Uncovering the neurological effects of West Nile virus during a record-breaking southern Spain outbreak in 2020-2021.

The 2020-21 West Nile Virus (WNV) outbreak in Andalusia, Spain, was the largest reported in the country, with eight cases of West Nile Neuroinvasive Disease (WNND) diagnosed in a tertiary hospital. Diagnosis of WNND is based on detecting WNV RNA, viral isolation, or demonstrating a specific immune response against the virus, with additional tests used to support the diagnosis. Treatment remains supportive, with variable outcomes. The potential efficacy of plasma exchange (PLEX) in select cases raises the possibility of an autoimmune component secondary to infectious pathology of the central nervous system. The influence of climate change on the expansion of WNV into new regions is a significant concern. It is crucial for physicians practicing in high-risk areas to be knowledgeable about the disease for early prevention and effective control measures.

An Exploratory Analysis on the 2D:4D Digit Ratio and Its Relationship with Social Responsiveness in Adults with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder produced by a lack of expression of paternally derived genes in the 15q11-13 region. Research has generally focused on its genetic and behavioral expression, but only a few studies have examined epigenetic influences. Prenatal testosterone or the maternal testosterone-to-estradiol ratio (MaTtEr) has been suggested to play an important role in the development of the 'social brain' during pregnancy. Some studies propose the 2D:4D digit ratio of the hand as an indirect MaTtEr measure. The relationship between social performance and MaTtEr has been studied in other neurodevelopmental conditions such as Autism Spectrum Disorder (ASD), but to our best knowledge, it has never been studied in PWS. Therefore, our study aims to clarify the possible existence of a relationship between social performance-as measured using the Social Responsiveness Scale (SRS)-and MaTtEr levels using the 2D:4D ratio. We found that, as a group, PWS individuals have shorter index and ring fingers than the control group, but no significant difference in the 2D:4D ratios. The 2D:4D ratio showed a correlation only with Restricted Interests and Repetitive Behavior Subscale, where a positive correlation only for male individuals with PWS was found. Considering only PWS with previous GH treatment during childhood/adolescence (PWS-GH), index and ring fingers did not show differences in length with the control group, but the 2D:4D ratio was significantly higher in the right or dominant hand compared to controls.

The impact of COVID-19 on campus-based support programs serving students with foster care experience: Focus groups with administrators and students.

The onset of the Coronavirus disease (COVID-19) pandemic forced higher education institutions to abruptly transition to remote services and online learning. Students with a foster care background are a subgroup of students who have been particularly hard hit by the pandemic, as were the campus-based programs (CSPs) designed to support them. The purpose of this study was to learn about the impact of the pandemic on CSPs and CSP participants. Focus groups were conducted with CSP administrators and separately with CSP students from two- and four-year colleges in California. The first theme that emerged from the data focused on challenges exacerbated by the pandemic, with six subthemes zeroing in on breaks in social connections, academic disruptions, technology woes, gaps in basic needs, employment challenges, and the toll on mental health. The second theme described participants' responses, including their creative and collaborative actions. Administrators quickly adapted service delivery, formed partnerships with new units and organizations to ensure students' needs were met, and found creative ways to stay connected with students during a time of pervasive isolation. Students talked about their own efforts to access resources, connect with peers, and use of strategies to manage challenges such as burnout and depression. A second subtheme highlighted the ways participants displayed resilience, such as creating boundaries to manage their own self-care and leaning on each other for support. The findings from this study increase our understanding of the experiences students faced during the pandemic and shed light on implications moving forward to support students with foster care histories in higher education.

Update in Diagnostics of Toscana Virus Infection in a Hyperendemic Region (Southern Spain).

The sandfly fever Toscana virus (TOSV, genus Phlebovirus, family Phenuiviridae) is endemic in Mediterranean countries. In Spain, phylogenetic studies of TOSV strains demonstrated that a genotype, different from the Italian, was circulating. This update reports 107 cases of TOSV neurological infection detected in Andalusia from 1988 to 2020, by viral culture, serology and/or RT-PCR. Most cases were located in Granada province, a hyperendemic region. TOSV neurological infection may be underdiagnosed since few laboratories include this virus in their portfolio. This work presents a reliable automated method, validated for the detection of the main viruses involved in acute meningitis and encephalitis, including the arboviruses TOSV and West Nile virus. This assay solves the need for multiple molecular platforms for different viruses and thus, improves the time to results for these syndromes, which require a rapid and efficient diagnostic approach.

Phylogenetic Analysis of the 2020 West Nile Virus (WNV) Outbreak in Andalusia (Spain).

During recent decades West Nile Virus (WNV) outbreaks have continuously occurred in the Mediterranean area. In August 2020 a new WNV outbreak affected 71 people with meningoencephalitis in Andalusia and six more cases were detected in Extremadura (south-west of Spain), causing a total of eight deaths. The whole genomes of four viruses were obtained and phylogenetically analyzed in the context of recent outbreaks. The Andalusian viral samples belonged to lineage 1 and were relatively similar to those of previous outbreaks which occurred in the Mediterranean region. Here we present a detailed analysis of the outbreak, including an extensive phylogenetic study. As part on this effort, we implemented a local Nextstrain server, which has become a constituent piece of regional epidemiological surveillance, wherein forthcoming genomes of environmental samples or, eventually, future outbreaks, will be included.

Evaluation of a Trio Toscana Virus Real-Time RT-PCR Assay Targeting Three Genomic Regions within Nucleoprotein Gene.

Toscana virus (TOSV) can cause central nervous system infections in both residents of and travelers to Mediterranean countries. Data mining identified three real-time RT-qPCR assays for detecting TOSV RNA targeting non-overlapping regions in the nucleoprotein gene. Here, they were combined to create a multi-region assay named Trio TOSV RT-qPCR consisting of six primers and three probes. In this study, (i) we evaluated in silico the three RT-qPCR assays available in the literature for TOSV detection, (ii) we combined the three systems to create the Trio TOSV RT-qPCR, (iii) we assessed the specificity and sensitivity of the three monoplex assays versus the Trio TOSV RT-qPCR assay, and (iv) we compared the performance of the Trio TOSV RT-qPCR assay with one of the reference monoplex assays on clinical samples. In conclusion, the Trio TOSV RT-qPCR assay performs equally or better than the three monoplex assays; therefore, it provides a robust assay that can be used for both research and diagnostic purposes.

Prevalencia de infecciones de transmisión sexual y por genitopatógenos en mujeres de la población general / Recent prevalence among females from the general population of agents responsible for sexually transmitted infections and other genital infections

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Successful development and clinical translation of a novel anterior lamellar artificial cornea.

Blindness due to corneal diseases is a common pathology affecting up to 23 million individuals worldwide. The tissue-engineered anterior human cornea, which is currently being tested in a Phase I/II clinical trial to treat severe corneal trophic ulcers with preliminary good feasibility and safety results. This bioartificial cornea is based on a nanostructured fibrin-agarose biomaterial containing human allogeneic stromal keratocytes and cornea epithelial cells, mimicking the human native anterior cornea in terms of optical, mechanical, and biological behavior. This product is manufactured as a clinical-grade tissue engineering product, fulfilling European requirements and regulations. The clinical translation process included several phases: an initial in vitro and in vivo preclinical research plan, including preclinical advice from the Spanish Medicines Agency followed by additional preclinical development, the adaptation of the biofabrication protocols to a good manufacturing practice manufacturing process, including all quality controls required, and the design of an advanced therapy clinical trial. The experimental development and successful translation of advanced therapy medicinal products for clinical application has to overcome many obstacles, especially when undertaken by academia or SMEs. We expect that our experience and research strategy may help future researchers to efficiently transfer their preclinical results into the clinical settings.

Effectiveness of a Hospital-at-Home Integrated Care Program as Alternative Resource for Medical Crises Care in Older Adults With Complex Chronic Conditions.

OBJECTIVES: To compare clinical outcomes in older patients with acute medical crises attended by a geriatrician-led home hospitalization unit (HHU) vs an inpatient intermediate-care geriatric unit (ICGU) in a post-acute care setting. DESIGN: Quasi-experimental longitudinal study, with 30-day follow-up. PARTICIPANTS: Older patients with chronic conditions attended at the emergency department or day hospital for an acute medical crisis. INTERVENTIONS: Patients were referred to geriatrician-led HHU or ICGU wards. SETTING: An acute care hospital, an intermediate care hospital, and the community of an urban area in the North of Barcelona, in Southern Europe. MEASUREMENTS: We compared health crisis outcomes (recovery from the acute health crisis, referral to an acute hospital, or death), length of stay, relative functional gain (RFG) at discharge, readmission to an acute care unit within 30 days of discharge, and mortality within 30 days of discharge. RESULTS: We included 171 older adults (57 in the HHU and 114 in the ICGU) with complex conditions at risk of negative outcomes. At baseline, HHU patients were significantly younger and less likely to be cognitively impaired and referred from an emergency department. Most patients in both groups recovered from their health crises (91.2% in the HHU group vs 88.6% in the ICGU group, P = .79). No differences were found between the 2 groups in 30-day mortality (8.6% vs 9.6%, P = >.99). There was a trend toward lower 30-day readmission to an acute care unit in the HHU group (10.5% vs 19.3% in the ICGU group, P = .19). HHU patients had higher RFG (mean 0.75 days vs 0.51 in the ICGU group, P = .01), and a longer stay in the unit (9.7 vs 8.2 days in the ICGU group, P < .01). CONCLUSIONS: These preliminary results suggest that the geriatrician-led HHU seems effective in resolving acute medical crises in older patients with chronic disease. Patients attended by the HHU obtained better functional outcomes compared to those from the ICGU, although the groups did have some baseline differences.

Analytical validation of viral CNS Flow Chip kit for detection of acute meningitis and encephalitis.

A new molecular assay (Viral CNS Flow Chip kit, Master Diagnóstica, Spain) has been developed for the detection of eight viruses causing acute meningitis and encephalitis, i.e. herpes simplex viruses 1-2, varicella zoster virus, human enterovirus, human parechovirus, Toscana virus, human cytomegalovirus and Epstein Barr virus. The new assay is a multiplex one-step RT-PCR followed by automatic flow-through hybridization, colorimetric detection and image analysis. The limit of detection was 50 copies/reaction, and 10 copies/reaction for human enterovirus and the other seven viruses, respectively. The analytical validation was performed with nucleic acids extracted from 268 cerebrospinal fluid samples and the results were compared with routine molecular assays. An excellent coefficient of agreement was observed between V-CNS and routine assays [kappa index: 0.948 (95%CI: 0.928-0.968)]. The overall sensitivity and specificity was 95.9% (95%CI: 91.2-98.3%) and 99.9% (95%CI: 99.6-100%), respectively. Viral CNS Flow Chip kit is an efficient multiplex platform for the detection of the main viruses involved in acute meningitis and encephalitis. The inclusion of a TOSV genome target may improve the laboratory diagnosis of viral neurological infections in endemic areas.

Analytical performance of the Alere(TM) i Influenza A&B assay for the rapid detection of influenza viruses / Evaluación del sistema Alere(TM) i Influenza A&B para la detección rápida de virus de la gripe

The analytical performance of the new Alere(TM) i Influenza A&B kit (AL-Flu) assay, based on isothermal nucleic acids amplification, was evaluated and compared with an antigen detection method, SD Bioline Influenza Virus Antigen Test (SDB), and an automated real-time RT-PCR, Simplexa(TM) Flu A/B & VRS Direct assay (SPX), for detection of influenza viruses. An ‘in-house’ RT-PCR was used as the reference method. Sensitivity of AL-Flu, SDB, and SPX was 71.7%, 34.8%, and 100%, respectively. Specificity was 100% for all techniques. The turnaround time was 13min for AL-Flu, 15min for SDB, and 75min for SPX. The Alere(TM) i Influenza A&B assay is an optimal point-of-care assay for influenza diagnosis in clinical emergency settings, and is more sensitive and specific than antigen detection methods (AU)

Se evaluó el nuevo ensayo Alere(TM) i Influenza A&B kit (AL-Flu), basado en la amplificación isotérmica de ácidos nucleicos, y se comparó con un método de detección de antígeno, SD Bioline Influenza Virus Antigen Test (SDB), y con una RT-PCR en tiempo real automática, Simplexa(TM) Flu A/B & VRS Direct assay (SPX), para la detección de virus de la gripe. Se utilizó una RT-PCR en tiempo real casera como método de referencia. La sensibilidad de AL-Flu, SDB y SPX fue del 71,7%, del 34,8% y del 100%, respectivamente. Se obtuvo una especificidad del 100% con todos los métodos. El tiempo de realización fue de 13min para AL-Flu, de 15min para SDB y de 75min para SPX. El ensayo Alere(TM) i Influenza A&B es óptimo para el diagnóstico de gripe en unidades de urgencias, al ser más sensible y específico que las técnicas de detección de antígeno (AU)

Analytical performance of the Alere™ i Influenza A&B assay for the rapid detection of influenza viruses.

The analytical performance of the new Alere™ i Influenza A&B kit (AL-Flu) assay, based on isothermal nucleic acids amplification, was evaluated and compared with an antigen detection method, SD Bioline Influenza Virus Antigen Test (SDB), and an automated real-time RT-PCR, Simplexa™ Flu A/B & VRS Direct assay (SPX), for detection of influenza viruses. An "in-house" RT-PCR was used as the reference method. Sensitivity of AL-Flu, SDB, and SPX was 71.7%, 34.8%, and 100%, respectively. Specificity was 100% for all techniques. The turnaround time was 13min for AL-Flu, 15min for SDB, and 75min for SPX. The Alere™ i Influenza A&B assay is an optimal point-of-care assay for influenza diagnosis in clinical emergency settings, and is more sensitive and specific than antigen detection methods.

Analytical performance of the automated multianalyte point-of-care mariPOC® for the detection of respiratory viruses.

The analytical performance of mariPOC® respi test (ArcDia® Laboratories, Turku, Finland) was evaluated using nucleic acid amplification techniques (NAATs) as the gold standard. The mariPOC assay allows automated detection of antigens from 8 respiratory viruses: influenza A and B viruses, respiratory syncytial virus, adenovirus, human metapneumovirus, and parainfluenza viruses 1-3. Positive results from samples with high viral load are available in 20min. Nasopharyngeal aspirates (n=192) from patients with acute respiratory infection and from previously positive samples were analyzed by mariPOC and NAATs (Simplexa(TM) FluA/FluB & RSV kit [n=118] and Luminex® Respiratory virus panel xTAG® RVP FAST [n=74]). Sensitivity, specificity, positive predictive value, and negative predictive value of mariPOC were 85.4%, 99.2%, 95.9%, and 97%, respectively, and 84.6% of positive results were reported in 20min. The good analytical performance and extended portfolio of mariPOC show this rapid assay as a good alternative for the etiological diagnosis of acute respiratory infection in laboratories that are not equipped with molecular assays.

Comparison of epidemiology and clinical characteristics of infections by human parechovirus vs. those by enterovirus during the first month of life.

UNLABELLED: Human parechoviruses (HPeV) have been recently recognized as important viral agents in paediatric infections. The aims of this study were to investigate the HPeV infection prevalence in infants <1 month in Spain and, secondly, to analyse the clinical and epidemiological characteristics of the infected patients compared with those infected by enterovirus (EV). Infants <1 month with neurological or systemic symptoms were included in a multicentre prospective study. EV and HPeV detection by RT-PCR and genotyping were performed in cerebrospinal fluids (CSF), sera or throat swabs. Out of the total of 84 infants studied during 2013, 32 were EV positive (38 %) and 9 HPeV positive (11 %). HPeV-3 was identified in eight cases and HPeV-5 in one. Mean age of HPeV-positive patients was 18 days. Diagnoses were fever without source (FWS) (67 %), clinical sepsis (22 %) and encephalitis (11 %). Leukocytes in blood and CSF were normal. Pleocytosis (p = 0.03) and meningitis (p = 0.001) were significantly more frequent in patients with EV infections than with HPeV. CONCLUSIONS: Although HPeV-3 infections were detected less frequently than EV, they still account for approximately 10 % of the cases analysed in infants younger than 1 month. HPeV-3 was mainly associated with FWS and without leukocytosis and pleocytosis in CSF. In these cases, HPeV screening is desirable to identify the aetiologic agent and prevent unnecessary treatment and prolonged hospitalization.

Características de la tuberculosis en la población inmigrante en el Área de Salud Sur de Granada / Characteristics of tuberculosis in the immigrant population in South Granada Health Area

INTRODUCCIÓN: La incidencia de la tuberculosis (TB) en la población autóctona en España continúa descendiendo, aumentando la proporción de casos en extranjeros. El objetivo de este estudio fue identificar las características diferenciales de la TB en la población inmigrante con respecto a la autóctona en el Área de Salud Sur de Granada, España. MÉTODOS: Estudio descriptivo incluyendo todos los casos de TB diagnosticados durante el período 2003-2010 a partir de una base de datos prospectiva. Se realizó un análisis de regresión logística para determinar las características diferenciales.: RESULTADOS: De los 319 casos de TB diagnosticados, 247 autóctonos y 72 (22,6%) inmigrantes, 272 eran pulmonares. Las siguientes variables se asociaron significativamente con los casos de TB en inmigrantes: edad < 35 años (OR = 4,75; IC:2,72-8,31), mayor porcentaje de cavitación en la radiografía torácica (OR = 2,26; IC:1,20-4,20), mayor porcentaje de TB pulmonar bacilífera (OR = 1,80; IC:1,02-3,16), mayor retraso diagnóstico en TB pulmonar bacilífera (mediana 32 días vs. 21 días; p = 0,043) y menor letalidad total (OR = 0,12; IC:0,01-0,89). CONCLUSIONES: La incidencia de la TB se ha mantenido constante en el Área Sur de Granada a expensas de los casos en población inmigrante. Comparados con los autóctonos, los pacientes inmigrantes con TB eran más jóvenes, tenían enfermedad más avanzada (mayor porcentaje de bacilíferos y de cavitación radiológica) y más retraso diagnóstico en TB pulmonar bacilífera, indicando peor control de la enfermedad. Son necesarias estrategias para un diagnóstico más precoz de la TB en la población inmigrante

INTRODUCTION: The incidence of tuberculosis (TB) among the native population in Spain continues to decrease, resulting in a higher proportion of foreign-born cases. The aim of this study was to identify the differential TB characteristics within the immigrant population with respect to the native population in the South Granada Health Area, Spain. METHODS: This was a descriptive study, including all cases of TB diagnosed during the period 2003-2010. Cases were identified through a prospective database. A logistic regression analysis was performed to determine differential characteristics. RESULTS: From 319 TB cases diagnosed, 247 were natives and 72 (22.6%) immigrants, and 272 were pulmonary tuberculosis. The following variables were significantly associated with immigrant TB cases: age < 35 years (OR = 4.75, CI: 2.72-8.31), higher percentage of cavitated chest X-ray (OR = 2.26, CI: 1.20-4.20), higher percentage of smear-positive cases (OR = 1.80, CI: 1.02-3.16), longer diagnostic delay in smear-positive pulmonary TB (median 32 days vs. 21 days P = .043), and lower total lethality (OR = 0.12; CI: 0.01-0.89). CONCLUSIONS: The incidence of TB has remained constant in the South Granada Health Area due to the increase in cases among immigrants. Compared with native TB patients, immigrant patients were younger and had more advanced disease (higher percentage of smear-positive cases and higher percentage of cavitated chest X-ray) and longer diagnostic delay in smear-positive pulmonary TB, indicating poorer TB control. Strategies for earlier diagnosis of TB in immigrants are essential

[Characteristics of tuberculosis in the immigrant population in South Granada Health Area]. / Características de la tuberculosis en la población inmigrante en el Área de Salud Sur de Granada.

INTRODUCTION: The incidence of tuberculosis (TB) among the native population in Spain continues to decrease, resulting in a higher proportion of foreign-born cases. The aim of this study was to identify the differential TB characteristics within the immigrant population with respect to the native population in the South Granada Health Area, Spain. METHODS: This was a descriptive study, including all cases of TB diagnosed during the period 2003-2010. Cases were identified through a prospective database. A logistic regression analysis was performed to determine differential characteristics. RESULTS: From 319 TB cases diagnosed, 247 were natives and 72 (22.6%) immigrants, and 272 were pulmonary tuberculosis. The following variables were significantly associated with immigrant TB cases: age<35 years (OR=4.75, CI: 2.72-8.31), higher percentage of cavitated chest X-ray (OR=2.26, CI: 1.20-4.20), higher percentage of smear-positive cases (OR=1.80, CI: 1.02-3.16), longer diagnostic delay in smear-positive pulmonary TB (median 32 days vs. 21 days P=.043), and lower total lethality (OR=0.12; CI: 0.01-0.89). CONCLUSIONS: The incidence of TB has remained constant in the South Granada Health Area due to the increase in cases among immigrants. Compared with native TB patients, immigrant patients were younger and had more advanced disease (higher percentage of smear-positive cases and higher percentage of cavitated chest X-ray) and longer diagnostic delay in smear-positive pulmonary TB, indicating poorer TB control. Strategies for earlier diagnosis of TB in immigrants are essential.

Design and validation of a real-time RT-PCR for the simultaneous detection of enteroviruses and parechoviruses in clinical samples.

Human enteroviruses (EVs) and parechoviruses (HPeVs) are important etiological agents causing infections such as meningitis, encephalitis and sepsis-like disease in neonates and young children. We have developed a real-time RT-PCR for simultaneous detection of EV and HPeV in clinical samples. Primers and probe sets were designed from the conserved 5'-noncoding region of the genomes. The sensitivity, specificity and reproducibility of the technique were measured using a set of 25 EV and 6 HPeV types. All EVs but no HPeVs were detected with the EV primers-probe set. The HPeV primers-probe set detected only the 6 HPeV types. The lower detection limit was found to be 4 and 40CCID50/ml for HPeV and EV respectively, demonstrating high sensitivity of the technique for both viruses. The threshold cycle values were highly reproducible on repeat testing of positive controls among assay runs. The assay was evaluated in 53 clinical samples of suspected meningitis, sepsis or febrile syndromes from children under 3 years. In 11 of these (21%) EVs were detected, while 4, i.e. 7.5%, were HPeV positive. Molecular typing was carried out for 73% of the viruses. In summary, the RT-PCR method developed demonstrated effectively both EV and HPeV detection, which can cause similar clinical symptoms in infants.

[Infection by human cytomegalovirus]. / Infección por citomegalovirus humano.

Prevalence of human cytomegalovirus infection is very high worldwide. Following primary infection, the virus remains latent, being able to cause recurrences either by reinfection with a new strain or by reactivation of the replication of the latent virus. The most severe disease is seen in congenital infection and in immunosuppressed patients, in whom the virus act as an opportunistic pathogen. Serological techniques are the methods of choice in primary infection and to determine the immune status against CMV in organ donor and receptor. Although well-standardized studies are lacking, the recent commercial availability of methods that measure cellular immune response are promising to predict the risk of CMV disease in immunosuppressed individuals. Molecular assays, that have gradually been substituting viral culture and/or antigen detection, are the most widely used methods for the diagnosis and control of CMV infection.