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.