I am a postdoc in the Department of Microbiology at Monash University in Melbourne, Australia.
My research focuses on the evolution of viruses that have significant disease burden in the paediatric population and combines clinical, experimental and computational approaches.
Understanding how widespread vaccine use is shaping the diversity and evolution of rotavirus
Rotavirus was first discovered in 1973 by Ruth Bishop and colleagues and is recognized as a leading cause of acute gastroenteritis in young children worldwide causing significant morbidity and mortality. In 2013, an estimated 215,000 children under five years of age died due to rotavirus infection. Whilst 90% of deaths occur in developing countries children in developed nations still experience a high burden of disease.
Rotavirus is a double-stranded RNA virus and can evolve via numerous mechanisms with the greatest diversity generated by genetic drift, reassortment and zoonotic transmission. Genetic drift arises from the error-prone nature of the virus replication machinery. Genomic reassortment is facilitated by the segmented rotavirus genome and occurs due to co-infections. Some animal rotavirus strains are able to cross the species barrier into humans, causing disease.
Rotavirus vaccines are recommended by the World Health Organisation (WHO) and the live-oral rotavirus vaccines Rotarix and RotaTeq have been included in the routine immunisation programs of over 90 countries worldwide. In all settings, vaccine introduction has resulted in substantial decreases in rotavirus hospitalisations and all-cause gastroenteritis mortality. High vaccine coverage in the population may act as a selective force, altering the evolution of rotavirus strains. Strains that can evade vaccine immunity (vaccine escape strains) may be selected and increase in dominance in the population.
Genotype diversity fluctuated geographically and temporally prior to vaccine introduction and this fluctuation appears to have been magnified in the vaccine-era. Molecular epidemiological studies in numerous countries have revealed changes in the diversity and distribution of wild-type rotavirus strains following vaccine introduction.
My research aims to understand how rotavirus has evolved in Australia since the National Immunisation Program began in 2007, highlight the emergence of zoonotic strains associated with sporadic disease and sustained outbreaks in many communities. I also have an interest in the increasing burden of rotavirus disease in the elderly population.
Abstract: Two live-attenuated oral vaccines (Rotarix™ and Rotateq®) against rotavirus gastroenteritis were licensed in 2006 and have been introduced into National Immunization Programs (NIPs) of several countries. Large scale use of rotavirus vaccines might cause antigenic pressure on circulating rotavirus types or lead to selection of new rotaviruses thus decreasing vaccine efficacy. We examined the nucleotide and amino acid sequences of the surface proteins VP7 and VP4 (cleaved to VP8(*) and VP5(*)) of a total of 108 G1P rotavirus strains collected over a 20-year period from 1992, including the years 2006-2009 when rotavirus vaccine (mainly Rotarix™) was available, and the years 2009-2012 after implementation of RotaTeq® vaccine into the NIP of Finland. In G1 VP7 no changes at amino acid level were observed. In VP8(*) periodical fluctuation of the sublineage over the study period was found with multiple changes both at nucleotide and amino acid levels. Most amino acid changes were in the dominant antigenic epitopes of VP8(*). A change in VP8(*) sublineage occurred between 2008 and 2009, with a temporal correlation to the use of Rotarix™ up to 30% coverage in the period. In contrast, no antigenic changes in the VP8(*) protein appeared to be correlated to the exclusive use of RotaTeq® vaccine after 2009. Nevertheless, long-term surveillance of antigenic changes in VP4 and also VP7 proteins in wild-type rotavirus strains is warranted in countries with large scale use of the currently licensed live oral rotavirus vaccines.
Pub.: 09 Jul '13, Pinned: 04 Jan '18
Abstract: Rotaviruses are the most important etiological agent of acute gastroenteritis in young children worldwide. Among the first countries to introduce rotavirus vaccines into their national immunization programs were Belgium (November 2006) and Australia (July 2007). Surveillance programs in Belgium (since 1999) and Australia (since 1989) offer the opportunity to perform a detailed comparison of rotavirus strains circulating pre- and postvaccine introduction. G1P rotaviruses are the most prominent genotype in humans, and a total of 157 G1P rotaviruses isolated between 1999 and 2011 were selected from Belgium and Australia and their complete genomes were sequenced. Phylogenetic analysis showed evidence of frequent reassortment among Belgian and Australian G1P rotaviruses. Although many different phylogenetic subclusters were present before and after vaccine introduction, some unique clusters were only identified after vaccine introduction, which could be due to natural fluctuation or the first signs of vaccine-driven evolution. The times to the most recent common ancestors for the Belgian and Australian G1P rotaviruses ranged from 1846 to 1955 depending on the gene segment, with VP7 and NSP4 resulting in the most recent estimates. We found no evidence that rotavirus population size was affected after vaccine introduction and only six amino acid sites in VP2, VP3, VP7, and NSP1 were identified to be under positive selective pressure. Continued surveillance of G1P strains is needed to determine long-term effects of vaccine introductions, particularly now rotavirus vaccines are implemented in the national immunization programs of an increasing number of countries worldwide.
Pub.: 09 Aug '15, Pinned: 04 Jan '18
Abstract: During 2013, a novel equine-like G3P rotavirus emerged as the dominant strain in Australian children with severe rotavirus gastroenteritis. Full genome analysis demonstrated that the strain was an inter-genogroup reassortant, containing an equine-like G3 VP7, a P VP4 and a genogroup 2 backbone I2-R2-C2-M2-A2-N2-T2-E2-H2. The genome constellation of the equine-like G3P was distinct to Australian and global G3P strains. Phylogenetic analysis demonstrated a genetic relationship to multiple gene segments of Japanese strains RVA/JPN/S13-30/2013/G3P and RVA/Human-wt/JPN/HC12016/2012/G1P. The Australian equine-like G3P strain displayed a distinct VP7 antigenic profile when compared with the previously circulating Australian G3P strains. Identification of similar genes in strains from several geographical regions suggested the equine-like G3P strain was derived by multiple reassortment events between globally co-circulating strains from both human and animal sources. This study reinforces the dynamic nature of rotavirus strains and illustrates the potential for novel human/animal reassortant strains to emerge within the human population.
Pub.: 22 Nov '15, Pinned: 04 Jan '18
Abstract: We describe the rotavirus genotypes before and after rotavirus vaccine introduction in Brazil. 86 studies reported 6,884 (15.2%) rotavirus-episodes among 45,305 children. Rotavirus caused 22.4% and 11.6% of cases before and after vaccine introduction. G1P and G9P, and G2P and heterotypic-strains were most common before and after vaccine introduction. The vaccines may have selected heterotypic strains in this highly-vaccinated population.
Pub.: 01 Dec '17, Pinned: 04 Jan '18
Abstract: A hyper-endemic rotavirus season was expected after a low-endemic 2014 season in the Netherlands. Rotavirus detections were however similar in 2015 and lower in 2016 compared with 2010-2013. Gastroenteritis consultations rates were also similar in 2015, but the age-distribution shifted to older children due to an accumulation of non-infected children. Results indicate a possible shift to a biennial rotavirus pattern.
Pub.: 27 Dec '17, Pinned: 04 Jan '18