Description of the characteristics of patients with diseases associated with immunosuppression and Cryptosporidium spp. infection seen at a referral children's hospital in Argentina, 2018-2023. / Caracterización de pacientes con enfermedades asociadas a inmunosupresión con infecciones por Cryptosporidium spp. atendidos en un hospital pediátrico referencial de Argentina, 2018-2023.

Cryptosporidium spp. is a diarrhea-causing protozoan. Immunocompromised patients may develop severe and persistent clinical forms. Here we describe the characteristics of patients with an underlying disease associated with immunosuppression (DAI) and Cryptosporidium spp. infection seen at a referral children's hospital in Argentina between 2018 and 2023. Demographic data, DAI, diarrhea characteristics, and co-infections were analyzed. A total of 30 patients with DAI and cryptosporidiosis were included. Most of them had undergone a solid organ transplant, had a hematologic neoplasm, or primary immunodeficiency. Persistent diarrhea was observed in 18 patients at the time of diagnosis. Co-infections were recorded in 6 patients. Cryptosporidiosis should be considered in the differential diagnosis of acute or persistent diarrhea in children with different types of DAI, such as solid organ transplant, hematologic neoplasms, and primary immunodeficiencies.

Cryptosporidium spp. es un protozoario productor de diarrea. Los pacientes inmunocomprometidos pueden desarrollar formas clínicas graves y persistentes. Se describen las características de pacientes con enfermedad de base asociada a inmunosupresión (EAI) con infección por Cryptosporidium spp. (IC) atendidos en un hospital pediátrico referencial de Argentina entre los años 2018 y 2023. Se analizaron datos demográficos, EAI, características de la diarrea y coinfecciones. Se incluyeron 30 pacientes con EAI e IC. La mayoría registró trasplante de órgano sólido, neoplasia hematológica e inmunodeficiencia primaria. Dieciocho presentaron diarrea persistente al momento del diagnóstico. Seis pacientes registraron coinfecciones. Se debe considerar la criptosporidiosis en el diagnóstico diferencial de enfermedad diarreica aguda o persistente en niños con distintos tipos de EAI, como el trasplante de órgano sólido, neoplasias hematológicas e inmunodeficiencias primarias.

Enteric viruses other than rotavirus and norovirus in children under 5 years of age with gastroenteritis in Argentina, 2010-2021. A descriptive study. / Virus entéricos distintos de rotavirus y norovirus en menores de 5 años con gastroenteritis en Argentina, 2010-2021. Estudio descriptivo.

Introduction. Data on the frequency of enteric adenoviruses, sapoviruses, and astroviruses in cases of sporadic acute gastroenteritis in Argentina are scarce. Methods. Descriptive design of a selection of fecal samples of children with diarrhea younger than 5 years referred between 2010 and 2021, with a previous negative result for rotavirus and norovirus. The presence of enteric adenovirus, sapovirus, and astrovirus was tested by molecular methods, with subsequent genotyping of positive samples. Results. At least 1 of the tested viruses was detected in 226 (39.4%) of the 574 selected samples. Specifically, adenovirus, sapovirus, and astrovirus were detected in 30.7%, 5.6%, and 3.1% of the samples, respectively. The most frequent viruses detected were adenovirus 41, sapoviruses GI.1 and GI.2, and astrovirus 1. Non-classic astroviruses were detected in 2 samples. Conclusions. Despite being less frequent, these enteropathogens are responsible for a large number of sporadic diarrhea events. Therefore, their study and surveillance contribute significantly to reduce the gap of undiagnosed cases.

Introducción. Los datos de frecuencia de los adenovirus entéricos, sapovirus y astrovirus en casos de gastroenteritis aguda esporádica en Argentina son escasos. Métodos. Diseño descriptivo sobre una selección de muestras de heces de menores de 5 años con diarrea remitidas durante el período 2010-2021, con resultado previo negativo para rotavirus y norovirus. Se estudió la presencia de adenovirus entéricos, sapovirus y astrovirus por métodos moleculares, con posterior genotipificación de las muestras positivas. Resultados. De 574 muestras seleccionadas, en 226 (39,4 %) se identificó al menos uno de los virus estudiados. En particular, se detectaron adenovirus, sapovirus y astrovirus en el 30,7 %, el 5,6 % y el 3,1 %, respectivamente. El adenovirus 41, los sapovirus GI.1 y GI.2, y el astrovirus 1 fueron los más frecuentemente detectados. Se identificaron dos muestras con astrovirus no clásicos. Conclusiones. A pesar de ser menos frecuentes, estos enteropatógenos son responsables de un número considerable de episodios de diarrea esporádica. Por lo tanto, su estudio y vigilancia contribuye significativamente a reducir la brecha de casos no diagnosticados.

National survey for pediatricians in Argentina: Vaccination in daily practice, perception of knowledge and barriers. / Encuesta nacional para pediatras de Argentina: vacunación en la práctica diaria, percepción de conocimientos y barreras.

Introduction. The decline in vaccination coverage has been very significant in the past decade. Pediatricians play a key role in catching-up coverage and increasing confidence in vaccination. Objectives. To describe pediatricians' perceptions of vaccine knowledge and practices and to identify barriers to access. Methods. Observational, analytical study using an online survey. Variables related to professional profile, training and barriers to vaccination were included. Results. A total of 1696 pediatricians participated (response rate: 10.7%). Their mean age was 50.4 years; 78.7% were women; 78.2% had ≥ 10 years of experience; 78.4% provided outpatient care and 56.0%, in the private subsector; and 72.5% received training in the past 2 years. Respondents described themselves as "trained" in convey the following aspects to their patients: benefits of vaccines: 97.2%; campaign objectives: 87.7%; contraindications: 82.4%; adverse effects: 78.9%; catch- up vaccination: 71.2%; reporting of events supposedly attributable to vaccination or immunization: 59.5%. The proportion was statistically higher in all aspects, among pediatricians with ≥ 10 years of experience and those who received training recently (p ≤ 0.01). The barriers identified in access to vaccination were false contraindications (62.3%), temporary vaccine shortage (46.4%), cultural reasons (41.4%), and restricted vaccination center hours (40.6%). Conclusions. The perception of the level of training varied depending on the vaccination-related aspect. Pediatricians with more years of professional experience and those who received recent updates perceived themselves as more trained. Multiple barriers associated with access to vaccination were identified.

Introducción. El descenso de las coberturas de vacunación fue muy significativo en la última década. Los pediatras son una pieza fundamental para recuperar coberturas y aumentar la confianza en la vacunación. Objetivos. Describir la percepción de los pediatras acerca del conocimiento y prácticas sobre vacunas, e identificar barreras en el acceso. Métodos. Estudio analítico observacional, mediante encuesta en línea. Se incluyeron variables del perfil del profesional, capacitación y barreras en inmunizaciones. Resultados. Participaron 1696 pediatras (tasa de respuesta: 10,7 %), media de 50,4 años. El 78,7 % fueron mujeres. El 78,2 % contaba con ≥10 años de ejercicio profesional. El 78,4 % realizaba atención ambulatoria y el 56,0 % en el subsector privado. El 72,5 % realizó una capacitación en los últimos 2 años. Se manifestaron "capacitados" para transmitir a sus pacientes los beneficios de las vacunas: 97,2 %; objetivos de campañas: 87,7 %; contraindicaciones: 82,4 %; efectos adversos: 78,9 %; recupero de esquemas: 71,2 %; notificación de ESAVI: 59,5 %. La proporción fue estadísticamente superior, en todos los aspectos, en pediatras con ≥10 años de ejercicio y en aquellos con capacitación reciente (p ≤ 0,01). Barreras identificadas en el acceso a la vacunación: falsas contraindicaciones (62,3 %); falta temporaria de vacunas (46,4 %); motivos culturales (41,4 %); horario restringido del vacunatorio (40,6 %). Conclusiones. La percepción del grado de capacitación fue variable según el aspecto de la vacunación. Aquellos con mayor tiempo de ejercicio profesional y con actualización reciente se manifestaron con mayor grado de capacidad. Se identificaron múltiples barreras frecuentes asociadas al acceso en la vacunación.

Genome-wide analyses of human noroviruses provide insights on evolutionary dynamics and evidence of coexisting viral populations evolving under recombination constraints.

Norovirus is a major cause of acute gastroenteritis worldwide. Over 30 different genotypes, mostly from genogroup I (GI) and II (GII), have been shown to infect humans. Despite three decades of genome sequencing, our understanding of the role of genomic diversification across continents and time is incomplete. To close the spatiotemporal gap of genomic information of human noroviruses, we conducted a large-scale genome-wide analyses that included the nearly full-length sequencing of 281 archival viruses circulating since the 1970s in over 10 countries from four continents, with a major emphasis on norovirus genotypes that are currently underrepresented in public genome databases. We provided new genome information for 24 distinct genotypes, including the oldest genome information from 12 norovirus genotypes. Analyses of this new genomic information, together with those publicly available, showed that (i) noroviruses evolve at similar rates across genomic regions and genotypes; (ii) emerging viruses evolved from transiently-circulating intermediate viruses; (iii) diversifying selection on the VP1 protein was recorded in genotypes with multiple variants; (iv) non-structural proteins showed a similar branching on their phylogenetic trees; and (v) contrary to the current understanding, there are restrictions on the ability to recombine different genomic regions, which results in co-circulating populations of viruses evolving independently in human communities. This study provides a comprehensive genetic analysis of diverse norovirus genotypes and the role of non-structural proteins on viral diversification, shedding new light on the mechanisms of norovirus evolution and transmission.

Norovirus passive surveillance as an alternative strategy for genetic diversity assessment in developing countries.

In developing countries, the acute gastroenteritis outbreaks submitted for viral testing are limited due to deficient surveillance programs. The aim of this study was to analyze a passive surveillance strategy for monitoring the molecular epidemiology of norovirus (NV) and counterbalance the genetic diversity data gap. Laboratory-confirmed rotavirus negative sporadic stool samples (N = 523) collected between 2010 and 2017 from children were selected from our archival collection and were tested for NV and sequencing was performed on the positive samples. Passive surveillance information was compared with the genetic diversity data that was available from local norovirus-confirmed gastroenteritis outbreaks. Each year, norovirus detection in the sporadic samples ranged from 12 to 29%. GI and GII norovirus were detected in 7 (1.3%) and 101 (19.3%) of the specimens, respectively. Four GI and six GII capsid genotypes were identified. Six out of 9 strains detected in the NV outbreaks panel were also identified in the set of sporadic samples either coincidently in the same year, the previous or the later year. Also, this set of samples depicted even better the circulating epidemic strain. Thus, implementing norovirus testing and genotyping in stool samples collected with other purposes represent a suitable strategy for providing genetic diversity information.

Persistent infection with a rotavirus vaccine strain in a child suffering from Severe Combined Immunodeficiency in Argentina.

Due to the high burden of disease associated with rotavirus, the massive vaccination in children before six months of age has been encouraged. Currently licensed oral live vaccines have shown low risk of associated adverse events in the general population. Noteworthy, postmarketing reports of severe gastroenteritis with persistent vaccine viral shedding in children with severe combined immunodeficiency (SCID) have led companies to include this inborn error of immunity as an additional contraindication. SCID is not usually screened in newborns from developing countries. Therefore, the administration of live attenuated vaccines represents the first contact of these patients with life-threatening pathogens. We describe a clinical case of an infant with SCID who suffered from persistent rotavirus symptomatic diarrhea after receiving the rotavirus oral vaccine and was found to be infected with the vaccine strain. This case attempts to contribute to the discussion of those diseases that need to be incorporated into a screening program since an early diagnosis permits clinicians to withhold live attenuated immunization.

Molecular epidemiology of norovirus outbreaks in Argentina, 2013-2018.

Noroviruses are a leading cause of endemic and epidemic acute gastroenteritis in all age groups. However, in Latin America, there are limited and updated data regarding circulating genotypes. The aim of this study was to assess the prevalence and genetic diversity of norovirus outbreaks in Argentina from 2013 to 2018. Stool samples from 29 acute gastroenteritis (AGE) outbreaks were available for viral testing. Norovirus was detected in samples from 18 (62.1%) outbreaks (2 GI and 16 GII). Both GI outbreaks were typed as GI.6[P11] whereas 10 different GII genotypes were detected, in which GII.4 viruses were the most frequently detected (29.4%, associated with GII.P31 and GII.P16) followed by GII.1[P33] and GII.6[P7] (17.6% each). Like GII.4 viruses, GII.2 viruses were also detected in association with different polymerases (GII.P2 and GII.P16). Our findings underscore the importance of dual RNA-dependent RNA polymerase-VP1 typing since recombinant strains with new polymerase sequences emerge frequently suggesting a possible role in improved fitness of these viruses. This study represents the most recent multi-year assessment of the molecular epidemiology of norovirus strains associated with AGE outbreaks in Argentina. Molecular surveillance of norovirus has to be considered to monitor possible changes in dominant genotypes which may assist to inform the formulation of future vaccines.

Recombinant Nontypeable Genotype II Human Noroviruses in the Americas.

We report multiple nontypeable genotype II noroviruses circulating in South America; nucleotides differed by >25% from those of other genotypes. These viruses have been circulating in the Americas for ≈20 years and show recombination with other genotypes. Clues to norovirus natural history can guide development of treatment and prevention plans.

Tendencia de los egresos hospitalarios por enfermedades infecciosas intestinales en niños en Argentina, 2005-2013 / Trends in hospital discharges for intestinal infectious disease in infants in Argentina, 2005-2013

Introducción. La diarrea aguda es uno de los problemas de salud pública más serios en los países en desarrollo por asociarse, generalmente, a condiciones de vida desfavorables. El objetivo de este trabajo es analizar la tendencia de los egresos hospitalarios por enfermedades infecciosas intestinales de los menores de 5 años en establecimientos oficiales del subsector público de Argentina en el período 2005-2013. Población y métodos. Se realizó un estudio ecológico de series temporales con datos provenientes de la Dirección de Estadísticas e Información en Salud, a nivel nacional y regional. Se calcularon las tasas de egresos específicas y se analizó el comportamiento estacional y la tendencia del evento. Resultados. En Argentina, se registraron 2 521 729 egresos en menores de 5 años, de los cuales el 9,0% presentó diagnóstico de enfermedad infecciosa intestinal. Los menores de 1 año representaron la tercera parte de las internaciones y el análisis de estacionalidad reveló dos picos anuales (verano e invierno). Globalmente, se observó una tendencia de tipo decreciente, con un leve aumento en el período 2007-2009. Las regiones del Noroeste y Noreste Argentino presentaron tasas de hasta 3-4 veces mayores que la región Pampeana. Conclusiones. Los egresos hospitalarios por enfermedades infecciosas intestinales en el subsector público representan alrededor del 10% del total de los egresos en los menores de 5 años. Este evento presenta un patrón estacional, con una tendencia levemente decreciente en los últimos años, a pesar de no distribuirse en forma homogénea en las diversas regiones.

Introduction. Acute diarrhea is one of the most serious public health problems in developing countries because it is generally associated with unfavorable living conditions. The objective of this study was to analyze trends in hospital discharges for intestinal infectious disease in children under age 5 recorded in official public hospitals from Argentina in the 2005-2013period. Population and methods. This was an ecological, time-series study based on data provided by the Health Statistics and Information Department, at a national and regional level. Specific hospital discharge rates were estimated, and seasonal behavior and trends were analyzed in relation to this event. Results. In Argentina, 2 521 729patients under age 5 were discharged in this period; of these, 9.0% were diagnosed with intestinal infectious disease. Children under age 1 accounted for a third of hospitalizations; two annual peaks (summer and winter) were observed in the seasonality analysis. Overall, a downward trend was observed, with a mild increase in the 2007-2009 period. Rates were up to 3 or 4 times higher in Northwest and Northeast Argentina than in the Pampa region. Conclusions. Hospital discharges for intestinal infectious disease in the public subsector account for approximately 10% of all discharges of children under age 5. This event shows a seasonal pattern, with a slightly downward trend over the past years in spite of its heterogeneous distribution across the different Argentine regions.

[Trends in hospital discharges for intestinal infectious disease in infants in Argentina, 2005-2013.] / Tendencia de los egresos hospitalarios por enfermedades infecciosas intestinales en niños en Argentina, 2005-2013.

INTRODUCTION: Acute diarrhea is one of the most serious public health problems in developing countries because it is generally associated with unfavorable living conditions. The objective of this study was to analyze trends in hospital discharges for intestinal infectious disease in children under age 5 recorded in official public hospitals from Argentina in the 2005-2013 period. POPULATION AND METHODS: This was an ecological, time-series study based on data provided by the Health Statistics and Information Department, at a national and regional level. Specific hospital discharge rates were estimated, and seasonal behavior and trends were analyzed in relation to this event. RESULTS: In Argentina, 2 521 729 patients under age 5 were discharged in this period; of these, 9.0% were diagnosed with intestinal infectious disease. Children under age 1 accounted for a third of hospitalizations; two annual peaks (summer and winter) were observed in the seasonality analysis. Overall, a downward trend was observed, with a mild increase in the 2007-2009 period. Rates were up to 3 or 4 times higher in Northwest and Northeast Argentina than in the Pampa region. CONCLUSION: Hospital discharges for intestinal infectious disease in the public subsector account for approximately 10% of all discharges of children under age 5. This event shows a seasonal pattern, with a slightly downward trend over the past years in spite of its heterogeneous distribution across the different Argentine regions.

INTRODUCCIÓN: La diarrea aguda es uno de los problemas de salud pública más serios en los países en desarrollo por asociarse, generalmente, a condiciones de vida desfavorables. El objetivo de este trabajo es analizar la tendencia de los egresos hospitalarios por enfermedades infecciosas intestinales de los menores de 5 años en establecimientos oficiales del subsector público de Argentina en el período 2005-2013. POBLACIÓN Y MÉTODOS: Se realizó un estudio ecológico de series temporales con datos provenientes de la Dirección de Estadísticas e Información en Salud, a nivel nacional y regional. Se calcularon las tasas de egresos específicas y se analizó el comportamiento estacional y la tendencia del evento. RESULTADOS: En Argentina, se registraron 2 521 729 egresos en menores de 5 años, de los cuales el 9,0% presentó diagnóstico de enfermedad infecciosa intestinal. Los menores de 1 año representaron la tercera parte de las internaciones y el análisis de estacionalidad reveló dos picos anuales (verano e invierno). Globalmente, se observó una tendencia de tipo decreciente, con un leve aumento en el período 2007-2009. Las regiones del Noroeste y Noreste Argentino presentaron tasas de hasta 3-4 veces mayores que la región Pampeana. CONCLUSIONES: Los egresos hospitalarios por enfermedades infecciosas intestinales en el subsector público representan alrededor del 10% del total de los egresos en los menores de 5 años. Este evento presenta un patrón estacional, con una tendencia levemente decreciente en los últimos años, a pesar de no distribuirse en forma homogénea en las diversas regiones.

Detection of novel GII.17 norovirus in Argentina, 2015.

During the winter of 2014-2015 a novel GII.17 norovirus strain emerged as a cause of large gastroenteritis outbreaks in Asia; displacing the long-term predominant strain, GII.4. Although sporadically detected, the emerging GII.17 virus was described in North America and Europe. In this study, we describe the presence of this novel strain in Argentina (South America), and provide new information on the genetic diversity of GII.17 noroviruses. Ten stool samples from individuals (1-88years old; median: 5years old) experiencing gastroenteritis symptoms from San Martín de los Andes, Argentina were tested for Norovirus using RT-PCR. Subsequently, Norovirus positive samples were analyzed by sequencing. Norovirus was found in four out of 10 samples received. Partial sequencing of the ORF2 was available for 3/4 samples: two samples belonged to genotype GII.4 and one to genotype GII.17 (Arg13099). Sequence analyses of the VP1 encoding region revealed that the GII.17 Argentinean strain presented characteristics from both, the new (cluster C), and older (cluster A and B) GII.17 strains. Phylogenetic and sequence analyses of the RdRp region showed that this strain was closely related to strains from genotypes GII.P3, GII.P13 and GII.P17; however, did not cluster within any of them. This study represents the first report of this emergent strain in South America, and presents further evidence of the genetic plasticity of the GII.17.

Increased frequency of rotavirus G3P[8] and G12P[8] in Argentina during 2008-2009: whole-genome characterization of emerging G12P[8] strains.

BACKGROUND: Group A rotaviruses are the leading cause of non-bacterial severe diarrhea disease in infants and young children. In humans, the most common genotypes are G1-G4 and G9. Recently, G12 strains have been sporadically reported in several countries, including Argentina, Brazil and Paraguay. OBJECTIVES: To analyze rotavirus strain diversity in Argentina during 2008-2009 and to describe the whole genome-based classification of emerging G12P[8] strains detected in our country. STUDY DESIGN: Rotavirus positive-samples (n=544) were collected from Argentinean children during 2008-2009, as a part of the National Surveillance Network for Viral Diarrheas. Specimens were genotyped by reverse transcription-polymerase chain reaction (RT-PCR) followed by nested-multiplex PCR. Sequencing of 11 genome segments was performed in 3 randomly selected G12P[8] strains. RESULTS: G9P[8] was the most frequent strain in 2008, but in 2009 G3P[8] and G12P[8] were the most frequent strains in different geographical regions of the country. The novel emerging G12P[8] strains presented the following combination of genes: G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 (i.e. genotype1, Wa-like strains). The phylogenetic analysis of the VP7 gene of the G12P[8] strains grouped them within lineage III. Previously reported Argentinean G12P[9] strains presented genes from genotype 3 (AU-1-like strains) with a VP7 gene from lineage II. CONCLUSIONS: The emergence of G12P[8] rotaviruses was due to the introduction of a new strain, rather than to a reassortment of the G12P[9] strains previously circulating in our country. This study assesses the temporal and geographical changes in genotypes prevalence as well as the periodic emergence of unusual G genotypes.