PEDIATRICS Vol. 108 No. 1 July 2001, pp. 220

The Rotavirus Vaccine Story

To the Editor.

Dr Margaret Rennels' defense of the current vaccine licensure procedure ("The Rotavirus Vaccine Story: A Clinical Investigator's View," Pediatrics. 2000;106:123-125) is very compelling and well-reasoned in regard to the association of intussusception with administration of the rotavirus vaccine. What Dr Rennels does not discuss, however, are the other significant problems that were associated with this vaccine that led many physicians to recommend to parents that the vaccine not be given, well before the association with intussusception became known. These problems included the high incidence of fever >102°F after vaccination and the short duration of immunity after vaccination. These problems were well-known before the vaccine was licensed, yet the American Academy of Pediatrics (AAP) made very strong statements in favor of the vaccine with the clear implication that physicians who did not administer the vaccine would be negligent in their care of infants. There was a great deal of debate in my practice group about the wisdom of giving this vaccine, given the very real possibility that we would be hospitalizing many 2-month-old infants for septic work-ups after rotavirus vaccination with the accompanying anxiety for parents, unnecessary morbidity for the child, and unnecessary hospitalization costs. We also felt that the cost of the vaccine was excessive and that the short duration of immunity would make it even less appealing to parents. We decided to give parents the option of giving the vaccine after informing them of its risks and benefits. Given this information, most parents declined to have the vaccine given to their infants. In contrast, the recent introduction of the Prevnar pneumococcal vaccine has been extremely successful in our practice, primarily because we felt confident, based on the scientific data, that the vaccine was both safe and efficacious.

The real lesson to be learned from the rotavirus vaccine debacle is that those involved in vaccine licensure must consider all the associated problems with a vaccine before rushing to push it onto our patients and their families. Dismissing the concerns of the primary care physicians in regard to this vaccine's propensity to cause high fever and its poor induction of long-term immunity were major mistakes by both the Advisory Committee on Immunization Practices (ACIP) and the AAP.

Jennifer White Gobel, MD, FAAP
Ramsey Clinic Pediatrics
St Paul, MN 55104

In Reply.

Dr Gobel's kind words regarding what was discussed in the article "The Rotavirus Vaccine Story: A Clinical Investigator's View" are appreciated. The article was intended by Dr Rennels only to discuss the association of the Rotashield vaccine with intussusception. However, it is important to address Dr Gobel's questioning why the vaccine was recommended when it was known to be associated with high fever and diminished protection the second year after vaccination. Dr Rennels was not a member of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention or the Committee on Infectious Diseases (COID) of the American Academy of Pediatrics (AAP) when the recommendation for the use of Rotashield was made. This letter is therefore authored by the current chairs of both of those committees, in collaboration with Dr Rennels. The ACIP and the COID did carefully consider both of the issues raised by Dr Gobel and concluded that the potential benefits of routine vaccination outweighed the risk of febrile reactions. The data upon which the decision was reached are as follows:

Rotavirus causes considerable morbidity throughout the world because it infects virtually all children, regardless of race, socioeconomic status, or geographic location. Every year in the United States alone, that results in an estimated 410 000 physician visits, 160 000 emergency department visits, 50 000 hospitalizations, and 20 to 40 deaths. It was against these statistics that the febrile reactions from the vaccine were considered.

Moderately high rates of febrile reactions were experienced in Finnish infants, but that was not the experience with US children. The rates of excess fever 39°C (102.2°F) in vaccinees versus placebo recipients in the 2 US studies utilizing rectal temperature measurements were 1% and 1.6%. This is within the range of high fevers attributed to other licensed vaccines. For example, fever >39°C was experienced by 1.2% of children given only the conjugate pneumococcal vaccine Prevnar.² There was concern that even these rates of fever from Rotashield might translate into increased "sepsis work-ups." Thus, the number of medical visits and hospitalizations in the postvaccination period were compared between vaccinees and placebo recipients. Those data were presented publicly to the Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration. There was no significant increase in the rate of all hospitalizations or of hospitalizations for fever in the postvaccination period among vaccinees versus placebo recipients. There was some increase in community health center visits by Finnish children. However, in the US studies there was no significant excess of outpatient medical visits by the vaccinated children. It was concluded from these data that there was no evidence that the febrile reactions would significantly detract from the overall benefits of the vaccine.

Dr Gobel is correct in pointing out that the efficacy of the rotavirus vaccine was lower the second year after vaccination. The efficacy against mild disease was only modest in either the first or second year after vaccination. However, the goal of rotavirus immunization was to protect infants and young children against severe, dehydrating disease. The vaccine was quite effective in preventing clinically significant disease, even the second season after immunization. In the Finnish study, protection against severe rotavirus gastroenteritis was 95% in year 1 and 90% in year 2 postvaccination.³ Unfortunately the US evaluations did not address protection against serious disease over a 2-year period.

The data on the risk-benefit ratio of the Rotashield vaccine was extensively scrutinized by both the ACIP and the COID before recommendations for its use were issued. Reasonable people may disagree with the recommendations, but those involved in the decision painstakingly evaluated all of the available safety and efficacy data.

Margaret Rennels, MD
Member, Advisory Committee on Immunization Practices and Committee on Infectious Diseases

Jon Abramson, MD
Chair, Committee on Infectious Diseases

John Modlin, MD
Chair, Advisory Committee on Immunization Practices

REFERENCES

1. American Academy of Pediatrics, Committee on Infectious Diseases Prevention of rotavirus disease: guidelines for use of rotavirus vaccine. Pediatrics. 1998; 102:1483-1491 [Abstract/Free Full Text]
2. Overturf GD, and the American Academy of Pediatrics, Committee on Infectious Diseases Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis. Pediatrics. 2000; 106:367-376 [Abstract/Free Full Text]
3. Joensuu J, Koskenniemi E, Pang X-L, Vesikari T Randomized placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis. Lancet. 1997; 350:1205-1210 [CrossRef][Medline]