Prospective evaluation of indirect costs due to acute rotavirus gastroenteritis in Spain: the ROTACOST study.

BACKGROUND: The effect of rotavirus in developed countries is mainly economic. This study aimed to assess the indirect costs induced by rotavirus acute gastroenteritis (RVAGE) in Spain. METHODS: A prospective observational study was conducted from October 2008 to June 2009. It included 682 children up to 5 years of age with acute gastroenteritis (AGE) who attended primary care (n = 18) and emergency room/hospital settings (n = 10), covering the regions of Galicia and Asturias (North-west Spain). All non-medical expenses incurred throughout the episode were recorded in detail using personal interviews and telephone contact. RESULTS: Among the 682 enrolled children, 207 (30.4%) were rotavirus positive and 170 (25%) had received at least one dose of rotavirus vaccine. The mean (standard deviation) indirect cost caused by an episode of AGE was estimated at 135.17 (182.70) Euros. Costs were 1.74-fold higher when AGE was caused by rotavirus compared with other etiologies: 192.7 (219.8) Euros vs. 111.6 (163.5) Euros (p < .001). The costs for absenteeism were the most substantial with a mean of 91.41 (134.76) Euros per family, resulting in a loss of 2.45 (3.17) days of work. In RVAGE patients, the absenteeism cost was 120.4 (154) Euros compared with 75.8 (123) for the other etiologies (p = .002), because of loss of 3.5 (3.6) vs 1.9 (2.9) days of work (p < .001). Meals costs were 2-fold-higher (48.5 (55) vs 24.3 (46) Euros, p < .001) and travel costs were 2.6-fold-higher (32 (92) vs 12.5 (21.1) Euros, p = .005) in RVAGE patients compared with those with other etiologies. There were no differences between RVAGE and other etiologies groups regarding costs of hiring of caregivers or purchase of material. Patients with RVAGE were admitted to hospital more frequently than those with other etiologies (47.8% vs 14%, p < .001). CONCLUSIONS: Rotavirus generates a significant indirect economic burden. Our data should be considered in the decision-making process of the eventual inclusion of rotavirus vaccine in the national immunization schedule of well developed countries

Homo antecessor y su relación con los neandertales y las poblaciones humanas modernas

Este trabajo examina las evidencias morfológicas del conjunto de fósiles humanos recuperados del nivel TD6-2 del yacimiento de la cueva de la Gran Dolina (sierra de Atapuerca, Burgos). Estos fósiles, incluidos en la especie Homo antecessor y con una cronología compatible con el MIS 21, presentan rasgos plesiomorfos del clado Homo, rasgos derivados compartidos con H. sapiens, rasgos derivados compartidos con H. neanderthalensis, rasgos derivados compartidos con estas dos últimas especies y rasgos derivados compartidos con poblaciones del Pleistoceno Medio de Eurasia. Este complejo mosaico, con un sello netamente europeo, podría ser explicado en el marco de un proceso de cladogénesis, ocurrido durante el Pleistoceno Inferior, posiblemente en el suroeste de Asia. La población polimórfica resultante de este proceso pudo originar diferentes pulsos migratorios al menos hacia Europa cuando las condiciones climáticas fueron favorables. Este proceso pudo ser muy complejo desde el punto de vista de las relaciones de la “población madre” con otros grupos humanos y tendría que contemplar al menos una migración hacia el continente africano a través del Corredor Levantino. Solo así se podría justificar el origen y evolución de H. sapiens en África durante el Pleistoceno Medio.This report examines the morphological evidences of the human fossils recovered from the TD6-2 level of the Gran Dolina cave site (Sierra de Atapuerca, Burgos, northern Spain). These fossils, which were included in the species Homo antecessor and might have been deposited during the MIS 21, exhibit plesiomorphic features for the Homo clade, apomorphic features shared with H. sapiens, apomorphic features shared with H. neanderthalensis, apomorphic features shared with the two latter species, and apomorphic features shared with the Eurasian Middle Pleistocene populations. This complex mosaic, which has a distinctly European hallmark, could be explained in the framework of a cladogenetic process occurred during the early Pleistocene, probably in Southwest Asia. The polymorphic population originated in this process might have been source of different migratory waves, at least towards Europe, during favourable climatic conditions. This process could have been very complex concerning the interactions of the “mother population” with other human groups and must consider at least one migration to the African continent through the Levantine Corridor. Only this way we could justify the origin and evolution of H. sapiens in Africa during the Middle Pleistocene.Este trabajo ha sido realizado en el marco del proyecto CGL2012-38434-C03-02, del Ministerio de Economía y Competitividad, el proyecto de excavaciones anual subvencionado por las Consejerías de Cultura y Turismo y Familia e Igualdad de Oportunidades de la Junta de Castilla y León, la Fundación Atapuerca y la Fundación Leakey, a través de donaciones realizadas por Gordon Getty y Dub Crook

Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection

Background The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques. Methods A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures. Results 66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007). Conclusion Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe casesThis work was supported by the Spanish Government (Research Program Health Research Fund (FIS; PI10/00540 y PI13/02382) National Plan I + D + I and FEDER funds) and Regional Galician funds (Promotion of Research Project 10 PXIB 918 184 PR) (FMT), and Ministerio de Ciencia e Innovación (SAF2011-26983) and the Plan Galego IDT, Xunta de Galicia (EM 2012/045) (AS). MC’s research activities had been supported by grants from Instituto de Investigación Sanitaria de Santiago de Compostela. FMT’s research activities have been supported by grants from Instituto Carlos III (Intensificación de la actividad investigadora). Investigators received funding from the European Union’s Seventh Framework Program under ECGA no. 279185 (EUCLIDS) during the production of this paperS

Further considerations on rotavirus vaccination and seizure-related hospitalization rates

Response to letter to the editor: Sánchez A, López-Lacort M, Muñoz-Quiles C, Martinez-Beneito MA, Díez-Domingo J. Letter to the editor regarding “Rotavirus infection beyond the gut”. Infect Drug Resist. 2019;12:707-708 https://doi.org/10.2147/IDR.S202716S

Rotavirus infection beyond the gut

The landscape of rotavirus (RV) infection has changed substantially in recent years. Autoimmune triggering has been added to clinical spectrum of this pathology, which is now known to be much broader than diarrhea. The impact of RV vaccines in these other conditions is becoming a growing field of research. The importance of host genetic background in RV susceptibility has been revealed, therefore increasing our understanding of vaccine effectiveness and giving some clues about the limited efficacy of RV vaccines in low-income settings. Also, interaction of RV with intestinal microbiota seems to play a key role in the process of infection vaccine effect. This article reviews current findings on the extraintestinal impact of RV infection and their widening clinical picture, and the recently described mechanisms of host susceptibility to infection and vaccine effectiveness. RV infection is a systemic disease with clinical and pathophysiological implications beyond the gut. We propose an “iceberg” model for this pathology with almost hidden clinical implications away from the gastrointestinal tract and eventually triggering the development of autoimmune diseases. Impact of current vaccines is being influenced by host genetics and gut microbiota interactions and these factors must be taken into account in the development of public health programs.This work was supported by grants from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud): project GePEM ISCIII/PI16/01478/Cofinanciado FEDER (AS) and project ReSVinext ISCIII/PI16/01569/Cofinanciado FEDER (FMT); Consellería de Sanidade, Xunta de Galicia (RHI07/2-intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007-2012, PI16/01569), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540) del plan nacional de I + D + I (FMT), and 2016-PG071 Consolidación e Estructuración REDES 2016GI-1344 G3VIP (Grupo Gallego de Genética Vacunas Infecciones y Pediatría, ED341D R2016/021) (AS and FMT)S

Rotavirus infection beyond the gut

The landscape of rotavirus (RV) infection has changed substantially in recent years. Autoimmune triggering has been added to clinical spectrum of this pathology, which is now known to be much broader than diarrhea. The impact of RV vaccines in these other conditions is becoming a growing field of research. The importance of host genetic background in RV susceptibility has been revealed, therefore increasing our understanding of vaccine effectiveness and giving some clues about the limited efficacy of RV vaccines in low-income settings. Also, interaction of RV with intestinal microbiota seems to play a key role in the process of infection vaccine effect. This article reviews current findings on the extraintestinal impact of RV infection and their widening clinical picture, and the recently described mechanisms of host susceptibility to infection and vaccine effectiveness. RV infection is a systemic disease with clinical and pathophysiological implications beyond the gut. We propose an "iceberg" model for this pathology with almost hidden clinical implications away from the gastrointestinal tract and eventually triggering the development of autoimmune diseases. Impact of current vaccines is being influenced by host genetics and gut microbiota interactions and these factors must be taken into account in the development of public health programs

The complete mitogenome of a 500-year-old Inca child mummy

In 1985, a frozen mummy was found in Cerro Aconcagua (Argentina). Archaeological studies identified the mummy as a seven-year-old Inca sacrifice victim who lived >500 years ago, at the time of the expansion of the Inca Empire towards the southern cone. The sequence of its entire mitogenome was obtained. After querying a large worldwide database of mitogenomes (>28,000) we found that the Inca haplotype belonged to a branch of haplogroup C1b (C1bi) that has not yet been identified in modern Native Americans. The expansion of C1b into the Americas, as estimated using 203 C1b mitogenomes, dates to the initial Paleoindian settlements (~18.3 thousand years ago [kya]); however, its internal variation differs between Mesoamerica and South America. By querying large databases of control region haplotypes (>150,000), we found only a few C1bi members in Peru and Bolivia (e.g. Aymaras), including one haplotype retrieved from ancient DNA of an individual belonging to the Wari Empire (Peruvian Andes). Overall, the results suggest that the profile of the mummy represents a very rare sub-clade that arose 14.3 (5–23.6) kya and could have been more frequent in the past. A Peruvian Inca origin for present-day C1bi haplotypes would satisfy both the genetic and paleo-anthropological findings.The research leading to these results has received funding from the “Ministerio de Ciencia e Innovación” (SAF2011–26983), the Plan Galego IDT (EM 2012/045) and a grant from the Sistema Universitario Gallego- Modalidad REDES (2012-PG226) from the Xunta de Galicia (A.S.); Instituto Carlos III (Intensificación de la actividad investigadora) and Fondo de Investigación Sanitaria (FIS; PI10/00540 and PI13/02382) of the Plan Nacional de I+ D+ I and Fondos FEDER (F.M.T)S

Comparative analysis of the Gran Dolina-TD6 (Spain) and Tighennif (Algeria) hominin mandibles

We present a comparative study of the Tighennif (Algeria) and Gran Dolina-TD6 (Spain) hominin mandibles, which represent two geographically near and contemporaneous populations separated by the Mediterranean sea, in order to test the hypothesis that these populations belong to the same evolutionary lineage, as it has been suggested by some authors. The Tighennif mandibles show a clear primitive structural pattern, derived in some features with regard to the oldest Homo specimens from H. habilis, as well as from the Javanese H. erectus. In addition, the Tighennif specimens share all these derived features with H. ergaster and, some of them, with H. antecessor. However, the Gran Dolina-TD6 specimens are remarkably smaller than those of Tighennif, and lack the robustness which characterizes the African Pleistocene mandibles. The main difference between both groups in terms of mandibular dimensions can be related to the higher corpus height characteristic of Tighennif specimens. The dental evidence reveals that North African Middle Pleistocene populations are morphologically closer to African Early Pleistocene populations than to TD6 fossils. We conclude that the Spanish and Algerian hominins belong to different hominin lineages. The Tighennif hominins, together with other contemporaneous (Thomas Quarry and Oulad Hamida 1), and perhaps later North African specimens (Sidi Abderrahaman, Salé, and Rabat [Kebitat]) should be considered as a subspecies of the H. ergaster species, i.e. H. ergaster mauritanicus, and may be the result of an evolution in isolation in this African area. In agreement with the mandibular and dental evidences, the Gran Dolina-TD6 hominins could belong to an exclusive Eurasian lineage.Nous présentons une analyse comparée des mandibules des hominidés de Tighennif (Algérie) et de la Gran Dolina-TD6 (Espagne), qui représentent deux populations proches dans l’espace et le temps mais séparées par la mer Méditerranée, afin de vérifier l’hypothèse que les deux échantillons appartiennent au même lignage évolutif, comme certains auteurs l’ont suggéré. Les mandibules de Tighennif ont un pattern morphologique structurel primitif, avec certains caractères dérivés par rapport à ceux des spécimens de H. habilis et de H. erectus de Java. Les mandibules de Tighennif partagent tous ces caractères dérivés avec H. ergaster et quelques uns avec H. antecessor. Néanmoins, les spécimens de la Gran Dolina-TD6 sont remarquablement plus petits que ceux de Tighennif, et sont moins robustes que les mandibules du Pléistocène d’Afrique. La principale différence entre les deux échantillons, en ce qui concerne les dimensions mandibulaires, est la grande hauteur du corps de la mandibule des spécimens de Tighennif. Les caractères dentaires révèlent que les populations du Pléistocène moyen du Nord de l’Afrique sont, du point de vue morphologique, plus proches des hominidés du Pléistocène inférieur de l’Afrique que de ceux de la Gran Dolina-TD6. Nous concluons donc que les hominidés de Tighennif et de la Gran Dolina-TD6 appartiennent à deux lignées différentes. Les hominidés de Tighennif pourraient être réunis avec les spécimens contemporains de Thomas Quarry et de Oulad Hamida 1, et peut-être avec d’autres plus tardifs comme ceux de Sidi Abderrahaman, Salé, et Rabat [Kebitat] du Nord de l’Afrique dans une même sous-espèce de H. ergaster, i.e. H. ergaster mauritanicus, qui serait le résultat d’une évolution locale en isolement relatif dans cette région de l’Afrique. Les hominidés de la Gran Dolina-TD6 appartiennent à une lignée exclusive de l’Eurasie, conformément aux données dentaires et mandibulaires

Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective roleThis work was supported by the Spanish Government (Research Program Health Research Fund (FIS; PI10/00540) National Plan I + D + I and FEDER funds), by Regional Galician funds (Promotion of Research Project 10 PXIB 918 184PR) (FMT), by Ministerio de Ciencia e Innovación (SAF2011-26983), and by the Plan Galego IDT, Xunta de Galicia (EM 2012/045) (AS). A grant was received from the Sistema Universitario Gallego -Modalidad REDES (2014-PG139) from the Xunta de Galicia (to AS and FMT). MCL research activities have been supported by grants from Instituto de Investigación Sanitaria de Santiago de Compostela. FMT research activities have been supported by grants from Instituto Carlos III (Intensificación de la actividad investigadora). Investigators received funding from the European Union’s seventh Framework program under ECGA no. 279185 (EUCLIDS) during the production of this paper. JH was supported by the Imperial College Comprehensive Biomedical Research Centre and the Wellcome Trust Centre for Respiratory Infection at Imperial College (DMPED P26077 to JH). Micropathology Ltd. provided support in the form of salaries for authors ES and CF, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ sectionS

Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseus Heteroplasia

Progressive osseous heteroplasia (POH; OMIM 166350) is a rare autosomal-dominant genetic disorder in which extra-skeletal bone forms within skin and muscle tissue. POH is one of the clinical manifestations of an inactivating mutation in the GNAS gene. GNAS gene alterations are difficult matter to address, as GNAS alleles show genetic imprinting and produce several transcript products, and the same mutation may lead to strikingly different phenotypes. Also, most of the publications concerning POH patients are either clinical depictions of a case (or a case series), descriptions of their genetic background, or a tentative correlation of both clinical and molecular findings. Treatment for POH is rarely addressed, and POH still lacks therapeutic options. We describe a unique case of POH in two monochorionic twins, who presented an almost asymptomatic vs. the severe clinical course, despite sharing the same mutation and genetic background. We also report the results of the therapeutic interventions currently available for heterotopic ossification in the patient with the severe course. This article not only critically supports the assumption that the POH course is strongly influenced by factors beyond genetic background but also remarks the lack of options for patients suffering an orphan disease, even after testing drugs with promising in vitro resultsThis study received support from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud): project GePEM ISCIII/PI16/01478/Cofinanciado FEDER) (AS) and project ReSVinext ISCIII/PI16/01569/Cofinanciado FEDER (FM-T); Consellería de Sanidade, Xunta de Galicia (RHI07/2-intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007–2012, PI16/01569), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540) del plan nacional de I + D + I and fondos FEDER (FM-T), and 2016-PG071 Consolidación e Estructuración REDES 2016GI-1344 G3VIP (Grupo Gallego de Genética Vacunas Infecciones y Pediatría, 3) (AS and FM-T)S