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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 -
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 -
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 -
Vaccine Jul 2024Case-control studies involving test-negative (TN) and syndrome-negative (SN) controls are reliable for evaluating influenza and rotavirus vaccine effectiveness (VE)... (Observational Study)
Observational Study Comparative Study
Vaccine effectiveness in reducing COVID-19-related hospitalization after a risk-age-based mass vaccination program in a Chilean municipality: A comparison of observational study designs.
BACKGROUND
Case-control studies involving test-negative (TN) and syndrome-negative (SN) controls are reliable for evaluating influenza and rotavirus vaccine effectiveness (VE) during a random vaccination process. However, there is no empirical evidence regarding the impact in real-world mass vaccination campaigns against SARS-CoV-2 using TN and SN controls.
OBJECTIVE
To compare in the same population the effectiveness of SARS-CoV-2 vaccination on COVID-19-related hospitalization rates across a cohort design, TN and SN designs.
METHOD
We conducted an unmatched population-based cohort, TN and SN case-control designs linking data from four data sources (public primary healthcare system, hospitalization registers, epidemiological surveillance systems and the national immunization program) in a Chilean municipality (Rancagua) between March 1, 2021 and August 31, 2021. The outcome was COVID-19-related hospitalization. To ensure sufficient sample size in the unexposed group, completion of follow-up in the cohort design, and sufficient time between vaccination and hospitalization in the case-control design, VE was estimated comparing 8-week periods for each individual.
RESULTS
Among the 191,505 individuals registered in the primary healthcare system of Rancagua in Chile on March 1, 2021; 116,453 met the cohort study's inclusion criteria. Of the 9,471 hospitalizations registered during the study period in the same place, 526 were COVID-19 cases, 108 were TN controls, and 1,628 were SN controls. For any vaccine product, the age- and sex-adjusted vaccine effectiveness comparing fully and nonvaccinated individuals was 67.2 (55.7-76.3) in the cohort design, whereas it was 67.8 (44.1-81.4) and 77.9 (70.2-83.8) in the TN and SN control designs, respectively.
CONCLUSION
The VE of a COVID-19 vaccination program based on age and risk groups tended to differ across the three observational study designs. The SN case-control design may be an efficient option for evaluating COVID-19 VE in real-world settings.
Topics: Humans; COVID-19; Chile; Middle Aged; Hospitalization; Male; Female; Adult; Aged; COVID-19 Vaccines; Case-Control Studies; Adolescent; SARS-CoV-2; Mass Vaccination; Young Adult; Vaccine Efficacy; Child; Child, Preschool; Infant; Cohort Studies; Immunization Programs; Aged, 80 and over
PubMed: 38749822
DOI: 10.1016/j.vaccine.2024.05.002 -
Nature Communications May 2024While preventing vertical HIV transmission has been very successful, HIV-exposed uninfected infants (iHEU) experience an elevated risk to infections compared to...
While preventing vertical HIV transmission has been very successful, HIV-exposed uninfected infants (iHEU) experience an elevated risk to infections compared to HIV-unexposed and uninfected infants (iHUU). Here we present a longitudinal multimodal analysis of infant immune ontogeny that highlights the impact of HIV/ARV exposure. Using mass cytometry, we show alterations in T cell memory differentiation between iHEU and iHUU being significant from week 15 of life. The altered memory T cell differentiation in iHEU was preceded by lower TCR Vβ clonotypic diversity and linked to TCR clonal depletion within the naïve T cell compartment. Compared to iHUU, iHEU had elevated CD56CD16PerforinCD38CD45RAFcεRIγ NK cells at 1 month postpartum and whose abundance pre-vaccination were predictive of vaccine-induced pertussis and rotavirus antibody responses post 3 months of life. Collectively, HIV/ARV exposure disrupted the trajectory of innate and adaptive immunity from birth which may underlie relative vulnerability to infections in iHEU.
Topics: Humans; HIV Infections; Infant; Female; Infant, Newborn; Infectious Disease Transmission, Vertical; Immunologic Memory; Memory T Cells; Male; Killer Cells, Natural; Receptors, Antigen, T-Cell; Adaptive Immunity; Cell Differentiation; Longitudinal Studies
PubMed: 38744812
DOI: 10.1038/s41467-024-47955-5 -
Journal of Animal Science and... May 2024Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to... (Review)
Review
Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to treat the disease, and the related vaccines have no obvious efficiency in some countries. Via analyzing the pathogenesis of rotavirus, it inducing diarrhea is mainly due to disturb enteric nervous system, destroy gut mucosal integrity, induce intracellular electrolyte imbalance, and impair gut microbiota and immunity. Many studies have already proved that prebiotics and probiotics can mitigate the damage and diarrhea induced by rotavirus infection in hosts. Based on these, the current review summarizes and discusses the effects and mechanisms of prebiotics and probiotics on rotavirus-induced diarrhea in piglets. This information will highlight the basis for the swine production utilization of prebiotics and probiotics in the prevention or treatment of rotavirus infection in the future.
PubMed: 38698473
DOI: 10.1186/s40104-024-01018-3 -
Frontiers in Immunology 2024This meta-analysis was performed to assess the prevalence and circulating strains of rotavirus (RV) among Chinese children under 5 years of age after the implantation of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis was performed to assess the prevalence and circulating strains of rotavirus (RV) among Chinese children under 5 years of age after the implantation of the RV vaccine.
MATERIAL AND METHODS
Studies published between 2019 and 2023, focused on RV-based diarrhea among children less than 5 years were systematically reviewed using PubMed, Embase, Web of Science, CNKI, Wanfang and SinoMed Data. We synthesized their findings to examine prevalence and genetic diversity of RV after the RV vaccine implementation using a fixed-effects or random-effects model.
RESULTS
Seventeen studies met the inclusion criteria for this meta-analysis. The overall prevalence of RV was found to be 19.00%. The highest infection rate was noted in children aged 12-23months (25.79%), followed by those aged 24-35 months (23.91%), and 6-11 months (22.08%). The serotype G9 emerged as the most predominant RV genotype, accounting for 85.48% of infections, followed by G2 (7.70%), G8 (5.74%), G1 (4.86%), and G3 (3.21%). The most common P type was P[8], representing 64.02% of RV cases. Among G-P combinations, G9P[8] was the most frequent, responsible for 78.46% of RV infections, succeeded by G8P[8] (31.22%) and G3P[8] (8.11%).
CONCLUSION
Despite the variation of serotypes observed in China, the G1, G2, G3, G8 and G9 serotypes accounted for most RV strains. The genetic diversity analysis highlights the dynamic nature of RV genotypes, necessitating ongoing surveillance to monitor changes in strain distribution and inform future vaccine strategies.
Topics: Humans; Rotavirus Infections; Rotavirus; China; Genetic Variation; Prevalence; Infant; Child, Preschool; Genotype; Rotavirus Vaccines; Male
PubMed: 38690265
DOI: 10.3389/fimmu.2024.1364429 -
Viruses Apr 2024Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus...
Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus drugs are available. It is crucial to develop effective and low-toxicity anti-rotavirus small-molecule drugs that act on novel host targets. In this study, a new anti-rotavirus compound was selected by ELISA, and cell activity was detected from 453 small-molecule compounds. The anti-RV effects and underlying mechanisms of the screened compounds were explored. In vitro experimental results showed that the small-molecule compound ML241 has a good effect on inhibiting rotavirus proliferation and has low cytotoxicity during the virus adsorption, cell entry, and replication stages. In addition to its in vitro effects, ML241 also exerted anti-RV effects in a suckling mouse model. Transcriptome sequencing was performed after adding ML241 to cells infected with RV. The results showed that ML241 inhibited the phosphorylation of ERK1/2 in the MAPK signaling pathway, thereby inhibiting IκBα, activating the NF-κB signaling pathway, and playing an anti-RV role. These results provide an experimental basis for specific anti-RV small-molecule compounds or compound combinations, which is beneficial for the development of anti-RV drugs.
Topics: Rotavirus; Animals; Mice; Rotavirus Infections; Virus Replication; Humans; Antiviral Agents; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase 1; NF-kappa B; Phosphorylation; Mice, Inbred BALB C; Cell Line; MAP Kinase Signaling System; Signal Transduction
PubMed: 38675964
DOI: 10.3390/v16040623 -
Viruses Apr 2024Rotavirus A (RVA) is the leading cause of diarrhea requiring hospitalization in children and causes over 100,000 annual deaths in Sub-Saharan Africa. In order to...
Rotavirus A (RVA) is the leading cause of diarrhea requiring hospitalization in children and causes over 100,000 annual deaths in Sub-Saharan Africa. In order to generate next-generation vaccines against African RVA genotypes, a reverse genetics system based on a simian rotavirus strain was utilized here to exchange the antigenic capsid proteins VP4, VP7 and VP6 with those of African human rotavirus field strains. One VP4/VP7/VP6 (genotypes G9-P[6]-I2) triple-reassortant was successfully rescued, but it replicated poorly in the first cell culture passages. However, the viral titer was enhanced upon further passaging. Whole genome sequencing of the passaged virus revealed a single point mutation (A797G), resulting in an amino acid exchange (E263G) in VP4. After introducing this mutation into the VP4-encoding plasmid, a VP4 mono-reassortant as well as the VP4/VP7/VP6 triple-reassortant replicated to high titers already in the first cell culture passage. However, the introduction of the same mutation into the VP4 of other human RVA strains did not improve the rescue of those reassortants, indicating strain specificity. The results show that specific point mutations in VP4 can substantially improve the rescue and replication of recombinant RVA reassortants in cell culture, which may be useful for the development of novel vaccine strains.
Topics: Rotavirus; Virus Replication; Capsid Proteins; Humans; Reassortant Viruses; Animals; Mutation; Cell Line; Reverse Genetics; Genotype; Point Mutation; Rotavirus Infections; Genome, Viral; Antigens, Viral
PubMed: 38675907
DOI: 10.3390/v16040565 -
The Lancet. Global Health Jun 2024Information on the causes of deaths from diarrhoea in children younger than 5 years is needed to design improved preventive and therapeutic approaches. We aimed to...
BACKGROUND
Information on the causes of deaths from diarrhoea in children younger than 5 years is needed to design improved preventive and therapeutic approaches. We aimed to conduct a systematic analysis of studies to report estimates of the causes of deaths from diarrhoea in children younger than 5 years at global and regional levels during 2000-21.
METHODS
For this systematic review and Bayesian multinomial analysis, we included 12 pathogens with the highest attributable incidence in the Global Enteric Multicenter Study. We searched PubMed, Scopus, Embase, Web of Science, Global Health Index Medicus, Global Health OVID, IndMed, Health Information Platform for the Americas (PLISA), Africa-Wide Information, and Cochrane Collaboration for articles published between Jan 1, 2000, and Dec 31, 2020, using the search terms "child", "hospital", "diarrhea", "diarrhoea", "dysentery", "rotavirus", "Escherichia coli", "salmonella", "shigella", "campylobacter", "Vibrio cholerae", "cryptosporidium", "norovirus", "astrovirus", "sapovirus", and "adenovirus". To be included, studies had to have a patient population of children younger than 5 years who were hospitalised for diarrhoea (at least 90% of study participants), at least a 12-month duration, reported prevalence in diarrhoeal stools of at least two of the 12 pathogens, all patients with diarrhoea being included at the study site or a systematic sample, at least 100 patients with diarrhoea, laboratory tests done on rectal swabs or stool samples, and standard laboratory methods (ie, quantitative PCR [qPCR] or non-qPCR). Studies published in any language were included. Studies were excluded if they were limited to nosocomial, chronic, antibiotic-associated, or outbreak diarrhoea or to a specific population (eg, only children with HIV or AIDS). Each article was independently reviewed by two researchers; a third arbitrated in case of disagreement. If both reviewers identified an exclusion criterion, the study was excluded. Data sought were summary estimates. Data on causes from published studies were adjusted when necessary to account for the poor sensitivity of non-qPCR methods and for attributable fraction based on quantification of pathogens in children who are ill or non-ill. The causes of deaths from diarrhoea were modelled on the causes of hospitalisations for diarrhoea. We separately modelled studies reporting causes of diarrhoea in children who were hospitalised in low-income and middle-income countries (LMICs) and in high-income countries (HICs).
FINDINGS
Of 74 282 papers identified in the initial database search, we included 138 studies (91 included data from LMICs and 47 included data from HICs) from 73 countries. We modelled estimates for 194 WHO member states (hereafter referred to as countries), including 42 HICs and 152 LMICs. We could attribute a cause to 1 003 448 (83·8%) of the estimated 1 197 044 global deaths from diarrhoea in children younger than 5 years in 2000 and 360 730 (81·3%) of the estimated 443 833 global deaths from diarrhoea in children younger than 5 years in 2021. The cause with the largest estimated global attribution was rotavirus; in LMICs, the proportion of deaths from diarrhoea due to rotavirus in children younger than 5 years appeared lower in 2021 (108 322 [24·4%] of 443 342, 95% uncertainty interval 21·6-29·5) than in 2000 (316 382 [26·5%] of 1 196 134, 25·7-28·5), but the 95% CIs overlapped. In 2000, the second largest estimated attribution was norovirus GII (95 817 [8·0%] of 1 196 134 in LMICs and 225 [24·7%] of 910 in HICs); in 2021, Shigella sp had the second largest estimated attribution in LMICs (36 082 [8·1%] of 443 342), but norovirus remained with the second largest estimated attribution in HICs (84 [17·1%] of 490).
INTERPRETATION
Our results indicate progress in the reduction of deaths from diarrhoea caused by 12 pathogens in children younger than 5 years in the past two decades. There is a need to increase efforts for prevention, including with rotavirus vaccine, and treatment to eliminate further deaths.
FUNDING
Bill & Melinda Gates Foundation via Johns Hopkins University and the University of Virginia.
Topics: Humans; Diarrhea; Bayes Theorem; Infant; Child, Preschool; Global Health; Cause of Death; Infant, Newborn
PubMed: 38648812
DOI: 10.1016/S2214-109X(24)00078-0