CDC trying to end confusion about live flu vaccine in health settings

SHEA study prompts change, but is it too problematic?

Moving to clear up the considerable confusion of the last flu season, the Centers for Disease Control and Prevention (CDC) has drafted new guidelines for health care workers who receive the live attenuated influenza vaccine (LAIV), Hospital Infection Control has learned. The CDC’s Advisory Committee on Immunization Practices (ACIP) is expected to soon release new guidelines that will allow the LAIV nasal spray vaccine to be used more liberally in health care settings with fewer restrictions on immunized workers.

Unlike the killed virus in the longstanding injected vaccine, LAIV contains weakened live influenza virus and is administered by nasal spray.

"The ACIP clearly is trying to assist hospitals in using both vaccines, but I think [LAIV] will cause hospitals some difficulties," says William Schaffner, MD, a liaison ACIP member and chairman of the department of preventive medicine at Vanderbilt University Medical Center in Nashville, TN. "I think we will see some hospitals trying to use the spray vaccine, and we will be very interested in their experience, but I don’t think it will be an overwhelming [number]."

Indeed, the debut of LAIV (FluMist, MedImmune Vaccines Inc., Gaithersburg, MD) during the 2003-2004 flu season was clouded by concerns that vaccinated health care workers could pose a theoretical risk to immunocompromised patients. Because LAIV uses a weakened live virus, recently immunized health care workers possibly could shed and transmit the live viral flu components of the vaccine to immunocompromised patients.

As the flu season neared last year, ACIP stated that the use of the traditional inactivated influenza vaccine is preferred for vaccinating health care workers based on the theoretical risk of LAIV transmission.1 However, the LAIV product label includes a more direct warning, stating: "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."

Faced with an infection threat to patients and an absence of clear public health guidelines, some hospitals erred on the side of caution and furloughed LAIV-immunized health care workers for up to three weeks. The 21-day period was based on studies of LAIV shedding in immunized children.

"Some hospitals were saying, Don’t come to work for three weeks,’ and asking visitors if they had received [LAIV]," says Tom Tolbert, MD, MPH, an infectious disease physician at Vanderbilt University Medical Center. "It was kind of ironic that people who had the common cold could come in and work with a mask, but if you had the vaccine, you couldn’t."

New study prompts change

Tolbert is the lead researcher of a recent study that directly resulted in the new CDC guidelines. As this issue went to press, he was slated to the present the study April 19, 2004, in Philadelphia at the annual conference of the Society for Healthcare Epidemiology of America. The findings were unveiled to ACIP at a meeting earlier this year. (See details of study under Legal liability trumps infection control.)

The data show health care workers who receive LAIV are unlikely to shed flu virus more than seven days after vaccination, meaning the 21-day furloughs are unnecessary.

"If you going to reduce the activities of health care workers, we think you could probably limit that to a week," Tolbert says. "In the first few days after vaccination with live flu vaccine in adults, [shedding] is fairly [common]. Half of the adults in our study shed. But by one week after that, that number was markedly reduced, and we did not find any evidence of shedding after day seven."

LAIV is indicated for prevention of influenza A and B in healthy children and adolescents (5-17) and healthy adults (18-49). 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.

"This is an attenuated virus. It is temperature sensitive, and it is not supposed to replicate in the lower respiratory tract," Tolbert says. "So in theory, if you were to transmit this virus, it should not cause disease. In actuality, you are almost secondarily vaccinating individuals. But the one caveat is that we don’t know if there is a chance that the attenuated virus could cause disease in an immunocompromised individual. There are people who think no’ and people who think yes.’"

In that regard, the new ACIP guidelines will stress that potential transmission from a recent vaccinee only poses a threat to the most severely immunocompromised patients.

"Those will be defined as being, for example, bone marrow transplant patients or hemapoietic stem cell transplant patients during the period when the immunosuppressed person requires care in a protected environment," says Jeff Stoddard, MD, MPH, senior director of MedImmune’s medical affairs influenza program.

"The health care workers in those units with those patients should preferentially be given the inactivated vaccine and not the live attenuated," he adds.

While the ACIP guidelines remain to be finalized, the draft version Stoddard has seen emphasizes the importance of flu vaccination for health care workers, he says.

"One thing that the new ACIP guidelines will say very clearly is that health care workers, first and foremost, need to be vaccinated against influenza," he says. "That was a point that got lost in the all the confusion last year. A lot of conscientious health care workers were surprised by how much focus there was on what one shouldn’t do in terms of immunization as opposed to what one should do."

In general, ACIP recommendations will express no preference between the inactivated vaccine and LAIV for most health care workers treating most patients, he says. Indeed, some see the arrival of the new vaccine as an opportunity to improve traditionally dismal levels of health care worker flu immunization.

"I think everyone on all sides of this debate would agree that health care workers need to improve their rate of immunization," Stoddard says. "Influenza is a major of cause of nosocomial infections and morbidity and mortality in many high-risk populations. The fact that so many health care workers in this country forgo immunization against this preventable disease is really a national disgrace. It needs to be rectified."

Devils and details

But while few would argue with that laudable goal, Schaffner finds a few devils in the details. For example, even if the furlough period can be safely reduced from 21 to seven days, the vaccine still presents logistical problems for hospitals, he notes.

"I believe the furlough issue will continue to pose difficulties," Schaffner says. "We’re in circumstances where hospitals are running on very tight budgets, and the notion of using a vaccine that will oblige a hospital to give a worker seven days off — or even if they arrange it around a weekend or whatever the call schedule is — it will present difficulties. It is still much easier to use the injectable vaccine."

Hospitals also must factor in that the mist vaccine is generally more expensive and the at-risk patient population remains somewhat nebulous, he adds.

"I think we will have, if you will, some [intense] discussions in hospitals about what severely immunocompromised’ means," Schaffner adds. "We understand bone marrow transplant patients. They have their own unit, but obviously people from other parts of the hospital go into that unit. So we will have to sort out who could or could not get the nasal spray vaccine based on that. Then there will be other clinicians who come forward with questions about other categories of immunocompromised patients — cancer patients at the nadir of their chemotherapy. Isn’t that comparable? There will be some HIV patients who are profoundly immunocompromised, and that question will come up. How can the ACIP distinguish between these patients?"

What about workers who receive LAIV from their own provider or visitors who have recently used the mist immunization?

"Hospitals dealt with that last year, and I think asking health care workers to tell their supervisor if they receive the spray vaccine will continue to be requested," he says. "I don’t know how much you can do about visitors in any practical sense."

Legal liability trumps infection control

That said, Schaffner thinks the likelihood of any actual transmission of vaccine virus to a patient is "infinitely small." The issue in many hospitals may be as much about legal liability as infection control.

"There remains the issue, which came up last year, about the distinction between the ACIP recommendations and what is stated in the package insert [the 21-day period]," he says. "For all of those reasons, plus cost, I believe that the injectable vaccine will continue to be the dominant vaccine used in the hospital environment. A few years from now when more experience [with LAIV] has accumulated, and if there is no evidence of transmission, then everyone may be a bit more relaxed about its use in the hospital setting."

A factor that gets somewhat lost within all the debate is that LAIV has not been primarily marketed to health care workers. "That has not necessarily been a targeted group," Stoddard says. "But certainly, we do feel that any vaccine that is licensed by the FDA to prevent influenza ought to be available to health care workers who are hoping to do the right thing and protect their patients."

Indeed, the needleless vaccine may have its greatest ultimate impact on children, a population the CDC is viewing with more concern regarding influenza. As of March 27, 2004, CDC had received reports of 142 influenza-associated deaths in U.S. residents age 18 and younger during the 2003-2004 season. There is accumulating evidence to suggest that immunizing greater numbers of children would not only protect the pediatric population but their adult high-risk contacts, Stoddard notes.

"Children over the age of 5 are on label [for LAIV]," he says. "We did our pivotal efficacy study in children down to 15 months, but we only got the label for kids over 5 years. That is because we need more data on the younger kids. We hope to have this vaccine licensed down to early infancy in the next couple of years."

But while it holds much potential to reduce the toll of annual flu, the "live" virus moniker has become something of a lightning rod.

"Unfortunately there are a lot of misconceptions about live, attenuated vaccines," Stoddard says. "People forget that polio was eradicated primarily through the use of live attenuated vaccines. People forget that every day pediatricians use four live attenuated vaccines in their patients: measles, mumps, rubella, and chickenpox."

And a couple of fairly staggering numbers may be lost in the minutiae as well: Every year, influenza hospitalizes 114,000 people and kills 36,000 in the United States.

"It is important to understand that influenza is the No. 1 vaccine preventable cause of death in this country," Stoddard points out. "It is one of the only communicable diseases that has not been brought under control despite having several tools in the armamentarium, including an inactivated vaccine."

Reference

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.