Date and Time
May 26, 2004
1:30 PM - 3:00 PM

Availability
Open to the public
No RSVP required

Speaker
Jon-Erik Holty

The mortality rate from inhalational anthrax during the 2001 attacks in the United States was significantly lower than had been observed historically. Current multi-drug therapy and intensive care may have improved survival. However, there has been no systematic evaluation of predictors of disease progression and mortality on which to base comparisons and treatment recommendations.

Holty and colleagues searched MEDLINE from 1964 to November 2003 and the bibliographies of all retrieved articles for case reports of inhalational anthrax presenting between 1900 and 2003. They considered articles in any language eligible for inclusion if the authors established a definitive diagnosis of inhalational anthrax. They performed a bootstrap and likelihood function analysis to account for variability and truncation in extracted time data. They estimated mortality as a function of duration between symptom onset and antibiotic initiation, using a Weibull model of disease progression and observed mortality rates. Finally, the researchers used logistic regression and Kaplan-Meier curves to evaluate the effects of patient characteristics and alternative treatment regimens on mortality and disease progression.

The researchers found 73 reports describing 60 cases of inhalational anthrax presenting between 1900 and 2001. The initiation of antibiotics during the prodromal (or precursory) phase of the disease significantly reduced mortality (OR 0.07; 95%CI: 0.02 to- 0.3). Victims of the 2001 anthrax attack experienced a mortality rate that was lower than in historical cases (46% verses 86%; p-value=0.009) and they were more likely to receive antibiotics during the prodromal phase (64% verses 16%; p-value=0.003). Combined analysis of the historical and 2001 cases demonstrated that the prodromal phase mean duration (4.5 days) was longer than historical accounts. Patients who progressed to the fulminant (or intensive) phase of the illness had a mortality rate of 96%, regardless of the treatment they received, and all patients with anthrax meningitis died. Most surviving patients (10/13) had pleural effusions requiring drainage. The observed mean time from symptom onset to antibiotic initiation during the U.S 2001 attack was 3.9 days. Initiation of antibiotics on day two rather than day four reduces mortality by an estimated 76%.

Holty and his colleagues concluded that rapid initiation of antibiotics during the prodromal, or precursory, phase of inhalational anthrax dramatically reduces mortality. Despite advances in supportive care, fulminant phase inhalational anthrax is usually fatal. Efforts to improve early diagnosis and timely initiation of appropriate antibiotics are critical in reducing mortality.