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February 9, 1999

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Hopkins Center For Civilian Biodefense Studies Co-Sponsors Symposium on Medical/Public Health Response To Bioterrorism

With weapons of biological and chemical terrorism in the headlines and firmly on the nation's public agenda, political leaders, physicians, research scientists, as well as law enforcement and intelligence experts will meet Feb. 16 and 17 at the Crystal Gateway Marriott to talk about what to do should bioterrorists launch an assault on civilians in the United States.

Health and Human Services Secretary Donna Shalala will give the keynote address.

"This is a timely and urgent agenda," says D.A. Henderson, M.D., the person credited with leading the World Health Organization's successful fight to eradicate smallpox from the world, and director of the new Hopkins Center for Civilian Biodefense Studies. Henderson has led the call for public and professional awareness of bioterrorism as a serious threat to the civilian population. "Until recently, I had doubts about publicizing the subject because of concern that it might entice someone to try spreading anthrax or some other biological weapon. However, events of the past two years have made it clear that likely perpetrators already envisage every possible scenario. And recent events in Iraq, Japan and Russia cast an ominous shadow."

The United States, like other nations, is ill prepared to cope with a bioterrorist attack, most experts agree. In fact, it could take days to weeks (depending on the microbe) before physicians or public health officials even realized an attack had been made. The first sign of attack is likely to be people sick or dying in emergency rooms or clinics. Further, some of the most serious biological weapons, such as smallpox, have the capacity to initiate a spreading epidemic of contagious disease that may be difficult to contain.

Henderson says the point of the symposium is not to look for quick fixes, but to marshal the expertise of public health professionals, government officials, intelligence specialists and others in the development of practical, long-term and short-term anti-terrorist strategies and measures. For example, public and private partnerships may be needed to make and stockpile protective vaccines or curative drugs, which are either non-existent or in dangerously short supply. Accordingly, a model of "first response" to a terrorist incident involving a biological agent must focus on primary care doctors, emergency room physicians and nurses, infectious disease specialists, infection control professionals, hospital epidemiologists, health officers, and laboratory directors and staff, among others.

Hopkins' new Center for Civilian Biodefense Studies (CCBS), established last year, intends to play a key role in developing national and international policies for dealing with the threat of biological weapons, according to Tara O'Toole, M.D., CCBS senior fellow and former assistant secretary of energy. "The Center's focus will be on those biological weapons that pose the greatest threat to civilian populations, including anthrax, smallpox, plague and viral hemorrhagic fevers, diseases that could cause unthinkable numbers of casualties," she says.

Highlights of the symposium will include in-depth examinations by leading experts of the following questions: Are current concerns about bioterrorism real and not inflammatory? Why must medicine and public health communities address the issue of bioterrorism? Which biological threats warrant the most concern? What is the possible aftermath of an act of biological terrorism? What issues regarding vaccines and pharmaceuticals must be addressed? What are the possible scenarios involving the use of anthrax and smallpox in civilian populations?

The symposium is sponsored by the Johns Hopkins Center for Civilian Biodefense Studies, the Department of Health and Human Services, the Infectious Diseases Society of America, the American Society for Microbiology, and 12 other professional organizations.

This is one of a series of papers that reviews the public health and medical consequences of selected biological agents deployed as weapons in a civilian community. It offers consensus recommendations of a Working Group for appropriate medical and public health measures to be taken following such an attack.

There are a number of candidate organisms terrorists could weaponize, but the Working Group identifies only a few that are widely known and feared and that would cause disease and deaths in sufficient numbers to cripple a city. Anthrax is one of the most serious of these.

Bacillus anthracis, the organism that causes anthrax, derives its name from the Greek word for coal, anthracis, because of its ability to cause black, coal-like cutaneous eschars.

Anthrax infection is a disease acquired following contact with infected animals or contaminated animal products or following the intentional release of anthrax spores as a biological weapon.

In the second half of this century, anthrax was developed as part of a larger biological weapons program by several countries, including the Soviet Union and the U.S. The number of nations believed to have biological weapons programs has steadily risen from 10 in 1989 to 17 in 1995, but how many are working with anthrax is uncertain.

Perhaps more insidious is the specter of autonomous groups with ill intentions using anthrax in acts of terrorism. The Aum Shinrikyo religious sect, infamous for releasing sarin gas in a Tokyo subway station in 1995, developed a number of biological weapons, including anthrax.

Given appropriate weather and wind conditions, 50 kilograms of anthrax released from an aircraft along a 2 kilometer line could create a lethal cloud of anthrax spores that would extend beyond 20 kilometers downwind. The aerosol cloud would be colorless, odorless and invisible following its release. Given the small size of the spores, people indoors would receive the same amount of exposure as people on the street.

There are currently no atmospheric warning systems to detect an aerosol cloud of anthrax spores. The first sign of a bioterrorist attack would most likely be patients presenting with symptoms of inhalation anthrax.

A 1970 analysis by the World Health Organization concluded that the release of aerosolized anthrax upwind of a population of 500,000 could lead to an estimated 125,000 casualties, of whom as many as 95,000 could be expected to die.

A later analysis, by the Office of Technology Assessment of the U.S. Congress, estimated that 130,000 to 3 million deaths could occur following the release of 100 kilograms of aerosolized anthrax over Washington D.C., making such an attack as lethal as a hydrogen bomb. The Centers for Disease Control and Prevention estimates that such a bioterrorist attack would carry an economic burden of $26.2 billion per 100,000 people exposed to the spores.

The largest experience with inhalation anthrax occurred after the accidental release of aerosolized anthrax spores in 1979 at a military biology facility in Svedlovsk, Russia. Some 79 cases of inhalation anthrax were reported, of which 68 were fatal.

One of the major problems with anthrax spores is the potentially long incubation period of subsequent infections. Exposure to an aerosol of anthrax spores could cause symptoms as soon as 2 days after exposure. However, illness could also develop as late as 6-8 weeks after exposure -- in Svedlovsk, one case developed 46 days after exposure.

Further, the early presentation of anthrax disease would resemble a fever or cough and would therefore be exceedingly difficult to diagnose without a high degree of suspicion. Once symptoms begin, death follows 1-3 days later for most people. If appropriate antibiotics are not started before development of symptoms, the mortality rate is estimated to be 90%.

There are a number of rapid diagnostic tests for identifying anthrax at national reference laboratories, but none is widely available.

If anthrax is suspected on clinical, laboratory or pathology grounds, then the Working Group recommends that hospital epidemiologists contact local and state health officials immediately so that the proper reference tests can be performed.

The U.S. has a sterile protein-based human anthrax vaccine that was licensed in 1970 and has been mandated for use in all U.S. military personnel. In studies with monkeys, inoculation with this vaccine at 0 and 2 weeks was completely protective against infection from an aerosol challenge at 8 and 38 weeks, and 88% effective at 100 weeks.

However, U.S. vaccine supplies are limited and U.S. production capacity is modest. There is no vaccine available for civilian use.

This is one of a series of papers that reviews the public health and medical consequences of selected biological agents deployed as weapons in a civilian community. It offers consensus recommendations of a Working Group for appropriate medical and public health measures to be taken following such an attack.

There are a number of candidate organisms terrorists could weaponize, but the Working Group identifies only a few that are widely known and feared and that would cause disease and deaths in sufficient numbers to cripple a city. Plague is one of the most serious of these.

Plague, the disease caused by the bacteria Yersinia pestis (Y pestis), has had a profound impact on human history. In AD 541, the first great plague pandemic began in Egypt and swept over the world in the next four years.

Population losses attributable to plague during those years were between 50 and 60 percent. In 1346, the second plague pandemic, also known as the Black Death or the Great Pestilence, erupted and within 5 years had ravaged the Middle East and killed more than 13 million in China and 20-30 million in Europe, one third of the European population.

Advances in living conditions, public health and antibiotic therapy make such natural pandemics improbable, but plague outbreaks following an attack with a biological weapon do pose a serious threat.

Plague is one of very few diseases that can create widespread panic following the discovery of even a small number of cases. This was apparent in Surat, India, in 1994, when an estimated 500,000 persons fled the city in fear of a plague epidemic.

In the 1950s and 1960s, the U.S. and Soviet biological weapons programs developed techniques to directly aerosolize plague particles, a technique that leads to pneumonic plague, an otherwise uncommon, highly lethal and potentially contagious form of plague. A modern attack would most probably occur via aerosol dissemination of Y pestis, and the ensuing outbreak would be almost entirely pneumonic plague.

More than 10 institutes and thousands of scientists were reported to have worked with plague in the former Soviet Union.

Given the availability of Y pestis in microbe banks around the world, reports that techniques for mass production and aerosol dissemination of plague have been developed, the high fatality rate in untreated cases and the potential for secondary spread, a biological attack with plague is a serious concern.

An understanding of the epidemiology, clinical presentation and the recommended medical and public health response following a biological attack with plague could substantially decrease the morbidity and mortality of such an event.

A plague outbreak developing after the use of a biological weapon would follow a very different epidemiologic pattern than a naturally occurring plague epidemic.

The size of a pneumonic plague epidemic following an aerosol attack would depend on a number of factors, including the amount of agent used, the meteorological conditions and methods of aerosolization and dissemination.

A group of initial pneumonic cases would appear in about 1-2 days following the aerosol cloud exposure, with many people dying quickly after symptom onset. Human experience and animal studies suggest that the incubation period in this setting is 1 to 6 days.

A 1970 World Health Organization assessment asserted that, in a worst case scenario, a dissemination of 50 kg of Y pestis in an aerosol cloud over a city of 5 million might result in 150,000 cases of pneumonic plague, 80,000-100,000 of which would require hospitalization, and 36,000 of which would be expected to die.

There are no effective environmental warning systems to detect an aerosol cloud of plague bacilli, and there are no widely available rapid, diagnostic tests of utility. The first sign of a bioterrorist attack with plague would most likely be a sudden outbreak of patients presenting with severe symptoms.

A U.S. licensed vaccine exists and in a pre-exposure setting appears to have some efficacy in preventing or ameliorating bubonic disease. The mortality of untreated pneumonic plague approaches 100%.

Research and development efforts for a vaccine that protects against inhalationally acquired pneumonic plague are ongoing. A number of promising antibiotics and intervention strategies in the treatment and prevention of plague infection have yet to be fully explored experimentally.

Given that naturally occurring antibiotic resistance is rare and the lack of confirmation of engineered antibiotic resistance, the Working Group believes initial treatment recommendations should be based on known drug efficacy, drug availability and ease of administration.

People with household or face-to-face contacts with known pneumonic cases should immediately initiate antibiotic prophylaxis and, if exposure is ongoing, should continue it for 7 days following the last exposure.

In addition to antibiotic prophylaxis, people with established ongoing exposure to a patient with pneumonic plague should wear simple masks and should have patients do the same.

This is one of a series of papers that reviews the public health and medical consequences of selected biological agents deployed as weapons in a civilian community. It offers consensus recommendations of a Working Group for appropriate medical and public health measures to be taken following such an attack.

There are a number of candidate organisms terrorists could weaponize, but the Working Group identifies only a few that are widely known and feared and that would cause disease and deaths in sufficient numbers to cripple a city. Smallpox is one of the most serious of these.

Smallpox, because of its high case-fatality rates and transmissibility, now represents one of the most serious bioterrorist threats to the civilian population. Over the centuries, naturally occurring smallpox, with its case-fatality rate of 30 percent or more and its ability to spread in any climate and season, has been universally feared as the most devastating of all the infectious diseases.

Smallpox was once worldwide in scope and before vaccination was practiced, almost everyone eventually contracted the disease. In 1980, the World Health Assembly announced that smallpox had been eradicated and recommended that all countries cease vaccination. That same year, the Soviet government embarked on an ambitious program to grow smallpox in large quantities and adapt it for use in bombs and intercontinental ballistic missiles. They succeeded.

Russia still possesses an industrial facility that is capable of producing tons of smallpox virus annually and also maintains a research program that is thought to be seeking to produce more virulent and contagious strains.

An aerosol release of smallpox virus would disseminate readily given its considerable stability in aerosol form and epidemiological evidence suggesting the infectious dose is very small. Even as few as 50-100 cases would likely generate widespread concern or panic and a need to invoke large-scale, perhaps national emergency control measures.

Several factors fuel the concern: the disease has historically been feared as one of the most serious of all pestilential diseases; it is physically disfiguring; it bears a 30 percent case-fatality rate; there is no treatment; it is communicable from person to person; and that no one in the U.S. has been vaccinated during the past 25 years. Vaccination ceased in this country in 1972, and vaccination immunity acquired before that time has undoubtedly waned.

Smallpox spreads directly from person to person, primarily by droplet nuclei expelled from the oropharynx of the infected person or by aerosol. Natural infection occurs following implantation of the virus on the oropharyngeal or respiratory mucosa.

Contaminated clothing or bed linen could also spread the virus. Special precautions need to be taken to insure that all bedding and clothing of patients are autoclaved. Disinfectants such as hypochlorite and quaternary ammonia should be used for washing contaminated surfaces.

A smallpox outbreak poses difficult problems because of the ability of the virus to continue to spread throughout the population unless checked by vaccination and/or isolation of patients and their close contacts.

Between the time of an aerosol release of smallpox and diagnosis of the first cases, an interval of as much as two weeks is apt to occur. This is because there is an average incubation period of 12 to 14 days.

After the incubation period, the patient experiences high fever, malaise, and prostration with headache and backache. Severe abdominal pain and delirium are sometimes present. A mascopapular rash then appears, first on the mucosa of the mouth and pharynx, face and forearms, spreading to the trunk and legs. Within one or two days, the rash becomes vesicular and later pustular. The pustules are characteristically round, tense and deeply embedded in the dermis; crusts begin to form about the eighth or ninth day. When the scabs separate, pigment-free skin remains, and eventually pitted scars form.

Approximately 140,000 vials of vaccine are in storage at the Centers for Disease Control and Prevention, each with doses for 50-60 people, and an additional 50-100 million doses are estimated to exist worldwide. This stock cannot be immediately replenished, since all vaccine production facilities were dismantled after 1980, and renewed vaccine production is estimated to require at least 24-36 months.

Treatment of smallpox is limited to supportive therapy and antibiotics as required for treating secondary bacterial infections. There are no proven antiviral agents effective in treating smallpox.

Recommendations of the Working Group include testing and ultimate consideration for FDA approval of a vaccinia strain grown in tissue culture rather than in the traditional and more costly calf-lymph, finding a rapid diagnostic test for smallpox virus in the asymptomatic early stages, and developing a more attenuated strain of vaccine.

-- JHMI --
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