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.
We identified a genotype G10P14 rotavirus strain in 5 children and 1 adult with acute gastroenteritis from the Northern Territory, Australia. Full genome sequence analysis identified an ...artiodactyl-like (bovine, ovine, and camelid) G10-P14-I2-R2-C2-M2-A11-N2-T6-E2-H3 genome constellation. This finding suggests artiodactyl-to-human transmission and strengthens the need to continue rotavirus strain surveillance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A ...birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. Methods This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0–5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0–5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. Findings 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90%) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13%) of 32 participants in the placebo group (difference in proportions 0·78, 95% CI 0·55–0·88; p<0·0001). 25 (93%) of 27 participants in the infant schedule group had a cumulative vaccine take after three doses compared with eight (25%) of 32 participants in the placebo group (difference in proportions 0·68, 0·44–0·81; p<0·0001). A serum IgA response was detected in 19 (63%) of 30 participants and 20 (74%) of 27 participants, and stool shedding of RV3-BB was detected in 21 (70%) of 30 participants and 21 (78%) of 27 participants in the neonatal and infant schedule groups, respectively. The frequency of solicited and unsolicited adverse events was similar across the treatment groups. RV3-BB vaccine was not associated with an increased frequency of fever or gastrointestinal symptoms compared with placebo. Interpretation RV3-BB vaccine was immunogenic and well tolerated when given as a three-dose neonatal or infant schedule. A birth dose strategy of RV3-BB vaccine has the potential to improve the effectiveness and implementation of rotavirus vaccines. Funding Australian National Health and Medical Research Council, the New Zealand Health Research Council, and the Murdoch Childrens Research Institute.
Human immunodeficiency virus type-1 (HIV-1) invades the central nervous system (CNS) during acute infection which can result in HIV-associated neurocognitive disorders in up to 50 % of patients, even ...in the presence of combination antiretroviral therapy (cART). Within the CNS, productive HIV-1 infection occurs in the perivascular macrophages and microglia. Astrocytes also become infected, although their infection is restricted and does not give rise to new viral particles. The major barrier to the elimination of HIV-1 is the establishment of viral reservoirs in different anatomical sites throughout the body and viral persistence during long-term treatment with cART. While the predominant viral reservoir is believed to be resting CD4
+
T cells in the blood, other anatomical compartments including the CNS, gut-associated lymphoid tissue, bone marrow, and genital tract can also harbour persistently infected cellular reservoirs of HIV-1. Viral latency is predominantly responsible for HIV-1 persistence and is most likely governed at the transcriptional level. Current clinical trials are testing transcriptional activators, in the background of cART, in an attempt to purge these viral reservoirs and reverse viral latency. These strategies aim to activate viral transcription in cells constituting the viral reservoir, so they can be recognised and cleared by the immune system, while new rounds of infection are blocked by co-administration of cART. The CNS has several unique characteristics that may result in differences in viral transcription and in the way latency is established. These include CNS-specific cell types, different transcription factors, altered immune surveillance, and reduced antiretroviral drug bioavailability. A comprehensive understanding of viral transcription and latency in the CNS is required in order to determine treatment outcomes when using transcriptional activators within the CNS.
Context
Habitat fragmentation is increasing as a result of anthropogenic activities, especially in urban areas. Dispersal through fragmented habitats is key for species to spread, persist in ...metapopulations and shift range in response to climate change. However, high habitat connectivity may also hasten the spread of invasive species.
Objective
To develop a model of spread in fragmented landscapes and apply it to the spread of an invasive insect in urban woodland.
Methods
We applied a patch-based model, based on electric network theory, to model the current and predicted future spread of oak processionary moth (OPM:
Thaumetopoea processionea
) from its source in west London. We compared the pattern of ‘effective distance’ from the source (i.e. the patch ‘voltage’ in the model) with the observed spread of the moth from 2006 to 2012.
Results
We showed that ‘effective distance’ fitted current spread of OPM. Patches varied considerably in their ‘current’ and ‘power’ (metrics from the model), which is an indication of their importance in the future spread of OPM.
Conclusions
Patches identified as ‘important’ are potential ‘pinch points’ and regions of high ‘flow’, where resources for detection and management will be most cost-effectively deployed. However, data on OPM dispersal and the distribution of oak trees limited the strength of our conclusions, so should be priorities for further data collection. This application of electric network theory can be used to inform landscape-scale conservation initiatives both to reduce the spread of invasives and to facilitate large-scale species’ range shifts in response to climate change.
Background: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. ...This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident.
Methods: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression.
Results: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05).
Conclusions: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.
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.
Rotavirus gastroenteritis is a leading global cause of mortality and morbidity in young children due to diarrhea and dehydration. Over 85% of deaths occur in developing countries. In industrialised ...countries, 2 live oral rotavirus vaccines licensed in 2006 quickly demonstrated high effectiveness, dramatically reducing severe rotavirus gastroenteritis admissions in many settings by more than 90%. In contrast, the same vaccines reduced severe rotavirus gastroenteritis by only 30-60% in developing countries, but have been proven life-saving. Bridging this "efficacy gap" offers the possibility to save many more lives of children under the age of 5. The reduced efficacy of rotavirus vaccines in developing settings may be related to differences in transmission dynamics, as well as host luminal, mucosal and immune factors. This review will examine strategies currently under study to target the issue of reduced efficacy and effectiveness of oral rotavirus vaccines in developing settings.
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.
A genotype G3P14 rotavirus strain was identified in a 12year old child presenting to the Emergency Department of the Royal Children's Hospital, Melbourne, with gastroenteritis. G3P14 strains have ...been previously identified in rabbits in Japan, China, the USA and Italy and a single lapine-like strain from a child in Belgium. Full genome sequence analysis of RVA/Human-wt/AUS/RCH272/2012/G3P14 (RCH272) revealed that the strain contained the novel genome constellation G3-P14-I2-R3-C3-M3-A9-N2-T6-E2-H3. The genome was genetically divergent to previously characterized lapine viruses and the genes were distantly related to a range of human bovine-like strains and animal strains of bovine, bat and canine/feline characteristics. The VP4, VP6, NSP2, NSP3, NSP4 and NSP5 genes of RCH272 clustered within bovine lineages in the phylogenetic analysis and shared moderate genetic similarity with an Australian bovine-like human strain RVA/Human-tc/AUS/MG6/1993/G6P14. Bayesian coalescent analysis suggested these genes of RCH272 and RVA/Human-tc/AUS/MG6/1993/G6P14 were derived from a population of relatively homogenous bovine-like ancestral strains circulating between 1943 and 1989. The VP7, VP1, VP2 and NSP1 genes shared moderate genetic similarity with the Chinese strain RVA/Bat-tc/CHN/MSLH14/2011/G3P3 and the VP3 gene clustered within a lineage comprised of canine and feline strains. This strain may represent the direct transmission from an unknown host species or be derived via multiple reassortment events between strains originating from various species. The patient lived in a household containing domesticated cats and dogs and in close proximity to a colony of Gray-headed Flying-foxes. However, without screening numerous animal populations it is not possible to determine the origins of this strain.
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