Consensus statement ularemia, a bacterial zoono

HISTORY AND POTENTIAL AS A BIOLOGICAL WEAPON

Tularemia was first described as a plague- like disease of rodents in 1911 and, shortly thereafter, was recognized as a po- tentially severe and fatal illness in hu- mans.12 Tularemia’s epidemic potential became apparent in the 1930s and 1940s, when large waterborne outbreaks oc- curred in Europe and the Soviet Union13-15 and epizootic-associated cases occurred in the United States.16,17 As well, F tularensis quickly gained notoriety as a virulent laboratory hazard.18,19 Public health concerns impelled substantial early investigations into tularemia’s ecol- ogy, microbiology, pathogenicity, and prevention.19-22

Francisella tularensis has long been

considered a potential biological weapon. It was one of a number of agents studied at Japanese germ warfare re- search units operating in Manchuria be- tween 1932 and 194523; it was also ex- amined for military purposes in the West. A former Soviet Union biologi- cal weapons scientist, Ken Alibeck, has suggested that tularemia outbreaks af- fecting tens of thousands of Soviet and German soldiers on the eastern Euro- pean front during World War II may have been the result of intentional use.24 Following the war, there were continu- ing military studies of tularemia. In the

1950s and 1960s, the US military devel- oped weapons that would disseminate F tularensis aerosols10; concurrently, it conducted research to better under- stand the pathophysiology of tulare- mia and to develop vaccines and anti- biotic prophylaxis and treatment regimens. In some studies, volunteers were infected with F tularensis by di- rect aerosol delivery systems and by ex- posures in an aerosol chamber.10 A live attenuated vaccine was developed that partially protected against respiratory and intracutaneous challenges with the virulent SCHU S-4 strain of F tularen- sis,6,7 and various regimens of strepto- mycin, tetracyclines, and chlorampheni- col were found to be effective in prophylaxis and treatment.25-27 By the late 1960s, F tularensis was one of sev- eral biological weapons stockpiled by the US military.10 According to Alibeck, a large parallel effort by the Soviet Union continued into the early 1990s and re- sulted in weapons production of F tu- larensis strains engineered to be resis- tant to antibiotics and vaccines.24

In 1969, a World Health Organiza-

tion expert committee estimated that an aerosol dispersal of 50 kg of virulent F tularensis over a metropolitan area with 5 million inhabitants would result in 250000 incapacitating casualties, includ- ing 19000 deaths.28 Illness would be expected to persist for several weeks and disease relapses to occur during the en- suing weeks or months. It was assumed that vaccinated individuals would be only partially protected against an aero- sol exposure. Referring to this model, the Centers for Disease Control and Preven- tion (CDC) recently examined the ex- pected economic impact of bioterrorist attacks and estimated the total base costs to society of an F tularensis aerosol attack to be $5.4 billion for every 100000 persons exposed.9

The United States terminated its bio-

logical weapons development pro- gram by executive order in 1970 and, by 1973, had destroyed its entire bio- logical arsenal.10 Since then, the US Army Medical Research Institute of In- fectious Diseases has been responsible for defensive medical research on F tu-

larensis and other potential biological warfare agents to better protect the US military, including protocols on decon- tamination, prophylaxis, clinical rec- ognition, laboratory diagnosis, and medical management.29 The CDC op- erates a national program for bioter- rorism preparedness and response that incorporates a broad range of public health partnerships.30,31