Fifty-three rotavirus-positive fecal specimens from children with diarrhea admitted to a Rio de Janeiro, Brazil, children's hospital between January 1997 and December 1998 were characterized for P and G types by using reverse transcription-PCR. Genotype P[4]G2 accounted for 21% of isolates, while uncommon genotypes P[8]G9, P[6]G9, and P[4]G9 accounted for 13% of the isolates
: Our data demonstrate the reemergence of RV-A genotype G2P[4] in Brazil from 2005 to 2008, and that the rate of G2P[4] detection decreased in 2009, probably reflecting natural oscillations of RV-A genotypes.
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.
Epidemiological data on species A rotavirus (RVA) infections have demonstrated the genetic diversity of strains circulating worldwide. Many G and P genotype combinations have been described over the years, varying regionally and temporally, especially in developing countries. However, the most common G and P genotype combinations identified in RVA human strains worldwide are G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8]. RVA genotype G1P[8] strains are responsible for more than 50% of child infections worldwide and component of the two vaccines (Rotarix® [RV1] and RotaTeq® [RV5]) licensed globally. For a better understanding of the evolutionary mechanisms of this genotype in Brazil, phylogenetic analyses based on the 11 RVA genome segments (genomic constellation) from 90 G1P[8] RVA strains collected in two eras - (i) pre-vaccination with RV1 (1996-February 2006); (ii) post-vaccination (March 2006-2013) - in different Brazilian states were performed. The results showed the Wa-like genomic constellation of the Brazilian G1P[8] strains with a I1-R1-C1-M1-A1-N1-T1-E1-H1 specificity, except for two strains (rj14055-07 and ba19030-10) that belong to a I1-R1-C1-M1-A1-N1-T3-E1-H1 genomic constellation, evidencing the occurrence of reassortment (Wa-like×AU-1-like) of the NSP3 gene. Reassortment events were also demonstrated between Brazilian G1P[8] strains and the RV1 vaccine strain in some genes in vaccinated and unvaccinated children. VP7 and VP8* antigenic site analysis showed that the amino acid substitutions observed in samples collected after the introduction of RV1 in Brazil were already detected in samples collected in the 1980s and 1990s, suggesting that mass Brazilian RV1 vaccination had no impact on the diversity observed inside antigenic sites for these two proteins.
This study aims to: estimate the prevalence of G2P[4] rotaviruses in Brazil between 2001-2011 from patients with acute gastroenteritis; perform phylogenetic analyses of G2P[4] Brazilian strains (from vaccinated and non-vaccinated children) based on VP7 and VP8(∗) encoding genes and analyze the antigenic regions of these proteins comparing with RV1; and assess the full genetic background of eleven selected Brazilian strains. The G2P[4] detection rate among RVA positive samples was 0/157 in 2001, 3/226 (1.3%) in 2002, 0/514 in 2003, 0/651 in 2004, 31/344 (9%)/2005, 112/227 (49%)/2006, 139/211 (66%)/2007, 240/284 (85%)/2008, 66/176 (37.5%)/2009, 367/422 (87%)/2010 and 75/149 (50%)/2011. For the VP7 and VP8(∗) encoding genes, 52 sequences were analyzed and shared up to 99% nucleotide identity with other contemporary G2P[4] strains detected worldwide, grouping into different clusters. Most differences inside antigenic epitopes of VP7 and VP8(∗) have been maintained in the G2P[4] Brazilian strains along the years, and all were present before RV1 introduction. Eleven G2P[4] strains (4-vaccinated/7-non-vaccinated) were completely characterized and possessed the typical DS-1-like genotype constellation (G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2) sharing up to 99% of nucleotide identity with contemporary worldwide strains. Reassortments between Brazilian G2P[4] human strains were observed. In conclusion, the data obtained in the current study suggests that implementation of RV1 vaccination might not influence the genetic diversity observed in G2P[4] analyzed strains. Several factors might have contributed to the increased prevalence of this genotype in Brazil since 2005: the introduction of RV1 into the Brazilian National Immunization Program has resulted in a decrease in the relative prevalence of predominant Wa-like RVA strains facilitating the increase of the heterotypic (DS-1-like) RVA strain G2P[4] in the Brazilian population; the genetic diversity found in different geographical regions throughout the years before, and after the introduction of RV1; the long period of low or no circulation of this genotype in Brazil previous to RV1 introduction could have created favorable conditions for the accumulation of immunological susceptible individuals.
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