[Genetic diversity of rotavirus group a: correlation between G3 type and severity of the infection. Valencia, Venezuela]. / Diversidad genotípica de rotavirus grupo a: correlación entre el tipo G3 y severidad de la infección. Valencia, Venezuela.

Genetic and antigenic rotavirus (RV) variabilities may have implications in the severity of the infection caused by these agents; however the studies are not conclusive. For that purpose, the mean severity scores of diarrhea episodes caused by RV types G1 and G3 were compared, at Ciudad Hospitalaria "Dr. Enrique Tejera" in Valencia, Venezuela, between 2001-2005. RV were identified by ELISA, G and P types by RT-PCR. The severity of infection was determined using the Ruuska-Vesikari system and the mean severity values were compared using the Student's t-test (two-tailed, 95% CI). RV were detected in 24.5% of patients (3193/13026), being G3 the most common (50.3%), followed by G1 (39.2%), G9 (6.2%), G2 (0.6%), G4 (0.6%) and of mixed infection 3.1% (G1 + G3). Type P[8] was present in 87.3% of samples, 10.9% P[4] and 1.8% P[6]. There were not statistically significant differences (P > or = 0.05) observed between the episodes caused by G1 and G3 when age, breast feeding, and degrees of malnutrition and dehydration were considered. Nevertheless, in the G3 positive group, fever, episodes of more than 6 days, 6 or more evacuations in 24 hours and 3 or more days with vomit, were observed. The mean severity score for the G3 episodes (11.1) was significantly higher (P < 0.05) than for G1 (7.8). These results show that G3 was associated with severe diarrhea, supporting the hypothesis that the knowledge of the variability and frequency of viral types is essential to measure the impact of an anti-rotavirus vaccine.

Molecular characterization of human adenovirus causing infantile acute gastroenteritis in Venezuela before and after rotavirus vaccine implementation.

Human adenoviruses (HAdV) of species F are commonly involved in pediatric acute gastroenteritis (AGE). The real impact on Venezuelan health is unknown. To investigate the prevalence and molecular diversity of HAdV in Venezuela, 630 fecal samples collected from children with AGE in 3 cities, from 2001 to 2013, were tested by PCR. Species F and types F40/41 were identified by REA. HAdV was detected in 123 cases (19.5%), most from outpatient females under 24 months old. A progressive and substantial increase in the detection rate was observed over time, significantly higher in rotavirus vaccinated than unvaccinated children (28.4% vs. 9.5%, P = 0.00019). Phylogenetic analysis of 28 randomly selected genomes showed high similarity among HAdV-F40/41 and those worldwide. HAdV-F of type 41 prevailed (79.8%) and clustered into 2 intratypic major clades. The significant involvement of HAdV-F41 in AGE suggests the importance of actively monitoring viral agents other than rotavirus, especially after vaccine introduction.

[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.

Severity and age of rotavirus diarrhea, but not socioeconomic conditions, are associated with rotavirus seasonality in Venezuela.

Rotavirus (RV) epidemiology presents differences between developing and developed countries among which are seasonality, age at first infection, variability of strain in circulation and severity of disease. Since, in Venezuela, we have distinct seasonal patterns of RV occurrence, we examined the epidemiological profile of RV disease associated to these differences by analyzing data from previous studies conducted in Venezuela. Data were collected from children <5 years of age with diarrhea seen in six hospitals located in five cities. Socio-demographic and clinical characteristics of RV illness were analyzed according to RV identification by ELISA assay and the seasonal patterns of RV circulation (marked versus minimal seasonality). A total of 6,742 episodes of diarrhea (1,820 rotavirus positive and 4,922 rotavirus negative) were evaluated: 1,951 in Caracas, Cumaná and Pto. Ordaz (minimal seasonality) and 4,791 in Mérida and Valencia (marked seasonality). Mean age (months) of children with RV was 8.14 +/- 6.74 and 12.21 +/- 9.62 (P < 0.0001) in areas with minimal and marked seasonality, respectively. RV disease was more frequent (33% vs. 24%; OR = 1.536; 95% CI: 1.36-1.73), more severe (dehydration: 64% vs. 29%; OR = 4.436; 95% CI: 3.61-5.44) and more common in infants than in older children (79% vs. 60%; OR = 2.521; 95% CI: 2.01-3.14) in cities with minimal seasonality than in those with marked seasonality. Socioeconomic conditions were not associated with seasonality. In environments with minimal seasonality, children are infected with RV at younger ages and the disease is more severe regardless of malnutrition and poverty.

[Epidemiological and clinical study of diarrhea by rotavirus in children <5 years of age attended in medical centers of the Miranda State, Venezuela]. / Estudio epidemiológico y clinico de las diarreas por rotavirus en niños menores de 5 años atendidos en centros asistenciales del estado Miranda-Venezuela.

To have a better knowledge of the epidemiological and clinical aspects of rotavirus (RV) infection treated at out-patient clinics, we carried out a study in five centers (one hospital type I, and four out-patient clinics) of Miranda state, between february 2006 and january 2007. We evaluated 194 children <5 years old with acute diarrhea and analyzed the following characteristics: gender, age, socioeconomic condition, breastfeeding, nutritional status, clinical characteristics, rotavirus diagnosis and typing by Enzyme Linked immuno Sorbent Asssay (EISA) and G typing by RT-PCR, respectively. The population presented the following characteristics: 53% males; mean age, 17.6 +/- 14.05 months; 68% belonged to worker and marginal class (Graffar 4 and 5); 59% were breast-fed during their first year of life; 13% were malnourished; 40% were dehydrated and 19% were infected with RV. RV infection was significantly and more frequently associated with vomiting (94%, P<0.0001) and malnourishment (30%, P=0.0010) than the episodes negative for rotavirus. In dehydrated cases, significantly greater malnourishment (21%, P=0.0232) and RV (28%, P=0.0407). We found significant differences between the hospital and out-patient clinics, in terms of Graffar 4 and 5 (90% vs .53%, P<0.0001), malnourished (23% vs. 6%, P=0.006), dehydration (63% vs 24%, P<0.0001) and RV (27% vs. 13%, P=0.027). Fourteen samples RV positive were genotyped and the G types were 29% G1, 21% G3 and 14% G4 types. This study suggests that RV cause severe diarrhea associated to malnutrition and poverty and significantly affect the population older than one year of age in the region studied.

Molecular detection of human enteric viruses circulating among children with acute gastroenteritis in Valencia, Venezuela, before rotavirus vaccine implementation.

BACKGROUND: The role of rotavirus as main etiologic agent of diarrhea has been well documented worldwide, including in Venezuela. However, information about the prevalence of gastrointestinal viruses such as calicivirus, adenovirus and astrovirus is limited and the contribution of other agents as Aichi virus and klassevirus is largely unknown. To explore the etiological spectrum of diarrhea associated with agents other than rotaviruses, 227 stool samples from children under 5 years old with acute gastroenteritis, collected in Valencia (Venezuela) from 2001 to 2005, and previously tested as rotavirus-negative, were analyzed for caliciviruses, adenoviruses, astroviruses, Aichi viruses, klasseviruses, picobirnaviruses and enteroviruses by specific RT-PCRs. RESULTS: At least one viral agent was detected in 134 (59%) of the samples analyzed, mainly from children under 24 months of age and most of them belonging to the lowest socioeconomic status. Overall, enterovirus was identified as the most common viral agent (37.9%), followed by calicivirus (23.3%), adenovirus (11.5%), astrovirus (3.5%), klassevirus (1.3%) and Aichi virus (0.4%), while no picobirnavirus was detected. Klasseviruses were found during 2004 and 2005 and Aichi viruses only in 2005, indicating their circulation in Venezuela; meanwhile, the rest of the viruses were detected during the whole study period. Coinfections with two or more viruses were found in 39 (29.1%) of the infected children, most under 24 months of age. Adenovirus was involved as the coinfecting agent in at least 46.9% of the cases, but no differences concerning socio-demographic variables were observed between the coinfected and the single infected children. CONCLUSIONS: The results show that various enteric viruses, including enteroviruses, caliciviruses and adenoviruses, accounted for a significant proportion of infantile diarrhea cases in Venezuela before rotavirus vaccine implementation. In addition, emerging viruses as Aichi virus and klassevirus were found, indicating the need to continue monitoring their spreading into the communities. Efforts are needed to develop more accurate methods to identify the major causes of diarrhea and to provide tools for more effective preventive measures.

Rotavirus mortality confirmed by etiologic identification in Venezuelan children with diarrhea.

BACKGROUND: Hospital-based studies to determine the etiology of deaths from diarrhea are scarce. In this study, we specifically analyzed deaths due to rotavirus to assess the rotavirus impact on diarrhea mortality. METHODS: To determine the rotavirus proportion contributing to mortality due to diarrhea, we analyzed data obtained from a hospital-based mortality surveillance, conducted over 7 years, in the Ciudad Hospitalaria Dr. Enrique Tejera, Valencia, Venezuela. Rotavirus was identified in stool samples collected from children who died of diarrhea, by a confirmatory ELISA and/or reverse transcription polymerase chain reaction. RESULTS: Our results show that rotavirus (21%; 21/100) is the leading cause of death due to diarrhea among children <5 years of age; rotavirus also has an important impact (2%; 21/1336) on deaths from all causes in this age group. Shigella spp. (19%; 13/69) was the second most important cause of death, followed by calicivirus (6%; 3/53). Furthermore, this study documents a seasonal pattern in the deaths due to rotavirus (odds ratio 3.28; 95% confidence interval 1.13-9.76). CONCLUSIONS: For Venezuela, it is estimated that approximately 300 children <5 years of age die of rotavirus each year, which means that 1 in 1800 children die by the age of 5. Rotavirus was found to be the main cause of death due to diarrhea, which supports previous estimations. This is the first study to present data of cause-specific mortality due to diarrhea based on hospital surveillance of diarrhea etiologies.

Epidemiologic and clinical characteristics of rotavirus disease during five years of surveillance in Venezuela.

BACKGROUND: To effectively introduce a rotavirus vaccine in developing countries, it is necessary to estimate the burden of rotavirus disease. Therefore we examined the epidemiologic and clinical features of rotavirus diarrhea in children younger than 5 years of age in Carabobo State and extrapolated these results to the rest of Venezuela. METHODS: From January 1, 1998 to December 31, 2002, we conducted surveillance for rotavirus diarrhea in all children younger than 5 years of age at the Ciudad Hospitalaria Dr Enrique Tejera, in Valencia (Carabobo). RESULTS: Rotavirus is the major cause of diarrhea in children younger than 5 years of age in Venezuela, accounting for one-fourth (23%) of all episodes of diarrhea requiring medical treatment and one-third (33%) of those requiring hospitalization. Rotavirus diarrhea was responsible for 3% of all hospitalizations and 2% of all medical visits. In Valencia, rotavirus had a marked seasonal peak during the dry and cold months of the year. Rotavirus was most frequent in children 3-23 months of age, and 61% of the cases occurred by the age of 1 year. In addition, rotavirus diarrhea was more severe in younger children. Overall, by the age of 5 years, 1 child in 72 will be hospitalized and 1 in 24 will visit the clinic for rotavirus disease. In Venezuela, we estimated that each year, 118,000 children experience rotavirus illness requiring medical care and 39,000 children require hospitalization. CONCLUSIONS: This study confirms the significant impact of rotavirus disease in Venezuela. Rotavirus vaccines currently in development could diminish the morbidity associated with this common cause of childhood diarrheal disease.

Diversidad genotípica de rotavirus grupo A: correlación entre el tipo G3 y severidad de la infección. Valencia, Venezuela / Genetic diversity of rotavirus group A: correlation between G3 type and severity of the infection. Valencia, Venezuela

La variabilidad genética y antigénica de los rotavirus (RV) parece tener implicaciones en la severidad de la infección, pero los estudios no son concluyentes. Por este motivo, en el presente trabajo se compararon las medias de severidad entre los episodios de diarrea causados por RV tipo G1 y G3, durante el período 2001-2005, en la Ciudad Hospitalaria “Dr. Enrique Tejera” de Valencia, Venezuela. RV se detectó por ELISA, los tipos G y P por RT-PCR. La severidad de la infección se estimó utilizando el sistema de Ruuska-Vesikari, las medias de severidad se compararon mediante la prueba t de Student (2 colas, 95%IC). RV se detectó en 24,5% (3.193/13.026) de los pacientes. G3 fue más frecuente (50,3%), seguido por G1 (39,2%), G9 (6,2%), G2 (0,6%), G4 (0,6%) y 3,1% mixtos (G1+G3). El 87,3% de las muestras resultaron P[8], 10,9% P[4] y 1,8% P[6]. Al comparar los episodios G1 y G3, no se observaron diferencias significativas (P>0,05) entre los grupos etarios, frecuencia de desnutridos, deshidratación y lactancia materna. Sin embargo, el grupo G3 se caracterizó por presencia significativa (P< 0,05) de fiebre, episodios con una duración ≥ 6 días, 6 o más evacuaciones en 24 horas y 3 o más días con vómitos. La media de severidad para los episodios G3 (11,1) fue mayor significativamente (P<0,05) a la G1 (7,8). Estos resultados muestran la asociación de G3 con diarreas severas y apoyan la importancia de conocer la variabilidad y frecuencia de los tipos virales para medir el impacto de las vacunas antirotavirus.

Genetic and antigenic rotavirus (RV) variabilities may have implications in the severity of the infection caused by these agents; however the studies are not conclusive. For that purpose, the mean severity scores of diarrhea episodes caused by RV types G1 and G3 were compared, at Ciudad Hospitalaria “Dr. Enrique Tejera” in Valencia, Venezuela, between 2001- 2005. RV were identified by ELISA, G and P types by RT-PCR. The severity of infection was determined using the Ruuska-Vesikari system and the mean severity values were compared using the Student’s t-test (two-tailed, 95%CI). RV were detected in 24.5% of patients (3193/13026), being G3 the most common (50.3%), followed by G1 (39.2%), G9 (6.2%), G2 (0.6%), G4 (0.6%) and of mixed infection 3.1% (G1+G3). Type P[8] was present in 87.3% of samples, 10.9% P[4] and 1.8% P[6]. There were not statistically significant differences (P≥0.05) observed between the episodes caused by G1 and G3 when age, breast feeding, and degrees of malnutrition and dehydration were considered. Nevertheless, in the G3 positive group, fever, episodes of more than 6 days, 6 or more evacuations in 24 hours and 3 or more days with vomit, were observed. The mean severity score for the G3 episodes (11.1) was significantly higher (P< 0.05) than for G1 (7.8). These results show that G3 was associated with severe diarrhea, supporting the hypothesis that the knowledge of the variability and frequency of viral types is essential to measure the impact of an anti-rotavirus vaccine.

Serum IgA levels induced by rotavirus natural infection, but not following immunization with the RRV-TV vaccine (Rotashield), correlate with protection.

To directly compare serum rotavirus specific IgA as a marker of protection in children vaccinated with the RRV-TV (Rotashield) vaccine and in naturally infected children, we studied pre-existing rotavirus IgA antibodies by ELISA assays in these groups of children within the first 5 days after the onset of a diarrhea episode, due or not to rotavirus. In immunized children, rotavirus IgA titers were similar between infected and non-RV infected children. In non-immunized children, the proportion with rotavirus IgA titers was significantly greater in non-RV infected children (58%) than in infected children (31%). Additionally, a titer >/=1:800 was associated with 68% protection. Thus, in this study serum rotavirus IgA showed a good correlation with protection in children pre-exposed to natural infection but not in those immunized with the RRV-TV vaccine.

Evaluation of serum antibody responses against the rotavirus nonstructural protein NSP4 in children after rhesus rotavirus tetravalent vaccination or natural infection.

The immune response elicited by the rotavirus nonstructural protein NSP4 and its potential role in protection against rotavirus disease are not well understood. We investigated the serological response to NSP4 and its correlation with disease protection in sera from 110 children suffering acute diarrhea, associated or not with rotavirus, and from 26 children who were recipients of the rhesus rotavirus tetravalent (RRV-TV) vaccine. We used, as antigens in an enzyme-linked immunosorbent assay (ELISA), affinity-purified recombinant NSP4 (residues 85 to 175) from strains SA11, Wa, and RRV (genotypes A, B, and C, respectively) fused to glutathione S-transferase. Seroconversion to NSP4 was observed in 54% (42/78) of the children who suffered from natural rotavirus infection and in 8% (2/26) of the RRV-TV vaccine recipients. Our findings indicate that NSP4 evokes significantly (P < 0.05) higher seroconversion rates after natural infection than after RRV-TV vaccination. The serum antibody levels to NSP4 were modest (titers of < or = 200) in most of the infected and vaccinated children. A heterotypic NSP4 response was detected in 48% of the naturally rotavirus-infected children with a detectable response to NSP4. Following natural infection or RRV-TV vaccination, NSP4 was significantly less immunogenic than the VP6 protein when these responses were independently measured by ELISA. A significant (P < 0.05) proportion of children who did not develop diarrhea associated with rotavirus had antibodies to NSP4 in acute-phase serum, suggesting that serum antibodies against NSP4 might correlate with protection from rotavirus diarrhea. In addition, previous exposures to rotavirus did not affect the NSP4 seroconversion rate.

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.

Human rotavirus specific T cells: quantification by ELISPOT and expression of homing receptors on CD4+ T cells.

Using an intracellular cytokine assay, we recently showed that the frequencies of rotavirus (RV)-specific CD4(+) and CD8(+) T cells secreting INFgamma, circulating in RV infected and healthy adults, are very low compared to the frequencies of circulating cytomegalovirus (CMV) reactive T cells in comparable individuals. In children with acute RV infection, these T cells were barely or not detectable. In the present study, an ELISPOT assay enabled detection of circulating RV-specific INFgamma-secreting cells in children with RV diarrhea but not in children with non-RV diarrhea without evidence of a previous RV infection. Using microbead-enriched CD4(+) and CD8(+) T cell subsets, IFNgamma-secreting RV-specific CD8(+) but not CD4(+) T cells were detected in recently infected children. Using the same approach, both CD4(+) and CD8(+) RV-specific T cells were detected in healthy adults. Furthermore, stimulation of purified subsets of PBMC that express lymphocyte homing receptors demonstrated that RV-specific INFgamma-secreting CD4(+) T cells from adult volunteers preferentially express the intestinal homing receptor alpha4beta7, but not the peripheral lymph node homing receptor L-selectin. In contrast, CMV-specific INFgamma-secreting CD4(+) T cells preferentially express L-selectin but not alpha4beta7. These results suggest that the expression of homing receptors on virus-specific T cells depends on the organ where these cells were originally stimulated and that their capacity to secrete INFgamma is independent of the expression of these homing receptors.

Serotipos y resistencia antimicrobiana de cepas de Shigella flexneri aisladas de niños con diarrea aguda: Relación entre el serotipo y la severidad del episodio / Serotype and antimicrobial resistance of Shigella flexneri strains isolated from children with acute diarrhea: Relationship between serotype and severity of the episode

Se determinó el serotipo, susceptibilidad a los antimicrobianos y la relación de severidad de la infección con el serotipo, a un grupo de 50 cepas de S. flexneri aisladas de niños menores de 5 años con diarrea: 25 niños deshidratados y 25 no deshidratados. Para la tipificación se utilizaron antisueros comerciales y la susceptibilidad a los antimicrobianos se realizó por el método de difusión en disco. Características epidemiológicas y clínicas de los episodios: media de edad 13,32 meses ± 12, clase obrera y marginal 94% (P< 0,05), eutróficos 80% (P<0,05), sangre macroscópica en heces 82% (P< 0,05), vómitos 60% (P> 0,05). El serotipo con mayor frecuencia fue el 2a (40%), seguido por el 3a (24%), 2b (18%), 1a (6%), 6 (4%), 3b (2%), 4a (2%), variante “X” (2%) y variante “Y” (2%). El mayor porcentaje de resistencia se observó a tetraciclina (96%), seguido por ampicilina (94%), cloranfenicol (90%), amoxicilina ácido clavulánico (84%) y trimetoprin-sulfametoxazol (72%). La desnutrición (36%, P< 0,05) y el serotipo 2a (56%, P< 0,05) se observaron con mayor frecuencia en los niños deshidratados, mientras que el serotipo 2b predominó en los no deshidratados (32%, P< 0,05). La prevalencia del serotipo 2a, su asociación con la severidad del episodio y la elevada resistencia a los antibióticos alertan sobre la problemática de la infección por Shigella en el país y refuerza la necesidad de estudios para ajustar pautas en el tratamiento.

Serotype, antimicrobial susceptibility, and severity of the infection according to serotype, were determined in a group of 50 Shigella flexneri strains isolated from children less than 5 years old with diarrhea: 25 children dehydrated and 25 non dehydrated. Commercial antisera were used for serotyping and antimicrobial susceptibility was determined by the disc diffusion method. Clinical and epidemiological characteristics of the episodes: mean age 13.22 ± 12 months; 94% belonged to laborer and marginal classes (P<0.05); 80% eutrophic (P<0.05); 82% macroscopic blood in feces (P<0.05); 60% vomits (P>0.05). The most frequent serotype was 2a (40%), followed by 3a (24%), 2b (18%), 1a (6%), 6 (4%), 3b (2%), 4a (2%), variant “X” (2%) and variant “Y” (2%). The highest resistance percent was found for tetracycline (96%), followed by ampicylline (94%), chloramphenicol (90%), amoxicylline clavulonic acid (84%) and trimetoprim-sulfametoxazol (72%). Malnourishment (32%, P<0.05) and serotype 2a (56%, P<0.05) were seen more frequently in dehydrated children, while serotype 2b predominated in non dehydrated children (32%, P<0.05). Prevalence of serotype 2a and its association with the severity of the episode and high antibiotic resistance alert regarding the problem of Shigella infections in our country and reinforce the need of further studies to adjust treatment norms.

Estudio epidemiológico y clínico de las diarreas por rotavirus en niños menores de 5 años atendidos en centros asistenciales del estado Miranda-Venezuela / Epidemiological and clinical study of diarrhea by rotavirus in children 5 years of age attended in medical centers of the Miranda State Venezuela

Con el objeto de conocer la epidemiología y clínica de la infección por rotavirus (RV) tratada de forma ambulatoria, se realizó un estudio en 5 centros (un hospital tipo I y 4 ambulatorios) del estado Miranda, entre febrero 2006 y enero 2007. Se evaluaron 194 niños menores de 5 años con diarrea aguda y se analizaron las siguientes variables: género, edad, estrato socioeconómico, alimentación, estado nutricional, clínica, diagnóstico de RV por Ensayo Inmuno Enzimático (ELISA) y su tipificación G por RT-PCR. La población presentó las siguientes características: 53 por ciento de varones, 17,6 ± 14,05 meses de edad (media), 68 por ciento de clase obrera y marginal (Graffar 4 y 5), 59 por ciento de lactancia materna en el primer año de vida, 13 por ciento de desnutrición, 40 por ciento de deshidratación y 19 por ciento de infección por RV. Los episodios RV positivos se asociaron significativamente a vómitos (94 por ciento, P < 0,0001) y a desnutrición (30 por ciento, P = 0,0010) al compararlos con los RV negativos. En los casos deshidratados fue mayor significativamente la desnutrición (21 por ciento, P = 0,00232) y la presencia de RV (28 por ciento, P = 0,0407). Encontramos entre la población del hospital y los ambulatorios diferencias respecto al graffar 4 y 5 (90 por ciento vs 53 por ciento, P < 0,0001), desnutrición (23 por ciento vs 6 por ciento, P = 0,006), deshidratación (63 por ciento vs 24 por ciento, P<0,0001) y RV (27 por ciento vs 13 por ciento, P = 0,027). Se tipificaron 14 cepas RV positivos resultando el 29 por ciento de tipo G1, 21 por ciento de G3 y 14 por ciento de G4. Este estudio sugiere que los RV, en la región estudiada, son causa de diarreas severas asociadas a desnutrición, pobreza y afectan significativamente a la población mayor de un año.

Estudio de la infección por rotavirus y calicivirus en neonatos de la Maternidad "Concepción Palacios" de Caracas / Study of rotavirus and calicivirus infections in neonates from the Maternity Hospital "Concepción Palacios", Caracas

En un estudio realizado en 1984 en la Maternidad "Concepción Palacios", Pérez-Schael y col. detectaron excreción asintomática de rotavirus en el 56% de los recién nacidos evaluados. El objetivo de este trabajo fue estudiar la infección por rotavirus en neonatos de la Maternidad y comparar datos con aquellos obtenidos anteriormente. Además, se investigó la presencia de calicivirus en dicha población. Entre agosto y diciembre de 2004, se recolectaron 307 muestras de heces provenientes de 215 neonatos sanos. Para la detección de los agentes virales se utilizaron ensayos tipo ELISA comerciales y no comerciales. Estos ensayos identificaron como positivas a rotavirus y calicivirus a un total de 14 y 58 muestras, respectivamente. Sin embargo, al realizar pruebas para corroborar la presencia de rotavirus por microscopia electrónica, EGPA y RT-PCR y para calicivirus por RT-PCR, ninguna de las muestras señaladas como positivas pudo ser confirmada. Estos resultados sugieren la no-circulación tanto de rotavirus como de calicivirus dentro de la Maternidad. Es posible que la interrupción de la transmisión de rotavirus dentro de la Institución pueda deberse a cambios en el manejo del par madre-neonato introducidos en la Maternidad desde 1995, promovidos por la OMS y UNICEF.

In a study carried out in 1984 at the "Concepción Palacios" Maternity Hospital, Perez-Schael et al (J Med Virol 1984, 14:127) detected asymptomatic excretion of rotavirus in 56% of the neonates evaluated. The purpose of this work was to study rotavirus infection in neonates at the Maternity Hospital and compare the new data with those previously obtained. We also studied calicivirus presence in said population. Between August and December 2004, 307 feces samples were collected from 215 healthy neonates. Commercial and non commercial ELISA type assays were used for detection of viral agents. These assays identified a total of 14 and 58 samples as rotavirus and calicivirus positive respectively. Nevertheless, when carrying out tests to corroborate rotavirus presence with electron microscopy, EGPA and RT-PCR, and for calicivirus with RT-PCR, none of the samples previously shown as positive could be confirmed. These results suggest the non-circulation of both rotavirus and calicivirus within the Maternity Hospital. It is possible that the interruption of rotavirus transmission within this Institution could be due to changes in the management of the mother-child unit promoted by WHO and UNICEF, and introduced at the Maternity Hospital since 1995.

Características etiológicas, clínicas y sociodemográficas de la diarrea aguda en Venezuela / Etiological, clinical, and sociodemographic characteristics of acute diarrhea in Venezuela

En cuatro ciudades de Venezuela se llevó a cabo un estudio para evaluar las características epidemiológicas, clínicas y etiológicas de la diarrea aguda en niños menores de 5 años. Entre junio de 1993 y mayo de 1995 se estudiaron 2.552 niños con diarrea y 793 controles que fueron atendidos en el hospital. Para el análisis estadístico de los resultados se empleó la prueba exacta de Fisher. Los rotavirus fueron los agentes más importantes, tanto por su frecuencia (30 por cien) como por su asociación con la deshidratación (58 por cien). Le siguieron en importancia Campylobacter spp. (13 por cien) y Escherichia coli serogrupos O clásicos (9 por cien), pero su asociación con la diarrea solo fue estadísticamente significativa en los niños menores de 3 meses, hecho de particular importancia desde el punto de vista del tratamiento. Se confirmó la importancia de la edad como factor determinante de la prevalencia y gravedad de la diarrea

In four cities of Venezuela a study was carried out to evaluate the epidemiological, clinical, and etiological characteristics of acute diarrhea in children under 5 years of age. The study was done between June 1993 and May 1995 and involved children who were seen in a hospital, 2 552 with diarrhea and 793 controls. The Fisher exact test was used for the statistical analysis of the results. Rotaviruses were the most important agents, both in terms of their frequency (30%) and their association with dehydration (58%). Following in importance were Campylobacter spp. (13%) and Escherichia coli classical O serogroups (9%), but their association with diarrhea was only statistically significant among children less than 3 months old, a fact that is particularly important from the standpoint of treatment. The importance of age was confirmed as a determining factor in the prevalence and severity of diarrhea.

Características etiológicas, clínicas y sociodemográficas de la diarrea aguda en Venezuela / Etiological, clinical, and sociodemographic characteristics of acute diarrhea in Venezuela

En cuatro ciudades de Venezuela se llevó a cabo un estudio para evaluar las características epidemiológicas, clínicas y etiológicas de la diarrea aguda en niños menores de 5 años. Entre junio de 1993 y mayo de 1995 se estudiaron 2.552 niños con diarrea y 793 controles que fueron atendidos en el hospital. Para el análisis estadístico de los resultados se empleó la prueba exacta de Fisher. Los rotavirus fueron los agentes más importantes, tanto por su frecuencia (30 por cien) como por su asociación con la deshidratación (58 por cien). Le siguieron en importancia Campylobacter spp. (13 por cien) y Escherichia coli serogrupos O clásicos (9 por cien), pero su asociación con la diarrea solo fue estadísticamente significativa en los niños menores de 3 meses, hecho de particular importancia desde el punto de vista del tratamiento. Se confirmó la importancia de la edad como factor determinante de la prevalencia y gravedad de la diarrea

Resultados de tres años de vigilancia de la resistencia a la amikacina en el Hospital Vargas / 3 years old surveillance results with amikacin at the Vargas Hospital

En el Hospital Vargas ha aumentado el uso de amikacina (An) desde 1983. Concomitantemente, se ha producido un aumento de la resistencia (R) a la misma, de 1984 a 1986, aunque permanece por debajo de la del resto de los aminoglucósidos (AG). Entre las enterobacterias el aumento fue de 5,2% a 16,3% (p<0,001) y entre los Acinectobacter calcoaceticus var. anitratus, de 40,9% a 70,0% (p<0,01). Sin embargo, con Pseudomona aeruginosa se ha observado una disminución de dicha R, de 47,3% a 28,6% (p<0,05). En las enterobacterias, la R es debida a la enzima AAC (6') I mediada por plásmidos; en Ac. calcoaceticus var. anitratus, a impermeabilidad; y en P. aeruginosa, a una combinación de ambos mecanismos. Al aumento de la R a An, puede haber contribuido, el mayor uso simultáneo de tobramicina (Tb), la falta de medidas de aislamiento para los pacientes infectados con cepas resistentes y el promedio de estadía largo. Se proponen soluciones para evitar las repercusiones negativas en términos de morbilidad y mortalidad

Resistencia a la amikacina en el Hospital Vargas: resultados preliminares / Amikacin resistance at the Hospital Vargas: preliminary results

Para 1979 el porcentage de resistencia a la amikacina en el Hospital Vargas entre los bacilos gram negativos era de 2,6%. Desde entonces el uso de amikacina se ha incrementado apreciablemente. Entre el 1 de marzo y el 4 de diciembre de 1984 se aislaron 500 cepas de enterobacterias no repetidas provenientes de pacientes hospitalizados. El porcentaje de resistencia a la amikacina fue de 5,2%, bastante más bajo que los porcentajes de resistencia a gentamicina (27,4%) y tobramicina (29,0%). La resistencia a amikacina fue transferible en el 75.0% de los casos. Todas las cepas resistentes a ese aminoglicósido y sus transcojugantes, fueron productores de la enzima AAC (6') I. Entre el 1§ de junio y el 4 de diciembre del mismo año también se aislaron 121 cepas de bacilos gram negativos no fermentadores. El 46,3%, mostró ser resistente a amikacina, el 52,1% a dibekacina, el 54,6% a tobramicina y el 62,8% a gentamicina. Concluimos que la resistencia a amikacina ha aumentado en el Hospital Vargas desde 1979, fundamentalmente a expensas de los bacilos gram negativos no fermentadores. Esto pudiera estar en relación con el aumento de su uso. Entre las enterobacterias es debida a la producción de la enzima AAC (6') I y fundamentalmente mediada por plasmidos. Sin embargo, la amikacina continúa siendo el aminoglicósido de elección para el tratamiento de las infecciones nosocomiales por bacilos gram negativos porque el porcentaje de resistencia de estos gérmenes a ese antibiótico permanece por debajo de los porcentajes de resistencia del resto de los aminoglicósidos