RESUMEN
BACKGROUND: Rotavirus is a leading cause of severe pediatric gastroenteritis; two highly effective vaccines are used in the US. We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort. METHODS: PREVAIL is a birth cohort of 245 mother-child pairs enrolled 2017-2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as RT-PCR detection of rotavirus vaccine virus in stools collected 4-28 days after dose one. Seroconversion was defined as a threefold rise in IgA between the six-week and six-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression. RESULTS: Pre-vaccination IgG (OR=0.84, 95% CI [0.75-0.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("non-secretors") with non-secretor mothers, versus all other combinations (OR 0.37 [0.16-0.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose one. Pre-vaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product. DISCUSSION: In this US cohort, pre-vaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response.
RESUMEN
BACKGROUND: Previously studied risk factors for rotavirus vaccine failure have not fully explained reduced rotavirus vaccine effectiveness in low-income settings. We assessed the relationship between histo-blood group antigen (HBGA) phenotypes and clinical rotavirus vaccine failure among children <2 years of age participating in the Vaccine Impact on Diarrhea in Africa Study in 3 sub-Saharan African countries. METHODS: Saliva was collected and tested for HBGA phenotype in children who received rotavirus vaccine. The association between secretor and Lewis phenotypes and rotavirus vaccine failure was examined overall and by infecting rotavirus genotype using conditional logistic regression in 218 rotavirus-positive cases with moderate-to-severe diarrhea and 297 matched healthy controls. RESULTS: Both nonsecretor and Lewis-negative phenotypes (null phenotypes) were associated with decreased rotavirus vaccine failure across all sites (matched odds ratio, 0.30 [95% confidence interval: 0.16-0.56] or 0.39 [0.25-0.62], respectively]. A similar decrease in risk against rotavirus vaccine failure among null HBGA phenotypes was observed for cases with P[8] and P[4] infection and their matched controls. While we found no statistically significant association between null HBGA phenotypes and vaccine failure among P[6] infections, the matched odds ratio point estimate for Lewis-negative individuals was >4. CONCLUSIONS: Our study demonstrated a significant relationship between null HBGA phenotypes and decreased rotavirus vaccine failure in a population with P[8] as the most common infecting genotype. Further studies are needed in populations with a large burden of P[6] rotavirus diarrhea to understand the role of host genetics in reduced rotavirus vaccine effectiveness.
Asunto(s)
Antígenos de Grupos Sanguíneos , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Humanos , Antígenos de Grupos Sanguíneos/genética , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , Gambia , Kenia/epidemiología , Malí/epidemiología , Diarrea/epidemiología , Diarrea/prevención & control , Rotavirus/genética , FenotipoRESUMEN
BACKGROUND: Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in US children. We report the RVA genotype prevalence as well as coinfection data from 7 US New Vaccine Surveillance Network sites during 3 consecutive RVA seasons, 2014-2016. METHODS: A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing. RESULTS: A total of 795 (76%) samples contained detectable RVA when tested at the CDC. Rotavirus disease was highest in children < 3 years of age. Four G types (G1, G2, G9, and G12) accounted for 94.6% of strains while 2 P types (P[4] and P[8]) accounted for 94.7% of the strains. Overall, G12P[8] was the most common genotype detected in all 3 seasons. Stepwise conditional logistic analysis found year and study site were significant predictors of genotype. Twenty-four percent of RVA-positive specimens contained other AGE pathogens. CONCLUSIONS: G12P[8] predominated over 3 seasons, but strain predominance varied by year and study site. Ongoing surveillance provides continuous tracking and monitoring of US genotypes during the postvaccine era.
Asunto(s)
Gastroenteritis , Vigilancia de la Población/métodos , Infecciones por Rotavirus/epidemiología , Rotavirus/aislamiento & purificación , Vacunas , Niño , Heces , Gastroenteritis/epidemiología , Genotipo , Humanos , Lactante , Filogenia , Prevalencia , Rotavirus/genética , Estados Unidos/epidemiologíaRESUMEN
Since 2013, group A rotavirus strains characterized as novel DS-1-like intergenogroup reassortant "equine-like G3" strains have emerged and spread across 5 continents among human populations in at least 14 countries. Here, we report a novel one-step TaqMan quantitative real-time reverse transcription-PCR assay developed to genotype and quantify the viral load for samples containing rotavirus equine-like G3 strains. Using a universal G forward primer and a newly designed reverse primer and TaqMan probe, we developed and validated an assay with a linear dynamic range of 227 to 2.3 × 109 copies per reaction and a limit of detection of 227 copies. The percent positive agreement, percent negative agreement, and precision of our assay were 100.00%, 99.63%, and 100.00%, respectively. This assay can simultaneously detect and quantify the viral load for samples containing DS-1-like intergenogroup reassortant equine-like G3 strains with high sensitivity and specificity, faster turnaround time, and decreased cost. It will be valuable for high-throughput screening of stool samples collected to monitor equine-like G3 strain prevalence and circulation among human populations throughout the world.
Asunto(s)
Infecciones por Rotavirus , Rotavirus , Animales , Heces , Genotipo , Caballos , Humanos , Filogenia , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Transcripción Reversa , Rotavirus/genética , Infecciones por Rotavirus/diagnóstico , Infecciones por Rotavirus/veterinariaRESUMEN
BACKGROUND: Despite the global roll-out of rotavirus vaccines (RotaTeq/Rotarix / ROTAVAC/Rotasiil), mortality and morbidity due to group A rotavirus (RVA) remains high in sub-Saharan Africa, causing 104,000 deaths and 600,000 hospitalizations yearly. In Cameroon, Rotarix™ was introduced in March 2014, but, routine laboratory diagnosis of rotavirus infection is not yet a common practice, and vaccine effectiveness studies to determine the impact of vaccine introduction have not been done. Thus, studies examining RVA prevalence post vaccine introduction are needed. The study aim was to determine RVA prevalence in severe diarrhoea cases in Littoral region, Cameroon and investigate the role of other diarrheagenic pathogens in RVA-positive cases. METHODS: We carried out a study among hospitalized children < 5 years of age, presenting with acute gastroenteritis in selected hospitals of the Littoral region of Cameroon, from May 2015 to April 2016. Diarrheic stool samples and socio-demographic data including immunization and breastfeeding status were collected from these participating children. Samples were screened by ELISA (ProSpecT™ Rotavirus) for detection of RVA antigen and by gel-based RT-PCR for detection of the VP6 gene. Co-infection was assessed by multiplexed molecular detection of diarrheal pathogens using the Luminex xTAG GPP assay. RESULTS: The ELISA assay detected RVA antigen in 54.6% (71/130) of specimens, with 45, positive by VP6 RT-PCR and 54, positive using Luminex xTAG GPP. Luminex GPP was able to detect all 45 VP6 RT-PCR positive samples. Co-infections were found in 63.0% (34/54) of Luminex positive RVA infections, with Shigella (35.3%; 12/34) and ETEC (29.4%; 10/34) detected frequently. Of the 71 ELISA positive RVA cases, 57.8% (41/71) were fully vaccinated, receiving two doses of Rotarix. CONCLUSION: This study provides insight on RVA prevalence in Cameroon, which could be useful for post-vaccine epidemiological studies, highlights higher than expected RVA prevalence in vaccinated children hospitalized for diarrhoea and provides the trend of RVA co-infection with other enteric pathogens. RVA genotyping is needed to determine circulating rotavirus genotypes in Cameroon, including those causing disease in vaccinated children.
Asunto(s)
Antígenos Virales/aislamiento & purificación , Proteínas de la Cápside/aislamiento & purificación , Coinfección/epidemiología , Diarrea/virología , Infecciones por Rotavirus/epidemiología , Rotavirus/genética , Bioensayo , Camerún/epidemiología , Niño Hospitalizado , Preescolar , Coinfección/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , Masculino , Prevalencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Infecciones por Rotavirus/diagnóstico , Infecciones por Rotavirus/tratamiento farmacológico , Vacunas contra Rotavirus/uso terapéutico , Vacunación , Vacunas Atenuadas/uso terapéuticoRESUMEN
BACKGROUND: Since 2006, the New Vaccine Surveillance Network has conducted active, population-based surveillance for acute gastroenteritis (AGE) hospitalizations and emergency department (ED) visits in 3 United States counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006 to 2016. METHODS: Childrenâ <â 3 years of age hospitalized or visiting the ED with AGE were enrolled from January 2006 through June 2016. Bulk stool specimens were collected and tested for rotavirus. Rotavirus-associated hospitalization and ED visit rates were calculated annually with 2006-2007 defined as the prevaccine period and 2008-2016 as the postvaccine period. Rotavirus genotype trends were compared over time. RESULTS: Over 11 seasons, 6954 children with AGE were enrolled and submitted a stool specimen (2187 hospitalized and 4767 in the ED). Comparing pre- and postvaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). In the postvaccine era, a biennial pattern of rotavirus rates was observed, with a trend toward an older median age. G1P[8] (63%) was the predominant genotype in the prevaccine period with a significantly lower proportion (7%) in the postvaccine period (Pâ <â .001). G2P[4] remained stable (8% to 14%) in both periods, whereas G3P[8] and G12P[8] increased in proportion from pre- to postvaccine periods (1% to 25% and 17% to 40%), respectively. CONCLUSIONS: The epidemiology and disease burden of rotavirus has been altered by rotavirus vaccination with a biennial disease pattern, sustained low rates of rotavirus in childrenâ <â 3 years of age, and a shift in the residual genotypes from G1P[8] to other genotypes.
Asunto(s)
Gastroenteritis , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Niño , Heces , Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Genotipo , Hospitalización , Humanos , Lactante , Rotavirus/genética , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , Estados Unidos/epidemiología , Espera VigilanteRESUMEN
In 2011, ticks were collected from livestock following an outbreak of Crimean Congo hemorrhagic fever (CCHF) in Gujarat state, India. CCHF-negative Hyalomma anatolicum tick pools were passaged for virus isolation, and two virus isolates were obtained, designated Karyana virus (KARYV) and Kundal virus (KUNDV), respectively. Traditional reverse transcription-PCR (RT-PCR) identification of known viruses was unsuccessful, but a next-generation sequencing (NGS) approach identified KARYV and KUNDV as viruses in the Reoviridae family, Orbivirus and Coltivirus genera, respectively. Viral genomes were de novo assembled, yielding 10 complete segments of KARYV and 12 nearly complete segments of KUNDV. The VP1 gene of KARYV shared a most recent common ancestor with Wad Medani virus (WMV), strain Ar495, and based on nucleotide identity we demonstrate that it is a novel WMV strain. The VP1 segment of KUNDV shares a common ancestor with Colorado tick fever virus, Eyach virus, Tai Forest reovirus, and Tarumizu tick virus from the Coltivirus genus. Based on VP1, VP6, VP7, and VP12 nucleotide and amino acid identities, KUNDV is proposed to be a new species of Coltivirus Electron microscopy supported the classification of KARYV and KUNDV as reoviruses and identified replication morphology consistent with other orbi- and coltiviruses. The identification of novel tick-borne viruses carried by the CCHF vector is an important step in the characterization of their potential role in human and animal pathogenesis.IMPORTANCE Ticks and mosquitoes, as well Culicoides, can transmit viruses in the Reoviridae family. With the help of next-generation sequencing (NGS), previously unreported reoviruses such as equine encephalosis virus, Wad Medani virus (WMV), Kammavanpettai virus (KVPTV), and, with this report, KARYV and KUNDV have been discovered and characterized in India. The isolation of KUNDV and KARYV from Hyalomma anatolicum, which is a known vector for zoonotic pathogens, such as Crimean Congo hemorrhagic fever virus, Babesia, Theileria, and Anaplasma species, identifies arboviruses with the potential to transmit to humans. Characterization of KUNDV and KARYV isolated from Hyalomma ticks is critical for the development of specific serological and molecular assays that can be used to determine the association of these viruses with disease in humans and livestock.
Asunto(s)
Coltivirus/clasificación , Coltivirus/aislamiento & purificación , Virus de la Fiebre Hemorrágica de Crimea-Congo/aislamiento & purificación , Fiebre Hemorrágica de Crimea/complicaciones , Orbivirus/clasificación , Orbivirus/aislamiento & purificación , Filogenia , Garrapatas/virología , Animales , Chlorocebus aethiops , Coltivirus/genética , Culicidae/virología , Genoma Viral , Virus de la Fiebre Hemorrágica de Crimea-Congo/clasificación , Virus de la Fiebre Hemorrágica de Crimea-Congo/genética , Fiebre Hemorrágica de Crimea/epidemiología , Fiebre Hemorrágica de Crimea/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , India , Mosquitos Vectores/virología , Orbivirus/genética , Reoviridae/clasificación , Reoviridae/genética , Reoviridae/aislamiento & purificación , Reoviridae/ultraestructura , Células Vero , Ensayo de Placa Viral , Proteínas Virales/genéticaRESUMEN
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.
Asunto(s)
Antígenos Virales/genética , Proteínas de la Cápside/genética , Infecciones por Rotavirus/virología , Vacunas contra Rotavirus/inmunología , Rotavirus/clasificación , Antígenos Virales/inmunología , Proteínas de la Cápside/inmunología , Preescolar , Técnicas de Genotipaje , Humanos , Lactante , Filogenia , Vigilancia de la Población , Rotavirus/genética , Rotavirus/inmunología , Infecciones por Rotavirus/prevención & control , Análisis de Secuencia de ARN , Estados UnidosRESUMEN
Group A Rotaviruses (RVAs) are the most important etiological agents of acute gastroenteritis (AGE) in children less than 5 years of age. Mortality resulting from RVA gastroenteritis is higher in developing countries than in developed ones, causing a huge public health burden in global regions like Africa and South-East Asia. This study reports RVA genotypes detected in Ashaiman, Greater Accra Region, Ghana, in the postvaccine introduction era for the period 2014-2016. Stool samples were collected from children less than 5 years of age who visited Ashaiman Polyclinic with AGE from November 2014 to May 2015 and from December 2015 to June 2016. The samples were tested by enzyme immunoassay (EIA), and one-step multiplex reverse transcription polymerase chain reaction was performed on the EIA positive samples for gel-based binomial genotyping. Of the 369 stool samples collected from children with AGE, 145 (39%) tested positive by EIA. Five VP7 (G1, G3, G9, G10, and G12) and three VP4 (P[4], P[6] and P[8]) genotypes were detected. Eight G/P combinations were identified of which, G3P[6], G12P[8], G1P[8], and G9P[4] were the most prevalent and responsible for 93 (68%) of the AGE cases, and seven mixed-types were detected which represented 8% of the RVA cases. High prevalence, diversity, and mixed-types of RVAs were detected from Ashaiman with the emergence of unusual genotypes.
Asunto(s)
Heces/virología , Gastroenteritis/virología , Genotipo , Infecciones por Rotavirus/epidemiología , Rotavirus/genética , Animales , Preescolar , Gastroenteritis/epidemiología , Ghana/epidemiología , Humanos , Lactante , Filogenia , Prevalencia , ARN Viral/genética , Infecciones por Rotavirus/transmisión , Infecciones por Rotavirus/virología , Análisis de Secuencia de ADN , Zoonosis/epidemiología , Zoonosis/virologíaRESUMEN
BACKGROUND: Although first detected in animals, the rare rotavirus strain G10P[14] has been sporadically detected in humans in Slovenia, Thailand, United Kingdom and Australia among other countries. Earlier studies suggest that the strains found in humans resulted from interspecies transmission and reassortment between human and bovine rotavirus strains. OBJECTIVES: In this study, a G10P[14] rotavirus genotype detected in a human stool sample in Honduras during the 2010-2011 rotavirus season, from an unvaccinated 30-month old boy who reported at the hospital with severe diarrhea and vomiting, was characterised to determine the possible evolutionary origin of the rare strain. METHODS: For the sample detected as G10P[14], 10% suspension was prepared and used for RNA extraction and sequence independent amplification. The amplicons were sequenced by next-generation sequencing using the Illumina MiSeq 150 paired end method. The sequence reads were analysed using CLC Genomics Workbench 6.0 and phylogenetic trees were constructed using PhyML version 3.0. FINDINGS: The next generation sequencing and phylogenetic analyses of the 11-segmented genome of the G10P[14] strain allowed classification as G10-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. Six of the genes (VP1, VP2, VP3, VP6, NSP2 and NSP4) were DS-1-like. NSP1 and NSP5 were AU-1-like and NSP3 was T6, which suggests that multiple reassortment events occurred in the evolution of the strain. The phylogenetic analyses and genetic distance calculations showed that the VP7, VP4, VP6, VP1, VP3, NSP1, NSP3 and NSP4 genes clustered predominantly with bovine strains. NSP2 and VP2 genes were most closely related to simian and human strains, respectively, and NSP5 was most closely related to a rhesus strain. MAIN CONCLUSIONS: The genetic characterisation of the G10P[14] strain from Honduras suggests that its genome resulted from multiple reassortment events which were possibly mediated through interspecies transmissions.
Asunto(s)
Virus Reordenados/genética , Infecciones por Rotavirus/virología , Rotavirus/genética , Preescolar , Heces/virología , Genoma Viral , Genotipo , Honduras , Humanos , Masculino , ARN Viral/genética , Rotavirus/aislamiento & purificación , Infecciones por Rotavirus/diagnósticoRESUMEN
We report the genome of a novel human triple-recombinant G4P[6-8_R] mono-reassortant strain identified in a stool sample from the Dominican Republic during routine facility-based rotavirus strain surveillance. The strain was designated as RVA/Human-wt/DOM/2013840364/2013/G4P[6-8_R], with a genomic constellation of G4-P[6-8_R]-I1-R1-C1-M1-(A1-A8_R)-N1-(T1-T7_R)-E1-H1. Recombinant gene segments NSP1 and NSP3 were generated as a result of recombination between genogroup 1 rotavirus A1 human strain and a genotype A8 porcine strain and between genogroup 1 rotavirus T1 human strain and a genotype T7 bovine strain, respectively. Analyses of the RNA secondary structures of gene segment VP4, NSP1 and NSP3 showed that all the recombinant regions appear to start in a loop (single-stranded) region and terminate in a stem (double-stranded) structure. Also, the VP7 gene occupied lineage VII within the G4 genotypes consisting of mostly porcine or porcine-like G4 strains, suggesting the occurrence of reassortment. The remaining gene segments clustered phylogenetically with genogroup 1 strains. This exchange of whole or partial genetic materials between rotaviruses by recombination and reassortment contributes directly to their diversification, adaptation and evolution.
Asunto(s)
Gastroenteritis/virología , Genoma Viral , Virus Reordenados/genética , Recombinación Genética , Infecciones por Rotavirus/virología , Rotavirus/genética , Adaptación Fisiológica/genética , Animales , Bovinos/virología , República Dominicana , Monitoreo Epidemiológico , Evolución Molecular , Heces/virología , Gastroenteritis/veterinaria , Variación Genética , Genómica , Genotipo , Humanos , Familia de Multigenes , Conformación de Ácido Nucleico , Filogenia , ARN Viral/química , ARN Viral/genética , Virus Reordenados/clasificación , Rotavirus/clasificación , Rotavirus/aislamiento & purificación , Análisis de Secuencia de ADN , Porcinos/virología , Proteínas no Estructurales Virales/genéticaRESUMEN
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.
Asunto(s)
Genotipo , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Vacunas contra Rotavirus/administración & dosificación , Rotavirus/clasificación , Rotavirus/aislamiento & purificación , Niño , Preescolar , Monitoreo Epidemiológico , Femenino , Humanos , Lactante , Masculino , Rotavirus/genética , Infecciones por Rotavirus/prevención & control , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Botswana introduced monovalent G1P rotavirus vaccine (RV1) in July 2012, providing one of the first opportunities to assess the effectiveness of routine RV1 vaccination in a high-burden setting in Africa. We sought to determine the effectiveness of RV1 against rotavirus diarrhea hospitalization using a case-control evaluation. METHODS: Vaccine age-eligible children <5 years of age admitted with diarrhea at 4 hospitals in Botswana were enrolled from June 2013 to April 2015. Card-confirmed vaccine history was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and nonrotavirus "test-negative" diarrhea controls. Vaccine effectiveness (VE) was computed using unconditional logistic regression models adjusting for age, birth month/year, and hospital. Sequence-based genotyping was performed on antigen-positive samples. RESULTS: Among 242 case patients and 368 controls, 82% (199/242) and 92% (339/368), respectively, had received ≥1 doses of RV1. Effectiveness of a full series (2 doses) of RV1 against rotavirus diarrhea requiring hospitalization was 54% (95% confidence interval [CI], 23%-73%); 1 dose of RV1 was 48% (95% CI, 1%-72%) effective. Effectiveness was 59% (95% CI, 4%-83%) against rotavirus caused by G2P, the most common (37%) circulating genotype. However, the effectiveness of 2 RV1 doses was significantly higher in children with no undernutrition (VE, 75% [95% CI, 41%-89%]), compared to those with moderate or severe undernutrition (VE, -28% [95% CI, -309% to 60%]) (P= .02). CONCLUSIONS: Routine RV1 vaccination in Botswana showed effectiveness similar to that in clinical trials in Africa, including against a serotype fully heterotypic to the vaccine. Undernutrition may in part explain the lower rotavirus VE in low-income settings.
Asunto(s)
Diarrea/prevención & control , Diarrea/virología , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/inmunología , Botswana/epidemiología , Estudios de Casos y Controles , Preescolar , Diarrea/epidemiología , Heces/virología , Femenino , Genotipo , Hospitalización , Humanos , Lactante , Modelos Logísticos , Masculino , Desnutrición/epidemiología , Estudios Prospectivos , Rotavirus/inmunología , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Vacunas contra Rotavirus/administración & dosificación , Potencia de la Vacuna , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunologíaRESUMEN
OBJECTIVES: The goal of the SURVAC pilot project was to strengthen disease surveillance and response in three countries; Cameroon (CAE), Democratic Republic of the Congo (DRC) and Central African Republic (CAR). METHODS: Seven laboratories involved in rotavirus surveillance were provided with equipment, reagents and supplies. CDC and WHO staff provided on-site classroom and bench training in biosafety, quality assurance, quality control (QC), rotavirus diagnosis using Enzyme Immunoassay (EIA) and genotyping of rotavirus strains using the Reverse Transcription Polymerase-chain reaction (RT-PCR). All laboratory data were reported through WHO/AFRO. RESULTS: Twenty-three staff members were trained on RT-PCR for rotavirus genotyping which was introduced for the first time in all three countries. In CAE, the number of samples analysed by EIA and RT-PCR increased tenfold between 2007 and 2013. In DRC, this number increased fivefold, from 2009 to 2013 whereas in CAR, it increased fourfold between 2011 and 2013. All laboratories passed WHO proficiency testing in 2014. CONCLUSION: Laboratory capacity was strengthened through equipping laboratories and strengthening a subregional laboratory workforce for surveillance of rotavirus gastroenteritis. Each of the three countries generated rotavirus surveillance and genotyping data enabling the mapping of circulating genotypes. These results will help monitor the impact of rotavirus vaccination in these countries.
RESUMEN
BACKGROUND: Rotavirus infection in adults is poorly understood and few rotavirus outbreaks among US adults have been reported in the literature. We describe an outbreak due to genotype G12P[8] rotavirus among medical students, faculty, and guests who attended a formal dinner event in April 2013. METHODS: A web-based questionnaire was distributed to event attendees to collect symptom and exposure data. A clinical case was defined as a person who developed diarrhea after attending the formal event. A laboratory-confirmed case was defined as a clinical case who attended the formal event, with rotavirus detected in stool by enzyme immunoassay or reverse transcription-polymerase chain reaction (RT-PCR) assay. RESULTS: Among 334 dinner attendees, 136 (41%) completed the web-based questionnaire; 58 (43%) respondents reported illness. Symptom onset ranged from 1 to 8 days, with peak onset 3 days after the event. In addition to diarrhea, predominant symptoms included fever (91%), abdominal pain (84%), and vomiting (49%). The median duration of illness was 2.5 days. Thirteen (22%) of 58 cases sought medical attention; none were hospitalized. Analysis of food exposures among questionnaire respondents did not identify significant associations between any specific food or drink item and illness. Stool specimens were negative for bacterial pathogens by culture and negative for norovirus by RT-PCR assay; 4 specimens were positive for rotavirus by enzyme immunoassay or PCR. G12P[8]-R1-C1-M1-A1-N1-T1-E1-H1 was identified as the causative full-genome genotype. CONCLUSIONS: Rotavirus outbreaks can occur among adults, including young adults. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults.
Asunto(s)
Diarrea/epidemiología , Brotes de Enfermedades , Gastroenteritis/epidemiología , Genotipo , Infecciones por Rotavirus/epidemiología , Rotavirus/clasificación , Rotavirus/genética , Adulto , Diarrea/patología , Diarrea/virología , Heces/virología , Femenino , Enfermedades Transmitidas por los Alimentos/epidemiología , Enfermedades Transmitidas por los Alimentos/patología , Enfermedades Transmitidas por los Alimentos/virología , Gastroenteritis/patología , Gastroenteritis/virología , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rotavirus/aislamiento & purificación , Infecciones por Rotavirus/patología , Infecciones por Rotavirus/virología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
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.
Asunto(s)
Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Antígenos Virales/análisis , Niño , Preescolar , Servicios Médicos de Urgencia , Ensayo de Inmunoadsorción Enzimática , Monitoreo Epidemiológico , Heces/virología , Femenino , Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Genotipo , Hospitalización , Humanos , Lactante , Masculino , ARN Viral/genética , Resultado del Tratamiento , Estados Unidos/epidemiología , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunologíaRESUMEN
UNLABELLED: Group A rotaviruses (RVs) remain a leading cause of childhood gastroenteritis worldwide. Although the G/P types of locally circulating RVs can vary from year to year and differ depending upon geographical location, those with G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and G12P[8] specificities typically dominate. Little is known about the evolution and diversity of G2P[4] RVs and the possible role that widespread vaccine use has had on their increased frequency of detection. To address these issues, we analyzed the 12 G2P[4] RV isolates associated with a rise in RV gastroenteritis cases at Vanderbilt University Medical Center (VUMC) during the 2010-2011 winter season. Full-genome sequencing revealed that the isolates had genotype 2 constellations typical of DS-1-like viruses (G2P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2). Phylogenetic analyses showed that the genome segments of the isolates were comprised of two or three different subgenotype alleles; this enabled recognition of three distinct clades of G2P[4] viruses that caused disease at VUMC in the 2010-2011 season. Although the three clades cocirculated in the same community, there was no evidence of interclade reassortment. Bayesian analysis of 328 VP7 genes of G2 viruses isolated in the last 39 years indicate that existing G2 VP7 gene lineages continue to evolve and that novel lineages, as represented by the VUMC isolates, are constantly being formed. Moreover, G2 lineages are characteristically shaped by lineage turnover events that introduce new globally dominant strains every 7 years, on average. The ongoing evolution of G2 VP7 lineages may give rise to antigenic changes that undermine vaccine effectiveness in the long term. IMPORTANCE: Little is known about the diversity of cocirculating G2 rotaviruses and how their evolution may undermine the effectiveness of rotavirus vaccines. To expand our understanding of the potential genetic range exhibited by rotaviruses circulating in postvaccine communities, we analyzed part of a collection of rotaviruses recovered from pediatric patients in the United States from 2010 to 2011. Examining the genetic makeup of these viruses revealed they represented three segregated groups that did not exchange genetic material. The distinction between these three groups may be explained by three separate introductions. By comparing a specific gene, namely, VP7, of the recent rotavirus isolates to those from a collection recovered from U.S. children between 1974 and 1991 and other globally circulating rotaviruses, we were able to reconstruct the timing of events that shaped their ancestry. This analysis indicates that G2 rotaviruses are continuously evolving, accumulating changes in their genetic material as they infect new patients.
Asunto(s)
Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Rotavirus/clasificación , Rotavirus/genética , Centros Médicos Académicos , Preescolar , Análisis por Conglomerados , Evolución Molecular , Gastroenteritis/epidemiología , Gastroenteritis/virología , Genoma Viral , Genotipo , Humanos , Lactante , Recién Nacido , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , Rotavirus/aislamiento & purificación , Análisis de Secuencia de ADN , Tennessee/epidemiologíaRESUMEN
Group A rotaviruses (RVAs) are the leading cause of severe gastroenteritis and eventually death among infants and young children worldwide, and disease prevention and management through vaccination is a public health priority. In August 2009, Rotarix™ was introduced in the South African Expanded Programme on Immunisation. As a result, substantial reductions in RVA disease burden have been reported among children younger than 5 years old. Rotavirus strain surveillance post-vaccination is crucial to, inter alia, monitor and study the evolution of vaccine escape strains. Here, full-genome sequence data for the 11 gene segments from 11 South African G1P[8] rotavirus strains were generated, including 5 strains collected from non-vaccinated children during the 2004-2009 rotavirus seasons and 6 strains collected from vaccinated children during the 2010 rotavirus season. These data were analyzed to gain insights into the overall genetic makeup and evolution of South African G1P[8] rotavirus strains and to compare their genetic backbones with those of common human Wa-like RVAs from other countries, as well as with the Rotarix™ and RotaTeq™ G1P[8] vaccine components. All 11 South African G1P[8] strains revealed a complete Wa-like genotype constellation of G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. On the basis of sequence similarities, the South African G1P[8] strains (with the exception of strain RVA/Human-wt/ZAF/1262/2004/G1P[8]) were closely related to each other (96-100% identity in all gene segments). Comparison to the Rotarix™ and RotaTeq™ G1P[8] vaccine components revealed a moderate nucleotide identity of 89-96% and 93-95%, respectively. The results indicated that none of the gene segments of these 11 South African G1P[8] strains were vaccine-derived. This study illustrates that large-scale next generation sequencing will provide crucial information on the influence of the vaccination program on evolution of rotavirus strains. This is the first report to describe full genomic analyses of G1P[8] RVA strains collected from both non-vaccinated and vaccinated children in South Africa.
Asunto(s)
Diarrea/virología , Genoma Viral , ARN Viral/genética , Rotavirus/genética , Rotavirus/aislamiento & purificación , Análisis de Secuencia de ADN , Preescolar , Análisis por Conglomerados , Femenino , Genotipo , Humanos , Lactante , Masculino , Filogenia , Rotavirus/clasificación , Homología de Secuencia , SudáfricaRESUMEN
Group A rotaviruses (RVAs) with distinct G and P genotype combinations have been reported globally. We report the genome composition and possible origin of seven G8P[4] and five G2P[4] human RVA strains based on the genetic evolution of all 11 genome segments at the nucleotide level. Twelve RVA ELISA positive stool samples collected in the representative countries of Eastern, Southern and West Africa during the 2007-2012 surveillance seasons were subjected to sequencing using the Ion Torrent PGM and Illumina MiSeq platforms. A reference-based assembly was performed using CLC Bio's clc_ref_assemble_long program, and full-genome consensus sequences were obtained. With the exception of the neutralising antigen, VP7, all study strains exhibited the DS-1-like genome constellation (P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2) and clustered phylogenetically with reference strains having a DS-1-like genetic backbone. Comparison of the nucleotide and amino acid sequences with selected global cognate genome segments revealed nucleotide and amino acid sequence identities of 81.7-100 % and 90.6-100 %, respectively, with NSP4 gene segment showing the most diversity among the strains. Bayesian analyses of all gene sequences to estimate the time of divergence of the lineage indicated that divergence times ranged from 16 to 44 years, except for the NSP4 gene where the lineage seemed to arise in the more distant past at an estimated 203 years ago. However, the long-term effects of changes found within the NSP4 genome segment should be further explored, and thus we recommend continued whole-genome analyses from larger sample sets to determine the evolutionary mechanisms of the DS-1-like strains collected in Africa.
Asunto(s)
Variación Genética , Genoma Viral , ARN Viral/genética , Infecciones por Rotavirus/virología , Rotavirus/genética , Análisis de Secuencia de ADN , África Oriental , África Austral , África Occidental , Análisis por Conglomerados , Heces/virología , Genotipo , Humanos , Datos de Secuencia Molecular , Filogenia , Rotavirus/aislamiento & purificación , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoRESUMEN
Respiratory syncytial virus (RSV) is the most predominant viral pathogen worldwide in children with lower respiratory tract infections. The Coronavirus disease 2019 (COVID-19) pandemic and resulting nonpharmaceutical interventions perturbed the transmission pattern of respiratory pathogens in South Africa. A seasonality shift and RSV resurgence was observed in 2020 and 2021, with several infected children observed. Conventional RSV-positive nasopharyngeal swabs were collected from various hospitals in the Free State province, Bloemfontein, South Africa, from children suffering from respiratory distress and severe acute respiratory infection between 2020 to 2021. Overlapping genome fragments were amplified and complete genomes were sequenced using the Illumina MiSeq platform. Maximum likelihood phylogenetic and evolutionary analysis were performed on both RSV-A/-B G-genes with published reference sequences from GISAID and GenBank. Our study strains belonged to the RSV-A GA2.3.2 and RSV-B GB5.0.5a clades. The upsurge of RSV was due to pre-existing strains that predominated in South Africa and circulating globally also driving these off-season RSV outbreaks during the COVID-19 pandemic. The variants responsible for the resurgence were phylogenetically related to pre-pandemic strains and could have contributed to the immune debt resulting from pandemic imposed restrictions. The deviation of the RSV season from the usual pattern affected by the COVID-19 pandemic highlights the need for ongoing genomic surveillance and the identification of genetic variants to prevent unforeseen outbreaks in the future.