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Rotaviruses are the most common cause of diarrhoeal disease among infants and young children.<ref name="pmid26337738">Template:Cite journal</ref> Nearly every child in the world is infected with a rotavirus at least once by the age of five.<ref name="pmid19252423" /> Immunity develops with each infection, so subsequent infections are less severe. Adults are rarely affected.<ref name="pmid18838873" />
The virus is transmitted by the faecal–oral route. It infects and damages the cells that line the small intestine and causes gastroenteritis (which is often called "stomach flu" despite having no relation to influenza). Although rotavirus was discovered in 1973 by Ruth Bishop and her colleagues by electron micrograph images<ref name="pmid19799704" /> and accounts for approximately one third of hospitalisations for severe diarrhoea in infants and children,<ref name="pmid34904636">Template:Cite journal</ref> its importance has historically been underestimated within the public health community, particularly in developing countries.<ref name="pmid17919334">Template:Cite journal</ref> In addition to its impact on human health, rotavirus also infects other animals, and is a pathogen of livestock.<ref name="isbn0-12-375158-6" />
Rotaviral enteritis is usually an easily managed disease of childhood, but among children under 5 years of age rotavirus caused an estimated 151,714 deaths from diarrhoea in 2019.<ref name="pmid35643565">Template:Cite journal</ref> In the United States, before initiation of the rotavirus vaccination programme in the 2000s, rotavirus caused about 2.7Template:Nbspmillion cases of severe gastroenteritis in children, almost 60,000 hospitalisations, and around 37 deaths each year.<ref name="pmid17357047">Template:Cite journal</ref> Following rotavirus vaccine introduction in the United States, hospitalisation rates have fallen significantly.<ref name=":1">Template:Cite journal</ref><ref name="pmid21183842">Template:Cite journal</ref> Public health campaigns to combat rotavirus focus on providing oral rehydration therapy for infected children and vaccination to prevent the disease.<ref name="pmid18026034" /> The incidence and severity of rotavirus infections has declined significantly in countries that have added rotavirus vaccine to their routine childhood immunisation policies.<ref name="pmid21734466" /><ref name="pmid20622508">Template:Cite journal</ref><ref name=":2">Template:Cite journal</ref>
Rotavirus is a genus of double-stranded RNA viruses in the family Reoviridae. There are 11 species of the genus, usually referred to as RVA, RVB, RVC, RVD, RVF, RVG, RVH, RVI, RVJ, RVK and RVL. The most common is RVA, and these rotaviruses cause more than 90% of rotavirus infections in humans.<ref name="pmid16418157" />
VirologyEdit
Types of rotavirusEdit
There are 11 species of rotavirus (sometimes informally called groups) referred to as RVA, RVB, RVC, RVD, RVF, RVG, RVH, RVI, RVJ, RVK and RVL.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="pmid31447474">Template:Cite journal</ref> Humans are primarily infected by rotaviruses in the species RVA. This one and the other species cause disease in other animals,<ref name="pmid20684716">Template:Cite journal</ref> for example, species RVH in pigs, RVD, RVF and RVG in birds, RVI in cats and RVJ in bats.<ref name="pmid21801631">Template:Cite journal</ref><ref name="pmid24960190">Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="pmid27932285">Template:Cite journal</ref>
Within group A rotaviruses there are different strains, called serotypes.<ref name="pmid19252426">Template:Cite journal</ref> As with influenza virus, a dual classification system is used based on two proteins on the surface of the virus. The glycoprotein VP7 defines the G serotypes and the protease-sensitive protein VP4 defines P serotypes.<ref name="pmid22284787">Template:Cite journal</ref> Because the two genes that determine G-types and P-types can be passed on separately to progeny viruses, different combinations are found.<ref name="pmid22284787" /> A whole genome genotyping system has been established for group A rotaviruses, which has been used to determine the origin of atypical strains.<ref name="pmid28748110">Template:Cite journal</ref> The prevalence of the individual G-types and P-types varies between, and within, countries and years.<ref name="pmid2556435">Template:Cite journal</ref> There are at least 36 G types and 51 P types<ref name="pmid33482744">Template:Cite journal</ref> but in infections of humans only a few combinations of G and P types predominate. They are G1P[8], G2P[4], G3P[8], G4P[8], G9P[8] and G12P[8].<ref name="pmid38015834">Template:Cite journal</ref>
StructureEdit
The genome of rotaviruses consists of 11 unique double helix molecules of RNA (dsRNA) which are 18,555 nucleotides in total. Each helix, or segment, is a gene, numbered 1 to 11 by decreasing size. Each gene codes for one protein, except genes 9, which codes for two.<ref name="pmid2556635">Template:Cite journal</ref> The RNA is surrounded by a three-layered icosahedral protein capsid. Viral particles are up to 76.5Template:Nbspnm in diameter<ref name="pmid16913048">Template:Cite book</ref><ref name="pmid8050286">Template:Cite book</ref> and are not enveloped.<ref name="pmid31317495">Template:Cite book</ref>
ProteinsEdit
There are six viral proteins (VPs) that form the virus particle (virion). These structural proteins are called VP1, VP2, VP3, VP4, VP6 and VP7. In addition to the VPs, there are six nonstructural proteins (NSPs), that are only produced in cells infected by rotavirus. These are called NSP1, NSP2, NSP3, NSP4, NSP5 and NSP6.<ref name="pmid20684716" />
At least six of the twelve proteins encoded by the rotavirus genome bind RNA.<ref name="pmid7595370">Template:Cite journal</ref> The role of these proteins in rotavirus replication is not entirely understood; their functions are thought to be related to RNA synthesis and packaging in the virion, mRNA transport to the site of genome replication, and mRNA translation and regulation of gene expression.<ref name="pmid11444036">Template:Cite book</ref>
Structural proteinsEdit
VP1 is located in the core of the virus particle and is an RNA-dependent RNA polymerase enzyme.<ref name="pmid17657346">Template:Cite journal</ref> In an infected cell this enzyme produces mRNA transcripts for the synthesis of viral proteins and produces copies of the rotavirus genome RNA segments for newly produced virus particles.<ref name="pmid22595300">Template:Cite journal</ref>
VP2 forms the core layer of the virion and binds the RNA genome.<ref name="pmid15010217">Template:Cite journal</ref>
VP3 is part of the inner core of the virion and is an enzyme called guanylyl transferase. This is a capping enzyme that catalyses the formation of the 5' cap in the post-transcriptional modification of mRNA.<ref name="isbn0-12-375147-02">Template:Cite book</ref> The cap stabilises viral mRNA by protecting it from nucleic acid degrading enzymes called nucleases.<ref name="pmid20025612">Template:Cite journal</ref>
VP4 is on the surface of the virion that protrudes as a spike.<ref name="pmid16571811">Template:Cite journal</ref> It binds to molecules on the surface of cells called receptors and drives the entry of the virus into the cell.<ref name="pmid12234525">Template:Cite journal</ref> VP4 has to be modified by the protease enzyme trypsin, which is found in the gut, into VP5* and VP8* before the virus is infectious.<ref name="pmid15010218">Template:Cite journal</ref> VP4 determines how virulent the virus is and it determines the P-type of the virus.<ref name="pmid12167342">Template:Cite journal</ref> In humans there is an association between the blood group (Lewis antigen system, ABO blood group system and secretor status) and susceptibility to infection. Non-secretors seem resistant to infection by types P[4] and P[8], indicating that blood group antigens are the receptors for these genotypes.<ref name="pmid24523471">Template:Cite journal</ref> This resistance is dependent on the rotavirus genotype.<ref name="pmid32192193">Template:Cite journal</ref>
VP6 forms the bulk of the capsid. It is highly antigenic and can be used to identify rotavirus species.<ref name="pmid9015109" /> This protein is used in laboratory tests for rotavirus infections.<ref name="pmid6321549">Template:Cite journal</ref>
VP7 is a glycoprotein that forms the outer surface of the virion. Apart from its structural functions, it determines the G-type of the strain and, along with VP4, is involved in immunity to infection.<ref name="pmid16913048" />
Nonstructural viral proteinsEdit
NSP1, the product of gene 5, is a nonstructural RNA-binding protein.<ref>Template:Cite journal</ref> NSP1 also blocks the interferon response, the part of the innate immune system that protects cells from viral infection. NSP1 causes the proteosome to degrade key signaling components required to stimulate production of interferon in an infected cell and to respond to interferon secreted by adjacent cells.
Targets for degradation include several IRF transcription factors required for interferon gene transcription.<ref name=Arnold2016>Template:Cite journal</ref>
NSP2 is an RNA-binding protein that accumulates in cytoplasmic inclusions (viroplasms) and is required for genome replication.<ref>Template:Cite journal</ref><ref name="pmid15010217" />
NSP3 is bound to viral mRNAs in infected cells and it is responsible for the shutdown of cellular protein synthesis.<ref>Template:Cite journal</ref> NSP3 inactivates two translation initiation factors essential for synthesis of proteins from host mRNA.
First, NSP3 ejects poly(A)-binding protein (PABP) from the translation initiation factor eIF4F. PABP is required for efficient translation of transcripts with a 3' poly(A) tail, which is found on most host cell transcripts. Second, NSP3 inactivates eIF2 by stimulating its phosphorylation.<ref name="pmid26727111">Template:Cite journal</ref> Efficient translation of rotavirus mRNA, which lacks the 3' poly(A) tail, does not require either of these factors.<ref name="Lopez2012">Template:Cite journal</ref>
NSP4 is a viral enterotoxin that induces diarrhoea and was the first viral enterotoxin discovered.<ref name="pmid19114772">Template:Cite journal</ref> It is a viroporin that elevates cytosolic Ca2+ in mammalian cells.<ref name="pmid28256607">Template:Cite journal</ref>
NSP5 is encoded by genome segment 11 of rotavirus A. In virus-infected cells NSP5 accumulates in the viroplasm.<ref>Template:Cite journal</ref>
NSP6 is a nucleic acid binding protein<ref>Template:Cite journal</ref> and is encoded by gene 11 from an out-of-phase open reading frame.<ref>Template:Cite journal</ref>
| RNA Segment (Gene) | Size (base pairs) | Protein | UniProt | Molecular weight kDa | Location | Copies per particle | Function |
|---|---|---|---|---|---|---|---|
| 1 | 3302 | VP1 | Template:UniProt | 125 | At the vertices of the core | 12 | RNA-dependent RNA polymerase |
| 2 | 2690 | VP2 | Template:UniProt | 102 | Forms inner shell of the core | 120 | RNA binding |
| 3 | 2591 | VP3 | Template:UniProt | 88 | At the vertices of the core | 12 | methyltransferase mRNA capping enzyme |
| 4 | 2362 | VP4 | Template:UniProt | 87 | Surface spike | 180 (60 trimers)<ref name="pmid36996819">Template:Cite journal</ref> | Cell attachment, virulence |
| 5 | 1611 | NSP1 | Template:UniProt | 59 | Nonstructural | 0 | 5'RNA binding, interferon antagonist |
| 6 | 1356 | VP6 | Template:UniProt | 45 | Inner Capsid | 780 (260 trimers)<ref name="pmid36996819"/> | Structural and species-specific antigen |
| 7 | 1104 | NSP3 | Template:UniProt | 37 | Nonstructural | 0 | Enhances viral mRNA activity and shut-offs cellular protein synthesis |
| 8 | 1059 | NSP2 | Template:UniProt | 35 | Nonstructural | 0 | NTPase involved in RNA packaging |
| 9 | 1062 | VP71 VP72 | Template:UniProt | 38 and 34 | Surface | 780 (260 trimers)<ref name="pmid36996819"/> | Structural and neutralisation antigen |
| 10 | 751 | NSP4 | Template:UniProt | 20 | Nonstructural | 0 | Viroporin (enterotoxin) |
| 11 | 667 | NSP5 NSP6 | Template:UniProt Template:UniProt | 22 | Nonstructural | 0 | ssRNA and dsRNA binding modulator of NSP2, phosphoprotein |
This table is based on the simian rotavirus strain SA11. RNA-protein coding assignments differ in some strains.
ReplicationEdit
The attachment of the virus to the host cell is initiated by VP4, which attaches to molecules, called glycans, on the surface of the cell.<ref name="pmid31317495"/> The virus enters cells by receptor mediated endocytosis and form a vesicle known as an endosome. Proteins in the third layer (VP7 and the VP4 spike) disrupt the membrane of the endosome, creating a difference in the calcium concentration. This causes the breakdown of VP7 trimers into single protein subunits, leaving the VP2 and VP6 protein coats around the viral dsRNA, forming a double-layered particle (DLP).<ref name="pmid20397068">Template:Cite book</ref>
The eleven dsRNA strands remain within the protection of the two protein shells and the viral RNA-dependent RNA polymerase creates mRNA transcripts of the double-stranded viral genome. By remaining in the core, the viral RNA evades innate host immune responses including RNA interference that are triggered by the presence of double-stranded RNA.<ref name="pmid27009959">Template:Cite journal</ref>
During the infection, rotaviruses produce mRNA for both protein biosynthesis and gene replication. Most of the rotavirus proteins accumulate in viroplasm, where the RNA is replicated and the DLPs are assembled. In the viroplasm the positive sense viral RNAs that are used as templates for the synthesis of viral genomic dsRNA are protected from siRNA-induced RNase degradation.<ref name="pmid15220450">Template:Cite journal</ref> Viroplasm is formed around the cell nucleus as early as two hours after virus infection, and consists of viral factories thought to be made by two viral nonstructural proteins: NSP5 and NSP2. Inhibition of NSP5 by RNA interference in vitro results in a sharp decrease in rotavirus replication. The DLPs migrate to the endoplasmic reticulum where they obtain their third, outer layer (formed by VP7 and VP4). The progeny viruses are released from the cell by lysis.<ref name="pmid15010218" /><ref name="pmid15579070">Template:Cite journal</ref><ref name="pmid20024520">Template:Cite journal</ref>
TransmissionEdit
Rotaviruses are transmitted by the faecal–oral route, via contact with contaminated hands, surfaces and objects,<ref name="pmid8393172">Template:Cite journal</ref> and possibly by the respiratory route.<ref name="pmid11052397">Template:Cite journal</ref> Viral diarrhoea is highly contagious. The faeces of an infected person can contain more than 10 trillion infectious particles per gram;<ref name="pmid9015109" /> fewer than 100 of these are required to transmit infection to another person.<ref name="pmid18838873">Template:Cite journal</ref>
Rotaviruses are stable in the environment and have been found in estuary samples at levels up to 1–5 infectious particles per USTemplate:Nbspgallon. The viruses survive between 9 and 19 days.<ref name="pmid6091548">Template:Cite journal</ref> Sanitary measures adequate for eliminating bacteria and parasites seem to be ineffective in control of rotavirus, as the incidence of rotavirus infection in countries with high and low health standards is similar.<ref name="pmid11052397" />
Signs and symptomsEdit
Rotaviral enteritis is a mild to severe disease characterised by nausea, vomiting, watery diarrhoea and low-grade fever. Once a child is infected by the virus, there is an incubation period of about two days before symptoms appear.<ref name="pmid10532018">Template:Cite journal</ref> The period of illness is acute. Symptoms often start with vomiting followed by four to eight days of profuse diarrhoea. Dehydration is more common in rotavirus infection than in most of those caused by bacterial pathogens, and is the most common cause of death related to rotavirus infection.<ref name="pmid1962726">Template:Cite journal</ref>
Rotavirus infections can occur throughout life: the first usually produces symptoms, but subsequent infections are typically mild or asymptomatic,<ref name="pmid16860702">Template:Cite journal</ref><ref name="pmid9015109">Template:Cite journal</ref> as the immune system provides some protection.<ref name="isbn0-471-49663-43">Template:Cite book</ref> Consequently, symptomatic infection rates are highest in children under two years of age and decrease progressively towards 45 years of age.<ref name="isbn0-89603-736-32">Template:Cite book</ref> The most severe symptoms tend to occur in children six months to two years of age, the elderly, and those with immunodeficiency. Due to immunity acquired in childhood, most adults are not susceptible to rotavirus; gastroenteritis in adults usually has a cause other than rotavirus, but asymptomatic infections in adults may maintain the transmission of infection in the community.<ref name="pmid14871633">Template:Cite journal</ref> There is some evidence to suggest blood group can impact on the susceptibility to infection by rotaviruses.<ref name="pmid32918943">Template:Cite journal</ref>
Disease mechanismsEdit
Rotaviruses replicate mainly in the gut,<ref name="pmid19457420">Template:Cite journal</ref> and infect enterocytes of the villi of the small intestine, leading to structural and functional changes of the epithelium.<ref name="pmid8050281">Template:Cite book</ref> There is evidence in humans, and particularly in animal models of extraintestinal dissemination of infectious virus to other organs and macrophages.<ref name="pmid16641274">Template:Cite journal</ref>
The diarrhoea is caused by multiple activities of the virus.<ref name="pmid15367586">Template:Cite journal</ref> Malabsorption occurs because of the destruction of gut cells called enterocytes. The toxic rotavirus protein NSP4 induces age- and calcium ion-dependent chloride secretion, disrupts SGLT1 (sodium/glucose cotransporter 2) transporter-mediated reabsorption of water, apparently reduces activity of brush-border membrane disaccharidases, and activates the calcium ion-dependent secretory reflexes of the enteric nervous system.<ref name="pmid19114772" /> The elevated concentrations of calcium ions in the cytosol (which are required for the assembly of the progeny viruses) is achieved by NSP4 acting as a viroporin. This increase in calcium ions leads to autophagy (self destruction) of the infected enterocytes.<ref name="pmid21151776">Template:Cite journal</ref>
NSP4 is also secreted. This extracellular form, which is modified by protease enzymes in the gut, is an enterotoxin which acts on uninfected cells via integrin receptors, which in turn cause and increase in intracellular calcium ion concentrations, secretory diarrhoea and autophagy.<ref name="pmid16731945">Template:Cite journal</ref>
The vomiting, which is a characteristic of rotaviral enteritis, is caused by the virus infecting the enterochromaffin cells on the lining of the digestive tract. The infection stimulates the production of 5' hydroxytryptamine (serotonin). This activates vagal afferent nerves, which in turn activates the cells of the brain stem that control the vomiting reflex.<ref name="pmid22722079">Template:Cite journal</ref>
Healthy enterocytes secrete lactase into the small intestine; milk intolerance due to lactase deficiency is a symptom of rotavirus infection,<ref name="pmid18492865">Template:Cite journal</ref> which can persist for weeks.<ref name="pmid12811680">Template:Cite journal</ref> A recurrence of mild diarrhoea often follows the reintroduction of milk into the child's diet, due to bacterial fermentation of the disaccharide lactose in the gut.<ref name="pmid6436397">Template:Cite journal</ref>
Immune responsesEdit
Specific responsesEdit
Rotaviruses elicit both B and T cell immune responses. Antibodies to the rotavirus VP4 and VP7 proteins neutralise viral infectivity in vitro and in vivo.<ref name="pmid19252425">Template:Cite journal</ref> Specific antibodies of the classes IgM, IgA and IgG are produced, which have been shown to protect against rotavirus infection by the passive transfer of the antibodies in other animals.<ref name="pmid22880110">Template:Cite journal</ref> Maternal trans-placental IgG might play a role in the protection neonates from rotavirus infections, but on the other hand might reduce vaccine efficacy.<ref name="pmid27847365">Template:Cite journal</ref>
Innate responsesEdit
Following infection by rotaviruses there is a rapid innate immune response involving types I and III interferons and other cytokines (particularly Th1 and Th2)<ref name="pmid28414969">Template:Cite journal</ref> which inhibit the replication of the virus and recruit macrophages and natural killer cells to the rotavirus infected cells.<ref name="pmid23486667">Template:Cite journal</ref> The rotavirus dsRNA activates pattern recognition receptors such toll-like receptors that stimulate the production of interferons.<ref name="pmid27994593" /> The rotavirus protein NSP1 counteracts the effects of type 1 interferons by suppressing the activity of the interferon regulatory proteins IRF3, IRF5 and IRF7.<ref name="pmid27994593">Template:Cite journal</ref>
Markers of protectionEdit
The levels of IgG and IgA in the blood and IgA in the gut correlate with protection from infection.<ref name="pmid7817873">Template:Cite journal</ref> Rotavirus specific serum IgG and IgA at high titres (e.g. >1:200) have been claimed to be protective and there is a significant correlation between IgA titres and rotavirus vaccine efficacy.<ref name="pmid23596320">Template:Cite journal</ref>
Diagnosis and detectionEdit
Diagnosis of infection with a rotavirus normally follows diagnosis of gastroenteritis as the cause of severe diarrhoea. Most children admitted to hospital with gastroenteritis are tested for rotavirus.<ref name="pmid17901797" /><ref name="pmid16650331">Template:Cite journal</ref>
Specific diagnosis of infection with rotavirus is made by finding the virus in the child's stool by enzyme immunoassay. There are several licensed test kits on the market which are sensitive, specific and detect all serotypes of rotavirus.<ref name="isbn0-12-375147-0">Template:Cite book</ref> Other methods, such as electron microscopy and PCR (polymerase chain reaction), are used in research laboratories.<ref name="isbn0-471-49663-4">Template:Cite book</ref> Reverse transcription-polymerase chain reaction (RT-PCR) can detect and identify all species and serotypes of human rotaviruses.<ref name="pmid15027000">Template:Cite journal</ref>
Treatment and prognosisEdit
Treatment of acute rotavirus infection is nonspecific and involves management of symptoms and, most importantly, management of dehydration.<ref name="pmid18026034">Template:Cite journal</ref> If untreated, children can die from the resulting severe dehydration.<ref name="pmid12608880">Template:Cite journal</ref> Depending on the severity of diarrhoea, treatment consists of oral rehydration therapy, during which the child is given extra water to drink that contains specific amounts of salt and sugar.<ref name="pmid8855579">Template:Cite journal</ref> In 2004, the World Health Organisation (WHO) and UNICEF recommended the use of low-osmolarity oral rehydration solution and zinc supplementation as a two-pronged treatment of acute diarrhoea.<ref name="WHO UNICEF">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Some infections are serious enough to warrant hospitalisation where fluids are given by intravenous therapy or nasogastric intubation, and the child's electrolytes and blood sugar are monitored.<ref name="pmid17901797">Template:Cite journal</ref> Rotavirus infections rarely cause other complications and for a well managed child the prognosis is excellent.<ref name="pmid17678424">Template:Cite journal</ref> Probiotics have been shown to reduce the duration of rotavirus diarrhoea,<ref name="pmid26644891">Template:Cite journal</ref> and according to the European Society for Pediatric Gastroenterology "effective interventions include administration of specific probiotics such as Lactobacillus rhamnosus or Saccharomyces boulardii, diosmectite or racecadotril."<ref name="pmid24739189">Template:Cite journal</ref>
PreventionEdit
{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Rotaviruses are highly contagious and cannot be treated with antibiotics or other drugs. Because improved sanitation does not decrease the prevalence of rotaviral disease, and the rate of hospitalisations remains high despite the use of oral rehydrating medicines, the primary public health intervention is vaccination.<ref name="pmid19252423">Template:Cite journal</ref> In 1998, a rotavirus vaccine was licensed for use in the United States. Clinical trials in the United States, Finland, and Venezuela had found it to be 80–100% effective at preventing severe diarrhoea caused by rotavirus A, and researchers had detected no statistically significant serious adverse effects.<ref name="pmid10219046">Template:Cite journal</ref><ref name="pmid11444025">Template:Cite book</ref> The manufacturer, however, withdrew it from the market in 1999, after it was discovered that the vaccine may have contributed to an increased risk for intussusception, a type of bowel obstruction, in one of every 12,000 vaccinated infants.<ref name="pmid15687880">Template:Cite journal</ref> The experience provoked intense debate about the relative risks and benefits of a rotavirus vaccine.<ref name="pmid16099078">Template:Cite journal</ref>
In 2006, two new vaccines against Template:Nowrap infection were shown to be safe and effective in children,<ref name="pmid18202442">Template:Cite journal</ref> and in 2009, the WHO recommended that rotavirus vaccine be included in all national immunisation programmes.<ref name="pmid20370550">Template:Cite journal</ref>
The incidence and severity of rotavirus infections has declined significantly in countries that have acted on this recommendation.<ref name="pmid21734466">Template:Cite journal</ref><ref name="pmid20622508" /><ref name=":2" /> A 2014 review of available clinical trial data from countries routinely using rotavirus vaccines in their national immunisation programs found that rotavirus vaccines have reduced rotavirus hospitalisations by 49–92% and all cause diarrhoea hospitalisations by 17–55%.<ref>Template:Cite journal</ref> In Mexico, which in 2006 was among the first countries in the world to introduce rotavirus vaccine, diarrhoeal disease death rates dropped during the 2009 rotavirus season by more than 65 percent among children age two and under.<ref>Template:Cite journal</ref> In Nicaragua, which in 2006 became the first developing country to introduce a rotavirus vaccine, severe rotavirus infections were reduced by 40 percent and emergency room visits by a half.<ref name="pmid22753550">Template:Cite journal</ref> In the United States, rotavirus vaccination since 2006 has led to drops in rotavirus-related hospitalisations by as much as 86 percent.<ref name="pmid35632617">Template:Cite journal</ref> The vaccines may also have prevented illness in non-vaccinated children by limiting the number of circulating infections.<ref name="pmid35632617" /><ref>Template:Cite journal</ref> In developing countries in Africa and Asia, where the majority of rotavirus deaths occur, a large number of safety and efficacy trials as well as recent post-introduction impact and effectiveness studies of Rotarix and RotaTeq have found that vaccines dramatically reduced severe disease among infants.<ref name=":2" /><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> In September 2013, the vaccine was offered to all children in the UK, aged between two and three months.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> A 2022 study found that the number of rotavirus cases in infants in England under one year of age was reduced by 77–88%. In all age groups, the number of laboratory-confirmed rotavirus infections was reduced by 69–83%.<ref name="pmid34043765">Template:Cite journal</ref> In Europe, hospitalisation rates following infection by rotaviruses have decreased by 65% to 84% following the introduction of the vaccine.<ref name="pmid25795258">Template:Cite journal</ref> Globally, vaccination has reduced hospital admissions and emergency department visits by a median of 67%.<ref name="pmid28430997">Template:Cite journal</ref>
Rotavirus vaccines are licensed in over 100 countries, and more than 80 countries have introduced routine rotavirus vaccination, almost half with the support of the GAVI vaccine alliance.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> To make rotavirus vaccines available, accessible, and affordable in all countries—particularly low- and middle-income countries in Africa and Asia where the majority of rotavirus deaths occur, PATH (formerly Program for Appropriate Technology in Health), the WHO, the U.S. Centers for Disease Control and Prevention, and GAVI have partnered with research institutions and governments to generate and disseminate evidence, lower prices, and accelerate introduction.<ref name="pmid21957215">Template:Cite journal</ref>
The vaccine may prevent type 1 diabetes.<ref>Template:Cite news</ref><ref>Template:Cite news</ref>
EpidemiologyEdit
Rotavirus A, which accounts for more than 90% of rotavirus gastroenteritis in humans,<ref name="pmid16418157">Template:Cite journal</ref> is endemic worldwide. Each year rotaviruses cause millions of cases of diarrhoea in developing countries, almost 2Template:Nbspmillion of which result in hospitalisation.<ref name="pmid17919334" /> In 2019, an estimated 151,714 children younger than five died from rotavirus infections, 90 percent of whom were in developing countries.<ref name="pmid35643565" /> Almost every child has been infected with rotaviruses by age five.<ref name="pmid19252423" /><ref name="pmid16494759">Template:Cite journal</ref> Rotaviruses are the leading single cause of severe diarrhoea among infants and children, are responsible for about a third of the cases requiring hospitalisation,<ref name=":1" /> and cause 37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than five.<ref name="pmid22030330">Template:Cite journal</ref> Boys are twice as likely as girls to be admitted to hospital for rotavirus infections.<ref name="pmid16397429">Template:Cite journal</ref><ref name="pmid8752285">Template:Cite journal</ref> In the pre-vaccination era, rotavirus infections occurred primarily during cool, dry seasons.<ref name="pmid19939844">Template:Cite journal</ref><ref name="pmid19056806">Template:Cite journal</ref> The number attributable to food contamination is unknown.<ref name="pmid10088906">Template:Cite journal</ref>
Outbreaks of rotavirus A diarrhoea are common among hospitalised infants, young children attending day care centres, and elderly people in nursing homes.<ref name="pmid14871633" /><ref name="pmid25944726">Template:Cite journal</ref> An outbreak caused by contaminated municipal water occurred in Colorado in 1981.<ref name="pmid6320684">Template:Cite journal</ref> During 2005, the largest recorded epidemic of diarrhoea occurred in Nicaragua. This unusually large and severe outbreak was associated with mutations in the rotavirus A genome, possibly helping the virus escape the prevalent immunity in the population.<ref name="pmid17229854">Template:Cite journal</ref> A similar large outbreak occurred in Brazil in 1977.<ref name="pmid6263087">Template:Cite journal</ref>
Rotavirus B, also called adult diarrhoea rotavirus or ADRV, has caused major epidemics of severe diarrhoea affecting thousands of people of all ages in China. These epidemics occurred as a result of sewage contamination of drinking water.<ref name="pmid6144874">Template:Cite journal</ref><ref name="pmid2555422">Template:Cite journal</ref> Rotavirus B infections also occurred in India in 1998; the causative strain was named CAL. Unlike ADRV, the CAL strain is endemic.<ref name="pmid15310177">Template:Cite journal</ref><ref>Template:Cite journal</ref> To date, epidemics caused by rotavirus B have been confined to mainland China, and surveys indicate a lack of immunity to this species in the United States.<ref name="pmid2479654">Template:Cite journal</ref> Rotavirus C has been associated with rare and sporadic cases of diarrhoea in children, and small outbreaks have occurred in families.<ref name="pmid20491826">Template:Cite journal</ref>
- Rotavirus seasonal distribution.png
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Preventable child deaths from rotavirus vaccination, 2016. Annual number of preventable deaths in children under five years old from rotavirus if full coverage of the rotavirus vaccine was achieved.<ref>Template:Cite journal</ref>
Other animalsEdit
Rotaviruses infect the young of many species of animals and they are a major cause of diarrhoea in wild and reared animals worldwide.<ref name="isbn0-12-375158-6">Template:Cite book</ref> As a pathogen of livestock, notably in young calves and piglets, rotaviruses cause economic loss to farmers because of costs of treatment associated with high morbidity and mortality rates.<ref name="pmid19781872">Template:Cite journal</ref> These rotaviruses are a potential reservoir for genetic exchange with human rotaviruses.<ref name="pmid19781872" /> There is evidence that animal rotaviruses can infect humans, either by direct transmission of the virus or by contributing one or several RNA segments to reassortants with human strains.<ref name="pmid17416132">Template:Cite journal</ref><ref name="pmid15066329">Template:Cite journal</ref><ref name="pmid26428261">Template:Cite journal</ref>
HistoryEdit
In 1943, Jacob Light and Horace Hodes proved that a filterable agent in the faeces of children with infectious diarrhoea also caused scours (livestock diarrhoea) in cattle.<ref name="pmid18015921">Template:Cite journal</ref> Three decades later, preserved samples of the agent were shown to be rotavirus.<ref name="pmid184047">Template:Cite journal</ref> In the intervening years, a virus in mice<ref name="pmid4998842">Template:Cite journal</ref> was shown to be related to the virus causing scours.<ref name="pmid965097">Template:Cite journal</ref> In 1973, Ruth Bishop and colleagues described related viruses found in children with gastroenteritis.<ref name="pmid19799704">Template:Cite journal</ref>
In 1974, Thomas Henry Flewett suggested the name rotavirus after observing that, when viewed through an electron microscope, a rotavirus particle looks like a wheel ({{#invoke:Lang|lang}} in Latin)<ref name="pmid77663" /><ref name="pmid4137164">Template:Cite journal</ref> the name was officially recognised by the International Committee on Taxonomy of Viruses four years later.<ref name="pmid43850">Template:Cite journal</ref> In 1976, related viruses were described in several other species of animals.<ref name="pmid965097" /> These viruses, all causing acute gastroenteritis, were recognised as a collective pathogen affecting humans and other animals worldwide.<ref name="pmid77663">Template:Cite journal</ref> Rotavirus serotypes were first described in 1980,<ref name="pmid2833405">Template:Cite journal</ref> and in the following year, rotaviruses from humans were first grown in cell cultures derived from monkey kidneys, by adding trypsin (an enzyme found in the duodenum of mammals and now known to be essential for rotavirus to replicate) to the culture medium.<ref name="pmid6273696">Template:Cite journal</ref> The ability to grow rotaviruses in culture accelerated the pace of research, and by the mid-1980s the first candidate vaccines were being evaluated.<ref name="pmid19072246">Template:Cite journal</ref>
ReferencesEdit
External linksEdit
Template:Viral systemic diseases Template:Viral proteins Template:Baltimore classification Template:Consumer Food Safety Template:Taxonbar Template:Authority control