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Vaccine May 2024We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly...
A randomized, double-blind, placebo-controlled phase I clinical trial of rotavirus inactivated vaccine (Vero cell) in a healthy adult population aged 18-49 years to assess safety and preliminary observation of immunogenicity.
We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly assigned to one of three groups (high-dose, medium-dose, and low-dose) at a 3:1 ratio to receive one vaccine dose or placebo. Adverse events up to 28 days after each dose and serious adverse events up to 6 months after all doses were reported. Geometric mean titers and seroconversion rates were measured for anti-rotavirus neutralizing antibodies using microneutralization tests. The rates of total adverse events in the placebo group, low-dose group, medium-dose group, and high-dose group were 29.17 % (12.62 %-51.09 %), 12.50 % (2.66 %-32.36 %), 50.00 % (29.12 %-70.88 %), and 41.67 % (22.11 %-63.36 %), respectively, with no significant difference in the experimental groups compared with the placebo group. The results of the neutralizing antibody assay showed that in the adult group, the neutralizing antibody geometric mean titer at 28 days after full immunization in the low-dose group was 583.01 (95 % confidence interval [CI]: 447.12-760.20), that in the medium-dose group was 899.34 (95 % CI: 601.73-1344.14), and that in the high-dose group was 1055.24 (95 % CI: 876.28-1270.75). The GMT of serum-specific IgG at 28 days after full immunization in the low-dose group was 3444.26 (95 % CI: 2292.35-5175.02), that in the medium-dose group was 6888.55 (95 % CI: 4426.67-10719.6), and that in the high-dose group was 7511.99 (95 % CI: 3988.27-14149.0). The GMT of serum-specific IgA at 28 days after full immunization in the low-dose group was 2332.14 (95 % CI: 1538.82-3534.45), that in the medium-dose group was 4800.98 (95 % CI: 2986.64-7717.50), and that in the high-dose group was 3204.30 (95 % CI: 2175.66-4719.27). In terms of safety, adverse events were mainly Grades 1 and 2, indicating that the safety of the vaccine is within the acceptable range in the healthy adult population. Considering the GMT and positive transfer rate of neutralizing antibodies for the main immunogenicity endpoints in the experimental groups, it was initially observed that the high-dose group had higher levels of neutralizing antibodies than the medium- and low-dose groups in adults aged 18-49 years. This novel inactivated rotavirus vaccine was generally well-tolerated in adults, and the vaccine was immunogenic in adults (ClinicalTrials.gov number, NCT04626856).
PubMed: 38796326
DOI: 10.1016/j.vaccine.2024.05.014 -
Viruses Apr 2024The suboptimal performance of rotavirus (RV) vaccines in developing countries and in animals necessitates further research on the development of novel therapeutics and...
The suboptimal performance of rotavirus (RV) vaccines in developing countries and in animals necessitates further research on the development of novel therapeutics and control strategies. To initiate infection, RV interacts with cell-surface -glycans, including histo-blood group antigens (HBGAs). We have previously demonstrated that certain non-pathogenic bacteria express HBGA like substances (HBGA) capable of binding RV particles in vitro. We hypothesized that HBGA bacteria can bind RV particles in the gut lumen protecting against RV species A (RVA), B (RVB), and C (RVC) infection in vivo. In this study, germ-free piglets were colonized with HBGA or HBGA bacterial cocktail and infected with RVA/RVB/RVC of different genotypes. Diarrhea severity, virus shedding, immunoglobulin A (IgA) Ab titers, and cytokine levels were evaluated. Overall, colonization with HBGA bacteria resulted in reduced diarrhea severity and virus shedding compared to the HBGA bacteria. Consistent with our hypothesis, the reduced severity of RV disease and infection was not associated with significant alterations in immune responses. Additionally, colonization with HBGA bacteria conferred beneficial effects irrespective of the piglet HBGA phenotype. These findings are the first experimental evidence that probiotic performance in vivo can be improved by including HBGA bacteria, providing decoy epitopes for broader/more consistent protection against diverse RVs.
Topics: Animals; Rotavirus Infections; Swine; Germ-Free Life; Rotavirus; Blood Group Antigens; Diarrhea; Swine Diseases; Virus Shedding; Bacteria; Immunoglobulin A; Antibodies, Viral; Cytokines
PubMed: 38793542
DOI: 10.3390/v16050660 -
Journal of Medical Virology Jun 2024The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to...
The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of vaccine-associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine-associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine-associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 [40.11%]) of vaccine-associated facial paralysis from 49 537 reports of all-cause facial paralysis. Vaccine-associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID-19) pandemic, which is attributable to the COVID-19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID-19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 [95% confidence interval, 27.60-29.03]; IC, 3.37 [IC, 3.35]), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella-zoster, meningococcal, Ad-5 vectored COVID-19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole-virus COVID-19 vaccines. Concerning age- and sex-specific risks, vaccine-associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine-associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine-induced facial paralysis, primarily owing to COVID-19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine-associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.
Topics: Humans; Facial Paralysis; Pharmacovigilance; Male; World Health Organization; Female; Adult; Middle Aged; Adolescent; Young Adult; Databases, Factual; Child; Child, Preschool; Aged; Incidence; Vaccines; Global Health; COVID-19; Infant; Vaccination; SARS-CoV-2
PubMed: 38783823
DOI: 10.1002/jmv.29682 -
Human Vaccines & Immunotherapeutics Dec 2024The COVID-19 pandemic has significantly disrupted healthcare systems at all levels globally, notably affecting routine healthcare services, such as childhood...
The COVID-19 pandemic has significantly disrupted healthcare systems at all levels globally, notably affecting routine healthcare services, such as childhood vaccination. This study examined the impact of these disruptions on routine childhood vaccination programmes in Tanzania. We conducted a longitudinal study over four years in five Tanzanian regions: Mwanza, Dar es Salaam, Mtwara, Arusha, and Dodoma. This study analyzed the trends in the use of six essential vaccines: Bacille Calmette-Guérin (BCG), bivalent Oral Polio Vaccine (bOPV), Diphtheria Tetanus Pertussis, Hepatitis-B and Hib (DTP-HepB-Hib), measles-rubella (MR), Pneumococcal Conjugate Vaccine (PCV), and Rota vaccines. We evaluated annual and monthly vaccination trends using time-series and regression analyses. Predictive modeling was performed using an autoregressive integrated moving average (ARIMA) model. A total of 32,602,734 vaccination events were recorded across the regions from 2019 to 2022. Despite declining vaccination rates in 2020, there was a notable rebound in 2021, indicating the resilience of Tanzania's immunization program. The analysis also highlighted regional differences in vaccination rates when standardized per 1000 people. Seasonal fluctuations were observed in monthly vaccination rates, with BCG showing the most stable trend. Predictive modeling of BCG indicated stable and increasing vaccination coverage by 2023. These findings underscore the robustness of Tanzania's childhood immunization infrastructure in overcoming the challenges posed by the COVID-19 pandemic, as indicated by the strong recovery of vaccination rates post-2020. We provide valuable insights into the dynamics of vaccination during a global health crisis and highlight the importance of sustained immunization efforts to maintain public health.
Topics: Humans; Tanzania; COVID-19; Vaccination; Longitudinal Studies; Infant; Child, Preschool; Immunization Programs; Child; BCG Vaccine; SARS-CoV-2; Pandemics
PubMed: 38780570
DOI: 10.1080/21645515.2024.2356342 -
BMC Pediatrics May 2024Rotavirus has a significant morbidity and mortality in children under two years. The burden of rotavirus diarrhea 4 years post introduction of rotavirus vaccine in...
Prevalence and factors associated with rotavirus diarrhea among children aged 3-24 months after the introduction of the vaccine at a referral hospital in Uganda: a cross-sectional study.
BACKGROUND
Rotavirus has a significant morbidity and mortality in children under two years. The burden of rotavirus diarrhea 4 years post introduction of rotavirus vaccine in Uganda is not well established. This study aimed to determine the prevalence, severity of dehydration and factors associated with rotavirus diarrhea among children aged 3 to 24 months after the introduction of the vaccine at Fort Portal Regional Referral hospital.
METHODS
This was a cross-sectional hospital-based study in which children with acute watery diarrhea were included. A rectal tube was used to collect a stool sample for those unable to provide samples. Stool was tested for rotavirus using rapid immunochromatographic assay. Data was analysed using SPSS version 22 with logistic regression done to determine the factors.
RESULTS
Out of 268 children with acute watery diarrhea, 133 (49.6%) were females. Rotavirus test was positive in 42 (15.7%), majority of whom had some dehydration 28(66.7%). The factors that were independently associated with rotavirus diarrhea were; age < 12 months (AOR = 8.87, P = 0.014), male gender (AOR = 0.08, P = 0.001), coming from a home with another person with diarrhea (AOR = 17.82, P = 0.001) or a home where the water source was a well (AOR = 50.17, P = 0.002).
CONCLUSION
The prevalence of rotavirus diarrhea was three times less in the post rotavirus vaccination period compared to pre-rota vaccination period. Majority of the participants with rotavirus diarrhea had some dehydration. There is need for provision of safe water sources to all homes. Surveillance to determine the cause of the non rota diarrhea should be done.
Topics: Humans; Uganda; Cross-Sectional Studies; Male; Female; Infant; Rotavirus Vaccines; Prevalence; Rotavirus Infections; Risk Factors; Child, Preschool; Dehydration; Diarrhea; Feces; Logistic Models; Diarrhea, Infantile
PubMed: 38778329
DOI: 10.1186/s12887-024-04842-8 -
Journal of Medical Virology May 2024Rotavirus gastroenteritis is accountable for an estimated 128 500 deaths among children younger than 5 years worldwide, and the majority occur in low-income countries....
Rotavirus gastroenteritis is accountable for an estimated 128 500 deaths among children younger than 5 years worldwide, and the majority occur in low-income countries. Although the clinical trials of rotavirus vaccines in Bangladesh revealed a significant reduction of severe rotavirus disease by around 50%, the vaccines are not yet included in the routine immunization program. The present study was designed to provide data on rotavirus diarrhea with clinical profiles and genotypes before (2017-2019) and during the COVID-19 pandemic period (2020-2021). Fecal samples were collected from 2% of the diarrheal patients at icddr,b Dhaka hospital of all ages between January 2017 and December 2021 and were tested for VP6 rotavirus antigen using ELISA. The clinical manifestations such as fever, duration of diarrhea and hospitalization, number of stools, and dehydration and so on were collected from the surveillance database (n = 3127). Of the positive samples, 10% were randomly selected for genotyping using Sanger sequencing method. A total of 12 705 fecal samples were screened for rotavirus A antigen by enzyme immunoassay. Overall, 3369 (27%) were rotavirus antigen-positive, of whom children <2 years had the highest prevalence (88.6%). The risk of rotavirus A infection was 4.2 times higher in winter than in summer. Overall, G3P[8] was the most prominent genotype (45.3%), followed by G1P[8] (32.1%), G9P[8] (6.8%), and G2P[4] (6.1%). The other unusual combinations, such as G1P[4], G1P[6], G2P[6], G3P[4], G3P[6], and G9P[6], were also present. Genetic analysis on Bangladeshi strains revealed that the selection pressure (dN/dS) was estimated as <1. The number of hospital visits showed a 37% drop during the COVID-19 pandemic relative to the years before the pandemic. Conversely, there was a notable increase in the rate of rotavirus positivity during the pandemic (34%, p < 0.00) compared to the period before COVID-19 (23%). Among the various clinical symptoms, only the occurrence of watery stool significantly increased during the pandemic. The G2P[4] strain showed a sudden rise (19%) in 2020, which then declined in 2021. In the same year, G1P[8] was more prevalent than G3P[8] (40% vs. 38%, respectively). The remaining genotypes were negligible and did not exhibit much fluctuation. This study reveals that the rotavirus burden remained high during the COVID-19 prepandemic and pandemic in Bangladesh. Considering the lack of antigenic variations between the circulating and vaccine-targeted strains, integrating the vaccine into the national immunization program could reduce the prevalence of the disease, the number of hospitalizations, and the severity of cases.
Topics: Humans; Bangladesh; Rotavirus; Rotavirus Infections; Child, Preschool; Genotype; Infant; COVID-19; Feces; Female; Male; Child; Diarrhea; Adolescent; Adult; Antigens, Viral; Infant, Newborn; Gastroenteritis; Young Adult; Prevalence; SARS-CoV-2; Middle Aged; Seasons
PubMed: 38773815
DOI: 10.1002/jmv.29681 -
FP Essentials May 2024Gastroenteritis is inflammation of the stomach and intestines; colitis is inflammation of the colon. Viruses are the most common cause, followed by bacteria and... (Review)
Review
Gastroenteritis is inflammation of the stomach and intestines; colitis is inflammation of the colon. Viruses are the most common cause, followed by bacteria and parasites. Incidence of the various infections varies by age, sex, location, and vaccine availability; vaccination has reduced rotavirus infections by as much as 90% in children. Postinfectious complications include irritable bowel syndrome (IBS) and lactose intolerance. Approximately 9% of patients with acute gastroenteritis or colitis develop postinfectious IBS, which accounts for more than 50% of all IBS cases. The diagnostic approach to gastroenteritis and colitis varies with symptom severity. Microbial studies are not needed with mild symptoms that resolve within a week, but longer-lasting or more severe symptoms (including bloody stool) warrant microbial studies. In addition, recent antibiotic exposure should prompt testing for . Multiplex antimicrobial testing is preferred; stool cultures and microscopic stool examinations are no longer first-line tests. Management depends on severity. Patients with mild or moderate symptoms are treated with oral hydration if tolerated; nasogastric or intravenous hydration are used for those with more severe illness. In addition, antiemetic, antimotility, and/or antisecretory drugs can be used for symptom control. Antimicrobial therapy is indicated for infections, travel-related diarrhea, other bacterial infections with severe symptoms, and parasitic infections.
Topics: Humans; Gastroenteritis; Colitis; Acute Disease; Anti-Bacterial Agents; Irritable Bowel Syndrome
PubMed: 38767886
DOI: No ID Found -
BioRxiv : the Preprint Server For... May 2024Acute gastroenteritis remains the second leading cause of death among children under the age of 5 worldwide. While enteric viruses are the most common etiology, the...
Acute gastroenteritis remains the second leading cause of death among children under the age of 5 worldwide. While enteric viruses are the most common etiology, the drivers of their virulence remain incompletely understood. We recently found that cells infected with rotavirus, the most prevalent enteric virus in infants and young children, initiate hundreds of intercellular calcium waves that enhance both fluid secretion and viral spread. Understanding how rotavirus triggers intercellular calcium waves may allow us to design safer, more effective vaccines and therapeutics, but we still lack a mechanistic understanding of this process. In this study, we used existing virulent and attenuated rotavirus strains, as well as reverse engineered recombinants, to investigate the role of rotavirus nonstructural protein 4 (NSP4) in intercellular calcium wave induction using , organoid, and model systems. We found that the capacity to induce purinergic intercellular calcium waves (ICWs) segregated with NSP4 in both simian and murine-like rotavirus backgrounds, and NSP4 expression alone was sufficient to induce ICWs. NSP4's ability to function as a viroporin, which conducts calcium out of the endoplasmic reticulum, was necessary for ICW induction. Furthermore, viroporin activity and the resulting ICWs drove transcriptional changes indicative of innate immune activation, which were lost upon attenuation of viroporin function. Multiple aspects of RV disease severity correlated with the generation of ICWs, identifying a critical link between viroporin function, intercellular calcium waves, and enteric viral virulence.
PubMed: 38765992
DOI: 10.1101/2024.05.07.592929 -
Diagnostic Microbiology and Infectious... Aug 2024Rotaviruses belong to genotype VP4-P[8] are a significant cause of severe loose diarrhea in infants and young children. In the present study, we characterised the...
Rotaviruses belong to genotype VP4-P[8] are a significant cause of severe loose diarrhea in infants and young children. In the present study, we characterised the complete genome of three of the Pakistani P[8]b RVA strains by Illumina HiSeq sequencing technology to determine the complete genotype constellation providing insight into the evolutionary dynamics of their genes using maximum likelihood analysis. The maximum genomic sequences of our study strains were similar to more recent human Wa-Like G1P[8]a, G3P[8]a, G4P[6], G4P[8], G9P[4], G9P[8]a, G11P[25],G12P[8]a and G12P[6] strains circulating around the world. Therefore, strains PAK274, PAK439 and PAK624 carry natively distinctive VP4 gene with universally common human Wa-Like genetic backbone. Comparing our study P[8]b strains with vaccines strains Rotarix and RotaTeq, multiple amino acid differences were examined between vaccine virus antigenic epitopes and Pakistani isolates. Over time, these differences may result in the selection for strains that will escape the vaccine-induced RVA-neutralizing-antibody effect.
Topics: Rotavirus; Humans; Rotavirus Infections; Pakistan; Rotavirus Vaccines; Epitopes; Genotype; Capsid Proteins; Genome, Viral; Antigens, Viral; Infant; Phylogeny; Vaccines, Attenuated; Child, Preschool
PubMed: 38759540
DOI: 10.1016/j.diagmicrobio.2024.116346 -
Human Vaccines & Immunotherapeutics Dec 2024Following the introduction of rotavirus vaccination into the Moroccan National Immunization Program, the prevalence of the disease has decreased by nearly 50%. However,...
Following the introduction of rotavirus vaccination into the Moroccan National Immunization Program, the prevalence of the disease has decreased by nearly 50%. However, evidence on the economic value of rotavirus vaccinations in Morocco is limited. This health economic analysis evaluated, from both country payer and societal perspectives, the costs and the cost-effectiveness of three rotavirus vaccines using a static, deterministic, population model in children aged < 5 years in Morocco. Included vaccines were HRV (2-dose schedule), HBRV (3-dose schedule) and BRV-PV 1-dose vial (3-dose schedule). One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty in model inputs. The model predicted that vaccination with HRV was estimated to result in fewer rotavirus gastroenteritis events (-194 homecare events, -57 medical visits, -8 hospitalizations) versus the 3-dose vaccines, translating into 7 discounted quality-adjusted life years gained over the model time horizon. HRV was associated with lower costs versus HBRV from both the country payer (-$1.8 M) and societal (-$4.1 M) perspectives, and versus BRV-PV 1-dose vial from the societal perspective (-$187,000), dominating those options in the cost-effectiveness analysis. However, costs of BRV-PV 1-dose vial were lower than HRV from the payer perspective, resulting in an ICER of approximately $328,376 per QALY, above the assumed cost effectiveness threshold of $3,500. Vaccination with a 2-dose schedule of HRV may be a cost-saving option and could lead to better health outcomes for children in Morocco versus 3-dose schedule rotavirus vaccines.
Topics: Humans; Rotavirus Vaccines; Child, Preschool; Rotavirus Infections; Infant; Cost-Benefit Analysis; Morocco; Female; Male; Infant, Newborn; Vaccination; Gastroenteritis
PubMed: 38757507
DOI: 10.1080/21645515.2024.2353480