August 2003

---Philip A. Brunell, MD

The respiratory virus season for 2003-2004 may prove to be a very interesting one. We may have one totally new player, severe acute respiratory syndrome-associated coronavirus (SARS-CoV), together with respiratory syncytial virus (RSV), influenza, human metapneumovirus (hMPV) and the usual “other respiratory viruses.” There are new Red Book recommendations for passive immunization against RSV and a new live-attenuated intranasal vaccine against influenza.

Jon Abramson, MD, the outgoing chair of the Red Book Committee, made an excellent presentation at the Infectious Diseases in Children Symposium West on the new recommendations for passive immunization against RSV. Palivizumab (Synagis, MedImmune) now is recommended for use in certain children with cardiac disease. The initial studies using the IV preparation suggested that these patients might fare worse than placebo recipients. More recent data using the hybridized human monoclonal palivizumab have demonstrated that recipients have decreased hospital days and oxygen requirements compared with controls. Specifically, the preparation is recommended for patients with moderate or severe pulmonary hypertension, cyanotic heart disease and those being treated for heart failure.

Whether to immunize the group of infants in the 32 to 35 week gestation category is a call the practitioner will still have to make. This is probably the largest group of infants for whom passive immunization may be considered. Collectively, they account for a considerable number of hospitalizations. Clinicians are advised to consider risk factors, eg, smoking in the household, day care attendance, older siblings in the household and other medical conditions in making a decision about whether or not to passively immunize.

The other major news is the licensure of a live-attenuated influenza vaccine that is administered intranasally (FluMist, MedImmune, Wyeth). This has been approved for children 5 years of age and older and for those up to 49 years of age. Unfortunately, this licensure could not be extended downward to the younger age group because of the concern about increased asthma attacks post-immunization in these younger vaccinees. It is this youngest group, along with the elderly, that suffers the greatest morbidity from influenza. It is of interest to revisit the pandemic of 1917-1919 when this was clearly apparent (see figure).

The vaccine does not need to be given by injection and may provide better and longer lasting protection that the inactivated vaccine. In addition, it may provide protection against antigenically related strains not contained in the vaccine. Unfortunately, we do not have adequate comparative data in a head-to-head study of the current vaccine and the killed vaccine (Pediatrics. 2002; 110[6]:e80). It does have some major drawbacks. The most glaring problem is the prohibition against use in younger children. It will cost approximately three times as much as the killed vaccine, about $46 per dose. When I told someone about the cost difference, she turned to her two sons and said, “You will take the old, killed vaccine.” The cost may also restrain purchases by some practitioners, eg, family practitioners in rural areas with a small volume of pediatric patients who may not want to stock this expensive vaccine. Stan L. Block, MD, reported this phenomenon with pneumococcal conjugate vaccine (Prevnar, Wyeth). Large HMOs will have to calculate the cost effectiveness of the live vaccine and try to make a business decision about the relative costs without good comparative data.

The other downside of the live vaccine is the 60-day interval between the two doses for those younger than 9 years of age who receive this vaccine for the first time. Two-week and one-month intervals are recommended, respectively, before immunization with killed and live vaccines. The added visits required also will enter into the cost equation.

One of the other major gaps is the contraindication for children with asthma and other high-risk groups who would continue to require killed vaccine. The use in pregnant women is not recommended and the effect of administration of intranasal steroids has not been adequately evaluated.

Wild card viruses

The other respiratory viruses of interest, SARS-CoV and hMPV, are wild cards. We do not have enough experience with either to judge the annual incidence. There also is little information on SARS in children. A colleague in Hong Kong has told me there were 40 cases although I was not told whether these were all laboratory confirmed. There were a handful of cases in children reported in The Lancet in May (2003;361:1701). SARS appears to be less severe in young children than older children and the elderly.

HMPV appears to be far less common than RSV, occurring in slightly older infants and appearing following RSV peaks (Emerg Infect Dis. 2003;9:6). Again, we need more information.

Each year we enter the influenza season not knowing how severe the epidemics will be. The past two seasons have been relatively mild. We have not had a pandemic with a major antigen shift in decades.

Although the first line of defense against influenza is immunization in the fall, antivirals are available in the event there is a dramatic antigen shift that will render the vaccine less effective. The most important measure we can use to prepare for influenza is to be certain to immunize those at increased risk.

We hope to see additional studies comparing the two current influenza vaccines so that judgments can be made about the relative effectiveness of the vaccines. Comparing attack rates during the same influenza season using the same criteria for evaluation should be invaluable in making important decisions about the place of the new vaccine. We look forward to additional studies in the youngest age group where there is the greatest need. Studies on the use of the vaccine in children with asthma are soon to be published. This may facilitate approval for this very important group of patients. We are certain to learn more about the new agents. The upcoming respiratory viral season will be a very interesting one.