-from Epidemiological Bulletin, Vol. 22 No. 3, September 2001-

Intentional Use of Biological and Chemical Agents:
Risks and Recommendations

The terrorist acts of 11 September 2001 in the United States have generated a sense of vulnerability that is now being enhanced by the widespread concern of bioterrorist attacks. The discovery of several cases of anthrax in the United States, and additional malicious attempts to spread the bacteria by mail have made this threat very real. This is an opportunity for countries to detect, investigate and respond to the occurrence of potentially epidemic diseases.

Background
Putting aside the use of chemical weapons in war situations around the world since the beginning of the 20th century, only three incidents involving biological or chemical attacks have been documented in the last 16 years. The first one was a deliberate salmonella poisoning in Oregon (United States) in 1984, which resulted in thousands of sick people but no death. The other two involved the use of sarin gas in Japan in 1994 and 1995, and resulted in fewer than 20 casualties (1). While there have not been large-scale terrorist attacks with biological agents in the past, the recent events have highlighted the need for local public health surveillance systems to be ready to identify, confirm and intervene in acute communicable disease outbreaks. This need is enhanced by dramatic increases in the volume and speed of travel and commerce that further complicates infection control efforts by creating new scenarios for the international spread of infectious diseases. In effect, any local outbreak is considered a threat to all nations. Also, advances in biotechnology increase concern for bioterrorism relating to the possible misuse of genetic research for the development of more potent biological weapons and the spread of new infectious diseases.

However, as public awareness of the threat of chemical and biological terrorism grows, it is important to consider that the actual risk of these forms of terrorism remains small. The reason this risk remains low is the inherent technical limitations involved in acquiring, producing and turning chemical and biological agents into viable weapons. Firstly, chemical and biological agents are difficult to come by. Their acquisition and transport are often complicated and require special equipment. Biological agents, because they are living organisms, require certain handling conditions to survive and be effective agents of disease. Security procedures to curtail access to these agents differ from country to country. Although some strains of dangerous microbes such as Bacillus anthracis (anthrax) can be found in natural sources (infected cattle, sheep and camels), it would take great effort to weaponize this agent.

Secondly, there are extreme obstacles to disseminating biological and chemical agents to specific targets. Biological agents must be kept alive and potent and both types of agents must be delivered in quantities sufficient to cause illness. Large quantities of agents would be needed to effectively contaminate drinking water or food and cause disease in many people. Large scale effects might be more efficiently achieved if the agent was delivered in the form of water or aerosol cloud that would then be inhaled by its victims. However, many variables, such as the equipment used and weather conditions could effect the outcome of such a strategy (2).

For all the above-mentioned limitations, the risk of biological and chemical terrorism remains low. However, the public needs to be educated about the possibilities of this type of warfare, and public health systems must be prepared to identify and contain such outbreaks. Some situations have been defined by the United States military as “epidemiological clues” for the intentional use of biological agents, which when seen together can help in determining if further investigation is needed. These include: more severe disease than expected for a given pathogen, as well as unusual routes of exposure, such as a preponderance of inhalational disease; a disease that is unusual for a given geographic area, that is found outside the normal transmission season, or that is impossible to transmit naturally in the absence of the normal vector for transmission; and unusual strains or variants of organisms or antimicrobial resistance patterns disparate from those circulating (3).

Biological and chemical agents
Several microorganisms have been identified as serious enough threats to warrant preparation by the public health system: B. anthracis (anthrax), variola virus (smallpox), Yersinia pestis (plague), Clostridium botulinum (botulism), Franciscella tularensis (tularemia) and hemorrhagic fever viruses (4). Chemical agents include mustard and sarin gas.

There has not been any case of smallpox in the Americas since its eradication from the Region in 1971. Some of the diseases mentioned above occur in endemic form in the Region. The natural form of anthrax is relatively frequent in South America and is present in cattle in the United States and Canada. Countries that report plague in the Region include Brazil, Peru, Bolivia and the United States (5). It is known that Tularemia occurs throughout much of North America (every state in the United States has reported human cases although most cases occur in the South Central and Western states.) (6) Finally, the botulinum toxin can be found worldwide (7).

Points regarding anthrax (8): Anthrax does not spread from person to person, but can be made into a powder that can, with relative ease, be made into a form that is easily dispersed. It requires that cases be detected as early and as quickly as possible; emergency room personnel must be trained and alert. The public health system must be strengthened and include knowledgeable staff in infectious diseases, in more or less the same way as required for emerging infectious diseases. A network of laboratories is necessary to identify the infectious agent.

Currently, a good anthrax vaccine is not available. The United States of America has stepped up its research on new anthrax vaccines. Now the best response to exposure is prophylaxis with antibiotics for 60 days after exposure. Anthrax is greatly sensitive to a wide array of antibiotics other than ciprofloxacine. Penicillin and doxycycline are recommended.

Points regarding smallpox (8): Currently, large populations have no immunity to smallpox; the number of individuals susceptible to the infection is larger than ever, given that immunization stopped over a quarter of a century ago, and very few people may have natural immunity. Although smallpox is more difficult to release, if it were released, its hazard potential would be much higher than that of anthrax. Smallpox would become an immediate international problem. Countries which in the past had the capacity to produce smallpox vaccine can no longer do so, and regaining that capacity would require training and revision of production procedures. An international initiative is necessary to re-establish capacity for smallpox vaccine production if it were needed.

The United States has decided to restart the production of smallpox vaccine. The strain to be used is the traditional one, i.e., the New York Board of Health strain. Two or maybe three sites will produce the vaccine. See Box 1 for sources of information on the other agents mentioned above.

The Pan American Health Organization (PAHO)’s response
Following the terrorist acts of 11 September, PAHO received numerous inquiries from the Organization’s Member States about the response that countries should prepare for in case additional events of this nature should occur. In response to these concerns, PAHO’s Director, Dr. George A.O. Alleyne, convened a consultation meeting of experts on bioterrorism from the Region of the Americas. The purpose of the consultation was to examine current and future challenges and opportunities facing PAHO and to provide recommendations for the Organization’s technical cooperation in regard to prevention, control and response to threats or acts of bioterrorism. This meeting took place at PAHO Headquarters on 24 October 2001. The themes discussed during the meeting generated the following conclusions and recommendations (8)

Conclusions

• Preparedness for the threat of natural and man-made disasters and the surveillance of emerging and reemerging infectious diseases provides some guidelines on how to deal with bioterrorism. Part of the role of the public health system of any country is to be prepared for mass casualties of any cause and kind. In particular, containment of the source of contamination should be managed by the disaster preparedness structure in each country.
• It is the health sector at the local level (hospitals, emergency personnel) that must deal with consequences of a bioterrorist attack. Indeed, it is possible that biological damages will not be apparent until the affected population seeks emergency room services due to sickness. First respondents in these cases will be hospitals, especially emergency health care personnel. Therefore, the health sector must be included early in the planning for these situations. Although the hospital capacity may be a concern in a bioterrorism situation, emergency plans in some countries include procedures to make beds available during emergencies.
• Epidemics, of known or unknown etiology, often induce panic and cause damage beyond the disease itself. In 1994, an outbreak of plague in India led to hundreds of thousands of people fleeing the city of Surat. Other consequences included embargoed flights to and from India, and restrictions on importation of Indian goods (9). Therefore, public information is a key part of the response to emergency situations and governments must provide complete and accurate information to prevent panic and maintain viable and effective public health surveillance networks.

Recommendations
Two sets of recommendations were issued by the PAHO consultation group. The first addressed national preparedness and the second, PAHO’s technical cooperation. Regarding national preparedness, recommendations deal with general preparedness, public health surveillance, and laboratory capacity:

General

• The threat of bioterrorism should be included in every country’s plan and structure to deal with disasters. These plans should be multisectoral and supported by training of all sectors and desktop simulation exercises.
• These plans should cover detection, diagnosis and response.
• Plans should include an inventory of the human and physical resources available.
• Countries should be prepared to provide up-to-date and accurate information relevant to the protection of public health. - Countries should share information on results of epidemiological investigations and cooperate with each other in response to events.
• Countries should have expert commissions on bioterrorism by creating new ones or preferably by using and expanding existing disaster preparedness bodies.

Surveillance

• Countries should take steps to enhance their ability to detect, identify, investigate and respond rapidly to reports of emerging infectious diseases. This may include the establishment of rapid response teams.
• Health care providers should receive training in diagnosis and reporting of clinical presentations consistent with man made epidemics, beginning with emergency room personnel, followed by primary health care staff.
• There should be specific written procedures for the safe handling and transportation of infectious disease materials.
• Treatment guidelines should be available to address the biological agents discussed.

Laboratory capacity

• Laboratory networks should be improved for the diagnosis of potential agents used in bioterrorism.
• Laboratory biosecurity should be strengthened to prevent theft, misuse, contamination or improper handling of these agents.
• There should be national and international quality control of laboratory diagnosis.
• Laboratory personnel should be trained in the recognition of findings suggestive of bioterrorism agents.
• Transfer of infectious samples among laboratories should be done according to established guidelines and confirmed by sending and receiving institutions.

PAHO’s technical cooperation
PAHO should:

• Provide authoritative, current information to countries on events related to bioterrorism, which could be used in the preparation of national plans.
• Make recommendations for prophylaxis and treatment of anthrax.
• Together with countries of the Region, explore the potential for production of smallpox vaccine, to include update of good manufacturing practices (GMP) for production.
• Support countries in the development of national plans to address bioterrorism.
• Provide training to countries in the surveillance, laboratory and information aspects related to the response to agents used in bioterrorism.
• Identify reference laboratories for confirmation, training, and provision of reagents.
• Promote the development of rapid diagnostic tests and availability of diagnostic reagents for anthrax and other potential agents of bioterrorism.
• Support quality control and proficiency testing in the laboratory for diagnosis of agents of bioterrorism, including the provision of an inventory of reagents available for this purpose.
• Support cooperation among countries, including through subregional networks.
• Coordinate rapid response to support countries to deal with bioterrorism.

References
(1) Geiger H. Terrorism, Biological Weapons, and Bonanzas: Assessing the Real Threat to Public Health. Am J Public Health. 2001;91:708-709
(2) WHO. Health Aspects of Biological and Chemical Weapons. (Unofficial Draft). Geneva. August 2001
(3) Pavlin A. Epidemiology of Bioterrorism. Emerging Infectious Diseases. 1999;15:4.
(4) MMWR, 21 April 2000/49(RR04), 1-4
(5) CDC Plague Home Page. Available at: http://www.cdc.gov/ncidod/dvbid/plague/index.htm. October 2001.
(6) Dennis D et al. Tularemia as a Biological Weapon. JAMA 2001;285:21:2763-2773
(7) Arnon et al. Botulinum Toxin as a Biological Weapon. JAMA 2001;285:8:1059-1070
(8) PAHO. Report of the Consultation Meeting on Bioterrorism. Washington, DC. 24 October 2001
(9) Tucker J. Historical Trends Related to Bioterrorism: An empirical Analysis. Emerging Infectious Diseases. 1999;15:4.

Source: Prepared by Ms. Anne Roca, Mr. Byron Crape, Ms. Genevieve Chase, Dr. Enrique Loyola and Dr. Carlos Castillo-Salgado of PAHO's Special Program for Health Analysis (SHA)

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Epidemiological Bulletin, Vol. 22 No. 3, September 2001