1. How much do you really know about this common cause of viral gastroenteritis? There are a number of common misunderstandings about the good, the bad, and the ugly of the virus, the infection, and the vaccines. Click through and test your rotavirus IQ.

2. Rotavirus was given its name when scientists observed its wheel-like appearance; it was named after rota, the Latin word for wheel.[1] The inner hub of the rotavirus (yellow on the slide) is usually referred to as the G-type, and the spokes coming off of the inner hub (red on the slide) are usually referred to as the P-type. The G-type and P-type define the serotype of the virus and are critical to vaccine development because they are the vaccine targets for stimulating a protective immune response.

3. This is a common misunderstanding.
Consider the case of 24-week-old JT. For the past 2 days he has had nonbilious vomiting and frequent watery stools. Attempts by his mother to feed him have been unsuccessful for approximately 8 hours, and now she is unable to arouse him. She calls 911.
JT is taken to the emergency department. On arrival he is tachycardic, tachypneic, and febrile, and is dehydrated. He is admitted to the pediatric intensive care unit, where he is noted to be obtunded and responsive only to painful stimuli. JT is diagnosed with acute rotavirus gastroenteritis. Severe rotavirus infection requiring hospitalization is most common among children months of age, with > 70% of cases occurring in children 6-24 months of age.[2,3]

4. All children are exposed to rotavirus by the age of 3 years
All children are exposed to rotavirus by the age of 3 years. Some, like JT, will become severely ill with gastroenteritis. Those most likely to become infected are being cared for in child care or hospital settings. Parent and caretakers are also at risk of being infected by their infected children. Preterm infants, particularly those who are very low birth weight (<1500 g) and low birth weight ( g),[4,5] are at increased risk for severe rotavirus infection requiring hospitalization.

5. Dehydration is common with severe rotavirus gastroenteritis
Dehydration is common with severe rotavirus gastroenteritis. Rehydration can be accomplished in most cases with oral hydration. Children in the United States with severe rotavirus disease rarely die, but in developing countries where oral rehydration therapy and critical care are in high demand but short supply, death is still all too common. The reader is referred to the US Centers for Disease Control and Prevention for recommendations for treatment of children with diarrhea and dehydration and a summary of treatment based on the degree of dehydration.[6]

6. Diarrhea is the second most common cause of death among children < 5 years of age worldwide.[7] Rotavirus is the most commonly identified pathogen in young children with diarrhea. Rotavirus infection results in an estimated 24 million outpatient visits, 2.4 million hospital admissions, and 527,000 deaths worldwide.[8] The relatively low burden of disease in the United States is a result of the rotavirus vaccination programs, beginning in 2006.

7. The classic triad of rotavirus infection -- fever, vomiting, and diarrhea -- occurs in 70% of infected children.[2] An additional 25% have 2 of these symptoms. By comparison, this clinical triad is present in only 42% of children with gastroenteritis unrelated to rotavirus.[2]

8. Gastroenteritis caused by rotavirus is more severe than gastroenteritis from other causes.[2] In a classic study of children requiring hospitalization for gastroenteritis, rotavirus-infected children were twice as likely to be dehydrated as those who were not rotavirus infected (83% vs 40%).[9] Typically, fever and vomiting develop initially followed by nonbloody diarrhea. Rotavirus-infected children can have up to 20 bowel movements per day.[1] Anorexia, abdominal cramping, irritability, and lethargy may also be part of the clinical picture.

9. Prior to implementation of rotavirus vaccination in the United States in 2006, mortality and morbidity from rotavirus infection were significant: 1 in 7 children saw a healthcare provider for rotavirus disease and approximately 1 in 24 emergency department visits were for rotavirus disease.[10] One in 80 children was admitted to the hospital for rotavirus disease and approximately 40 died as a result of rotavirus disease annually. Rotavirus was a more common cause of hospitalization in children than influenza.[11-13]

10. Data from show that the estimated median direct cost associated with hospitalization for rotavirus gastroenteritis was $4565. The average hospital length of stay was 1.9 days and the median costs for short-stay, emergency department, and outpatient visits were $3160, $867, and $75, respectively.[14] Parents lost on average 3.4 days of work.

11. Rotavirus has a worldwide distribution, and is found in both developed and developing countries. Prevalence varies by geographic region.[15] The greatest burden of diseases is in Africa, India, and south Asia.

12. This is a common misunderstanding.
Parents cannot prevent their children from getting a rotavirus infection. The primary mode of rotavirus transmission is fecal to oral. Rotavirus is highly communicable and transmissible. Close person-to-person contact and environmental surfaces are common vectors of transmission. It is impossible to keep contaminated fingers and objects from going into children's mouths. Even if a child is not cared for in a daycare setting, he or she is likely to have contact with other children or objects that other children have touched.
Rotavirus is an extremely hardy pathogen. The incubation period is 1-3 days and large quantities of virus are shed in stool from just prior to onset of symptoms until about 10 days after onset.[1] Rotavirus is highly transmissible. Under experimental conditions, almost 50% of rotavirus remains viable on contaminated hands for 60 minutes.[1]

13. Rotavirus has been found in hand-washing and food-preparation areas and on commonly used fomites such as diaper-disposal containers, diaper-changing surfaces, and toys. This demonstrates how easily the virus can be spread throughout different settings such as the home, daycare facilities, and hospitals.
About one third to one fourth of children hospitalized for rotavirus infection acquired their infection in the hospital.[11] Even with the best infection control efforts, the burden of hospital-acquired rotavirus remained unchanged prior to implementation of the rotavirus vaccination.[11]

14. This is a common misunderstanding.
Velazquez and colleagues[16] evaluated Mexican children from birth through 2 years of age for evidence of rotavirus infection by serologic testing and by testing for rotavirus in stool during any episodes of gastroenteritis. They found that multiple infections commonly occurred during the first 2 years of life.[16] By the age of 2 years, 95% had at least 1 infection, about 66% had at least 2 infections, and about 15% had 5 or more infections. In the United States, the slope of the curve is a little less steep, with 95% of children infected by the age of 5 years.

15. The initial infection will most likely be severe; subsequent infections are more commonly mild or asymptomatic and are almost always of a different serotype. This slide shows that the initial rotavirus infection conferred 87% protection against subsequent moderate-to-severe infections, but only 38% protection against subsequent asymptomatic infections. After 2 rotavirus infections, no children had subsequent moderate-to-severe infections. After 3 rotavirus infections, subsequent infections were completely asymptomatic in 99% of children.[16] Thus, the first rotavirus infection tends to be the most severe and subsequent infections are commonly mild or asymptomatic.

16. If the first rotavirus infection was caused by a G1 rotavirus type (horizontal rows), the second rotavirus infection (vertical columns) tended to be caused by a non-G1 rotavirus type, such as G2 or G3. By contrast, if the first infection was caused by a G3 rotavirus type, subsequent infections tended to be caused by G1 or G2 rotavirus types. Very few second infections (2 of 22) were caused by the same serotype as the first infection. Thus, prior rotavirus infection with a specific G-type offered some protection against subsequent infections with the same G-type. Recent data suggest that this may not hold true in other countries, such as in the slums of India.[17]

17. Certain rotavirus G-types and P-types occur together and at a much higher frequency than others. P[8]G1 is the most common serotype worldwide and accounts for more than two thirds of rotavirus infections in the United States and worldwide. Infections with G1, G2, G3, G4, and G9 together comprise almost 95% of rotavirus serotypes observed. The second most common isolate is G2, which has a P-type (P[4]) that is infrequently seen with any other G-type. The other common isolates are P[8]G3, P[8]G4, and P[8]G9.

18. This is a common misunderstanding.
Two rotavirus vaccines, the pentavalent bovine-human reassortant vaccine (RV5, RotaTeq®, Merck & Co., Inc., Whitehouse Station, NJ) and the attenuated human rotavirus vaccine (RV1, Rotarix®, Brentford, United Kingdom) have been licensed in the United States since 2006 and 2008, respectively. These vaccines underwent extensive safety and efficacy trials involving a combined total of > 130,000 study participants before being licensed in the United States and other countries.[18,19]

19. Following implementation of these vaccines, the rotavirus season in the United States was significantly delayed, the duration was shorter, and the magnitude was dramatically decreased compared with previous years (see the solid line at the bottom vs the dotted line at the top of the slide). Even though only about one third of the target infant population was fully vaccinated and only about one half received ≥ 1 dose, a marked decline (greater than two thirds) in rotavirus disease was seen. Despite a slight rebound the following season, all of the studies published to date have demonstrated a marked reduction in disease burden.[11]

20. Compared with 2006, 2008 rates of hospitalization for rotavirus infection in all age groups were significantly decreased. The greater than expected disease reduction among predominately unvaccinated, older children was most likely the result of herd immunity -- indirect protection conferred by younger, vaccinated children within the household or community.[20]

21. RotaTeq is administered as a 3-dose series to infants at 2, 4, and 6 months of age. Rotarix is administered as a 2-dose series at 2 and 4 months of age. The minimum age for administration of the initial dose of either vaccine is 6 weeks and the maximum age at which the final dose should be administered is 8 months 0 days. Vaccine should be administered to preterm infants at the time of hospital discharge or during the first follow-up visit after discharge, as long as the infant is between 6 weeks and 14 weeks, 6 days of age.[21,22] The recommended minimum interval between doses is 4 weeks.

22. This is a common misunderstanding.
Rotavirus vaccine can be administered concomitantly with other vaccines recommended for children between 6 weeks and 8 months of age.[21,22] Current American Academy of Pediatrics (AAP) and Advisory Committee on Immunization Practices (ACIP) recommendations include a maximum age of 14 weeks, 6 days for the first dose administration and a maximum age of 8 months, 0 days for the last vaccine dose. Unlike some other recommended childhood vaccinations, there is no catch-up vaccination schedule for rotavirus.

23. This is a common misunderstanding.
Parents often express concern about their children receiving a live vaccine and multiple vaccinations.[23] Healthcare providers must be able to address parental concerns about vaccine safety. Both parents and healthcare providers should be reassured by the safety data from the prelicensure trials of RotaTeq and Rotarix. An impressive number of study participants were included and many were followed extensively to identify side effects. The incidence of serious nongastroenteritis adverse events in vaccine recipients was similar to that of participants receiving placebo.[24] Ongoing post-licensure monitoring in the United States has not detected any serious adverse side effects in healthy infants.[25,26]

24. This is a common misunderstanding.
This misunderstanding is based largely on the experience with the first rotavirus vaccine, Rotashield®, which was withdrawn from the market within 1 year because of an association with an increased risk for intussusception. Prelicensure[18,19] and postlicensure data[25,26] showed no appreciable increase in the risk for intussusception. An interim analysis of Rotarix postlicensure safety data suggested a small increase in the risk for intussusception within 31 days after the first dose (most cases occurred within 7 days); the relative risk was 1.8 (99% confidence interval, 1.0, 3.1).[27] Although results were preliminary, revised labeling to inform healthcare providers of this finding was added to the package insert.

25. Recent information about the risk for intussusception comes from studies conducted in Mexico[28] and Brazil.[29] In Mexico there was a > fivefold increased risk within the first 7 days after the first vaccine dose, equating to an intussusception rate of 1 in 51,000 vaccinated infants.[28] In Brazil, there was an approximate twofold increased risk within 7 days of the second dose, equating to an intussusception rate of 1 in 68,000 vaccinated infants.[29] Although 2 additional deaths would be expected to occur as a result of intussusception in Mexico, 663 childhood deaths and 11,551 hospitalizations would be prevented.[28] In Brazil, 5 additional deaths would be expected, but 1300 childhood deaths and 80,000 hospitalizations would be prevented.[29] Data from Australia also suggest an increased risk for intussusception in the immediate window after the first dose for both RotaTeq and Rotarix, but no increase in the overall risk.[30]

26. Some clinicians are hesitant to administer rotavirus vaccines to infants or children with certain preexisting conditions, but there are only a few true contraindications.
* Infants with severe latex allergy may receive RotaTeq.[21,22]

27. Recommendations for routine vaccination have not been made for children with these conditions. The potential risks and benefits of vaccine administration should be weighed for each patient, and consultation with an infectious disease specialist or immunologist should be considered.
Some experts recommend that children at risk for a latex allergy developing (eg, children with spina bifida)* should preferably receive RotaTeq to minimize latex exposure. If RotaTeq is unavailable, Rotarix should be administered because the benefit of vaccination is considered greater than the risk for sensitization.[21,22]
Caution should also be exercised when considering administration of the rotavirus vaccine to an infant residing in a household or in close contact with a person with known severe compromised immune function. It has been argued that the risk for transmission of a vaccine strain with associated clinical symptoms is much lower than the risk for wild-type rotavirus disease from an unvaccinated child.[7]
*If RotaTeq is unavailable, Rotarix should be administered because the benefit of vaccination is considered greater than the risk for sensitization.[21,22]

28. In March 2010, the United States Food and Drug Administration (FDA) recommended that clinicians stop using Rotarix after it was discovered that the vaccine contained DNA sequences from PCV1, a porcine circovirus.[32] Soon after, RotaTeq was found to contain PCV1 and a related virus, PCV2.[33] PCV1 and PCV2 are highly prevalent in healthy pigs. Although PCV2 can cause wasting disease in pigs, it has never been linked to disease in humans. Human exposure to porcine circoviruses occurs through pork ingestion and inhalation of pig feces.[34] In May 2010, the FDA reversed its recommendation to suspend use of Rotarix.[32] Clinicians and parents should be assured that circoviruses have not been shown to cause disease in humans.

29. Regardless of public health efforts and hygiene practices, most children will become infected with rotavirus by 3 years of age, and there is no treatment other than supportive care. Despite the availability of 2 rotavirus vaccines since 2006, more than 500,000 children continue to die each year from severe rotavirus disease; 85% live in developing countries. In developed countries where children have ready access to vaccines and treatment for severe rotavirus diseases, death from rotavirus is rare. In 2009, the World Health Organization recommended that all countries include rotavirus vaccines in their national immunization programs. Efforts are underway by the Program for Appropriate Technology in Health (PATH)[35] and the Global Alliance for Vaccines and Immunisation (GAVI)[36] to accelerate access to these life-saving vaccines by those who need them most.

30. Thank you for participating in this activity.