Aportaciones moleculares al diagnóstico de las multiparasitaciones por geohelmintos

El diagnóstico de las geohelmintiasis por Ancylostoma duodenale, Necator americanus, Ascaris lumbricoides, Trichuris trichiura y Strongyloides stercoralis es actualmente uno de los grandes retos diagnósticos en parasitología, siendo además definidas por la Organización Mundial de la Salud (OMS) como las enfermedades más prevalentes dentro de las Negleted Tropical Diseases (NTDs). Actualmente el diagnóstico basado en técnicas parasitológicas convencionales para las uncinariasis, ascariasis y tricuriasis hacen necesario la puesta a punto de técnicas diagnósticas más sensibles y específicas para su correcta detección y para una mejor evaluación de los programas de control con administración masiva de fármacos establecidos por la OMS. En el caso de la estrongiloidiasis, debido a la forma de la presentación de la enfermedad (crónica con un elevado porcentaje de asintomáticos), a la carencia de una técnica de referencia “gold standard” y a la frecuencia de su aparición en nuestro país como una de las primeras causas de eosinofilia no filiada en población inmigrante y viajeros a zona endémica, este reto es aún mayor. Los objetivos en los cuales se encuentra enmarcada esta tesis doctoral responden, de una forma seria, novedosa y actual, al problema del diagnóstico de estas patologías con que se encuentra el personal sanitario del Sistema Nacional de Salud y los investigadores cuya línea de trabajo está dirigida al estudio de estas parasitosis..

Estimación Bayesiana de la prevalencia de Estrongiloidiasis en la población infantil de Cubal (Angola) y de los parámetros de tests diagnósticos en ausencia de gold standard

El diagnóstico de certeza de Strongyloides stercoralis es la detección de larvas por microscopía; sin embargo su sensibilidad es baja. La técnica de Baermann mejora dicha sensibilidad, pero es insuficiente por las limitaciones que presenta. Como alternativa, las técnicas moleculares suponen una notable mejora de sensibilidad, especificidad y rapidez. Sin embargo, actualmente no existe un gold standard. La Estadística Bayesiana permite abordar esta problemática en ausencia de gold standard estimando la sensibilidad y la especificidad de estas pruebas diagnósticas y la prevalencia de la enfermedad en contexto de zonas endémicas. Por esto nos planteamos estimar la prevalencia de la estrongiloidiasis en población infantil de una zona rural de Cubal (Angola) y la sensibilidad y especificidad de dos pruebas diagnósticas específicas de esta enfermedad, las técnicas de Baermann y PCR en tiempo real (PCRrt), empleadas en el contexto de ausencia de gold standard. Para ello la población se dividió en niños que caminaban descalzos y niños que caminaban calzados. Se utilizó inferencia Bayesiana para estimar tres modelos dependiendo de las distribuciones a priori fijadas para los parámetros de interés, a partir de: 1) una búsqueda bibliográfica; 2) datos de un estudio de una población de Etiopía cuyas a priori se determinaron a partir de la búsqueda bibliográfica; 3) una combinación de los dos anteriores. Tras observar los datos de la población de Cubal se obtuvieron las distribuciones a posteriori generando muestras aleatorias por el método de Monte Carlo de Cadenas de Markov. El modelo 2 presentó un bajo valor de DIC (32.02) y una mayor precisión de los intervalos de probabilidad. La sensibilidad para la técnica Baermann y su intervalo de probabilidad al 95% fue 51.54% (35.72%-69.14%), mientras que para PCRrt fue de 81.75% (67.54%-92.85%). La especificidad para Baermann fue de 94.66% (92.27%-96.73%) y para PCRrt 89.90% (85.70%-93.91%). Las prevalencias estimadas fueron 14.15% (9.02%-20.00%) para la población que camina descalza y 11.10% (6.48%-16.71%) para la que camina calzada. A la vista de estos resultados se puede concluir que la Estadística Bayesiana permite estimar la validez de las pruebas diagnóstico en estudio así como determinar la prevalencia de estrongiloidiasis en ausencia de gold standard

Primer registro de la anomalía isotópica positiva de carbono del Valanginano en la Plataforma Mendocina, Cuenca Neuquina. Argentina: implicaciones paleoclimáticas

The Tithonian-Valanginian time interval in the Mendoza Shelf (Neuquén Basin, Argentina) is well exposed in the Río Salado, Puesto Loncoche and Cuesta del Chihuido sedimentary sections. From those localities, more than fifty preserved oyster shells of the genus Aetostreon sp. were selected and sampled in order to perform the first δ13C curves for this particular time interval. Mineralogical and cathodoluminiscence properties, inner micromorphology of the valves, added to major and trace element geochemistry were analyzed in order to highlight the best C-O isotopic preservation. The δ13C isotope curves show values varying between 0 and-3‰ VPDB for the Tithonian-Berriasian basal section, and a positive excursion of ~2.4-2.7‰ VPDB in the Valanginian upper section. This δ13C up section trend is here considered in order to reveal eminent correlations with other sections from the Neuquén Basin, as well as the Weissert Event from the Tethys area, also on the basis of their ammonite faunal zones. The palaeotemperatures obtained from δ18O preserved values, added to a detailed sedimentological study suggest that observed δ13C anomaly may responds to a global climatic change from warm and dry to warm and humid conditions.El intervalo Titoniano-Valanginiano en la Plataforma Mendocina (Cuenca Neuquina, Argentina) se encuentra muy bien representado en las secciones sedimentarias estudiadas de Río Salado, Puesto Loncoche y Cuesta del Chihuido. En estas localidades más de cincuenta valvas de ostras del género Aetostreon sp. fueron seleccionadas y muestreadas con el objeto de obtener las primeras curvas de δ13C de este particular intervalo temporal. Las propiedades mineralógicas, la respuesta a la catodoluminiscencia, así como la micromorfología interna de las valvas, sumado al análisis geoquímico de los elementos mayoritarios y trazas fueron utilizados para indicar las zonas con el más alto grado de preservación isotópica del C y O. La curva de δ13C muestra valores que varían entre 0 y -3‰ VPDB para la sección basal de edad titoniana-berriasiana y una excursión positiva de ~2.4-2.7‰ VPDB para la sección cuspidal de edad valanginiana. Esta tendencia del δ13C hacia el tope de la sección revela una eminente correlación con otras secciones de la Cuenca Neuquina como así también con el Evento Weissert para el área del Tetis, también respaldada por la fauna de amonites presente. Las paleotemperaturas obtenidas aquí a partir de los datos de δ18O, sumado al estudio sedimentológico de detalle sugieren que la anomalía de δ13C podría ser la respuesta a un cambio climático desde condiciones cálidas y áridas a cálidas y húmedas registrado a nivel globalCentro de Investigaciones Geológica

Detoxifying enzymes at the cross-roads of inflammation, oxidative stress, and drug hypersensitivity: role of glutathione transferase P1-1 and aldose reductase

9 p.-2 figPhase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including toxicants and drugs. Genotyping studies have established several drug metabolizing enzymes as markers for risk of drug hypersensitivity. However, other candidates are emerging that are involved in drug metabolism but also in the generation of danger or costimulatory signals. Enzymes such as aldo-keto reductases (AKR) and glutathione transferases (GST) metabolize prostaglandins and reactive aldehydes with proinflammatory activity, as well as drugs and/or their reactive metabolites. In addition, their metabolic activity can have important consequences for the cellular redox status, and impacts the inflammatory response as well as the balance of inflammatory mediators, which can modulate epigenetic factors and cooperate or interfere with drug-adduct formation. These enzymes are, in turn, targets for covalent modification and regulation by oxidative stress, inflammatory mediators, and drugs. Therefore, they constitute a platform for a complex set of interactions involving drug metabolism, protein haptenation, modulation of the inflammatory response, and/or generation of danger signals with implications in drug hypersensitivity reactions. Moreover, increasing evidence supports their involvement in allergic processes. Here, we will focus on GSTP1-1 and aldose reductase (AKR1B1) and provide a perspective for their involvement in drug hypersensitivityThis work has been supported by grants SAF2012-36519 from MINECO and SAF-2015-68590-R from MINECO/FEDER and ISCIII RETIC RIRAAF RD12/0013/0008 to DP,and RD12/0013/0002 to J A.Peer reviewe

Primer registro de la anomalía isotópica positiva de carbono del Valanginano en la Plataforma Mendocina, Cuenca Neuquina. Argentina: implicaciones paleoclimáticas

The Tithonian-Valanginian time interval in the Mendoza Shelf (Neuquén Basin, Argentina) is well exposed in the Río Salado, Puesto Loncoche and Cuesta del Chihuido sedimentary sections. From those localities, more than fifty preserved oyster shells of the genus Aetostreon sp. were selected and sampled in order to perform the first δ13C curves for this particular time interval. Mineralogical and cathodoluminiscence properties, inner micromorphology of the valves, added to major and trace element geochemistry were analyzed in order to highlight the best C-O isotopic preservation. The δ13C isotope curves show values varying between 0 and-3‰ VPDB for the Tithonian-Berriasian basal section, and a positive excursion of ~2.4-2.7‰ VPDB in the Valanginian upper section. This δ13C up section trend is here considered in order to reveal eminent correlations with other sections from the Neuquén Basin, as well as the Weissert Event from the Tethys area, also on the basis of their ammonite faunal zones. The palaeotemperatures obtained from δ18O preserved values, added to a detailed sedimentological study suggest that observed δ13C anomaly may responds to a global climatic change from warm and dry to warm and humid conditions.El intervalo Titoniano-Valanginiano en la Plataforma Mendocina (Cuenca Neuquina, Argentina) se encuentra muy bien representado en las secciones sedimentarias estudiadas de Río Salado, Puesto Loncoche y Cuesta del Chihuido. En estas localidades más de cincuenta valvas de ostras del género Aetostreon sp. fueron seleccionadas y muestreadas con el objeto de obtener las primeras curvas de δ13C de este particular intervalo temporal. Las propiedades mineralógicas, la respuesta a la catodoluminiscencia, así como la micromorfología interna de las valvas, sumado al análisis geoquímico de los elementos mayoritarios y trazas fueron utilizados para indicar las zonas con el más alto grado de preservación isotópica del C y O. La curva de δ13C muestra valores que varían entre 0 y -3‰ VPDB para la sección basal de edad titoniana-berriasiana y una excursión positiva de ~2.4-2.7‰ VPDB para la sección cuspidal de edad valanginiana. Esta tendencia del δ13C hacia el tope de la sección revela una eminente correlación con otras secciones de la Cuenca Neuquina como así también con el Evento Weissert para el área del Tetis, también respaldada por la fauna de amonites presente. Las paleotemperaturas obtenidas aquí a partir de los datos de δ18O, sumado al estudio sedimentológico de detalle sugieren que la anomalía de δ13C podría ser la respuesta a un cambio climático desde condiciones cálidas y áridas a cálidas y húmedas registrado a nivel globalCentro de Investigaciones Geológica

Asthma, much more than a respiratory disease: influence of depression and anxiety

[Abstract] OBJECTIVE: The goals of this study are to compare self-reported depression and anxiety in subjects diagnosed of asthma and healthy controls. METHODS: We designed a case-control study. Subjects were recruited using a consecutive sampling method from a single institution. Two groups were created: Asthma and healthy controls. Data of medical history and demographic background were collected from the medical record. Self-reported depression level was assessed using Beck's depression inventory (BDI). Self-reported anxiety was measured with the “State-trait anxiety inventory” (STAI). RESULTS: Fifty-one subjects with asthma, and fifty healthy patients were included in this study. BDI scores (p<0.001) were higher for asthma (10.22±7.3) than in the control group (5.2±6.56). STAI state (p<0.001) was higher in asthma (42.61±11.5) than in controls (34.88±9.25). STAI trait (p<0.001) showed higher scores in asthma (43.14±10.89) than in controls (34.62±9.19). CONCLUSIONS: These study findings showed that BDI, and STAI trait and state scores are significantly higher in subjects who suffer from asthma than healthy controls

Field and laboratory comparative evaluation of a LAMP assay for the diagnosis of urogenital schistosomiasis in Cubal, Central Angola

Objetive: To evaluate the performance of Rapid-Heat LAMPellet assay in field conditions for diagnosis of urogenital schistosomiasis in an endemic area in Cubal, Angola, and to assess the reproducibility in a reference laboratory. Methods: A total of 172 urine samples from school-age children were tested for microhaematuria, microscopic detection of Schistosoma haematobium eggs and LAMP for DNA detection. Urine samples were stored in a basic equipped laboratory. Field-LAMP tests were performed with and without prior DNA extraction from urine samples, and the results were read by turbidity and by colour change. When field procedures were finished, samples were sent to a reference laboratory to be reanalysed by LAMP. Results: A total of 83 of 172 (48.3%) were positive for microhaematuria, 87/172 (50.6%) were microscopy-positive for S. haematobium eggs detection, and 127/172 (73.8%) showed LAMP-positive results for detecting S. haematobium using purified DNA and 109/172 (63.4%) without prior DNA extraction. MacNemar's test showed a statistical significant relation between LAMP results and microscopy-detected S. haematobium infections and microhaematuria (P < 0.001 in both cases), respectively. When samples of purified DNA were reanalysed in a reference laboratory in Spain using the same LAMP methodology, the overall reproducibility achieved 72.1%. Conclusions: The ease of use, simplicity and feasibility demonstrated by LAMP assay in field conditions together with the acceptable level of reproducibility achieved in a reference laboratory support the use of LAMP assay as an effective test for molecular diagnosis of urogenital schistosomiasis in endemic remote areas.This study was supported by Mundo Sano Foundation (www.mundosano.org) and by the Institute of Health Carlos III, ISCIII, Spain (www.isciii.es), grants: RICET RD16/0027/0018, DTS16/00207, PI16/01784 European Union cofinancing by FEDER (Fondo Europeo de Desarrollo Regional) ‘Una manera de hacer Europa’.S

Señales geoquímicas en pingüinos del Paleógeno de Isla Marambio (Seymour island), Península Antártica

Trace elements, particularly rare earth elements (REE), are widely used as proxies to reconstruct paleoenvironmental and taphonomic conditions. We traced these elements in fossil penguin bones collected along the Paleogene sequence exposed in Seymour Island (=Isla Marambio) to test them as indicators of the tectonic changes to which this region was exposed. The results indicated the contents of REE in thirteen samples of the analyzed bone tissues. The negative europium anomaly in the samples from Bartonian and Priabonian beds reflects regional events. This signal coincides in time with the opening of the Drake Passage, and with the tectonic changes that occurred between the end of the Eocene and the beginning of the Oligocene, between the western margin of South America and the Antarctic Peninsula.Los elementos traza, y particularmente los Elementos de las Tierras Raras (REE por sus siglas en inglés), son ampliamente utilizados como indicadores para la reconstrucción de condiciones paleoambientales y tafonómicas. Rastreamos estos elementos en huesos fósiles de pingüinos recolectados a lo largo de la secuencia del Paleógeno expuestos en la Isla Marambio (=Seymour Island) para testearlos como indicadores de los cambios tectónicos a los que estuvo expuesta la región. Los resultados indicaron las concentraciones de REE en el interior de las trece muestras de tejido óseo analizado. La anomalía de europio negativa en las muestras de nivel Bartoniano y Priaboniano refleja eventos regionales. Esta señal coincide en el tiempo con la apertura del Pasaje de Drake, y con los cambios tectónicos que ocurrieron entre finales del Eoceno y principios del Oligoceno, entre el margen occidental de las costas de América del Sur y la Península Antártica.Facultad de Ciencias Naturales y MuseoCentro de Investigaciones Geológica

Epidemiology of intestinal helminthiases in a rural community of Ethiopia: Is it time to expand control programs to include Strongyloides stercoralis and the entire community?

Soil transmitted helminths are highly prevalent worldwide. Globally, approximately 1.5 billion people are infected with Ascaris lumbricoides, Trichuris trichiura or hookworm. Endemic countries carry out periodic mass treatment of at-risk populations with albendazole or mebendazole as a control measure. Most prevalence studies have focused on school aged children and therefore control programs are implemented at school level, not at community level. In this study, the prevalence of intestinal helminths, including Strongyloides stercoralis, was examined using a comprehensive laboratory approach in a community in north-western Ethiopia. A cross-sectional survey was conducted on 792 individuals ≥5 years old in randomly selected houses in a rural district. Stools were examined using three techniques: a formol-ether concentration, the Baermann technique and a real time polymerase chain reaction test (these last two specific for S. stercoralis). Statistical analyses were performed between two large age groups, children (≤14 years old) and adults (≥15 years old). The prevalence of helminths was 91.3%; (95% CI: 89.3-93.3%). Hookworm was the most prevalent, 78.7% (95% CI 75.6-81.4%), followed by S. stercoralis 55.7% (95% CI 52.2-59.1%). Co-infection with both was detected in 45.4% (95% CI 42.0-49.0%) of the participants. The mean age of hookworm-infected individuals was significantly higher than non-infected ones (p = 0.003). Also, S. stercoralis infection was significantly associated with age, being more prevalent in adults (p = 0.002). This is the highest prevalence of S. stercoralis detected in Ethiopia so far. Our results highlight the need of searching specifically for infection by this parasite since it usually goes unnoticed if helminth studies rely only on conventional diagnostic techniques, i.e. Kato-Katz. Moreover, the focus of these programs on children undermines the actual prevalence of hookworm. The adult population acts as a reservoir for both hookworm and S. stercoralis and this fact may negatively impact the current control programs in Ethiopia which only target treatment of school aged children. This reservoir, together with a lack of adequate water, sanitation and hygiene, increases the probability of re-infection in children. Finally, the high prevalence of S. stercoralis found calls for a comprehensive diagnostic approach in endemic areas in addition to a revision of control measures that is, adding ivermectin to current albendazole/mebendazole, since it is the drug of choice for S. stercoralis.This study was funded by the Mundo Sano Foundation and the Spanish Network on Tropical Diseases Research (Red de Investigación cooperativa de Enfermedades Tropicales-RICET RD12/0018/0001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Risk associations for intestinal parasites in symptomatic and asymptomatic schoolchildren in central Mozambique.

Chronic infections by enteric parasites including protist and helminthic species produces long-term sequelae on the health status of infected children. This study assesses potential associations linked with enteric parasite infections in symptomatic and asymptomatic children in Zambézia province, Mozambique. In this prospective cross-sectional study, stool samples and epidemiological questionnaires on demographics and risk associations were collected from symptomatic children (n = 286) from clinical settings and asymptomatic (n = 807) children from 17 schools and creches aged 3‒14 years. We detected enteric parasites by PCR-based methods. We calculated prevalence (adjusted for age, sex, house construction, drinking water, and latrine use) and odds ratios (OR) for risk associations with logistic regression, after adjusting for district, neighbourhood, and symptoms. Numbers and adjusted prevalences (95% confidence intervals in brackets) for the symptomatic and asymptomatic populations were G. duodenalis 120, 52%(22-82), 339, 42% (25-59); followed by S. stercoralis 52, 14%(9‒20), 180, 20%(15-25). Risk associations for G. duodenalis included drinking untreated river/spring water, OR 2.91 (1.80-4.70); contact with ducks, OR 14.96 (2.93‒76.31); dogs, OR 1.92 (1.04-3.52); cats, OR 1.73 (1.16-2.59), and a relative with diarrhoea, OR 2.59 (1.54‒4.37). Risk associations for S. stercoralis included having no latrine, OR 2.41 (1.44-4.02); drinking well water, OR 1.82 (1.02-3.25), and increasing age, OR 1.11 (1.04-1.20). We found a high prevalence of intestinal parasites regardless of the children's symptoms. Drinking well or river water, domestic animals, and latrine absence were contributing factors of human infections.This study was funded by the Health Institute Carlos III (ISCIII), Ministry of 273 Economy and Competitiveness (Spain), under project PI16CIII/00024. Additional funds 274 were provided by the Spanish Tropical Diseases Research Network (RICET, ISCIII) under 275 project RD16CIII/0003/0004 for the testing of Entamoeba histolytica and E. dispar.S