Wrinkles in the Force

Larry I. Lutwick, MD, Norberto E. Soto, MD


April 26, 2002


Schmeckman hesitated, considering his response before speaking. Lady Purple, his mentor, had always cautioned him about pulling out dirty laundry in public. "It is important not to take this information out of the context of the overall issue. Vaccines, perhaps second only to the flush toilet, have been extraordinarily important in the prevention of morbidity and mortality from infectious processes. However, `stuff' occasionally does hit the fan. This occurred in the early days of vaccine manufacture. Now, tight controls have virtually eliminated most of these `wrinkles in the force.'

"Certainly, individuals may have allergic reactions to a component of any vaccine, and a rare, idiosyncratic reaction can occur. However, several `blips' related to biologically contaminated vaccines did occur, primarily in the `Jurassic Age' of vaccine production. These were not related to biologic warfare (even though the specter of such heinous events is not difficult to imagine in the past,[2] present,[3] or future[4]). The 4 events I will tell you about were all related to either contamination with another agent or inadequate inactivation of the vaccine strain."

Schmeckman continued his didactic monologue:

"One of the first observed instances of such an event occurred more than 100 years ago, during the infancy of immunization, involving a smallpox vaccination program. As highlighted in a succinct review of the early days of viral hepatitis,[5] MacCallum discussed an outbreak of icterus among shipyard workers in Bremen, Germany, as an early example of a `wrinkle in the force.' It is also probably the first recognition of the transmission of a long incubation-type hepatitis by blood or body fluid. The outbreak, described in the German literature by Lurman,[6] involved workers vaccinated with lymph from vesicles of other smallpox vaccinees, which occurred several months after exposure in the staff of three separate facilities. In retrospect, the episode was an omen of things to come for the transmission of a variety of unknown human viral pathogens via blood or body fluids.

"Another, much more publicized episode also involved hepatitis transmission, but this time was associated with the yellow-fever vaccine in soldiers during World War II. An epidemic of more than 10,000 cases of jaundice occurred in army personnel in the western US between March and June of 1942, resulting in 31 deaths.[7] The cases peaked 14 weeks after yellow-fever vaccination, and the epidemic was clearly associated with certain lots of vaccine. Evaluation revealed that this `wrinkle' was associated with the pooled human sera used in the biologic, which was thought to be needed to `stabilize' the live, attenuated 17D yellow-fever vaccine. MacCallum[5] noted that investigators in Brazil had already found that serum was unnecessary, but because of the war this information was not disseminated.

"MacCallum also noted that a circulating serum antigen was found in some patients that precipitated with convalescent sera. This may have been the first identification of hepatitis B surface antigen (HBsAg), which was more formally described by Blumberg as Australia antigen in 1965.[8] If this antigen had been better characterized, and if it was in fact HBsAg, blood product transmission of hepatitis B could have been diminished perhaps 20 years sooner.

"In 1950, a batch of pertussis immune globulin collected from convalescent patients became inadvertently contaminated with tetanus toxin in Hungary. The episode was first reported in 1997,[9] as the Hungarian government had kept the records secret until that time. Although the circumstances surrounding the event are unclear, it is now believed that 22 individuals developed tetanus and 11 of them died. After careful dissection of the information, the recent report was able to suggest a human lethal dose of tetanus toxin.[9] However, this is not a fact that most physicians need to know. One would certainly hope that having a fully immunized population would further minimize any risk of such a fiasco.

"Finally, the famous Cutter incident is worth mentioning.[10] An outbreak of about 160 cases of paralytic infection occurred in recipients (and family contacts) of certain lots of the Cutter-manufactured inactivated poliovirus vaccine. Fortunately, this manufacturer was the smallest of the 5 producers of this vaccine. The problem was caused by the difficulties of inactivating agglutinated virus with formalin, and this was promptly solved. No further cases occurred with the killed poliomyelitis vaccine. In fact, due to a very small but finite number of paralytic polio cases related to the live, attenuated vaccine, current vaccination practices are returning to the killed vaccine, now in a more immunogenic form.[11]"

"It sounds like we get way more bangs from vaccines than bites," remarked Tess, the ID Fellow.

"True," responded Schmeckman, "but we can all learn from these episodes. Keeping them in context is vital, however, to avoid blowing their overall relevance out of proportion. As my favorite author, Harlan Ellison, said, `The 2 most common elements in the world today are hydrogen and stupidity.'"