User:Colin/Rotaviral enteritis

Rotaviral enteritis, is the leading severe diarrhoeal disease of infants and young children, affecting nearly every child at least once by the age of five. It is caused by rotavirus, a genus of double-stranded RNA virus in the taxonomic family Reoviridae. Rotavirus infects cells that line the small intestine, and produces an enterotoxin. The toxin causes gastroenteritis with severe diarrhoea and potentially fatal dehydration.

There are seven species of rotavirus, referred to as A, B, C, D, E, F, and G. Rotavirus A, which is responsible for more than 90% of rotaviral infections in humans, is further subdivided into strains called serotypes. Although rotavirus was discovered in 1973, and is now known to account for up to 50% of infants and children hospitalised with severe diarrhoea, the importance of rotavirus is not widely recognised within the public health community, particularly in developing countries.

Rotaviral enteritis is spread by the fecal–oral route; large numbers of rotavirus are excreted by infected people. With each infection, immunity develops and subsequent infections are less severe. Public health campaigns to reduce morbidity and mortality from rotaviral enteritis focus on the benefits of oral rehydration therapy and vaccination.

In developing countries, rotaviral enteritis has been estimated to result in an average of 611,000 deaths each year in children under five years of age, and almost two million hospitalisations. In the United States each year there are an estimated 2.7 million cases of severe rotaviral enteritis in children, resulting in almost 60,000 hospitalisations, and around 37 deaths. Rotaviral enteritis is also an important veterinary disease; as with humans, young animals are most susceptible.

Signs and symptoms
Rotaviral gastroenteritis is a mild to severe disease characterised by vomiting, watery diarrhoea, and low-grade fever. Once a child is infected by the virus, it takes about two days, (the incubation period), before symptoms appear. Symptoms often start with vomiting followed by four to eight days of profuse diarrhoea. Most children recover completey from the infection.

Rotavirus A infections occur throughout life, but most recurrent infections are mild or asymptomatic. Children six months to two years of age, the elderly, and the immunocompromised are particularly susceptible to more severe symptoms. Symptoms usually accompany primary infection, which is followed by protection against subsequent symptomatic infection. Symptomatic infection rates are highest in children under two years of age, and lowest in those over 45 years of age. Rotavirus infection is common in the newborn but is often associated with mild or asymptomatic disease. Rotavirus infections of adults also occur, and frequent asymptomatic adult infections may be important in maintaining the transmission of infection in the community.

Cause
The causitive agent is the rotavirus, which is transmitted by the fecal-oral route, contact contaminated surfaces and objects, and possibly by the respiratory route. The faeces of an infected person can contain more than 10 million million (10 trillion) infectious particles per gram; only 10–100 of these are required to transmit infection to another person.

Rotaviruses are stable in the environment and have been found in estuary samples at levels as high as 1–5 infectious particles per gallon. Sanitary measures adequate for bacteria and parasites seem to be ineffective in endemic control of rotavirus, as similar incidence of rotavirus infection is observed in countries with both high and low health standards.

There are seven species of rotavirus, referred to as A, B, C, D, E, F, and G. Humans are primarily infected by species A, B and C, most commonly by species A. All seven species cause disease in animals.

Within rotavirus A there are different strains, called serotypes. Two genes determine these serotypes, and a strain of rotavirus A is classified both by its G and P type. Serotyping of rotavirus A is thus complex; each virus has a P-type and a G-type. P-type is indicated by a number for the P-serotype and by a number in square brackets for the coresponding P-genotype. G-serotypes and are similarly numbered but the G-genotype number is the same as the G-serotype. For example, the rotavirus strain Wa is defined as P1A [8] G1. This dual classification system is similar to that used for influenza virus. Because the genes that determine G-types and P-types can be passed on separately to offspring various, combinations occur in any one strain.

Mechanism
The diarrhoea is caused by several mechanisms which include: inadequate digestion that occurs because of the destruction of enterocytes, an activation of the enteric nervous system, and the flow of fluid into the gut from the tissues and blood that is caused by the rotavirus protein, NSP4, which is a toxin. The toxin causes cells to become permeable and damaged. Healthy enterocytes secrete lactase into the small intestine and milk intolerance caused by lactase deficiency is a particular symptom of rotavirus infection and this can persist for weeks. Often this causes a recurrence of mild diarrhoea following the reintroduction of milk into the child's diet. The diarrhoea is caused by bacterial fermentation of lactose in the gut.

Diagnosis
Diagnosis of infection with rotavirus normally follows diagnosis of gastroenteritis as the cause of severe diarrhea. Most children admitted to hospital with gastroenteritis are tested for rotavirus A. Specific diagnosis of infection with rotavirus A is made by identification of the virus in the patient's stool by enzyme immunoassay. Several licensed test kits are used which are sensitive, specific and detect all serotypes of rotavirus A. Other methods, electron microscopy and polyacrylamide gel electrophoresis, are used in research laboratories. Reverse transcription-polymerase chain reaction (RT-PCR) can detect and identify all species and serotypes of human rotavirus.

Prevention
In 2003 the World Health Organization and the U.S. Centers for Disease Control established the Rotavirus Vaccine Program to reduce child morbidity and mortality from diarrhoeal disease by making a vaccine against rotavirus available for use in developing countries.

In 2006, two vaccines against Rotavirus A infection were shown to be safe and effective in children: Rotarix by GlaxoSmithKline and RotaTeq by Merck. Both are taken orally and contain disabled live virus. Rotavirus vaccines are currently only available in Europe, and the US.

Treatment
Treatment of acute rotaviral enteritis is nonspecific and involves management of symptoms and, most importantly, maintenance of hydration. If untreated, children can die from the resulting severe dehydration. Depending on the severity of diarrhoea, treatment consists of oral rehydration with plain water, water plus salts, or water plus salts and sugar. Some infections are serious enough to warrant hospitalisation where fluids are given by intravenous drip or nasogastric tube, and the child's electrolytes and blood sugar are monitored.

Prognosis
Rotaviral enteritis rarely leads to complications in the well managed child. There are reports of complications involving the central nervous system (CNS) where rotavirus was detected in the fluid of the CNS in cases of encephalitis and meningitis,  and recent studies have confirmed that rotavirus infection is not confined only to the gut but can cause viremia.

Rotavirus A
Rotavirus A is endemic worldwide and each year, rotavirus causes millions of cases of diarhoea in developing countries, almost 2 million resulting in hospitalisation and an estimated 611,000 resulting in death. The major role of rotavirus in causing diarrhoea is not widely recognised within the public health community, particularly in developing countries. Almost every child has been infected with rotavirus by age five. Boys are twice as likely to be admitted to hospital than girls Rotavirus A account for more than 90% of rotavirus gastroenteritis in humans. Over 2.7 million cases of rotavirus gastroenteritis occur annually in the U.S., 60,000 children are hospitalised and around 37 die from the results of the infection. In some children symptomatic re-infections by rotavirus occur and these are often, but not always, caused by different serotypes.

In temperate areas, rotavirus occurs primarily in the winter, but in the tropics it occurs throughout the year. This is partly explained by seasonal changes in temperature and humidity. The number attributable to food contamination is unknown.

Outbreaks of rotavirus A diarrhoea are common among hospitalised infants, young children attending day care centres, and elderly persons in nursing homes. An outbreak caused by contaminated municipal water occurred in Colorado in 1981. 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. A similar large outbreak occurred in Brazil in 1977.

Rotavirus B
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. Rotavirus B caused infections in India in 1998 and this strain was named CAL. Unlike ADRV, the CAL strain is endemic.

Epidemics of rotavirus B involving thousands of people have occurred in China as a result of sewage contamination of drinking water. To date, outbreaks caused by rotavirus B have been confined to mainland China, but seroepidemiological surveys indicate a lack of immunity to rotavirus B in the US.

Rotavirus C
Rotavirus C has been associated with rare and sporadic cases of diarrhoea in children in many countries but outbreaks were first reported in Japan and England.

History
In 1943, Jacob Light and Horace Hodes proved that an infectious agent causing scours in cattle was a virus. Three decades later, preserved samples of that virus were shown to be rotavirus. In 1973, Ruth Bishop and collegues from the Royal Children's Hospital in Melbourne, Australia discovered a virus that caused gastroenteritis in children. Thomas Henry Flewett suggested this be named rotavirus after observing that, viewed through an electron microscope, a rotavirus particle looks like a wheel (rota in Latin).

In the mid-1980s the first candidate vaccines were evaluated. 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 to 100% effective at preventing severe diarrhoea caused by rotavirus A, and researchers had detected no statistically significant serious adverse effects. The manufacturer of the vaccine, however, withdrew it from the market in 1999, after it was discovered that the vaccine may have contributed to an increased risk for intussusception, or bowel obstruction, in one of every 12,000 vaccinated infants. The experience provoked intense debate about the relative risks and benefits of a rotavirus vaccine. In 2006, two vaccines against Rotavirus A infection were shown to be safe and effective in children.

Veterinary
Rotaviral enteritis is also a common disease of young animals, including mammals; apes, cattle, pigs, sheep, rats, cats and dogs, mice, rabbits and birds including chickens and turkeys. Animal rotaviruses are a potential reservoir for genetic exchange with human rotaviruses. 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. Rotaviral enteritis in livestock can lead to economic loss to farmers because of costs of treatment associated with high morbidity and mortality rates.