RESUMO
Rotaviruses belonging to species A (RVA) remain among the most common causes of severe gastroenteritis in children aged <5 years, leading to substantial morbidity and mortality worldwide. Genome reassortment events between two human strains or human and animal strains represent one of the mechanisms which appear to generate the broad genetic variability of circulating. According to a nucleotide, sequence-based classification system, RVA strains are currently classified into three genotype constellations including Wa-like (genogroup I), DS-1-like (genogroup II), and AU-like (genogroup III). The present study reports the detection of an unusual RVA G4P[6] strain (coded as strain HSE005), which might have originated from a natural reassortment event between human and animal RVA strains. Molecular characterization of this isolate showed that it belonged to genogroup II, genotype G4P[6]. In addition, two genes (VP3 and NSP4) of this strain denoted evidence of reassortment events involving strains of distinct zoonotic evolutionary origins. Therefore, we propose that a new G4P[6] strain was identified, highlighting a possible first zoonotic transmission including a reassortment event that involved the VP3 gene.
Assuntos
Gastroenterite/virologia , Genótipo , Rotavirus/genética , Brasil , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , RNA Viral , Rotavirus/classificação , Rotavirus/isolamento & purificaçãoRESUMO
BACKGROUND: Noroviruses (NoVs) cause acute gastroenteritis (AGE) worldwide, affecting children in particular. We aimed to estimate the burden of disease due to NoV among children aged <6 years in Brazil, Chile, Philippines and Thailand. METHODS: This was a prospective, hospital-based, observational study. Children were recruited over one year between 2014 and 2017. Four cohorts were analysed: community-acquired AGE outpatients and inpatients, nosocomial AGE inpatients, and asymptomatic outpatients. We collected demographic and clinical data, and a stool sample that was tested for NoV. Positive samples were tested for Rotavirus (RV) and NoV-genotyped. Disease severity was assessed by the Vesikari and modified Vesikari scores. Prevalence and incidence of NoV-AGE were estimated by cohort and country. RESULTS: 1637 participants yielded valid laboratory results. The proportion of NoV-positive cases was 23.8% (95% CI 20.8-27.2) in the outpatient cohort, 17.9% (15.0-21.3) in the hospital cohort, 21.4% (12.7-33.8) in the nosocomial cohort and 9.6% (6.9-13.2) in the asymptomatic cohort. Genotype GII.4 was predominant (58%). Less than 4% samples had RV coinfection. In general, NoV-positive subjects had more severe presentations than NoV-negative subjects. CONCLUSIONS: NoV caused AGE with substantial burden throughout the studied settings, with higher relative frequency in Brazil where RV vaccination coverage is high.
Assuntos
Infecções por Caliciviridae , Norovirus , Brasil/epidemiologia , Infecções por Caliciviridae/epidemiologia , Criança , Chile , Fezes , Genótipo , Humanos , Lactente , Norovirus/genética , Filipinas/epidemiologia , Estudos Prospectivos , RNA Viral , Tailândia/epidemiologiaRESUMO
BACKGROUND: Rotavirus antigenemia and RNAemia (the presence of rotavirus RNA in serum) have been commonly identified among paediatric patients with acute gastroenteritis. In this study we examined the association between rotavirus antigenemia and clinical features, and sought to determine the genotypes of rotaviruses detected in paired stool and serum samples. METHODS: Paired stool and serum samples were obtained from children hospitalised for acute gastroenteritis in Belém, Brazil, between June 2012 and June 2015. The 20-point Vesikari scoring system was used to assess the disease severity upon a retrospective medical record review. Stool and serum samples were primarily screened for the presence of rotavirus antigen using a commercial ELISA assay. The rotavirus isolates from stool and serum samples were genotyped by using the classical reverse-transcriptase polymerase chain reaction (RT-PCR) and/or through nucleotide sequencing of VP4 and VP7 genes. Viral load was estimated using real-time RT-PCR. RESULTS: In total rotavirus antigen was detected in 109 (24.2%) stool samples from 451 children, whereas antigenemia occurred in 38.5% (42/109) of these patients. We demonstrated that patients positive for rotavirus RNA in paired stool and serum samples were more likely to have a higher frequency of vomiting episodes in a 24-h period (p = 0.0035). Our findings also suggested that children not vaccinated against rotavirus are more likely to develop antigenemia, as compared to those given at least one vaccine dose (p = 0.0151). G12P [8] and G2P [4] genotypes were predominant throughout the study period, accounting for 52.3% (57/109) and 27.5% (30/109) of the typed isolates, respectively. Ten stool-serum pairs could be typed for VP4 and VP7 genes. Seven of these pairs showed concordant results with G2P [4] genotype being detected in stool and serum samples, whereas discrepancies between genotypes (G2P [4]/G2P[NT] and G12P [8]/G2P[NT]) were seen in three pairs. CONCLUSIONS: Rotavirus antigenemia and RNAemia occur in a significant number of children hospitalised for acute gastroenteritis in Belém, Brazil, and may contribute to a greater disease severity, particularly translated into a greater number of vomiting episodes. This study documented a high concordance of genotypes detected in a subgroup of paired stool and serum samples.
Assuntos
Antígenos Virais/análise , Gastroenterite/imunologia , RNA Viral/análise , Infecções por Rotavirus/imunologia , Rotavirus/imunologia , Doença Aguda , Antígenos Virais/sangue , Brasil , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Fezes/química , Fezes/virologia , Feminino , Gastroenterite/complicações , Gastroenterite/virologia , Genótipo , Hospitalização , Humanos , Masculino , Estudos Prospectivos , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/genética , Índice de Gravidade de Doença , Vômito/etiologiaRESUMO
Species A rotavirus still remains a major cause of acute gastroenteritis in infants and young children. Globally, six genotypes (G1P[8], G2P[4], G3P[8], G4P[8], G9P[8] and G12P[8]) account for >90% of circulating strains; however, genotype G12 in combination with P[6] or P[9] has been detected at increasing rates. We sought to broaden our knowledge about the rotavirus strains circulating during the early post-vaccine-introduction period. Stool samples were obtained from children hospitalised for acute gastroenteritis in Belém, Northern Brazil, from May 2008 to May 2011 and examined by reverse transcription polymerase chain reaction and nucleotide sequencing. A total of 122 out of the original 1076 rotavirus strains were judged to be non-typeable in the first analysis and were therefore re-examined. G2P[4] was the most prevalent genotype (58.0%), followed by G1P[8] (16.9%), and G12P[6] (7.5%). G12P[6] strains were identified at similar rates during the first (2.5%) and second (3.9%) years, and the rate jumped to 15.6% in the third year. Analysis of VP7 sequences of the G12P[6] strains showed that they belonged to lineage III. In addition, co-circulating G12P[6] strains displaying long and short RNA patterns were found to belong to the Wa-like and DS-1-like constellation, respectively. Additional unusual circulating strains G12P[9] and G3P[9] were also identified. This hospital-based study showed a high prevalence of G12P[6] strains in the third year of surveillance. Our results highlight the need for continuous longitudinal monitoring of circulating rotavirus strains after introduction of rotavirus vaccines in Brazil and elsewhere.
Assuntos
Gastroenterite/virologia , Rotavirus/genética , Antígenos Virais/imunologia , Brasil , Criança , Criança Hospitalizada , Gastroenterite/imunologia , Genótipo , Humanos , Epidemiologia Molecular/métodos , Filogenia , Prevalência , RNA Viral/genética , Rotavirus/imunologia , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/imunologia , Análise de Sequência de DNA/métodosRESUMO
The species A rotaviruses (RVA) are important gastroenteric pathogens that infect humans and animals. RVA genotype G3P[9] has been described in human-animal reassortment events, and the complexity of its hosts motivates the genetic investigation of this strain. Therefore, the aim of this study is to analyse a G3P[9] sample that was detected in a child with acute gastroenteritis. The 1A3739 sample featured the constellation G3P[9]-I18-R3-C3-Mx-A19-N3-T3-E3-H6. The sequence for VP3 gene was not obtained. The phylogeny showed a closer relationship among genes VP7, VP1, NSP3, NSP4, and NSP5 with genes of animal origin, such as chiropter, alpaca, equine, and simian. In addition, the genes VP6 and NSP1 belong to the new genotypes I18 and A19, respectively. The emergence of strains such as these can interfere with the effectiveness of the RVA vaccine, and continuous monitoring is therefore important. Additional studies are needed to determine the evolutionary source and to identify a possible reservoir of RVA in nature.
Assuntos
Gastroenterite/virologia , Genótipo , Vírus Reordenados/genética , Infecções por Rotavirus/virologia , Rotavirus/genética , Pré-Escolar , Evolução Molecular , Feminino , Humanos , Filogenia , Recombinação Genética , Rotavirus/isolamento & purificação , Análise de Sequência de DNARESUMO
BACKGROUND: Rotavirus (RV) vaccine, Rotarix, was introduced into the Brazil national immunization program in 2006. To estimate population-level vaccine effect, we conducted a time-trend analysis on all-cause gastroenteritis (GE)-related death certificate-reported deaths (DCRDs), hospital deaths (HDs) and hospitalizations trends in <5-year-olds before and after RV vaccine introduction. METHODS: National level all-cause GE-related death certificate [Mortality Information System] and admission (Hospital Information System) data were aggregated and analyzed. Negative-binomial regression models (adjusting for age, year and region) compared DCRDs, HDs and hospitalization trends in <5-year-olds between baseline (2001-2005) and postvaccine introduction periods (Mortality Information System: 2007-2009 and Hospital Information System: 2007-2010). Negative-binomial regression models were fitted to data for each outcome before 2006, and the predicted annual frequencies of each outcome were plotted against corresponding observed annual frequencies. RESULTS: During the postvaccine introduction period, there was an overall age-independent GE-related DCRDs reduction (20.9%, P = 0.04) observed in children <5 years of age; a reduction was also seen in infants <1 year of age (20.8%, P = 0.003). Age-independent GE-related HDs and hospitalizations reductions (57.1%, P < 0.0001 and 26.6%, P < 0.0001, respectively) were observed in <5-year-olds; HDs reductions were also observed for each age group (<1-year-olds: 55.0%, P < 0.0001 and 1- to <5-year-olds: 59.5%, P < 0.0001). Observed annual frequencies of GE-related DCRDs, HDs and hospitalizations were lower than the predicted value in each age group in all years after 2006. CONCLUSIONS: GE-related DCRDs, HDs and hospitalizations were significantly reduced in <1 and in 1- to <5-year-old Brazilian children after Rotarix introduction, which provides additional evidence of the direct and indirect population-level effect of RV vaccination on GE-related mortality and morbidity in children.
Assuntos
Gastroenterite/epidemiologia , Gastroenterite/mortalidade , Hospitalização , Vacinas contra Rotavirus/administração & dosagem , Brasil/epidemiologia , Pré-Escolar , Feminino , Gastroenterite/prevenção & controle , Humanos , Programas de Imunização , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Análise de SobrevidaRESUMO
In March 2006, Brazil introduced the monovalent rotavirus (RV) vaccine (Rotarix™) into the public sector. This study assessed the severity of rotavirus gastroenteritis (RVGE) according to the vaccination status among hospitalized children. We identified 1023 RVGE episodes among not vaccinated (n = 252), partially vaccinated (n = 156) and fully vaccinated (n = 615) children. Very severe gastroenteritis (scored ≥ 15) was reported in 16.7, 17.9 and 13.5% of not vaccinated, partially vaccinated and fully vaccinated children, respectively. There was a trend for a shorter duration of RV diarrhoea among vaccinated children than in not vaccinated children (p = 0.07). A protective effect of vaccination was noted when mean duration of symptoms and hospital stay are analysed, comparing unvaccinated, partially vaccinated and fully vaccinated children (p < 0.05). We showed a vaccination dose effect trend, with fully vaccinated children having less-severe RVGE than not vaccinated and partially vaccinated children.
Assuntos
Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Rotavirus/isolamento & purificação , Vacinação/estatística & dados numéricos , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Gastroenterite/virologia , Humanos , Programas de Imunização , Incidência , Masculino , Vigilância da População , Estudos Prospectivos , Infecções por Rotavirus/epidemiologia , Vacinas contra Rotavirus/imunologia , Índice de Gravidade de DoençaRESUMO
The present study aimed to provide a molecular characterization of circulating rotavirus (RVA) strains in Rio Branco, Acre, in the post-rotavirus vaccination period, particularly with regard to the emerging, increasingly prevalent G12P[8] genotype. A total of 488 fecal specimens from diarrheic and non-diarrheic children were obtained between January and December 2012. RVA detection was initially performed using enzyme-linked immunosorbent assay (ELISA) method, followed by reverse-transcription polymerase chain reaction (RT-PCR) using specific primers. RVA was detected in 18.3% (44/241) of the children with acute diarrhea and in 1.2% (3/247) of the non-diarrheic children (P < 0.001), with overall RVA-positivity of 9.6% (47/488). The most common genotype was G2P[4] with 43.2% (19/44) of the diarrheic cases, followed by G12P[8] (27.3%, 12/44), G3P[6] (18.2%, 8/44), G3P[8] (4.5%, 2/44), and G12P[6] (2.3%, 1/44). G12 samples belonged to lineage III and were from children aged 4-52 months. All of these children had acute diarrhea associated with fever (83.3%, 10/12) and vomiting (66.7%, 8/12). Most of the cases occurred in August (58.3%, 7/12), 75% (9/12) of which having received the full vaccination scheme with Rotarix™. For the first time G12 was reported at relative high prevalence in Brazil. Our findings warrant further monitoring studies on the molecular characterization of circulating RVA strains after rotavirus vaccine introduction in Brazil and elsewhere, since the occurrence of either unusual our emerging genotypes may pose a challenge to vaccination strategies.
Assuntos
Genótipo , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Rotavirus/classificação , Rotavirus/genética , Brasil/epidemiologia , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Fezes/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Epidemiologia Molecular , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/isolamento & purificação , Infecções por Rotavirus/patologia , Infecções por Rotavirus/virologia , Estações do AnoRESUMO
Group C rotavirus (RVC) is potentially an important pathogen associated with acute gastroenteritis (AG), especially in outbreaks. This study aims to detect and molecularly characterize RVC in hospitalized children with AG in Belém, Brazil. From May 2008 to April 2011, 279 stools were subjected to reverse-transcription polymerase chain reaction targeting VP7, VP6, VP4, and NSP4 genes. RVC positivity rate was 2.1% (6/279) and phylogenetic analysis of positive samples yields genotype G4-P[2]-I2-E2. No evidence of zoonotic transmission and VP7 gene demonstrated close relationship with Asian strains. RVC surveillance is worth to expand information on evolutionary and epidemiological features of this virus.
Assuntos
Gastroenterite/virologia , Variação Genética , Genótipo , Filogenia , Infecções por Rotavirus/virologia , Rotavirus/classificação , Rotavirus/genética , Brasil/epidemiologia , Criança Hospitalizada , Pré-Escolar , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Humanos , Lactente , Masculino , Epidemiologia Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/isolamento & purificação , Infecções por Rotavirus/epidemiologia , Proteínas não Estruturais Virais/genética , Proteínas Estruturais Virais/genéticaRESUMO
The monovalent human rotavirus (RV) vaccine, RIX4414 (Rotarix™, GlaxoSmithKline Biologicals) was introduced into Brazil's Expanded Program on Immunization in March 2006. One year after vaccine introduction, the G2P[4] strain was found to be predominant, with an apparent extinction of many non-G2 strains. This study investigated the diversity of circulating strains in the three years following RIX4414 introduction. Between May 2008 and May 2011, stool samples were collected from children aged ≥12 weeks who were hospitalized for severe lab confirmed RV-gastroenteritis (≥3 liquid or semi-liquid motions over a 24-h period for <14 days, requiring ≥1 overnight hospital stay and intravenous rehydration therapy) in Belém, Brazil. RV-gastroenteritis was detected by ELISA and the G- and P-types were determined by RT-PCR assays. During the first year of surveillance nucleotide sequencing was used for typing those samples not previously typed by RT-PCR. A total of 1,726 of 10,030 severe gastroentertis hospitalizations (17.2%) were due to severe RVGE. G2P[4] was detected in 57.2% of circulating strains over the whole study period, however it predominated during the first 20 months from May 2008 to January 2009. G1P[8] increased in the last part of the study period from May 2010 to May 2011 and represented 36.6% (112/306) of the circulating strains. G2P[4] was the predominant RV strain circulating during the first 20 months of the study, followed by G1P[8]. These findings probably reflect a natural fluctuation in RV strains over time, rather than a vaccine-induced selective pressure.