Objectives: Definition of biological warfare.Definition of biological warfare. History.History. Classification.Classification. Over view & pathogenesis.Over view & pathogenesis. Criteria's & future trends.Criteria's & future trends.
DEFINITION Biological Warfare (BW)Biological Warfare (BW) The intentional use of living infectious microorganisms or toxins derived from living organisms to cause death or disease in humans, animals or plants.
History of biological warfare In 1346,In 1346, during the siege of Kaffa, the attacking Tarter force hurled the corpses of those who died of plague into the city to attempt to inflict a plague epidemic upon the enemy. Catapults used by tartar forcesInfected rat flea Catapults used by tartar forces Infected rat flea
History of biological warfare In 1767,In 1767, during the French and Indian War, British forces in North America donated blankets from smallpox patients to the Native Americans.
History of biological warfare "But the idea that the last smallpox virus sits in a few small freezers is absolutely not true. At least 10 countries have quietly kept it.“ Richard Preston, author of the Hot Zone and The Cobra Event only two officially well-guarded lab stock the smallpox virus in the world, in a Russian and an American lab in a Russian and an American lab.
History of biological warfare In 1940,In 1940, during World War II, the Japanese operated a secret BW research facility (unit 731) & dropped Bubonic plague infected fleas and grain (to attract the local rats) in China.
History of biological warfare In 1979,In 1979, an accidental release of anthrax from a weapons facility in Sverdlovsk, USSR, killed at least 66 people.
History of biological warfare In 1994,In 1994, a Japanese sect of the Aum Shinrikyo cult attempted an aerosolized release of anthrax from the tops of buildings in Tokyo.
History of biological warfare From September to November 2001,From September to November 2001, a total of 23 confirmed or suspected cases of bioterrorism-related anthrax (10 inhalation, 13 cutaneous) occurred in the United States.
History of biological warfare 32,000 persons with potential exposures Initiated antibiotic prophylaxis to prevent anthrax infections.
Biological Warfare Agent CDC Category A CDC Category B CDC Category C CDC Category Bacterial agent Viral agent Toxin agent Microbial Category
Biological Warfare Agent CDC Category A Anthrax Plague Smallpox Tularaemia Viral haemorrhagic fevers Botulinum toxin Agents Easily disseminated High mortality Public panic and social disruption Special action for public health Features
Biological Warfare Agent CDC Category B Q fever Brucellosis Glanders & melioidosis Viral encephalitis Enteric pathogens Ricin toxin Staphylococcal enterotoxin B Moderately easy to disseminate Moderate morbidity, low mortality Require enhancement of diagnostic capacity and surveillance AgentsFeatures
Biological Warfare Agent CDC Category C Emerging infectious diseases such as: Hantavirus Yellow fever Emerging agents Availability Easy to produce and disseminate Potential for high mortality and morbidity AgentsFeatures
Anthrax Bacillus anthracis,Caused by contact with spores of Bacillus anthracis, a spore forming, gram-positive bacilli. The spore is extremely hardy and can survive extremes of temperature, dryness, and moisture. It is estimated that between 130000 and 3 million deaths would follow the release B.anthracis. of 100 kg of B.anthracis.
The disease can occur in three forms:The disease can occur in three forms: Inhalation Cutaneous Gastrointestinal Anthrax Reprinted from Borioet al."
Clinical forms of anthrax I. Inhalation: I. Inhalation: Resembling a viral respiratory illness initiates inhalational anthrax which is thereafter followed by hypoxia and dyspnoea and mediastinal widening observed radiographiclly. The incubation period ranges from 1 to 7 days but may be longer, up to 60 days. Host factors, dose of exposure, and antimicrobial prophylaxis may alter the length of the incubation period.
Earlier symptoms include muscle aches, malaise, mild fever and may proceed to respiratory failure, shock, and meningitis. Mortality rate is very high, despite supportive care including appropriate antibiotics. Pathogenesis of Anthrax:
Inglesby, T. V. et al. JAMA 2002;287:2236-2252.
Anthrax: Inhalational Reprinted from Mayer et al."
Postexposure prophylaxis Interim recommendations for postexposure prophylaxis for prevention of inhalational anthrax after intentional exposure to B. anthracis
Antimicrobial treatment Inhalational anthrax treatment protocol for cases associated with this bioterrorism attack
Clinical forms of anthrax II. Cutaneous Cutaneous anthrax is characterized by a skin lesion ranging from an early stage of a papular, vesicular, to a depressed black eschar. The incubation period ranges from 1 to 12 days. The lesion is generally painless, but fever, malaise, headache and regional lymphadenopathy are present. The case fatality rate for cutaneous anthrax is 20% without, and less than 1% with, antibiotic treatment.
Anthrax: Cutaneous Day 4 Day 6 Day 10 Eschar formation Vesicle development Day 2
Left, Forearm lesion on day 7—vesiculation and ulceration of initial macular or papular anthrax skin lesion. Right, Eschar of the neck on day 15 of illness, typical of the last stage of the lesion. Anthrax: Cutaneous
Anthrax: Cutaneous Notice the edema and typical lesions
Anthrax: Cutaneous Cutaneous anthrax in an infant, associated with the recent outbreak in postal facilities. Photograph copyright and courtesy of Dr. Max Khan and Dr. Michael Traister (used with permission).
Clinical forms of anthrax III. Gastrointestinal Gastrointestinal anthrax is manifested by severe abdominal pain, fever and septicaemia. After ingestion of raw or undercooked contaminated meat there is an incubation period of 1/7 days. Oropharyngeal and abdominal forms have also been observed. Pharyngeal lesions are present at the base of the tongue and dysphagia, fever, and regional lymphadenopathy can be seen. Lower bowel inflammation usually causes loss of appetite, nausea and fever followed by abdominal pain, bloody diarrhoea and haematemesis. The mortality rate is 25/60%.
Brucellosis Caused by Brucella, which is a systemic zoonotic disease. Brucella is small gram-negative, aerobic, non-motile coccobacilli that grow within monocytes and macrophages. Brucella have been considered potential candidates for use in biological warfare which are very infectious by aersol. The organisms are readily lyophilized which enhancing their infectivity. The infectious dose is only 10 to 100 organism. Brucella replicates within the macrophage endoplasmic reticulum (ER).
Brucellosis Brucellosis presents after an incubation period normally ranging from 1- 4 weeks. The disease in humans is characterized by a fever, sweats, anorexia, fatigue, malaise, weight loss, and depression. Without adequate and prompt antibiotic treatment, some patients develop a ‘chronic’ brucellosis syndrome. The recommended treatment is doxycycline (200 mg/day) plus rifampin (900 mg/day) for 6 weeks. Alternative effective treatment consists of doxycycline (200 mg/day) for 6 weeks plus streptomycin (1 gm/day) for 3 weeks.
Botulinum Caused by Clostridium botulinum, is a sporeforming, obligate anaerobe whose natural habitat is soil. C. botulinum organisms elaborate a very potent neurotoxin that is one of the most potent toxins known in the world These organisms produce very resilient spores that are capable of surviving for up to 2 hours at 100 C. This neurotoxin is heat labile and is rapidly inactivated (less than five minutes) at 85C.
Pathogenesis of Botulinum: Arnon, S. S. et al. JAMA 2001;285:1059-1070
Botulinum Exposure is likely to occur following inhalation of aerosolized toxin or ingestion of food or water contaminated with the toxin or its microbial spores. It is tasteless,odorless and, depending on the dosage, and may take from 2 to 14 days before the symptoms appear. The symptoms include double vision, difficulty in swallowing and speaking, muscle weakness, vomiting and eventually respiratory failure. The protein is a neurotoxin and once the symptoms appear the damage is irreversible (after ~48 hours). The amount of antiserum required to treat 100,000s of exposed people is not available. Many people would be beyond saving even if given the antitoxin.
New Approach for Botulinum as BWs F Fused with proteins stabilizer. E Encapsulated with protective material C Clone the botulinum gene into common bacteria that inhabit the human gut (e.g. E. coli).
Viral Hemorrhagic Fevers Viral HF is caused by several families of RNA viruses and leads to diseases such as yellow fever, Ebola, and hantavirus. These viruses are highly contagious transmission by aerosol, contact with bodily fluids, and animal or insect vectors. In general, people with these illnesses present with fever, myalgia, hypotension, flushing, shock and generalized mucosal hemorrhage.
Ebola Hemorrhagic Fever Ebola hemorrhagic fever is one of the most virulent viral diseases, causing death in 50-90% of all clinically-ill cases. The disease has its origins in the jungles of Africa and Asia. Transmitted by direct contact with the blood, & secretions of infected persons. After an incubation period of 2 to 21 days, Ebola is often characterized by the sudden onset of fever, weakness, muscle pain, headache and sore throat. No specific treatment or vaccine exists for Ebola hemorrhagic fever. Severe cases require intensive supportive care, as patients are frequently dehydrated and in need of intravenous fluids.
Hanta Virus Hanta virus are known to cause two different diseases in humans: 1. HEMORRHAGIC FEVER WITH RENAL SYNDROME (HFRS) 2. HANTAVIRUS PULMONARY DISEASE (HPS)
criteria for biological weapon threats The criteria for the selection of bioterrorism warfare agents are: Their intrinsic virulence The facility of production Conservation and dissemination.
criteria for biological weapon threats The majority of the agents have common points : Aerosolisation is the most probable route of contamination. An intracellular phase. High risk of spread in the community.
Future trends & the development of biological weapons I. Targeting the immune system: Rather than infecting a target population with a single disease, by targeting the immune system it will insure the opportunistic infections of many different kinds of microorganism. Rather than infecting a target population with a single disease, by targeting the immune system it will insure the opportunistic infections of many different kinds of microorganism. For example, the naturally occurring staphylococcal enterotoxin B (SEB) exerts its effects via specific effects on the immune system. For example, the naturally occurring staphylococcal enterotoxin B (SEB) exerts its effects via specific effects on the immune system. Physiological systems other than the immune system could also be targets for such attack. Physiological systems other than the immune system could also be targets for such attack.
Future trends & the development of biological weapons II.‘ Designer’ biological weapons Novel weapons could use normal proteins involved in immune system modulation, which become toxic when:Novel weapons could use normal proteins involved in immune system modulation, which become toxic when: Present in a high concentration. Present in tissues from which they are normally absent. Delivering to cells that are in a different stage of development.
III.Genetic targeting Used to target the genetic characteristics of different ethnic groups Used to target the genetic characteristics of different ethnic groups. Future trends & the development of biological weapons Recently Israel was working on a BW that would specifically harm Arabs carrying certain genes. Arabs carrying certain genes. In the fall of 1998 there was a report that white South Africa government had ordered a program to develop a genetically engineered BW that would specifically kill blacks.
Future trends & the development of biological weapons IV.Genetically-modified BWs Adaptation of an existing pathogen to increase its virulence or durability in the environment.Adaptation of an existing pathogen to increase its virulence or durability in the environment. Alteration of benign microrganisms so that they are able to produce a toxin, venom or bio-regulator.Alteration of benign microrganisms so that they are able to produce a toxin, venom or bio-regulator. Alteration of deadly microrganisms so that they are able to defeat standard identification, detection and diagnostic methods.Alteration of deadly microrganisms so that they are able to defeat standard identification, detection and diagnostic methods. Development of micro-organisms which are resistant to antibiotics and standard vaccine.Development of micro-organisms which are resistant to antibiotics and standard vaccine.
Future trends & the development of biological weapons IV.Genetically-modified BWs The Associated Press reported that the Bacteriology Division of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) reported that Russia had developed an new form of anthrax which are resistant to the vaccine that American troops receive. The Soviet civilian biological warfare agency in 1973 experimented with various harmful and antidote-resistant organisms, including various harmful and antidote-resistant organisms, including a combination of smallpox with Venezuelan equine encephalitis, known as ‘Veepox’. ‘Veepox’.
Other BW CATEGORIES Other BW CATEGORIES : Protozoans are not listed as BWs, but that does not mean they could not be used as BW.Protozoans are not listed as BWs, but that does not mean they could not be used as BW. For example, a variety of protozoa species are candidates for BWs Cryptosporidium spp., Entamoeba histolytica, and Giardia lamblia.For example, a variety of protozoa species are candidates for BWs Cryptosporidium spp., Entamoeba histolytica, and Giardia lamblia. All have resting forms that render then resistant to environmental stress and to common water purification treatments.All have resting forms that render then resistant to environmental stress and to common water purification treatments. These parasites would also qualify as "Environmental Systems" BW as they could pollute a region’s water and food supply.These parasites would also qualify as "Environmental Systems" BW as they could pollute a region’s water and food supply.