Intussusception and Rotavirus Vaccines
The first licensed rotavirus vaccine, rhesus rotavirus reassortant tetravalent vaccine (RRV-TV, Rotashield, Wyeth Vaccines) was introduced into the US infant immunization schedule in October 1998. Reassortant vaccines use the segmented rotavirus genome to incorporate human rotavirus genes coding for surface proteins into the genome of animal rotavirus strains, which are rarely pathogenic to humans, creating an animal-human reassortant strain. RRV-TV was a mix of four rhesus-human reassortant strains, expressing human rotavirus G1-4 surface proteins. Prelicensure trials identified more intussusception cases in the RRV-TV arm compared with placebo, which was not statistically significant. However, intussusception was included as a potential adverse event after immunization in the product information. By March 1999, the US Vaccine Adverse Event Reporting Scheme (VAERS) had received 15 reports of intussusception. After initial examination, the Centre for Disease Control recommended suspending further vaccinations in July 1999 pending further investigations, with the manufacturer voluntarily ceasing distribution. After review of several investigations, the US Advisory Committee on Immunization Practices withdrew its recommendation that RRV-TV be administered at 2,4 and 6 months, because of a significantly raised association with intussusception, especially after the first dose. Case-control and case-series studies indicated the odds of intussusception cases having received a first dose of RRV-TV 3–7 days prior were as high as 37.2, with the risk period extending from 3 to 14 days postvaccination. (Table 1) This corresponded to an estimated excess of 1 additional case per 4670–9474 infants vaccinated, and risk appeared increased with administration of first dose after 3 months of age. However, ecologic studies suggested a much lower population attributable risk.
RRV-TV and Intussusception
The first licensed rotavirus vaccine, rhesus rotavirus reassortant tetravalent vaccine (RRV-TV, Rotashield, Wyeth Vaccines) was introduced into the US infant immunization schedule in October 1998. Reassortant vaccines use the segmented rotavirus genome to incorporate human rotavirus genes coding for surface proteins into the genome of animal rotavirus strains, which are rarely pathogenic to humans, creating an animal-human reassortant strain. RRV-TV was a mix of four rhesus-human reassortant strains, expressing human rotavirus G1-4 surface proteins. Prelicensure trials identified more intussusception cases in the RRV-TV arm compared with placebo, which was not statistically significant. However, intussusception was included as a potential adverse event after immunization in the product information. By March 1999, the US Vaccine Adverse Event Reporting Scheme (VAERS) had received 15 reports of intussusception. After initial examination, the Centre for Disease Control recommended suspending further vaccinations in July 1999 pending further investigations, with the manufacturer voluntarily ceasing distribution. After review of several investigations, the US Advisory Committee on Immunization Practices withdrew its recommendation that RRV-TV be administered at 2,4 and 6 months, because of a significantly raised association with intussusception, especially after the first dose. Case-control and case-series studies indicated the odds of intussusception cases having received a first dose of RRV-TV 3–7 days prior were as high as 37.2, with the risk period extending from 3 to 14 days postvaccination. (Table 1) This corresponded to an estimated excess of 1 additional case per 4670–9474 infants vaccinated, and risk appeared increased with administration of first dose after 3 months of age. However, ecologic studies suggested a much lower population attributable risk.
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