A potpourri of (mostly) influenza issues

Recalling the issues with Guillian-Barre Syndrome (GBS) following receipt of swine influenza vaccine in 1976, the federal vaccine establishment took great care to establish systems to monitor the safety of last year’s monovalent pandemic H1N1 vaccine.

The Vaccine Safety Risk Assessment Working Group (yielding the unwieldy acronym VSRAWG), which reported to the National Vaccines Advisory Committee, was established. There are representatives from all three federal vaccine committees: FDA’s Vaccines Advisory Committee, CDC’s Immunization Practices Committee and HHS’s National Vaccines Advisory Committee. This committee has been meeting via conference calls at two-week intervals since December to monitor H1N1 vaccine adverse events from a variety of sources.

A partial list of these sources follows:

1. The original vaccine trials, sponsored either by manufacturers or National Institute of Allergy and Infectious Diseases;
2. The Vaccine Adverse Event Reporting System (VAERS);
3. The Vaccine Safety Datalink (VSD);
4. A Real-time Immunization Monitoring System;
5. The Defense Medical Surveillance System;
6. Veterans Affairs Databases;
7. The Indian Health Services; and
8. Enhanced GBS surveillance in the Emerging Infections Program (EIP) at CDC

With so many data sources reporting, it is not surprising that some “signals” have turned up that need further examination.

‘Weak signals’

To summarize the findings to date: There is a “potential weak signal” between H1N1 vaccination and GBS in only one of the six systems that are reporting GBS data. A weak signal linking H1N1 vaccine with Bell’s Palsy has emerged in two monitoring systems. Finally, a weak signal between receipt of H1N1 vaccine and thrombocytopenia has emerged in three reporting systems.

Those weak signals noted, it is a long, long way from detection of a “signal” to establishing a cause and effect relationship. Further analyses that must be done, some of which are already underway, include verification of the diagnosis, other ways of examining the data that might or might not suggest an association, evidence of clustering of the event after vaccine administration, biologic plausibility, underlying diseases or conditions in the populations studied and the like.

One must also recognize that with so many reporting systems being observed, an association might be seen by chance alone more than once. Are there confounding factors which might have generated the signal? In other words, the signal must be validated.

As noted above, these additional examinations of the data are already underway. My best guess is that, when all these examinations are completed and the data analyzed, the pandemic H1N1 vaccine will be found to have a safety profile virtually identical to that of seasonal influenza vaccine. Only time will tell us whether that will be sufficient to reassure a somewhat skeptical citizenry.

Of far greater concern, in my judgment, is the news very recently being reported from Australia and New Zealand. There have been numerous reports of adverse reactions, especially fever and convulsions, in children younger than 5 years of age following administration of seasonal influenza vaccine. These reports have been so unusually frequent that health authorities in both countries have asked physicians to stop immunizing children in that age group until the cause for these reactions can be determined.

To set the context in these countries: It is the fall season in these countries, and the usual seasonal influenza vaccination programs are underway. The vaccine being used is a trivalent pediatric formulation, containing the usual recommended doses of an influenza A (H3N2) vaccine, an influenza A H1N1 component consisting of the 2009 pandemic H1N1 strain, and an influenza B component, and produced by Commonwealth Serum Laboratories (CSL). CSL is the sole vaccine producer in Australia, but not in New Zealand. The adverse events, mostly febrile convulsions, appear to occur only after CSL vaccine, but have not been limited to a single lot of vaccine. Of interest is the fact that monovalent pandemic H1N1 vaccine, produced by CSL, was widely used in both countries in children younger than age 5 years, and no such adverse events were seen.

One can only speculate, based on current information, about what may be the cause of these adverse events; the progress of this investigation will be monitored closely. All three virus components have been used in vaccines previously without untoward events, leaving speculation that some impurity may have crept into this pediatric formulation to cause these adverse events.

Point/counter follow-up

On a different topic: Readers might recall that in the January issue of Infectious Disease News, Don Kaye and I participated in a point/counterpoint about the future of H3N2 influenza: Don held that, following the lessons of history, H3N2 would most likely disappear, and I was reluctant to go that far, believing that H3N2 would still be around for a while. It’s time for me to concede that point to Dr. Kaye; H3N2 influenza has all but disappeared – certainly from North America, and from most of the rest of the world as well.

Lyme disease

Still a different topic: The IDSA has finally released the report of the special independent Review Panel on Lyme Disease. To no one’s great surprise, the panel completely reaffirmed the 2006 guidelines that caused such a ruckus, particularly in Connecticut. The surprise is that there has been so far so little reaction from the many Lyme Disease support groups or their organizations such is the International Lyme and Associated Diseases Society (ILADS). Perhaps this is a result of the fact that so far, at least, this report appears only on the IDSA website. It is not clear to me whether this report will be published in Clinical Infectious Diseases, but this writer hopes so. Will this report change any minds? Almost surely no; those who believe they are inflicted with chronic Lyme disease will continue to believe that, and further will believe that the deck was simply stacked against them.

SHEA follow-up

One final note: last month, describing the Fifth Decennial International Conference on Nosocomial Infections, I wrote that the attendees numbered in excess of about 4,500. Neil Fishman, president of SHEA, a major sponsoring organization, (who should know) wrote that the registered attendees numbered just over 3,300. I’ll accept his figures and withdraw mine, noting only that, either way, it was still a huge crowd of people.

Stay tuned for more on the Australia/New Zealand seasonal influenza vaccine adverse events investigation.