Introduction:
Before the introduction of rotavirus vaccines, rotavirus gastroenteritis was a leading cause of childhood morbidity and mortality in children under five years of age worldwide (1, 2). To date, more than 100 countries have introduced rotavirus vaccines into their national immunization programs, significantly reducing the burden of rotavirus associated hospitalizations and deaths (3, 4). However, vaccine efficacy is higher in resource-rich countries and the societal impact of rotavirus gastroenteritis remains large. Rotavirus infections result in an estimated 120,000 to 200,000 deaths annually in resource-limited countries and causes significant societal and healthcare costs in resource-rich countries (5-7).
Rotavirus , a genus of the family Reoviridae , is a genetically diverse group of dsRNA viruses. Most cases of disease belong to group A rotavirus which can be classified into 42 G and 58 P types based on serological and genetic characterization of outer capsid proteins VP7 (G-type) and VP4 (P-type). At least 16 G and 19 P types are recognized in humans (8-10). With the increasing availability of rotavirus whole genome sequences, rotaviruses are now classified into genome constellations based on sequence similarities of all 11 dsRNA segments (9, 11). Three genome constellations have been identified to date: Wa-like, DS-1 like and AU-1 like, with the first two being the most common (9, 11, 12). Genome-based classification offers additional information on genome diversity, possible zoonotic transmission, segment reassortment, antigenic drift and strain evolution and is becoming increasingly adopted; however, VP7 and VP4 genotyping remains widely used in most laboratories (12).
Six genotypes of group A rotavirus: G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and G12P[8] account for >90% of the rotavirus infections worldwide (13). Continued evolution of the rotavirus genome, due to an error-prone RNA polymerase, may give rise to unpredictable strain predominance which varies greatly by year and by geographic location (13, 14). In recent years, uncommon genotypes have emerged and spread globally including G9P[8], G3P[8], G12P[8] and vaccine-derived G1P[8] (15-19).
Rotavirus infections manifest as a spectrum of symptoms ranging from asymptomatic to life-threatening (8). Previous studies have presented conflicting data on the association of rotavirus genotypes/strains and illness severity. For example, studies from Latin America, India, Iran, Cambodia and the UK found that children with emerging G9 and G12 strain infections had more severe acute gastroenteritis (AGE) than those with other genotypes (18, 20). However, the association of clinical severity with genotype was not evident in studies conducted in France, US, Korea and Italy (21, 22).
Rotavirus vaccination is the best strategy to reduce the burden of severe and life-threatening rotavirus gastroenteritis. Rotarix is monovalent, live-attenuated vaccine of a human G1P[8] rotavirus strain; RotaTeq® is a live-attenuated vaccine of five human-bovine reassortant viruses displaying antigens of G1, G2, G3, G4 and P[8] strains (23). Although the implementation of vaccines has reduced the rotavirus burden, increased vaccine-induced immune pressure against wild-type rotavirus strains may select for immune escape mutants or antigenically distinct strains (24). Therefore, post-vaccine-implementation surveillance of circulating rotavirus genotypes is vital to monitor changes in transmission patterns, identification of vaccine-induced novel heterotypic genotypes (or neutralization escape mutants), and discovery of potentially pathogenic vaccine related strains (25).
In the province of Alberta, Canada, the monovalent rotavirus vaccine (RV1) Rotarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium) was included in the routine universal childhood immunization schedule in June 2015 and was replaced by the pentavalent RotaTeq® in May 2018, and was again introduced from May 2021 onward (26). However, the impact of RV1 vaccination on the emergence of novel rotavirus genotypes, the presence of RV1 derived strains, and genotype specific clinical characteristics in children with rotavirus AGE are not well understood. To fill this knowledge gap, we examined the genotype distribution and clinical characteristics of rotavirus illness in children with AGE in four consecutive seasons between 2014 and 2018 before and after rotavirus vaccine introduction in Alberta.