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Human rotavirus is widely recognized as the major etiological agent of serious acute gastroenteritis in infants and young children throughout the world (1). Although gastroenteritis is no longer a major cause of death in children in North America, this illness remains an important cause of morbidity in infants and young children (2,3). It accounts for approximately 30% to 50% of the cases of hospitalized diarrhea in paediatric patients in developed countries, and is a major cause of day care centre and nosocomially acquired diarrhea (4–6). While rotavirus infection can lead to profound disease and even death caused by severe dehydration and electrolyte imbalance (7), these are now relatively rare events in North America (2), particularly if early oral rehydration therapy is instituted (8). In contrast, deaths from rotaviral illness still remain an important problem in many parts of the less developed world.
The recognition that rotavirus is a leading cause of severe diarrhea in infants and young children has provided much impetus for rotavirus vaccine development. Initial attempts in the 1970s used monovalent vaccines from animal strains but clinical trials did not demonstrate sufficient efficacy to recommend routine use. More recently, polyvalent animal-human rotavirus reassortant oral vaccines that include human G or P proteins have been developed. These oral vaccines provide broader coverage against the prevalent human serotypes while still having low human pathogenicity. A tetravalent rhesus rotavirus vaccine (RV-TV) produced by Wyeth-Lederle is nearing the approval stage in the United States and Canada, and one from Pasteur-Merieux is well along in development. The RV-TV live oral vaccine has been evaluated in four large field trials including close to 10,000 children, which have been conducted in the United States, Venezuela and Finland (9–14). The RV-TV vaccine demonstrated 31% to 68% efficacy against any rotavirus diarrhea, 64% to 100% against doctor visits and a reduction in the duration of the diarrhea. The vaccine appears to be safe in normal healthy infants. The only significant side effect reported has been an increase in fever (higher than 38°C, 21% vaccine versus 6% placebo; higher than 39°C, 2% versus 1%) on day 3 to 4 after the receipt of the vaccine, especially with the first dose. Data on safety in immunocompromised infants are not available.
A number of questions arise about the timeliness and impact of any universal rotavirus vaccine program in Canada. Clearly, a universal rotavirus vaccine program in less developed countries where deaths due to rotavirus are still of major concern would save lives if the efficacy is high (15). In Canada, a universal program is unlikely to save many lives given the current low mortality rate but it could decrease morbidity by decreasing rotavirus hospital admissions for severe diarrhea. Currently, at the Children’s Hospital of Eastern Ontario, which cares for all children who require hospital admission in the region, rotavirus infection accounts for only 0.4% of patients admitted in July 1996 to June 1997, a very low proportion. A universal program would only halve the rate of milder disease that does not require admission. Because rotavirus causes 50% or less of all viral gastroenteritis in infants and young children (16), the public and parental perception may well be that the vaccine is of little benefit in ‘controlling’ infant diarrhea overall. Thus, if a universal infant rotavirus vaccine program is recommended, the recommendation will need to be based upon careful cost-benefit analyses using current Canadian data on rotavirus hospitalization and out-patient morbidity. Furthermore, these analyses must be reviewed against the impact of spending a similar amount of money on parental education programs about oral rehydration therapy, therapy that could benefit all infants with viral gastroenteritis regardless of the viral etiology. If a universal program is not considered cost effective, data must also be closely scrutinized to determine whether there are subgroups or sub-populations at higher risk for significant morbidity for whom a targeted vaccine program might be beneficial, eg, populations remote from medical services. If data support either a universal or targeted rotavirus immunization program, the program will need to be accompanied by a strong physician and parent education campaign to prevent unrealistic expectations of the benefits of the vaccine if the vaccine is to succeed and be perceived as helpful.
Reviewed by the Canadian Paediatric Society Board of Directors