ESAT-6 and Ag85A Synthetic Peptides as Candidates for an Immunodiagnostic Test in Children with a Clinical Suspicion of Tuberculosis.

BACKGROUND: Tuberculosis (TB) is being underdetected in children as most are smear-negative. This work was aimed at evaluating ESAT-6 and Ag85A synthetic peptides' serodiagnostic potential for diagnosing children having a clinical suspicion of TB. METHODS: The study involved 438 children: 77 Creole nonindigenous (13 suspected of having TB and 64 healthy ones) and 361 Warao indigenous children (39 suspected of TB and 322 healthy children). The approach's diagnostic information was compared using operational characteristics and receiver-operating characteristic (ROC) curves. RESULTS: Ag85A P-29879 had 94.6% sensitivity (AUC = 0.741: 0.651 to 0.819 95% CI) in indigenous children. ESAT-6 P-12036 and P-12037 had 100% and 92.3% of sensitivity (AUC = 0.929: 0.929: 0.846 to 0.975 95% CI and 0.791: 63.9 to 98.7 95% CI, respectively) in Creole children. ESAT-6 peptides also allowed a differentiation between children with TB and healthy ones. CONCLUSIONS: Further validation of this approach could lead to developing a complementary tool for rapid TB diagnosis in children.

Clinical factors affecting the efficacy of melasma treatment using the Q-switched 1064 Nd: YAG laser mode in a group of Venezuelan female patients.

The influence of melasma risk factors on the effectiveness of laser toning treatment in Venezuelan females was investigated. Clinical evaluation was performed (n = 64) including ultrasound and thyroid hormone profile. All patients underwent face exposure with laser toning, eight sessions weekly. VISIA percentiles corresponding to dark brown spots determined before and after treatment were compared by ANOVA. Differences between percentile values before and after treatment for each patient were calculated and expressed as percentages. An improvement of ≥30% was considered as significant. Spearman rank correlations between improvement and clinical parameters were determined. A significant increase (p > .005) of the median of the percentiles in the overall group was observed. However, only 62.5% of the patients exhibited an improvement of ≥30% at the right malar, 73.4% at the frontal and 71.8% at the left malar areas. Hormonal contraception during treatment (right malar: p < .0001 left malar: p = .0035), thyroid disorders (right malar: p < .0001; frontal: p = .011; left malar: p < .0001) and photoaging (right malar: p = .0235; frontal: p = .0237; left malar: p = .0137) were inversely associated to melasma improvement after treatment. Prolonged use of sunscreen improved significantly (right malar: p < .001; frontal: p = .016 and left malar: p = .025) treatment effectiveness.

Intestinal parasitic infections and atopic dermatitis among Venezuelan Warao Amerindian pre- school children.

BACKGROUND: We evaluated the influence of intestinal parasitic infection on food sensitization associated to the severity of Atopic Dermatitis (AD) in a group of Warao Amerindian pre- school children. METHODS: Feces examinations were performed in fresh stool specimens. Diagnosis of AD was done according to Hannifin and Rajka criteria and SCORAD index. Skin prick tests (SPT) were performed using extracts of cow's milk (CM), hen's egg (HE), Dermatophagoides pteronyssinus and Dermatophagoides farinae . Serum CM and HE-IgE levels (ELISA) were measured. Quantikine (R&D systems) assays were used for the determination of IL-13, TNF-α IL-6, and sCD23 in supernatants of CM- and HE- whole blood stimulated samples. RESULTS: Atopic Dermatitis was reported in 23% of the children. It was significantly (p < 0.0001) associated toward both CM and HE- SPT positivity (p < 0.001). Giardia duodenalis infection (37%) was associated to the presence of AD (p = 0.005) and to a significant increase in the levels of CM stimulated TNF-α (p=0.006), IL-13 (p = 0.01), sCD23 (p = 0.001), CM-IgE (p = 0.012) and CM-SPT (p < 0.0001). Similarly, G. duodenalis infection was particularly associated with the increase on the levels of HE-stimulated TNF-α (p = 0.001), sCD23 (p = 0.001), HE-IgE levels (p = 0.002) and HE-SPT (p = 0.001). CONCLUSION: Gut inflammation caused by G. duodenalis may enhance food allergic reactivity contributing to the manifestation of AD in these children. However, other environmental factors (not considered in this work) as well as an atopic background among the Warao population would also contribute to the presence of AD.

Factores inmunológicos que pueden influir en la presencia de síntomas clínicos en niños con giardiasis / Immunological factors influencing the presence of clinical symptoms in children with giardiasis

El objetivo de este trabajo fue evaluar el perfil de la respuesta inmune según sintomatología intestinal en niños con giardiasis. Se realizó un estudio transversal clínico, inmunológico y parasitológico en 182 escolares (6-7 años) de la región de Barlovento, Estado Miranda. La evaluación clínica fue realizada haciendo énfasis en los síntomas intestinales y evaluación antropométrica. Se realizaron exámenes de heces seriadas. Los niveles de IgA secretora (total y específicos a G. duodenalis) así como los niveles de citocinas fueron determinados mediante ELISA. Los niveles de óxido nítrico usando el método colorimétrico de Griess. Análisis estadístico mediante Med calc Software, Versión 12.4.0. Encontramos que Los niveles plasmáticos de TNF-α y de óxido nítrico (en saliva) fueron más elevados en los niños con síntomas intestinales y giardiasis (P<0.001) mientras que los niveles de TGF-β, IL-10 y los niveles de IgA secretora total y especifica a G. duodenalis fueron más elevados (P<0.0001) en el grupo de asintomáticos. Los niveles de IL-6 fueron más elevados en los niños con giardiasis independientemente de la sintomatología. La co-infeccion con A. lumbricoides se asoció negativamente a la presencia de síntomas intestinales. Los indicadores antropométricos (Talla/edad, peso/Edad y Peso/ Talla) se asociaron positivamente a la presencia de citocinas reguladoras (P<0.005) y niveles de IgA secretora (P<0.0001). Así, Diferencias en el perfil de la respuesta inmune podrían asociarse a síntomas intestinales inducidos por giardiasis. Deficiencias en el estado nutricional se asocian a procesos inflamatorios y a la generación de síntomas mientras que la co-infección con helmintos intestinales favorece la reducción de la sintomatología.

We evaluated the immune profile associated to intestinal symptoms in children with giardiasis. A crosssectional study including clinical, immunological and parasitological aspects in 182 children (6-7 years) from the area of Barlovento, Miranda state, Venezuela was carried out. Clinical evaluation was performed with emphasis on intestinal symptoms and anthropometric parameters were also determined. Serial stool examinations were carried out. Secretory IgA levels (total and specific against G. duodenalis) and cytokine levels were determined by ELISA. Nitric oxide levels were determined using the Griess colorimetric method. Statistical analysis was performed by Med Calc Software, Version 12.4.0. We found that plasma levels of TNF-α and nitric oxide (salivary) were higher in children with intestinal symptoms and giardiasis (P<0.001) while the levels of TGF-β, IL-10 and IgA levels (total and anti-G. duodenalis) were higher (P<0.0001) in the asymptomatic group. The levels of IL-6 were higher in children with giardiasis regardless of symptoms. Coinfection with A. lumbricoides was associated negatively with the presence of intestinal symptoms. Anthropometric indicators (height / age, weight / age and weight / height) were positively associated with the presence of regulatory cytokines (P<0.005) and secretory IgA levels (P<0.0001). Therefore, differences in the immune profile may be associated with intestinal symptoms induced by giardiasis. Co-infection with intestinal helminths helps to reduce symptoms while nutritional deficiencies are associated with inflammatory processes and the generation of symptoms.

Evaluación de la posible asociación entre la presencia de parásitos intestinales y Helicobacter pylori en población infantil de la etnia Warao, Venezuela / Evaluation of the possible association between the presence of intestinal parasites and Helicobacter pylori in children of ethnic Warao

Las infecciones por microorganismos gastrointestinales constituyen hoy en día una de las principales causas de morbilidad y mortalidad en países en vías de desarrollo. Nos planteamos como objetivo evaluar la posible asociación entre la presencia de parásitos intestinales y la infección por Helicobacter pylori, y el comportamiento de anticuerpos séricos y secretores en una población infantil de la etnia Warao del Edo. Delta Amacuro, Venezuela. La presencia de parásitos se determinó por examen microscópico directo de las heces. Los niveles séricos de IgE total, IgG anti H. pylori e IgA anti Giardia duodenalis; y los secretores IgA total y específica a G. duodenalis y H. pylori en muestra de saliva, se determinaron utilizando el método de ELISA. El 65% de los niños estaban parasitados por protozoarios, observándose un 47% de poliparasitismo. Encontramos una mayor seroprevalencia de H. pylori en el grupo de niños no parasitados (46%) comparado con los parasitados (25%) (P<0,05). Sin embargo, los niños seropositivos a H. pylori y parasitados con G. duodenalis mostraron niveles séricos de IgE total mayores que los no parasitados (P<0,01); en contraparte, los niveles de IgA secretora total y especifica a H. pylori y G. duodenalis estaban disminuidos (P<0,05). Es posible que la respuesta inflamatoria generada por Giardia pueda aumentar los niveles de IgE total y disminuir la respuesta de IgA secretora favoreciendo la instauración de la infección por H. pylori.

The infections for gastrointestinal microorganisms represent nowadays one of the major reasons of morbidity and mortality in developing countries. We had evaluated both, the possible association between the presence of intestinal parasites and infection by Helicobacter pylori, and the production of serum and salivary antibodies in Amerindian Warao children from the Orinoco Delta, Venezuela. The prevalence of parasites was determined by faecal examination. The levels of serum antibodies (total IgE, specific anti- H. pylori IgG and anti G. duodenalis IgA) and salivary antibodies (total and specific IgA to G. duodenalis and H. pylori), was determined by ELISA. 65% of the child population was parasitized by protozoos, and a 47% of polyparasitism was observed. We found a major seroprevalence of H. pylori in the group of children not parasitized (46 %) compared with the parasitized ones (25 %) (P<0.05). Nevertheless, the seropositive children to H. pylori and parasitized with G. duodenalis showed levels of total IgE higher than the non parasitized ones (P<0.01); in contrast, levels of total and specific secretory IgA to H. pylori and G. duodenalis were decreased (P<0.05). It is possible that the inflammatory response generated by G. duodenalis infection may increase levels of total IgE and diminish secretory IgA response favoring the establishment of infection by H. pylori.

Escherichia coli diarreogénica asociada a casos de diarrea aguda en niños de Cumaná, Venezuela / Diarrheagenic Escherichia coli associated with acute diarrhea in children of Cumana, Venezuela

Para establecer la prevalencia de cepas de E. coli diarreogénicas (ECD) asociadas a casos de diarrea aguda infantil en Cumaná, Venezuela; se tomaron muestras de heces de 200 niños con enfermedad diarreica aguda, menores de 5 años, y de 30 niños sanos incluidos como control. El aislamiento e identificación bacteriana se realizó por coprocultivos y pruebas bioquímicas convencionales. Para determinar la presencia de los genes de patogenicidad de cada tipo de ECD se usó la técnica de reacción en cadena de la polimerasa (PCR), determinando los genes eae y bfp (ECEP), st y lt (ECET), ipaH y virF (ECEI), Stx1/Stx2 (ECST), aafII (ECEA) y daaE (ECAD). Se realizaron 169 aislamientos de E. coli, de las cuales se determinó por PCR que el 10,65% fueron positivas para ECEP (1,18% “típicas”; 9,47% “atípicas”); ECET (5,91%); ECEA (1,78%); ECEI (0,59%). No se observaron diferencias estadísticas significativas en cuanto a la frecuencia de cada “patotipo” en relación a la edad, pero si en relación con el sexo (p< 0,05). Las características clínicas más relevantes fueron: fiebre, vómito y dolor abdominal y el mayor porcentaje de los niños afectados estuvo en las clases obrera y marginal. Estos resultados muestran que las cepas de ECD, son agentes etiológicos importantes en la enfermedad diarreica aguda infecciosa en la población infantil de Cumaná.

To establish the prevalence of strains of diarrheagenic Escherichia coli (DEC) associated to acute diarrhea in childrem of Cumaná, Venezuela, stool samples were taken from 200 children aged < 5 years with acute diarrheal disease, and from 30 healthy children used as control. Isolation and bacterial identification was performed by conventional biochemical tests and stool cultures. The presence of pathogenic genes of each type of DEC was investigated by the technique of polymerase chain reaction (PCR), determining the genes eae and bfp (EPEC), st and lt (ETEC), ipaH and virF (EIEC) Stx1/Stx2 (STEC), aafII (EAEC) and daaE (ADEC). From 169 E. coli, isolates we determined by PCR 10.65% positive for EPEC (1.18% “typical”, 9.47% “atypical”); ETEC (5.91%); EAEC (1.78 %), EIEC (0.59%). There were no statistically significant differences regarding the frequency of each “pathotype” in relation to age, but it did occur when related to the sex (p<0.05). The most relevant clinical features were: fever, vomiting and abdominal pain and the greatest percentage of children affected were of the working and marginal classes. These results shown that the strains of DEC are important etiological agents in acute infectious diarrhea in children of Cumaná.

Características clínicas y epidemiológicas de la infección por rotavirus en niños de Cumaná, Venezuela / Clinical and epidemiological characteristics of rotavirus infection in children of Cumaná, Venezuela

Se estudió la tasa de detección de rotavirus humano del grupo A (RVH-A), así como su asociación con la clínica y epidemiología, en niños menores de 5 años con diarrea aguda que acudieron al Hospital Universitario “Antonio Patricio de Alcalá”, Cumaná, Venezuela, entre marzo de 2006 y septiembre de 2007. De 241 muestras fecales colectadas en este estudio, 47 (19,5%) resultaron positivas a RVH-A por ensayo inmunoenzimático y estuvieron presentes durante los 19 meses de estudio, con picos de mayor tasa de detección en los meses de marzo, abril y mayo (30,0%, 28,6% y 43,8%, respectivamente) de 2006 y septiembre (37,5%) de 2007. El 34% de los casos ocurrió en el grupo etario de 7 a 12 meses, y los varones fueron los más afectados (55,3%), así como las clases socioeconómicas obrera y marginal (72,4%). Los niños que recibieron alimentación no materna fueron mayormente infectados por RVH-A (61,7%). Se observó que la mayoría de los niños (72,3%) presentaron de 1 a 4 evacuaciones diarias, casi todas (83,0%) entre semilíquidas y líquidas, pero con pocos vómitos (38,2%) y muy pocos casos con fiebre (10,6%), sin embargo la deshidratación si resultó ser un síntoma significativo (OR=6,307; IC-95%=2,337-21,4; p = 0,0001) en los niños enfermos. Al comparar estos resultados con los de otros trabajos previos en la misma zona, se notó una disminución de la tasa de detección de RVH-A de más del doble, y los síntomas clínicos de la enfermedad rotaviral son los mismos reportados por otros autores. De 32 niños vacunados contra rotavirus, en 30 (93,8%) no se les detectó RVH-A en sus heces, y hubo una asociación significativa (OR=0,02434, IC-95%=0,0377-0,9171; p=0,037) entre los niños vacunados y la protección.

The detection rate of group A human rotavirus (HRV-A), as well as its association with clinical and epidemiological parameters, was studied in children younger than 5 years old with acute diarrhea attending to the University Hospital “Antonio Patricio de Alcalᔠof Cumaná, between march 2006 and september 2007. Of 241 fecal samples collected in this study, 47 (19.5%) were positive to HRV-A by immunoassay. Rotavirus were present throughout the study and the major detection rates were on march, april and may of 2006 (rates were 30,0%, 28,6% y 43,8%, respectively) and september of 2007 (37,5%). Thirty four percent of cases with HRV-A occurred in children of 7 - 12 months and males were the most affected (55.3%), as well as the worker and marginal socioeconomic classes (72,4%). Children that not received maternal feeding were the group mainly infected by HRV-A (61.7%). Most of the children (72.4%) had one to four evacuations/day, with few vomits (38.2%) and fever (10.6%). Almost all the feces (83.0%) had a liquid or semi-liquid aspect. When these results were compared with previous data of the same geographic area, we observed a two-fold decrease of the detection rate of HRV-A and the clinical symptoms were the same as reported by other authors. Of 32 children vaccinated against rotavirus, 30 (93.8%) did not have HVR-A in their feces and there was a significant association between the vaccinated children and protection.

Ascaris lumbricoides: an overview of therapeutic targets.

A. lumbricoides is the largest of the common nematode parasites of man and has been associated with intestinal pathology, respiratory symptoms and malnutrition in children from endemic areas. Current anthelmintic treatments have proven to be safe. However, a reduced efficacy of single dose drugs has been reported. In veterinary practice, anthelmintic drug resistance is an irreversible problem. Thus, research and development of sensitive tools for early detection of drug resistance as well as new anthelmintic approaches are urgently needed. In this review, we summarized data providing information about current drug therapy against A. lumbricoides and other intestinal helminths, new drugs in experimental trials, future drugs perspectives and the identification of immunogenic parasite molecules that may be suitable vaccine targets. In addition to the WHO recommended drugs (albendazole, mebendazole, levamisole, and pyrantel pamoate), new anthelmintic alternatives such as tribendimidine and Nitazoxanide have proved to be safe and effective against A. lumbricoides and other soil-transmitted helminthiases in human trials. Also, some new drugs for veterinary use, monepantel and cyclooctadepsipeptides (e.g., PF1022A), will probably expand future drug spectrum for human treatments. The development of genomic technology has provided a great amount of available nematode DNA sequences, coupled with new gene function data that may lead to the identification of new drug targets through efficient mining of nematode genomic databases. On the other hand, the identification of nematode antigens involved in different parasite vital functions as well as immunomodulatory molecules in animals and humans may contribute to future studies of new therapeutic approaches.

[Diarrheagenic Escherichia coli associated with acute diarrhea in children of Cumaná, Venezuela]. / Escherichia coli diarreogénica asociada a casos de diarrea aguda en niños de Cumaná, Venezuela.

To establish the prevalence of strains of diarrheagenic Escherichia coli (DEC) associated to acute diarrhea in children of Cumaná, Venezuela, stool samples were taken from 200 children aged < 5 years with acute diarrheal disease, and from 30 healthy children used as control. Isolation and bacterial identification was performed by conventional biochemical tests and stool cultures. The presence of pathogenic genes of each type of DEC was investigated by the technique of polymerase chain reaction (PCR), determining the genes eae and bfp (EPEC), st and lt (ETEC), ipaH and virF (EIEC) Stx1/Stx2 (STEC), aafII (EAEC) and daaE (ADEC). From 169 E. coli, isolates we determined by PCR 10.65% positive for EPEC (1.18% "typical", 9.47% "atypical"); ETEC (5.91%); EAEC (1.78 %), EIEC (0.59%). There were no statistically significant differences regarding the frequency of each "pathotype" in relation to age, but it did occur when related to the sex (p<0.05). The most relevant clinical features were: fever, vomiting and abdominal pain and the greatest percentage of children affected were of the working and marginal classes. These results shown that the strains of DEC are important etiological agents in acute infectious diarrhea in children of Cumaná.

[Clinical and epidemiological characteristics of rotavirus infection in children of Cumaná, Venezuela]. / Características clínicas y epidemiológicas de la infección por rotavirus en niños de Cumaná, Venezuela.

The detection rate of group A human rotavirus (HRV-A), as well as its association with clinical and epidemiological parameters, was studied in children younger than 5 years old with acute diarrhea attending to the University Hospital "Antonio Patricio de Alcalá" of Cumaná, between march 2006 and september 2007. Of 241 fecal samples collected in this study, 47 (19.5%) were positive to HRV-A by immunoassay. Rotavirus were present throughout the study and the major detection rates were on march, april and may of 2006 (rates were 30,0%, 28,6% y 43,8%, respectively) and september of 2007 (37,5%). Thirty four percent of cases with HRV-A occurred in children of 7 - 12 months and males were the most affected (55.3%), as well as the worker and marginal socioeconomic classes (72,4%). Children that not received maternal feeding were the group mainly infected by HRV-A (61.7%). Most of the children (72.4%) had one to four evacuations/day, with few vomits (38.2%) and fever (10.6%). Almost all the feces (83.0%) had a liquid or semi-liquid aspect. When these results were compared with previous data of the same geographic area, we observed a two-fold decrease of the detection rate of HRV-A and the clinical symptoms were the same as reported by other authors. Of 32 children vaccinated against rotavirus, 30 (93.8%) did not have HVR-A in their feces and there was a significant association between the vaccinated children and protection.

Efecto de las parasitosis intestinales sobre los parámetros antropométricos en niños de un área rural de Río Chico Estado Miranda, Venezuela / Effect of intestinal parasites on anthropometric parameters in children from a rural area of Rio Chico Miranda State, Venezuela

Las infecciones parasitarias tienen una alta prevalencia en poblaciones de países en desarrollo y modifican la condición nutricional afectando mayormente los grupos con mayor déficit nutricional. De 166 niños, pertenecientes a familias de la comunidad Madre Nueva de Río Chico, Estado Miranda - Venezuela; 51 escolares (28 niñas, 54,9 por ciento y 23 niños, 45,1. por ciento) siendo el 30,7 por ciento del total de los niños, entregaron muestra de heces para realizar examen al fresco. Las variables peso (kg), talla parada (cm), circunferencia de brazo izquierdo (CBI) (cm), pliegues de tríceps y subescapular (mm), índice de masa corporal (IMC) (kg/m2), área magra (mm) y área grasa (mm) fueron seleccionadas para establecer la relación. El 75 por ciento del grupo total presentó normalidad en crecimiento dimensional. El examen de heces mostró que 74 por ciento estaban parasitados, con similar incidencia en niños y niñas, la carga parasitaria fue leve según criterios de la OMS. Los parásitos mayormente encontrados fueron: Ascaris lumbricoides, Tenia y Giardia intestinalis. La media de las variables resultó ser menor en el grupo de parasitados, sin diferenciarse significativamente, del grupo no parasitado. La diferencia de las variables entre los niños, rango de edad de 10 - 13 años y los niños, rango de edad ≤ 6 años, fue una tendencia a la disminución en la ganancia de todas las variables excepto talla, para el grupo de parasitados. La alta prevalencia y la baja carga parasitaria no afectaron el estado nutricional de los niños; por lo que a los indicadores relacionados al acceso a los alimentos y recursos económicos suficientes a los hogares, se les debería prestar mayor atención

Intestinal parasitic infections have a high prevalence in populations of developing countries and affect mainly those individuals who have greater nutritional deficit. From 166 children, belonging to families of the community of "Nueva Madre de Rio Chico, Edo. Miranda, Venezuela"; 51 (28 girls, 54.9 percent and 23 boys, 45.1 percent) 30, 7 percent from the total children, delivered stool and fresh examination was made. The following variables were selected: weight (kg), tall (cm), left arm circumference (LAC) (cm), triceps folds (mm) and subscapular folds (mm), body mass index (BMI) (kg/m2), lean area (mm) and fat area (mm), to establish a relationship between parasites and anthropometric variables. 75 percent of the total group presented normal dimensional growth. The stool examination showed that 74 percent were infected, with similar incidence between boys and girls; the parasite load was mild according to criteria of WHO. The parasites with bigger frequency were: Ascaris lumbricoides, Taenia and Giardia intestinalis. The media of the anthropometric variables were lower in subjects with parasites and did not differ significantly from the group without parasites. The difference observed between the anthropometric values found for children in the age range: 10 - 13 years, and children in the age range ≤ 6 years was a trend towards a decrease in gain for all variables except tall for the group of parasitized children. The high prevalence and low parasite load did not affect the nutritional status of children, therefore, the indicators related to access to food and adequate financial resources to households, should be paid more attention

Reactividad alérgica a Anisakis simplex y su asociación con asma bronquial en niños escolares del estado Nueva Esparta, Venezuela / Anisakis simplex allergic reactivity and its association with bronchial asthma in scholar children from Nueva Esparta state, Venezuela

La reactividad alérgica frente a Anisakis simplex se ha convertido en un problema de salud pública en muchos países del mundo. En Venezuela, se ha reportado la presencia de mamíferos marinos infectados y se ha evidenciado la presencia del parásito en pescados de consumo masivo procedentes de las zonas costeras de oriente y occidente del país. No obstante, la importancia de este helminto en el desarrollo y severidad de patologías alérgicas no ha sido evaluada en el país. El objetivo de este estudio fue evaluar la reactividad alérgica al An. simplex en un grupo de 144 niños del estado de Nueva Esparta, así como su posible relación con la severidad de asma bronquial y rinitis alérgica. Todos los niños fueron evaluados utilizando un cuestionario socioeconómico validado y modificado de Graffar y un cuestionario validado según los criterios de ARIA (International Consensus Report) para rinitis alérgica, GINA (WHO/NIH Global Initiative for Asthma) para asma bronquial y Hannifin para dermatitis atópica, respectivamente. Se realizaron encuestas para evaluar las principales fuentes de alergenos a los cuales se expone la población de estudio. Se realizó la evaluación física de los niños y se practicaron pruebas cutáneas, así como pruebas de funcionalismo pulmonar. Encontramos un alto porcentaje (45%) de niños con pruebas de piel positiva al An. simplex. Se observó una mayor prevalencia y severidad, de asma y rinitis en aquellos niños con pruebas de piel positivas a An. simplex. Dado que ha sido previamente reportada la reactividad cruzada entre Ascaris lumbricoides y An. simplex, es importante considerar que la alta reactividad encontrada frente al An. simplex pueda deberse a la co-infección por Ascaris. De igual forma, la sensibilización frente a An. simplex, ya sea especifica o por reactividad cruzada existe, lo que sugiere que las autoridades locales deben considerar ciertas medidas preventivas, para evitar el consumo de pescados crudos o posiblemente parasitados con este helminto, que podrían exacerbar la patología respiratoria.

Allergic reactivity to Anisakis simplex has become in a health problem in many parts of the World. In Venezuelan coasts, it has been found infecting marine mammals and also different parasites fishes commonly consumed by human. However, the association of this helminth with the development and severity of allergic reactivity has not been previously evaluated in Venezuela. The aim of this study was to evaluate the allergic reactivity to An. simplex in a group 144 children from Nueva Esparta, state, and its possible relation with bronquial asthma and rhinitis allergic severity. All children were evaluated using a validated socioeconomic questionnaire modified by Graffar, and a validate questionnaire according to ARIA (International Consensus Report) for allergic rhinitis, GINA (WHO/NIH Global Initiative for Asthma) for bronquial asthma and Hannifin for atopic dermatitis. Surveys were performed in order to evaluate the main sources of allergens to which the study population exposes itself. Children physical evaluation and skin prick test were performed, as well as pulmonary function test. We found a high percentage (45%) of children with positive skin prick test to An. simplex. Moreover, a greatest prevalence and severity of asthma and rhinitis, was observed in those children with positive skin prick test to An. simplex. Since it has been reported the presence of the crossed reactivity between Ascaris lumbricoides and An. simplex, it’s important to consider that the high reactivity found to An. simplex might be due to the Co-infection with A. lumbricoides. Nevertheless, the sensibilization to An. simplex, due by specific or by crossed reactivity exists, and it should be considered by local health authorities in order to prevent the exacerbation of the respiratory pathologies mediated by the consumption of fresh fishes potentially infected.

Antibody responses and resistance against Ascaris lumbricoides infection among Venezuelan rural children: the influence of ethnicity.

We studied the production of anti parasite antibodies and the resistance against A. lumbricoides infection among the school population of three different Venezuelan ethnic groups: Warao Amerindians, Afro- Americans and white 'Creole' descendents. The prevalence and intensity of A. lumbricoides were determined before and after 1 year of anthelminthic treatment. Parasitic loads were associated to pre-treatment serum levels of anti A. lumbricoides IgE and IgG4 antibodies. The intensity of the infection and the proportion of re-infected children were significantly lower (p < 0.0001) among the Warao Amerindians, exhibiting higher levels of IgE (p < 0.0001) and lower levels of IgG4 (p < 0.0001) compared to their non-Amerindian counterparts. IgE levels correlated inversely with the proportion of re-infected children, whereas the levels of IgG4 were positively associated. These results suggest that ethnicity may influence the balance of IgE/IgG4 levels, modulating the intensity of A. lumbricoides and the resistance to the infection.

Associations of a novel IL4RA polymorphism, Ala57Thr, in Greenlander Inuit.

BACKGROUND: A novel IL4RA polymorphism, Ala57Thr, was identified in Greenlander Inuit. OBJECTIVE: We sought to determine whether the novel Thr57 allele is population specific and to assess the associations of Ala57Thr and Ile50Val with atopy in 2 Inuit populations. METHODS: Ala57Thr and Ile50Val were genotyped in 651 Inuit living in Denmark, 1295 Inuit living in Greenland, and 1329 individuals from 7 populations from widely differing global locations. In Inuit the polymorphisms were evaluated for associations with atopy, rhinitis, asthma, and pulmonary function. RESULTS: Thr57 was in linkage disequilibrium with Ile50 (D' = 1, r(2) = 0.13) and was common (33%) in the Inuit but rare (<0.6%) in all other populations. In Inuit living in Denmark, the Thr57 allele (in a dose-dependent manner) and the Ile50/Thr57 haplotype were associated with lower risk of atopy (P(linear) = .003 and P = .034, respectively), with similar trends observed for atopic rhinitis and atopic asthma. In Inuit living in Greenland, Thr57 was not associated with atopy or atopic diseases, but Ile50 was weakly associated with lower risk of atopy. CONCLUSION: The novel IL4RA Ala57Thr was common in and population specific to Greenlander Inuit, with Thr57 associated with a lower risk of atopy in those living in Denmark. Hence a full investigation of genotype-phenotype relationships in a given population can only be achieved if each gene is screened for novel polymorphisms in that population. CLINICAL IMPLICATIONS: Clinical risk attributable to variations in a gene in an ethnic group requires that all variations of the gene are known for that group.

Role of the low affinity IgE receptor (CD23) on the IgE response against Ascaris lumbricoides in Warao Amerindian children from Venezuela

El objetivo de este estudio fue investigar los mecanismos inmunitarios frente a helmintos gastrointestinales involucrados en la producción de IgE, particularmente el papel del receptor de baja afinidad para la IgE (CD23) en niños indígenas de la etnia Warao del Delta del Orinoco en Venezuela. Estudiamos un grupo no seleccionado (159) de niños Warao escolares con una alta prevalencia e intensidad de infección por parásitos helmintos, y un grupo control de 70 niños no parasitados de una comunidad rural criolla del mismo Estado. Los niveles totales y específicos de IgE anti-A lumbricoides, determinados por ELISA, fueron extremadamente elevados en los niños Warao (p < 0,001). Sin embargo, solo un reducido grupo de esos niños fue capaz de desarrollar una respuesta de IgE específica clínicamente significativa (> 0,7UI/mL) frente a antígenos de A lumbricoides. El número de células circulantes, T CD4+, B CD20+ CD21+ y la expresión del receptor de baja afinidad para IgE (CD23) determinados por citometría de flujo, fueron significativamente (p < 0,001) más elevados en los niños Warao, particularmente en aquellos con adecuados niveles de IgE específica frente al parásito. Se encontró una alta correlación (p < 0,001) entre los niveles totales y específicos de IgE específica y la expresión del receptor para la IgE (CD23) y una correlación significativa (p < 0,005) entre el número de células circulantes CD20+CD23+ y CD4+. Concluimos entonces que los antígenos de A. lumbricoides podrían estimular la producción de IgE total y específica a través de una vía dependiente del receptor CD23. Sin embargo, los factores ambientales y genéticos que podrían determinar la capacidad de desarrollar respuestas IgE eficientes en la población Warao, requiere de mayor estudio

Role of the low affinity IgE receptor (CD23) on the IgE response against Ascaris lumbricoides in Warao Amerindian children from Venezuela.

The objective of this study was to investigate the immune mechanisms against gastrointestinal helminths involved in the production of IgE, particularly the role of the low affinity IgE receptor (CD23) in Amerindian Warao children from the Orinoco Delta, Venezuela. We studied a group of unselected (n = 159) Warao school children with high prevalence and intensity of helminthic infection and a similar non- parasitized (n = 70) control group of a "creole" community also located at the Delta of the Orinoco. The levels of total and specific anti-Ascaris IgE, determined by ELISA, were extremely higher in the Warao children (p < 0.001) compared to the control group. However, only a reduced group of these children were able to develop a clinically significant (> 0.7 PRU/mL) IgE response against A lumbricoides antigens. Circulating T helper cells (CD3+CD4+), activated B (CD20+, CD20+CD21+) lymphocytes and the expression of the low affinity receptor for IgE (CD23), determined by flow cytometry, were significantly (p < 0.001) elevated in the Warao children, particularly in those with an enhanced capacity to mount efficient specific anti Ascaris IgE responses. Strong correlations (p < 0.001) were found between the number of circulating CD20+CD23+ cells and the level of total and anti-A lumbricoides IgE. Also, a significant (p < 0.005) correlation between CD20+CD23+ and CD4+ circulating cells was observed. We conclude that A lumbricoides antigens may stimulate the production of total and specific IgE through a CD23 dependent pathway. However the different environmental and genetics factors involved in the capacity to develop efficient specific responses among the Warao population still need to be elucidated.

Factores inmunológicos protectores frente a la infección por Ascaris lumbricoides en niños indígenas y criollos de comunidades rurales de Venezuela / Immunological factors protective for Ascaris lumbricoides infection in indigenous and native children from rural communities in Venezuela

El objetivo de este trabajo fue estudiar los mecanismos inmunológicos involucrados en la protección a la infección por Ascaris lumbricoides en niños de diferentes comunidades rurales. La prevalencia y la carga parasitaria fueron determinadas por el método de Kato-Katz, los niveles de IgE especifica frente a A lumbricoides mediante la técnica de ELISA y el numero de linfocitos T (CD3+; CD3+ CD4+) y B (CD20+; CD20+CD23+) circulantes por Citometría de Flujo. Los niños fueron clasificados según sus niveles de IgE en respondedores (>0,7UI/ml) y no respondedores (<0,7UI/ml), y se compararon los distintos parámetros de acuerdo a esta clasificación. Las cargas parasitarias fueron significativamente más bajas (p<0.0001) en los niños respondedores. Las sub-poblaciones de linfocitos T y B circulantes fueron mas elevadas (p<0.0001) en los grupos de respondedores. Se observó una correlación negativa entre la carga parasitaria con los niveles de IgE especifica anti A. lumbricoides y el numero de linfocitos T CD4+ circulantes. Nuestros resultados sugieren un papel protector frente a la infección por A.lumbricoides tanto de la IgE específica como de la respuesta T cooperadota

The role of parasites in genetic susceptibility to allergy: IgE, helminthic infection and allergy, and the evolution of the human immune system.

There have been numerous studies in the mouse illustrating the dichotomy of T cell responses, with the common classification orchestrated around Th1 vs. Th2 responses. This classification is now widely applied to human disease as well and the generic conclusion is that the Th1 responses are more likely to occur secondary to specific microbiologic insult but also inflammatory responses. In contrast, the Th2 response is the prevalent response in subjects with atopy and allergic disease but is also the mechanism for protection against helminthic infections. Unfortunately, the paradigm of Th1 vs. Th2 is not as clear in the human as it is in mouse models. Even so, the immunological mechanisms responsible for IgE production that are protective in helminthic infections, i.e. Schistosoma, are similar to those for the production of specific IgE against allergens. In fact, there also appear to be associations in the memory T cell subpopulation CD4+CD45RO+ and the elicitation of IgE against both parasites and allergens. In this review, we present the overall contemporary scheme on the role of parasites in genetic susceptibility to allergic IgE, helminthic infections with specific discussion of its implications for the evolution of the human immune system.

Secretory IgA antibody responses in Venezuelan children infected with Giardia duodenalis.

We standardized and evaluated an ELISA technique for the detection of total and specific anti-Giardia duodenalis secretory IgA antibodies (sIgA). Samples of saliva and serum of 161 Venezuelan schoolchildren were analysed. After stool examination, 66 children were diagnosed to be infected with Giardia duodenalis, 22 with other protozoa, and 73 non-parasitized. The mean (+ 2 SD) values of secretory IgA in the non-parasitized group was considered as the criterion of positivity. The levels of total and specific anti-Giardia sIgA were significantly higher in children with Giardia compared with the group with other protozoa (p < 0.01) and the non-parasitized group (p < 0.001). The ELISA technique developed showed values of sensitivity and specificity of 74 and 94 per cent, respectively, a predictive value of 92 per cent for positive samples and 80 per cent for negative samples. Specific anti-Giardia IgA serum levels showed a low sensitivity (57 per cent) and a predictive value for negative samples (53 per cent). Our results suggest that secretory anti-Giardia IgA levels measured in saliva samples may reflect local intestinal IgA responses elicited by these parasites. Thus, determinations of the levels of sIgA anti-Giardia could be a useful diagnostic tool for giardiasis in children.