Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

Based on the Canada Communicable Disease Report (CCDR) Online publication 22 January 2008;34(ACS-1):1-33.

According to a recent National Advisory Committee on Immunization (NACI) statement published in the Canada Communicable Disease Report, infants and their families are likely to benefit from immunization with a vaccine that would prevent the great majority of rotavirus (RV)-related physician and emergency room visits, as well as hospitalizations for severe disease. The pentavalent RV vaccine is approved for use in infants aged six to 32 weeks, with the first dose to be given within 12 weeks of age.

Approximately 20% of all childhood gastroenteritis in Canada is caused by RV and almost all children experience an episode by five years of age. Among children requiring hospitalization, over half are between six and 24 months of age. The proportion of RV gastroenteritis in hospitalized children also varies, from a seasonal high of 60% to 78% between April and May to a lower proportion between December and February.

Noteworthy, too, is the fact that RV causes the majority of gastroenteritis episodes in children requiring hospitalization, at rates that range from one in 62 to one in 312 under the age of five. Even among children who do not require hospitalization, the annual health care burden attributable to RV infection in Canada is high, accounting for some 41,000 physician consultations and 17,000 emergency room visits each year.

The efficacy of the pentavalent RV vaccine has been evaluated in three phase III clinical trials involving almost 72,000 infants. Approximately half of those received the vaccine and the other half received placebo. Three doses of the vaccine were given orally, beginning at six to 12 weeks of age, with a four- to 10-week interval between doses. The overall efficacy of this three-dose schedule against severe RV gastroenteritis caused by the four G serotypes contained in the vaccine was 98.2%; overall efficacy against RV gastroenteritis of any severity was 73.8%.

The vaccine was also found to be 74% effective against RV infection caused by non-vaccine serotype G9, although data on these particular incidence rates are limited. In a small sample of approximately 4500 infants, investigators also found that the vaccine was 62.6% effective against G1-G4 RV gastroenteritis during the second season and 88% effective against severe disease.

Results from the largest of these studies, the REST (Rotavirus Efficacy and Safety Trial), showed that the vaccine reduced G1-G4 RV-associated hospitalizations or emergency room visits by 94.5% and non-urgent office or clinic visits by 86%. “Further, there was a reduction of 58.9%… in all gastroenteritis-related hospitalizations after the first dose,” NACI stated, “[while] among the parents/guardians of the 68,038 infants studied, there was an 86.6%… reduction in work days lost.”

Based on REST data, the overall efficacy of the vaccine in the prevention of emergency room visits or hospitalizations due to all serotypes of RV was 83% two weeks after the first dose, 81% two weeks after the second dose and 95% two weeks after the third dose.

Indeed, based on the Rotavirus Gastroenteritis Cohort Model—and assuming that approximately 94% of rotavirus disease in Canada is caused by the strains of RV contained in the vaccine—“implementation of universal immunization of all Canadian infants could be expected to prevent as many as 56,000 cases of RV gastroenteritis, 33,000 physician visits, 15,000 emergency department visits and 5000 hospitalizations annually,” NACI speculated.

Risk of Intussusception

Experience with an earlier RV vaccine, Rotashield, withdrawn from the US market after 15 children developed intussusception during a two-week interval after receiving the vaccine, dictates that the newer vaccine be very carefully scrutinized for adverse events. (Note: Rotashield was not available in Canada.) In the three phase III studies involving 71,725 infants, six cases of intussusception were documented following receipt of the vaccine vs. five in the placebo group and there was no evidence of clustering of cases within a seven- to 14-day window after vaccination from any dose—the period of greatest risk for intussusception associated with the previous vaccine.

A post-marketing safety study is currently being carried out by the Centers for Disease Control and Prevention and the FDA to monitor vaccine recipients for any signs of intussusception, as is the manufacturer of the vaccine. To date, however, after some 3.6 million doses have been delivered, there is no evidence that infants who receive the vaccine are at increased risk of intussusception. “This is very reassuring,” NACI members commented, “as the association between intussusception and Rotashield was observed following immunization of only approximately 600,000 infants.”

As for other serious adverse events, the incidence among the entire cohort of infants enrolled in the phase III studies was virtually identical at slightly over 2% for both vaccine recipients and placebo controls.

Hepatitis A Vaccine

Another vaccine currently indicated for children from the age of 12 months is the hepatitis A vaccine. In a double-blind, placebo-controlled trial carried out in 1037 healthy seronegative children in a community where the annual incidence of hepatitis A was estimated to be at least 3%, the inactivated hepatitis A vaccine proved 100% protective against clinical disease after a single dose (P<0.001) (Werzberger et al. N Engl J Med 1992;327(7):453-7).

One hundred per cent protection against infection was seen as early as 21 days following a single 0.6-mL intramuscular injection—a finding that led to premature unblinding of the trial to allow placebo recipients to be vaccinated. Cases occurring at or after 50 days’ post-injection were evaluable. In the placebo group, 25 cases had occurred from day 50 and three cases before day 21. The active-treatment group reported no cases from day 50 and seven cases before day 21. No serious adverse reactions were reported during the vaccination study and those that were reported were mild, self-limiting and predictable for any intramuscular injection. Infants from the age of 12 months may receive the first dose of the inactivated vaccine at any time, with a booster dose given six to 18 months after the first dose.

The vaccine is also felt to be particularly practical for anyone who travels, military personnel and those who live in communities where hepatitis A infection is common.

Questions and Answers

This question-and-answer session was conducted with Dr. John Yaremko, staff pediatrician, Montreal Children’s Hospital and Assistant Professor of Pediatrics, McGill University, Quebec.

Q: Have you already been recommending the RV vaccine to parents since it was approved in 2006?

A: Yes, I have been offering it to my patients because I work in an office as well as in emergency at the Montreal Children’s Hospital and there is no question that during the peak season, I see many infants with diarrhea and vomiting and the most likely cause is RV. I also see it in my practice in infants and often in their siblings; even about one-third of parents get the infection as well so it is very common. Children will not die from RV gastroenteritis but they can get quite sick from it and there is a lot of stress on the family when a child goes through this.

Q: What do you say to parents who are considering having their infants vaccinated against RV?

A: Parents who have had more than one child have probably experienced at least one episode of RV, so if there is a way to avoid it, they will vaccinate. Once you have experienced the nastiness of the infection, you do not want to have to go through it again.