Dataset Information

Whole-Genome Analyses Identifies Multiple Reassortant Rotavirus Strains in Rwanda Post-Vaccine Introduction.

ABSTRACT: Children in low-and middle-income countries, including Rwanda, experience a greater burden of rotavirus disease relative to developed countries. Evolutionary mechanisms leading to multiple reassortant rotavirus strains have been documented over time which influence the diversity and evolutionary dynamics of novel rotaviruses. Comprehensive rotavirus whole-genome analysis was conducted on 158 rotavirus group A (RVA) samples collected pre- and post-vaccine introduction in children less than five years in Rwanda. Of these RVA positive samples, five strains with the genotype constellations G4P[4]-I1-R2-C2-M2-A2-N2-T1-E1-H2 (n = 1), G9P[4]-I1-R2-C2-M2-A1-N1-T1-E1-H1 (n = 1), G12P[8]-I1-R2-C2-M1-A1-N2-T1-E2-H3 (n = 2) and G12P[8]-I1-R1-C1-M1-A2-N2-T2-E1-H1 (n = 1), with double and triple gene reassortant rotavirus strains were identified. Phylogenetic analysis revealed a close relationship between the Rwandan strains and cognate human RVA strains as well as the RotaTeq^® vaccine strains in the VP1, VP2, NSP2, NSP4 and NSP5 gene segments. Pairwise analyses revealed multiple differences in amino acid residues of the VP7 and VP4 antigenic regions of the RotaTeq^® vaccine strain and representative Rwandan study strains. Although the impact of such amino acid changes on the effectiveness of rotavirus vaccines has not been fully explored, this analysis underlines the potential of rotavirus whole-genome analysis by enhancing knowledge and understanding of intergenogroup reassortant strains circulating in Rwanda post vaccine introduction.

SUBMITTER: Rasebotsa S

PROVIDER: S-EPMC7828107 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Whole-Genome Analyses Identifies Multiple Reassortant Rotavirus Strains in Rwanda Post-Vaccine Introduction.

Rasebotsa Sebotsana S Uwimana Jeannine J Mogotsi Milton T MT Rakau Kebareng K Magagula Nonkululeko B NB Seheri Mapaseka L ML Mwenda Jason M JM Mphahlele M Jeffrey MJ Sabiu Saheed S Mihigo Richard R Mutesa Leon L Nyaga Martin M MM

Viruses 20210112 1

Children in low-and middle-income countries, including Rwanda, experience a greater burden of rotavirus disease relative to developed countries. Evolutionary mechanisms leading to multiple reassortant rotavirus strains have been documented over time which influence the diversity and evolutionary dynamics of novel rotaviruses. Comprehensive rotavirus whole-genome analysis was conducted on 158 rotavirus group A (RVA) samples collected pre- and post-vaccine introduction in children less than five y ...[more]

PMID: 33445703

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Project description:BACKGROUND:A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS:We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS:From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS:The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

Project description:Acute gastroenteritis due to group A rotaviruses (RVAs) is the leading cause of infant and childhood morbidity and mortality particularly in developing countries including Pakistan. In this study we have characterized the whole genomes of five RVA strains (PAK56, PAK419, PAK585, PAK622, and PAK663) using the Illumina HiSeq platform. The strains PAK56 and PAK622 exhibited a typical Wa-like genotype constellation (G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 and G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, respectively), whereas PAK419, PAK585, and PAK663 exhibited distinct DS-1-like genotype constellations (G3P[4]-I2-R2-C2-M2-A2-N2-T1-E2-H2, G1P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2, and G3P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2, respectively). Despite their DS-1-like genotype constellation, strain PAK585 possessed the typical Wa-like G1P[8] genotypes, whereas both PAK419 and PAK663 possessed the G3 genotype. In addition, PAK419 also possessed the Wa-like NSP3 genotype T1, suggesting that multiple reassortments have occurred. On Phylogenetic analysis, all of the gene segments of the five strains examined in this study were genetically related to globally circulating human G1, G2, G3, G6, G8, G9, and G12 strains. Interestingly, the NSP2 gene of strain PAK419 showed closest relationship with Indian bovine strain (India/HR/B91), suggesting the occurrence of reassortment between human and bovine RVA strains. Furthermore, strains PAK419, PAK585, and PAK663 were closely related to one another in most of their gene segments, indicating that these strains might have been derived from a common ancestor. To our knowledge this is the first whole genome-based molecular characterization of human rotavirus strains in Pakistan. The results of our study will enhance our existing knowledge on the diversity and evolutionary dynamics of novel RVA strains including DS-1-like intergenogroup reassortant strains spreading in Asian countries including Pakistan, in the pre-vaccine era. Therefore, continuous surveillance is recommended to monitor the evolution, spread and genetic stability of novel reassortant rotavirus strains derived from such events.

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Dataset Information

Whole-Genome Analyses Identifies Multiple Reassortant Rotavirus Strains in Rwanda Post-Vaccine Introduction.

Publications

Whole-Genome Analyses Identifies Multiple Reassortant Rotavirus Strains in Rwanda Post-Vaccine Introduction.

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