Long-term Consistency in Rotavirus Vaccine Protection: RV5 and RV1 Vaccine Effectiveness in US Children, 2012-2013.

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.

Effect of monovalent rotavirus vaccine on rotavirus disease burden and circulating rotavirus strains among children in Morocco.

Rotarix(TM) vaccine was introduced into the National Program of Immunization of Morocco in October 2010, reaching quickly 87% of the target population of children nationally. The incidence of rotavirus gastroenteritis and the prevalence of circulating rotavirus strains has been monitored in three sentinel hospitals since June 2006. The average percentage of rotavirus positive cases among all children under 5 years old hospitalized for gastroenteritis during the pre-vaccine period (2006-2010) was 44%.

Comparative genomic analysis of genogroup 1 (Wa-like) rotaviruses circulating in the USA, 2006-2009.

Group A rotaviruses (RVA) are double stranded RNA viruses that are a significant cause of acute pediatric gastroenteritis. Beginning in 2006 and 2008, respectively, two vaccines, Rotarix™ and RotaTeq®, have been approved for use in the USA for prevention of RVA disease. The effects of possible vaccine pressure on currently circulating strains in the USA and their genome constellations are still under investigation.

Full genomic characterization of a novel genotype combination, G4P[14], of a human rotavirus strain from Barbados.

Since 2004, the Pan American Health Organization (PAHO) has carried out rotavirus surveillance in Latin America and the Caribbean. Here we report the characterization of human rotavirus with the novel G-P combination of G4P[14], detected through PAHO surveillance in Barbados. Full genome sequencing of strain RVA/Human-wt/BRB/CDC1133/2012/G4P[14] revealed that its genotype is G4-P[14]-I1-R1-C1-M1-A8-N1-T1-E1-H1.

Rotavirus genotypes in Belarus, 2008-2012.

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.

Approach to molecular characterization of partially and completely untyped samples in an Indian rotavirus surveillance program.

Surveillance networks for rotavirus document the burden of the disease using the proportion of children hospitalized with gastroenteritis positive for rotavirus by enzyme immunoassay. They also describe genotypes of circulating viruses by polymerase chain reaction for the VP7 and VP4 genes, which determine G and P types, respectively. A proportion of samples cannot be genotyped based on initial testing and laboratories need to assess further testing strategies based on resources and feasibility.

WHO global rotavirus surveillance network: a strategic review of the first 5 years, 2008-2012.

Since 2008, the World Health Organization (WHO) has coordinated the Global Rotavirus Surveillance Network, a network of sentinel surveillance hospitals and laboratories that report to ministries of health (MoHs) and WHO clinical features and rotavirus testing data for children aged <5 years hospitalized with acute gastroenteritis. In 2013, WHO conducted a strategic review to assess surveillance network performance, provide recommendations for strengthening the network, and assess the network's utility as a platform for other vaccine-preventable disease surveillance. The strategic review team determined that during 2011 and 2012, a total of 79 sites in 37 countries met reporting and testing inclusion criteria for data analysis.

Real-time RT-PCR assays to differentiate wild-type group A rotavirus strains from Rotarix(®) and RotaTeq(®) vaccine strains in stool samples.

Group A rotaviruses (RVA) are the leading cause of severe diarrhea in young children worldwide. Two live-attenuated RVA vaccines, Rotarix(®) and RotaTeq(®) are recommended by World Health Organization (WHO) for routine immunization of all infants. Rotarix(®) and RotaTeq(®) vaccines have substantially reduced RVA associated mortality but occasionally have been associated with acute gastroenteritis (AGE) cases identified in vaccinees and their contacts.

Genetic analysis of G12P[8] rotaviruses detected in the largest U.S. G12 genotype outbreak on record.

In 2006-07, 77 cases of gastroenteritis in Rochester, NY, USA were associated with rotavirus genotype G12P[8]. Sequence analysis identified a high degree of genetic relatedness among the VP7 and VP4 genes of the Rochester G12P[8] strains and between these strains and currently circulating human G12P[8] strains. Out of 77 samples, two and seven unique nucleotide sequences were identified for VP7 and VP4 genes, respectively.

Diagnostic performance of rectal swab versus bulk stool specimens for the detection of rotavirus and norovirus: implications for outbreak investigations.

Background: In January of 2008, during the peak of the rotavirus season in Guatemala, a gastroenteritis outbreak with high mortality among infants was reported in Guatemala. Despite extensive efforts, the investigation was limited by the lack of bulk stool specimens collected, particularly from the more severely dehydrated or deceased children.

Objectives: We evaluated the diagnostic performance of rectal swab specimens compared with bulk stool for the detection of rotavirus and norovirus.

Detection of PCV-2 DNA in stool samples from infants vaccinated with RotaTeq®.

Rotarix® and RotaTeq® vaccines have led to a dramatic reduction in rotavirus disease worldwide. However, the detection of porcine circovirus type 1 (PCV-1) and 2 (PCV-2) DNA in these vaccines raised some safety concerns. Studies examining shedding of rotavirus in stool from rotavirus vaccine recipients have been performed but no published data exist regarding the shedding of PCV virus in stools of vaccinees.

Comparison of 2 assays for diagnosing rotavirus and evaluating vaccine effectiveness in children with gastroenteritis.

We compared rotavirus detection rates in children with acute gastroenteritis (AGE) and in healthy controls using enzyme immunoassays (EIAs) and semiquantitative real-time reverse transcription PCR (qRT-PCR). We calculated rotavirus vaccine effectiveness using different laboratory-based case definitions to determine which best identified the proportion of disease that was vaccine preventable. Of 648 AGE patients, 158 (24%) were EIA positive, and 157 were also qRT-PCR positive.

Detection of novel rotavirus strain by vaccine postlicensure surveillance.

Surveillance for rotavirus-associated diarrhea after implementation of rotavirus vaccination can assess vaccine effectiveness and identify disease-associated genotypes. During active vaccine postlicensure surveillance in the United States, we found a novel rotavirus genotype, G14P[24], in a stool sample from a child who had diarrhea. Unusual rotavirus strains may become more prevalent after vaccine implementation.

Sensitive and specific quantitative detection of rotavirus A by one-step real-time reverse transcription-PCR assay without antecedent double-stranded-RNA denaturation.

A real-time quantitative reverse transcription-PCR (qRT-PCR) assay using the recombinant thermostable Thermus thermophilus (rTth) enzyme was developed to detect and quantify rotavirus A (RVA). By using rTth polymerase, significant improvement was achieved over the existing real-time RT-PCR assays, which require denaturation of the RVA double-stranded RNA (dsRNA) prior to assay setup. Using a dsRNA transcript for segment 7, which encodes the assay target NSP3 gene, the limit of detection for the improved assay was calculated to be approximately 1 genome copy per reaction.

One year survey of human rotavirus strains suggests the emergence of genotype G12 in Cameroon.

In this study the emergence of rotavirus A genotype G12 in children <5 years of age is reported from Cameroon during 2010/2011. A total of 135 human stool samples were P and G genotyped by reverse transcriptase PCR. Six different rotavirus VP7 genotypes were detected, including G1, G2, G3, G8, G9, and G12 in combinations with P[4], P[6] and P[8] VP4 genotypes.

Diversity of circulating rotavirus strains in children hospitalized with diarrhea in India, 2005-2009.

Background: India accounts for 22% of the 453,000 global rotavirus deaths among children <5 years annually. The Indian Rotavirus Strain Surveillance Network provides clinicians and public health partners with valuable rotavirus disease surveillance data. Our analysis offers policy-makers an update on rotavirus disease burden with emphasis on regional shifts in rotavirus strain epidemiology in India.

Effectiveness of pentavalent and monovalent rotavirus vaccines in concurrent use among US children <5 years of age, 2009-2011.

Background: We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) visits in US children.

Methods: We enrolled children <5 years of age hospitalized or visiting the ED with AGE symptoms from November 2009-June 2010 and from November 2010-June 2011 at 7 medical institutions. Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped.

Dose sparing and enhanced immunogenicity of inactivated rotavirus vaccine administered by skin vaccination using a microneedle patch.

Skin immunization is effective against a number of infectious diseases, including smallpox and tuberculosis, but is difficult to administer. Here, we assessed the use of an easy-to-administer microneedle (MN) patch for skin vaccination using an inactivated rotavirus vaccine (IRV) in mice. Female inbred BALB/c mice in groups of six were immunized once in the skin using MN coated with 5 μg or 0.

Symptomatic infection and detection of vaccine and vaccine-reassortant rotavirus strains in 5 children: a case series.

Vaccine or vaccine-reassortant rotavirus strains were detected in fecal specimens from 5 of 106 (4.7%) immunocompetent children who required treatment for rotavirus gastroenteritis at a large pediatric hospital in Texas in 2009-2010. Four strains were related to pentavalent rotavirus vaccine, whereas one was related to monovalent rotavirus vaccine.

Systematic review of regional and temporal trends in global rotavirus strain diversity in the pre rotavirus vaccine era: insights for understanding the impact of rotavirus vaccination programs.

Recently, two rotavirus vaccines have been recommended for routine immunization of infants worldwide. These vaccines proved efficacious during clinical trials and field use in both developing and developed countries, and appear to provide good protection against a range of rotavirus genotypes, including some that are not included in the vaccines. However, since conclusive data that the vaccines will protect against a wide variety of rotavirus strains are still lacking and since vaccines may exert some selection pressure, a detailed picture of global strain prevalence from the pre-rotavirus vaccine era is important to evaluate any potential changes in circulating strains observed after widespread introduction of rotavirus vaccines.

Identification of porcine rotavirus-like genotype P[6] strains in Taiwanese children.

The molecular characterization of genotype P[6] rotavirus strains collected from children admitted to hospital with acute dehydrating diarrhoea during a 6-year surveillance period in Taiwan is described in this study. In total, three G4P[6] strains, one G5P[6] and one G12P[6] were characterized by sequencing and phylogenetic analysis of the VP4, VP7, VP6 and NSP4 genes. Whilst all four genes of the single Taiwanese G12P[6] strain clustered with the respective genes of globally common human rotavirus strains, the G4 and G5 strains showed remarkable similarities to porcine rotavirus strains and putative porcine-origin human P[19] strains reported previously from Taiwan.

Remaining issues and challenges for rotavirus vaccine in preventing global childhood diarrheal morbidity and mortality.

Rotavirus vaccines have had a dramatic impact on morbidity and mortality from diarrhea among children in high- and middle-income countries that have introduced the vaccine into their national immunization programs. Widespread introduction of rotavirus vaccine in developing countries is imminent and their full potential in reducing the global burden from severe childhood diarrhea may soon be realized. The objectives of this paper are to describe the remaining issues and challenges in ensuring the success of the global rotavirus vaccination program and to discuss further research needed to help address them.

First reports of human rotavirus G8P[4] gastroenteritis in the United States.

In 2009, three children were hospitalized in Rochester, NY, with sequence-confirmed G8P[4] rotavirus gastroenteritis-the first U.S. detection of this uncommon strain more typically found in Africa.