 10% among the population of Spain, increasing significantly with age. From the, approximately, 150 cases of acute hepatitis E recorded in the international literature, males older than 40 years, suffering a mild, locally acquired disease predominate. In addition, hepatitis E might be more frequent in the North of the country than in other regions. Although the disease does not usually have a great clinical relevance, the occasional finding of cases of fulminant hepatitis, and of ribavirin-resistant, chronic hepatitis E virus infections among the immunocompromised would recommend the surveillance of the infection by the public health authority and a better implementation of specific diagnostic procedures in clinical laboratories.

Prevalence of BK virus replication among recipients of solid organ transplants.

BACKGROUND: BK virus (BKV) has been implicated as a cause of nephritis and graft loss in 2%-9% of kidney transplant recipients, but the prevalence among recipients of other solid organ transplants (SOTs) has not been well established. Our objective was to determine the prevalence of BKV infection for all types of SOT recipients at our medical center. METHODS: A total of 156 consecutive SOT recipients were studied, of whom 49 received kidney transplants, 43 received heart transplants, and 64 received liver transplants. Samples were obtained a median of 559 days (range, 1-9481 days) after transplantation. Nested polymerase chain reaction was performed for detection of BKV DNA in urine and plasma specimens. RESULTS: BKV was found in 19% of urine specimens and 6% of plasma specimens. The prevalence of viruria after kidney, heart, and liver transplantation was 26.5%, 25.5%, and 7.8%, respectively. BKV viremia was detected in 12.2% of kidney transplant recipients and 7% of heart transplant recipients. Mean creatinine levels were higher in patients with BKV viruria or viremia (1.9 and 3.5 mg/dL, respectively) than in patients with no BKV replication (1.3 mg/dL). Independent factors related to impaired renal function were renal transplantation (odds ratio [OR], 14.4); BKV replication, including viruria or viremia (OR, 3.3); and mycophenolate use (OR, 2.6). CONCLUSION: BKV is common in all types of SOT recipients, particularly those who have received heart or kidney transplants.

High expression of tumor necrosis factor alpha receptors in peripheral blood mononuclear cells of obese type 2 diabetic women.

The tumor necrosis factor system plays an important role in the pathogenesis of obesity and type 2 diabetes (DM), by a complex and only partially understood mechanism. In this study we analyze the mRNA expression levels of TNFalpha and its receptors (TNFR1 and TNFR2), in peripheral blood mononuclear cells (PBMC) from eleven, non-morbid, obese and 14, obese, type 2 DM women, by real-time quantitative PCR. We show an increase in the TNFR2 to TNFR1 ratio (mTNFR2/mTNFR1) in type 2 DM (r = 0.63; p = 0.021, after adjusting for age). Likewise, a positive correlation between mTNFR2/mTNFR1 and glucose was observed (r = 0.5; p = 0.029) in the whole group. We performed an oral glucose tolerance test with 75 g of glucose in obese, non-diabetic women in order to evaluate the effect of an acute glucose increase on the tumor necrosis factor system at 60 min and 120 min. We show that except for a positive association of mTNFR1 with body mass index at 60 min and of mTNFR2 with plasmatic triglycerids levels, no other significant differences were elicited by acute glucose in obese, non-diabetic women. These findings are in agreement with a functional role for the TNF system in obese women in obesity-linked, type 2 diabetes.

Epidemiología de la infección por el virus de la hepatitis E en España / Epidemiology of hepatitis E virus infection in Spain

La información generada durante los últimos 20 años permite ya describir los rasgos generales de la epidemiología y la ecología del virus de la hepatitis E en España. Las cepas del genotipo 3, y en especial las del subgenotipo 3f, circulan entre el ganado porcino y entre algunos mamíferos salvajes, y se transmitirían esporádicamente a las personas por contacto directo con los reservorios o por el consumo de alimentos procedentes de ellos. Asimismo, los mariscos bivalvos contaminados por el virus a través de las aguas residuales podrían desempeñar algún papel en dicha transmisión. Con las dificultades que aún plantea la interpretación de los datos, puede estimarse que la prevalencia de anticuerpos frente al virus de la hepatitis E en la población española sería inferior al 10%, aumentando significativamente con la edad. Entre los, aproximadamente, 150 casos de hepatitis E aguda comunicados ya en la literatura internacional, predominan los casos autóctonos observados en varones mayores de 40 años. Por otra parte, la enfermedad podría ser más frecuente en las regiones del norte de España que en otras. Aunque las hepatitis E agudas que suceden en nuestro medio no suelen presentar gran trascendencia clínica, los hallazgos puntuales de casos de hepatitis fulminante y de infecciones crónicas en pacientes inmunodeprimidos que no responden bien a la terapia con ribavirina aconsejan vigilar esta infección e incorporar su diagnóstico etiológico a la rutina de los laboratorios clínicos en mayor medida que la actual

The general features of the epidemiology and ecology of hepatitis E virus in Spain are already known after 20 years of investigations. Genotype 3 strains, mainly from sub-genotype 3f, circulated among swine livestock and certain wild mammals, and would be sporadically transmitted to humans through direct contact with the reservoirs or by consumption of foods derived from them. Bivalve shellfish contaminated by hepatitis E virus from sewage could also play a role in transmission. Although the interpretation of results from seroprevalence studies in low endemic settings is still controversial, antibody to hepatitis E virus displays an overall prevalence less than 10% among the population of Spain, increasing significantly with age. From the, approximately, 150 cases of acute hepatitis E recorded in the international literature, males older than 40 years, suffering a mild, locally acquired disease predominate. In addition, hepatitis E might be more frequent in the North of the country than in other regions. Although the disease does not usually have a great clinical relevance, the occasional finding of cases of fulminant hepatitis, and of ribavirin-resistant, chronic hepatitis E virus infections among the immunocompromised would recommend the surveillance of the infection by the public health authority and a better implementation of specific diagnostic procedures in clinical laboratorie

Cross-sectional study of BK virus infection in pediatric kidney transplant recipients.

BKV reactivation is associated with impaired graft function in adult kidney transplant patients. The clinical impact of BKV infection in the pediatric transplant population has not yet been fully evaluated. The objective of our study was to determine the prevalence of BKV infection in consecutive pediatric kidney transplant recipients in our center. Forty consecutive unselected pediatric kidney transplant recipients were studied. Mean age at screening was 15.6 +/- 5.3 yr and samples were obtained a median of 60.5 months after transplantation (3-123). BKV-DNA was analyzed in urine and plasma by qualitative nested-PCR. A review of the literature was performed. Prevalence of viruria and viremia was 50% and 12.5%, respectively. Viremia was associated with the presence of hematuria (p = 0.02). The mean creatinine level in children without BKV replication was 1.6 mg/dL, BKV viruria was 0.9 mg/dL, and BKV viremia was 0.8 mg/dL. A literature review showed that viruria and viremia were found in 28.2% and 8.5% of cases, respectively; BKV nephropathy was found in 3.8% and graft loss in 11% of the patients with BKV nephropathy and in 0.4% of the children studied. Recipient serostatus was the most important risk factor. The rate of BKV replication and nephropathy among pediatric kidney recipients is similar to that of adults, but the incidence of graft loss is significantly lower.