2004: a look back

December 2004

---Philip A. Brunell, MD

As we look ahead to 2005, it is well to review where we have been. 2004 has been a year in which the fragility of the vaccine supply has become more apparent as well as some of the challenges we face. The publications of guidelines on otitis have been landmark accomplishments.

It is important to remember that the guidelines are just that. They must be interpreted for each patient. They are not rules that leave no room for deviation or interpretation. The otitis media with effusion (OME) guidelines provide guidance on management of this condition based on new data on the natural history and assessments of the benefits and risks of tube placement. They are based on recent information on the natural history of OME and reiterate the need not to rush to tubes before the condition has been allowed to resolve spontaneously. They recognize the need to adequately assess the special cases of children who are otherwise compromised and to perhaps intercede a bit earlier than in children who are otherwise normal. The more conservative recommendations were based on recognition of the natural history of OME, better data on the long-term assessment of intervention and the complications of tube placement. Draining tubes are common; they require additional therapy, sometimes hospitalization for IV antibiotics and even surgical intervention, when chronic drainage is unresponsive to antimicrobial therapy.

The most salient points of the acute otitis media (AOM) guidelines were the differentiation of OME from AOM and the criteria for its diagnosis. Based on the natural history of untreated AOM, more conservative use of antimicrobials is advocated, which now is supported by a number of studies in which antibiotic therapy was withheld to observe whether the condition would resolve spontaneously. There is special emphasis given to treatment to relieve pain. Both conditions have decreased membrane motility, but AOM, as the name indicates, has symptoms and signs of acuteness – pain, fever, accompanied by bulging and sometime by discharge of pus through the membrane. Redness in itself is not as useful, as this also may be seen with OME and simply may reflect the flushing of the integument in febrile youngsters.

Antibiotic therapy is recommended for the very young and for acutely ill older kids. Watchful waiting is appropriate in moderately ill kids, especially when the diagnosis is uncertain and, most important, when caretakers can be relied on to initiate therapy if the condition worsens or is unresolved after an appropriate period of waiting. Ampicillin in “high dosage” continues to be the mainstay of initial therapy.

PCV7 impact

Although the pneumococcal conjugate vaccine (Prevnar, Wyeth) has had a major impact on invasive disease, it has been relatively unimpressive in reducing office visits for otitis. It has reduced the number of patients with five to six attacks of AOM and those needing tubes. It appears to have reduced the frequency of some antibiotic-resistant vaccine strains. It also appears to have created some herd immunity, as there has been a reduction of pneumococcal illness in some groups of adults. There has been concern all along about replacement of vaccine strains with other organisms. There is some evidence that this has occurred, but thus far it appears to be clinically of little consequence. The major problem has been the periodic interruption of vaccine supply, which has necessitated revised schedules. Thus far, this does not appear to have been of major consequence, as all the trends for incidence of pneumococcal disease appear to be decreasing.

The plight of the pipeline

The vaccine pipeline continues to be a major problem, not only for pneumococcus but especially for influenza. Bacterial contamination of about half of this year’s flu vaccine has created a significant problem. The lack of elasticity in the pipeline has been illustrated by the great difficulty in getting vaccine from alternative sources. There have been contingency plans that attempt to assure the available vaccine will be used for high-risk individuals, including kids from 6 months to 2 years of age. In the face of all this, there appears to be another threat of avian flu, which now seems to have jumped from one human to another. If recombination of human with avian strains occurs, we may be in for a pandemic for which we are ill prepared. There has been stockpiling of antiviral drugs, which are not likely to be very useful in the face of a pandemic. However, we should not overlook these drugs this year, with vaccine shortages looming.

To what have we to look forward in the coming year? The measles-mumps-rubella-varicella vaccine (MMRV, Merck) is moving closer to approval. This probably will resolve the issue of a second dose of varicella vaccine. It would be given with the second dose of MMR as MMRV. There has been relatively little additional progress in development of other combination vaccines, but there needs to be some more effort in this area, as we appear to be moving closer to a recommendation for immunization with the new meningococcal conjugate vaccine (Menactra, Aventis). The second-generation rotavirus vaccines will first be used in less developed countries but could be reintroduced in the United States. There will be efforts to address vaccine supply issues and the development of a pneumococcal vaccine that can be made from a single antigen, eg pneumolysin, which does not require that multiple serotypes be included in the vaccine. We will need to develop a faster way of getting influenza vaccines on line, especially if we are faced with a pandemic of avian flu. One of the main challenges will be to encourage industry to get more involved in vaccines — but more about this next month. In the meantime, have a happy holiday and a great New Year.