Rotavirus strain surveillance for three years following the introduction of rotavirus vaccine into Belém, Brazil.

The monovalent human rotavirus (RV) vaccine, RIX4414 (Rotarix™, GlaxoSmithKline Biologicals) was introduced into Brazil's Expanded Program on Immunization in March 2006. One year after vaccine introduction, the G2P[4] strain was found to be predominant, with an apparent extinction of many non-G2 strains. This study investigated the diversity of circulating strains in the three years following RIX4414 introduction. Between May 2008 and May 2011, stool samples were collected from children aged ≥12 weeks who were hospitalized for severe lab confirmed RV-gastroenteritis (≥3 liquid or semi-liquid motions over a 24-h period for <14 days, requiring ≥1 overnight hospital stay and intravenous rehydration therapy) in Belém, Brazil. RV-gastroenteritis was detected by ELISA and the G- and P-types were determined by RT-PCR assays. During the first year of surveillance nucleotide sequencing was used for typing those samples not previously typed by RT-PCR. A total of 1,726 of 10,030 severe gastroentertis hospitalizations (17.2%) were due to severe RVGE. G2P[4] was detected in 57.2% of circulating strains over the whole study period, however it predominated during the first 20 months from May 2008 to January 2009. G1P[8] increased in the last part of the study period from May 2010 to May 2011 and represented 36.6% (112/306) of the circulating strains. G2P[4] was the predominant RV strain circulating during the first 20 months of the study, followed by G1P[8]. These findings probably reflect a natural fluctuation in RV strains over time, rather than a vaccine-induced selective pressure.

Diversity of rotavirus strains circulating in Northern Brazil after introduction of a rotavirus vaccine: high prevalence of G3P[6] genotype.

Rotavirus A (RVA) is the most common cause of severe acute gastroenteritis in infants and young children worldwide, causing 453,000 deaths annually. In Brazil, the most frequent genotype identified was G1 during almost three decades in the pre-vaccination period; however, after anti-rotavirus vaccine introduction, there was a predominance of G2 genotype. The aim of this study was to determine the G and P genotypes of rotaviruses isolated from children under 5 years of age with acute gastroenteritis in the Northern region of Brazil, and discuss the emergence of G3P[6] genotype. A total of 783 stool specimens were obtained between January 2011 and March 2012. RVA antigen was detected in 33% (272/783) of samples using a commercial enzyme-linked immunosorbent assay and type-specificity was determined by reverse-transcription polymerase chain reaction. The most common binary combination was G2P[4], representing 41% of cases, followed by G3P[6] (15%), G1P[8] (8%), G3P[8] (4%), G9P[8] (3%), and G12P[6] (2%). G3P[6] strains were analyzed further and phylogenetic analysis of VP7 gene showed that G3 strains clustered into lineage I and showed a high degree of amino acid identity with vaccine strain RV3 (95.1-95.6%). For VP4 sequences, G3P[6] clustered into lineage Ia. It was demonstrated by the first time the emergence of unusual genotype G3P[6] in the Amazon region of Brazil. This genotype shares neither VP7 nor VP4 specificity with the used vaccine and may represent a challenge to vaccination strategies. A continuous monitoring of circulating strains is therefore needed during the post-vaccine era in Brazil.

Identification of lineage III of G12 rotavirus strains in diarrheic children in the Northern Region of Brazil between 2008 and 2010.

This study reports on the surveillance for rotavirus genotypes and the identification of G12 human rotavirus in the Northern Region of Brazil. Rotavirus-positive samples were collected from children <5 years of age with acute diarrhea from January 2008 to October 2010. G2P[4] was the most prevalent genotype, accounting for 45.6% (126/303) of cases. Five rotavirus strains bearing G12P[6] genotype specificity were detected. Phylogenetic analysis of the VP7 gene showed that G12 strains clustered into lineage III. This is the first detection of G12 strains from lineage III in Latin America, broadening the current evidence for the worldwide emergence of this genotype.

Effectiveness of the monovalent G1P[8] human rotavirus vaccine against hospitalization for severe G2P[4] rotavirus gastroenteritis in Belém, Brazil.

BACKGROUND: Brazil initiated universal immunization of infants with the G1P[8] human rotavirus (RV) vaccine in March 2006. This study evaluated vaccine effectiveness (VE) against severe rotavirus gastroenteritis (RVGE) hospitalizations. METHODS: Matched case-control study conducted at 4 hospitals in Belém from May 2008 to May 2009. Cases were children hospitalized with RVGE age-eligible to have received 2 doses of the human RV vaccine (≥ 12 weeks of age and born after March 6, 2006). For each case, 1 neighborhood and 1 hospital control without gastroenteritis was selected, matching by birth date (± 8 and ± 6 weeks, respectively). Matched odds ratio of 2-dose RV vaccination in cases versus controls was used to estimate VE (1 - odds ratio × 100%). RESULTS: Of 538 RVGE cases, 507 hospital controls and 346 neighborhood controls included, 54%, 61%, and 74% had received both RV vaccine doses. VE against RVGE hospitalization was 75.8% (95% confidence interval [CI]: 58.1-86.0) using neighborhood controls and 40.0% (95% CI: 14.2-58.1) using hospital controls. VE in children 3 to 11 months and ≥ 12 months of age was 95.7% (95% CI: 67.8-99.4) and 65.1% (95% CI: 37.2-80.6) using neighborhood controls, and 55.6% (95% CI: 12.3-77.5) and 32.1% (95% CI: -3.7-55.5) using hospital controls. G2P[4] accounted for 82.0% of RVGE hospitalizations. G2P[4]-specific VE was 75.4% (95% CI: 56.7-86.0) using neighborhood controls and 38.9% (95% CI: 11.1-58.0) using hospital controls. CONCLUSIONS: Although fully heterotypic G2P[4] was the predominant RV strain, good VE was demonstrated. VE was highest in children aged 3 to 11 months. However, protection in children ≥ 12 months of age, important for optimal public health impact, was significantly sustained based on estimates obtained using neighborhood controls.