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Nature Reviews. Disease Primers Nov 2017Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for... (Review)
Review
Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases.
Topics: Humans; Rotavirus Infections
PubMed: 29119972
DOI: 10.1038/nrdp.2017.83 -
JAMA Pediatrics Oct 2018Rotavirus infection is the global leading cause of diarrhea-associated morbidity and mortality among children younger than 5 years.
IMPORTANCE
Rotavirus infection is the global leading cause of diarrhea-associated morbidity and mortality among children younger than 5 years.
OBJECTIVES
To examine the extent of rotavirus infection among children younger than 5 years by country and the number of deaths averted because of the rotavirus vaccine.
DESIGN, SETTING, AND PARTICIPANTS
This report builds on findings from the Global Burden of Disease Study 2016, a cross-sectional study that measured diarrheal diseases and their etiologic agents. Models were used to estimate burden in data-sparse locations.
EXPOSURE
Diarrhea due to rotavirus infection.
MAIN OUTCOMES AND MEASURES
Rotavirus-associated mortality and morbidity by country and year and averted deaths attributable to the rotavirus vaccine by country.
RESULTS
Rotavirus infection was responsible for an estimated 128 500 deaths (95% uncertainty interval [UI], 104 500-155 600) among children younger than 5 years throughout the world in 2016, with 104 733 deaths occurring in sub-Saharan Africa (95% UI, 83 406-128 842). Rotavirus infection was responsible for more than 258 million episodes of diarrhea among children younger than 5 years in 2016 (95% UI, 193 million to 341 million), an incidence of 0.42 cases per child-year (95% UI, 0.30-0.53). Vaccine use is estimated to have averted more than 28 000 deaths (95% UI, 14 600-46 700) among children younger than 5 years, and expanded use of the rotavirus vaccine, particularly in sub-Saharan Africa, could have prevented approximately 20% of all deaths attributable to diarrhea among children younger than 5 years.
CONCLUSIONS AND RELEVANCE
Rotavirus-associated mortality has decreased markedly over time in part because of the introduction of the rotavirus vaccine. This study suggests that prioritizing vaccine introduction and interventions to reduce diarrhea-associated morbidity and mortality is necessary in the continued global reduction of rotavirus infection.
Topics: Child, Preschool; Cross-Sectional Studies; Diarrhea; Female; Global Health; Humans; Incidence; Male; Prognosis; Retrospective Studies; Rotavirus Infections; Rotavirus Vaccines; Survival Rate; Vaccination
PubMed: 30105384
DOI: 10.1001/jamapediatrics.2018.1960 -
Viruses Mar 2017Rotaviruses (RVs) are a major cause of acute viral gastroenteritis in young animals and children worldwide. Immunocompetent adults of different species become resistant... (Review)
Review
Rotaviruses (RVs) are a major cause of acute viral gastroenteritis in young animals and children worldwide. Immunocompetent adults of different species become resistant to clinical disease due to post-infection immunity, immune system maturation and gut physiological changes. Of the 9 RV genogroups (A-I), RV A, B, and C (RVA, RVB, and RVC, respectively) are associated with diarrhea in piglets. Although discovered decades ago, porcine genogroup E RVs (RVE) are uncommon and their pathogenesis is not studied well. The presence of porcine RV H (RVH), a newly defined distinct genogroup, was recently confirmed in diarrheic pigs in Japan, Brazil, and the US. The complex epidemiology, pathogenicity and high genetic diversity of porcine RVAs are widely recognized and well-studied. More recent data show a significant genetic diversity based on the VP7 gene analysis of RVB and C strains in pigs. In this review, we will summarize previous and recent research to provide insights on historic and current prevalence and genetic diversity of porcine RVs in different geographic regions and production systems. We will also provide a brief overview of immune responses to porcine RVs, available control strategies and zoonotic potential of different RV genotypes. An improved understanding of the above parameters may lead to the development of more optimal strategies to manage RV diarrheal disease in swine and humans.
Topics: Animals; Humans; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Swine; Swine Diseases; Zoonoses
PubMed: 28335454
DOI: 10.3390/v9030048 -
Frontiers in Immunology 2023Rotavirus (RV) causes 200,000 deaths per year and imposes a serious burden to public health and livestock farming worldwide. Currently, rehydration (oral and... (Review)
Review
Rotavirus (RV) causes 200,000 deaths per year and imposes a serious burden to public health and livestock farming worldwide. Currently, rehydration (oral and intravenous) remains the main strategy for the treatment of rotavirus gastroenteritis (RVGE), and no specific drugs are available. This review discusses the viral replication cycle in detail and outlines possible therapeutic approaches including immunotherapy, probiotic-assisted therapy, anti-enteric secretory drugs, Chinese medicine, and natural compounds. We present the latest advances in the field of rotavirus antivirals and highlights the potential use of Chinese medicine and natural compounds as therapeutic agents. This review provides an important reference for rotavirus prevention and treatment.
Topics: Humans; Rotavirus Infections; Gastroenteritis; Antiviral Agents; Rotavirus; Hospitalization
PubMed: 37006293
DOI: 10.3389/fimmu.2023.1041149 -
Emerging Infectious Diseases 1998Rotavirus, the most common diarrheal pathogen in children worldwide, causes approximately one third of diarrhea-associated hospitalizations and 800,000 deaths per year.... (Review)
Review
Rotavirus, the most common diarrheal pathogen in children worldwide, causes approximately one third of diarrhea-associated hospitalizations and 800,000 deaths per year. Because natural infection reduces the incidence and severity of subsequent episodes, rotavirus diarrhea might be controlled through vaccination. Serotypespecific immunity may play a role in protection from disease. Tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) (which contains a rhesus rotavirus with serotype G3 specificity and reassortant rhesus-human rotaviruses with G1, G2, and G4 specificity) provides coverage against the four common serotypes of human rotavirus. In clinical trials in industrialized countries, RRV-TV conferred 49% to 68% protection against any rotavirus diarrhea and 61% to 100% protection against severe disease. This vaccine was licensed by the U.S. Food and Drug Administration on August 31, 1998, and should be cost-effective in reducing diarrheal diseases in industrialized countries. The vaccine's efficacy and cost-effectiveness in developing countries should be evaluated.
Topics: Animals; Humans; Rotavirus; Rotavirus Infections; Viral Vaccines
PubMed: 9866732
DOI: 10.3201/eid0404.980406 -
Human Vaccines & Immunotherapeutics Dec 2023Rotavirus is one of the main pathogens causing severe diarrhea in infants and young children < 5 years of age. The development of the next-generation rotavirus vaccine...
Rotavirus is one of the main pathogens causing severe diarrhea in infants and young children < 5 years of age. The development of the next-generation rotavirus vaccine is of great significance for preventing rotavirus infection and reducing severe mortality. The current study aimed to develop and evaluate the immunogenicity of inactivated rotavirus vaccine (IRV) in rhesus monkeys. Monkeys received two or three IRV injections intramuscularly at a 4-week interval. Neutralizing antibodies, cellular immunity, PBMC gene expression profiling, and immune persistence were evaluated. Three-dose immunization of IRV induced a higher level of neutralizing, IgG and IgA antibodies compared to two-dose immunization. IRV induced IFN-γ secretion to mediate cellular immune responses, including robust pro-inflammatory and antiviral responses. Chemokine-mediated signaling pathways and immune response were broadly activated by IRV injection. The IRV-induced neutralizing antibodies resulting from two doses returned to baseline levels 20 weeks after full immunization, while those resulting from three doses returned to baseline levels 44 weeks after full immunization. Increasing immunization dose and injection number will help to improve IRV immunogenicity and neutralizing antibody persistence.
Topics: Animals; Rotavirus; Macaca mulatta; Antibodies, Viral; Rotavirus Vaccines; Leukocytes, Mononuclear; Rotavirus Infections; Antibodies, Neutralizing; Vaccines, Inactivated
PubMed: 36994772
DOI: 10.1080/21645515.2023.2189598 -
PloS One 2023Rotavirus vaccination has reduced mortality and hospital admissions due to rotavirus diarrhoea, but its effect on rotavirus infections and the impact of rotavirus...
Rotavirus vaccination has reduced mortality and hospital admissions due to rotavirus diarrhoea, but its effect on rotavirus infections and the impact of rotavirus genotypes are still unclear. Real-time PCR was used to detect rotavirus and other pathogens in faeces samples from children below five years of age with acute diarrhoea, collected before (n = 827) and after (n = 807, 92% vaccinated) the introduction of vaccination in Rwanda in 2012. Rotavirus was genotyped by targeting VP7 to identify G1, G2, G3, G4, G9 and G12 and VP4 to identify P[4], P[6] and P[8]. In vaccinated children, rotavirus infections were rarer (34% vs. 47%) below 12 months of age, severe dehydration was less frequent, and rotavirus was more often found as a co-infecting agent. (79% vs 67%, p = 0.004). Norovirus genogroup II, astrovirus, and sapovirus were significantly more often detected in vaccinated children. The predominant rotavirus genotypes were G2P[4] and G12P[6] in 2009-2010 (50% and 12%), G9P[8] and G1P[8] in 2011-2012 (51% and 22%), and G12P[8] in 2014-2015 (63%). Rotavirus vaccination in Rwanda has reduced the severity of rotavirus gastroenteritis and rotavirus infection frequency during the first year of life. Rotavirus infections were frequent in vaccinated children with diarrhoea, often as co-pathogen. Rotavirus genotype changes might be unrelated to vaccination because shifts were observed also before its introduction.
Topics: Child; Humans; Infant; Rotavirus Infections; Rotavirus; Rwanda; Antigens, Viral; Diarrhea; Genotype; Vaccination; Rotavirus Vaccines
PubMed: 37098095
DOI: 10.1371/journal.pone.0284934 -
The Pediatric Infectious Disease Journal Oct 2021Live, oral rotavirus vaccines are more effective at preventing rotavirus disease in countries with low child mortality compared with high child mortality. Among several... (Review)
Review
Live, oral rotavirus vaccines are more effective at preventing rotavirus disease in countries with low child mortality compared with high child mortality. Among several hypotheses, poorer protection in malnourished children, who are more prevalent in countries with high child mortality, may partially explain this difference. We conducted a literature search to identify articles with a laboratory-confirmed rotavirus endpoint that evaluated differences by malnutrition status in rotavirus vaccine effectiveness and vaccine efficacy (VE) or the prevalence of rotavirus infection or illness among children <5 years old. We identified 7 analyses from 11 countries published from 2007 to 2019 that stratified rotavirus VE by malnutrition status. Among well-nourished children, VE point estimates ranged from 71% to 84% in observational studies and 26% to 61% in clinical trials. Among malnourished children, they ranged from -28% to 45% in observational studies and -3% to 61% in clinical trials. The relative difference between VE in well-nourished and malnourished children by length-for-age ranged from 37% to 64%, by weight-for-age ranged from 0% to 107%, and by weight-for-height ranged from -65% to 137%. We identified 3 cohort and 6 cross-sectional studies of natural rotavirus infection and illness and none reported that malnourished children were more susceptible to rotavirus infection or illness than well-nourished children. Overall, rotavirus vaccines may offer less protection to children with malnutrition than well-nourished children. As malnourished children often have worse outcomes from diarrhea, high rotavirus vaccine coverage and a better understanding of the performance of oral rotavirus vaccines in this population is important, though our finding that malnourished children may be less susceptible to rotavirus provides important context and information for vaccine evaluation design.
Topics: Child; Child Nutrition Disorders; Clinical Trials as Topic; Cross-Sectional Studies; Gastroenteritis; Global Health; Hospitalization; Humans; Malnutrition; Observational Studies as Topic; Rotavirus Infections; Rotavirus Vaccines; Vaccine Efficacy
PubMed: 34117200
DOI: 10.1097/INF.0000000000003206 -
The Journal of Infectious Diseases Sep 2020Although the etiology of type 1 diabetes (T1D) is not well understood, it is believed to comprise both genetic and environmental factors. Viruses are the most well... (Review)
Review
Although the etiology of type 1 diabetes (T1D) is not well understood, it is believed to comprise both genetic and environmental factors. Viruses are the most well studied environmental trigger, and there is a small but growing body of research on the potential influence of rotavirus on T1D. Rotavirus infections were initially identified as possible triggers of T1D given similarities between viral peptide sequences and T1D autoantigen peptide sequences. Furthermore, rotavirus infection has been shown to modify T1D risk in T1D-prone mice. However, research into associations of rotavirus infections with T1D development in humans have yielded mixed findings and suggested interactions with age and diet. As global availability of rotavirus vaccines increases, recent studies have assessed whether rotavirus vaccination modifies T1D development, finding null or protective associations. Overall, evidence to date suggests a possible triggering relationship between some wild-type rotavirus infections and T1D, but the potential effect of rotavirus vaccination remains unclear.
Topics: Animals; Diabetes Mellitus, Type 1; Gastroenteritis; Humans; Mice; Mice, Inbred NOD; Rotavirus Infections; Rotavirus Vaccines; Vaccination
PubMed: 32249284
DOI: 10.1093/infdis/jiaa168 -
Microbiological Research Jul 2022Human rotaviruses are the utmost etiologic agents of infantile gastroenteritis in children under five years of age. To reduce childhood morbidity and mortality caused by... (Review)
Review
Human rotaviruses are the utmost etiologic agents of infantile gastroenteritis in children under five years of age. To reduce childhood morbidity and mortality caused by this rotavirus infection, numerous efforts are being made worldwide in the form of better and universal immunisation programmes. Though few vaccines are in action, the lack of approved antiviral agents that have potential combative effects against the rotavirus infection in the host, remains a point of concern. This review focuses on recent insights into the development of naturally derived, RNA-silencing-based drug substances that show their anti-rotaviral activities by targeting and influencing different host and/or viral factors that contribute directly or indirectly to successful viral pathogenesis.
Topics: Antiviral Agents; Child; Child, Preschool; Gastroenteritis; Humans; Immunization; Rotavirus; Rotavirus Infections
PubMed: 35487138
DOI: 10.1016/j.micres.2022.127046