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Flu mystified: Hospitals are in a fog of live viral vaccine issues
New FluMist vaccine raises liability concerns
Faced with an infection threat to immunocompromised patients and an absence of clear public health guidelines, some hospitals are furloughing health care workers who receive the new live attenuated influenza vaccine (LAIV), Hospital Infection Control has learned.
"Hospitals are doing draconian things in my part of the country," says Dennis Maki, MD, chief of infectious diseases at the University of Wisconsin Hospital and Clinics in Madison. "Some of the hospitals have put in policies that if any health care worker gets [LAIV], they must have a 21-day unpaid vacation. I think that’s crazy."
LAIV is a newly licensed influenza vaccine for the 2003-2004 flu season (brand name FluMist, MedImmune Vaccines Inc., Gaithersburg, MD). The product is indicated for prevention of influenza A and B in healthy children and adolescents (5-17) and healthy adults (18-49).
While few doses of the standard killed virus remain, there are some 4 million doses left of FluMist.
Unlike the killed virus in the longstanding injected vaccine, LAIV contains weakened live influenza virus and is administered by nasal spray. LAIV contains three distinct influenza viral strains. When the viruses in LAIV are sprayed into the nose, they stimulate the immune system to develop protective antibodies that will prevent infection by the naturally occurring influenza viruses. Cold-adapted and temperature-sensitive, LAIV viruses grow in the nose and throat rather than in the lower respiratory tract where the temperature is higher.
The concern for hospitals is that recently immunized health care workers possibly could shed and transmit the live viral flu components of the vaccine to immunocompromised patients. How long that shedding and possible transmission could occur after receiving LAIV is one of the areas of contention.
It is no small irony that health care workers immunized for flu actually are causing problems for hospitals, which have been trying to get them vaccinated with little success for years. The original concept was that health care workers who care for immunocompromised patients should not receive the live vaccine, but that message was apparently not delivered strongly enough to head off the controversy.
As the flu season neared, the Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) recommended that use of the traditional inactivated influenza vaccine is "preferred" for vaccinating health care workers based on the "theoretical risk" of LAIV transmission.1
The root of the current troubles is apparent when contrasting that cautiously worded recommendation with the more direct warning in the product label: "As with other live virus vaccines, FluMist should not be administered to individuals with known or suspected immune deficiency diseases. . . . Due to the possible transmission of vaccine virus, vaccine recipients or their parents/ guardians should be advised to avoid close contact (e.g., within the same household) with immunocompromised individuals for at least 21 days."
However, the label doesn’t cite health care workers specifically, and there are no data explicitly on the risks of nosocomial transmission of LAIV from immunized providers to patients. Throw in some issued and then retracted guidance from the CDC regarding immunized health care workers, and the LAIV situation was thoroughly beset with confusion and questions as this issue of HIC went to press.
"It is recommended that [LAIV] not be used by health care workers, because people do not want to have a live attenuated virus transmitted to immune-compromised patients," says William Schaffner, MD, chairman of the department of preventive medicine at Vanderbilt University Medical Center in Nashville.
"But there are several problems. No. 1, some health care workers who didn’t get the word or chose to ignore it went out and got [LAIV] somewhere else — not in the hospital — and then went back to work. The question is what do you do with them? No. 2, there are some patients who are admitted, and it turns out in the last seven days or so they have had LAIV. If so, do they have to be put on some type of respiratory isolation? No. 3 is the [recently immunized] visitor. These issues are really perplexing and bedeviling hospitals out there," he points out.
CDC removes recommendations from web
The CDC attempted to address such concerns in guidance posted from Oct. 31 through Nov. 4 on its influenza web site (www.cdc.gov/ncidod/diseases/flu/index.htm). The agency cited data that showed the maximum duration of live vaccine virus shedding in immunized adults was six days. The CDC stated at that time that for a "seven-day period after having received LAIV, it would be prudent for health care workers to avoid close contact with patients known to have severe immunosuppression (e.g., bone marrow transplant recipients). It is anticipated that incidental or brief contact between LAIV recipients and immunocompromised people sometimes can occur inside and outside of hospital or other medical settings.
Nonetheless, it also is likely that the risk of LAIV virus transmission during such encounters is low. In addition, all health care workers should practice good hygiene by washing their hands frequently, and covering their mouths and noses when sneezing or coughing," the CDC stated. However, it must be reiterated that the CDC then removed the recommendation for further review of the issue.
"The 21-day [label] criteria came out of the Food and Drug Administration (FDA) and the package insert based on a childhood study of shedding with this FluMist brand," says Scott Harper, MD, medical epidemiologist in the CDC influenza branch.
"The FDA, of course, always takes a very conservative tack, and we don’t have data in adults with this particular vaccine. That is one reason why it has been complicated. Originally on the CDC site, it did say seven days — based on the data that we had — but after a couple of days of talking with FDA we decided to take that down. There are further discussions going on with the FDA and the company; so at the present time, CDC does not actually have an official recommendation," he adds.
In the interim, the CDC has referred clinicians back to the ACIP statement, essentially discouraging health care workers from taking the live vaccine in the first place. "The CDC [position is] that the specific group of health care workers that has contact with immunosuppressed patients should get [the regular] inactivated vaccine," Harper says. "But there have been many, many calls about what happens if they go ahead and get [LAIV] anyway. What about visitors to hospitals and all of these other issues? It has been contentious."
Part of the problem appears to be lack of data, particularly in the area of transmission of the live vaccine. "The data on the transmissibility of LAIV are meager," Schaffner says. "They come from studies in day-care centers. There is not much transmission, but kids put out more virus than adults, and it is easier to infect kids than adults."
According to ACIP, studies show that vaccinated immunocompetent children can shed vaccine viruses for up to 21 days.2 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.3
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.
While transmission occurred, the thinking is that adults (read health care workers) do not shed the virus as long as children, thus caregivers may not pose a threat to patients for the full 21 days extrapolated from the pediatric data. The problem is lack of data to justify that position, but the CDC is trying to rectify that situation.
"There are data in adults in previous versions of this vaccine," Harper adds. "[We] are poring through trying to get those data now."
Hospitals left hanging
Meanwhile, back at the hospital, the frustrated epidemiologist struggles to hammer out some reasonable policy for an issue complicated by looming liability, staffing woes, and patient safety concerns.
"It has left hospitals hanging," Maki says. "I’m disappointed that [the CDC] has not given more guidance on this issue."
Yet hospitals may be taking such measures as furloughing, because the product label opens them to possible liability if they allow vaccinated workers to stay on the job. Such a label warning makes hospitals and their attorneys "very nervous" about liability issues if a patient were to become infected by an immunized worker, says Schaffner.
While acknowledging the clear liability concerns, Maki says the issue of visitors reduces the whole problem to a kind of paradox. "Visitors who may have had [LAIV] are going to have to contact with patients — their family members at the minimum," he explains. "That is totally ignored. If this genuinely poses a risk, then just focusing on health care workers is not enough. But if we are not worried about visitors, it’s probably not necessary to be all that worried about health care workers."
Faced with the 21-day furlough issue at his hospital, Maki successfully argued for a policy that discourages workers to use the vaccine but allows them to work in masks and gloves if they are immunized with LAIV.
"I fought it pretty hard," he says. "I don’t think those [furloughs] are justified based on available data. The viral shedding appears to be pretty minimal. There are no data to suggest that LAIV poses a risk to immunocompromised [patients]. If it does, then why did the FDA approve it? Putting that boxed warning [on the label] has really put hospitals in a dilemma."
1. 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.
2. 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.
3. 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.