Infectious disease “hit list”

Virginia Tech is responding to several diseases that have been identified by the Centers for Disease Control and Prevention (CDC) as potential bioterrorism agents, including the following.

Anthrax is caused by a bacterium that can remain dormant and protected as a spore. It is usually found in the soil and can infect animals and people. It can infect an open wound, the digestive system if one eats infected meat or milk products, or the respiratory system if inhaled (as with weapon exposure, since otherwise spores are rarely airborne in sufficient concentrations). It is not contagious from person to person or between animals. Infection of humans requires at least 5,000 spores. Inhalation anthrax requires early diagnosis for antibiotic treatment to be most effective. Once the lungs fill with fluid, the bacterial load can be overwhelming. The Germans in World War I used anthrax to infect animal feed and livestock. Japan and the United States weaponized it during World War II. The current human vaccine requires six injections and an annual booster. With funding from the Department of Defense, faculty members, postdoctoral fellows, and students at Virginia Tech are developing an improved vaccine to protect humans and animals (see brucellosis).

Brucellosis is a zoonotic disease caused by the brucella bacterium. Humans can contract the disease from consuming improperly cooked meat or meat and milk by-products. Symptoms are insidious, with malaise, chills, fever, sweats, weakness, muscle pain, and headache. A persistent form of the disease characterized by intermittent fever and joint pain is called undulant fever. It may also cause chronic, vague symptoms of the central nervous system and gastrointestinal tract, and chronic joint pain and fatigue. There is no vaccine for humans. Preventing the disease in animals reduces the occurrence in humans. Brucella abortus, which causes pregnant cattle to abort, has been essentially eradicated from U.S. herds in part due to a vaccine strain, B. abortus RB51, developed at Virginia Tech in the 1990s with USDA funding. Brucella melitenis is the principal cause of human disease, although another form was the subject of weapons study. Scientists at the Center for Molecular Medicine and Infectious Diseases (CMMID) in the College of Veterinary Medicine are creating a multivalent vaccine that will protect humans from both brucellosis and anthrax simultaneously. Essentially they are developing strains of B. melitensis to express protective antigens of anthrax. They have a co-operative research agreement with scientists and physicians at Walter Reed Army Institute of Medical Research to test the strains in monkeys as a prelude to testing in humans.

Rift Valley Fever (RVF) is an acute zoonotic disease normally transmitted by mosquito from domestic ruminants (endemic in Africa) to humans. It mainly affects sheep, cattle, and, to a lesser extent, goats. In the most serious cases, the disease tends to be nonspecific with numerous abortions in pregnant animals and sudden death in young lambs. Listlessness, loss of appetite, regurgitation, and foul smelling diarrhea are symptoms in less severe cases. During periods of heavy rainfall, which may cause a mosquito population to expand, and when the virus is actively replicating in an animal’s circulation, the disease is easily transmitted by many species of mosquitoes to other animals. Humans are readily infected through contact with aerosol from infected animals and their tissues. Thus, RVF has the potential to be exploited as a bioterrorism agent. Even mosquitoes could transmit the disease to humans with significant mortality and morbidity. Even though the disease has been mainly confined to sub-Saharan Africa, recent out breaks of RVF in ruminants and humans in Egypt, Yemen, and Saudi Arabia clearly show that the disease could occur in other parts of the world. Therefore, the CMMID group is also developing a RB51 recombinant vaccine expressing the glycoproteins of the virus, which has been shown to provide protection against a challenge in a mouse model. In fact, the group is developing multivalent vaccines based on the RB51 platform against many potential bioterrorism agents.

Tularemia is caused by the bacterium, Francisella turlarenis, which is so infectious that as few as 10 organisms can cause disease. Compare that to the 5,000 organisms required to cause anthrax. Protected by a polysaccharidecontaining envelope, it survives for weeks at low temperatures in water, soil, and hay. While not contagious among humans, there are many animal hosts, such as rats, and it is spread through contaminated water, soil, air, food, and tissues, and the bites of ticks, flies, and mosquitoes. It can infect the lungs, lymph nodes, spleen, liver, and kidney. It is likely underdiagnosed, with fewer than 200 cases per year in the United States in the 1990s. It has been prepared as an aerosol biological weapon by several countries, including the United States and the former Soviet Union. Inhalation exposure progresses to serious disease in three to five days and can incapacitate a person within two days. Infections respond favorably to several antibiotics. Decontamination involves common substances, such as bleach, alcohol, and soap and water, depending on the contaminated surface. However, simple, rapid, and reliable diagnostic tests to detect F. tularenisis in environmental and specimen samples are needed. A complete sequence of the genome is needed so that genes’ functions and mechanisms of actions can be understood, variants spotted, and DNA-based vaccines developed. Thomas Inzana, professor of microbiology, is working on a diagnostic test and a subunit vaccine.

Anthrax
(Illustrations by Lori Ganoe)

Brucellosis

Rift Valley Fever

Tularemia

Sources: CDC, American Medical Association, and Virginia Tech faculty members. Note that the United States destroyed its stockpile of biological weapons in the 1970s and is one of many nations to have ratified a treaty banning biological weapons.