Vanderbilt study changes CDC flu vaccine guidance

No live viral shedding after seven days

Shedding of virus after use of live attenuated influenza vaccine (LAIV) in adults occurs the first few days after vaccination, but is minimal by one week after immunization. The data suggest that the recommendations for LAIV use in health care workers could be modified to include separation from patients for, at most, seven days after vaccination, reports Tom Tolbert, MD, MPH, instructor of medicine in the division of infectious diseases at Vanderbilt University Medical Center in Nashville, TN.

Following intranasal vaccination with LAIV, nasal wash samples were collected in adult volunteers at baseline and at four points after vaccination (on days 3, 7, 10, and between days 17-21 post-vaccination).1 Specimens were inoculated for cell culture and read at regular intervals for cytopathic effect as well as hemadsorption. Positive specimens underwent indirect immunofluorescence assay testing to determine the strain of influenza (A or B) isolated.

Overall, 20 adults underwent nasal wash sampling following LAIV vaccination. No samples were positive for influenza at baseline. Post-
vaccination, influenza was recovered from 50% (10/20) of specimens on day 3; 5.5% (1/18) of available specimens on day 7, and from none of the specimens from day 10 (0/19) or days 17-21 (0/20).

"Half the group shed at three days post-vaccination," Tolbert tells Hospital Infection Control. "But by seven days, we only had one of 18 volunteers shed. [Two subjects missed that visit.] No one shed on days after that at day 10 and at three weeks. There are obviously some limitations. It is a small number, and we were enrolling at a time when there was [wild] influenza [circulating]. But we feel pretty good that all of the influenza that we captured was really actual vaccine influenza."

The specific influenza strain detected varied, with 3/11 (27%) cultures positive for influenza A alone, 5/11 (45%) positive for influenza B alone, and 3/11 (27%) positive for both influenza A and B strains. People with a positive nasal wash culture were significantly younger than those who did not shed (mean age 26.4 years in those with a positive culture vs. 38.6 years in those without shedding). A greater proportion of those who did not shed vaccine virus reported influenza vaccination in prior years; 3/10 (30%) who shed vaccine virus had prior vaccination, while 8/10 (80%) without shedding had prior vaccination.

The actual amount of live viral shedding could not be determined in the lab arm of the study. "That is probably the one piece of data that it is unfortunate that we don’t have," he says.

"Especially that person who shed out to day 7 — did they have a higher degree [as opposed to duration] of shedding? The one person who shed on day 7 also shed on day 3, so we had 10 of our 20 people who shed at some point," Tolbert explains.

One thought is that older adults may shed less because they have been exposed to more wild influenza and previous vaccine. "There may be a sense that if you have had prior flu vaccination, you’re risk of shedding is less; but I don’t think we can truly say that because it was not statistically significant," Tolbert says.

According to the Centers for Disease Control and Prevention (CDC), studies show vaccinated immunocompetent children can shed vaccine viruses for up to 21 days.2,3 The CDC also cites data in a child-care center setting that assessed transmissibility of vaccine viruses from 98 vaccinated to 99 unvaccinated subjects, all ages 8 to 36 months. Eighty percent of vaccine recipients shed at least one viral strain, with a mean of 7.6 days duration.4

One influenza type B isolate was recovered from a placebo recipient and was confirmed to be vaccine-type virus. The estimated probability of acquiring vaccine virus after close contact with a single LAIV recipient was 0.58% to 2.4%. The type B isolate retained the cold-adapted, temperature-sensitive, attenuated phenotype, and it possessed the same genetic sequence as a virus shed from a vaccine recipient in the same children’s play group.

References

1. Talbot TR, Crocker DD, Peters J, et al. Degree and duration of mucosal shedding following use of the trivalent intranasal live attenuated influenza vaccine in adults. Presented at the Society for Healthcare Epidemiology of America. Philadelphia; April 17-20, 2004.

2. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices. Using live, attenuated influenza vaccine for prevention and control of influenza. MMWR 2003; 52(RR13):1-8.

3. Clements ML, Stephens I. "New and Improved Vaccines Against Influenza." In: Levine MM, Woodrow GC, Kasper JB, et al., eds. New Generation Vaccines. New York City: Marcel Dekker Inc.; 1997, pp. 645-670.

4. Vesikari T, et al. Randomized, double-blind, placebo-controlled trial of the safety, transmissibility, and phenotypic stability of a live, attenuated, cold-adapted influenza virus vaccine (CAIV-T) in children attending day care [Abstract G-450]. Presented at the 41st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Chicago; 2001.