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

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.

Introduction. The decline in vaccination coverage has been very significant in the past decade. Pediatriciansplay 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%; catchup 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 perceivedthemselves as more trained. Multiple barriers associated with access to vaccination were identified.

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.

Genetic diversity of rotavirus A in Argentina during 2019-2022: detection of G6 strains and insights regarding its dissemination.

One of the challenges associated with introducing a vaccine is monitoring its impact through clinical and molecular surveillance. The aims of this study were to analyze the genetic diversity of rotavirus A in Argentina between 2019 and 2022 and to assess the phylogenetic and phylodynamic features of the unusual G6 strains detected. A significant decline in the Wa-like genogroup strains was observed, and G6 strains were detected for the first time in Argentina, in association with P[8] and P[9]. Spatiotemporal analysis showed that the G6-lineage I strains detected recently in Argentina and Brazil might have emerged from European strains. This study provides recent evidence of the genetic diversity of rotaviruses in isolated cases. It is considered important to support continuous surveillance of rotavirus in the post-vaccine scenario, mainly to evaluate potential changes that may occur after the COVID-19 pandemic.

Role of Noroviruses in Sporadic Acute Gastroenteritis Cases from Children Attending a Large Referral Children's Hospital in Buenos Aires City, Argentina.

BACKGROUND: Noroviruses (NVs) are recognized as the leading cause of sporadic and epidemic acute gastroenteritis worldwide, in all age groups. Although there is increasing knowledge that NVs are responsible for many acute gastroenteritis outbreaks in Argentina, studies to estimate prevalence in sporadic cases are scarce. METHODS: A descriptive, observational and cross-sectional study was conducted with children under 5 years with acute gastroenteritis attending the outpatient department at the "Ricardo Gutiérrez" Children's Hospital (RGCH) in Buenos Aires City between June 2017 and June 2021. Sociodemographic, clinical and epidemiologic data were recorded. Stool samples were tested and genotyped for norovirus. Association between norovirus detection and demographic and clinical variables was assessed. RESULTS: A total of 350 children with acute diarrhea were included, of which stool samples were collected for 332 (94.9%). Norovirus was detected in 81 cases (24.4%). Vomiting and moderate/severe diarrhea were more frequent in norovirus-positive than norovirus-negative children. However, the presence of watery diarrhea and a history of rotavirus vaccination were significantly associated with norovirus etiology. GII and GII.4 were the most frequently detected genogroup and genotype, respectively. CONCLUSIONS: NVs were detected with high frequency, mostly in children between 6 months and 2 years old, reinforcing the hypothesis of a newly updated scenario of norovirus predominance over rotavirus. Watery diarrhea, complete vaccination against rotavirus and vomiting are 3 key parameters that should raise suspicion of possible norovirus gastroenteritis. Continuous and active norovirus surveillance in this age group is important because children represent a priority group for norovirus vaccine design and development.

Rotavirus Vaccine Impact since Its Introduction in the National Immunization Program of Argentina.

INTRODUCTION: Rotavirus (RV) is the most common cause of childhood diarrhea. Argentina introduced RV vaccination in the National Immunization Program in January 2015. This study evaluates the impact of RV vaccine implementation on the burden of acute diarrheal disease (ADD) and RV positive cases, and hospitalizations among children in Argentina. METHODS: A counterfactual time-series analysis was performed. Data on ADD (2013-2018) and RV diarrhea (2012-2018) cases in children aged < 5 years were collected from the National Healthcare Surveillance System (clinical and laboratory data). Data on hospital discharges following ADD and RV diarrhea (2011-2017) were retrieved from the Health Statistics and Information Office. All data were classified by the age groups < 1 year, < 2 years, 2-5 years. Vaccine impact was defined as the difference between the predicted time trend (simulated using 2012-2014 data) and the actual post-vaccination data (2015-2018). RESULTS: A significant reduction of 22.1% of notified ADD cases and 15.4% of hospital discharges following ADD among children < 2 years was observed in the 3 years after RV vaccine implementation. Data also showed a significant decline of 54.0% and 59.4% of notified RV cases in children < 2 and < 1 years, respectively, and a reduction of 39.3% and 40.8% in RV hospital discharges for the same age groups. CONCLUSION: This study shows a significant reduction in notified ADD cases and RV cases and hospital discharges following ADD and RV cases in children < 2 years after RV vaccine introduction in Argentina in 2015.

A New Gnotobiotic Pig Model of P[6] Human Rotavirus Infection and Disease for Preclinical Evaluation of Rotavirus Vaccines.

Human rotavirus (HRV) is a leading cause of gastroenteritis in children under 5 years of age. Licensed vaccines containing G1P[8] and G1-4P[8] strains are less efficacious against newly emerging P[6] strains, indicating an urgent need for better cross protective vaccines. Here, we report our development of a new gnotobiotic (Gn) pig model of P[6] HRV infection and disease as a tool for evaluating potential vaccine candidates. The Arg HRV (G4P[6]) strain was derived from a diarrheic human infant stool sample and determined to be free of other viruses by metagenomic sequencing. Neonatal Gn pigs were orally inoculated with the stool suspension containing 5.6 × 105 fluorescent focus units (FFU) of the virus. Small and large intestinal contents were collected at post inoculation day 2 or 3. The virus was passaged 6 times in neonatal Gn pigs to generate a large inoculum pool. Next, 33-34 day old Gn pigs were orally inoculated with 10-2, 103, 104, and 105 FFU of Arg HRV to determine the optimal challenge dose. All pigs developed clinical signs of infection, regardless of the inoculum dose. The optimal challenge dose was determined to be 105 FFU. This new Gn pig model is ready to be used to assess the protective efficacy of candidate monovalent and multivalent vaccines against P[6] HRV.

Phylogeography of Rotavirus G8P[8] Detected in Argentina: Evidence of Transpacific Dissemination.

Rotavirus is one of the leading causes of diarrhea in children. In 2018, G8P[8], an unusual association of genotypes, was detected with moderate frequency in symptomatic children in Argen-tina, unlike a previous sporadic identification in 2016. The aim of this study was to analyze the dissemination pattern of the G8P[8]-lineage IV strains detected in Argentina. Nucleotide sequences of the VP7 gene of Argentine G8P[8] strains (2016, 2018 and 2019) were studied by discrete phylodynamic analyses, together with other worldwide relevant G8-lineage IV strains. Bayes Factor (BF) was used to assess the strength of the epidemiological association between countries. Phylodynamic analyses determined an evolutionary rate of 3.7 × 10-3 (HDP95%: 1.4 × 10-3-8.2 × 10-3) substitutions/site/year. Likewise, the most recent common ancestor was 32.2 years old, dating back to 1986 (HDP95% = 1984-1988). The spatiotemporal dynamics analysis revealed South Korea as being the country of origin of the Argentine strains (posterior probability of the ancestral state: 0.8471), which was also evidenced by a significant rate of diffusion from South Korea to Argentina (BF: 55.1). The detection of G8 in South America in 2016-2017 was not related to the cases detected in 2018-2019, revealing a new G8 introduction to the region and supporting a transpacific dissemination.

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.

Emergence of unusual rotavirus G9P[4] and G8P[8] strains during post vaccination surveillance in Argentina, 2017-2018.

INTRODUCTION: In 2015, Argentina included Rotarix™ monovalent vaccine for universal administration and it showed a sharp decline in all-cause and rotavirus-confirmed cases as well as an immediate predominance of the G2P[4] genotype. The aim of this study was to analyze the impact of rotavirus vaccination on laboratory-confirmed cases and genotype distribution in Argentina following its introduction. MATERIAL AND METHODS: Prevalence and seasonality of laboratory-confirmed rotavirus cases data were assessed. Analyses of circulating genotypes were performed by conventional binary characterization (G and P typing). Phylogenetic study of VP7 gene was performed from emergent unusual strains. RESULTS: During 2017-2018, 1183 rotavirus cases (13.2%) were detected, and prevalence was uniform among different age subgroups. Weekly distribution showed a raise of confirmed cases around late July and early August. In 2017 the most frequently detected genotypes were G2P[4] and G3P[8]. However, in 2018 G12P[8] genotype increased and it was detected at a high rate. Noteworthy, the detection of uncommon G9P[4] and G8P[8] strains (bearing DS-1-like genetic backbones) was observed at moderate rates. DISCUSSION: Following four years of universal vaccination, the prevalence of rotavirus remained low in children under 5 years of age with a shift of the seasonal peak in early spring. The emergence of uncommon genotypes was due to introduction of new strains rather than to reassortment of local strains. Continuous monitoring of rotavirus burden of disease and genotype distribution provides useful evidence to evaluate existing immunization strategies and to contribute in the development of new vaccines as well.

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.

Genotype distribution of Group A rotavirus in children before and after massive vaccination in Latin America and the Caribbean: Systematic review.

BACKGROUND: During the last decade, most of Latin American and the Caribbean (LAC) countries have implemented oral live rotavirus vaccines in their national vaccination programs with remarkable results. However, it has been suggested that massive vaccination could lead to the replacement of circulating genotypes or the emergence of new variants or neutralizing antibodies escape mutants, which may reduce the effectiveness of the vaccine. The objective was to analyze the genetic diversity of Group A rotavirus before and after the introduction of universal vaccination in LAC. METHODS: We conducted a systematic review of studies published in PubMed, Scielo and LILACS. There were considered only LAC countries with rotavirus massive vaccination strategy which had described circulating genotypes data in children under 5 years of age, either for surveillance or vaccine effectiveness purposes, from 2001 to 2017. Systematic review stages were carried out following the recommendations of PRISMA. RESULTS: Of the 18 countries that included any of the two licensed rotavirus vaccines in their national schedules since 2006, only 7 (~39%) presented studies of RVA genetic diversity before and after implementation, and met the inclusion criteria. Four of them (Argentina, Brazil, Colombia and Nicaragua) experienced a rapid switch from Wa-like to DS-1-like strains. Also, G1P[8] association, considered the most predominant worldwide in the pre-vaccination era, decreased significantly and was only frequently detected in Venezuela and Nicaragua. No defined pattern of emergence at high frequencies of unusual associations was observed in the post vaccination period, except for some evidence of G9P[4] in Colombia, G3P[6] and G1P[4] in Nicaragua. CONCLUSIONS: Even though the evidence shows a DS-1-like change trend, data from studies conducted in Latin America and the Caribbean are diverse and still not sufficient to assess the impact of vaccines on viral ecology or if genetic diversity is influenced by natural mechanisms of fluctuation.

Impacto de la vacunación para Rotavirus, ¿cuál es el rol de los Calicivirus humanos? / Impact of Rotavirus vaccination: what is the role of human Caliciviruses?

Las enfermedades infecciosas constituyen la segunda causa de mortalidad en los menores de 5 años. La diarrea aguda y la neumonía son las que generan la mayor carga de enfermedad. Argentina introdujo la vacunación sistemática contra rotavirus en el año 2015. El objetivo de este trabajo es describir el cambio epidemiológico de las diarreas agudas luego de la implementación de la vacuna rotavirus en Argentina, así como la eventual aparición de otros virus como nuevos agentes causales de esta patología y los desafíos para su diagnóstico. Para lograr el objetivo se realizó una revisión bibliográfica. En Argentina dos años después del inicio de la estrategia de vacunación con coberturas entre 61-75% se evidenció un descenso de 10% de las diarreas agudas globalmente y de 50% en las diarreas causadas por rotavirus. También se observó un desplazamiento de la estacionalidad en la ocurrencia de diarreas agudas de 10 semanas respecto a la etapa pre vacunación. A nivel mundial se ha descripto posterior a la introducción de la vacunación contra rotavirus una mayor relevancia de otros agentes (calicivirus humano) como causa de diarrea aguda, con un comportamiento diferencial en cuanto a la morbimortalidad, manejo clínico y diagnóstico. Se requiere un sistema de vigilancia continua e integrada para comprender la epidemiología y la evolución de estos agentes virales para ajustar medidas de prevención y control de la enfermedad

Infectious diseases are the second cause of mortality in children under 5 years of age. Acute diarrhea and pneumonia cause the greatest burden of disease. Argentina introduced routine rotavirus vaccination in 2015. The aim was to describe epidemiological changes in acute diarrhea after the implementation of rotavirus immunization in Argentina, as well as the possible appearance of other viruses as new causative agents and the challenges for its diagnosis. To achieve the objective, a bibliographic review was carried out. Argentina achieved coverage between 61-75% two years after the introduction in the national calendar. A decrease in acute diarrhea (10%) and diarrhea caused by rotavirus (50%) was observed. There was also change in the acute diarrhea seasonality, showing a delay in the occurrence of 10 weeks compared to the pre-vaccination stage. After the introduction of rotavirus vaccination a greater relevance of other agents (human calicivirus) has been described worldwide causing acute diarrhea, with a differential behavior in terms of morbidity, mortality, clinical management and diagnosis. A continuous and integrated surveillance system is required to understand the epidemiology and evolution of these viral agents to adjust measures for the prevention and control of the disease

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.