2004-2005 already shaping up to be busy influenza year for pediatricians

November 2004

---Philip A. Brunell, MD

The bacterial contamination of vaccine lots at Chiron’s British manufacturing plant, announced Oct. 5, will leave us with a significant shortfall of killed influenza vaccine (KIV). Chiron was expected to supply almost half of the vaccine for the current flu year.

We will not be able to compensate for this loss, as there is only a very limited capacity to increase production from existing sources. Aventis Pasteur will apparently be able to provide an additional 5 million doses, and an additional 2 million doses may be available from a Canadian manufacturer. There will also be an additional million doses of FluMist (MedImmune).

The United Kingdom was aware of the problem before this information got to the United States, so they got an earlier jump on alternatives, but it is likely other countries have been affected and also will be seeking additional vaccine. This shortfall will have implications for the allocation of existing vaccine supplies and will compel us to examine alternative measures for coping with this year’s flu season. The lack of adequate vaccine supplies does not imply that we will have a major epidemic. So far this year in the United States, there have been only scattered cases, and fortunately they have been type A Fujian, which is included in this year’s vaccine. We will learn, however, how curtailed use of vaccine will impact influenza morbidity.

Two major steps to address the current problem (I am trying to avoid the use of the term “crisis,” as we seem to have a new “crisis” every day) are limiting the use of existing vaccine to high-risk groups and allocating the existing vaccine to make it available to these groups. On Oct. 12, Aventis Pasteur, the remaining manufacturer of KIV, and the CDC issued a plan for distribution of the 22.4 million doses of vaccine that had not been shipped at that time.

Approximately 33 million doses had been shipped. Approximately 14 million doses will be shipped during the next few weeks directly to providers who work with high-priority patients, including private providers who care for young children. There were also provisions for redistribution of existing supplies. The Web site www.cdc.gov/other.htm#states is a good source for information on the current situation in your own state.

The major impact of the shortage is the redesignation of the target groups. The groups of concern to those caring for children include:

• all children aged 6 to 23 months;
• people ages 2 to 64 years with underlying chronic medical conditions;
• children aged 6 months to 18 years on chronic aspirin therapy;
• health care workers involved in direct patient care; and
• out-of-home caregivers and household contacts of children aged younger than 6 months.

A second dose should be given to those children 6 to 23 months of age. Vaccine should not be reserved for these persons but given on a first-come basis to those in the above categories. The question of how to manage the immunization of someone for whom two doses of vaccine was recommended and did not return is still moot. But in light of the shortage this year and the uncertainty among experts about the need for this, it probably is appropriate to give only a single dose this season.

The use of FluMist is encouraged for health care workers not involved in care of immunocompromised patients, those who are not pregnant and those not in contact with infants younger than 6 months old. There will be about 3 million doses of this vaccine this year, and the price has been reduced.

The CDC has issued suggestions on general hygiene in an attempt to curtail the spread of disease. These might be useful for distribution to patients: www.cdc.gov/flu/professionals/flugallery/images04_05/notonlyway2.pdf.

Probably the most important message for us is the need to try to reduce the spread in offices and particularly waiting rooms. It is important to remember that classical influenza does not often occur in the very young. During the flu season, croup, bronchiolitis, pneumonia and upper respiratory infection can result from influenza infection in the very young.

Rapid testing, antivirals

Can office rapid testing aid diagnosis? Testing is expensive and not perfect and may mean patients will be waiting in the office until the results of “rapid tests” are available. Rapid tests might be more useful during the beginning of an epidemic than during the height, when one can read about it in the newspapers. Testing may also be useful in determining whether the outbreak is type A, which would be more likely to be responsive to the less expensive antiviral drugs, amantadine and rimantadine, than the neuraminidase inhibitors. The vast majority of influenza in the past few years has been type A.

There are rapid tests that are CLIA-waived: the QuickVue (Quidel) and the ZstatFlu (ZymeTx). The former requires nasal specimens and the latter a throat swab. The QuickVue A+B test (but not the QuickVue Influenza test) can be used to distinguish A strains from B strains. The ZstatFlu will also distinguish between the strains. Again, their sensitivities in children have been less than perfect.

This season, antiviral drugs may have a more important role than in the past. It is important to appreciate that amantadine can be used for prophylaxis as well as for treatment. Although rimantadine is not recommended in children younger than 13 years, some have recommended it. One should check the age recommendations and dosage before prescribing (www.cdc.gov/mmwr/preview/mmwrhtml/rr5306a1.htm).

In unimmunized high-risk children who have intimate exposure to a known case or in institutionalized children, prophylaxis may be indicated. In vitro resistance occurs when used in this setting. The effect on amantadine’s efficacy in this case is not clear.

Treatment options include two classes of drugs, the M2 inhibitors, amantadine and rimantadine, which are effective only for A strains, not B, and the neuraminidase inhibitors, which are effective against both. The latter are far more expensive. Oseltamivir (Tamiflu, Roche) produces vomiting in some kids. Amantadine may result in central nervous system stimulation and may be worth avoiding in children with seizure disorders. Both classes of drugs must be started soon after onset, and they will shorten the lengths of illness by about a day.

Chemoprophylaxis may be useful in high-risk individuals who have been immunized but have not had time to mount an immune response. In this situation, it would be used for two weeks, and in those who are to receive two doses, for four weeks after the first dose of vaccine and two weeks after the second. It also may be useful in some severely immunocompromised individuals who are thought to be unable to mount an immune response to vaccination or in health care workers involved in direct patient care who have been unable to obtain vaccine. FluMist should not be administered until 48 hours after cessation of influenza antiviral therapy, and influenza antiviral medications should not be administered for two weeks after receipt of FluMist.

Virulent and avian strains

In this year’s vaccine, the A/Fujian/411/2002 (H3N2)-like strain will be included. You will recall that this strain, which widely circulated in the United States last influenza season, was not the one used in last year’s vaccine.

Finally, the spread of avian influenza in Asia will be carefully watched. This H5N1 strain, as you recall, has jumped from chicken to man. As of this writing, there are more than 40 cases in Vietnam and Thailand with many deaths. So far, almost all the cases involve avian-to-human and not human-to-human spread. If human-to-human spread becomes common, we may be in for a lot of trouble. At the moment, we have more than we can come to grips with in terms of controlling influenza this season.