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1.
JAMA Netw Open ; 2(9): e1912242, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31560386

RESUMO

Importance: Rotavirus vaccines have been recommended for universal US infant immunization for more than 10 years, and understanding their effectiveness is key to the continued success of the US rotavirus vaccine immunization program. Objective: To assess the association of RotaTeq (RV5) and Rotarix (RV1) with inpatient and emergency department (ED) visits for rotavirus infection. Design, Setting, and Participants: This case-control vaccine effectiveness study was performed at inpatient and ED clinical settings in 7 US pediatric medical institutions from November 1, 2009, through June 30, 2016. Children younger than 5 years seeking medical care for acute gastroenteritis were enrolled. Clinical and epidemiologic data, vaccination verification, and results of stool sample tests for laboratory-confirmed rotavirus were collected. Data were analyzed from November 1, 2009, through June 30, 2016. Main Outcomes and Measures: Rotavirus vaccine effectiveness for preventing rotavirus-associated inpatient and ED visits over time for each licensed vaccine, stratified by clinical severity and age. Results: Among the 10 813 children included (5927 boys [54.8%] and 4886 girls [45.2%]; median [range] age, 21 [8-59] months), RV5 and RV1 analyses found that compared with controls, rotavirus-positive cases were more often white (RV5, 535 [62.2%] vs 3310 [57.7%]; RV1, 163 [43.1%] vs 864 [35.1%]), privately insured (RV5, 620 [72.1%] vs 4388 [76.5%]; RV1, 305 [80.7%] vs 2140 [87.0%]), and older (median [range] age for RV5, 26 [8-59] months vs 21 [8-59] months; median [range] age for RV1, 22 [8-59] months vs 19 [8-59] months) but did not differ by sex. Among 1193 rotavirus-positive cases and 9620 rotavirus-negative controls, at least 1 dose of any rotavirus vaccine was 82% (95% CI, 77%-86%) protective against rotavirus-associated inpatient visits and 75% (95% CI, 71%-79%) protective against rotavirus-associated ED visits. No statistically significant difference during this 7-year period was observed for either rotavirus vaccine. Vaccine effectiveness against inpatient and ED visits was 81% (95% CI, 78%-84%) for RV5 (3 doses) and 78% (95% CI, 72%-82%) for RV1 (2 doses) among the study population. A mixed course of both vaccines provided 86% (95% CI, 74%-93%) protection. Rotavirus patients who were not vaccinated had severe infections 4 times more often than those who were vaccinated (74 of 426 [17.4%] vs 28 of 605 [4.6%]; P < .001), and any dose of rotavirus vaccine was 65% (95% CI, 56%-73%) effective against mild infections, 81% (95% CI, 76%-84%) against moderate infections, and 91% (95% CI, 85%-95%) against severe infections. Conclusions and Relevance: Evidence from this large postlicensure study of rotavirus vaccine performance in the United States from 2010 to 2016 suggests that RV5 and RV1 rotavirus vaccines continue to perform well, particularly in preventing inpatient visits and severe infections and among younger children.

2.
J Virol ; 93(1)2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30333170

RESUMO

Rotavirus is the leading global cause of diarrheal mortality for unvaccinated children under 5 years of age. The outer capsid of rotavirus virions consists of VP7 and VP4 proteins, which determine viral G and P types, respectively, and are primary targets of neutralizing antibodies. Successful vaccination depends upon generating broadly protective immune responses following exposure to rotaviruses presenting a limited number of G- and P-type antigens. Vaccine introduction resulted in decreased rotavirus disease burden but also coincided with the emergence of uncommon G and P genotypes, including G12. To gain insight into the recent predominance of G12P[8] rotaviruses in the United States, we evaluated 142 complete rotavirus genome sequences and metadata from 151 clinical specimens collected in Nashville, TN, from 2011 to 2013 through the New Vaccine Surveillance Network. Circulating G12P[8] strains were found to share many segments with other locally circulating strains but to have distinct constellations. Phylogenetic analyses of G12 sequences and their geographic sources provided evidence for multiple separate introductions of G12 segments into Nashville, TN. Antigenic epitopes of VP7 proteins of G12P[8] strains circulating in Nashville, TN, differ markedly from those of vaccine strains. Fully vaccinated children were found to be infected with G12P[8] strains more frequently than with other rotavirus genotypes. Multiple introductions and significant antigenic mismatch may in part explain the recent predominance of G12P[8] strains in the United States and emphasize the need for continued monitoring of rotavirus vaccine efficacy against emerging rotavirus genotypes.IMPORTANCE Rotavirus is an important cause of childhood diarrheal disease worldwide. Two immunodominant proteins of rotavirus, VP7 and VP4, determine G and P genotypes, respectively. Recently, G12P[8] rotaviruses have become increasingly predominant. By analyzing rotavirus genome sequences from stool specimens obtained in Nashville, TN, from 2011 to 2013 and globally circulating rotaviruses, we found evidence of multiple introductions of G12 genes into the area. Based on sequence polymorphisms, VP7 proteins of these viruses are predicted to present themselves to the immune system very differently than those of vaccine strains. Many of the sick children with G12P[8] rotavirus in their diarrheal stools also were fully vaccinated. Our findings emphasize the need for continued monitoring of circulating rotaviruses and the effectiveness of the vaccines against strains with emerging G and P genotypes.


Assuntos
Antígenos Virais/genética , Proteínas do Capsídeo/genética , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/imunologia , Rotavirus/classificação , Antígenos Virais/imunologia , Proteínas do Capsídeo/imunologia , Pré-Escolar , Técnicas de Genotipagem , Humanos , Lactente , Filogenia , Vigilância da População , Rotavirus/genética , Rotavirus/imunologia , Infecções por Rotavirus/prevenção & controle , Análise de Sequência de RNA , Estados Unidos
3.
Pediatrics ; 141(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29212881

RESUMO

BACKGROUND: Infants born prematurely or with underlying conditions are at increased risk of severe rotavirus disease and associated complications. Given the theoretical risk of nosocomial transmission of vaccine-type rotavirus, rotavirus vaccination is recommended for infants at or after discharge from neonatal care settings. Because the first dose should be administered by 104 days of age, some infants may be age-ineligible for vaccination if delayed until discharge. METHODS: This prospective cohort included infants admitted to an urban academic medical center between birth and 104 days who received care in intensive care settings. Pentavalent human-bovine reassortant rotavirus vaccine (RV5) was used, per routine clinical care. Stool specimens were collected weekly (February 2013-April 2014) and analyzed for rotavirus strains using real-time reverse transcription-polymerase chain reaction. Demographic and vaccine data were collected. RV5 safety was not assessed. RESULTS: Of 385 study infants, 127 were age-eligible for routine vaccinations during hospitalization. At discharge, 32.7% were up-to-date for rotavirus vaccination, compared with 82.7% for other vaccinations. Of rotavirus-unvaccinated infants, 42.6% were discharged at age >104 days and thus vaccination-ineligible. Of 1192 stool specimens collected, rotavirus was detected in 13 (1.1%): 1 wild-type strain from an unvaccinated infant; 12 vaccine-type strains from 9 RV5-vaccinated infants. No vaccine-type rotavirus cases were observed among unvaccinated infants (incidence rate: 0.0 [95% confidence interval: 0.0-1.5] cases per 1000 patient days at risk). CONCLUSIONS: These data suggest that delaying rotavirus vaccination until discharge from the hospital could lead to missed vaccination opportunities and may be unnecessary in institutions using RV5 with comparable infection control standards.


Assuntos
Infecção Hospitalar/prevenção & controle , Recém-Nascido Prematuro , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Rotavirus/imunologia , Centros Médicos Acadêmicos , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Alta do Paciente , Estudos Prospectivos , Medição de Risco , Rotavirus/isolamento & purificação , Fatores de Tempo , Estados Unidos , Vacinação/normas , Vacinação/tendências
4.
Genome Announc ; 5(47)2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29167260

RESUMO

We report here the full coding region sequences for all 11 segments of the first equine-like G3P[8] rotavirus strain detected in the United States, strain RVA/Human-wt/USA/3000390639/2015/G3P[8]. The full genotype constellation of this strain is G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2.

5.
J Clin Virol ; 95: 66-71, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28889082

RESUMO

BACKGROUND: Viruses are major etiological agents of childhood gastroenteritis. In recent years, several molecular platforms for the detection of viral enteric pathogens have become available. OBJECTIVE/STUDY DESIGN: We evaluated the performance of three multiplex platforms including Biofire's Gastrointestinal Panel (FilmArray), Luminex xTAG® Gastrointestinal Pathogen Panel (GPP), and the TaqMan Array Card (TAC) for the detection of five gastroenteritis viruses using a coded panel of 300 archived stool samples. RESULTS: The FilmArray detected a virus in 199 (96.1%) and the TAC in 172 (83.1%) of the 207 samples (187 samples positive for a single virus and 20 samples positive for more than one virus) whereas the GPP detected a virus in 100 (78.7%) of the 127 (97 positive for one virus and three positive for more than one virus) samples. Overall the clinical accuracy was highest for the FilmArray (98%) followed by TAC (97.2%) and GPP (96.9%). The sensitivity of the FilmArray, GPP and TAC platforms was highest for rotavirus (100%, 95.8%, and 89.6%, respectively) and lowest for adenovirus type 40/41 (97.4%, 57.9% and 68.4%). The specificity of the three platforms ranged from 95.6% (rotavirus) to 99.6% (norovirus/sapovirus) for the FilmArray, 99.6% (norovirus) to 100% (rotavirus/adenovirus) for GPP, and 98.9% (astrovirus) to 100% (rotavirus/sapovirus) for TAC. CONCLUSION: The FilmArray demonstrated the best analytical performance followed by TAC. In recent years, the availability of multi-enteric molecular testing platforms has increased significantly and our data highlight the strengths and weaknesses of these platforms.


Assuntos
Gastroenterite/diagnóstico , Gastroenterite/virologia , Reação em Cadeia da Polimerase Multiplex/métodos , Norovirus/isolamento & purificação , Rotavirus/isolamento & purificação , Sapovirus/isolamento & purificação , Viroses/diagnóstico , Fezes/virologia , Humanos , Técnicas de Diagnóstico Molecular/instrumentação , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase Multiplex/instrumentação , Norovirus/genética , Rotavirus/genética , Sapovirus/genética , Sensibilidade e Especificidade , Viroses/virologia
6.
Hum Vaccin Immunother ; 13(4): 928-935, 2017 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-27936349

RESUMO

Thirty-three infants aged ∼2 months had serial stool samples collected after receipt of Rotarix® vaccine dose 1, and were assessed for shedding of porcine circovirus type 1 DNA and Rotavirus group A RNA by molecular methods. We did not find strong evidence that porcine circovirus type 1 replication occurred. Porcine circovirus type 1 genome with the same sequence as that in Rotarix® was detected in a few infants as late as day ≥ 13; while this timing could suggest there may have been replication and not just transient passage through the gastrointestinal tract, the lack of increase in copy number in any infant supports transient passage and there are inherent limitations to the results. We found that 21% of infants did not shed Rotarix® RVA RNA beyond the day 3 sample, which may suggest lack of vaccine virus replication. Of the infants in whom Rotarix RVA RNA shedding continued, peak copy numbers were reached on days 3-5 for ∼40%, and after day 5 in ∼60%, and shedding can be prolonged (≥ 45 days).


Assuntos
Circovirus/isolamento & purificação , DNA Viral/isolamento & purificação , Fezes/virologia , RNA Viral/isolamento & purificação , Vacinas contra Rotavirus/administração & dosagem , Rotavirus/isolamento & purificação , Eliminação de Partículas Virais , Circovirus/genética , DNA Viral/genética , Feminino , Humanos , Lactente , Masculino , RNA Viral/genética , Rotavirus/genética , Fatores de Tempo , Vacinas Atenuadas/administração & dosagem
7.
J Infect Dis ; 214(suppl 3): S258-S262, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27587631

RESUMO

During the Ebola virus outbreak of 2013-2016, the Viral Special Pathogens Branch field laboratory in Sierra Leone tested approximately 26 000 specimens between August 2014 and October 2015. Analysis of the B2M endogenous control Ct values showed its utility in monitoring specimen quality, comparing results with different specimen types, and interpretation of results. For live patients, blood is the most sensitive specimen type and oral swabs have little diagnostic utility. However, swabs are highly sensitive for diagnostic testing of corpses.


Assuntos
Surtos de Doenças , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/diagnóstico , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Serviços de Laboratório Clínico , Ebolavirus/genética , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Humanos , Laboratórios , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Serra Leoa/epidemiologia
8.
J Virol Methods ; 236: 41-46, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27421626

RESUMO

Techniques such as the real-time reverse transcription-polymerase chain reaction (qRT-PCR) can detect RNA in samples with a low viral load. However, these amplicons typically are either too short or at insufficient concentrations for use in subsequent sequencing reactions for genotyping and detection confirmation. The assay developed in this study detects rotavirus G genotypes and P genotypes with viral loads as low as 6.2 and 8.2 copies per reaction, respectively. The assay was validated using a panel of 91 stool samples, 32 reference rotavirus strains, and 6 non-target enteric virus samples.


Assuntos
Fezes/virologia , Reação em Cadeia da Polimerase/métodos , Infecções por Rotavirus/virologia , Rotavirus/isolamento & purificação , Humanos , Rotavirus/genética , Sensibilidade e Especificidade
9.
J Infect Dis ; 214(5): 732-8, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27302190

RESUMO

BACKGROUND: Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3-7 geographically diverse sites in the United States since 2006. METHODS: Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. RESULTS: In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%-3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. CONCLUSIONS: Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure.


Assuntos
Genótipo , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/administração & dosagem , Rotavirus/classificação , Rotavirus/isolamento & purificação , Criança , Pré-Escolar , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Masculino , Rotavirus/genética , Infecções por Rotavirus/prevenção & controle , Estados Unidos/epidemiologia
10.
Infect Genet Evol ; 43: 338-42, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27237948

RESUMO

Here we report the genome of a novel rotavirus A (RVA) strain detected in a stool sample collected during routine surveillance by the Centers for Disease Control and Prevention's New Vaccine Surveillance Network. The strain, RVA/human-wt/USA/2012741499/2012/G24P[14], has a genomic constellation of G24-P[14]-I2-R2-C2-M2-A3-N2-T9-E2-H3. The VP2, VP3, VP7 and NSP3 genes cluster phylogenetically with bovine strains. The other genes occupy mixed clades containing animal and human strains. Strain RVA/human-wt/USA/2012741499/2012/G24P[14] most likely is the product of interspecies transmission and reassortment events. This is the second report of the G24 genotype and the first report of the G24P[14] genotype combination in humans.


Assuntos
Genoma Viral , Genótipo , Filogenia , Vírus Reordenados/genética , Rotavirus/genética , Proteínas não Estruturais Virais/genética , Animais , Bovinos , Pré-Escolar , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Vírus Reordenados/classificação , Rotavirus/classificação , Infecções por Rotavirus/virologia , Texas
11.
PeerJ ; 4: e1560, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26839745

RESUMO

Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8-100% sensitivity, 99.7-100% specificity, 85-95% efficiency and a limit of detection of 4-60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81-92% efficiency and limit of detection of 150-600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8-100% sensitivity, 100% specificity, 86-89% efficiency and a limit of detection of 12-400 copies per singleplex reactions. The VP4 qRT-PCRs exhibited 82-90% efficiency and limit of detection of 120-4000 copies in multiplex reaction. Discussion. The one-step multiplex qRT-PCR assay will facilitate high-throughput rotavirus genotype characterization for monitoring circulating rotavirus wild-type strains causing rotavirus infections, determining the frequency of Rotarix® and RotaTeq® vaccine strains and vaccine-derived reassortants associated with AGE, and help to identify novel rotavirus strains derived by reassortment between vaccine and wild-type strains.

12.
J Gen Virol ; 97(2): 389-402, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26590163

RESUMO

During the 2008-2009 rotavirus season of the Centers for Disease Control and Prevention New Vaccine Surveillance Network, one case of paediatric acute gastroenteritis associated with a rotavirus G14P[24] strain was identified. This was the first detection of the genotype G14 and P[24] in humans, and the first detection of the G14P[24] combination. To gain an insight into the origins and the evolution of this strain, we determined the complete ORF sequences of all 11 genes. A majority of the genes identified were similar to the simian strain TUCH, except for the VP1 and VP7 genes that clustered only distantly with the bovine and equine strains, respectively. In addition, this strain carried AU-1-like NSP2 and NSP4 genes. Using codon-partitioning and protein-based phylogenetic approaches, we determined that the VP7 genotype of strain 2009727118 was actually G3; therefore, the proposed full genomic classification of the 2009727118 strain is G3-P[24]-I9-R2-C3-M3-A9-N3-T3-E3-H6. These findings indicate the possibility that the 2009727118 strain originated by interspecies transmission and multiple reassortment events involving human, bovine and equine rotaviruses, resulting in the introduction of some genes into the genome of simian rotaviruses. Additionally, we found evidence of mutational saturation in the third codon position of the VP7 ORF which presented an issue with homoplasy in phylogenetic analyses.


Assuntos
Antígenos Virais/genética , Proteínas do Capsídeo/genética , Genoma Viral , Genótipo , Vírus Reordenados/genética , Infecções por Rotavirus/virologia , Rotavirus/genética , Pré-Escolar , Análise por Conglomerados , Evolução Molecular , Feminino , Humanos , Dados de Sequência Molecular , Mutação , Filogenia , RNA Viral/genética , Vírus Reordenados/classificação , Vírus Reordenados/isolamento & purificação , Recombinação Genética , Rotavirus/classificação , Rotavirus/isolamento & purificação , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos
13.
Clin Infect Dis ; 61(12): 1792-9, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26449565

RESUMO

BACKGROUND: Using a multicenter, active surveillance network from 2 rotavirus seasons (2012 and 2013), we assessed the vaccine effectiveness of RV5 (RotaTeq) and RV1 (Rotarix) rotavirus vaccines in preventing rotavirus gastroenteritis hospitalizations and emergency department (ED) visits for numerous demographic and secular strata. METHODS: We enrolled children hospitalized or visiting the ED with acute gastroenteritis (AGE) for the 2012 and 2013 seasons at 7 medical institutions. Stool specimens were tested for rotavirus by enzyme immunoassay and genotyped, and rotavirus vaccination histories were compared for rotavirus-positive cases and rotavirus-negative AGE controls. We calculated the vaccine effectiveness (VE) for preventing rotavirus associated hospitalizations and ED visits for each vaccine, stratified by vaccine dose, season, clinical setting, age, predominant genotype, and ethnicity. RESULTS: RV5-specific VE analyses included 2961 subjects, 402 rotavirus cases (14%) and 2559 rotavirus-negative AGE controls. RV1-specific VE analyses included 904 subjects, 100 rotavirus cases (11%), and 804 rotavirus-negative AGE controls. Over the 2 rotavirus seasons, the VE for a complete 3-dose vaccination with RV5 was 80% (confidence interval [CI], 74%-84%), and VE for a complete 2-dose vaccination with RV1 was 80% (CI, 68%-88%).Statistically significant VE was observed for each year of life for which sufficient data allowed analysis (7 years for RV5 and 3 years for RV1). Both vaccines provided statistically significant genotype-specific protection against predominant circulating rotavirus strains. CONCLUSIONS: In this large, geographically and demographically diverse sample of US children, we observed that RV5 and RV1 rotavirus vaccines each provided a lasting and broadly heterologous protection against rotavirus gastroenteritis.


Assuntos
Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/imunologia , Antígenos Virais/análise , Criança , Pré-Escolar , Serviços Médicos de Emergência , Ensaio de Imunoadsorção Enzimática , Monitoramento Epidemiológico , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Genótipo , Hospitalização , Humanos , Lactente , Masculino , RNA Viral/genética , Resultado do Tratamento , Estados Unidos/epidemiologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
14.
JAMA Pediatr ; 169(11): 1040-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26389824

RESUMO

IMPORTANCE: A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus. OBJECTIVE: We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTS: Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURES: Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis. RESULTS: One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE: Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations.


Assuntos
Fucosiltransferases/genética , Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Rotavirus/isolamento & purificação , Estudos de Casos e Controles , Pré-Escolar , Fezes/virologia , Feminino , Gastroenterite/genética , Gastroenterite/virologia , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Estudos Prospectivos , Infecções por Rotavirus/genética , Infecções por Rotavirus/virologia , Saliva/virologia , Estados Unidos
15.
J Virol Methods ; 223: 96-104, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26231786

RESUMO

The current two-step VP7 and VP4 genotyping RT-PCR assays for rotaviruses have been linked consistently to genotyping failure in an estimated 30% of RVA positive samples worldwide. We have developed a VP7 and VP4 multiplexed one-step genotyping assays using updated primers generated from contemporary VP7 and VP4 sequences. To determine assay specificity and sensitivity, 17 reference virus strains, 6 non-target gastroenteritis viruses and 725 clinical samples carrying the most common VP7 (G1, G2, G3, G4, G9, and G12) and VP4 (P[4], P[6], P[8], P[9] and P[10]) genotypes were tested in this study. All reference RVA strain targets yielded amplicons of the expected sizes and non-target genotypes and gastroenteritis viruses were not detected by either assay. Out of the 725 clinical samples tested, the VP7 and VP4 assays were able to assigned specific genotypes to 711 (98.1%) and 714 (98.5%), respectively. The remaining unassigned samples were re-tested for RVA antigen using EIA and qRT-PCR assays and all were found to be negative. The overall specificity, sensitivity and limit of detection of the VP7 assay were in the ranges of 99.0-100%, 94.0-100% and 8.6×10(1) to 8.6×10(2) copies of RNA/reaction, respectively. For the VP4 assay, the overall specificity, sensitivity and limit of detection assay were in the ranges of 100%, 94.0-100% and ≤1 to 8.6×10(2) copies of RNA/reaction, respectively. Here we report two highly robust, accurate, efficient, affordable and documentable gel-based genotyping systems which are capable of genotyping 97.8% of the six common VP7 and 98.3% of the five common VP4 genotypes of RVA strains which are responsible for approximately 88.2% of all RVA infections worldwide.


Assuntos
Antígenos Virais/genética , Proteínas do Capsídeo/genética , Técnicas de Genotipagem/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Rotavirus/classificação , Rotavirus/isolamento & purificação , Primers do DNA/genética , Humanos , Rotavirus/genética , Sensibilidade e Especificidade
16.
Genome Announc ; 3(3)2015 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-26089432

RESUMO

This is a report of the complete genomic sequence of a rare rotavirus group A G8-P[14]-I2-R3-C2-M2-A3-N2-T6-E2-H3 strain detected in a stool sample from a 57-year-old subject.

17.
Infect Genet Evol ; 33: 206-11, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25952569

RESUMO

We report the genomic characterization of a rare human G8P[14] rotavirus strain, identified in a stool sample from Guatemala (GTM) during routine rotavirus surveillance. This strain was designated as RVA/Human-wt/GTM/2009726790/2009/G8P[14], with a genomic constellation of G8-P[14]-I2-R2-C2-M2-A13-N2-T6-E2-H3. The VP4 gene occupied lineage VII within the P[14] genotype. Phylogenetic analysis of each genome segment revealed close relatedness to several zoonotic simian, guanaco and bovine strains. Our findings suggest that strain RVA/Human-wt/GTM/2009726790/2009/G8P[14] is an example of a direct zoonotic transmission event. The results of this study reinforce the potential role of interspecies transmission and reassortment in generating novel and rare rotavirus strains which infect humans.


Assuntos
Genoma Viral , Genômica , Filogenia , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Rotavirus/classificação , Rotavirus/genética , Animais , Genes Virais , Guatemala/epidemiologia , Humanos , Fases de Leitura Aberta , Infecções por Rotavirus/transmissão , Zoonoses/virologia
18.
Genome Announc ; 2(6)2014 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-25502675

RESUMO

This is a report of the complete genomic sequence of a reassortant rotavirus group A G9-P[4]-I2-R2-C2-M2-A2-N2-T2-E6-H2 strain designated RVA/Human-wt/USA/ LB1562/2010/G9P[4].

19.
Infect Genet Evol ; 28: 480-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25218086

RESUMO

This study describes group A rotavirus (RVA) genotype prevalence in Belarus from 2008 to 2012. In 2008, data from 3 sites in Belarus (Brest, Mogilev, Minsk) indicated that G4P[8] was the predominant genotype. Data from Minsk (2008-2012) showed that G4P[8] was the predominant RVA genotype in all years except in 2011 when G3P[8] was most frequently detected. Other RVA genotypes common in Europe (G1P[8], G2P[4]) were detected each year of the study. This study reveals the dominance of genotype G4P[8] in Belarus and helps to establish the baseline genotype prevalence prior to RVA vaccine introduction in the country.


Assuntos
Genótipo , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Rotavirus/classificação , Rotavirus/genética , Proteínas do Capsídeo/genética , Variação Genética , História do Século XXI , Humanos , Filogenia , Vigilância da População , Prevalência , RNA Viral , República de Belarus/epidemiologia , Infecções por Rotavirus/história
20.
Genome Announc ; 2(2)2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24675848

RESUMO

This is a report of the complete genomic sequence of a rare rotavirus group A G3-P[9]-I2-R2-C2-M2-A3-N2-T1-E2-H3 strain designated RVA/Human-wt/USA/12US1134/2012/G3P[9].

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