Vaccine Rotarix Research Articles

Diversity of Rotavirus Strains Circulating in Botswana before and after introduction of the Monovalent Rotavirus Vaccine

BackgroundGlobally, rotavirus is the leading cause of acute gastroenteritis (AGE) in children aged <5 years. Botswana introduced the monovalent rotavirus vaccine (Rotarix) in July 2012. To study the impact of this vaccine on rotavirus genotypes circulating in Botswana, a comparison of the genotypes pre-vaccination (2011–2012) and post-vaccination (2013–2018) periods was conducted. Subjects and methodsResidual samples from 284 children <5 years of age that tested positive for rotavirus by enzyme immunoassay were genotyped. One hundred and five samples were from the pre-vaccination period and 179 were from the post-vaccination period. Genotyping was performed using two multiplexed one-step reverse transcription polymerase chain reaction (RT-PCR) assays for the amplification and genotyping of rotavirus VP7 (G) and VP4 (P) genes. ResultsPrior to vaccine introduction, the predominant rotavirus circulating genotypes were G9P[8] (n = 63, 60%) and G1P[8] (n = 22, 21%). During the vaccine period, G2P[4] was the predominant genotype (n = 49, 28%), followed by G9P[8] (n = 40, 22%) and G1P[8] (n = 33, 18.5%). There was a significant decline in the prevalence of G9P[8] (p = 0.001) in the post-vaccination period. There was also a notable decline in G1P[8]. A spike in G2P[4] was observed in 2013, one year post-vaccine introduction. Rotavirus strain G3P[4] (n = 8) was only detected in the post-vaccine introduction period. In 2018 there was a marked increase in genotype G3P[8] (p = 0.0003). ConclusionsThe distribution of circulating rotavirus genotypes in Botswana changed after vaccine implementation. Further studies are needed to examine whether these changes are related to vaccination or simply represent natural secular variation.

Whole genome characterization and evolutionary analysis of OP354-like P[8] Rotavirus A strains isolated from Ghanaian children with diarrhoea.

In 2010, the rare OP354-like P[8]b rotavirus subtype was detected in children less than 2 years old in Ghana. In this follow-up study, to provide insight into the evolutionary history of the genome of Ghanaian P[8]b strains RVA/Human-wt/GHA/GHDC949/2010/G9P[8] and RVA/Human-wt/GHA/GHM0094/2010/G9P[8] detected in an infant and a 7-month old child hospitalised for acute gastroenteritis, we sequenced the complete genome using both Sanger sequencing and Illumina MiSeq technology followed by phylogenetic analysis of the near-full length sequences. Both strains possessed the Wa-like/genotype 1 constellation G9P[8]b-I1-R1-C1-M1-A1-N1-T1-E1-H1. Sequence comparison and phylogenetic inference showed that both strains were identical at the lineage level throughout the 11 genome segments. Their VP7 sequences belonged to the major sub-lineage of the G9-lineage III whereas their VP4 sequences belonged to P[8]b cluster I. The VP7 and VP4 genes of the study strains were closely related to a Senegalese G9P[8]b strain detected in 2009. In the remaining nine genome segments, both strains consistently clustered together with Wa-like RVA strains possessing either P[8]a or P[8]b mostly of African RVA origin. The introduction of a P[8]b subtype VP4 gene into the stable Wa-like strain backbone may result in strains that might propagate easily in the human population, with a potential to become an important public health concern, especially because it is not certain if the monovalent rotavirus vaccine (Rotarix) used in Ghana will be efficacious against such strains. Our analysis of the full genomes of GHM0094 and GHDC949 adds to knowledge of the genetic make-up and evolutionary dynamics of P[8]b rotavirus strains.

Differences in the amino acid composition of the antigen epitopes of the VP7 protein of Russian rotaviruses with the G9 genotype and the vaccine strains RotaTeq, Rotavac, and Rotarix

Introduction. Rotaviruses of group A (RVA) with genotype G9P[8] are a common cause of acute gastroenteritis in children in Russia. In Nizhny Novgorod, the part of G9P[8] among all RVA strains reached 63.1% during 20162017 epidemic season. Two live rotavirus vaccines, RotaTeq and Rotarix have been successfully introduced into the national immunization programs worldwide. In addition, the Indian vaccine Rotavac, based on the strain with G9P[8] genotype, is used on a regional level. The parent strains for all mentioned vaccines were isolated more than 30 years ago. There is no data about phylogenetic analysis and comparative analysis of antigenic epitopes of Russian G9P[8] wild-type isolates and vaccine strains. In the present study, for the first time, we provide a comparative phylogenetic analysis and research of the amino acid composition of the B- and T-cell epitopes of the VP7 protein between Russian rotaviruses with the G9 genotype and the vaccine strains in RotaTeq, Rotarix and Rotavac composition. Materials and methods. The nucleotide and amino acid sequences of the VP7 gene of RVA with genotype G9 were studied. The rotaviruses had been previously isolated from children hospitalized with acute gastroenteritis in the infectious hospital in Nizhny Novgorod during 20112016. Results. A phylogenetic analysis of the nucleotide sequences of the VP7 gene showed that the Nizhny Novgorod strains belong to the G9-III allele. Based on the amino acid sequences VP7, three B-cell epitopes (71a, 71b and 72) and two T-cell epitopes (1628 aa and 4052 aa) were analyzed. The smallest number of substitutions was found in the RotaTeq vaccine registered in Russia: from 0 to 3 aa differences at the epitope. The same (from 0 to 3 aa differences at the epitope) was found between the wild-type strains RVA and the Rotavac vaccine. The largest number of amino acid differences was found between the vaccine strain Rotarix and the Nizhny Novgorod G9 strains (from 3 to 10 aa at the epitope). Conclusion. In the present work, based on nucleotide sequences VP7 gene, we provide phylogenetic and comparative analyses of the amino acid composition of antigenic epitopes of G9 RVA isolated in Russia vs rotavirus strains in vaccines RotaTeq, Rotavac and Rotarix. The accumulation of mutations in antigenic epitopes can help the virus to escape the immune response. Continuous molecular monitoring of wild-type RVA strains is necessary for estimation of the possible impact of vaccines on the genotype diversity of the rotavirus population in the wild and to monitor the emergence of novel antigenic variants.

Immunogenicity and safety of the diphtheria, pertussis, tetanus and inactivated poliovirus vaccine when co-administered with the human rotavirus vaccine (Rotarix) in healthy Japanese infants: a phase IV randomized study

ABSTRACT Rotavirus infections have been reported to account for 40–50% of all hospitalized acute gastroenteritis cases in young children (<5 years) in Japan. Since 2011, Rotarix containing the live attenuated human rotavirus RIX4414 strain (HRV) has been licensed in Japan for infants. Vaccination against rotavirus is optional in Japan whereas administration of diphtheria, pertussis, tetanus, and inactivated poliovirus (DPT-IPV) vaccine is part of the national routine immunization program. In this open-label, randomized, controlled, multicenter study, we evaluated the immunogenicity and safety of the DPT-IPV vaccine (Squarekids) administered concomitantly or staggered with the liquid HRV (Rotarix) vaccine in healthy Japanese infants. A total of 292 infants aged 6–12 weeks were randomly assigned to receive DPT-IPV vaccine and HRV vaccine co-administered (n = 147) or staggered (n = 145). Immune responses to DPT-IPV vaccine were evaluated by measuring the post-vaccination serum antibody titers/concentrations to each antigen at one month following the third dose of DPT-IPV vaccine. Seroprotection/seropositivity against each of the diphtheria, pertussis (pertussis toxin and filamentous hemagglutinin), tetanus, and poliovirus type 1, 2 and 3 antigens was 92.8% or higher in both groups. In terms of immunogenicity, DPT-IPV vaccine co-administered with HRV vaccine was shown to be non-inferior to DPT-IPV vaccine with a staggered administration. The safety profile was comparable in the two vaccine groups with no vaccine-related serious adverse events, no deaths and no cases of intussusception. These results support co-administration of HRV vaccine with DPT-IPV vaccine in Japan. ClinicalTrials.gov NCT02907216

Impact of rotavirus vaccination on rotavirus genotype distribution and diversity in England, September 2006 to August 2016.

IntroductionRotavirus vaccination with the live-attenuated monovalent (a G1P[8] human rotavirus strain) two-dose Rotarix vaccine was introduced in England in July 2013. Since then, there have been significant reductions in rotavirus gastroenteritis incidence.AimWe assessed the vaccine’s impact on rotavirus genotype distribution and diversity 3 years post-vaccine introduction.MethodsEpidemiological and microbiological data on genotyped rotavirus-positive samples between September 2006 and August 2016 were supplied by EuroRotaNet and Public Health England. Multinomial multivariable logistic regression adjusting for year, season and age was used to quantify changes in genotype prevalence in the vaccine period. Genotype diversity was measured using the Shannon’s index (H′) and Simpson’s index of diversity (D).ResultsWe analysed genotypes from 8,044 faecal samples. In the pre-vaccine era, G1P[8] was most prevalent, ranging from 39% (411/1,057) to 74% (527/709) per year. In the vaccine era, G1P[8] prevalence declined each season (35%, 231/654; 12%, 154/1,257; 5%, 34/726) and genotype diversity increased significantly in 6–59 months old children (H’ p < 0.001: D p < 0.001). In multinomial analysis, G2P[4] (adjusted multinomial odds ratio (aMOR): 9.51; 95% confidence interval (CI): 7.02–12.90), G3P[8] (aMOR: 2.83; 95% CI: 2.17–3.81), G12P[8] (aMOR: 2.46; 95% CI: 1.62–3.73) and G4P[8] (aMOR: 1.42; 95% CI: 1.02–1.96) significantly increased relative to G1P[8].ConclusionsIn the context of reduced rotavirus disease incidence, genotype diversity has increased, with a relative change in the dominant genotype from G1P[8] to G2P[4] after vaccine introduction. These changes will need continued surveillance as the number and age of vaccinated birth cohorts increase in the future.

The evolving epidemiology of rotavirus A infection in Brazil a decade after the introduction of universal vaccination with Rotarix\xae

BackgroundBrazil introduced the monovalent rotavirus vaccine (Rotarix®) in 2006. This study aimed to assess the epidemiology and genotype distribution of species-A rotavirus (RVA) in Brazil, comparing the pre- and post-vaccination periods.MethodsLaboratory-based RVA surveillance included 866 municipalities in 22 Brazilian states, over a 21-year period. A total of 16,185 children with diarrheal diseases (DD) aged up to 12 years between 1996 and 2005 (pre-vaccination period, n = 7030) and from 2006 to 2017 (post-vaccination period, n = 9155) were enrolled. RVA was detected using ELISA immune assay and/or polyacrylamide gel electrophoresis and genotyped using nested PCR and/or nucleotide sequencing. RVA-positivity and genotypes detection rates were compared in distinct periods and age groups and Rotarix vaccination status.ResultsRVA-positivity in pre- and post-vaccination periods was, respectively: 4–11 months bracket, 33.3% (668/2006) and 16.3% (415/2547) (p < 0.001); 12–24 months, 28.2% (607/2154) and 22.2% (680/3068) (p < 0.001); 25–48 months, 17.4% (215/1235) and 29.4% (505/1720) (p < 0.001). Genotypes distribution in the pre- and post-vaccination periods was, respectively: G1P [8]/G1P[Not Typed], 417/855 (48.8%) and 118/1835 (6.4%) (p < 0.001); G2P [4]/G2P[NT], 47/855 (5.5%) and 838/1835 (45.7%) (p < 0.001); G3P [8]/G3P[NT], 55/855 (6.4%) and 253/1835 (13.8%) (p < 0.001); G9P [8]/G9P[NT], 238/855 (27.8%) and 152/1835 (8.3%) (p < 0.001); G12P [8]/G129P[NT], 0/871 (0%) and 249/1835(13.6%) (p < 0.001). Concerning infants aged 4–11 months, RVA frequency in fully vaccinated and non-vaccinated individuals was 11.9% (125/1052) and 24.5% (58/237) (p < 0.001), respectively. In children aged 12–24 months, RVA detection rate was 18.1% (253/1395) and 29.6% (77/260) (p < 0.001), for the vaccinated and non-vaccinated individuals, respectively (p < 0.001).ConclusionsRVA infection was significantly less frequent in children aged ≤2 years with DD after implementing vaccination, mainly among vaccinated children. It was also observed a decrease of P [8] circulation and emergence of G2P[4] in 2005, and afterwards in the post-vaccine era, with spreading of G12P[8] in 2014–2015 and of G3P[8] in 2017. Continuous RVA surveillance must be carried out in this scenario.

Projected impact, cost-effectiveness, and budget implications of rotavirus vaccination in Mongolia

IntroductionRotavirus disease in Mongolia is estimated to cause more than 50 deaths yearly and many more cases and hospitalizations. Mongolia must self-finance new vaccines and does not automatically access Gavi prices for vaccines. Given the country’s limited resources for health, it is critical to assess potential new vaccine programs. This evaluation estimates the impact, cost-effectiveness, and budget implications associated with a nationwide rotavirus vaccine introduction targeting infants as part of the national immunization program in Mongolia, in order to inform decision-making around introduction. MethodsThe analysis examines the use of the two-dose vaccine ROTARIX®, and three-dose vaccines ROTAVAC® and RotaTeq® compared to no vaccination from the government and the societal perspective. We use a modelling approach informed by local data and published literature to analyze the impact and cost-effectiveness of rotavirus vaccination over a ten-year time period starting in 2019, using a 3% discount rate. Our main outcome measure is the incremental cost-effectiveness ratio (ICER) expressed as US dollar per DALY averted. We assessed uncertainty around a series of parameters through univariate sensitivity analysis. ResultsRotavirus vaccination in Mongolia could avert more than 95,000 rotavirus cases and 271 deaths, over 10 years. Averted visits and hospitalizations represent US$2.4 million in health care costs saved by the government. The vaccination program cost ranges from $6 to $11 million depending on vaccine choice. From the governmental perspective, ICER ranged from $412 to $1050 and from $77 to $715 when considering the societal perspective. Sensitivity analysis highlights vaccine price as the main driver of uncertainty. ConclusionIntroduction of rotavirus vaccination is likely to be highly cost-effective in Mongolia, with ICERs estimated at only a fraction of Mongolia’s per capita GDP. From an economic standpoint, ROTAVAC® is the least costly and most cost-effective product choice.

Rotavirus VP6 as a potential vaccine candidate.

By the age of 5years, virtually all children have been infected by group A rotavirus (RVA), which is responsible for around half million mortality annually prior to vaccination. Relatively high rate of the morbidity and mortality highlights the necessity of applying preventive procedures particularly in developing countries. Two live attenuated RVA vaccines (Rotarix and RotaTeq) are licensed and now being used in many countries worldwide. Although these vaccines are shown to reduce the mortality up to 50%, several key questions yet remained to answer. Indeed, the licensed RV vaccines were found to be less effective in countries of sub-Saharan Africa and Southeast Asia. Therefore, developing next generation RVA vaccines is warranted. VP6 is highly abundant and conserved protein that forms the middle layer of RV particles and was shown to be both antigenic and immunogenic. Although it does not induce neutralizing antibodies, different VP6 preparations were found to induce homologous and cross-reactive immune responses with partial protection from RVA replication. Although the molecular mechanisms are not fully elucidated, VP6-based RVA vaccine candidates are worthy of further consideration. This review aims to focus on different aspects of VP6 protein and its potentiality for an alternative RV vaccine against RV disease.

Effectiveness of oral rotavirus vaccination in England against rotavirus-confirmed and all-cause acute gastroenteritis

BackgroundThe monovalent oral rotavirus vaccine Rotarix® was introduced into the UK infant immunisation programme in 2013. We estimated vaccine effectiveness (VE) in the first two years of the programme. MethodsWe used a test-negative case-control design and enhanced national surveillance data for 1869 vaccine-eligible children tested for rotavirus infection to obtain adjusted odds ratios and VE against laboratory-confirmed rotavirus infections. Linked anonymised UK primary care and hospitalisation data from the Clinical Practice Research Datalink (40,723 children) and random-effects Poisson regression were used in a cohort study to estimate VE against all-cause acute gastroenteritis (AGE) and AGE hospitalisations. ResultsVE against laboratory-confirmed infection was 69% (95% Confidence Interval: 40–84%) for one dose and 77% (95%CI: 66–85%) for two doses. Two-dose VE in children aged <12 months and ≥12 months was 85% (95%CI: 74–91%) and 54% (95%CI: 15–75%), respectively. In contrast, we found no evidence that the vaccine was effective against all-cause AGE (VE = −20%, 95%CI: −36% to −5%), or against AGE hospitalisations (VE = 35%, 95% CI: −86% to 77%). ConclusionsIn this first detailed assessment of VE of the Rotarix® vaccine in the English national programme, we show that Rotarix® was highly effective in preventing laboratory-confirmed rotavirus infection in young children. This provides reassurance about the vaccine’s performance in real-life settings and gives key information for future cost-effectiveness analyses. The high VE against rotavirus-specific AGE, and the exceptionally successful implementation of the national rotavirus vaccine programme (with >90% vaccine coverage), explains the lack of VE against all-cause AGE because most AGE in the post-vaccine era would not have been due to rotavirus, although some underestimation of VE could also have occurred due to differential healthcare utilisation by vaccinated and unvaccinated infants. This highlights the importance of using specific vaccine-preventable endpoints for these scenarios.

Molecular characterization of G2P[4] and G9P[8] rotaviruses strains isolated from Moroccan children fully vaccinated with Rotarix™ between 2013 and 2014

ABSTRACTBackground: Here, we describe the characterization of the VP7 and VP4 genes of rotavirus group A (RVA) strains isolated from Moroccan infants with acute gastroenteritis (AGE) after receiving the Rotarix.Methods: Stool samples were collected from seven infants suffering with AGE. Vesikari 20-point was used while collecting the AGE information. RT-PCR followed by sequencing was employed to determine partial sequences from VP7 and VP4 encoding genes. RVA genotypes were determined using the RotaC online classification tool.The Neighbor-Joining phylogenetic tree was performed in the MEGA 6.06 software as well as the amino acid (aa) alignments of VP7 and VP8* antigenic epitopes.Results: Five children had gastroenteritis episodes defined as severe on the Vesikari scale. Analysis of VP7 gene sequences revealed five G2 and two G9 genotypes. These genotypes were associated with P[4] and P[8], respectively. Phylogenetic analysis demonstrated that G2 and G9 sequences grouped together with Italian strain belonging to lineage II and III respectively. Their P[4] sequences showed only 65-73% identity and grouped into two separate sub-clusters. The Moroccan P[8] isolates did not display this correlation and segregate to lineage III. The VP8* aa of P[8] when compared with that of the Rotarix vaccine, has a six aa differences.Conclusion: Although, this study does not reveal prevalence rates of RVA in infants after the vaccine introduction, it reports the detection and genetic characteristics of the G2P[4] and G9P[8] RVA types in vaccinated children in Morocco. The findings are suggestive of continuous surveillance program on rotavirus evolution in the vaccinated population.

Prevalence and molecular typing of rotavirus in children with acute diarrhoea in Northeastern Colombia.

ABSTRACTAfter the introduction of the rotavirus vaccine, the number of rotavirus-associated deaths and the predicted annual rotavirus detection rate had slightly declined worldwide. Taking in account that in Colombia, Rotarix vaccine was introduced in 2009, the purpose of this study was to evaluate the presence of rotavirus A in children under five years who were treated for acute diarrhoea in Bucaramanga, Colombia and, moreover, to determine the genotypes of rotavirus present in those children. We performed an analytical cross-sectional study of rotavirus A in faecal samples from children up to five years of age. Stool samples were screened for rotavirus A using a lateral-flow immunochromatographic assay and confirmed using a VP6 sandwich ELISA. Genotyping of rotavirus A-positive samples was performed by PCR and sequencing of VP7 and VP4 genes. The overall prevalence of rotavirus was 30.53% (95% confidence interval [CI] 21.2 - 39.7). Most of the children with rotavirus (86.2%) had received two doses of the rotavirus vaccine. G3 strains accounted for the vast majority of cases (82.8%), followed by G12 strains (13.8%) and G3/G9 coinfections (3.4%). Among the P genotypes, P[8] was the most prevalent (69%), followed by P[9] (31%). The most common G[P] genotype combination was G3P[8], followed by G3P[9]. The main finding in this study was that rotavirus, in a Colombian region, is still an important pathogen in children under five years old, previously vaccinated. The results showed that different factors, such as kindergarten attendance, could explain the epidemiology and transmission of rotavirus in Bucaramanga.

Spread of the emerging equine-like G3P[8] DS-1-like genetic backbone rotavirus strain in Brazil and identification of potential genetic variants.

In 2013, the equine-like G3P[8] DS-1-like rotavirus (RVA) strain emerged worldwide. In 2016, this strain was reported in northern Brazil. The aims of the study were to conduct a retrospective genetic investigation to identify the possible entry of these atypical strains in Brazil and to describe their distribution across a representative area of the country. From 2013 to 2017, a total of 4226 faecal samples were screened for RVA by ELISA, PAGE, RT-PCR and sequencing. G3P[8] represented 20.9 % (167/800) of all RVA-positive samples, further subdivided as equine-like G3P[8], DS-1-like (11.0 %; 88/800) and Wa-like G3P[8] (9.9 %; 79/800). Six equine-like G3P[8] DS-1-like samples were selected for whole-genome investigation, confirming the backbone I2-R2-C2-M2-A2-N2-T2-E2-H2. During 2013-2014, Wa-like G3P[8] was predominant and no equine-like G3P[8] DS-1-like was detected. Equine-like G3P[8] DS-1-like was first identified in Paraná in March/2015, suggesting that the strain entered Brazil through the Southern region. Equine-like G3P[8] rapidly spread across the area under surveillance and displayed a marked potential to replace Wa-like G3P[8] strains. Brazilian equine-like G3P[8] DS-1-like strains clustered with contemporary equine-like G3P[8] DS-1-like detected worldwide, but exhibited a distinct NSP2 genotype (N2) compared to the previously reported Amazon equine-like G3P[8] DS-1-like strain (N1). Two distinct NSP4 E2 genotype lineages were also identified. Taken together, these data suggest that different variants of equine-like G3P[8] DS-1-like strains might have been introduced into the country at distinct time points, and co-circulated in the period 2015-2017. The global emergence of equine-like G3P[8] DS-1-like strains, predominantly in countries using the Rotarix vaccine, raises the question of whether vaccines may be inducing selective pressures on zoonotic strains.

Effectiveness of the Oral Human Attenuated Rotavirus Vaccine: A Systematic Review and Meta-analysis-2006-2016.

BackgroundGastroenteritis caused by rotavirus accounts for considerable morbidity in young children. We aimed to assess the vaccine effectiveness (VE) of the oral rotavirus vaccine Rotarix, as measured by laboratory-confirmed rotavirus infection after referral to hospital and/or emergency departments in children aged <5 years with gastroenteritis.MethodsWe performed a systematic search for peer-reviewed studies conducted in real-life settings published between 2006 and 2016 and a meta-analysis to calculate the overall Rotarix VE, which was further discriminated through stratified analyses.ResultsThe overall VE estimate was 69% (95% confidence interval [CI], 62% to 75%); stratified analyses revealed a non-negligible impact of factors such as study design and socioeconomic status. Depending on the control group, VE ranged from 63% (95% CI, 52% to 72%) to 81% (95% CI, 69% to 88%) for unmatched and matched rotavirus test–negative controls. VE varied with socioeconomic status: 81% (95% CI, 74% to 86%) in high-income countries, 54% (95% CI, 39% to 65%) in upper-middle-income countries, and 63% (95% CI, 50% to 72%) in lower-middle-income countries. Age, rotavirus strain, and disease severity were also shown to impact VE, but to a lesser extent.ConclusionsThis meta-analysis of real-world studies showed that Rotarix is effective in helping to prevent hospitalizations and/or emergency department visits due to rotavirus infection.

Epidemiology of Rotavirus A in Nigeria: Molecular Diversity and Current Insights.

Rotavirus induced acute gastroenteritis AGE has been a major disease burden in Nigeria, since it was first reported in 1985. Prevalence rates have increased with severe public health consequences particularly among children. The vaccine Rotarix® has been introduced and is commercially available in Nigeria. However routine rotavirus vaccination is yet to be introduced into the National Immunization Program. Molecular epidemiology of rotavirus in Nigeria has shown the presence of various genotypes, with genotype G12P[8] being the most recent introduction. There are however gaps in molecular data on rotavirus in Nigeria. We therefore reviewed molecular data on rotavirus isolated in Nigeria and also analyzed VP4 and VP7 genes of Nigerian rotavirus strains in Genbank. We have shown that there is a distinct trend in rotavirus molecular epidemiology in Nigeria, with new genotype introductions occurring after the year 2010. We also observed from our analysis the emergence of genotype G12 Lineage III as a dominant genotype. This information elucidates rotavirus molecular epidemiology in Nigeria and gives insight to the expanding landscape of rotavirus genotypes. We recommend the institution of molecular surveillance country wide, before considering the inclusion of rotavirus vaccination into the National Immunization Program in Nigeria, in other to monitor evolution of divergent or recombinant strains.

A DS-1 like G9P[6] human strain CDC-6 as a new rotavirus vaccine candidate

Human rotavirus vaccine Rotarix® (G1P[8]) has shown broad cross protection against homotypic and heterotypic Wa-like human rotavirus strains among children worldwide. This vaccine, however, appears to induce slightly less or non-consistent protection against DS-1 like rotavirus P[4] strains in some settings. In addition, children who are secretor or Lewis-negative and are vaccinated with Rotarix® often experience breakthrough infection with P[6] strains. By contrast, P[6] strains infect all children, irrespective of their secretor or Lewis status. In the present study, we report successful adaptation of a DS-1 like human rotavirus G9P[6] strain (CDC-6) to high growth in Vero cells and identify sequence changes that may be critical for enhanced growth in vitro and attenuation in vivo. This human G9P[6] strain could serve as a promising new and potential low-cost vaccine candidate for global use, particularly in targeted population with secretor or Lewis-negative status and high prevalent DS-1 like P[6] strains.

Prevalence of rotavirus and rapid changes in circulating rotavirus strains among children with acute diarrhea in China, 2009–2015

Rotavirus is a leading cause of morbidity and mortality in young children worldwide. In China, the universal immunization of children with the rotavirus vaccine has not been introduced, and the two globally distributed vaccines (RotaTeq and Rotarix) are not licensed in the country. We aim to determine the prevalence and strain diversity of rotavirus in children with diarrhea aged≤five years across China. Sentinel-based surveillance of acute diarrhea was conducted at 213 participating hospitals in China from January 1, 2009, through December 31, 2015. Group A rotavirus (RVA) was tested by using enzyme-linked immunosorbent assays, and G- and P-genotype of RVA were tested by RT-PCR methods. Of 33,616 children with diarrhea, 10,089 (30%) were positive for RVA; RVA-associated diarrhea was identified in 2247 (39.5%, n = 2247/5685) inpatients and 7842 (28.1%, n = 7842/27931) outpatients. Children living in low-middle-income regions suffered from the highest burden of rotavirus, with 40.7% of diarrhea cases attributed to rotavirus infection, followed by 31.3% in upper-middle-income and 11.2% in high-income regions. The majority of children (88.9%, n = 8976/10089) who tested positive for RVA were children aged≤2 years. The seasonal peak of RVA was in the winter. Among all 2533 RVA strains genotyped, five strain combinations, G9P[8], G3P[8], G1P[8], G2P[4] and G3P[4], contributed to 71.3% (1807/2533) of the RVA-associated diarrhea cases. The predominant strain of RVA has rapidly evolved from G3P[8] and G1P[8] to G9P[8] in the recent years, with the proportion of G9P[8] having increased remarkably from 3.4% in 2009 to 60.9% in 2015. The burden of diarrhea attributed to rotavirus is high in China, highlighting the potential value of vaccination. The rapid shift of RVA strains highlights the importance of conducting rotavirus surveillance to ensure that currently marketed vaccines provide protective efficacy against the circulating strains.

Effects of geographic and economic heterogeneity on rotavirus diarrhea burden and vaccination impact and cost-effectiveness in the Lao People’s Democratic Republic

Rotavirus enteritis is responsible for nearly 200,000 child deaths worldwide in 2015. Globally, many low- and middle-income countries have introduced rotavirus vaccine, resulting in documented reductions in hospitalizations and child mortality. We examined the potential impact and cost-effectiveness of introducing rotavirus vaccination in Lao People’s Democratic Republic using an Excel-based spreadsheet model. We estimated mortality risk factors, patterns of care seeking, and vaccination access to predict outcomes for regional, provincial, and socioeconomic subpopulations for one birth cohort through their first five years of life and life course in Disability-Adjusted Life Years estimates. Socioeconomic status was defined by categorizing households into regional wealth quintiles based on a national asset index. We modeled a two-dose ROTARIX vaccine under current Gavi pricing and efficacy estimates from Bangladesh and Vietnam. DPT1 and DPT2 coverages were used to estimate rotavirus vaccination coverage. Probabilistic sensitivity analysis was used to assess the impact of uncertainty on model parameters on predicted incremental cost-effectiveness ratios (ICERs), including scenarios of increases in vaccination coverage. Rotavirus vaccination would prevent 143 child deaths/year, or 28% of annual rotavirus burden. The estimated national level ICER for rotavirus vaccination was $140/DALY, with regional socioeconomic subpopulation estimates ranging from $72/DALY for the poorest in the Central region to $353/DALY for the richest in the North region, indicating high cost-effectiveness. Within regions, ICERs are most favorable for children in the poorer and poorest quintiles. However, the full benefits of rotavirus vaccination will only be realized by reducing disparities in vaccination coverage, access to treatment, and environmental health. Improving vaccination coverage to equitable levels alone would prevent 87 additional child deaths per year.

Reports of lower respiratory tract infection following dose 1 of RotaTeq and Rotarix vaccines to the Vaccine Adverse Event Reporting System (VAERS), 2008–2016

ABSTRACTA 2018 manufacturer post-licensure safety study identified a possible association between Rotarix (RV1) rotavirus vaccine and lower respiratory tract infections (LRTI) in infants within 0–6 days following receipt of RV1 dose 1.We reviewed reports to the Vaccine Adverse Event Reporting System (VAERS) of LRTI occurring 0–6 days and 0–29 days post vaccination following RotaTeq (RV5) or Rotarix (RV1) vaccinations in conjunction with either Prevnar (PCV7) or Prevnar 13 (PCV13), in infants aged 6 to 15 weeks. There was no significant difference in LRTI reports to VAERS in the 0–6 days and 0–29 days following receipt of either RV5 or RV1 given with either pneumococcal vaccine.

Prevalence and clinical profile of rotavirus A infection among diarrhoeal children and phylogenetic analysis with vaccine strains in Chengdu, West China, 2009-2014.

Rotaviruses are the most common cause of severe diarrhoeal disease in young children. However, little is known about the epidemiological and clinical profile of rotavirus A (RVA) in diarrhoeal children or the efficacy of Lanzhou lamb rotavirus vaccine (LLR) in Chengdu, China. This study aimed to determine the prevalence and clinical profile of RVA in diarrhoeal children and provide gene analysis information for RVA vaccination programmes. A total of 1121 faecal samples were collected from outpatient children with diarrhoea between 2009 and 2014. RT-PCR was performed to detect RVA infection and other gastroenteritis viruses. VP4 and VP7 genes of 13 RVA strains were sequenced to compare their similarity with vaccine strains. The overall RVA infection rate was 17.48%. G1 (54.72%) and G3 (18.87%) were the predominant G genotypes; P[8] (72.36%) and P[4] (11.38%) were the main P genotypes. Sixteen genotypes were identified; G1P[8] (57.33%) and G9P[8] (12.00%) were the most prevalent. The proportion of coinfection with RVA and other gastroenteritis viruses was 18.88%. RVA was mostly detected in winter and in diarrhoeal children 1-2 years of age. The genotypes of Rotarix and RotaTeq vaccines were consistent with RVA strains prevalent in Sichuan and shared high identity. RVA was one of the major aetiological agents of diarrhoeal children in Chengdu. Genotype distribution differed within each year and the gene analysis implied low efficacy of LLR. Continuous epidemiological monitoring of RVA is essential for the national vaccination programme.

The Impact of Rotavirus Vaccines on Genotype Diversity: A Comprehensive Analysis of 2 Decades of Australian Surveillance Data.

Introduction of rotavirus vaccines into national immunization programs (NIPs) could result in strain selection due to vaccine-induced selective pressure. This study describes the distribution and diversity of rotavirus genotypes before and after rotavirus vaccine introduction into the Australian NIP. State-based vaccine selection facilitated a unique comparison of diversity in RotaTeq and Rotarix vaccine states. From 1995 to 2015, the Australian Rotavirus Surveillance Program conducted genotypic analysis on 13051 rotavirus-positive samples from children <5 years of age, hospitalized with acute gastroenteritis. Rotavirus G and P genotypes were determined using serological and heminested multiplex reverse-transcription polymerase chain reaction assays. G1P[8] was the dominant genotype nationally in the prevaccine era (1995-2006). Following vaccine introduction (2007-2015), greater genotype diversity was observed with fluctuating genotype dominance. Genotype distribution varied based on the vaccine implemented, with G12P[8] dominant in states using RotaTeq, and equine-like G3P[8] and G2P[4] dominant in states and territories using Rotarix. The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia.