Recommendations for the coming influenza season

November 2005

Recommendations for the coming influenza season have been published by the CDC (MMWR. 2005;54(RR08):1-40), and additions have been made to deal with issues such as those who have been displaced by the recent hurricanes and what to do about prioritizing immunization in the event of a shortfall of vaccine this season.

The prospects of having an adequate supply appear to be much better than a while ago. The FDA anticipates the production of more vaccine than last year. At this time, we do not know the exact number of doses to be distributed. Despite Chiron’s lowered projections announced on Oct. 17, 2005, we still anticipate that there will be significantly more vaccine produced than last year (www.fda.gov/cber/flu/flu2005.htm).

Patients between 6 and 36 months of age and their contacts remain a priority. It is essential that those who have not reached their 9th birthday who have not had prior immunizations or infection with influenza virus be recalled promptly as these children will require two doses of vaccine about a month apart. Among the contacts are yourself and those in your office or clinic and the parents, siblings and caretakers of these children.

In addition, children who have contact with those in other high-risk groups (eg, grandparents) should be immunized. Children of all ages in high-risk groups (eg, those with chronic respiratory disease and other chronic conditions that put them at increased risk) also should be immunized. Pregnant teenagers and those children who are receiving salicylates also are at increased risk. New categories of increased risk are those patients with any condition that may compromise respiratory function and those with increased risk of aspiration or handling of secretions (eg, cognitive dysfunction, spinal cord injuries, seizure disorders or other neuromuscular disorders). There have been changes in the composition of this year’s vaccine. The changes reflect the anticipated influenza strains that we project will be prevalent this year. The trivalent strains of both live and killed vaccines will contain A/California/7/2004 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like and B/Shanghai/361/2002-like antigens. Although additional vaccine will be available to replace what Chiron will not supply, there still appears to be a need to prioritize immunization.

Besides the severe illness influenza virus produces in infants and children, there is some associated mortality. It is estimated that about 92 deaths occurred annually in children younger than 5 in the 1990s and 153 laboratory-confirmed deaths from 40 states in the 2003 to 2004 season, about 40% of which were in children younger than 2; 70% did not have an underlying condition that would have identified them as “high risk.”

Although mild reactions to influenza vaccine are slightly greater in infants who are exposed to these antigens for the first time, the vaccine is safe and should be given at the same visit as other vaccines that may be indicated. Reactions usually start about six to 12 hours post-vaccination and last one or two days. These vaccines are produced in eggs, and severely egg-allergic children are at risk of severe reactions. It should be given to pregnant women after the first trimester.

For those children who have not reached their 9th birthday and have not been immunized previously, two doses approximately a month apart are required to achieve optimal protection. Although there has been some interest in giving one of these doses in the preceding spring, this is not recommended at the present. If only one dose was received the previous season, only a single dose need be given in the subsequent season for those children younger than 9.

Influenza vaccine coverage under the Vaccines for Children (VFC) program was expanded in March 2003 to include all VFC-eligible children aged 6 to 23 months and VFC-eligible children aged 2 to 18 years who are household contacts of children aged 0 to 23 months. Efficacy for two doses still is much lower in the younger age group.

Live, intranasal influenza vaccine appears to be more protective, although there are no published data of a head-to-head comparison. Live vaccine may offer longer and broader protection. It is approved only for those older than 5. Evidence on the effectiveness of influenza vaccine in protecting against otitis, a common complication, is equivocal. There may be some effect if measured during the influenza season but not in the overall incidence. Influenza is one of many viruses associated with otitis. Because of concern, which appears unfounded, about vaccines preserved with thimerasol, manufacturers, since 2001, have made an effort to eliminate it from vaccines.. At the current time, there are low or no mercury options for those who remain concerned. Three are presented in the table below for trivalent inactivate influenza vaccine. Live, intranasal vaccine does not contain mercury.

New strains of virus

Point mutations in influenza RNA occur frequently, and they cumulatively may result in “genetic drift,” which requires a change in the vaccine. So far this year, there appears to be a pretty good match of circulating strains with those contained in the 2005 to 2006 vaccines.

We have witnessed a different kind of change in the circulating avian virus in which there has been a transfer of an entire segment of genetic material, or reassortment, from migrating birds to domestic chickens. This has lead to increased virulence and death of these chickens. Although the epicenter of the avian epidemic is in Southeast Asia, these strains now are quite widespread, having been found in Europe. There is concern that they may spread to East Africa. There have been about 120 confirmed cases of avian flu (H5N1) in humans, almost half of which have been fatal. Epidemiologic studies indicate that there has been more spread than these figures suggest and that intimate contact with infected chickens appears to put one at greatest risk. In humans the disease appears to be much more fulminant than the usual influenza infections and has raised the specter of a pandemic similar to the one in the 1918 pandemic. Studies of material obtained from permafrost in the Arctic indicate that the strain of virus in that epidemic, which was quite virulent, probably arose from an avian source and was probably not merely a reassortment. The hemagglutinin in that virus appears not to depend upon tissue trypsin for activation and the polymerase appears also to differ from more recent strains, although some of the same sequences have been found in the current H5N1 strains (Nature. 2005;437:889-893)(Science. 2005;310:28-29). Efforts are under way to produce vaccines against H5N1 and to stockpile antivirals.

There has been much discussion about the stockpiling of oseltamivir (Tamiflu, Roche), which is in short supply. The starting material is grown in China, and there are rumors that China is secretly been producing it. U.S. Sen. Charles E. Schumer has been applying pressure to get Roche, to permit other companies to manufacture this drug. Oseltamivir has the advantage over zanamivir (Relenza, GlaxoSmithKline), the other neuraminidase inhibitor, in that it does not have to be inhaled and is approved for treatment of children older than 1 year. Zanamivir has the advantage over the M2 inhibitors, rimantidine and amantadine, in that it is effective against type B influenza and against the avian flu. The main disadvantage is its much greater cost. Although zanamivir produces few adverse effects, vomiting has been reported in children.

Although resistance is lower than with M2 inhibitors, some have been reported. In fact, nine of 50 isolates from Japan have been found to be resistant. It is important that antiviral drugs be started as soon as possible after the onset of symptoms. In epidemic situations, it probably is best to give the drug without testing to confirm influenza or the type. This may result in many false starts with the accompanying costs. It is well to remember that these drugs shorten the course of these infections, sometimes by as little as one day. They usually do not eliminate symptoms. In adults, there has been a reduced rate of complications. Prophylaxis with oseltamivir in children has been found to be effective in preventing disease. It can be used for children as young as 13 for this purpose (NEJM. 2005,353;1363-1373).

Finally, I would strongly recommend “Respiratory Hygiene/Cough Etiquette in Healthcare Settings,” which can be obtained from www.cdc.gov/flu/professionals/pdf/resphygiene.pdf.