Rotavirus

Rotavirus is so named due to the fact that when visualized via electron microscopy, the virus presents as small round structures similar to wheels with spokes. It is the most common cause of diarrhea in children below 5 years. The disease can be mild to moderate in developed countries while severe illness with increased mortality is often encountered in developing countries. Rotaviruses belong to the Reoviridae family of non-enveloped viruses. It is unique in that its genome consists of 11 segments of double stranded RNA. There are 7 major groups of Rotaviruses (A through G). Only A, B and C groups infect humans with the A group causing the majority of infections.

Epidemiology

The peak age for rotavirus infections is 4 months to 23 months. By the age of 4 years, almost all children have been exposed to rotavirus infections. The first episode of infection is likely to be symptomatic while re-infections are less severe due to the shielding effect of the immune system from past infections. Genetic re-assortment (exchange of the segmented genome between different groups of viruses) is an important mechanism in the evolution of this virus.

Though rotavirus diarrheas are predominant among children, adults who are immunocompromised or travelers may also suffer from the disease when there are outbreaks. Outbreaks of rotavirus diarrhea in older children and adults have been reported in China. This rotavirus has been called ?adult diarrhea rotavirus? (ADRV).  In temperate regions, rotavirus infections often peak in the winter months while in the tropical regions the disease is present throughout the year. Overcrowding and the poor hygiene prevalent in these regions could be responsible for such a pattern. Though rotavirus gastroenteritis has low incidence of fatality, mortality is greater in the developing countries due to a high of malnutrition, less access to therapy, exposure to large infective doses and its synergy with other intestinal pathogens.

Rotavirus is also a major veterinary pathogen causing disease in turkeys, sheep, swine, camel and infant cattle (Nebraska Calf diarrhea). The genes of some animal strains are closely related to human strains which indicate genetic re-assortment between the different strains of the virus. Despite this, to date no major outbreaks have been reported which are linked to direct contact with infected animals.

Clinical features

Acute rotaviral infections in children are characterized by vomiting and fever for 2 to 3 days which progresses to profuse watery diarrhea which continues for another 4 to 5 days. Unlike other agents causing pediatric gastroenteritis, rotaviral gastroenteritis presents with severe and prolonged vomiting, which further complicates the treatment. Chronic rotavirus diarrheas and extra-intestinal infection are common in immunocompromised children. Some conditions associated with chronic rotavirus infections are as follows:

• severe combined immunodeficiency (SCID) 
• X linked agammaglobulinemias 
• cartilage hair hypoplasia 
• Digeorge?s syndrome
• Acquired Immunodeficiency Syndrome.

It has been observed that rotavirus which has been shed from such chronically affected individuals has altered genome segments. Immunohistochemical stains of autopsy specimens of such patients have shown that virus replication takes place in the hepatocytes and renal tubular cells of immunodeficient children at the time of their death.

Rotavirus has also been detected in association with a   number of syndromes other than gastroenteritis such as the following:       

• respiratory infections 
• necrotizing enterocolitis (in infants) 
• pneumatosis intestinalis 
• hepatic abscess 
• biliary atresia (group C) 
• myositis 
• Kawasaki?s disease 
• pancreatitis 
• seizures 
• meningoencephalitis

Since rotaviral infections are universal, these are more likely to be coincidental than causative and an etiologic association has not yet been established.

Dehydration is the main complication of rotavirus induced diarrheas. Large amounts of the virus are shed in the stool during diarrheal episodes (107 to 1012 / gm of stool). The virus can be detected in stool for about one week after the symptoms subside. The virus may be shed for more than a month in immunocompromised patients. Sensitive molecular methods like PCR can detect very small amounts of the virus even after one week. This may be useful in identifying an asymptomatic individual. Since rotavirus infections are transmitted by the oro-fecal route; such patients become reservoirs for transmission of infection and continuing the chain.

Treatment

Like other causes of viral diarrhea there is no specific therapy for rotavirus diarrheas. Research in understanding the rotavirus pathogenesis has shown that the enteric nervous system plays a role in increasing the intestinal secretions during infection. There has been little advancement in clinical research from the therapy point of view over the years and the mainstay remains re-hydration with fluids and supportive management. Most of the research is focused on the prevention of rotavirus infection and towards the development of a safe and effective vaccine.

Vaccines

Vaccine candidates are designed to protect against Group A rotavirus infections only. Polyvalent ?cocktail? containing two or more serotypes has shown to be effective in preventing severe disease. A tetravalent human re-assortment vaccine was licensed by the UD FDA in 1998 (Rotashield) for universal use. The vaccine was administered in three doses per child at 2, 4 and 6 months of age over a period of one year. This vaccine was removed from the market when a strong epidemiological link was found between administration of the first dose and development of intussusceptions in children.

In 2006, the European Medicines Agency and the US FDA licensed two oral vaccines containing the live attenuated virus; Rotarix by GlaxoSmithKline and RotaTeq manufactured by Merck & Co. Inc. respectively. These vaccines have been demonstrated to be safe and effective in preventing severe rotavirus gastroenteritis in clinical trials conducted across Europe, Latin America and the United States. The above vaccine can also be co-administered with other vaccines such as HiB, OPV, IPV, HepB, PCV 7 & DTaP.

The Rotarix (GSK) is a Human monovalent vaccine belonging to the G1 P (8) strain. It is a lyophilized preparation which is to be reconstituted and administered in two doses along with the triple vaccine DPT (1 & 2 ).  RotaTeq (Merck) is a bovine pentavalent vaccine consisting of the following strains: G1, G2, G3, G4, P (8). It is available as a liquid preparation to be administered in three doses along with the triple vaccine.

Diagnosis

Since there is no specific therapy for the treatment of rotavirus diarrheas, microbiological diagnosis is not mandatory. Diagnosis becomes critical when there are large scale outbreaks within a small setting in order to isolate the possible source and control the spread. This also helps prevent the unnecessary use of antibiotics during outbreaks. Commercial antigenic assays, RT- PCR, Immunelectron microscopy and viral cultures are available for diagnostic purposes. Detection of the antigens from stool or rectal swabs is often the method of choice used for diagnosis in routine clinical microbiology laboratories. VP6 is a major structural protein that is targeted by immunoassays for the diagnosis of rotavirus infections.