Reflecting on 2003

January 2004

The selection of the top 10 news stories in Infectious Disease News in 2003, as covered in last month’s issue, was no surprise, of course; however, a few additional thoughts are in order.

The severe acute respiratory syndrome (SARS) outbreak and its subsequent control represents a public health triumph of major magnitude. The rapidity with which the causative coronavirus was identified, diagnostic tests developed, and infection control measures put into place could only have happened in this era of instantaneous electronic communications, and furthermore required the closest possible collaboration of health ministries of the countries involved. The leadership roles of WHO and the CDC have been widely applauded, and rightly so. Ultimately, even the Chinese government had to come clean, and admit they had a serious problem — although that happened only after a socially conscious physician in China leaked some key information.

There have now been two laboratory-acquired cases of SARS, the most recent in December 2003. The Taiwanese patient may have exposed a number of persons during travel to Singapore, and those so exposed were placed under surveillance. As of late December, no secondary cases had been reported.

We are all keeping our fingers crossed, as it were; looking for cases that might signify a possible reoccurrence of SARS. The conditions in the Chinese markets that facilitated the transfer of this virus into humans are basically unchanged, so we must simply remain alert, and in the hospital setting, maintain close surveillance of undiagnosed pneumonia. The CDC’s revised SARS guidelines are very helpful in this regard.

Worst fears realized

Turning attention to the current epidemic of influenza, last May I wrote in this column of the uneasiness that I and other members of the FDA Vaccines Advisory Committee felt with our decision about putting the A/Panama (H3N2) strain in the vaccine again for this year. Our worst fears did indeed come to pass. The dilemma presented with selection of the A H3N2 strain was really very simple. It appeared quite likely from surveillance data that the A/Fujian strain would emerge to become the dominant strain in the 2003-2004 season, but no suitable A/Fujian strain was available for inclusion in the vaccine. All strains available had been isolated or passaged at least once in tissue culture; that raised significant safety concerns relating to possible contamination with minute quantities of DNA of host cell origin, and use of such strains in vaccine production is in fact presently forbidden by FDA regulations.

Thus, if the committee deferred making the choice, hoping that a suitable A/Fujian strain could be found, that would risk a third straight year of major delay in vaccine availability. Alternatively, the committee could simply vote to use the A/Panama strain again, accepting the fact that there would be some loss of efficacy against the A/Fujian variant. The committee chose the latter course, considering that there really was no viable alternative

The CDC has already initiated retrospective studies to better estimate efficacy of the vaccine. My prediction is that it will be in the range of 40% to 60% effective, in contrast to the expected 75% to 85% efficacy when there is a close match of the vaccine strain with the wild strain.

Meanwhile, the epidemic has swept the country, and is already apparently subsiding in Texas and Colorado, the two states with the earliest initial involvement. There has been extensive morbidity among children and young adults, but thus far no excess mortality among the elderly and high-risk populations. Reports of death in children have prompted a run on influenza vaccine by parents and other relatively healthy persons who have infrequently received influenza vaccine in the past; supplies of the killed vaccine are now all but exhausted.

Several additional points need to be made about influenza and the vaccine. First, Health and Human Services Secretary Tommy G. Thompson has moved to provide $50 million to vaccine manufacturers to carry out the research needed to move vaccine production to tissue culture-based systems, and to move away from the 50+ year-old egg-based production. This is a welcome move, and should ultimately shorten the time frame needed for vaccine production, and minimize the kinds of problems we experienced this year. Second, there has been much media coverage of the fact that the supply of killed vaccine is all but gone. This will likely prompt reconsideration of the role that the federal government should perhaps play in ensuring an adequate vaccine supply. This might, for example, take the form of a guarantee of sale of a certain number of doses. Presently, the number of doses made is entirely up to the manufacturers, who do not wish to have a large unsold inventory of vaccine left at the end of the season. Finally, there seems a good chance the epidemic will have subsided by mid-January 2004, with three months of influenza season yet remaining. The hallmark of influenza A (H3N2) has long been excess mortality, sometimes marked, in the elderly and chronically ill; thus far there has been none. That leaves me wondering whether we will see a second wave of A/Fujian influenza in the late winter months, involving particularly older persons and associated with significant excess mortality. It could happen, and certainly is not without precedent.

Mad cow

The case of bovine spongiform encephalopathy (BSE) that was reported in a cow in Washington state this past December occurred far too late to be considered in the top 10 stories for 2003, but I suspect it will be a serious candidate for that dubious distinction in 2004. Details of that event in the media are sketchy and sometimes contradictory; hopefully, the true story will unfold in the near future. Several facts are clear already, however. This is the first case of mad cow disease in the United States, though we do not yet know the history of this animal. Likely some contaminated central nervous system tissue from an infected animal found its way, after rendering, into animal feed as a protein supplement. The source of the putative infected animal(s) is obviously not known at this time, and indeed may never be known. Assurances of purity and safety of animal feeds by the United Stated Department of Agriculture notwithstanding, many people who should know, claim that some forbidden supplements still are finding their way into animal feed. A scenario in which only one animal was exposed is wholly implausible; thus, I think it is quite likely that we shall see additional cases of mad cow disease in the future. It is possible that entire herds may need to be quarantined or even destroyed, as was done in the United Kingdom.

The occurrence of even this one case will have a substantial impact on the testing of cattle in the United States. Previously, only one animal in about 1,700 was tested at slaughter. Although it may not be necessary to test every animal, as is done in the United Kingdom, it will be necessary to test many, many more animals then is currently the case. Universal testing may be necessary to win back the export business that has suddenly been embargoed.

This will not have substantial effect on infectious disease practice, of course, (except perhaps as you might wish to alter your dietary habits) but it is certainly something of which to be very aware, recognizing that variant Creutzfeldt-Jakob Disease may occur here sometime in the future. Many patients will surely solicit your advice about eating beef in the future. As for me, and especially at my age, I will continue to enjoy beef when it appears on our table.

(On Dec. 28, 2003, USDA officials reported that the infected cow was actually from Canada. If confirmed, this would change the level of concern considerably. The Canadians are not pleased, and so far have not accepted this finding. Stay tuned.)