Since the anthrax mailings of 2001, policymakers have been implementing programs todecrease the vulnerability of the United States to terrorist use of biological weapons. This reportdiscusses high-threat biological agents, focusing on the Centers for Disease Control and Prevention(CDC) definition for Category A pathogens (bacteria and viruses), their treatment and detection,current policies, and possible future approaches to reducing their threat. Terrorist use of biologicalagents would be a low probability, but potentially high consequence, event. While there is stilldebate over whether terrorist groups have the ability to effectively use biological weapons as aweapon of mass destruction, the anthrax mailings of 2001 highlighted their potential as a terrorweapon. Policy approaches for reducing vulnerability to biological terrorism involve bothaddressing biological agents as a group, and focusing on specific agents perceived as posing thegreatest threat. Treatments for exposed victims vary depending on the nature of the pathogen andexperience in treatment of these diseases is limited, due to the rarity of naturally occurring cases. Biological agents, for the purposes of this report, are pathogens which can infect and causeserious illness in humans. (1) The level of threat abiological agent may constitute is open tointerpretation. Depending on what aspects of a pathogen are considered priorities, differentbiological agents are likely to be identified as high threat. For example, the National Institute ofJustice provides an extensive list of biological agents of concern in their handbook on purchasingprotective equipment. (2) , (3) In comparison, handbooks regarding battlefieldtreatment of biologicalweapon casualties contain a shorter list of agents. (4) The CDC identifies a number of differentcategories of biological agents, and rank the various biological agents into categories. Category A diseases -- anthrax, plague, smallpox, tularemia, and viral hemorrhagic fevers --are of the highest threat. (5) The CDC views CategoryA pathogens as easily disseminated ortransmitted from person to person; resulting in high mortality rates; having the potential for majorpublic health impact; potentially causing public panic and social disruption; and requiring specialaction for public health preparedness. This is in contrast to the Category B agents which lack suchpotential. (6) The Category A pathogens will bediscussed in this report. Anthrax is a disease caused by the bacterium Bacillus anthracis . (7) Bacillus anthracis respondsto environmental stresses, such as nutrient depletion or oxygen exposure, by forming spores. Whilethe bacterium is dormant in spore form, these spores are very hardy and can remain viable fordecades in ideal conditions. Anthrax spores are primarily found in soil, and are endemic to manyparts of the world. Anthrax is primarily an animal disease, infecting animals when they ingest Bacillus anthracis spores during grazing. Anthrax is not a person-to-person contagious disease. The forms of anthrax infection are cutaneous, intestinal, and inhalation. The type of anthrax infection depends on how the victim came into contact with the spores. Cutaneous anthrax is themost common form of the disease and occurs when anthrax spores contact broken skin. Intestinalanthrax occurs after consumption of anthrax-spore-contaminated food, usually meat. Intestinalanthrax is less common than cutaneous anthrax. Inhalation anthrax is the least common naturallyoccurring form of anthrax. Inhalation anthrax occurs when spores are inhaled and germinate in thelungs. The symptoms usually appear 48 to 72 hours after exposure. The effects of the three forms of the disease, differ from each other drastically. Cutaneous anthrax is marked by a swollen, painlessblack ulcer where the infection occurred. In contrast, intestinal anthrax is characterized by nausea,vomiting, and fever followed by abdominal pain, vomiting of blood, and severe diarrhea. Inhalationanthrax manifests with symptoms resembling a common cold: fever, fatigue, and a dry cough. Thesymptoms progress to severe difficulty breathing and shock as the bacteria multiply. The recovery rate for anthrax infection depends both on type of infection and how early treatment begins. Early treatment of anthrax victims is strongly suggested, as late treatment is notas effective in many cases. Cutaneous infection typically has a fatality rate of less than 5% with earlytreatment, increasing to 20% without any treatment. Intestinal anthrax has a higher mortality rate,with fatalities ranging from 25% to 75% depending on effectiveness of treatment. Some medicalexperts assert that aggressive early treatment of intestinal anthrax will lower the fatality rate. (8) Untreated inhalation anthrax is almost uniformly fatal. With early treatment within the incubationperiod, the fatality rate can be dramatically reduced. In the aftermath of the anthrax mailings of2001, 5 of the 11 people diagnosed with inhalation anthrax died, but historically greater than 90%of inhalation anthrax cases have been fatal, even with treatment. (9) All forms of anthrax are treated with antibiotics. Several different antibiotics may be used, including ciprofloxacin, penicillin, and doxycycline. Some anthrax strains may be less sensitive toantibiotics and therefore difficult to treat. Prophylaxis is available to protect against anthrax both via vaccination and post-exposure antibiotic treatment. While a vaccine against anthrax has been licensed by the FDA, it is notcurrently available to the general public due to vaccine shortage. The Department of HomelandSecurity, working with the Department of Health and Human Services and other federal agencies,is coordinating development of civilian anthrax vaccine policy. The Department of Defense anthraxvaccination policy, and the amount of vaccine needed to implement this policy, includes vaccinationof troops thought to be potentially exposed to anthrax. (10) After the anthrax mailings of 2001, thoseindividuals thought to be potentially exposed to anthrax spores were offered vaccination andantibiotic prophylaxis using the drug ciprofloxacin. Plague is a disease caused by the bacterium Yersinia pestis . Plague bacteria are sensitive to sunlight and humidity and do not form spores. Instead, plague bacteria naturally reside in hostcreatures, such as rodents, and are found in many parts of the world, including the United States. Plague usually travels within animal populations, via insect vectors, generally migrating from oneanimal to another through biting insects such as fleas. The three kinds of plague are bubonic, septicemic, and pneumonic. Bubonic plague and septicemic plague occur when plague bacteria enter the body through the bite of an infected insect. Pneumonic plague occurs when plague bacteria are inhaled into the lungs, or develops out of abubonic or septicemic infection. Pneumonic plague, unlike the other forms, does not have to passthrough an insect vector. It is person-to-person contagious. Bubonic plague is the most well-known form. It is also known as the Black Death, and was responsible for the European plagues of the 14th century. Victims of bubonic plague developswollen, painfully inflamed lymph glands, (11) andalso suffer fever, headache, chills, and generalweakness. Septicemic plague occurs in a manner similar to bubonic plague, except the swelling ofthe lymph glands does not occur. Instead, the bacteria multiply in the blood, causing shock andinternal bleeding in addition to the more general symptoms of fever and weakness. The symptomsof pneumonic plague include fever, weakness and cough, possibly combined with severe nausea,abdominal pain, diarrhea, and difficulty breathing. The recovery rate for treatment of the different forms of plague vary. Naturally occurring plague in the United States has an overall fatality rate of 14%. The majority of these cases arebubonic with some septicemic, and very rarely pneumonic, plague. The fatality rate for septicemicplague is markedly higher than that for bubonic (33% versus 11% between 1980-1984), (12) mainlyascribed to difficulties in diagnosing septicemic plague at an early stage. Pneumonic plague has amuch higher fatality rate. It approaches 100% as the time between infection and treatment increases. For effective treatment, therapy must begin within 18 hours or victims are not likely to survive. (13) For untreated forms, the fatality rate is 60% for bubonic plague and 100% for septicemic andpneumonic plague. All forms of plague are treated using antibiotic therapy. The Food and Drug Administration has approved several antibiotics for treatment of plague, and others not yet approved for such havebeen shown to be effective. Natural antibiotic resistance in plague bacteria is known, so not all casescan be cured using a single antibiotic. (14) A plague vaccine has been approved for human use, but its production was discontinued in 1998 because of manufacturing difficulties. Additionally, the vaccine was not effective againstpneumonic plague, limiting its utility. Several Investigational New Drug (IND) vaccines are underdevelopment. (15) Smallpox is a disease caused by the virus variola. Naturally occurring variola virus has been eradicated, and the only remaining, legal stocks of the virus are held at secured facilities in theUnited States and Russia. (16) Smallpox is aperson-to-person contagious disease. Typical victims of smallpox suffer an outbreak of rash, followed by scabbing pustules covering their body. The rash and pustules form over a three week period following an incubation time ofapproximately one to two weeks. Survivors of smallpox are generally scarred by the disease. Thedisease has two rare variants; one is known as flatpox, the other hemorrhagic smallpox. (17) The fatality rates for the forms of the disease differ. For smallpox, the fatality rate is approximately 30%, though in a population lacking natural resistance this rate may increase.