Report of the Rotavirus Vaccine and Intussusception Working Group
Findings of the National Vaccine Advisory Committee/National Vaccine Program Office Workshop (September 5-7, 2001) on the association of Rhesus Rotavirus Vaccine-Tetravalent (RRV-TV) with intussusception were presented.
- The rate of intussusception in the US appears to have declined during the past decade, and this was occurring prior to the use of the rotavirus vaccine.
- Six studies1 (four published) were reviewed. All studies agree that there is a strong association with RRV-TV and intussusception three to seven days post vaccine dose one and two. The overall risk is approximately 1:10,000 after the first dose of vaccine. Intussusception rates vary geographically. One ecologic study2 suggested that the risk of intussusception following RRV-TV was shifted to an earlier age, but overall the risk during infancy was not increased, though some experts believe this study has major limitations. Most studies have shown no association between natural rotavirus disease and intussusception.
- A lamb-derived rotavirus vaccine is currently being use in China.
The ACIP decided that more time is needed to further evaluate available information, and will decide at the February 2002 meeting as to whether or not it wants to reverse its previous decision to not recommend the rotavirus vaccine in the US.
Influenza Vaccine-Related Issues
An Influenza Working Group meeting was held on September 10-11, 2001. One new finding in favor of increased utilization of an influenza vaccine in children is that the rate of febrile seizures is higher in children with influenza than with other respiratory virus infections. Also, the hospitalization rate for otherwise healthy children is highest in the 0-1 year age group, and higher in the first six months of life than in the second six months. High-risk children have a higher incidence rate of hospitalization (two to four times that of otherwise healthy children). In children younger than three years influenza accounts for 35% of excess outpatient department visits. There is a higher incidence of acute otitis media (AOM) in unvaccinated children.3 Day care studies showed that the incidence of AOM was less among children who received the cold-adapted influenza vaccine.4 No serious adverse events were recognized in four randomized controlled trials5 using trivalent inactivated influenza vaccine and live attenuated influenza vaccines; the trivalent inactivated vaccine proved to be more efficacious in older children. Among five published studies reviewed it appears to be more efficient economically to vaccinate high-risk children. Additional cost studies are pending.
The ACIP will reconsider this issue at its February 2002 meeting to decide whether to go forward with a universal recommendation or a staged recommendation, first encouraging administration of influenza vaccination for those younger than two years of age, and later encouraging more inclusive administration.
Hepatitis B Vaccine
The ACIP discussed whether or not to recommend a preference for giving the first dose of the hepatitis B vaccine soon after birth, and before hospital discharge, while continuing to allow physicians to wait up until two months of age to administer the first dose. The committee decided in favor of stating a preference for administration of the initial dose soon after birth and prior to hospital discharge for infants of hepatitis B surface-antigen negative mothers.
Also, the weight or age at which a premature infant born to a mother known to be HBsAg negative should receive the first dose of the hepatitis B vaccine is under ACIP review. Currently, the recommendation for preterm infants weighing < 2 kg at birth is to wait until the infant is two months of age when other routine immunizations are given. The ACIP will consider reducing the age to one month.
Oral Polio Vaccine (OPV) Use for Outbreak Control
Possible methods for controlling a polio outbreak in the US were discussed. There was general agreement that OPV would be the preferred vaccine for use in the event of an outbreak, and the CDC is working with manufacturers and the FDA toward the development of a stockpile of OPV. IPV could be used while waiting for the availability of OPV. The use of monovalent vaccine could be considered when the serotype of the causative virus is known, although available lots of vaccine may be all trivalent vaccine. Because of the higher risk of vaccine-associated paralytic polio in adults, informed consent would be required before administering OPV to adults.
Thimerosal: Institute of Medicine (IOM) Report and Status of Vaccines Containing Thimerosal
As one part of an Immunization Safety Review Project, the IOM Immunization Safety Review Committee reviewed the safety of thimerosal-containing vaccines. The committee concluded that although there is no evidence that thimerosal-containing vaccines have affected the nervous system of recipients, the evidence is inadequate to prove or reject the biologic plausibility of neurodevelopmental disorders caused by the administration of thimerosal-containing vaccines. The IOM recommends the use of thimerosal-free vaccines, and not thimerosal-containing vaccines. There is no evidence that single dose vaccines without thimerosal cause harm, although multiple dose vials of vaccine with preservatives other than thimerosal could prove harmful if sterility of the vaccine is not maintained.
Except for influenza vaccines, no thimerosal-containing vaccines are being distributed by US manufacturers. GlaxoSmithKline announced a “voluntary exchange program” where they will exchange thimerosal-containing vaccines for thimerosal-free vaccines and a similar arrangement is under consideration by other vaccine manufacturers.
A recent survey of 225 private immunization sites located in 16 states showed that 5.5% of vaccine doses contained thimerosal, the greatest numbers of which were DTaP-Hib and DTaP. There are shortages of DTaP vaccine in some areas which may not be correctable by the end of 2001. There has been an increasing backorder of DTaP; a number of central vaccine depot sites have been out of DTaP and 50% of the sites have had significant shortages. If an immediate cessation of the use of all thimerosal-containing vaccines remaining in physicians’ offices were implemented, national shortages would be even greater. A joint statement6 issued by the AAP, AAFP, ACIP, and the USPHS on June 22, 2000 reviewed the progress to that date made in removing
thimerosal as a preservative from vaccines. This statement again noted that there was no substantial evidence of harm caused by low levels of thimerosal in vaccines and the risk was only theoretical. The statement also noted that great progress had been made to reaching the goal of removing thimerosal as a preservative in routinely recommended childhood vaccines.
Shortages of thimerosal-free vaccines should be alleviated as soon as possible to eliminate the theoretical risk of harm. Thimerosal-containing vaccines being phased out continue to be considered safe and effective.
Rubella Vaccine and Pregnancy
Current ACIP and AAP recommendations7 are that women should avoid conception for three months following receipt of the rubella vaccine. This recommendation is based on finding vaccine virus in the eye of one aborted fetus conceived seven weeks after vaccination with an older version of the rubella vaccine. With the current rubella vaccine (RA/7), viremia is cleared by 21 days (usually within 7-11 days) after vaccine administration. Available data show that none of 419 rubella-susceptible pregnant women in the US who were inadvertently vaccinated with RA/7 vaccine had infants with evidence of congenital rubella syndrome (CRS). One hundred fifty-seven women were vaccinated in the first three months of pregnancy without evidence of CRS among their offspring. Canada and the UK implemented the policy to avoid rubella vaccination for one month prior to conception ten years ago and have seen no CRS. The ACIP voted to change its policy to reflect the time interval to avoid conception for one month following receipt of the rubella vaccine.
Pneumococcal Conjugate Vaccine (PCV7)
Preliminary data suggest reduction in vaccine-serotype-related invasive disease (~ 21% in those younger than two years of age in the year 2000) as compared to the number of cases in 1998-1999. This represents a sharp reduction in invasive disease caused by serotypes in the vaccine, with no specific evidence of reduction in other serotypes. A measurable reduction of invasive disease caused by serotypes contained in the vaccine is increasing with time, with a 40% reduction in the latter half of last year.
Additional surveillance studies are being planned to further examine the impact of PCV7 and to examine risk factors for vaccine failure. Demand for this vaccine is high (~ 1.5 million doses per month). There are widespread shortages (50% of central vaccine storage depots have < a 15 day supply on hand and 10% have no vaccine). Recommendations published in a September 2001 MMWR8 were based on supposition that shortages would be resolved by November 2001, and were not ACIP guidelines. Unfortunately, it now appears that shortages will persist into the second quarter of 2002. Shortages are approximately 50/50 for the public and private sectors.
The ACIP will reconstitute a Pneumococcal Conjugate Vaccine Workgroup to review the PCV7 shortage and consider alternative strategies, with possible revision of guidelines as to how available vaccine best be utilized, with expedient publication anticipated.
Varicella-Zoster Virus Vaccine Update
Beginning in March 1995, Merck & Co., Inc., began to manage a pregnancy registry in conjunction with the Centers for Disease Control and Prevention for varicella vaccine, to assess the risks of congenital varicella syndrome and other birth defects in infants of women who inadvertently received varicella vaccine during pregnancy or within 3 months of conception. No abnormal features have been reported that suggested the occurrence of congenital varicella syndrome or other birth defects related to maternal vaccine exposure during pregnancy among the offspring of 412 pregnant women, 97 of whom were seronegative at the time of receipt of the vaccine. The registry is being continued.9
The incidence of varicella infection continues to decrease in the US. Comparing 1995 to 2000, the infection rate decrease appears to be approximately 80% with a substantial decrease in varicella-related hospitalizations. Although the incidence of zoster infection has not increased over the past five years, it is too early to tell if the incidence has decreased. During investigations of various varicella outbreaks, significant factors associated with vaccine failure include systemic steroid exposure at the time of breakthrough disease or shortly before, most often administered for asthma; and MMR given within 30 days of varicella vaccination. When MMR and varicella vaccine were administered simultaneously there was no decrease in effectiveness. Inhalational steroid exposure was not found to be a risk factor.10
Centers for Disease Control. (1991). Hepatitis B virus: A comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: Recommendations of the Immunization Practices Advisory Committee (ACIP). Morbidity and Mortality Weekly Report, 40(RR-13),1-25.
Centers for Disease Control and Prevention (CDC). (1999). Prevention of varicella: Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, 48(RR-06),1-5. Available online: www.cdc.gov/mmwr/preview/mmwrhtml/rr4806a1.htm
CDC. (1999). Withdrawal of rotavirus vaccine recommendation. Journal of the American Medical Association, 282(22), 2113.
CDC.(2000). Preventing pneumococcal disease among infants and young children: Recommendations of the Advisory Committee on Immunization Practices. Morbidity and Mortality Weekly Report, 49(RR-9),1-29. Available online: www.cdc.gov/mmwr/preview/mmwrhtml/rr4909a1.htm
CDC. (2001). Impact of the 1999 AAP/USPHS joint statement on thimerosal in vaccines on infant hepatitis B vaccination practices. Morbidity and Mortality Weekly Report, 50(46), 94-97. Available online: www.cdc.gov/mmwr/preview/mmwrhtml/mm5006a3.htm
CDC. (2001). Prevention and Control of Influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, 50(RR-04), 1-46. Available online: www.cdc.gov/mmwr/preview/mmwrhtml/rr5004a1.htm