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Biomedical and Environmental Sciences :... Mar 2024This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A (RVA) in the Pearl River Delta region of Guangdong Province, China.
OBJECTIVE
This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A (RVA) in the Pearl River Delta region of Guangdong Province, China.
METHODS
This study included individuals aged 28 days-85 years. A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens, including RVA, using a Gastrointestinal Pathogen Panel, followed by genotyping, virus isolation, and complete sequencing to assess the genetic diversity of RVA.
RESULTS
The overall RVA infection rate was 14.59% (103/706), with an irregular epidemiological pattern. The proportion of co-infection with RVA and other pathogens was 39.81% (41/103). Acute gastroenteritis is highly prevalent in young children aged 0-1 year, and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea. G9P[8] (58.25%, 60/103) was found to be the predominant genotype in the RVA strains, and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis. Recombination analysis showed that gene reassortment events, selection pressure, codon usage bias, gene polymorphism, and post-translational modifications (PTMs) occurred in the G9P[8] and G3P[8] strains.
CONCLUSION
This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China, further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity. Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.
Topics: Child; Humans; Infant; Child, Preschool; Rotavirus; Rotavirus Infections; Phylogeny; Feces; Gastroenteritis; Genotype; China; Polymorphism, Genetic
PubMed: 38582992
DOI: 10.3967/bes2024.031 -
Heliyon Apr 2024While the gut microbiome modulates the pathogenesis of enteric viruses, how infections caused by rotavirus A (RVA), with or without diarrhoea, alter the gut microbiota...
BACKGROUND
While the gut microbiome modulates the pathogenesis of enteric viruses, how infections caused by rotavirus A (RVA), with or without diarrhoea, alter the gut microbiota has been sparsely studied.
METHODS
From a cohort of 224 vaccine naïve Gabonese children with and without diarrhoea (n = 177 and n = 67, respectively), 48 stool samples were analysed: (i) RVA with diarrhoea (n = 12); (ii) RVA without diarrhoea (n = 12); (iii) diarrhoea without RVA (n = 12); (iv) healthy controls without diarrhoea and RVA (n = 12). The 16S rRNA metabarcoding using Oxford Nanopore sequencing data was analysed for taxonomic composition, abundance, alpha and beta diversity, and metabolic pathways.
FINDINGS
Alpha diversity showed that children with acute diarrhoea (with and without RVA infection), and children with acute diarrhoea without RVA had low microbial diversity compared to healthy children (p = 0.001 and p = 0.006, respectively). No significant differences observed when comparing children with RVA with or without diarrhoea. Beta diversity revealed high microbial heterogeneity in children without diarrhoea. Proteobacteria (68%) and Firmicutes (69%) were most common in the diarrhoea and non-diarrhoea groups, respectively. Proteobacteria (53%) were most common in children without RVA, while Firmicutes (55%) were most common with RVA. At the genus level, (21%), (10%) and (4%) were abundant in children with diarrhoea, while (11%), (8%), (6%) and (5%) were abundant in children without diarrhoea. Metabolites involved in amino acid, carbohydrate, lipid, nucleotide, and vitamin metabolism were quantitatively altered.
INTERPRETATION
Although host physiology dictates the intestinal milieu, diarrhoea per se can alter a balanced gut microbiota, whereas infectious diarrhoea disrupts the gut microbiome and reduces its diversity.
PubMed: 38576575
DOI: 10.1016/j.heliyon.2024.e28727 -
Human Vaccines & Immunotherapeutics Dec 2024Rotavirus is the most common cause of diarrhea in children worldwide. In 2016, rotavirus infection resulted in 258 173 300 episodes of diarrhea and 128 500 child deaths...
Rotavirus vaccine dose-two dropout and its associated factors among children who received rotavirus vaccine dose-one in Sub-Saharan African countries: A multilevel analysis of the recent demographic and health survey.
Rotavirus is the most common cause of diarrhea in children worldwide. In 2016, rotavirus infection resulted in 258 173 300 episodes of diarrhea and 128 500 child deaths in the globe. The study aimed to assess the magnitude of Rotavirus vaccine dose-two dropout and associated factors among children who received rotavirus vaccine dose-one in sub-Saharan African countries. The appended and most recent demographic and health survey (DHS) dataset of 17 sub-Saharan African countries was used for data analysis. A total of 73,396 weighted samples were used. Factors associated with the outcome variable were considered significant if their -values were ≤ .05 in the multilevel mixed-effect logistic regression model. The overall Rotavirus vaccine dose-two dropouts was 10.77% (95% CI 10.55%, 11.00%), which ranged from 2.77% in Rwanda to 37.67% in Uganda. Being younger, late birth order, having difficulty accessing health facilities, having no media exposure, having no work, having home delivery, having no antenatal follow-up, and having no postnatal checkup were factors significantly associated with the outcome variable. The overall Rotavirus vaccine dose-two dropout was higher in sub-Saharan African countries which implies that vaccine dropout is still a great issue in the region. Special attention should be given to those mothers who are young, who have no work, who give birth at home, who experienced difficulty in accessing health facilities, and late birth orders. Furthermore, targeted interventions should be considered for improving access and utilization of media, antenatal care, and postnatal care services.
Topics: Child; Humans; Female; Pregnancy; Rotavirus Vaccines; Multilevel Analysis; Diarrhea; Africa South of the Sahara; Demography
PubMed: 38575525
DOI: 10.1080/21645515.2024.2335730 -
Human Vaccines & Immunotherapeutics Dec 2024Vaccine co-administration is a useful strategy for improving vaccine coverage and adherence. In Italy, an update to the national immunization program (NIP) in 2023... (Review)
Review
Vaccine co-administration is a useful strategy for improving vaccine coverage and adherence. In Italy, an update to the national immunization program (NIP) in 2023 included recommendations for co-administration of pediatric vaccines, including the four-component vaccine for meningococcus B (4CMenB), pneumococcal conjugate vaccine (PCV), hexavalent vaccines, and oral rotavirus vaccines. Safety is a major concern when considering vaccine co-administration; therefore, a literature review of the available evidence on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines was performed. Of 763 publications screened, two studies were reviewed that reported safety data on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines in infants aged 0-24 months. Overall, these studies supported that there were no significant safety signals when co-administering 4CMenB with PCV, hexavalent/pentavalent, and rotavirus vaccines, compared with individual vaccination. This review provides key insights for healthcare professionals on the tolerability of co-administering 4CMenB with routine vaccines.
Topics: Humans; Infant; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis, Serogroup B; Rotavirus Vaccines; Vaccination; Vaccines, Conjugate; Infant, Newborn; Pneumococcal Vaccines
PubMed: 38566502
DOI: 10.1080/21645515.2024.2333106 -
Bulletin of the World Health... Apr 2024To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019.
OBJECTIVE
To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019.
METHODS
We used child mortality and vaccine coverage data from the Global Burden of Disease Study. We used a modified child survival framework and applied a mixed-effects regression model to estimate the reduction in deaths in children younger than 5 years associated with eight vaccines.
FINDINGS
Between 1990 and 2019, the diphtheria-tetanus-pertussis (DTP), measles, rotavirus and type b vaccines were significantly associated with an estimated 86.9 (95% confidence interval, CI: 57.2 to 132.4) million fewer deaths in children younger than 5 years worldwide. This decrease represented a 24.2% (95% CI: 19.8 to 28.9) reduction in deaths relative to a scenario without vaccines. The DTP and measles vaccines averted 46.7 (95% CI: 30.0 to 72.7) million and 37.9 (95% CI: 25.4 to 56.8) million deaths, respectively. Of the total reduction in child mortality associated with vaccines, 84.2% (95% CI: 83.0 to 85.1) occurred in 73 countries supported by Gavi, the Vaccine Alliance, with an estimated 45.4 (95% CI: 29.8 to 69.2) million fewer deaths from 2000 to 2019. The largest reductions in deaths associated with these four vaccines were in India, China, Ethiopia, Pakistan and Bangladesh (in order of the size of reduction).
CONCLUSION
Vaccines continue to reduce childhood mortality significantly, especially in Gavi-supported countries, emphasizing the need for increased investment in routine immunization programmes.
Topics: Child; Humans; Infant; Immunization Programs; Vaccination; Measles Vaccine; Child Mortality; Whooping Cough; Measles; Diphtheria-Tetanus-Pertussis Vaccine
PubMed: 38562199
DOI: 10.2471/BLT.23.290129 -
Vaccine: X Jun 2024Estimates suggest that 78,000 children died due to rotavirus gastroenteritis annually between 2011 and 2013 in India. The north eastern state of Assam reported 38.4%...
BACKGROUND
Estimates suggest that 78,000 children died due to rotavirus gastroenteritis annually between 2011 and 2013 in India. The north eastern state of Assam reported 38.4% pediatric diarrheal admissions testing positive for rotavirus. Rotavirus vaccine (RVV) was introduced in Assam in 2017 following which the National Family Health Survey-5 (NFHS-5) (2019) revealed low RVV coverage in Assam with wide variation between the districts. the current study was conceptualized and undertaken to capture the enablers and barriers to RVV coverage in Assam.
METHODS
Qualitative study conducted in 5 randomly selected districts in Assam. Participants (key informants) were recruited by purposive sampling at each level of the health system including healthcare officials, service providers and caregivers based on availability. Thirty-five in-depth interviews (IDIs) and five focus group discussions (FGDs) were conducted. Interviews were tape recorded and transcribed. Data was coded and analyzed using the thematic framework approach.
RESULTS
Findings from the qualitative data collection were collated and analyzed under 7 identified themes. Difficult terrain, limited service provider availability and no catch-up training for new recruits were some of the barriers to RVV coverage. In contrast, Information, Education & Communication (IEC) in vernacular language, RVV safety profile, development partner support and adequate RVV supply were identified as some of the enablers of RVV coverage.
CONCLUSION
Few broad recommendations to overcome identified barriers include comprehensive inter-sectoral coordination, regular monitoring and frequent refresher training sessions. There is a need for a future study utilizing existing coverage data and larger sample size to triangulate the findings of this study.
PubMed: 38559753
DOI: 10.1016/j.jvacx.2024.100479 -
Clinical and Experimental Immunology Jun 2024Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is acquired early in childhood and modulates...
Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is acquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus-specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titers between human cytomegalovirus seropositive and seronegative infants. There was no evidence of an association between human cytomegalovirus serostatus at 9 months and rotavirus-specific antibody titers at 12 months (geometric mean ratio 1.01, 95% CI: 0.70, 1.45; P = 0.976) or fold-increase in RV-IgA titer between 9 and 12 months (risk ratio 0.999, 95%CI: 0.66, 1.52; P = 0.995) overall. However, HIV-exposed-uninfected infants who were seropositive for human cytomegalovirus at 9 months old had a 63% reduction in rotavirus antibody geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were seronegative for human cytomegalovirus (geometric mean ratio 0.37, 95% CI: 0.17, 0.77; P = 0.008). While the broader implications of human cytomegalovirus infections on oral rotavirus vaccine response might be limited in the general infant population, the potential impact in the HIV-exposed-uninfected infants cannot be overlooked. This study highlights the complexity of immunological responses and the need for targeted interventions to ensure oral rotavirus vaccine efficacy, especially in vulnerable subpopulations.
Topics: Humans; Rotavirus Vaccines; Cytomegalovirus; Infant; Antibodies, Viral; Cytomegalovirus Infections; HIV Infections; Male; Rotavirus Infections; Female; Immunogenicity, Vaccine; Rotavirus; Immunoglobulin A; Administration, Oral; Immunoglobulin M; Vaccination
PubMed: 38546123
DOI: 10.1093/cei/uxae029 -
Vaccines Mar 2024Bacterial lipopolysaccharides (LPSs) have been shown to promote enteric viral infections. This study tested the hypothesis that elevated levels of bacterial LPS improve...
Abundance of Selected Lipopolysaccharide-Rich Bacteria and Levels of Toll-like Receptor 4 and Interleukin 8 Expression Are Significantly Associated with Live Attenuated Rotavirus Vaccine Shedding among South African Infants.
Bacterial lipopolysaccharides (LPSs) have been shown to promote enteric viral infections. This study tested the hypothesis that elevated levels of bacterial LPS improve oral rotavirus vaccine replication in South African infants. Stool samples were collected from infants a week after rotavirus vaccination to identify vaccine virus shedders ( = 43) and non-shedders ( = 35). Quantitative real-time PCR was used to assay for selected LPS-rich bacteria, including , and , and to measure the gene expression of bacterial LPS, host Toll-like Receptor 4 (TLR4) and Interleukin-8 (IL-8). The abundance of selected LPS-rich bacteria was significantly higher in vaccine shedders (median log 4.89 CFU/g, IQR 2.84) compared to non-shedders (median log 3.13 CFU/g, IQR 2.74), = 0.006. The TLR4 and IL-8 gene expressions were increased four- and two-fold, respectively, in vaccine shedders versus non-shedders, but no difference was observed in the bacterial LPS expression, = 0.09. A regression analysis indicated a significant association between the abundance of selected LPS-rich bacteria and vaccine virus shedding (Odds ratio 1.5, 95% CI = 1.10-1.89), = 0.002. The findings suggest that harbouring higher counts of LPS-rich bacteria can increase the oral rotavirus vaccine take in infants.
PubMed: 38543907
DOI: 10.3390/vaccines12030273 -
Vaccines Mar 2024Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the...
Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8*) or expressed P2-VP8* as a fusion protein with lumazine synthase (LS-P2-VP8*) to allow the formation and secretion of protein particles that present VP8* on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8*-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8*-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8*-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8* compared to the P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines.
PubMed: 38543894
DOI: 10.3390/vaccines12030260 -
Viruses Mar 2024Porcine rotavirus A (PoRVA) is an enteric pathogen capable of causing severe diarrhea in suckling piglets. Investigating the prevalence and molecular characteristics of...
Porcine rotavirus A (PoRVA) is an enteric pathogen capable of causing severe diarrhea in suckling piglets. Investigating the prevalence and molecular characteristics of PoRVA in the world, including China, is of significance for disease prevention. In 2022, a total of 25,768 samples were collected from 230 farms across China, undergoing porcine RVA positivity testing. The results showed that 86.52% of the pig farms tested positive for porcine RVA, with an overall positive rate of 51.15%. Through the genetic evolution analysis of VP7, VP4 and VP6 genes, it was revealed that G9 is the predominant genotype within the VP7 segment, constituting 56.55%. VP4 genotypes were identified as P[13] (42.22%), P[23] (25.56%) and P[7] (22.22%). VP6 exhibited only two genotypes, namely I5 (88.81%) and I1 (11.19%). The prevailing genotype combination for RVA was determined as G9P[23]I5. Additionally, some RVA strains demonstrated significant homology between VP7, VP4 and VP6 genes and human RV strains, indicating the potential for human RV infection in pigs. Based on complete genome sequencing analysis, a special PoRVA strain, CHN/SD/LYXH2/2022/G4P[6]I1, had high homology with human RV strains, revealing genetic reassortment between human and porcine RV strains in vivo. Our data indicate the high prevalence, major genotypes, and cross-species transmission of porcine RVA in China. Therefore, the continuous monitoring of porcine RVA prevalence is essential, providing valuable insights for virus prevention and control, and supporting the development of candidate vaccines against porcine RVA.
Topics: Humans; Animals; Swine; Rotavirus; Phylogeny; Rotavirus Infections; Genome, Viral; Genotype
PubMed: 38543818
DOI: 10.3390/v16030453