Enteric viruses are significantly associated with acute gastroenteritis globally. Despite a decrease in severe rotavirus associated diarrhoea, Ghana still records high diarrhoea burden. Meanwhile aetiological investigations in hospital settings do not routinely include viral testing. Rotavirus vaccination is thought to alter enteric viral populations and impact evolution. To better understand virus-specific effects in acute gastroenteritis in both children and adults, we tested fecal samples from 228 patients at two hospitals in Accra from January to December 2019, using multiplex and singleplex PCR assays. The clinical impact of detected viruses was assessed using a modified Vesikari score system. Partial viral genome sequences were obtained by Sanger Sequencing and their genetic diversity and evolutionary history, traced by phylogenetic analyses. At least one enteric virus was found in 86 (37.7%) patient samples, with 36.9% of the population under five infected. Single infections of rotavirus, norovirus, adenovirus, sapovirus and astrovirus were 33, 14, 8, 6, and 1, respectively, while coinfections were 24. Rotavirus accounted for 33.3% of 24 clinically severe cases (modified Vesikari score > 7). Three out of 10 rotavirus cases with evidence of vaccination experienced severe gastroenteritis. Diverse genotypes, including RVA G2P[4], G1P[8], G12P[8] and G12P[6]; AdV F40 and F41; NoV GII.4 Sydney 2012, GII.6 and GI.3, several of which clustered with contemporary strains from the Americas, Europe and Asia, were detected. This study also provides the first report of SaV GI.1, GI.7 and GII.8 detection in humans in Ghana. RVA G2P[4] and AdV F were associated with higher proportions of hospitalizations. While RVA continues to have a profound clinical impact on gastroenteritis, AdV and SaV produce an equally severe disease. In contrast, NoV and AstV showed a generally mild to moderate impact on clinical disease severity.

Rotavirus is a leading cause of severe diarrheal disease in infants and young children worldwide. Vaccination offers the best protection against this disease, and two rotavirus vaccines were developed in India and included in its routine immunization program. The Government of India's decision to adopt this intervention was supported by a solid base of evidence from clinical trials, as well as substantial research regarding rotavirus disease burden and the potential health and economic value of immunization. Following program implementation, multiple studies were initiated, including three evaluations of effectiveness and several investigations regarding intussusception. These additional data regarding vaccine impact, safety, and delivery from post-introduction evaluations in conditions of real-world use will further strengthen and sustain the immunization program. This manuscript evaluates the status of existing and forthcoming evidence regarding rotavirus vaccination in India through a literature review and consultation with relevant stakeholders. Studies evaluating vaccine impact, effectiveness, safety, health economics, and acceptability, as well as operational and programmatic research, were included in the review. Overall, we found that the evidence base did not contain any major gaps. Nevertheless, additional smaller-scale research studies would be valuable in providing a more complete picture of rotavirus vaccine performance and benefit. Documentation of India's experience with rotavirus vaccines may provide lessons learned for other countries in the Asia region, where rotavirus disease burden remains high, yet vaccine adoption has been slow, as well as for countries worldwide that may be considering implementation of the Indian-made rotavirus vaccines.

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.

Despite the adoption of rotavirus vaccines, sporadic outbreaks of the virus have been reported in many parts of the world. These outbreaks are facilitated by several factors including the ease of transmission of rotavirus through water environments. This systematic review aimed to determine the global prevalence of rotavirus in water environments.

Comprehensive Boolean searches were conducted in PubMed, SCOPUS, and Web of Science. A total of 75 eligible studies were included in the study, from which data was extracted for both systematic review and meta-analysis. Extracted prevalence data was grouped according to six water categories: drinking water, untreated sewage, treated sewage, surface water, groundwater, and others. A single-group prevalence meta-analysis was conducted in RStudio version 4.3.3 subjecting the data to the random-effects model.

The included studies were conducted in 32 countries that span 5 continents: Africa, Asia, Europe, North America, and South America. The pooled prevalence of rotavirus in water environments was 40.86%. Among the individual water environments, untreated sewage had the highest prevalence (68.27%), followed by treated sewage (53.07%), surface water (33.40%), groundwater (25.64%) and drinking water (9.46%). Continental stratification of the prevalence data was as follows: Africa (51.75%), Asia (32.48%), Europe (55.90%), North America (41.80%), and South America (28.51%).

There is a high prevalence of rotavirus in water environments, especially in untreated sewage, and in Europe. Further research is needed to find more efficient methods that can effectively eliminate rotavirus to insignificant levels in water environments.

Rotavirus (RV) induced diarrhea led to hospitalization and mortality prior to the introduction of the rotavirus vaccine (RVV). The estimated RVV coverage was 86% in children less than one year of age in Pakistan.

To determine the difference in the number of diarrheal episodes among children who received and who did not receive RVV, along with the parental and physician's perspectives on the barriers toward RV immunization in children aged less than 1 year in Karachi, Pakistan.

A mixed-methods study design was conducted in three Primary Healthcare (PHC) private clinics located in different districts of Karachi, Pakistan. Data for RVV status and diarrheal episodes were collected, from medical records in June 2020 for children born between October 2019 to March 2020. Three In-depth Interviews (IDIs) with physicians and three focus group discussions (FGDs) with mothers were conducted for information on awareness and approach towards diarrhea, knowledge, and acceptance of RVV, and barriers towards RV immunization.

A total of 430 infants visited the three PHC centres coded as A (n = 144), B (n = 146), and C (n = 140). The mean age of infants was 2.6 ± 0.2 months, 49.5 % were males and 87 (20.2 %) were partial/not vaccinated for RV. Reported diarrheal episodes were 104 (24.2 %), and of these 76 (73.1 %) were partially or not vaccinated, and 83 (79.8 %) were stunted. Recorded diarrhea was significantly associated with partial/not vaccinated status (p < 0.001), stunting (p < 0.001), and by PHC centre location (p < 0.001). PHC-C had the lowest percentage of reported diarrhea, stunting, and non/partially vaccinated status. Qualitative study (FGDs) showed that mothers had lack of awareness and knowledge on the prevention of diarrhea by RVV. Physicians' IDIs pointed towards a lack of sufficient training on RVV.

Diarrheal episodes in infants were associated with partial or unvaccinated for RVV, low nutritional status, and areas of residence. Low levels of knowledge and awareness in caretakers and lack of training for RVV in PHC physicians were perceived as barriers in controlling diarrheal diseases.

Diarrheal diseases substantially affect public health impact in low- and middle-income countries (LMIC), particularly in Africa, where previous studies have indicated a lack of comprehensive data. With a growing number of primary studies on enteric infections in Africa, this study aimed to estimate the incidence and mortality of diarrheal pathogens across all ages in Africa in the year 2020. We also explored different methodological assumptions to allow comparison with other approaches.

Through a systematic review and meta-analysis of data from African LMICs, we estimated the etiology proportions for diarrheal diseases and deaths. We combined the etiology proportions with incidence data collected from a population survey in Africa from 2020 and mortality data from the Global Health Observatory of WHO.

We estimated 1,008 billion diarrhea cases (95% UI 447 million-1,4 billion) and 515,031 diarrhea deaths (95% UI 248,983-1,007,641) in the African region in 2020. In children under five, enteroaggregative E. coli (EAEC) (44,073 cases per 100,000 people, 95% UI 18,818 - 60,922) and G. lamblia (36,116 cases per 100,000 people, 95% UI 15,245 - 49,961) were the leading causes of illness. Enteroinvasive E. coli (EIEC) (155 deaths per 100,000 people, 95% UI 106.5-252.9) and rotavirus (61.5 deaths per 100,000 people, 95% UI 42.3-100.3) were the primary causes of deaths. For children over five and adults, Salmonella spp. caused the largest number of diarrheal cases in the population of children ≥ 5 and adults (122,090 cases per 100,000 people, 95% UI 51,833 - 168,822), while rotavirus (16.4 deaths per 100,000 people, 95% UI 4.2-36.7) and enteroaggregative E. coli (EAEC) (14.6 deaths per 100,000 people, 95% UI 3.9-32.9) causing the most deaths. Geographically, the highest incidence of diarrhea was in Eastern Africa for children under five (114,389 cases per 100,000 people, 95% UI 34,771 - 172,884) and Central Africa for children over five and adults (117,820 cases per 100,000 people, 95% UI 75,111-157,584). Diarrheal mortality was highest in Western Africa for both children below five and above (children < 5: 194.5 deaths per 100,000 people, 95% UI 120-325.4; children ≥ 5 and above: 33.5 deaths per 100,000 people, 95% UI 12.9-75.1).

These findings provide new information on the incidence and mortality of sixteen pathogens and highlight the need for surveillance and control of diarrheal infectious diseases in Africa. The cause-specific estimates are crucial for prioritizing diarrheal disease prevention in the region.

Rotaviruses are non-enveloped double-stranded RNA virus that causes acute diarrheal diseases in children (< 5 years). More than 90% of the global rotavirus infection in humans was caused by Rotavirus group A. Rotavirus infection has caused more than 200000 deaths annually and predominantly occurs in the low-income countries. Rotavirus evolution is indicated by the strain dynamics or the emergence of the unprecedented strain. The major factors that drive the rotavirus evolution include the genetic shift that is caused by the reassortment mechanism, either in the intra- or the inter-genogroup. However, other factors are also known to have an impact on rotavirus evolution. This review discusses the structure and types, epidemiology, and evolution of rotaviruses. This article also reviews other supplemental factors of rotavirus evolution, such as genetic reassortment, mutation rate, glycan specificity, vaccine introduction, the host immune responses, and antiviral drugs.

In January 2018, Afghanistan introduced the monovalent oral rotavirus vaccine (Rotarix) nationwide, administered as a 2-dose series at six and ten weeks of age. We describe characteristics of intussusception cases and assess potential intussusception risk associated with Rotarix vaccination in Afghan infants.

Multi-center prospective active hospital-based surveillance for intussusception was conducted from May 2018 to March 2022 in four sentinel sites in Afghanistan. We applied the Brighton Level 1 criteria for intussusception and verified vaccination status by reviewing vaccine cards. We used the self-controlled case series (SCCS) methodology to compare intussusception incidence in the 1 to 21 days after each dose of Rotarix vaccination against non-risk periods.

A total of 468 intussusception cases were identified in infants under 12 months, with 264 cases aged between 28 and 245 days having confirmed vaccination status contributing to the SCCS analysis. Most case-patients (98 %) required surgery for treatment, and over half (59 %) of those who underwent surgery required intestinal resection. Nineteen (7 %) case-patients died. Eighty-six percent of case-patients received the first dose of Rotarix, and 69 % received the second dose before intussusception symptom onset. There was no increased risk of intussusception in the 1-7 days (relative incidence: 0.9, 95 % CI: 0.1, 7.5), 8-21 days (1.3, 95 % CI: 0.4, 4.2), or 1-21 days (1.1, 95 % CI: 0.4, 3.4) following receipt of the first dose or in the 1-7 days (0.2, 95 % CI: 0.3, 1.8), 8-21 days (0.7, 95 % CI: 0.3, 1.5), or 1-21 days (0.6, 95 % CI: 0.3, 1.2) following the second dose.

Rotarix vaccination was not associated with an increased intussusception risk, supporting its continued use in Afghanistan's immunization program. However, there was a high level of death and resection due to intussusception among Afghan infants.

Species A rotaviruses are the leading viral cause of acute gastroenteritis in children under 5 years of age worldwide. Despite progress in the characterization of the pathogenesis and immunology of rotavirus-induced gastroenteritis, correlates of protection (CoPs) in the course of either natural infection or vaccine-induced immunity are not fully understood. There are numerous factors such as serological responses (IgA and IgG), the presence of maternal antibodies (Abs) in breast milk, changes in the intestinal microbiome, and rotavirus structural and non-structural proteins that contribute to the outcome of the CoP. Indeed, while an intestinal IgA response and its surrogate, the serum IgA level, are suggested as the principal CoPs for oral rotavirus vaccines, the IgG level is more likely to be a CoP for parenteral non-replicating rotavirus vaccines. Integrating clinical and immunological data will be instrumental in improving rotavirus vaccine efficacy, especially in low- and middle-income countries, where vaccine efficacy is significantly lower than in high-income countries. Further knowledge on CoPs against rotavirus disease will be helpful for next-generation vaccine development. Herein, available data and literature on interacting components and proposed CoPs against human rotavirus disease are reviewed, and limitations and gaps in our knowledge in this area are discussed.

In children with ileocolic intussusception, sedatives such as midazolam, ketamine and propofol may facilitate radiologic enema reduction, but studies on their separate and joint effects remain controversial.

We aimed to systematically analyze studies for the effects of sedatives on the radiologic reduction of ileocolic intussusception in children.

We searched PubMed, EMBASE, CINAHL, Scopus and Web of Science from database inception through March 2023 for articles that enrolled children with ileocolic intussusception who underwent non-operative pneumatic or hydrostatic enema reduction under ultrasound or fluoroscopic guidance with or without the use of sedatives. The primary and secondary outcomes were success rate in radiologic reduction of ileocolic intussusception and risk of perforation, respectively. Effect estimates from the individual studies were extracted and combined using the Hartung-Knapp-Sidik-Jonkman log-odds random-effects model. Heterogeneity between studies was checked using Cochran's Q test and the I2 statistic.

A total of 17 studies with 2094 participants were included in the final review, of which 15 were included in the meta-analysis. Nine studies reported on the success rate of radiologic reduction performed under sedation in all participants, while six studies compared the success rate in two patient groups undergoing the procedure with or without sedation. The pooled success rate of non-operative reduction under sedation was 87 % (95 % CI: 80-95 %), P = 0.000 with considerable heterogeneity (I2 = 85 %). A higher success rate of 94 % (95 % CI: 88-99 %) and homogeneity (I2 = 12 %) were found in studies with pneumatic enema reduction. Among comparative studies, the odds of success of non-operative reduction were increased when the procedure was performed under sedation, with a pooled odds ratio of 2.41 (95 % CI: 1.27-4.57), P = 0.010 and moderate heterogeneity (I2 = 60 %). In a sensitivity analysis, homogeneity was found between analyzed studies when two outliers were excluded (I2 = 0.73 %). The risk of perforation was not significantly different (OR 1.52, 95 % CI: 0.09-23.34), P = 0.764 indicating small study effects. No publication, bias was detected on visual inspection of the funnel plots or the Begg's and Egger's bias tests. Most studies were categorized as having a low risk of bias using Joanna Briggs Institute checklists.

In selected patient groups, sedation can increase the success rate of radiologic enema reduction in children with ileocolic intussusception without evidence of increased risk of perforation. Systematic review protocol registration: PROSPERO CRD42023404887.

To estimate gastroenteritis disease and its etiological agents in children under the age of 5 years living in South Africa.

A mini literature review of pertinent articles published in ScienceDirect, PubMed, GoogleScholar, and Scopus was conducted using search terms: "Gastroenteritis in children," "Gastroenteritis in the world," Gastroenteritis in South Africa," "Prevalence of gastroenteritis," "Epidemiological surveillance of gastroenteritis in the world," and "Causes of gastroenteritis".

A total of 174 published articles were included in this mini review. In the last 20 years, the mortality rate resulting from diarrhea in children under the age of 5 years has declined and this is influenced by improved hygiene practices, awareness programs, an improved water and sanitation supply, and the availability of vaccines. More modern genomic amplification techniques were used to re-analyze stool specimens collected from children in eight low-resource settings in Asia, South America, and Africa reported improved sensitivity of pathogen detection to about 65%, that viruses were the main etiological agents in patients with diarrhea aged from 0 to 11 months but that Shigella, followed by sapovirus and enterotoxigenic Escherichia coli had a high incidence in children aged 12-24 months. In addition, co-infections were noted in nearly 10% of diarrhea cases, with rotavirus and Shigella being the main co-infecting agents together with adenovirus, enteropathogenic E. coli, Clostridium jejuni, or Clostridium coli.

This mini review outlines the epidemiology and trends relating to parasitic, viral, and bacterial agents responsible for gastroenteritis in children in South Africa. An increase in sequence-independent diagnostic approaches will improve the identification of pathogens to resolve undiagnosed cases of gastroenteritis. Emerging state and national surveillance systems should focus on improving the identification of gastrointestinal pathogens in children and the development of further vaccines against gastrointestinal pathogens.

Rotavirus A (RVA) remains a leading cause of acute gastroenteritis (AGE) hospitalizations in children worldwide. During the COVID-19 pandemic, a reduction in vaccination coverage in Brazil and elsewhere was observed, and some reports have demonstrated a reduction in AGE notifications during the pandemic. This study aims to investigate the diversity and prevalence of RVA genotypes in children and adults presenting with AGE symptoms in Brazil during the COVID-19 pandemic between 2020 and 2022. RVA was screened using RT-qPCR; then, G and P genotypes were characterized using one-step multiplex RT-PCR. A total of 2173 samples were investigated over the three-year period, and we detected RVA in 7.7% of samples (n = 167), being 15.5% in 2020, 0.5% in 2021, and 13.8% in 2022. Higher RVA prevalence was observed in the Northeastern region (19.3%) compared to the Southeastern (6.1%) and Southern regions (5.5%). The most affected age group was children aged between 0 and 6 months old; however, this was not statistically significant. Genotyping and phylogenetic analysis identified the emergence of G6P[8] during the period; moreover, it was detected in 10.6% of samples in 2020 and in 83.5% in 2022. In contrast, the prevalence of G3P[8], the previous dominant genotype, decreased from 72.3% in 2020 to 11.3% in 2022. We also identified unusual strains, such as G3P[9] and G9P[4], being sporadically detected during the period. This is the first report on the molecular epidemiology and surveillance of RVA during the COVID-19 pandemic period in Brazil. Our study provides evidence for the importance of maintaining high and sustainable levels of vaccine coverage to protect against RVA disease. Furthermore, it highlights the need to maintain nationwide surveillance in order to monitor future trends and changes in the epidemiology of RVA in Brazil.

Children five years or younger in low- and middle-income countries (LMICs) are severely affected by diarrheal disease, especially in the sub-Saharan region. Hence, this study aimed at determining the prevalence and determinants of diarrhoea disease among children under 5 years in Epworth Township, Zimbabwe. A descriptive cross-sectional study was conducted at a local clinic in Epworth Township, Harare. A convenience sampling strategy was used to recruit study participants for participation, and 386 children were enrolled in the study. The majority were male children (n = 229; 59.3%), whereas there were more female caregivers (n = 370; 95.9%) than male caregivers (n = 16; 4.1%). The prevalence of diarrhoea disease in the study was 25.1%. The determinants associated with diarrhoea were being partially vaccinated (AOR 2.38, CI: 95% 2.80-8.22), collecting water more than 1 kilometre from a household (AOR 4.55; CI: 95% 2.10-9.85), and using untreated water (AOR 6.22; CI: 95% 2.13-18.20). The age of the caregiver (being older than 21) and using a clean water container (AOR 0.05; CI: 95% 0.02-0.13) were protective factors. Provision of primary health care, especially the prevention of a disease through immunization and rendering environmental health services, could reduce the prevalence of diarrhoea in disadvantaged townships.

Rotavirus group A (RVA) is the most important cause of acute diarrhoea and severe dehydration in young mammals. Infection in livestock is associated with significant mortality and economic losses and, together with wildlife reservoirs, acts as a potential source of zoonotic transmission. Therefore, molecular surveillance of circulating RVA strains in animal species is necessary to assess the risks posed to humans and their livestock. An RVA molecular epidemiological surveillance study on clinically diseased livestock species revealed high prevalence in cattle and pigs (31 per cent and 18 per cent, respectively) with significant phylogenetic diversity including a novel and divergent ovine artiodactyl DS-1-like constellation G10-P[15]-I2-R2-C2-M2-A11-N2-T6-E2-H3. An RVA gene reassortment occurred in an RVA asymptomatic pig and identified as a G5-P[13] strain, and a non-structural protein (NSP)2 gene had intergenomically reassorted with a human RVA strain (reverse zoonosis) and possessed a novel NSP4 enterotoxin E9 which may relate to the asymptomatic RVA infection. Analysis of a novel sheep G10-P[15] strain viral protein 4 gene imparts a putative homologous intergenic and interspecies recombination event, subsequently creating the new P[15] divergent lineage. While surveillance across a wider range of wildlife and exotic species identified generally negative or low prevalence, a novel RVA interspecies transmission in a non-indigenous pudu deer (zoo origin) with the constellation of G6-P[11]12-R2-C2-M2-A3-N2-T6-E2-H3 was detected at a viral load of 11.1 log10 copies/gram. The detection of novel emerging strains, interspecies reassortment, interspecies infection, and recombination of RVA circulating in animal livestock and wildlife reservoirs is of paramount importance to the RVA epidemiology and evolution for the One Health approach and post-human vaccine introduction era where highly virulent animal RVA genotypes have the potential to be zoonotically transmitted.

G3 rotaviruses rank among the most common rotavirus strains worldwide in humans and animals. However, despite a robust long-term rotavirus surveillance system from 1997 at Queen Elizabeth Central Hospital in Blantyre, Malawi, these strains were only detected from 1997 to 1999 and then disappeared and re-emerged in 2017, 5 years after the introduction of the Rotarix rotavirus vaccine. Here, we analysed representative twenty-seven whole genome sequences (G3P[4], n = 20; G3P[6], n = 1; and G3P[8], n = 6) randomly selected each month between November 2017 and August 2019 to understand how G3 strains re-emerged in Malawi. We found four genotype constellations that were associated with the emergent G3 strains and co-circulated in Malawi post-Rotarix vaccine introduction: G3P[4] and G3P[6] strains with the DS-1-like genetic backbone genes (G3-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 and G3-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2), G3P[8] strains with the Wa-like genetic backbone genes (G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1), and reassortant G3P[4] strains consisting of the DS-1-like genetic backbone genes and a Wa-like NSP2 (N1) gene (G3-P[4]-I2-R2-C2-M2-A2-N1-T2-E2-H2). Time-resolved phylogenetic trees demonstrated that the most recent common ancestor for each ribonucleic acid (RNA) segment of the emergent G3 strains was between 1996 and 2012, possibly through introductions from outside the country due to the limited genetic similarity with G3 strains which circulated before their disappearance in the late 1990s. Further genomic analysis revealed that the reassortant DS-1-like G3P[4] strains acquired a Wa-like NSP2 genome segment (N1 genotype) through intergenogroup reassortment; an artiodactyl-like VP3 through intergenogroup interspecies reassortment; and VP6, NSP1, and NSP4 segments through intragenogroup reassortment likely before importation into Malawi. Additionally, the emergent G3 strains contain amino acid substitutions within the antigenic regions of the VP4 proteins which could potentially impact the binding of rotavirus vaccine-induced antibodies. Altogether, our findings show that multiple strains with either Wa-like or DS-1-like genotype constellations have driven the re-emergence of G3 strains. The findings also highlight the role of human mobility and genome reassortment events in the cross-border dissemination and evolution of rotavirus strains in Malawi necessitating the need for long-term genomic surveillance of rotavirus in high disease-burden settings to inform disease prevention and control.

Histo-blood group antigens (HBGAs) may influence immune responses to rotavirus vaccination.

HBGA phenotyping was determined by detection of antigens A, B, H and Lewis a and b in saliva using enzyme-linked immunosorbent assay. Secretor status was confirmed by lectin antigen assay if A, B and H antigens were negative or borderline (OD ± 0.1 of threshold of detection). PCR-RFLP analysis was used to identify the FUT2 'G428A' mutation in a subset. Rotavirus seropositivity was defined as serum anti-rotavirus IgA ≥ 20 AU/mL.

Of 156 children, 119 (76 %) were secretors, 129 (83 %) were Lewis antigen positive, and 105 (67 %) were rotavirus IgA seropositive. Eighty-seven of 119 (73 %) secretors were rotavirus seropositive, versus 4/9 (44 %) weak secretors and 13/27 (48 %) non-secretors.

Most Australian Aboriginal children were secretor and Lewis antigen positive. Non-secretor children were less likely to be seropositive to rotavirus antibodies following vaccination, but this phenotype was less common. HBGA status is unlikely to fully explain underperformance of rotavirus vaccines among Australian Aboriginal children.

Following the World Health Organization (WHO) recommendation, 38/47 countries have introduced rotavirus vaccines into the program of immunization in the WHO Regional Office for Africa (WHO/AFRO). Initially, two vaccines (Rotarix and Rotateq) were recommended and recently two additional vaccines (Rotavac and Rotasiil) have become available. However, the global supply challenges have increasingly forced some countries in Africa to switch vaccine products. Therefore, the recent WHO pre-qualified vaccines (Rotavac, Rotasiil) manufactured in India, offer alternatives and reduce global supply challenges related to rotavirus vaccines; Methods: Using a questionnaire, we administered to the Program Managers, Expanded Program for Immunization, we collected data on vaccine introduction and vaccine switch and the key drivers of the decisions for switching vaccines products, in the WHO/AFRO. Data was also collected fromliterature review and the global new vaccine introduction status data base maintained by WHO and other agencies.

Of the 38 countries that introduced the vaccine, 35 (92%) initially adopted Rotateq or Rotarix; and 23% (8/35) switched between products after rotavirus vaccine introduction to either Rotavac (n = 3), Rotasiil (n = 2) or Rotarix (n = 3). Three countries (Benin, Democratic Republic of Congo and Nigeria) introduced the rotavirus vaccines manufactured in India. The decision to either introduce or switch to the Indian vaccines was predominately driven by global supply challenges or supply shortage. The withdrawal of Rotateq from the African market, or cost-saving for countries that graduated or in transition from Gavi support was another reason to switch the vaccine; Conclusions: The recently WHO pre-qualified vaccines have offered the countries, opportunities to adopt these cost-effective products, particularly for countries that have graduated or transitioning from full Gavi support, to sustain the demand of vaccines products.

Oral rotavirus vaccines were incorporated into the National Immunisation Program (NIP) for all Australian infants in July 2007. Initially each of the eight jurisdictions implemented Rotarix or RotaTeq rotavirus vaccine, however from July 2017 all states and territories have administered Rotarix only. This review evaluates the health impact of the oral rotavirus vaccine program for Australian children less than 5 years old over the first 15 years of the rotavirus vaccine program, observing long-term changes in rotavirus-related health care attendances, public health notifications, and vaccine effectiveness and safety data for both Rotarix and RotaTeq rotavirus vaccines. We searched Medline for studies published between January 2006 and May 2022 using the search terms 'rotavirus', 'rotavirus vaccine' and 'Australia'. Of 491 items identified, 76 items - 36 peer-reviewed articles and 40 reports - were included in the review. We found evidence that the introduction of the oral rotavirus vaccine program in Australia was associated with a prompt reduction in rotavirus-coded and all-cause gastroenteritis hospitalisations of vaccine-eligible children. In the context of less complete coverage, reduced vaccine timeliness and lower vaccine effectiveness, a less substantial and inconsistent reduction in severe rotavirus disease was observed among Aboriginal and Torres Strait Islander children, particularly those living in rural and remote northern Australia. Additional studies report no evidence for the emergence of non-vaccine serotypes and/ or replacement serotypes in Australia during the vaccine era. While the health impact for young children and consequent cost-savings of the oral rotavirus vaccine program have been high, it is important to find strategies to improve rotavirus vaccine impact for Aboriginal and Torres Strait Islander populations to ensure health benefits for all Australian children.

Oral rotavirus vaccines have lower effectiveness in high child mortality settings. We evaluated the impact of additional dose(s) schedules of rotavirus vaccine on vaccine immunogenicity and reduction in episodes of gastroenteritis.

We searched Medline (via PubMed), Cochrane databases and ClinicalTrials.gov for randomised controlled trials from 1973 to February 2022, evaluating the immunological and clinical impact of additional dose vs standard dose oral rotavirus vaccine schedules. We extracted immunogenicity - proportion of children with evidence of anti-rotavirus IgA seroresponse, and clinical - proportion of children with at least one episode of severe rotavirus gastroenteritis, outcome data and used random effects meta-analysis where appropriate. We assessed the methodological quality of the studies using the Cochrane risk of bias tool. The study protocol was registered in PROSPERO (CRD42021261058).

We screened 536 items and included 7 clinical trials. Our results suggest moderate to high level evidence that an additional dose rotavirus vaccine schedule improves IgA vaccine immune response, including additional doses administered as a booster dose schedule >6 months old; IgA vaccine seroresponse 74·3% additional dose schedule vs 56·1% standard dose schedule RR 1·3 (95%CI, 1·15 - 1·48), and when administered to children who were seronegative at baseline; IgA vaccine seroresponse 48.2% additional dose schedule vs 29.6% standard dose schedule RR 1.86 (95%CI 1.27 to 2.72). Only one study evaluated reduction in gastroenteritis episodes and found little benefit in first year of life, 1·8% vs 2·0% RR 0·88 (95% CI, 0·52 to 1·48), or second year of life, 1·7% vs 2·9% RR 0·62 (95%CI, 0·31 - 1·23).

Administering an additional dose of oral rotavirus vaccines is likely to result in an improved vaccine immune response, including when administered as a booster dose to older children. Evidence of an impact on diarrhoeal disease is needed before additional dose rotavirus vaccine schedules can be recommended as vaccine policy.

BM was funded by the National Health and Medical Research Council, the Royal Australasian College of Physicians Paediatrics and Child Health Division, and the Australian Academy of Science.

A head-to-head comparison of the most widely used oral rotavirus vaccines has not previously been done, particularly in a high child mortality setting. We therefore aimed to compare the immunogenicity of RotaTeq (Merck, Kenilworth, NJ, USA) and Rotarix (GlaxoSmithKline, Rixensart, Belgium) rotavirus vaccines in the same population and examined risk factors for low seroresponse.

We did a randomised, controlled, open-label, parallel, phase 4 trial in urban slums within Mirpur and Mohakahli (Dhaka, Bangladesh). We enrolled eligible participants who were healthy infants aged 6 weeks and full-term (ie, >37 weeks' gestation). We randomly assigned participants (1:1), using block randomisation via a computer-generated electronic allocation with block sizes of 8, 16, 24, and 32, to receive either three RotaTeq vaccine doses at ages 6, 10, and 14 weeks or two Rotarix doses at ages 6 and 10 weeks without oral poliovirus vaccine. Coprimary outcomes were the rotavirus-specific IgA seroconversion in both vaccines, and the comparison of the rotavirus IgA seroconversion by salivary secretor phenotype in each vaccine arm. Seroconversion at age 18 weeks in the RotaTeq arm and age of 14 weeks in the Rotarix arm was used to compare the complete series of each vaccine. Seroconversion at age 14 weeks was used to compare two RotaTeq doses versus two Rotarix doses. Seroconversion at age 22 weeks was used to compare the immunogenicity at the same age after receiving the full vaccine series. Safety was assessed for the duration of study participation. This study is registered with ClinicalTrials.gov, NCT02847026.

Between Sept 1 and Dec 8, 2016, a total of 1144 infants were randomly assigned to either the RotaTeq arm (n=571) or Rotarix arm (n=573); 1080 infants (531 in the RotaTeq arm and 549 in the Rotarix arm) completed the study. Rotavirus IgA seroconversion 4 weeks after the full series occurred in 390 (73%) of 531 infants age 18 weeks in the RotaTeq arm and 354 (64%) of 549 infants age 14 weeks in the Rotarix arm (p=0·01). At age 14 weeks, 4 weeks after two doses, RotaTeq recipients had lower seroconversion than Rotarix recipients (268 [50%] of 531 vs 354 [64%] of 549; p<0·0001). However, at age 22 weeks, RotaTeq recipients had higher seroconversion than Rotarix recipients (394 [74%] of 531 vs 278 [51%] of 549; p<0·0001). Among RotaTeq recipients, seroconversion 4 weeks after the third dose was higher than after the second dose (390 [73%] of 531 vs 268 [50%] of 531; p<0·0001]. In the RotaTeq arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·08), 18 weeks (p=0·01), and 22 weeks (p=0·02). Similarly, in the Rotarix arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·02) and 22 weeks (p=0·01). 65 (11%) of 571 infants had adverse events in the RotaTeq arm compared with 63 (11%) of 573 infants in the Rotarix arm; no adverse events were attributed to the use of either vaccine. One death due to aspiration occurred in the RotaTeq arm, which was not related to the vaccine.

RotaTeq induced a higher magnitude and longer duration of rotavirus IgA response than Rotarix in this high child mortality setting. Additional vaccination strategies should be evaluated to overcome the suboptimal performance of current oral rotavirus vaccines in these settings.

US Centers for Disease Control and Prevention.

The leading cause of gastroenteritis among young children worldwide is the Group A rotaviruses (RV), which produce a wide range of symptoms, from a limited diarrhea to severe dehydration and even death. After an RV infection, immunity is not complete and less severe re-infections usually occur. These infections could be ameliorated by nutritional interventions with bioactive compounds, such as prebiotics. The aim of this research was to study the impact of a particular galactooligosaccharide (B-GOS) on the RV symptomatology and immune response during two consecutive infections. Lewis neonatal rats were inoculated with SA11 (first RV infection) on day 6 of life and with EDIM (second RV infection) on day 17 of life. B-GOS group was administered by oral gavage with a daily dose of B-GOS between days three to nine of life. Clinical and immunological variables were assessed during both infective processes. In the first infection, after the prebiotic intervention with B-GOS, a lower incidence, duration, and overall severity of the diarrhea (p < 0.05) was observed. In addition, it improved another severity indicator, the fecal weight output, during the diarrhea period (p < 0.05). The second RV infection failed in provoking diarrhea in the groups studied. The immune response during first infection with SA11 was not affected by B-GOS administration and had no impact on second infection, but the prebiotic intervention significantly increased IFN-γ and TNF-α intestinal production after the second infection (p < 0.05). In summary, B-GOS supplementation is able to reduce the incidence and severity of the RV-associated diarrhea and to influence the immune response against RV infections.