Rotavirus infection

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Rotavirus infection is the most common cause of severe diarrhea in the children. It is one of the causes of the gastroenteritis disease. Children vaccination against the rotavirus is very important to prevent any upcoming infection by the virus. Other care measures have been held in order to prevent the occasion of the rotavirus infection. These measures include: access to clean safe drinking water, washing hands regularly and personal and food hygiene. The infection can be transmitted feco-orally and it occurs through multiple viral replication. Rotavirus infections should be differentiated from other organisms which cause watery diarrhea like the adenovirus, e. coli bacteria and taenia spp. Children are in a high risk for getting infected by rotavirus especially the children who are left in a child care center and the unvaccinated children. Patients present with diarrhea, vomiting and low grade fever. They may appear pale and signs of dehydration like sunken eye and may be observed in severe cases. Prevention of dehydration and following the rehydration measures is the first line of management of rotavirus infection.

Rotavirus discovery goes back to the last century after the infection of several children with gastroenteritis of unknown reason. Studies have been held for long time through the years from 1940 till 1973. In 1973, Dr. Ruth Bishop was able to identify the pathogen causing the disease as Rotavirus.

There is no known classification for the rotavirus infection but it can be classified according to the age into adult rotavirus infection and child rotavirus infection.

Rotavirus is transmitted by the feco-oral route. It is transmitted from the infected children to other individuals before and after the occurance of the diarrhea. It can also spread through infected hands, food and objects like toys. Pathogenesis of the rotavirus takes place in the intestine where virus replication takes place and severe watery diarrhea takes place. Rotavirus protein number 4 plays an important role in causing the diarrhea and the rotavirus clinical manifestations. The infection destroys number of the intestinal digestive enzymes and malabsorption takes place leading to diarrhea. Rotavirus infection is not limited to the intestine only. It can affects the central nervous system causing meningitis.

Rotaviruses are a genus of viruses belonging to the Reoviridae family. Seven major groups have been identified, three of which (groups A, B, and C) infect humans, with group A being the most common and widespread one. They cause vomiting and diarrhea and are the most common cause of severe diarrhea in children, killing about 600,000 children every year in developing countries (as of 2005).

Rotavirus must be differentiated from other diseases and pathogens that cause watery diarrhea. In the below table it is differentiated from the other viruses that can cause the diarrhea like adenovirus, bacteria like the E. coli, and parasites like the taenia spp.

Rotavirus infection is the leading cause of severe diarrhea among the infants and children. It affects approximately, 120 million individuals annually causing death of 600,000-650,000 world-wide. It occurs more in the winter. It affects children more than adults. It is more common in developing countries. There is no racial predilection.

Children are in a high risk for getting infected by rotavirus especially the children who are left in a child care center and the unvaccinated children. However, adults can be in the risk as well. The immunocompromised patients and adults who are in contact with infected children are in risk for rotavirus infection.^[1][2]

Rotavirus infection is a self-limited disease. It may lead to dehydration, occasionally. Dehydration is one of the most important complications that may occur following the infection. Seizures are also a complication of the rotavirus infection. The disease prognosis is good.

Rotavirus clinical manifestations usually start to develop two days after the infection. It is more severe in children more than adults. Its severity depends on whether it is the first infection or recurrent. The first infection is more severe. It may be asymptomatic or causes watery diarrhea and in very severe cases it may cause severe dehydration. The children infected by the rotavirus present with high grade fever as well as vomiting.^[3][4]

Patients infected with rotavirus infection may appear lethargic and pale in severe cases. They also have low blood pressure and fever due to infection. Signs of dehydration are more noticed in the infants as they could have sunken eye and depressed fontanelle. Convulsions also may be noticed in severe cases.

Diagnosis of Rotavirus infection is feasible through several diagnostic techniques. These techniques include electron microscopy, reverse transcriptase polymerase chain reaction and RNA electrophoresis. Stool examination for the virus is important to detect the extracted viruses. Also, ELISA and immunochromatographic assays can be used for antigen detection.

There are no x-ray findings associated with rotavirus infection.

There are no CT scan findings associated with rotavirus infection. However, it may be used to exclude other neurological diseases in case the rotavirus affects the nervous system.

There are no ultrasound findings associated with rotavirus infection.

There are no other imaging findings associated with rotavirus infection.

The most important aspect of treating viral gastroenteritis in children and adults is to prevent dehydration. This treatment should begin at home. A physician may give specific instructions about what kinds of fluid to give. CDC recommends that families with infants and young children keep a supply of oral rehydration solution (ORS) at home at all times and use the solution when diarrhea first occurs in the child. Medications, including antibiotics (which have no effect on viruses) and other treatments, should be avoided unless specifically recommended by a physician.

Surgical intervention is not recommended for the management of rotavirus infection.

Rotavirus infection prevention relies completely on children vaccination against the infection. New vaccines have been shown to be safe and effective in 2006. These two rotavirus vaccines are the Rotarix and Rotateq.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Rotavirus discovery goes back to the last century after the infection of several children with gastroenteritis of unknown reason. Studies have been held for long time through the years from 1940 till 1973. In 1973, Dr. Ruth Bishop was able to identify the pathogen causing the disease as Rotavirus.

• Through the 18th and 19th century, the diarrhea was the leading cause of death among the children without knowing the pathogen which causes this diarrhea. This continues till 1973.^[1]
• Through 1941-1943, Dr. Jacob Light and Dr. Horace Hodes did some studies on diarrhea which was epidemic at this time in Baltimore and Washington. They found an agent which was believed to be the cause of this diarrhea and after several years it was known to be the rotavirus.^[2]
• In 1965, a study was made by Dr. Alan Ferris on the gastroenteritis cases in Melbourne that time. The most common cause at this time was the bacterial pathogens but he found the number of cases are increased in the winter. The explanation of this increase was unknown pathogen that causes the disease in the winter season.
• In 1972, Dr. Albert Kabikian published an article indicating a discovery of a viral particles in the infected stool during an outbreak of gastroenteritis in Ohio.^[3]
• Through 1972-1973, more studies were held by Dr. Ruth Bishop, et all, in order to identify the unknown pathogen causing gastroenteritis in the childern. It was on the duodenum of the infected childrens at which a virus was observed in the duodenal villi in the infected individuals. The virus was orbit shaped and named at this time reovirus or orbivirus and several other names to be named in the last by Rotavirus.^[4][5]

Literature references can be found at the links below.

Outbreaks of group A rotavirus diarrhea are common among hospitalized infants, young children attending day care centers, and elderly persons in nursing homes. Among adults, multiple foods served in banquets were implicated in 2 outbreaks. An outbreak due to contaminated municipal water occurred in Colorado, 1981.

Several large outbreaks of group B rotavirus involving millions of persons as a result of sewage contamination of drinking water supplies have occurred in China since 1982. Although to date outbreaks caused by group B rotavirus have been confined to mainland China, sero-epidemiological surveys have indicated lack of immunity to this group of virus in the U.S. Recent studies led to the identification of group B rotavirus occurring at a sporadic frequency in Calcutta, India and subsequently from other Asian countries as well. Thus, group B rotavirus infection may be more common than presumed earlier, but studies on this pathogen are very limited. Group B rotaviruses are difficult to isolate and cannot be easily adapted to cell culture, a property that precludes their detailed analysis.

The newly recognized group C rotavirus has been implicated in rare and isolated cases of gastroenteritis. However, it was associated with three outbreaks among school children: one in Japan, 1989, and two in England, 1990.

During 2005 the largest recorded outbreak in Nicaragua occurred. This unusual large and severe outbreak was probably due to a mutation in the rotavirus A genome, possibly helping the virus evade the prevalent immunity in the population which had no protection against this type.

For more information on recent outbreaks see the CDC Morbidity and Mortality Weekly Reports.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

There is no known classification for the rotavirus infection but it can be classified according to the age into adult rotavirus infection and child rotavirus infection.

Rotavirus has no known classification but it can be classified based on the age of the individual into:

• Adult rotavirus infection
• Child rotavirus infection

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Rotavirus is transmitted by the feco-oral route. It is transmitted from the infected children to other individuals before and after the occurance of the diarrhea. It can also spread through infected hands, food and objects like toys. Pathogenesis of the rotavirus takes place in the intestine where virus replication takes place and severe watery diarrhea takes place. Rotavirus protein number 4 plays an important role in causing the diarrhea and the rotavirus clinical manifestations. The infection destroys number of the intestinal digestive enzymes and malabsorption takes place leading to diarrhea. Rotavirus infection is not limited to the intestine only. It can affects the central nervous system causing meningitis.

• After entrance the virus to the body through the mouth, replication takes place in the small intestine where it can cause severe watery diarrhea.
• The pathogenesis of the rotavirus infection depends on the enzymes destruction and the enterotoxins of the virus itself.
• Virus virulence factors have a significant role in the pathogenesis of the rotavirus infections. The rotavirus has 11 genes at which each gene plays a role in the pathogenesis e.g. gene 3 helps in the virus replication, genes 4 and 9 help in the infection initiation, and gene 5 is responsible for the protein coding resulting in interfering the action of the antiviral drugs.^[1]
• The main site of infection to the rotavirus are the intestinal villi. By the help of the viral protein number 4, rotavirus can bind its receptors initiating its infection. After the infection, replication takes place releasing viruses into the intestinal lumen. Proceeding from the virus replication, rotavirus produces the enterotoxins e.g. non structural protein 4 which will have a significant effect in causing the watery diarrhea.
• Rotavirus diarrhea is a watery diarrhea, not like the bacterial diarrhea, which occurs via many mechanisms dicussed as the following:
  • The non-structural protein 4 stimulate free calcium ions
  • The infection by the virus destroys the intestinal digestive enzymes like the maltase which is responsible for the carbohydrates digestion. This enzyme destruction increases the fluids in the lumen and causes malabsorption which leads to diarrhea.^[2]
  • Rotavirus infection is not limited to the intestine only. It can affects the central nervous system causing meningitis.

• Rotavirus spreads easily among infants and young children. Children can spread the virus both before and after they become sick with diarrhea. They can also pass rotavirus to family members and other people with whom they have close contact.^[3]
• People who are infected with rotavirus shed rotavirus in their stool – this is often how the virus spreads from a person’s body to other people and into the environment. They shed the virus most when they are sick and during the first 3 days after they recover.
• The virus spreads by the fecal-oral route; this means the virus is shed by an infected person and then enters a susceptible person’s mouth to cause infection. Rotavirus can be spread by the following:
  • Hands
  • Objects (toys, surfaces)
  • Food
  • Water

Rotavirus may be associated with the following diseases:^[4]

• Necrotizing enterocolitis
• Intussusception
• Kawasaki’s syndrome
• Type 1 diabetes mellitus

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Rotaviruses are a genus of viruses belonging to the Reoviridae family. Seven major groups have been identified, three of which (groups A, B, and C) infect humans, with group A being the most common and widespread one. They cause vomiting and diarrhea and are the most common cause of severe diarrhea in children, killing about 600,000 children every year in developing countries (as of 2005). New vaccines have been shown to be safe and effective in 2006 [2].

Rotaviruses have a genome consisting of 11 double-stranded RNA segments surrounded by a distinctive three-layered icosahedral protein capsid. The first layer is formed by the protein VP2, with each vertex having a copy of the proteins VP1 and VP3. The second layer is formed by the protein VP6. The outermost protein layer is composed of the structural glycoprotein VP7 and the spike protein VP4. Viral particles are up to 70nm in diameter and have a buoyant density of 1.36 g/ml in CsCl. By negative staining electron microscopy they resemble ‘wheels’ from which they derive their name (rota is Latin for wheel).

Rotaviruses tend to affect gastrointestinal epithelial cells that are at the tip of the villus. Their triple protein coats make them very resistant to the normally prohibitive pH of the stomach, and also digestive enzymes (lipases and proteases) in the gastrointestinal tract.

When they infect a cell, they are ingested by the cell in endocytosis in 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 Ca²⁺ concentration. This facilitates the breakdown of VP7 trimers into single protein subunits, leaving the VP2 and VP6 coats around the viral dsRNA, forming a double-layer particle (DLP).

While the eleven dsRNA strands are still within the protection of the two protein shells, RNA-dependent RNA polymerase creates viral mRNA transcripts of the double-stranded viral genome. This is more easily done within the environment in the “core” of the virus than in the host cell’s aqueous environment, which significantly slows down the detachment of the two RNA strands to begin mRNA synthesis. Encapsidation of the viral RNA may also serve to evade host immune responses that are triggered by the presence of double-stranded RNA.

During the infection, rotavirus produces mRNA to support both protein translation and genome replication. Most of the rotavirus proteins accumulate in structures known as viroplasms, where the RNA is replicated and the DLPs are assembled. Viroplasms are electron-dense, perinuclear, punctate structures found as early as 2 hours after virus infection. Viroplasms are viral factories and are thought to be formed by two viral non-structural proteins, NSP5 and NSP2. Expression of certain forms of NSP5, especially one that is tagged at the NH2-terminus, results in the formation of viroplasms. Inhibition of NSP5 using intrabodies or RNA interference results in a profound decrease in rotavirus replication. The DLPs can migrate to the endoplasmic reticulum where they obtain their third, outer layer (formed by VP7 and VP4).

Rotaviruses are transmitted by the fecal-oral route. Person-to-person spread through contaminated hands is probably the most important means by which rotaviruses are transmitted in close communities such as pediatric and geriatric wards, day care centers and family homes.

Infected food handlers may contaminate foods that require handling and no further cooking, such as salads, fruits, and hors d’oeuvres. Rotaviruses are quite stable in the environment and have been found in estuary samples at levels as high as 1-5 infectious particles/gal. 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.

The virus has not been isolated from any food associated with an outbreak, and no satisfactory method is available for routine analysis of food. However, it should be possible to apply procedures that have been used to detect the virus in water and in clinical specimens, of which reverse transcription (RT)-PCR amplification is the most sensitive method to food analysis.

• The Bad Bug Book by the U.S. Food & Drug Administration, 1992.
• New vaccines for diarrhoea virus shown effective, New Scientist, 5 January 2006
• Diarrhoea vaccines prove their mettle, news@nature.com, 5 January 2006

• Nosocomial infection

• CDC Viral Gastroenteritis FAQs: Center for Disease Control and Prevention of Food Illness Fact Sheet
• Loci index for genome Rotavirus: Available from the GenBank Taxonomy database, which contains the names of all organisms that are represented in the genetic databases with at least one nucleotide or protein sequence.
• Encyclopedia of Children’s Health: Rotavirus Infections: Description, causes and symptoms, diagnosis, treatment, prognosis, prevention, parental concerns, and resources.
• Rotavirus, Emerging Infectious Diseases, Vol 4 No 4, Oct 1998.
• PATH’s Rotavirus Vaccine Program
• Rotavirus disease and vaccine resources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Rotavirus infection most commonly causes watery diarrhea and it is the leading cause of death in the children and infants. Rotavirus infection should be differentiated from other pathogens and diseases that cause diarrhea. In the below table it is differentiated from the other viruses that can cause the diarrhea like adenovirus, bacteria like the E. coli and shigella, and parasites like the protozoa.

Rotavirus must be differentiated from other diseases and pathogens that cause watery diarrhea. In the below table it is differentiated from the other viruses that can cause the diarrhea like adenovirus, bacteria like the E. coli, and parasites like the taenia spp.

Rotavirus infection must be differentiated from other causes of viral, bacterial, and parasitic gastroentritis.

∞Small bowel diarrhea: watery, voluminous with less than 5 WBC/high power field

Large bowel diarrhea: Mucousy and/or bloody with less volume and more than 10 WBC/high power field
† It could be as high as 1000 based on patient’s immunity system.

The table below summarizes the findings that differentiate inflammatory causes of chronic diarrhea^{[1][2][3][4][4]}

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Rotavirus infection is the leading cause of severe diarrhea among the infants and children. It affets about 120 million individual annually causing death of 600,000-650,000. It occurs more in the winter. It affects the children more than the adults. It is more in the developing countries. There is no race predilection.

• Rotavirus infections affect about 120 million individual per year, causing the death of 600,000 – 650,000.
• Rotavirus is endemic worldwide. It is the leading cause of severe diarrhea among infants and children, being responsible for about 20% of cases, and accounts for about half of the cases requiring hospitalization. Almost every child has been infected with rotavirus by age 5.
• Over 3 million cases of rotavirus gastroenteritis occur annually in the U.S.
• In temperate areas, it occurs primarily in the winter, but in the tropics it occurs throughout the year. The number attributable to food contamination is unknown.

Humans of all ages are susceptible to rotavirus infection. Children 6 months to 2 years of age, premature infants, the elderly, and the immunocompromised are particularly susceptible to more severe symptoms caused by infection with group A rotavirus.

There is no racial predilection for rotavirus infection.

Rotavirus infections are more prevelant in the developing countries more than the developed countries.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Children are in a high risk for getting infected by rotavirus especially the children who are left in a child care center and the unvaccinated children. However, the adults can be in the risk as well. The immunocompromised patients and adults who are in contact with infected children are in a risk for rotavirus infection.^[1][2]

In the united states, children are most at a high risk for getting rotavirus disease. Risk factors associated to rotavirus infection includes:

• Those in child care centers or other settings with many young children are most at risk for infection.
• Unvaccinated children, aged 3 to 35 months old, can be severely infected by rotavirus.

• Older adults have, to some extent, a risk of getting infected.
• Adults who are caring for infected children by rotavirus.
• Immunocompromised patients like HIV patients.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

There is insufficient evidence to recommend routine screening for rotavirus infeciton.

There is insufficient evidence to recommend routine screening for rotavirus infeciton.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Rotavirus infection is a self-limited disease. It may lead in some cases to dehydration and it is one of the important complications that may occur following the infection. Seizures are also a complication of the rotavirus infection. The disease prognosis is good.

Rotavirus gastroenteritis is a self-limiting, mild to severe disease characterized by vomiting, watery diarrhea, and low-grade fever. The infective dose is presumed to be 10-100 infectious viral particles. Because a person with rotavirus diarrhea often excretes large numbers of virus (10⁸-10¹⁰ infectious particles/ml of feces), infection doses can be readily acquired through contaminated hands, objects, or utensils. Asymptomatic rotavirus excretion has been well documented and may play a role in perpetuating endemic disease.^[1]

The incubation period ranges from 1-3 days. Symptoms often start with vomiting followed by 4-8 days of diarrhea. Temporary lactose intolerance may occur. Recovery is usually complete. However, severe diarrhea without fluid and electrolyte replacement may result in death. Childhood mortality caused by rotavirus is relatively low in the U.S., with an estimated 100 cases/year, but reaches over 500,000 cases/year worldwide (as of 2005). Association with other enteric pathogens may play a role in the severity of the disease.

Clinically, the most severe disease occurs in children under two years of age.

Repeated rotavirus infections may increase the risk of celiac disease in genetically susceptible children. Complications of the rotavirus infection in severe cases include the following:

• Dehydration
• Seizures

Rotavirus infection prognosis is good as the disease is self limited.