Introduction of rotavirus vaccines into national immunization programs (NIPs) could result in strain selection due to vaccine-induced selective pressure. This study describes the distribution and ...diversity of rotavirus genotypes before and after rotavirus vaccine introduction into the Australian NIP. State-based vaccine selection facilitated a unique comparison of diversity in RotaTeq and Rotarix vaccine states.
From 1995 to 2015, the Australian Rotavirus Surveillance Program conducted genotypic analysis on 13051 rotavirus-positive samples from children <5 years of age, hospitalized with acute gastroenteritis. Rotavirus G and P genotypes were determined using serological and heminested multiplex reverse-transcription polymerase chain reaction assays.
G1P8 was the dominant genotype nationally in the prevaccine era (1995-2006). Following vaccine introduction (2007-2015), greater genotype diversity was observed with fluctuating genotype dominance. Genotype distribution varied based on the vaccine implemented, with G12P8 dominant in states using RotaTeq, and equine-like G3P8 and G2P4 dominant in states and territories using Rotarix.
The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P8), and in states and territories using Rotarix (equine-like G3P8 and G2P4), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia.
Severe diarrhea from rotavirus remains an important cause of illness in infants. In this trial, investigators in Indonesia assessed the potential benefit of a neonatal rotavirus vaccine.
Background. RotaTeq vaccine was introduced into the Australian National Immunisation Program in 2007. This study identified and characterised rotavirus strains excreted by infants who presented with ...symptoms of gastroenteritis following recent RotaTeq vaccination. Methods. Fecal samples (N = 61) from children who developed gastroenteritis following recent RotaTeq vaccination were forwarded to the Australian Rotavirus Surveillance Program (ARSP). RotaTeq-positive samples were genotyped and regions of the VP3, VP4, VP6, and VP7 genes were sequenced. Also, 460 rotavirus-positive ARSP routine surveillance samples were analyzed by dot-blot Northern hybridization to detect RotaTeq vaccine-derived strains circulating in the community. Results. Thirteen of the 61 samples collected from infants developing gastroenteritis after RotaTeq vaccination contained vaccine-derived (vd) rotavirus strains. Of these, 4 contained a vdG1P8 strain derived by reassortment between the G1P5 and G6P8 parental vaccine strains. Northern hybridization analysis of 460 surveillance samples identified 3 samples that contained RotaTeq vaccine—derived strains, including 2 vdG1P8 reassortant vaccine strains. Conclusions. During replication and excretion of RotaTeq vaccine, reassortment of parental strains can occur. Shedding of RotaTeq vaccine strains in 7 of 13 infants was associated with underlying medical conditions that may have altered their immune function. The benefits of vaccination outweigh any small risk of vaccine-associated gastroenteritis.
The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand ...between January 2012 and April 2014. Healthy, full-term (≥ 36 weeks gestation) babies, who were 0-5 d old were randomly assigned (1:1:1) to receive 3 doses of oral RV3-BB vaccine with the first dose given at 0-5 d after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Vaccine take (serum immune response or stool shedding of vaccine virus after any dose) was detected after 3 doses of RV3-BB vaccine in >90% of participants when the first dose was administered in the neonatal and infant schedules. The aim of the current study was to characterize RV3-BB shedding and virus replication following administration of RV3-BB in a neonatal and infant vaccination schedule. Shedding was defined as detection of rotavirus by VP6 reverse transcription polymerase chain reaction (RT-PCR) in stool on days 3-7 after administration of RV3-BB. Shedding of rotavirus was highest following vaccination at 8 weeks of age in both neonatal and infant schedules (19/30 and 17/27, respectively). Rotavirus was detected in stool on days 3-7, after at least one dose of RV3-BB, in 70% (21/30) of neonate, 78% (21/27) of infant and 3% (1/32) placebo participants. In participants who shed RV3-BB, rotavirus was detectable in stool on day 1 following RV3-BB administration and remained positive until day 4-5 after administration. The distinct pattern of RV3-BB stool viral load demonstrated using a NSP3 quantitative qRT-PCR in participants who shed RV3-BB, suggests that detection of RV3-BB at day 3-7 was the result of replication rather than passage through the gastrointestinal tract.
Live vaccines such as measles mumps rubella (MMR) are generally contraindicated in immunosuppressed populations because of potential morbidity and mortality.2 This has not been applied to rotavirus ...vaccines, in which risk of vaccine-associated disease is felt to be less than the risk from being exposed to natural infection.2 Current guidelines support the administration of rotavirus vaccine to children infected with HIV, the largest immunosuppressed population studied to date.3 The side effect profile is likely to involve gastrointestinal symptoms (vomiting and diarrhea). Studies of RotaTeq have shown that viral shedding occurred in 9% of 360 recipients after dose 1, 0% after dose 2, and 0.3% after dose 3, usually between days 1 and 15 after the dose.5 This is the first reported case of persistent rotavirus vaccine excretion and chronic diarrhea in a severely immunocompromised patient. Because the diagnosis of a primary immune deficiency, such as SCID, is often made in the first year of life, it is important to consider this diagnosis when treating children with prolonged diarrhea and faltering growth, especially as we enter the universal rotavirus vaccination era.
Serum rotavirus IgA responses are an imperfect non-mechanistic correlate of protection, and the lack of an accurate serological marker is a challenge to the development of new rotavirus vaccines. ...Serological responses to rotavirus NSP2 occur following wild-type infection; however, it is unknown if serological responses to NSP2 occur following administration of rotavirus vaccines. The phase IIa immunogenicity trial of RV3-BB provided an opportunity to investigate the serological responses to NSP2 following vaccination. Healthy, full-term babies (n = 96) were previously recruited as part of a phase IIa safety and immunogenicity trial in Dunedin, New Zealand between January 2012 and April 2014. Participants received three doses of oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Serum IgA and IgG antibody responses to total RV3-BB and NSP2 protein (RV3-BB) were assessed using ELISA. Despite significant serum IgA response against total RV3-BB, we were unable to demonstrate a significant serological response to NSP2 in participants receiving RV3-BB when compared to placebo. Heterotypic antibodies against multiple NSP2 genotypes were detected following RV3-BB vaccination. Our data demonstrates that while serological responses to NSP2 were detectable in a subset of participants, it is a less useful marker when compared to total rotavirus serum IgA response.
► Group A rotaviruses are the leading cause of acute gastroenteritis in children. ► We analysed Australian rotavirus NSP2 gene sequences. ► Phylogenetic analysis shows conservation of Australian NSP2 ...gene sequences. ► NSP2 genes exhibited recombination, reassortment and interspecies transmission.
The rotavirus non-structural protein NSP2 is one of the earliest and most abundant viral proteins produced during infection. This protein has multiple essential roles in the replication cycle involving RNA binding, viroplasm formation, helicase and can hydrolyse the γ-phosphate of RNA and NTPs acting as an RTPase and NTPase. In studying sequences from rotavirus strains isolated in Australia between 1984 and 2009, the NSP2 gene was seen to be highly conserved and clustered with defined NSP2 genotypes N1 and N2 according to the full genome based rotavirus classification system. Phylogenetic analysis indicated that NSP2 gene sequences isolated from Australian rotavirus strains formed four distinct lineages. Temporal variation was observed in several clusters during the 26 year period, with lineage D identified throughout the entire study period and lineage A only detected since 1999. Phylogenetic analysis and dendrograms identified NSP2 genes that exhibited reassortment between different virus VP7 genotypes, as well as a sequence from a human strain that grouped closely with the NSP2 genes of bovine rotavirus strains. This study also identified a sequence that fell between lineages and exhibited evidence of recombination, the first time that intergenic recombination has been detected in a NSP2 gene sequence. This study increases the understanding of the evolution mechanisms of NSP2 in view of improved vaccine design.
Background:
Mycobacterium avium subspecies paratuberculosis (MAP) is the most enduring infectious candidate that may be associated with inflammatory bowel disease (IBD). It is possible that the ...inconsistencies in the prevalence studies of MAP in adults reflect clinical differences in adult patients studied, including duration of disease and treatment regimens, and also in lack of specificity of some of the assays used. The aim was to determine the presence of MAP in children with symptoms of Crohn's disease (CD) and ulcerative colitis (UC), using gut biopsy tissue and peripheral blood mononuclear cells (PBMC) collected at initial endoscopic examination prior to clinical treatment.
Methods:
Mucosal biopsies and/or PBMC specimens were collected from a total of 142 children, comprising 62 with CD, 26 with UC, and 54 with non‐IBD. MAP‐specific IS900 polymerase chain reaction (PCR) analysis was performed on all biopsies and PBMC specimens. Conventional MAP culture technique was performed on a subset of 10 CD, 2 UC, and 4 non‐IBD patients to isolate MAP.
Results:
MAP was identified by IS900 PCR significantly more often in mucosal biopsies from CD 39% (22/56) than from non‐IBD 15% (6/39) patients (P < 0.05), and in PBMC from CD 16% (8/50) than from non‐IBD 0% (0/31) patients (P < 0.05). Viable MAP were cultured from mucosal biopsies from 4/10 CD, 0/2 UC, and 0/4 non‐IBD patients, but were not cultured from PBMC specimens.
Conclusions:
This unique study on the occurrence of MAP in gut tissue and blood from pediatric IBD patients suggests the possible involvement of MAP in the early stages of development of CD in children. Inflamm Bowel Dis 2009
In this study, we investigated the molecular epidemiology of group A rotaviruses in cases of acute gastroenteritis in Goroka, Papua New Guinea. From April 2008 through November 2010, 813 diarrheal ...stool samples were collected from children < 5 years of age hospitalized with acute gastroenteritis. Rotavirus antigen was detected in 31.2% of samples using a commercial enzyme-linked immunosorbent assay. Genotyping revealed the presence of the globally circulating strains G1P8 (50.0%), G3P8 (23.0%), and G2P4 (8.2%). The globally emerging strains G9 and G12 were detected in 1.2% and 6.1% of samples, respectively. Mixed infections were detected in a high proportion of samples (11.9%), with 9.0% and 3.7% of samples displaying multiple G and P genotypes, respectively.
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