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.

24th Annual Meeting of the European Society for Pediatric Infectious Diseases

Basel, Switzerland / May 3-5, 2006

One of the first studies of rotaviral gastroenteritis (RGE) at the community practice level in Canada has suggested that these infections must be taken more seriously than at present because it is generally overlooked that they are the foremost cause of severe dehydrating gastroenteritis in infants six months to three years of age and can be life-threatening if left untreated. During the scientific sessions here this week, the Canadian study group reported that rotavirus is the leading cause of hospitalizations for gastroenteritis in infants and children in Canada, accounting for 78% of admissions. According to investigators, in order to comprehend the potential impact of the recently developed safe and effective rotavirus vaccines at the population level, it is necessary to understand the severity of the disease and the extent of its impact on health care resource utilization.

Severity of Rotavirus Gastroenteritis

According to Dr. Marc Lebel, CHUM-Hôpital Ste-Justine, Montreal, Quebec, a lead author of the three-part study, RGE is clinically more severe than gastroenteritis of other etiologies. “Its multiple symptoms, including severe diarrhea, frequent vomiting and fever, increase the risk of rapid dehydration and make oral rehydration difficult, which may explain why so many cases go on to receive additional emergency care,” he told delegates.

The first arm of the study sought to determine the severity of RGE and health care resource utilization (HCRU) in community practices. Stool specimens from 395 children under three years of age from across Canada who presented with gastroenteritis were tested for rotavirus antigen; of the 369 results deemed conclusive, 200 (54.2%) were found to be rotavirus-positive and 169 (45.8%) were antigen-negative. Dr. Lebel said that compared to rotavirus-negative children, those with positive antigen tests were more likely to have diarrhea (100% vs. 95.9%, P=0.0037), vomiting (85.5% vs. 50.9%, P<0.0001), fever (62.0% vs. 34.3%, P<0.0001) and all three symptoms simultaneously (57.5% vs. 18.9%, P<0.0001).

“After consultation with a family physician or pediatrician, rotavirus-positive cases were significantly more likely to be hospitalized [odds ratio (OR) 4.5], to visit the emergency room [OR 2.3] and/or to receive intravenous rehydration [OR 4.9] than rotavirus-negative children,” Dr. Lebel continued, adding that these data demonstrate RGE to be clinically more severe than other GEs and put a greater burden on health care resources. Rotavirus vaccination, therefore, has the potential to significantly reduce HCRU in young Canadian children, he concluded.

Serotype Distribution of Rotavirus in Canada

Because rotavirus infection induces type-specific immunity, the second arm of this study measured the distribution of rotavirus G-serotype infections in order to predict the potential impact of immunization. Results showed that of 197 rotavirus-positive children tested, a G-serotype was identified in 175 (88.8%). The vast majority of RGE cases (99%) were of G1-4 serotype and G9 origin, often found in conjunction with P1, and the most prevalent G-serotype found in this contemporary study was G1 (55.4%). Dr. Lebel noted that this was a surprising finding since the prevalence of G2 serotype was much higher during the 1997-1998 rotavirus outbreak in Toronto (31.5%) compared to the first six months of 2005 (3.4%). “This illustrates the seasonal variability of rotavirus types associated with clinically relevant disease and underscores the important contribution of non-G1 serotypes to the prevalence of rotavirus disease,” he explained.

Another surprising finding, Dr. Lebel reported, was that the majority of RGE symptoms were observed between February and May. They peaked in April, when 67% of cases were rotavirus-positive. It had been more or less accepted that rotavirus infections were always most prevalent during the coldest winter months.

The introduction of the new rotavirus vaccines now in clinical trials are expected to have a significant effect on disease caused by rotavirus. It is noteworthy that one of the vaccines contains the five serotypes G1, G2, G3, G4 and the emerging G9, that protect against 98% of severe RGE infections and 95% of all rotavirus disease in Canada. The other investigational vaccine is immunogenic for serotypes P1G1.

Burden on Canadian Families

Noting that data on the economic and psychosocial impact of RGE on families are essential for evaluation of vaccination, the authors focused the third section of this study on the burden of RGE on Canadian families in terms of quality of life, work loss and household contacts. Dr. Lebel reported that at least one parent missed work in 111 out of 200 RGE cases (56%) and they lost an average of 2.9 working days. “Overall, an average RGE requiring hospitalization costs 3.1 lost work days, compared to 2.3 days lost for those visiting an emergency room [but not hospitalized] and 2.1 days lost for those seeking physician consultation only,” he said.

Depending on the measurement tool used, RGE reduced the quality of life of children by 8% measured by a health utilities index (HUI) and 31% on a visual analogue scale (VAS). Caregivers’ (usually parents) quality of life was reduced by 7% on a Euro Qol-5D (EQ-5D) scale and 12% on the VAS. The investigators estimated that 100,000 RGE cases would induce 186 HUI and 755 VAS quality-adjusted life-years (QALY) lost to the sick children and 200 EQ-5D and 320 VAS QALY lost to children’s caregivers. They believe these estimates can be used to perform cost-effectiveness analyses that capture reduction in mortality induced by rotavirus vaccination.

Citing another important finding, the investigators reported that in 93 of 100 RGE cases (47%) at least one other family member suffered gastroenteritis within two weeks and more than half the additional cases were adults. “Our results show that in Canada, RGE impacts the quality of life of not only the child but also the parents,” they concluded.

Vaccination Simplified

According to Dr. Keith Reisinger, Medical Director, Primary Physicians Research, Pittsburgh, Pennsylvania, “While the economic and health benefits of childhood vaccination have been clearly demonstrated, coverage rates for varicella vaccination are not optimum, ranging upward from only 63%, whereas measles-mumps-rubella [MMR] vaccine coverage is greater than 90%.”

In Canada, coverage rates based on a 2004 national survey of children two, seven and 17 years of age indicate that 94% of two-year-olds had received at least one dose of the MMR vaccine, while 32% had received the varicella vaccine (the first year, the vaccine was offered as a publicly-funded vaccine in some but not all provinces). At age 7, 79% of children had received at least two doses of the MMR vaccine, while only 9% had received at least one dose of varicella vaccine. At the age of 17, 62% of adolescents had received at least two doses of the measles vaccine, while 93% had received at least one dose of the MMR vaccine but only 1% had received at least one dose of the varicella vaccine.

“One attractive strategy to improve vaccine coverage rates and reduce varicella disease is to use a combined MMR and varicella vaccine. A quadrivalent MMRV vaccine can facilitate universal vaccination against all four diseases by improving compliance and coverage rates for varicella vaccination, as well as reduce physician visits and the number of injections given to children,” Dr. Reisinger suggested. Such a combination exists and is expected to become available in Canada in the near future.

He explained that the quadrivalent vaccine, which contains the same varicella component as the commonly used varicella virus vaccine (live) (VVL) but at a higher dose, and the same components as MMR II, is as immunogenic as concomitant MMR II and VVL given separately and offers high protection from the first dose.

“In a multicentre study of 480 healthy 12- to 23-month-old infants randomized to the MMRV vaccine or MMR II plus [VVL], response rates were greater than 90% in both groups and antibody titres were equivalent,” Dr. Reisinger reported. “Other trials have demonstrated that the quadrivalent formulation can be administered as a second dose to four- to six-year-old children in place of MMR II and [VVL].”

There was no difference in injection site rashes, bruises, swelling or erythema between the treatment groups, but there was a statistically significant reduction in pain, tenderness and soreness in the quadrivalent vaccine-treated patients. The combination MMRV vaccine has been in use in the US since last year and is becoming the new standard approach for vaccination, which Dr. Reisinger characterized as a rapid development. The benefits are to decrease the number of injections in children and improve compliance. It is a convenient and effective alternative to separate MMR and varicella vaccines, Dr. Reisinger concluded.