Chinese curses, anthrax, and the risk of bioterrorism.

You have to love the Chinese. The English translation of their famous ancient curse, “May you live in interesting times,” almost sounds like a blessing. As we all know, however, “interesting” isn’t what they really mean. Enter the study by Fine et al1 published in this issue of Annals. It offers emergency physicians a guide to evaluation and treatment options for patients presenting with fever and flu-like illness on the basis of an increasing probability that the patient has anthrax. The study is an excellent demonstration of the power of sensitivity analysis. The resulting recommendations are reasonable and practical; they also provide the first data-driven (dare I say evidence-based) recommendations on this topic. However, like the Chinese curse, it’s not so easy to interpret. Let’s start with the article’s strengths. The authors correctly note that when a rapid definitive diagnostic test is lacking, such as with anthrax, the management plan depends on certain disease characteristics and factors that influence the outcomes of various testing and treatment strategies. These include the prevalence of anthrax, its mortality rate, the sensitivity and specificity of diagnostic tests, and the incidence of influenza. If all these factors were established, an effective protocol could be created for varying probabilities of anthrax. The problem is that this information is not known and can only be approximated over a range of values. In addition, some factors, such as the probability that a patient has influenza, vary by the time of year. Therefore, one must test all the values for the various factors and examine the effect on outcomes. Only then can potential management options be accurately evaluated. To accomplish this end, one must use the strategy of sensitivity analysis. This is, in fact, what the authors did ... for most factors. In applying the findings of this investigation, however, one must be wary of several of the authors’ assumptions that were not subject to analysis. First are the postulated mortality rates for various treatment strategies. These were taken at face value and not investigated further. The data used to calculate mortality rates for the various evaluation and treatment strategies are derived from a single limited study. The investigators relied on information generated during the October 2001 anthrax event in the United States and the opinions of an expert panel.2 (They did not incorporate data from the victim exposed in Connecticut during November 2001; therefore, my comments will not reflect this case.) How robust are these data? With respect to the October 2001 anthrax attack, the sum total of cases available for analysis is just 10 patients with inhalational anthrax. Of these, 4 died. The 95% confidence intervals (CIs) for this small number of data points are wide enough to drive a truck through. The actual mortality rate could be as low as 17% or as high as 69%. Both these rates are consistent with the data. The same wide CIs apply to the 10% mortality rate (95% CI 2% to 40%) for victims treated early, the 50% mortality rate (95% CI 24% to 76%) for those with positive blood culture results and empiric 3-day treatment, and so on. And what of the expert panel? I think you must remember that, until the anthrax attack of 2001, experts believed the mortality for treated inhalational disease exceeded 90%.3,4 Although the true rate remains unknown, it is unlikely to be as high as 90%. One must be careful not to assign too much significance to expert panel opinion. It can change as the composition of the panel changes. Unfortunately, no sensitivity analysis was performed on any of these mortality rates. If the real mortality rates are, in fact, different than those assumed by the authors, the conclusions of the investigation could be significantly changed. I N F E C T I O U S D I S E A S E / E D I T O R I A L