In a subsequent open-label study that included 382 infants in 37 states, BIG-IV treatment within 3 days of admission significantly shortened mean length of hospital stay, compared with treatment within 4–7 days of admission: 2.0 vs. 2.9 weeks (N. Engl. J. Med. 2006; 354:462–71).
Rotavirus Vaccine
Two phase III trials of live, attenuated rotavirus vaccines for severe rotavirus gastroenteritis were among this year's most important pediatric infectious disease studies, said Dr. Englund. The vaccines—an oral pentavalent human-bovine reassortant rotavirus vaccine (RotaTeq) and a two-dose oral monovalent human rotavirus vaccine (Rotarix)—were independently studied in large, multicenter trials that included more than 60,000 children each (N. Engl. J. Med. 2006; 354:11–22; N. Engl. J. Med. 2006;354:23–33). Compared with placebo, both vaccines demonstrated significant efficacy in reducing severe gastroenteritis and hospital admissions associated with rotavirus, and both reduced all diarrhea-associated hospital admissions by approximately half, which suggested that a high proportion of the diarrhea-associated admissions in the study areas were linked to rotavirus, noted Dr. Englund.
Both vaccines also had good safety profiles. In particular, there was no evidence of an increased intussusception risk following vaccine administration as had been reported with the first-generation rotavirus vaccine (RotaShield) that was on the market in the late 1990s.
Perhaps the most important outcome of both of these studies “is that they set the standard now for what all vaccine manufacturers are going to do or have the ability to do in the future,” said Dr. Englund.
As a result of the positive data coming out of these large trials, the Advisory Committee on Immunization Practices (ACIP) issued a recommendation in the summer of 2006 that all U.S. infants be immunized against rotavirus with three doses of the already Food and Drug Administration-approved RotaTeq vaccine, administered at 2, 4, and 6 months.
Because the rotavirus burden is highest in underdeveloped countries, “efforts should be made to conduct clinical trials in these regions and to determine ways to pay for the vaccine, which is relatively expensive,” Dr. Englund noted. “Such efforts are worthwhile considering the vaccine has the potential to prevent 5% of childhood deaths worldwide.”
Mumps Vaccination Update
Mumps also made its way into the infectious disease news this year. In response to outbreaks of the disease in early 2006 in the Midwestern United States, the ACIP updated its 1998 criteria for mumps immunity and mumps vaccination recommendations. Among the key changes, Dr. St. Geme noted, were the criteria for acceptable presumptive evidence of immunity for school-age children and adults at high risk, including those who work in health care facilities, international travelers, and college students. “Previously, documentation of adequate vaccination for these populations was one dose of a live mumps virus vaccine; now it's two doses,” he said.
Also, routine vaccination with two doses of a live mumps virus vaccine is recommended for health care workers born during or after 1957 without other evidence of immunity. One dose is recommended for health care workers born before 1957 without other evidence of immunity. In outbreak settings, a second dose of a live mumps virus vaccine should be considered for children ages 1–4 years and adults at low risk, within a 28-day interval. For health care workers born before 1957 without other evidence of immunity, two doses should be seriously considered (MMWR 2006;55:1–2).
Live Attenuated Influenza Virus Vaccine
The theoretical potential of secondary transmission of influenza has been a concern related to the use of the live attenuated influenza virus vaccine (FluMist). In previous studies, shedding of vaccine viruses has not been associated with viral transmission to close contacts.
In an effort to estimate the probability of transmission in a “worst-case scenario,” Dr. Timo Vesikari of the University of Tampere (Finland) and colleagues conducted a trial in a day care setting, said Dr. Englund. “This study was designed by the authors to maximize opportunity for transmission by including young children without immunity and without prior exposure or minimum exposure to influenza in a close-contact setting,” she said.
The study included 197 children between 9–36 months of age from 52 different day care center rooms who were randomized 1:1 to receive the vaccine or placebo. Nasal swabs were taken at regular intervals to determine postvaccination viral shedding, genotype and phenotype of shed viruses, and the probability of secondary transmission of the vaccine influenza strains (Pediatr. Infect. Dis. J. 2006; 25:590–5).
Of the 98 children who received the vaccine, 80% shed at least one vaccine influenza strain. All of the vaccine virus isolates retained their cold adaptation and temperature sensitivity characteristics. There was one confirmed transmission of a vaccine strain to a placebo recipient, but the child did not exhibit any signs or symptoms of clinically significant influenza. The probability of secondary transmission of influenza from one vaccinated child was calculated to be approximately 0.58%.