Rotavirus Vaccine Research Articles

Virus-like Particles vaccine based on co-expression of G5 Porcine rotavirus VP2-VP6-VP7 induces a powerful immune protective response in mice

Porcine rotavirus (PoRV), a member of the Reoviridae family, constitutes a principal etiological agent of acute diarrhea in piglets younger than eight weeks of age, and it is associated with considerable morbidity and mortality within the swine industry. The G5 genotype rotavirus strain currently predominates in circulation. To develop a safe and effective porcine rotavirus vaccine, we generated an insect cell-baculovirus expression system, and successfully expressed these three viral proteins and assembled them into virus-like particles (VLPs) co-displaying VP2, VP6, and VP7. Transmission electron microscopy (TEM) analysis revealed that the VP2-VP6-VP7 VLPs exhibited a "wheeled" morphology resembling that of native rotavirus particles, with an estimated diameter of approximately 65nm. To evaluate the immunogenicity and protective efficacy of these VP2-VP6-VP7 VLPs, we immunized BALB/C mice with four escalating doses of the VLPs, ranging from 5 to 40μg of VLP protein per dose. ELISA-based assessments of PoRV-specific antibodies and T cell cytokines, including IL-4, IL-2, and IFN-γ, demonstrate that immunization with VP2-VP6-VP7 VLPs can effectively elicit both humoral and cellular immune responses in mice, resulting in a notable induction of neutralizing antibodies. On days 4, 6, 8, and 10 post-infection (dpi), the VLP-vaccinated group exhibited significantly reduced levels of PoRV RNA copy numbers when compared to the PBS controls. Histological examination of the duodenum, ileum, and kidneys revealed that VP2-VP6-VP7 VLPs provided effective protection against PoRV induced intestinal injury. Collectively, these findings indicate that the VLPs generated in this study possess strong immunogenicity and suggest the considerable promise of the VLP-based vaccine candidate in the prevention and containment of Porcine Rotavirus infections.

Rotaviruses and Rotavirus Vaccines: Special Issue Editorial

Rotaviruses and Rotavirus Vaccines: Special Issue Editorial

Infectious etiology of intussusception in Indian children less than 2 years old: a matched case-control analysis

BackgroundEnteric infections are hypothesized to be associated with intussusception in children. A small increase in intussusception following rotavirus vaccination has been seen in some settings. We conducted post-marketing surveillance for intussusception following rotavirus vaccine, Rotavac introduction in India and evaluated association of intussusception with enteric pathogens.MethodsIn a case-control study nested within a large sentinel hospital-based surveillance program in India, stool samples from 272 children aged less than 2 years admitted for intussusception and 272 age-, gender- and location-matched controls were evaluated with Taqman array card based molecular assays to detect enteric viruses, bacterial enteropathogens and parasites. Matched case-control analysis with conditional logistic regression evaluated association of enteropathogens with intussusception. Population attributable fractions (PAF) were calculated for enteropathogens significantly associated with intussusception.ResultsThe most prevalent enteropathogens in cases and controls were enteroaggregative Escherichia coli, adenovirus 40/41, adenovirus C serotypes and enteroviruses. Children with intussusception were more likely to harbor adenovirus C serotypes (adjusted odds-ratio (aOR) = 1.74; 95% confidence interval (CI) 1.06–2.87) and enteroviruses (aOR = 1.77; 95% CI 1.05–2.97) than controls. Rotavirus was not associated with increased intussusception risk. Adenovirus C (PAF = 16.9%; 95% CI 4.7% − 27.6%) and enteroviruses (PAF = 14.7%; 95% CI 4.2% − 24.1%) had the highest population attributable fraction for intussusception.ConclusionAdenovirus C serotypes and enteroviruses were significantly associated with intussusception in Indian children. Rotavirus was not associated with risk of intussusception.

Exploring the evolution of rotavirus vaccines and its impact on global public health

Rotavirus, a prevalent pathogen within the Reoviridae family, poses a significant threat to children, particularly infants and young children, causing gastroenteritis. High transmissibility and severe diarrhea lead to dehydration, severe infection, and death, especially in regions with limited resources and poor sanitation. Rotavirus infections spread through contaminated food, water, and fomites, primarily affecting developing countries due to inadequate sanitation standards. Vaccination has emerged as a crucial preventive strategy against rotavirus gastroenteritis, with the aim of reducing the global burden of the disease. The early rotavirus vaccines, exemplified by Rota-Shield, faced challenges such as safety concerns, emphasizing the importance of rigorous safety evaluation and post-marketing surveillance. Subsequent vaccines, Rotarix and RotaTeq, have shown efficacy and safety, significantly reducing rotavirus-related morbidity and mortality worldwide. The global implementation of rotavirus vaccination programs has expanded vaccine access, leading to a decrease in disease incidence and hospitalizations. Despite these achievements, challenges persist, such as hesitantness to apply the vaccine and disparities in vaccine access. Future research directions include the development of next-generation vaccines with greater coverage and the exploration of novel vaccine delivery strategies. A sustained commitment to research, infrastructure strengthening, and community involvement is essential to eliminate the burden of rotavirus disease worldwide. The objective of this review is to explore the evolution of rotavirus vaccines and impact on global public health.

Cross-sectional study exploring the prevalence and clinical manifestations of acute diarrhea among under-five children in primary care hospital in democratic republic of the congo

Background: Acute diarrhea (AD), which is defined as frequent passing of liquid stools compared to normal, is a serious and worrying problem and remains a concern for health care systems because of its high mortality cause in children under 5 years old. Our study aimed to present the prevalence and to describe the clinical manifestation of AD among under-five children. Methods: From June 2022 to May 2023, we conducted a retrospective, descriptive and cross-sectional study including all patients aged 0 to 5 years hospitalized for AD. Results: Out of 512 patients, only 197 (38.5%) children with AD were selected for our study. The average age is 25.5 months, and the sex ratio is 1.11. Some families (75.1%) have clean latrines, and 21.8% use water from the river. Inaccessibility to clean water and intolerance or food poisoning were the causes of acute diarrhea in children. Major signs and symptoms are fever, dehydration and vomiting. Weight loss and malnutrition are the major complications of AD in children. The treatment of AD is provided by oral rehydration solutions and antibiotics. Conclusion: The study highlights the significant prevalence of acute diarrhea among under-five children underscores the importance of preventive measures and government intervention, such as the introduction of rotavirus vaccination. However, conclusions regarding prevalence rates should be interpreted with caution due to the lack of detailed population data.

Potential impact of rotavirus vaccine introduction in India’s Universal Immunisation Programme on private sector vaccine utilisation: an interrupted time series analysis

BackgroundDespite free immunisation services through the Universal Immunisation Programme (UIP), around 14% of Indian households seek immunisation in the private sector. We examined the potential impact of rotavirus vaccine (RVV) introduction in the Universal Immunisation Programme (UIP) on private-sector rotavirus vaccine utilisation.MethodsWe analysed nationally representative private-sector vaccine sales data. The intervention under consideration is RVV introduction in the UIP in selected Indian states. The outcome is the ‘monthly RVV sales volume’—a proxy for vaccine utilisation. We performed a Poisson regression interrupted time series analysis to detect the pre-intervention trend, post-intervention level change and trend change relative to the pre-intervention for monthly rotavirus vaccine utilisation.ResultsPoisson segmented regression analysis showed that immediately after RVV introduction in the UIP private-sector RVV sales showed a decline in Rajasthan by 37.4% (Incidence Risk Ratio (IRR): 0.626; 95% CI: 0.504–0.779), in Tamil Nadu by 26% (IRR: 0.740; 95% CI: 0.513–1.068), in Uttar Pradesh-East by 72.2% (IRR: 0.278; 95% CI: 0.178–0.436) and in Kerala by 3% (IRR: 0.970; 95% CI: 0.651–1.447). Rajasthan, Tamil Nadu and Kerala had sustained reduction in the postintervention trend relative to the preintervention trend by 20.1% (IRR: 0.799; 95% CI: 0.763–0.836), 6.4% (IRR: 0.936; 95% CI: 0.906–0.967) and 3.3% (IRR: 0.967; 95% CI: 0.926–0.960) per month, respectively. However, in Haryana and UP-west, in the first-month post-UIP introduction, the private-sector RVV sales increased by 101% and 3.8%, respectively which was followed by a sustained decrease of 14.2% (IRR: 0.858; 95% CI: 0.688–1.070) and 5.8% (IRR: 0.942; 95% CI: 0.926–0.960) per month, respectively. In terms of long-term impact, the private sector RVV sales post-UIP introduction decreased at a monthly rate of 4.4% (IRR: 0.956, 95% CI: 0.939–0.974) in Rajasthan but increased by 5.5% (IRR: 1.055; 95% CI: 1.040–1.070) in UP-east, 0.3% (IRR: 1.003, 95% CI: 0.976–1.031)) in Kerala and 0.2% (IRR: 1.002, 95% CI: 0.993–1.011) in Tamil Nadu whereas Haryana and UP-west had a reduction in RVV utilisation by 2.8% (IRR: 0.972; 95% CI: 0.955–0.990) and 1% (IRR: 0.990; 95% CI: 0.982–0.998), respectively.ConclusionsThe study provides evidence that access to RVV through UIP leads to a reduction in private-sector RVV utilisation. We recommend strengthening UIP to expand the basket of new vaccines.

Gastroenteritis: A Comprehensive Review

Gastroenteritis, commonly referred to as stomach flu, is an acute inflammation of the gastrointestinal tract, marked by symptoms including diarrhea, vomiting, abdominal cramps, and fever. This review article provides a comprehensive overview of gastroenteritis, addressing its etiology, epidemiology, pathophysiology, diagnosis, management, and prevention strategies. The condition is caused by a variety of infectious agents such as viruses (noroviruses, rotaviruses), bacteria (Campylobacter, Salmonella), and parasites (Giardia lamblia), with transmission typically occurring through contaminated food, water, or person-to-person contact. Globally, gastroenteritis remains a significant public health issue, with high morbidity and mortality rates, particularly in children under five in developing countries. Diagnosis often relies on clinical evaluation and laboratory tests, while management focuses on rehydration therapy and symptomatic relief. Preventive measures include personal hygiene, food safety practices, environmental sanitation, and vaccination, with rotavirus vaccines significantly reducing severe cases in children. Emerging trends in gastroenteritis research aim at developing rapid diagnostic tools, novel therapeutic approaches, and new vaccines, highlighting the importance of a multidisciplinary approach to mitigate the global impact of this disease.

Associations between Histo-Blood Group Antigen Status in Mother-Infant Dyads and Infant Oral Rotavirus Vaccine Immunogenicity in rural Zimbabwe.

Histo-blood group antigen (HBGA) phenotypes may contribute to poor oral rotavirus vaccine (RVV) immunogenicity, since rotavirus binds intestinal epithelial HBGA glycans, while maternal HBGA status shapes breastmilk composition, which influences the composition of the infant microbiome. We investigated associations between maternal/infant HBGA phenotypes and RVV immunogenicity in rural Zimbabwe. We undertook salivary FUT2/FUT3 phenotyping in mother-infant pairs. Serum anti-rotavirus IgA was measured by ELISA. We explored adjusted associations between FUT2/FUT3 status and RVV seroconversion (primary outcome, N=322), and seropositivity and geometric mean titre (secondary outcomes, N=776). Infants of FUT2-positive or FUT3-positive women were less likely to seroconvert post-RVV than infants of FUT2-negative or FUT3-negative women (FUT2-positive 20.1% versus FUT2-negative 27.5%, adjusted relative risk (aRR) 0.47, 95%CI 0.26, 0.82; P=0.008; FUT3-positive 18.1% versus FUT3-negative 30.0%, aRR 0.45, 95%CI 0.25, 0.78; P=0.005). Compared to FUT2-positive infants with FUT2-positive mothers, FUT2-positive infants with FUT2-negative mothers were twice as likely to seroconvert (36.8% versus 21.9%, aRR 2.12, 95%CI 1.23, 3.63; P=0.006). Compared to FUT3-positive infants with FUT3-positive mothers, FUT3-positive infants with FUT3-negative mothers were three times as likely to seroconvert (48.3% versus 18.2%, aRR 2.99, 95%CI 1.82, 4.90; P<0.001). Maternal and infant FUT2 and FUT3 status influences infant RVV immunogenicity.

Frequency and genotyping of group A rotavirus among Egyptian children with acute gastroenteritis: a hospital-based cross-sectional study

BackgroundThis hospital-based cross-sectional study aims to investigate the epidemiologic and clinical characteristics of rotavirus group A (RVA) infection among children with acute gastroenteritis and to detect the most common G and P genotypes in Egypt.MethodsA total of 92 stool samples were collected from children under five who were diagnosed with acute gastroenteritis. RVA in stool samples was identified using ELISA and nested RT-PCR. Common G and P genotypes were identified utilizing multiplex nested RT-PCR assays.ResultsRVA was detected at a rate of 24% (22 /92) using ELISA and 26.1% (24 /92) using VP6 nested RT-PCR. The ELISA test demonstrated diagnostic sensitivity, specificity, and accuracy of 91.7%, 100%, and 97.8%, respectively. G3 was the most prevalent G type (37.5%), followed by G1 (12.5%), whereas the most commonly detected P type were P[8] (41.7%) and P[6] (8.2%). RVA-positive samples were significantly associated with younger aged children (p = 0.026), and bottle-fed (p = 0.033) children. In addition, RVA-positive samples were more common during cooler seasons (p = 0.0001). Children with rotaviral gastroenteritis had significantly more frequent episodes of diarrhea (10.87 ± 3.63 times/day) and vomiting (8.79 ± 3.57 times/day) per day (p = 0.013 and p = 0.011, respectively). Moreover, they had a more severe Vesikari clinical score (p = 0.049).ConclusionRVA is a prevalent cause of acute gastroenteritis among Egyptian children in our locality. The discovery of various RVA genotypes in the local population, as well as the identification of common G and P untypeable strains, highlights the significance of implementing the rotavirus vaccine in Egyptian national immunization programs accompanied by continuous monitoring of strains.

Protective role of antibodies in enteric virus infections: Lessons from primary and secondary immune deficiencies.

Enteric viruses are the main cause of acute gastroenteritis worldwide with a significant morbidity and mortality, especially among children and aged adults. Some enteric viruses also cause disseminated infections and severe neurological manifestations such as poliomyelitis. Protective immunity against these viruses is not well understood in humans, with most knowledge coming from animal models, although the development of poliovirus and rotavirus vaccines has extended our knowledge. In a classical view, innate immunity involves the recognition of foreign DNA or RNA by pathogen recognition receptors leading to the production of interferons and other inflammatory cytokines. Antigen uptake and presentation to T cells and B cells then activate adaptive immunity and, in the case of the mucosal immunity, induce the secretion of dimeric IgA, the more potent immunoglobulins in viral neutralization. The study of Inborn errors of immunity (IEIs) offers a natural opportunity to study nonredundant immunity toward pathogens. In the case of enteric viruses, patients with a defective production of antibodies are at risk of developing neurological complications. Moreover, a recent description of patients with low or absent antibody production with protracted enteric viral infections associated with hepatitis reinforces the prominent role of B cells and immunoglobulins in the control of enteric virus.

Has Ghana's Rotavirus Vaccine Switch Met Programmatic Expectations? An Analysis of National Surveillance Data; 2018-2022.

Ghana introduced a 2-dose schedule rotavirus vaccine, Rotarix, into childhood immunization in 2012 but switched to a 3-dose schedule vaccine, Rotavac, in 2020 on account of programmatic advantages offered by the latter, including lower cost per fully immunized child and lower cold chain volume requirement. The objective of the study was to assess the effect of the vaccine switch on the trends of rotavirus vaccine uptake and health facility outpatient department (OPD) attendance due to diarrhea among children aged 1-11 months. A retrospective analysis was conducted on childhood immunization and diarrhea surveillance data for 2018-2022. The uptake of the different rotavirus vaccine products and the proportion of health facility OPD attendance attributed to diarrhea, respectively, were compared between the pre- and postswitch study periods. The uptake of rotavirus vaccine was sustained following the switch. There were no significant differences in vaccination coverages (rota1, Rotarix coverage [94.3%], vs rota1, Rotavac coverage [95.3%]; P = .757; rota2, Rotarix coverage [91.3%], vs rota2, Rotavac coverage [92.7%]; P = .789). The proportions of health facility OPD attendance due to diarrhea were comparable (preswitch [12.4%] vs postswitch [12.1%]; P = .838). Ghana's rotavirus vaccine switch yielded expected programmatic benefits without any untoward effects. The trends of vaccine uptake and reduction in diarrhea morbidity were sustained. These experiences and lessons from the rotavirus vaccine switch are vital for potential switches for other vaccines in the current immunization schedule to mitigate the annual vaccine expenditure.

Evaluating the Compatibility of Three Aluminum Salt-Adjuvanted Recombinant Protein Antigens (Trivalent NRRV) Combined with a Mock Trivalent Sabin-IPV Vaccine: Analytical and Formulation Challenges.

In this work, we describe compatibility assessments of a recombinant, trivalent non-replicating rotavirus vaccine (t-NRRV) candidate with a mock trivalent Sabin inactivated polio vaccine (t-sIPV). Both t-sIPV and t-NRRV are incompatible with thimerosal (TH), a preservative commonly used in pediatric pentavalent combination vaccines (DTwP-Hib-HepB) distributed in low- and middle-income countries (LMICs), preventing the development of a heptavalent combination. The compatibility of t-NRRV with a mock DTwP-Hib-HepB formulation is described in a companion paper. This case study highlights the analytical and formulation challenges encountered when combining a mock t-sIPV vaccine (unadjuvanted) with Alhydrogel® (AH) adjuvanted t-NRRV. Selective and stability-indicating competition ELISAs were implemented to monitor antibody binding to each of the six antigens (±AH). Simple mixing caused the undesired desorption of t-NRRV from AH with the concomitant binding of t-sIPV to AH. Although the former effect was mitigated by dialyzing sIPV bulks, decreased sIPV storage stability was observed at accelerated temperatures in the bivalent combination with a rank-ordering of P[8] > P[6] > P[4] and sIPV3 > sIPV2 > sIPV1. The compatibility of AH-adsorbed t-sIPV with alternative preservatives was evaluated, and parabens (methyl, propyl) were identified for potential use in this multi-dose bivalent formulation. Along with a companion paper, the lessons learned are discussed to facilitate the future formulation development of pediatric combination vaccines with new antigens.

Health Technology Assessment of Vaccines in Italy: History and Review of Applications

Background/Objectives. Many vaccines have been developed in recent decades, and many more will be available in the future. When new safe and effective vaccines are available, decision-makers must extensively assess them before including them in the national immunization plan and issuing recommendations. The Health Technology Assessment (HTA) could be an objective, transparent, and comprehensive approach to guiding the decision-making process for the use of vaccines. Objectives and Methods. The aim of this study was to review the indications for HTA use contained in Italian institutional documents on vaccination, namely the National Immunization Plans (NIPs) and available full Italian HTA reports on vaccines, assessing their availability at the time of national recommendations’ introductions. Results. HTA has been recognised as an eligible approach to deciding upon the introduction of vaccines through the NIPs of 2012–2014 and 2017–2019, and the last NIP, of 2023–2025, highlights the lack of funding dedicated to the production of independent HTA reports that can be used for issuing recommendations. In 2007–2023, twenty full HTA reports on vaccines were published in Italy: eight reports on influenza vaccines, five on Human Papilloma Virus (HPV), three each on meningococcal and pneumococcal vaccines, and one on rotavirus vaccine. HTA was applied with different purposes, namely the evaluation of new vaccines or their re-assessment, but it was not always timely with respect to both the marketing authorisation and the issuing of national recommendations for use. Conclusions. As HTA can be considered the best tool to disentangle the overall value of vaccines, it would be desirable for it to be used more and more to provide the evidence for efficient resource use. This calls for action to improve the transfer of HTA results to decision-makers, to try to fill the gap between research and decision and foster evidence-based recommendations.

Safety of Rotavirus Vaccination in Infants That Were Exposed to Biologics In Utero: A Systematic Review

Safety of Rotavirus Vaccination in Infants That Were Exposed to Biologics In Utero: A Systematic Review

Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi.

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease.

Full genome sequence analysis of the predominant and uncommon G9P[4] rotavirus strains circulating in Tehran, Iran, 2021–2022: Evidence for inter and intra-genotype recombination

Group A rotaviruses (RVAs) are a major cause of acute gastroenteritis in children under 5 years of age worldwide. Herein, the genetic sequences of 11 RNA segments from three uncommon G9P[4] RVA strains found in the stool samples of children under 5 years of age in Iran were analyzed using next-generation sequencing (NGS) technology. The genomic constellations of these three uncommon G9P[4] strains indicated the presence of the double and quadruple reassortants of two G9P[4] strains, containing the VP7/NSP2 and VP7/VP2/NSP2/NSP4 genes on a DS-1-like genetic background, respectively. The genome of one strain indicated a Wa-like genetic backbone in a single-reassortant with the VP4 of the DS1-like human strains. With the exception of VP1, VP2, VP7, NSP2, NSP3, and NSP4 genes, which clustered with RVA of human origins belonging to cognate gene sequences of genogroup 1/2 genotypes/lineages, the remaining five genes (VP8/VP4, VP3, VP6, NSP1, NSP5) displayed direct evidence of recombination. It is presumed that the presence of uncommon G9P[4] strains in Iran is not linked to vaccination pressure, but rather to the high prevalence of RVA co-infection or the direct import of these uncommon RVA reassortants strains from other countries (especially those that have implemented RV vaccination).

Effectiveness of Lanzhou Lamb Rotavirus Vaccine and RotaTeq Against Hospitalized Rotavirus Infections Among Children During 2020-2023 in Guangdong Province, China: A Test-Negative Case-Control Study.

The evidence regarding the effectiveness of Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5) against gastroenteritis (RVGE) caused by emerging genotypes in Chinese children remains limited. We conducted a test-negative case-control study using gastroenteritis surveillance data from four cities (2020-2023) in Guangdong Province, China. Children aged 2months to 5years hospitalized with acute gastroenteritis were enrolled. Cases were rotavirus-positive; controls were rotavirus-negative. Vaccine effectiveness (VE) was estimated using multivariable logistic regressions. Among 2650 children, 218 (8.2%) were rotavirus-positive, predominantly G8P[8]. Also, 1543 (58.23%) children were unvaccinated, while 632 (23.85%) and 475 (17.92%) received at least one dose of RV5 and LLR, respectively. Adjusted RV5 VE against any RVGE severity was 51.7% [95% confidence interval (CI) -58.1-85.3%]) for one dose, 37.6% (95% CI -58.5-75.4%) for two doses, and 64.1% (95% CI 38.0-79.2%) for three doses. For LLR, VE against any RVGE severity was 38.7% (95% CI 5.7-60.2%) for one dose, 74.6% (95% CI 35.3-90.0%) for two doses, and 58.8% (95% CI -217.6-94.6%) for three doses. Against severe RVGE, RV5 VE was 67.2% (95% CI -144.7-95.6%) for one dose, 74.0% (95% CI -92.1-96.5%) for two doses, and 86.6% (95% CI 56.8-95.9%) for three doses. For LLR, VE against severe RVGE was 57.7% (95% CI 20.3-77.6%) for one dose, 73.4% (95% CI 11.9-92.0%) for two doses, and -27.8% (95% CI -949.7-84.4%) for three doses. Both RV5 and LLR provided protection against RVGE, including the emerging G8P[8] genotype. Three doses of RV5 offered strong protection, while two doses of LLR also appeared to be an effective strategy against rotavirus infection.

Rotavirus Vaccine Effectiveness Against Severe Acute Gastroenteritis: 2009-2022.

Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022). We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or polymerase chain reaction assays. VE was calculated as (1-adjusted odds ratio)×100%. Adjusted odds ratios were calculated by multivariable unconditional logistic regression. Among 16 188 enrolled children age 8 to 59 months, 1720 (11%) tested positive for rotavirus. Case-patients were less often vaccinated against rotavirus than control-patients (62% versus 88%). VE for receiving ≥1 dose against rotavirus-associated ED visits or hospitalization was 78% (95% confidence interval [CI] 75%-80%). Stratifying by a modified Vesikari Severity Score, VE was 59% (95% CI 49%-67%), 80% (95% CI 77%-83%), and 94% (95% CI 90%-97%) against mild, moderately severe, and very severe disease, respectively. Rotavirus vaccines conferred protection against common circulating genotypes (G1P[8], G2P[4], G3P[8], G9P[8], and G12[P8]). VE was higher in children <3 years (73% to 88%); protection decreased as age increased. Rotavirus vaccines remain highly effective in preventing ED visits and hospitalizations in US children.

Factors associated with antibiotic use in children hospitalized for acute viral gastroenteritis and the relation to rotavirus vaccination

ABSTRACT Evidence on unnecessary antibiotic use in children with acute viral gastroenteritis (AGE) is scarce. We characterized the extent and correlates of antibiotic use among children hospitalized with viral AGE. A single-center study enrolled children aged 0–59 months hospitalized for AGE between 2008 and 2015 in Israel. Information was collected on laboratory tests, diagnoses, antibiotic treatment, and rotavirus vaccination. Stool samples were tested for rotavirus antigen, GII-norovirus, and stool cultures were performed for bacterial enteropathogens. Data from 2240 children were analyzed. Rotavirus vaccine was given to 79% of eligible children. Rotavirus test was performed on 1419 (63.3%) children. Before the introduction of universal rotavirus vaccination (2008–2010), rotavirus positivity in stool samples was 37.0%, which declined to 17.3% during the universal vaccination years (2011–2015). Overall, 1395 participants had viral AGE. Of those, 253 (18.1% [95% CI 16.1–20.2]) had unnecessary antibiotic treatment, mostly penicillin 46.6%, ceftriaxone 34.0% and azithromycin 21.7%. A multivariable analysis showed an inverse association between rotavirus vaccination and unnecessary antibiotic treatment (odds ratio = 0.53 [95% CI 0.31–0.91]), while positive associations were found with performing chest-X-ray test (3.00 [1.73–5.23]), blood (3.29 [95% CI 1.85–5.86]) and urine cultures (7.12 [3.77–13.43]), levels of C-reactive protein (1.02 [1.01–1.02]) and leukocytes (1.05 [1.01–1.09]). The results were consistent in an analysis of children with laboratory-confirmed rotavirus or norovirus AGE, or after excluding children with CRP > 50 mg/L. In conclusion, antibiotic prescription was common among hospitalized children with viral AGE, which was inversely related to rotavirus vaccination, possibly due to less severe illness in the vaccinated children.

Shigella and ETEC have replaced rotavirus as main causes of childhood diarrhea in Rwanda after ten years of rotavirus vaccination.

The causes of diarrhea after ten years of rotavirus vaccination in Rwanda were investigated in 496 children with and 298 without diarrhea using a real-time PCR. Rotavirus was detected in 11% of children with diarrhea (OR 2.48, P=0.002). Comparison of population attributable fractions (PAF) show that Shigella (PAF=11%) and ETEC-eltB (PAF=12%) have replaced rotavirus as the main causative agents. The PAF for rotavirus had declined from 41% pre-vaccination to 6.5%, indicating that rotavirus has become one among several similarly important causes of childhood diarrhea in Rwanda. A rotavirus genotype shift to G3P[8] points at the importance of continued genotype surveillance.