2Objectives: Definition of biological warfare. History. Classification. Over view & pathogenesis.Criteria's & future trends.
3DEFINITION Biological Warfare (BW) The intentional use of living infectious microorganisms ortoxins derived from livingorganisms to cause death ordisease in humans, animalsor plants.
4History of biological warfare In 1346, during the siege of Kaffa,the attacking Tarter force hurled thecorpses of those who died of plagueinto the city to attempt to inflict a plagueepidemic upon the enemy.Catapults used by tartar forces Infected rat flea
5History of biological warfare In 1767, during the French andIndian War, British forces inNorth America donated blanketsfrom smallpox patients to the NativeAmericans.
6History of biological warfare only two officially well-guardedlab stock the smallpoxvirus in the world,in a Russian and an American lab."But the idea that the last smallpoxvirus sits in a few small freezers isabsolutely not true. At least 10 countries havequietly kept it.“Richard Preston, author of the Hot Zoneand The Cobra Event
7History of biological warfare In 1940, during World War II, the Japaneseoperated a secret BW research facility (unit 731)& dropped Bubonic plague infected fleas andgrain (to attract the local rats) in China.
17Biological Warfare Agent CDC Category AAgentsFeaturesEasily disseminatedHigh mortalityPublic panic and social disruptionSpecial action for public healthAnthraxPlagueSmallpoxTularaemiaViral haemorrhagic feversBotulinum toxin
18Biological Warfare Agent CDC Category BAgentsFeaturesQ feverBrucellosisGlanders & melioidosisViral encephalitisEnteric pathogensRicin toxinStaphylococcal enterotoxin BModerately easy to disseminateModerate morbidity, low mortalityRequire enhancement of diagnostic capacity and surveillance
19Biological Warfare Agent CDC Category CAgentsFeaturesEmerging infectious diseases such as:HantavirusYellow feverEmerging agentsAvailabilityEasy to produce and disseminatePotential for high mortality and morbidity
21Anthrax Caused by contact with spores of Bacillus anthracis, a spore forming, gram-positive bacilli.The spore is extremely hardy and cansurvive extremes of temperature, dryness,and moisture.It is estimated that between and3 million deaths would follow the releaseof 100 kg of B.anthracis.
22Anthrax The disease can occur in three forms: Inhalation Cutaneous GastrointestinalReprinted from Borioet al."
23Clinical forms of anthrax 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.
24Pathogenesis of Anthrax: Earlier symptoms include muscleaches, malaise, mild fever and mayproceed to respiratory failure, shock,and meningitis.Mortality rate is very high, despitesupportive care including appropriateantibiotics.
25Inglesby, T. V. et al. JAMA 2002;287:2236-2252. Pathogenesis of Anthrax:Inglesby, T. V. et al. JAMA 2002;287:
26Reprinted from Mayer et al." Anthrax: InhalationalReprinted from Mayer et al."
27Postexposure prophylaxis Interim recommendations for postexposure prophylaxis for prevention ofinhalational anthrax after intentional exposure to B. anthracis
28Antimicrobial treatment Inhalational anthrax treatment protocol for cases associated with this bioterrorism attack
29Clinical forms of anthrax II. CutaneousCutaneous 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.
30Anthrax: Cutaneous Eschar formation Day 6 Day 4 Day 10 Vesicle development Day 2Day 4Day 10Eschar formation
31Anthrax: CutaneousLeft, 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.
34Anthrax: CutaneousNotice the edemaand typical lesions
35Anthrax: CutaneousCutaneous 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).
36Clinical forms of anthrax III. GastrointestinalGastrointestinal anthrax is manifested by severe abdominal pain, fever and septicaemia.After ingestion of raw or undercooked contaminated meat there is anincubation 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%.
39Brucellosis 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 macrophageendoplasmic reticulum (ER).
40BrucellosisBrucellosis 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.
41BotulinumCaused 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 worldThese 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.
42Pathogenesis of Botulinum: Arnon, S. S. et al. JAMA 2001;285:
43BotulinumExposure 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.
44New Approach for Botulinum as BWs Fused with proteins stabilizer.Encapsulated with protective materialClone the botulinum gene into common bacteria that inhabit the human gut (e.g. E. coli).
45Viral 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.
46Ebola 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.
47Hanta VirusHanta virus are known to cause two different diseases in humans:1. HEMORRHAGIC FEVER WITH RENAL SYNDROME (HFRS)2. HANTAVIRUS PULMONARY DISEASE (HPS)
48criteria for biological weapon threats The criteria for the selection of bioterrorism warfare agents are:Their intrinsic virulenceThe facility of productionConservation and dissemination.
49criteria 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.
50Future trends & the development of biological weapons 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 .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.
51Future trends & the development of biological weapons ‘Designer’ biological weaponsNovel 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.
52Future trends & the development of biological weapons Genetic targetingUsed to target the genetic characteristics of different ethnic groups.In the fall of 1998 there was a report that white South Africa governmenthad ordered a program to develop a genetically engineered BW that wouldspecifically kill blacks.Recently Israel was working on a BW that would specifically harmArabs carrying certain genes.
53Future trends & the development of biological weapons Genetically-modified BWsAdaptation 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 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.
54Future trends & the development of biological weapons Genetically-modified BWsThe Associated Press reported that the Bacteriology Division of theU.S. Army Medical Research Institute of Infectious Diseases(USAMRIID) reported that Russia had developed an new form ofanthrax which are resistant to the vaccine that American troops receive.The Soviet civilian biological warfare agency in 1973 experimented withvarious harmful and antidote-resistant organisms, includinga combination of smallpox with Venezuelan equine encephalitis, known as‘Veepox’.
55Other BW CATEGORIES :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.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.