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.

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.

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.

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.

Rotavirus epidemiology and surveillance before vaccine introduction in Argentina, 2012-2014.

Group A Rotavirus has been widely described as one of the most important infantile diarrheal pathogens worldwide. In Argentina, it is responsible for over 200,000 acute diarrhea cases and from 30 to 50 deaths annually in children under 5 years. The aim of this study is to analyze frequency, seasonality, age group distribution, and circulating genotypes based on data notified in the 2012-2014 period and in turn to assess the pre-vaccine scenario, considering that rotavirus vaccine was introduced in 2015. Data were taken from the Viral Diarrhea Notification module of the Argentine SNVS-SIVILA surveillance tool. Analyses of circulating genotypes were performed on rotavirus-positive stool specimens by conventional binary characterization of the outermost capsid genes. Overall data showed rotavirus detection in about 25% of samples tested, and higher rates in children under 2 years old were observed. Rotavirus positive cases were distributed according to a typical winter seasonal pattern. A heterogeneous regional pattern of prevalence was also observed, with higher rates detected in the North region. Genotype co-circulation and annual fluctuation were observed. In general, G1P[8], G2P[4], G3P[8], and G12P[8] were the most frequently detected genotypes. This study represents the last survey taken of a population considered to be naïve. J. Med. Virol. 89:423-428, 2017. © 2016 Wiley Periodicals, Inc.

Serological evidence of Rickettsia and Coxiella burnetii in humans of Buenos Aires, Argentina.

In Buenos Aires city (Argentina), the circulation of these agents has been detected mainly in vectors and animals, few human cases having been described. The aim of our study was to determine the seroprevalence of Rickettsia (spotted fever--SFG--and typhus--TG--groups) and Coxiella burnetii (Q fever agent) in residents of Buenos Aires city. The study involved 99 participants. Rickettsia IgG antibodies against SFG and TG were detected by IFA in 28.3% and 16.2% of serum samples, respectively. SFG titers were mostly 1/64 (53.6%) with a maximum of 1/512 (3.5%) whereas TG titers ranged between 1/64 (62.5%) and 1/256 (6.3%). Only one sample showed a titer of 1/32 for C. burnetii (phases I and II). The circulation of these pathogens in urban areas such as the city of Buenos Aires should be considered by health services, especially at the primary care level.

Genetic diversity of G3 rotavirus strains circulating in Argentina during 1998-2012 assessed by full genome analyses.

Seasonal shifts in the predominant strains and the periodic emergence of new strains are epidemiological features of human rotaviruses. After the sporadic detection in two samples in 1998, G3P[8] strains reemerged as the predominant rotavirus during 2008-2009 in Argentina. Notably, in 2011 6.3% (37/587) of samples presented the G3P[6] genotypes, which coincided with the recent detection of G3P[6] and G2P[6] strains in South America and Europe. Analyses of the 11 gene segments of four G3P[8] and two G3P[6] strains revealed that G3P[8] strains detected a decade apart (1998 and 2009) presented minor differences, while the G3P[6] strains presented a complete different genomic constellation albeit showing a similar VP7 gene. This study provides insights in the dynamics and evolution of one of the genotypes with the wider range of hosts and inter-species transmission potential.

[Rotavirus epidemiology and surveillance in Argentina: 2009-2011]. / Vigilancia epidemiológica de rotavirus en la Argentina: 2009-2011.

It has been estimated that in Argentina, rotavirus causes approximately 80,000 to 100,000 clinic consultations annually and is responsible for 40% of acute diarrhea related hospital admissions in children under 5 years. In this study, national rotavirus surveillance data from 2009-2011 was consulted to asses prevalence, seasonality, age-group distribution as well as the national and regional genotypes circulating. It is essential to get deeper insight into the epidemiology and burden of rotavirus diarrhea for design of strategies and health interventions in order to prevent and control high impact human diseases.

Vigilancia epidemiológica de rotavirus en la Argentina: 2009-2011 / Rotavirus epidemiology and surveillance in Argentina: 2009-2011

Se estima que, en la Argentina, rotavirus produce entre 80 000 y 100 000 consultas médicas por año y es responsable del 40% de las internaciones por diarrea aguda en los menores de 5 años. El objetivo del presente trabajo es analizar los datos del período 2009-2011 en relación con la vigilancia nacional de rotavirus. Se estudió la prevalencia y distribución según el grupo etario, la frecuencia temporal y los genotipos circulantes. Resulta fundamental conocer la epidemiología y la carga de esta enfermedad para el diseño de estrategias e intervenciones en salud con el propósito de prevenir y controlar las enfermedades que tienen un alto impacto en la población.

It has been estimated that in Argentina, rotavirus causes approximately 80 000 to 100 000 clinic consultations annually and is responsible for 40% of acute diarrhea related hospital admissions in children under 5 years. In this study, national rotavirus surveillance data from 2009-2011 was consulted to asses prevalence, seasonality, agegroup distribution as well as the national and regional genotypes circulating. It is essential to get deeper insight into the epidemiology and burden of rotavirus diarrhea for design of strategies and health interventions in order to prevent and control high impact human diseases.

Vigilancia epidemiológica de rotavirus en la Argentina: 2009-2011 / Rotavirus epidemiology and surveillance in Argentina: 2009-2011

Se estima que, en la Argentina, rotavirus produce entre 80 000 y 100 000 consultas médicas por año y es responsable del 40% de las internaciones por diarrea aguda en los menores de 5 años. El objetivo del presente trabajo es analizar los datos del período 2009-2011 en relación con la vigilancia nacional de rotavirus. Se estudió la prevalencia y distribución según el grupo etario, la frecuencia temporal y los genotipos circulantes. Resulta fundamental conocer la epidemiología y la carga de esta enfermedad para el diseño de estrategias e intervenciones en salud con el propósito de prevenir y controlar las enfermedades que tienen un alto impacto en la población.(AU)

It has been estimated that in Argentina, rotavirus causes approximately 80 000 to 100 000 clinic consultations annually and is responsible for 40% of acute diarrhea related hospital admissions in children under 5 years. In this study, national rotavirus surveillance data from 2009-2011 was consulted to asses prevalence, seasonality, agegroup distribution as well as the national and regional genotypes circulating. It is essential to get deeper insight into the epidemiology and burden of rotavirus diarrhea for design of strategies and health interventions in order to prevent and control high impact human diseases.(AU)

Vigilancia epidemiológica de rotavirus en la Argentina: 2009-2011. / [Rotavirus epidemiology and surveillance in Argentina: 2009-2011].

It has been estimated that in Argentina, rotavirus causes approximately 80,000 to 100,000 clinic consultations annually and is responsible for 40

of acute diarrhea related hospital admissions in children under 5 years. In this study, national rotavirus surveillance data from 2009-2011 was consulted to asses prevalence, seasonality, age-group distribution as well as the national and regional genotypes circulating. It is essential to get deeper insight into the epidemiology and burden of rotavirus diarrhea for design of strategies and health interventions in order to prevent and control high impact human diseases.