Primeros casos autóctonos de hepatitis e en Uruaguay / First autochthonous hepatitis E cases in Uruguay

Con el objetivo de describir los primeros casos autóctonosde Hepatitis E se realizó un estudio descriptivo. La población,9 enfermos, se identificó en el periodo noviembre 2009a julio 2010. Se seleccionaron por IgG e IgM específicaspara VHE y se realizó búsqueda de ARN viral en suero porRT-PCR. Presentaron una media de 51 años, 8 del sexo masculino, educación terciaria, nivel socioeconómico medio alto, atención en el sector privado y residencia urbana. La clínica fue similar a Hepatitis A, con transaminasas elevadas por encima de 1500 (mU/ml), la glutamicopiruvica convalores máximos de 5270 (mU/ml). Todos presentaron hiperbilirrubinemia a predominio directa, aumento de lagamaglutamil transferasa y de Fosfatasa Alcalina. Se demostrócirculación en Uruguay del VHE con manifestaciones clínicas, lo que traduce la presencia de una enfermedad emergente. Se plantea introducir el diagnostico del VHE en forma protocolizada en pacientes sin diagnostico etiológico de hepatitis.

In order to describe the first autochthonous Hepatitis E cases, we carried out a descriptive study. The population, 9 patients, was identified from November 2009 to July 2010. They were selected by specificIgG and IgM for HEV and we made viral RNA search in serum by RT-PCR. Patients average age was 51 years old, 8 male, tertiary education, upper middle socioeconomic level, health attention in private sector and urban residence. Clinic results similar to hepatitis A, with elevated transaminases over 1500 (mU/ml) and glutamic pyruvic with maximum values of 5270 (mU/ml). All patients presented hyperbilirubinemia (direct predominance) and increased gamma glutamyl transferase and alkaline phosphatase. Circulation of HEV with clinical manifestations was demonstrated in Uruguay, this showsthe presence of an emergent disease. We suggest introducing a formalized HEV diagnosis in patients without etiologic diagnosis of hepatitis.

Development of human antibodies against linear antigenic and immunogenic regions of respiratory syncytial virus (RSV) nucleocapsid and phospho-proteins shows the site-directed characteristics.

BACKGROUND: The successful development of an RSV vaccine requires a better understanding of the pathogenesis of primary infection, susceptibility to reinfection, and the immunopathology of enhanced illness in children immunized with a non-replicating RSV candidate vaccine. The exact role of different immune parameters in RSV pathogenesis remains controversial. OBJECTIVES: To study the contribution of antibodies directed to the linear antigenic and immunogenic regions of the N and P proteins in the titer rise and avidity maturation of total anti-RSV antibodies. STUDY DESIGN: The occurrence of antibodies directed against three linear antigenic and immunogenic regions in each of the nucleocapsid (N): N3 (Thr11 to Gly30), N25 (Ser231 to Ala250) and N39 (Thr371 to Leu391), and the phospho-(P) proteins of respiratory syncytial virus (RSV), subgroup A: P49 (Pro91 to Asp110), P56 (Ser161 to Lys180) and P62 (Glu221 to Phe241), were analyzed in ELISA with (a) 32 paired sera from humans with recent or previous RSV subgroup A and/or B infection diagnosed by conventional ELISA, detection of antigen in nasopharyngeal aspirates and measurement of antibody avidity change; and (b) 40 RSV antibody-positive sera (HCS) obtained from patients during their convalescence from RSV infection and possessing clearly demonstrable titers of RSV IgG in conventional enzyme immunoassays (EIA) based on whole RSV antigen. RESULTS: The titer rise of antibodies directed to the combined three peptides representing the RSV N protein was well correlated with the rise in anti-RSV antibodies measured in whole antigen ELISA. Surprisingly, the rise in antibodies against a truncated main C-terminal epitope (Gln381 to Leu391) of the N protein (represented by subgroup A specific sequence of the N39/1 peptide) was inversely correlated with the titer rise of total anti-RSV antibodies. The titer rise of antibodies to the C-terminal linear site of the RSV N (N39/1) protein was subgroup-specific during the course of primary RSV infection. A titer rise in antibodies to the C-terminal linear sites of RSV N (i.e. N39/1) and P (P62) proteins had a dominating appearance in sera from newborn infants (6-7 months) and from patients with RSV reinfections. Anti-RSV antibody titers of late convalescent sera correlated with the titers of antibodies directed to the C-terminal linear site of RSV P (P62) protein. The avidity maturation of the anti-RSV immune response followed the titer rise of anti-P62 antibodies during the course of primary or secondary RSV infection.

Etiology and severity of community acquired pneumonia in children from Uruguay: a 4-year study.

The 4-year study (1987-1990) covered the major clinical-epidemiological characteristics of pneumonia in children as diagnosed at the emergency service of the Children's Hospital, as well as etiologies, and factors involved in the most severe cases. Etiology was determined in 47.7% of the 541 pneumonia cases, involving 283 pathogens of which 38.6% were viruses and 12.6% bacteria. Viral and mixed etiologies were more frequent in children under 12 months of age. Bacteria predominated in ages between 6 and 23 months. Among the viruses, respiratory syncytial virus predominated (66%). The bacterial pneumonias accounted for 12.2% of the recognized etiologies. The most important bacterial agents were S. pneumoniae (64%) and H. influenzae (19%). H. influenzae and mixed infections had a relevant participation during the 1988 season, pointing to annual variations in the relative participation of pathogens and its possible implication in severity of diseases. Correlation of severity and increased percentage of etiological diagnosis was assessed: patients with respiratory rates over 70 rpm, or pleural effusion and/or extensive pulmonary parenchyma compromise yielded higher positive laboratory results. Various individual and family risk factors were recognized when comparing pneumonia children with healthy controls.

Acute respiratory infections in children from a deprived urban population from Uruguay.

To obtain base line data on incidence, duration, clinical characteristics and etiology of acute respiratory infections (ARI), 276 children from deprived families living in Montevideo were followed during 32 months. The target population was divided into two groups for the analysis of the results: children aged less than 12 months and those older than this age. During the follow-up period 1.056 ARI episodes were recorded. ARI incidence was 5.2 per child/year. It was 87% higher in infants than in the older group, as was the duration of the episodes. Most of the diseases were mild. Tachypnea and retractions were seldom observed, but 12 children were referred to the hospital, and 2 infants died. Viral etiology was identified in 15.3% of the episodes. RSV was the predominant agent producing annual outbreaks. Moderate to heavy colonization of the upper respiratory tract by Streptococcus pneumoniae (32.3%) and Hemophilus sp. (18.9%) was recorded during ARI episodes. This community-based study furnish original data on ARI in Uruguay. It enabled to assess the impact of these infections on childhood.

Evaluation of immunoglobulin E-specific antibodies and viral antigens in nasopharyngeal secretions of children with respiratory syncytial virus infections.

Enzyme immunoassays were developed to detect the presence of specific immunoglobulin E (IgE) antibodies and respiratory syncytial (RS) virus structural proteins in nasopharyngeal secretions in order to improve the knowledge on some aspects of the pathogenesis of severe acute lower respiratory tract infections caused by RS virus. These assays were used to analyze clinical specimens from children with RS virus-associated infections (bronchiolitis and pneumonia), and the findings were correlated with the patients' clinical symptoms. The results indicate the presence of specific IgE against the two external glycoproteins (G and F) and the absence of detectable IgE levels for the internal viral antigens. There was a correlation between the levels of IgE-specific antibodies and the amount of viral protein F in the secretions, indicating that the IgE response against the viral glycoproteins might be related to the antigen load. In addition, a correlation was found between higher levels of both viral protein F-specific IgE and F antigen with higher respiratory rates in children with pneumonia. These findings may be relevant because they suggest an association between the virus load and the immune response in the pathogenesis of RS virus infections.

Microbial agents associated with pneumonia in children from Uruguay.

The etiology of severe pneumonia, not frequently encountered in a community-based study, was determined in 204 hospitalized children less than 5 years of age. Potential pathogens were identified in 41% of episodes. Viruses were isolated or antigen was detected in 36.3% of cases; 82.4% of these cases were due to respiratory syncytial virus. Bacteria or bacterial antigens were identified in 13.2% of cases; Streptococcus pneumoniae and Haemophilus influenzae were the most frequently identified bacterial pathogens isolated from blood and/or pleural effusions. Mixed infections were identified in 4.9% of the episodes. Among the 17 patients with pleural effusion whose pleural space was drained, the etiology was suggested for 10 (58.8%). A clear-cut seasonal variation was seen, with the highest prevalence between May and October. Viral infections were more common in the first 6 months of life, although viral and bacterial infections were distributed throughout the first 5 years of life.

Identification of viruses in a study of acute respiratory tract infection in children from Uruguay.

For the purpose of identifying viral agents associated with acute respiratory tract infections (ARI) in children less than 5 years old, a longitudinal community study was undertaken in Montevideo, Uruguay, from May 1985 to December 1987. This report includes results obtained by cell culture and immunofluorescence techniques for detection of respiratory syncytial virus (RSV), influenza A and B viruses, parainfluenza 1 and 3 viruses, and adenovirus. Two populations were studied: children visited at home by pediatricians (group 1) and children with an ARI episode who attended an outpatient clinic (group 2). Nasopharyngeal aspirates were obtained at the time of an ARI episode: 858 from group 1 and 488 from group 2. Viruses were identified in 15.3% of group 1 specimens and in 17.6% of group 2 specimens. RSV was the most frequently recovered agent, accounting for 67.9% and 58.1%, respectively, of all viruses detected. The sensitivity and specificity of RSV isolation by cell culture are compared with detection by indirect immunofluorescence.

Antigenic characterization of respiratory syncytial virus associated with acute respiratory infections in Uruguayan children from 1985 to 1987.

The occurrence of subgroup A and B strains of respiratory syncytial virus (RSV) was studied during three epidemic years, 1985 to 1987, in Uruguay. A set of monoclonal antibodies was selected according to their reactivity with local RSV isolates and used for the typing of RSV directly in nasopharyngeal cells by indirect immunofluorescence. Of 77 specimens, 69 could be typed as belonging to subgroup A or B, 5 could not be typed with the restricted set of monoclonal antibodies employed, and 3 reacted with both subgroup-specific antibodies. In 1985 and 1986 subgroup A predominated, accounting for 65.7% of all typed specimens, but in 1987 subgroup B surpassed subgroup A, accounting for 82.4% of the samples.

Comparación entre la inmunoflurescencia y el ensayo inmunoenzimático para el diagnóstico rápido del virus respiratorio sincicial en secreciones nasofaríngeas / Rapid detection of respiratory syncytial virus antigens in nasopharyngeal secretions: comparison of immunofluorescence and enzyme immunoassay

Un ensayo inmunoenzimático comercial Abboutt-RSV-EIA fue evaluado comprarándolo con la inmunofluorescencia indirecta. Aspirados nasofaríngeos de 95 niños con infección respiratoria aguda baja fueron procesados por inmunofluorescencia y por enzimoinmunoensayo para revelar la presencia de antígenos del virus respiratorio sincicial. De los 60 materiales positivos por inmunofluorescencia, 46 también lo fueron por enzimoinmunoensayo (sensibilidad 78,7%); de 35 negativos, 34 fueron también negativos por el Abbout-RSV-EIA (especificidad 97,1%). Según los resultados presentados, la evaluada es aceptable como una alternativa para el diagnóstico rápido de VRS en lugares donde no se cuente con otros recursos (AU)

Comparación entre la inmunoflurescencia y el ensayo inmunoenzimático para el diagnóstico rápido del virus respiratorio sincicial en secreciones nasofaríngeas / Rapid detection of respiratory syncytial virus antigens in nasopharyngeal secretions: comparison of immunofluorescence and enzyme immunoassay

Un ensayo inmunoenzimático comercial Abboutt-RSV-EIA fue evaluado comprarándolo con la inmunofluorescencia indirecta. Aspirados nasofaríngeos de 95 niños con infección respiratoria aguda baja fueron procesados por inmunofluorescencia y por enzimoinmunoensayo para revelar la presencia de antígenos del virus respiratorio sincicial. De los 60 materiales positivos por inmunofluorescencia, 46 también lo fueron por enzimoinmunoensayo (sensibilidad 78,7%); de 35 negativos, 34 fueron también negativos por el Abbout-RSV-EIA (especificidad 97,1%). Según los resultados presentados, la evaluada es aceptable como una alternativa para el diagnóstico rápido de VRS en lugares donde no se cuente con otros recursos

[Comparison between immunofluorescence and immunoenzymatic assay for the rapid diagnosis of the respiratory syncytial virus in nasopharyngeal secretions]. / Comparación entre la inmunofluorescencia y el ensayo inmunoenzimático para el diagnóstico rápido del virus respiratorio sincicial en secreciones nasofaríngeas.

An enzyme immunoassay, RSV-EIA Abbot, was evaluated by comparison with indirect immunofluorescence. Nasopharyngeal secretions obtained from 95 infants and young children with acute respiratory infections were examined for the presence of respiratory syncytial virus antigens with both methods. Specimens were stored at -70 degrees C before being tested by EIA. Out of 60 samples positive by indirect immunofluorescence, 46 were also positive by RSV-EIA (sensitivity 78.7%) and 34 out of 35 immunofluorescence negative specimens were negative by RSV-EIA (specificity 97.1%). Therefore, the EIA appears to be an acceptable test for the rapid detection of RSV as an alternative for indirect immunofluorescence.

[Antigenic variants of the respiratory syncytial virus in Argentina and Uruguay]. / Variantes antigénicas del virus respiratorio sincicial en Argentina y Uruguay.

The characterization of RSV antigenic variants was carried out on 160 nasopharyngeal aspirates from children under 5 years of age, from Argentina and Uruguay, with acute respiratory infection and a previously positive etiological diagnosis for RSV. Results for Argentina were: 20.9% of samples belonged to subtype A, 76.9% to subtype B and the remaining 2.2% to new subtypes as yet uncharacterized. Results for Uruguay were: 5.6% of samples belonged to subtype A, 81% to subtype B and 13.5% to other subtypes. Subtype B was predominant in both countries. The correlation of RSV antigenic variants with the clinical picture and epidemiological profile is currently underway.

Variantes antigénicas del virus respiratorio sincicial en Argentina y Uruguay. / [Antigenic variants of the respiratory syncytial virus in Argentina and Uruguay]

The characterization of RSV antigenic variants was carried out on 160 nasopharyngeal aspirates from children under 5 years of age, from Argentina and Uruguay, with acute respiratory infection and a previously positive etiological diagnosis for RSV. Results for Argentina were: 20.9

of samples belonged to subtype A, 76.9

to subtype B and the remaining 2.2

to new subtypes as yet uncharacterized. Results for Uruguay were: 5.6

of samples belonged to subtype A, 81

to subtype B and 13.5

to other subtypes. Subtype B was predominant in both countries. The correlation of RSV antigenic variants with the clinical picture and epidemiological profile is currently underway.

Comparación entre la inmunofluorescencia y el ensayo inmunoenzimático para el diagnóstico rápido del virus respiratorio sincicial en secreciones nasofaríngeas. / [Comparison between immunofluorescence and immunoenzymatic assay for the rapid diagnosis of the respiratory syncytial virus in nasopharyngeal secretions]

An enzyme immunoassay, RSV-EIA Abbot, was evaluated by comparison with indirect immunofluorescence. Nasopharyngeal secretions obtained from 95 infants and young children with acute respiratory infections were examined for the presence of respiratory syncytial virus antigens with both methods. Specimens were stored at -70 degrees C before being tested by EIA. Out of 60 samples positive by indirect immunofluorescence, 46 were also positive by RSV-EIA (sensitivity 78.7

) and 34 out of 35 immunofluorescence negative specimens were negative by RSV-EIA (specificity 97.1

). Therefore, the EIA appears to be an acceptable test for the rapid detection of RSV as an alternative for indirect immunofluorescence.