The vaccine crisis that wasn’t

May 2005

As this is written (late April), the 2004-2005 influenza season can safely be declared over. All the major indices of influenza activity have returned to normal seasonal levels, including visits to sentinel physicians for influenza-like illness and pneumonia and influenza mortality.

Only one state (Kentucky) is reporting anything more than sporadic or local activity. For the last several weeks, the majority of the virus isolates tested at CDC have been influenza B, rather than the previously prevailing influenza A (H3N2). Is this the “herald wave” that presages an influenza B outbreak next year? Time will tell, but that “predictor” has been far from absolute. If we do have an influenza B year in 2005-2006, the “experts” will point to this increase in influenza B isolated as predicting it; if not, only few will notice.

The outbreak was quite modest in intensity, compared to previous influenza A (H3N2) years, and certainly compared to the A/Fujian outbreak we experienced in 2003-2004. That outbreak, as many will recall, was early and quite sharp, thanks to a susceptible population and an unfortunate, but unavoidable mismatch in the influenza A (H3N2) vaccine virus antigen. Some degree of antigenic drift was seen this year also in the influenza A (H3N2) isolates; 80% of isolates were A/California/7/2004-like, a strain against which the A/Fujian vaccine antigen was somewhat less effective. Vaccine efficacy data are not yet available, but might well show some reduced vaccine efficacy. Nonetheless, the resulting outbreak was quite modest. Considering also the sharply reduced supply of vaccine, one might reasonably conclude that we were exceedingly fortunate.

Recall that it was last September that we learned that the British regulatory authorities had suspended Chiron’s license to produce influenza vaccine, and that the expected 45 to 48 million doses from their facility in Liverpool would not be available. CDC and the Advisory Committee on Immunization Practices went into a crisis mode, and hastily developed a priority list of targeted vaccine recipients; the target groups consisted primarily of those at increased risk of serious complications or death from influenza, and those who were likely to transmit influenza to others. Thus, the population older than 65 years, those with serious underlying cardiac or pulmonary disease, and health care workers were the largest target populations.

In retrospect, this priority system appeared to work generally well. Sanofi-Pasteur managed to squeeze out several million additional doses on top of the 50 to 52 million doses they produced, and MedImmune expanded their production of live attenuated vaccine, so that in the end more than 60 million doses of vaccine were available. There certainly were distribution problems, however. Some states had plenteous vaccine, and others had little; these distribution imbalances carried all the way down to the individual hospital, office, pharmacy, and clinic levels. Although there were a few notorious instances of price gouging and profiteering, there seemed to be an encouraging level of cooperation at all levels to correct the imbalances. By the end of December, many states had widened their target groups in an effort to use available vaccine supplies, so that most people who really wanted vaccine were able to obtain it. Even after vaccination efforts ceased, there were still about four million doses left unused.

In February, CDC released their Behavioral Risk Factor Surveillance data assessing vaccine utilization within target groups through the end of December, 2004; the results showed that most of the vaccine given through that date was indeed administered to people in priority groups. Among people 65 years or older, vaccine coverage was nearly 59%; the comparison figure in 2003 was 65.5%. Among non-institutionalized adults with high-risk conditions, coverage was 43%. Among children with high-risk conditions, coverage was 50.7%; children between 6 and 23 months of age were better immunized than those between the ages of 2 and 17.

One of the groups that were not well immunized was health care workers; coverage was only 42.6%. This is actually a slight increase over the 35% figure widely quoted from previous years. A major campaign to immunize 75% to 80% of health care workers was initiated last fall by the Society for Healthcare Epidemiology of America and the National Foundation for Infectious Diseases, but clearly fell far short of its goal as a result of the vaccine shortage. Not only did many hospitals simply not have vaccine available at the right time, but also it was difficult to persuade healthy healthcare workers that they were actually a priority target group in the face of a nationwide shortage.

What of next year — assuming, for the moment, that we will not face an impending pandemic of avian influenza? Predicting what influenza will do is a fool’s game, and those that do soon learn humility. That noted, it is reasonable to hope that after two successive seasons of influenza A (H3N2) epidemics, we might have an “off” year, or an A (H1N1) or an influenza B year. There are no new variant A (H3N2) strains lurking — at least to my knowledge — that might arise to cause serious trouble next year, yet. It is always important, however, to assess influenza activity during the southern hemisphere season, between June and September.

Vaccine supply issues are expected to improve, though perhaps not to the point of abundance. Sanofi-Pasteur reached capacity in the 55 to 56 million doses delivered last year, but certainly expect to do so again. Several other manufacturers, notably GlaxoSmithKline (GSK), are applying to the FDA for licenses to market their vaccines in the United States, and GSK hopes to provide about 10 million doses. The British authorities have reinstated Chiron’s license, and they are again making vaccine, anticipating FDA’s concurrence in the near future. If all goes well, it is possible that Chiron will be able to supply between 25 and 30 million doses of vaccine. MedImmune will continue to market live attenuated vaccine, and I anticipate 3 to 4 million doses there. If all of this works as we hope, we could have available between 90 and 100 million doses, the same amount we were anticipating last year. As always with this disease, however, expect the unexpected!

On a far different note, elsewhere in this issue of IDN is an obituary of Maurice Hilleman, one of the pioneers of vaccinology. An enormous debt of gratitude is owed to this man by the nation’s children and their parents. Almost half of the pediatric vaccines used today were developed by Maurice Hilleman. We will miss him sorely.