Rotavirus

1. Causative Organism
2. Clinical Signs, Symptoms and Complications
3. Method of Transmission
4. Public Health Significance
5. Prevention - Non Immunisation Methods
6. Prevention - Immunisation
7. Vaccine/s and Vaccination
8. Efficacy and Effectiveness
9. Availability
10. Dosage and Administration
11. Indications and Recommendations
12. Adverse Events
13. Contraindications
14. Risks vs Benefits

Causative Organism

Rotaviruses constitute a distinct genus of the family Reoviridae, which are non-enveloped, double-shelled viruses. The genome is composed of 11 segments of double-stranded RNA, coding for six structural and five non-structural proteins. A rotavirus has a characteristic wheel-like appearance when viewed by electron microscopy (the name rotavirus is derived from the Latin rota, meaning "wheel").

Clinical Signs, Symptoms and Complications

• Rotavirus infections are the single most common cause of severe diarrhoea in children under two years of age.
• The incubation period for rotavirus disease is approximately 2-4 days.
• The disease is characterised by sudden onset of vomiting and watery diarrhoea lasting 3 - 8 days; fever and abdominal pain also occur frequently.
• The disease is mostly mild. However 1-2% of those infected, develop dehydration associated with severe loss of sodium and chloride in the stools and a compensated metabolic acidosis.
• In immune compromised children chronic infection may persist.
• Immunity after infection is incomplete, but repeat infections tend to be less severe than the original infection.
• Most children have been infected by age 3.
• Breastfeeding does not prevent rotavirus but the illness can be milder in breastfed infants.
• Adults can become infected but most will have no symptoms.
  

Method of Transmission

• Rotaviruses are transmitted via the faecal-oral route.
• Person-to-person spread through contaminated hands is probably the most common means by which rotaviruses are transmitted in close communities such as paediatric and geriatric wards, daycare centres or family homes.
• Infection via airborne droplets has been demonstrated in a mouse model.
• 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 high levels.
• Similar incidence of rotavirus infection is observed in countries with both high and low health standards suggesting that sanitary measures adequate for bacteria and parasites seem to be ineffective in endemic control of rotavirus.
  

Public Health Significance

• Rotavirus is a significant cause of infant diarrhoea worldwide.
• Every year rotavirus is associated with 25 million clinic visits, 2 million hospitalisations, and more than 600,000 deaths worldwide among children younger than 5 years of age.
• In less developed countries rotavirus is a common cause of mortality.
• In more developed countries rotavirus causes hospitalisations.

Prevention

Non-Immunisation Methods:

• Thorough hand washing before preparing food, after using the bathroom, and after changing nappies or cleaning up vomit.
• Exclusion of children with diarrhoea from school or childcare.

Immunisation:

Vaccine description
Several types of vaccine against rotavirus have been evaluated including live attenuated strains from both humans and animals.
An oral human-rhesus reassortment rotavirus vaccine was licensed and used in the US from 1998-1999. It was later withdrawn from the market following reports of an association with intussusception.

There are currently two licensed vaccines likely to be available in developed countries in the near future.
Pentavalent WC3 - based bovine - human reassortment vaccine.

RotaTeq^®, Merck, Sharp & Dohme
Contains 5 bovine-human reassortants representing the serotypes G1, G2, G3, G4 and P[8] suspended in a liquid sodium citrate and phosphate buffer at an aggregate viral titre of approximately 6.7x107 to 12.4x107 infectious units per dose. Licensed in United States, Mexico and Australia (May 2006). This is the only currently approved rotavirus vaccine by the US FDA.

Monovalent human G1 rotavirus vaccine (Rotarix^®, GSK)
Monovalent vaccine derived from a human strain. Currently licensed in Mexico and Dominican Republic (May 2006). Contains 106.5 median cell-culture infective doses of the RIX4414 vaccine strain reconstituted with liquid calcium carbonate buffer.

Efficacy and Effectiveness

RotaTeq® - Pentavalent WC3 - based bovine - human reassortment vaccine
Efficacy has been evaluated in 2 studies in infants (3,484 vaccines and 3,499 placebo). Efficacy against any severity of gastroenteritis caused by the serotypes in the vaccine was 73.8%, efficacy against severe rotavirus gastroenteritis 98.2%. There also appears to be reasonable protection against the non-vaccine serotype G9.

Rotarix® - Monovalent human G1 vaccine
Clinical trials in approximately 1,600 subjects in Latin America and Europe under a year of age observed efficacy against any type of rotavirus gastroenteritis of between 62.9% - 73%, and against severe gastroenteritis of 78.3% - 90%.
In clinical studies evaluating cross-protection of non-G1 serotypes (G2, G3, G4 and G9) the observed effectiveness against severe gastroenteritis was 74%

Availability

• Pending licensure in most jurisdictions, including New Zealand.

Dosage and Administration

Pentavalent WC3 — based bovine — human reassortment vaccine
(RotaTeq®, Merck)

• Three 2-ml oral doses 4 —10 weeks apart.
• First dose between 6-12 weeks of age.
• Last dose by 32 weeks of age.

Monovalent human G1 rotavirus vaccine (Rotarix®, GSK)

• First dose between 6 and 14 weeks of age.
• Second dose between 14 and 24 weeks of age.

Indications and Recommendations

• Likely to recommended as a universal vaccine for all infants.
  

Contraindications

 RotaTeq®

• Hypersensitivity to any component of the vaccine.
• Individuals who develop symptoms suggestive of hypersensitivity after receiving a dose of RotaTeq® should not receive further doses of RotaTeq®.

Rotarix®

• Hypersensitivity to any component of the vaccine.
• Rotarix® should not be administered to individuals with any previous evidence of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract.

Adverse Events

Pentavalent WC3 — based bovine — human reassortment vaccine
(RotaTeq®, Merck)

In the large scale (34,837 vaccine recipients and 34,788 placebo recipients), placebo-controlled Rotavirus Efficacy and Safety Trial (REST), RotaTeq® did not increase the risk of intussusception relative to placebo (see table below). Active surveillance was employed to identify potential cases of intussusception at days 7,14, and 42 after each dose and every 6 weeks thereafter for 1 year after dose one. There were no clustering of cases among vaccine recipients at any time period after any dose. Following the 1-year safety follow-up period, 3 cases of intussusception were reported in children who had received placebo during the study.

Confirmed Cases of Intussusception in Recipients of RotaTeq® as Compared with Placebo Recipients during REST.

Rotavirus Fact sheet for parents and caregivers.