ABSTRACT
BACKGROUND: Histo-blood group antigen (HBGA) status may affect vaccine efficacy due to rotavirus strains binding to HBGAs in a P genotype-dependent manner. This study aimed to determine if HBGA status affected vaccine take of the G3P[6] neonatal vaccine RV3-BB. METHODS: DNA was extracted from stool samples collected in a subset (n = 164) of the RV3-BB phase IIb trial in Indonesian infants. FUT2 and FUT3 genes were amplified and sequenced, with any single-nucleotide polymorphisms analyzed to infer Lewis and secretor status. Measures of positive cumulative vaccine take were defined as serum immune response (immunoglobulin A or serum-neutralizing antibody) and/or stool excretion of RV3-BB virus. Participants were stratified by HBGA status and measures of vaccine take. RESULTS: In 147 of 164 participants, Lewis and secretor phenotype were determined. Positive vaccine take was recorded for 144 (97.9%) of 147 participants with the combined phenotype determined. Cumulative vaccine take was not significantly associated with secretor status (relative risk, 1.00 [95% CI, .94-1.06]; P = .97) or Lewis phenotype (relative risk, 1.03 [95% CI, .94-1.14]; P = .33), nor was a difference observed when analyzed by each component of vaccine take. CONCLUSIONS: The RV3-BB vaccine produced positive cumulative vaccine take, irrespective of HBGA status in Indonesian infants.
Subject(s)
Blood Group Antigens , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Infant , Infant, Newborn , Humans , Rotavirus Vaccines/genetics , Indonesia , GenotypeABSTRACT
BACKGROUND: Rotavirus is a major cause of gastroenteritis in childrenâ <5 years of age. The disease burden in older children, adults, and the elderly is underappreciated. This study describes rotavirus disease and genotypic diversity in the Australian population comprising childrenâ ≥5 years of age and adults. METHODS: Rotavirus positive fecal samples were collected from laboratories Australia-wide participating in the Australian Rotavirus Surveillance Program between 2010 and 2018. Rotavirus samples were genotyped using a heminested multiplex reverse-transcription polymerase chain reaction. Notification data from the National Notifiable Diseases Surveillance System were also analyzed. RESULTS: Rotavirus disease was highest in children aged 5-9 years and adultsâ ≥85 years. G2P[4] was the dominant genotype in the populationâ ≥5 years of age. Genotype distribution fluctuated annually and genotypic diversity varied among different age groups. Geographical differences in genotype distribution were observed based on the rotavirus vaccine administered to infantsâ <1 year of age. CONCLUSIONS: This study revealed a substantial burden of rotavirus disease in the populationâ ≥5 years of age, particularly in children 5-9 years and the elderly. This study highlights the continued need for rotavirus surveillance across the population, despite the implementation of efficacious vaccines.
Subject(s)
Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Adult , Aged , Australia/epidemiology , Child , Child, Preschool , Feces , Genotype , Humans , Infant , Rotavirus/genetics , Rotavirus Infections/prevention & controlABSTRACT
BACKGROUND: Household studies are crucial for understanding the transmission of SARS-CoV-2 infection, which may be underestimated from PCR testing of respiratory samples alone. We aim to combine the assessment of household mitigation measures; nasopharyngeal, saliva, and stool PCR testing; along with mucosal and systemic SARS-CoV-2-specific antibodies, to comprehensively characterize SARS-CoV-2 infection and transmission in households. METHODS: Between March and September 2020, we obtained samples from 92 participants in 26 households in Melbourne, Australia, in a 4-week period following the onset of infection with ancestral SARS-CoV-2 variants. RESULTS: The secondary attack rate was 36% (24/66) when using nasopharyngeal swab (NPS) PCR positivity alone. However, when respiratory and nonrespiratory samples were combined with antibody responses in blood and saliva, the secondary attack rate was 76% (50/66). SARS-CoV-2 viral load of the index case and household isolation measures were key factors that determine secondary transmission. In 27% (7/26) of households, all family members tested positive by NPS for SARS-CoV-2 and were characterized by lower respiratory Ct values than low transmission families (Median 22.62 vs. 32.91; IQR 17.06-28.67 vs. 30.37-34.24). High transmission families were associated with enhanced plasma antibody responses to multiple SARS-CoV-2 antigens and the presence of neutralizing antibodies. Three distinguishing saliva SARS-CoV-2 antibody features were identified according to age (IgA1 to Spike 1, IgA1 to nucleocapsid protein (NP)), suggesting that adults and children generate distinct mucosal antibody responses during the acute phase of infection. CONCLUSION: Utilizing respiratory and nonrespiratory PCR testing, along with the measurement of SARS-CoV-2-specific local and systemic antibodies, provides a more accurate assessment of infection within households and highlights some of the immunological differences in response between children and adults.
Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Viral , COVID-19/diagnosis , Child , Humans , Immunoglobulin AABSTRACT
To accelerate the formulation development of live-virus vaccine (LVV) candidates, more rapid approaches to rank-order formulations and estimate their real-time storage stability losses are needed. In this case-study, we utilize new and previously described stability data of a live, rotavirus vaccine candidate (RV3-BB) in three different liquid formulations to model and compare predicted vs. experimental RV3-BB stability profiles. Linear-regression extrapolations of limited real-time (2-8 °C) stability data and Arrhenius modeling of accelerated (15, 25, 37 °C) stability data provided predictions of RV3-BB real-time stability profiles (2-8 °C, 24 months). Good correlations of modeled versus experimental stability data to rank-order the RV3-BB formulations were achieved by employing (1) a high-throughput RT-qPCR assay to measure viral titers, (2) additional assay replicates and stability time-points, and (3) a -80 °C control for each formulation to benchmark results at each stability time-point and temperature. Instead of accumulating two-year, 2-8 °C storage stability data, the same rank-ordering of the three RV3-BB formulations could have been achieved by modeling 37°, 25°, 15° (and 2-8 °C) stability data over 1, 3 and 12 months, respectively. The results of this case-study are discussed in the context of accelerating LVV formulation development by expeditiously identifying stable formulations, estimating their shelf-lives, and determining vaccine vial monitoring (VVM) designations.
Subject(s)
Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Antibodies, Viral , Drug Stability , Humans , Rotavirus Infections/prevention & control , Vaccines, AttenuatedABSTRACT
Julie Bines discusses an accompanying study by Sheila Isanaka and colleagues on nutrient supplementation and immune responses to rotavirus vaccination.
Subject(s)
Dietary Supplements , Immunogenicity, Vaccine , Prenatal Nutritional Physiological Phenomena , Rotavirus Infections/prevention & control , Rotavirus Vaccines/immunology , Rotavirus/immunology , Africa , Female , Humans , Infant , Male , Pregnancy , Rotavirus Vaccines/administration & dosageABSTRACT
BACKGROUND: A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization. RESULTS: Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (P<0.001), 51% (95% CI, 7 to 76) in the infant-schedule group (P=0.03), and 63% (95% CI, 34 to 80) in the neonatal-schedule and infant-schedule groups combined (combined vaccine group) (P<0.001). Similar results were observed in the intention-to-treat analysis (1649 participants); the vaccine efficacy was 68% (95% CI, 35 to 86) in the neonatal-schedule group (P=0.001), 52% (95% CI, 11 to 76) in the infant-schedule group (P=0.02), and 60% (95% CI, 31 to 76) in the combined vaccine group (P<0.001). Vaccine response, as evidenced by serum immune response or shedding of RV3-BB in the stool, occurred in 78 of 83 participants (94%) in the neonatal-schedule group and in 83 of 84 participants (99%) in the infant-schedule group. The incidence of adverse events was similar across the groups. No episodes of intussusception occurred within the 21-day risk period after administration of any dose of vaccine or placebo, and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant-schedule group. CONCLUSIONS: RV3-BB was efficacious in preventing severe rotavirus gastroenteritis when administered according to a neonatal or an infant schedule in Indonesia. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612001282875 .).
Subject(s)
Gastroenteritis/prevention & control , Rotavirus Infections/prevention & control , Rotavirus Vaccines/immunology , Administration, Oral , Double-Blind Method , Feces/virology , Female , Gastroenteritis/epidemiology , Gastroenteritis/virology , Humans , Immunization Schedule , Indonesia , Infant , Infant, Newborn , Intention to Treat Analysis , Male , Rotavirus/isolation & purification , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: VP4 [P] genotype binding specificities of rotaviruses and differential expression of histo-blood group antigens (HBGAs) between populations may contribute to reduced efficacy against severe rotavirus disease. P[6]-based rotavirus vaccines could broaden protection in such settings, particularly in Africa, where the Lewis-negative phenotype and P[6] rotavirus strains are common. METHODS: The association between HBGA status and G3P[6] rotavirus vaccine (RV3-BB) take was investigated in a phase 2A study of RV3-BB vaccine involving 46 individuals in Dunedin, New Zealand, during 2012-2014. FUT2 and FUT3 genotypes were determined from DNA extracted from stool specimens, and frequencies of positive cumulative vaccine take, defined as an RV3-BB serum immune response (either immunoglobulin A or serum neutralizing antibody) and/or stool excretion of the vaccine strain, stratified by HBGA status were determined. RESULTS: RV3-BB produced positive cumulative vaccine take in 29 of 32 individuals (91%) who expressed a functional FUT2 enzyme (the secretor group), 13 of 13 (100%) who were FUT2 null (the nonsecretor group), and 1 of 1 with reduced FUT2 activity (i.e., a weak secretor); in 37 of 40 individuals (93%) who expressed a functional FUT3 enzyme (the Lewis-positive group) and 3 of 3 who were FUT3 null (the Lewis-negative group); and in 25 of 28 Lewis-positive secretors (89%), 12 of 12 Lewis-positive nonsecretors (100%), 2 of 2 Lewis-negative secretors, and 1 of 1 Lewis-negative weak secretor. CONCLUSIONS: RV3-BB produced positive cumulative vaccine take irrespective of HBGA status. RV3-BB has the potential to provide an improved level of protection in settings where P[6] rotavirus disease is endemic, irrespective of the HBGA profile of the population.
Subject(s)
Blood Group Antigens , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/immunology , Antibodies, Viral/blood , Cohort Studies , Feces/enzymology , Fucosyltransferases/genetics , Humans , Infant, Newborn , Galactoside 2-alpha-L-fucosyltransferaseABSTRACT
PURPOSE OF REVIEW: Trace elements are vital components involved in major body functions. Cases of trace elements deficiencies are increasingly encountered in clinical practice, although often underrecognized. This review gives a thorough insight into the newest findings on clinical situations associated with trace elements deficiencies in children and adults, their recognition and management. RECENT FINDINGS: Trace elements deficiencies are frequently found in various conditions, most commonly in burns, bariatric surgery, intestinal failure, renal replacement therapy, oncology, critical illness and cardiac surgery. The main trace elements involved are selenium, zinc, copper and iron. Trace elements deficiencies are associated with increased risk of morbidity and mortality. Recognition of clinical signs of trace elements deficiencies can be challenging. Although trace elements supplementation is indisputable in many circumstances, it is still debatable in other situations such as sepsis and cardiac surgery. SUMMARY: Recent findings on trace elements deficiencies could have important implications on health outcomes. Trace elements delivery is a core component of nutritional care. Front-line clinicians should be aware of at-risk clinical situations to provide correct and timely intervention. Future research should be directed towards investigating the potential benefits of antioxidant trace elements supplementation in children in whom studies are scarce, especially in critical conditions such as burns, sepsis and cardiac surgery.
Subject(s)
Deficiency Diseases/etiology , Trace Elements/deficiency , Deficiency Diseases/diagnosis , Deficiency Diseases/therapy , Humans , Trace Elements/administration & dosageABSTRACT
Intestinal failure is a complex and debilitating condition characterised by inadequate small intestinal function requiring parenteral or intravenous nutrition to maintain health and, for children, to enable growth and development. Although parenteral nutrition can be prescribed in many hospitals, children with chronic intestinal failure have improved outcomes when managed at a paediatric centre by a multidisciplinary team with specialised expertise in the comprehensive management of intestinal failure. Recent advances in the medical, surgical and nutritional approach have been effective at optimising intestinal rehabilitation and achieving enteral autonomy while limiting complications of intestinal failure. The role of intestinal transplantation in the management of the child with intestinal failure continues to evolve as an option for children with life-threatening complications of intestinal failure. The aim of this review is to highlight key advances in the care of children with intestinal failure.
Subject(s)
Intestinal Diseases , Short Bowel Syndrome , Child , Humans , Intestinal Diseases/surgery , Intestine, Small , Intestines , Parenteral Nutrition , Short Bowel Syndrome/therapyABSTRACT
BACKGROUND AND AIMS: The aim of the study was to aid decisions on prognosis and transplantation; this study describes the outcome of children with intestinal failure managed by the multidisciplinary intestinal rehabilitation program at the Royal Children's Hospital, Melbourne. METHODS: Retrospective review of children requiring parenteral nutrition (PN) for >3 months who were assessed for home PN between 1991 and 2011. RESULTS: A total of 51 children were included. Forty-two (82%) had short bowel syndrome (SBS), 5 (10%) had chronic intestinal pseudo-obstruction syndrome, and 4 (8%) had congenital enteropathies. Median small bowel length for patients with SBS was 45âcm (interquartile range 30-80) or 23.9% of the expected length for age (interquartile range 17.0%-40.6%). Overall survival rate was 84% (43/51). Mortality in children (nâ=â7) occurred after a median of 13.2 months (range 6.2-29.2) with intestinal failure-associated liver disease (IFALD) being the only predictor (Pâ=â0.001). Out of 50 children 21 (42%) had IFALD. Children who were premature (Pâ=â0.013), had SBS (Pâ=â0.038), and/or frequent sepsis (Pâ=â0.014) were more likely to develop IFALD. PN weaning occurred in 27 of 35 (77%) SBS survivors, after a median of 10.8 months (up to 8.2 years), with longer residual small bowel (Pâ=â0.025), preservation of the ileocecal valve (Pâ=â0.013) and colon (Pâ=â0.011) being predictors. None of 5 (0%) patients with chronic intestinal pseudo-obstruction syndrome and 2 of 4 (50%) patients with congenital enteropathies weaned off PN. Overall sepsis rate was 7.3 episodes/1000 line days. Frequency of sepsis and longevity of central lines improved with time as patients grew older (both Pâ<â0.001). CONCLUSIONS: Long-term PN with intestinal rehabilitation was effective in treating most children with intestinal failure. Children with severe refractory IFALD may have benefited from intestinal transplantation.
Subject(s)
Liver Failure/complications , Parenteral Nutrition, Total , Patient Care Team , Short Bowel Syndrome/mortality , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective Studies , Short Bowel Syndrome/complications , Short Bowel Syndrome/rehabilitation , Survival Analysis , Tertiary Care Centers , VictoriaABSTRACT
Background: 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. Methods: 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. Results: G1P[8] 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 G12P[8] dominant in states using RotaTeq, and equine-like G3P[8] and G2P[4] dominant in states and territories using Rotarix. Conclusions: The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia.
Subject(s)
Genetic Variation , Rotavirus Infections/epidemiology , Rotavirus Infections/virology , Rotavirus Vaccines/administration & dosage , Rotavirus/classification , Rotavirus/isolation & purification , Australia/epidemiology , Child, Preschool , Epidemiological Monitoring , Female , Genotype , Genotyping Techniques , Humans , Infant , Infant, Newborn , Longitudinal Studies , Male , Multiplex Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Rotavirus/genetics , Rotavirus Infections/prevention & control , Rotavirus Vaccines/immunology , Serotyping , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunologyABSTRACT
This report from the Australian Rotavirus Surveillance Program (ARSP) and collaborating laboratories Australia-wide, describes the rotavirus genotypes identified in children and adults with acute gastroenteritis during the period 1 January to 31 December 2016. During this period, 949 faecal specimens were referred for rotavirus G and P genotype analysis, of which 230 were confirmed as positive for wildtype rotavirus, and 184 were identified as rotavirus vaccine-like. Genotype analysis of the 230 samples from both children and adults revealed that G2P[4] was the dominant genotype in this reporting period nationally, identified in 29% of samples, followed by equine-like G3P[8] and G12P[8] (19% and 15% respectively). Genotype distribution remained distinct between States using RotaTeq® and Rotarix® vaccines. In RotaTeq ® States, G12P[8] strains were more common, while G2P[4] and equine-like G3P[8] genotypes were more common in Rotarix® States and Territories. This report highlights the continued dominance of G12P[8] strains in RotaTeq® States and co-dominance of G2P[4] and equine-like G3P[8] in States and Territories using Rotarix®.
Subject(s)
National Health Programs , Population Surveillance , Rotavirus Infections/epidemiology , Rotavirus Infections/virology , Rotavirus , Australia/epidemiology , Child, Preschool , Feces/virology , Female , Genotype , History, 21st Century , Humans , Infant , Infant, Newborn , Male , Molecular Typing , Rotavirus/classification , Rotavirus/genetics , Rotavirus/isolation & purification , Rotavirus Infections/history , Rotavirus Infections/prevention & control , Rotavirus Vaccines/immunologyABSTRACT
BACKGROUND AND AIM: Short bowel syndrome (SBS) is primarily characterized by malabsorption and malnutrition, resulting from loss of intestinal absorptive area following massive small bowel resection (SBR). Bile acids and the gut microbiota are functionally linked within the gut-liver axis; however, SBS-associated disturbances within the gut-liver axis remain largely unexplored. The aim of this study was to characterize the evolution of bile acid alterations within the gut-liver axis at both short-term and long-term time points and to relate these changes to alterations in colonic bacterial composition. METHODS: Four-week-old piglets were assigned to 75% SBR, sham-operation or non-operation control groups. High throughput sequencing was employed to determine bacterial abundance in colonic content and ultra-performance liquid chromatography used to determine the bile acid concentration of gall bladder, portal serum, and fecal samples. RESULTS: Bile acid complexity and relative abundance are altered in the SBS piglet model at two weeks post-SBR, and these changes persisted at six weeks post-SBR. Our examination of the microbial profile revealed an early and persistent loss in bacteria belonging to the Clostridiales order. CONCLUSIONS: This study provides evidence of an early and persistent disturbance of the bile acid profile throughout the entero-hepatic circulation with an increase in the proportion of primary bile acids and a decrease in secondary bile acids following SBR. These changes were associated with a loss of bacteria belonging to the Clostridiales order consistent with a disturbance in the bile-microbial axis following SBR.
Subject(s)
Bile Acids and Salts/metabolism , Clostridiales/growth & development , Colon/microbiology , Gastrointestinal Microbiome , Liver/metabolism , Short Bowel Syndrome/metabolism , Short Bowel Syndrome/microbiology , Animals , Animals, Newborn , Bile Acids and Salts/blood , Colon/physiopathology , Disease Models, Animal , Feces/chemistry , Gallbladder/metabolism , Short Bowel Syndrome/physiopathology , Swine , Time FactorsABSTRACT
The Australian Rotavirus Surveillance Program, together with collaborating laboratories Australia-wide, reports the rotavirus genotypes responsible for the hospitalisation of children with acute gastroenteritis during the period 1 January to 31 December 2015. During the survey period, 1,383 faecal samples were referred for rotavirus G and P genotype analysis, and of these, 1,031 were confirmed as rotavirus positive. A total of 634 specimens had been collected from children under 5 years of age, while 397 were from older children and adults. Genotype analysis of samples from both children and adults revealed that G12P[8] was the dominant genotype in this reporting period, identified in 48.2% of strains nationally. Genotype G3P[8] was the second most common strain nationally, representing 22.8% of samples, followed by G2P[4] and G1P[8] (9% and 8% respectively). G3P[8] was further divided as equine-like G3P[8] (13.2% of all strains) and other wild-type G3P[8] (9.6%). This report highlights the continued predominance of G12P[8] strains as the major cause of disease in this population. Genotype distribution was distinct between jurisdictions using RotaTeq and Rotarix vaccines. Genotype G12P[8] was more common in states using RotaTeq, while equine-like G3P[8] and G2P[4] were more common in the states and territories using Rotarix. This survey highlights the dynamic change in rotavirus genotypes observed since vaccine introduction, including the emergence of a novel equine-like G3P[8] as a major strain. The prolonged dominance of G12P[8] for a 4th consecutive year further illustrates the unexpected trends in the wild type rotaviruses circulating in the Australian population since vaccine introduction.
Subject(s)
Population Surveillance , Rotavirus Infections/epidemiology , Rotavirus Infections/microbiology , Rotavirus/genetics , Adolescent , Adult , Age Distribution , Annual Reports as Topic , Australia/epidemiology , Child , Child, Preschool , Feces/virology , Female , Gastroenteritis/epidemiology , Gastroenteritis/virology , Genotype , History, 21st Century , Humans , Infant , Infant, Newborn , Male , Middle Aged , Rotavirus Infections/history , Rotavirus Infections/prevention & control , Rotavirus Vaccines/immunology , Young AdultABSTRACT
Rotavirus, the commonest cause of severe dehydrating gastroenteritis world-wide, was discovered less than 50 years ago. It causes about 450,000 deaths per year in children <5 years of age and hospitalises millions more. Rotavirus vaccines have been shown to have a major impact on hospital admissions due to rotavirus gastroenteritis and all-cause gastroenteritis and reduce mortality in developing countries. In Australia, there has been a 71% decrease in rotavirus hospitalisations in children 0-5 years of age. From the discovery of rotavirus as the major causative agent for severe gastroenteritis, through vaccine development and vaccine post-marketing surveillance activities, Australian scientists and clinicians have played a significant role in the global effort to reduce the burden of rotavirus infection.
Subject(s)
Gastroenteritis/history , Rotavirus Infections/history , Rotavirus Vaccines/history , Australia/epidemiology , Child, Preschool , Developed Countries , Developing Countries , Gastroenteritis/epidemiology , Gastroenteritis/prevention & control , Gastroenteritis/virology , Global Health , History, 20th Century , History, 21st Century , Humans , Infant , Rotavirus Infections/epidemiology , Rotavirus Infections/prevention & controlABSTRACT
BACKGROUND & AIMS: Despite the mortality associated with liver disease observed in patients with short bowel syndrome (SBS), mechanisms underlying the development of SBS-associated liver disease (SBS-ALD) are poorly understood. This study examines the impact of bacterially-mediated bile acid (BA) dysmetabolism on farnesoid X receptor (FXR) signalling pathways and clinical outcome in a piglet model of SBS-ALD. METHODS: 4-week old piglets underwent 75% small bowel resection (SBR) or sham operation. Liver histology and hepatic inflammatory gene expression were examined. Abundance of BA biotransforming bacteria was determined and metabolomic studies detailed the alterations in BA composition of stool, portal serum and bile samples. Gene expression of intestinal and hepatic FXR target genes and small heterodimer partner (SHP) transrepression targets were assessed. RESULTS: Histological evidence of SBS-ALD included liver bile duct proliferation, hepatocyte ballooning and fibrosis. Inflammatory gene expression was increased. Microbiota changes included a 10-fold decrease in Clostridium and a two-fold decrease in Bacteroides in SBS-ALD piglets. BA composition was altered and reflected a primary BA dominant composition. Intestinal and hepatic regulation of BA synthesis was characterised by a blunted intestinal FXR activation response and a failure of SHP to repress key hepatic targets. CONCLUSIONS: We propose a pathological scenario in which microbial dysbiosis following SBR results in significant BA dysmetabolism and consequent outcomes including steatorrhoea, persistent diarrhoea and liver damage. Furthermore alterations in BA composition may have contributed to the observed disturbance in FXR-mediated signalling pathways. These findings provide an insight into the complex mechanisms mediating the development of liver disease in patients with SBS.
Subject(s)
Bile Acids and Salts/metabolism , Liver Diseases/etiology , Liver Diseases/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Short Bowel Syndrome/complications , Short Bowel Syndrome/metabolism , Animals , Disease Models, Animal , Female , Humans , Liver/pathology , Liver Diseases/microbiology , Microbiota , Short Bowel Syndrome/microbiology , Signal Transduction , Sus scrofaABSTRACT
Abstract: This report from the Australian Rotavirus Surveillance Program describes the circulating rotavirus genotypes identified in children and adults during the period 1 January to 31 December 2022. After two years of a lower number of stool samples received as a result of the coronavirus disease 2019 (COVID-19) pandemic, this reporting period saw the highest number of samples received since the 2017 surveillance period, with samples received from all states and territories. During this period, 1,379 faecal specimens had been referred for rotavirus G- and P- genotype analysis, of which 1,276 were confirmed as rotavirus positive. In total, 1,119/1,276 were identified as wildtype rotavirus, 155/1,276 identified as the Rotarix vaccine strain and 2/1,276 that could not be confirmed as vaccine or wildtype due to sequencing failure. Whilst G12P[8] was the dominant genotype nationally among wildtype samples (28.2%; 315/1,119), multiple genotypes were identified at similar frequencies including G9P[4] (22.3%; 249/1,119) and G2P[4] (20.3%; 227/1,119). Geographical differences in genotype distribution were observed, largely driven by outbreaks reported in some jurisdictions. Outbreaks and increased reports of rotavirus disease were reported in the Northern Territory, Queensland, and New South Wales. A small number of unusual genotypes, potentially zoonotic in nature, were identified, including: G8P[14]; G10[14]; caninelike G3P[3]; G6P[9]; and G11P[25]. Ongoing rotavirus surveillance is crucial to identify changes in genotypic patterns and to provide diagnostic laboratories with quality assurance by reporting incidences of wildtype, vaccine-like, or false positive rotavirus results.
Subject(s)
Feces , Genotype , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Humans , Rotavirus Infections/epidemiology , Rotavirus Infections/virology , Rotavirus/genetics , Australia/epidemiology , Feces/virology , Child, Preschool , Infant , Child , Adult , COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2/genetics , Adolescent , Female , Male , Disease Outbreaks , Vaccines, Attenuated , Infant, Newborn , Annual Reports as Topic , Epidemiological Monitoring , Middle AgedABSTRACT
BACKGROUND: Wastewater-based epidemiology (WBE) surveillance has been proposed as an early warning system (EWS) for community SARS-CoV-2 transmission. However, there is limited data from low-and middle-income countries (LMICs). This study aimed to assess the ability of WBE surveillance to detect SARS-CoV-2 in formal and informal environments in Indonesia using different methods of sample collection, to compare WBE data with patterns of clinical cases of COVID-19 within the relevant communities, and to assess the WBE potential to be used as an EWS for SARS-CoV-2 outbreaks within a community. MATERIALS AND METHODS: We conducted WBE surveillance in three districts in Yogyakarta province, Indonesia, over eleven months (27 July 2021 to 7 January 2022 [Delta wave]; 18 January to 3 June 2022 [Omicron wave]). Water samples using grab, and/or passive sampling methods and soil samples were collected either weekly or fortnightly. RNA was extracted from membrane filters from processed water samples and directly from soil. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) was performed to detect the SARS-CoV-2 N and ORF1ab genes. RESULTS: A total of 1,582 samples were collected. Detection rates of SARS-CoV-2 in wastewater reflected the incidence of community cases, with rates of 85% at the peak to 2% at the end of the Delta wave and from 94% to 11% during the Omicron wave. A 2-week lag time was observed between the detection of SARS-CoV-2 in wastewater and increasing cases in the corresponding community. CONCLUSION: WBE surveillance for SARS-CoV-2 in Indonesia was effective in monitoring patterns of cases of COVID-19 and served as an early warning system, predicting the increasing incidence of COVID-19 cases in the community.
Subject(s)
COVID-19 , SARS-CoV-2 , Wastewater , Indonesia/epidemiology , COVID-19/epidemiology , COVID-19/diagnosis , COVID-19/virology , Humans , SARS-CoV-2/isolation & purification , SARS-CoV-2/genetics , Wastewater/virology , Wastewater-Based Epidemiological MonitoringABSTRACT
Animal rotaviruses A (RVAs) are considered the source of emerging, novel RVA strains that have the potential to cause global spread in humans. A case in point was the emergence of G8 bovine RVA consisting of the P[8] VP4 gene and the DS-1-like backbone genes that appeared to have jumped into humans recently. However, it was not well documented what evolutionary changes occurred on the animal RVA-derived genes during circulation in humans. Rotavirus surveillance in Vietnam found that DS-1-like G8P[8] strains emerged in 2014, circulated in two prevalent waves, and disappeared in 2021. This surveillance provided us with a unique opportunity to investigate the whole process of evolutionary changes, which occurred in an animal RVA that had jumped the host species barrier. Of the 843 G8P[8] samples collected from children with acute diarrhoea in Vietnam between 2014 and 2021, fifty-eight strains were selected based on their distinctive electropherotypes of the genomic RNA identified using polyacrylamide gel electrophoresis. Whole-genome sequence analysis of those fifty-eight strains showed that the strains dominant during the first wave of prevalence (2014-17) carried animal RVA-derived VP1, NSP2, and NSP4 genes. However, the strains from the second wave of prevalence (2018-21) lost these genes, which were replaced with cognate human RVA-derived genes, thus creating strain with G8P[8] on a fully DS-1-like human RVA gene backbone. The G8 VP7 and P[8] VP4 genes underwent some point mutations but the phylogenetic lineages to which they belonged remained unchanged. We, therefore, propose a hypothesis regarding the tendency for the animal RVA-derived genes to be expelled from the backbone genes of the progeny strains after crossing the host species barrier. This study underlines the importance of long-term surveillance of circulating wild-type strains in order to better understand the adaptation process and the fate of newly emerging, animal-derived RVA among the human population. Further studies are warranted to disclose the molecular mechanisms by which spillover animal RVAs become readily transmissible among humans, and the roles played by the expulsion of animal-derived genes and herd immunity formed in the local population.
ABSTRACT
Hospitals are complex places that provide a rich learning environment for students, staff, patients and their families, professional groups and the community. The "new" Royal Children's Hospital opened in late 2011. Its mission is focused on improving health and well-being of children and adolescents through leadership in healthcare, research and education. Addressing the need to create "responsive learning environments" aligned with the shift to student-centred pedagogy, two distinct learning environments were developed within the new Royal Children's Hospital; (i) a dedicated education precinct providing a suite of physical environments to promote a more active, collaborative and social learning experience for education and training programs conducted on the Royal Children's Hospital campus and (ii) a suite of learning spaces embedded within clinical areas so that learning becomes an integral part of the daily activities of this busy Hospital environment. The aim of this article is to present the overarching educational principles that lead the design of these learning spaces and describe the opportunities and obstacles encountered in the development of collaborative learning spaces within a large hospital development.