Biological terrorism is synonymous with biological warfare and germ warfare and probably more appropriate in the civilian context. The specter of biological warfare looms large over our country like never before. Physicians need to educate themselves and their staff about clinical presentation and management of various biological agents. Now more than ever before we must be able to recognize early and respond immediately to an act of Biological warfare.
World history is replete with instance of biological warfare. The first recorded instance dates back to 600 BC when the Athenians contaminated the river pleisthenes with the poisonous plant helleborus during the siege of Kirrha. The defenders were rendered helpless from the effects of diarrhea and could not continue the fight. The myth that biological agents could be developed and used only by developed countries with advanced laboratories was shattered in September 1984. The followers of Bhagwan Rajneesh introduced salmonella into restaurants in the town of the Dalles, Oregaon, as a dry run for suppressing voter turn out in an upcoming election. Seven hundred and fifty people fell ill and 45 were hospitalized. In 1995 investigations into Aum Shinrikyo's sarin gas attack in Tokyo revealed that the cult had conducted at least four attacks with anthrax between June to July 1993.
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The ease with which biological terrorism could be carried out means that it is probably not a question whether biological terrorist attack will occur but where and when.
The question foremost in our mind is why Biological terrorism? The advantages conferred by this agent include its capacity to cause devastation even when used in miniscule amounts. It is odorless, easily concealed and difficult to detect. A terrorist could carry in his or her pocket enough Botulinum toxins to kill- if it is properly dispersed the population of an entire city. And because it does not set of metal detectors a terrorist would have no problem boarding a commercial plane and transporting the agent to any city of the world where civilian population are largely unprotected from this kind of attack. Many biological agents were easy to obtain till only a short while ago. Manufacturing requires basic skills in microbiology. Its capacity to terrorize and cause panic is unmatched.
The likely method of a large-scale attack would be aerosolized dispersal of an agent either by a low flying aircraft or a small device planted in a ventilation system or a crowded location. Vectors infested with microbiologic agents may be introduced. Small-scale attacks may be carried out by contamination of food or water supplies.
Biological agents include bacteria, ricketsia, viruses and toxins. Infectious agents: Anthrax, Brucellosis, Cholera, Glanders, Plague, Tularemia, typhoid, Q fever, Smallpox, Viral Equine Encephalitis (VEE, Viral Hemorrhagic Fever (VHF). Toxins: Botulism, Staphylococcus type B enteroxin (SEB), Ricin, T 2 Mycotoxin.
7. The properties that confer advantage to the agent include secondary transmission, low infective dose, prolonged illness, lethality and ability of the agent to persist in adverse environmental conditions. Anthrax has a high fatality rate and is able to persist in soil for years. Brucellosis causes prolonged disability. Plague has high secondary transmission and can persist in soil for a year. Small pox has a high secondary transmission, high mortality and is very stable in environment. Agents causing VHF & VEE are unstable in environment and so difficult to transmit. Botulinum toxin has a low infective dose, high mortality and is able to persist in environment.
14. Anthrax, Botulinum toxin and viral hemorrhagic fever viruses cause fatal infection. Brucellosis and tularemia can cause havoc in a community if enough people are afflected simultaneously. Fortunately most biologic agents would not be effectively dispersed via aerosol. Many of them are not stable enough to withstand temperature changes, exposure to sunlight and drying. Stable agents include anthrax and smallpox. Agents unstable for dispersal include VEE, VHF, SEB and botulinum.
15. Anthrax is one of the most feared agents. The causative organism includes Bacillus anthracis. The spores 1- 2 um in diameter once inhaled easily travel through the airways and get deposited in the alveoli. Natural reservoir of Anthrax includes livestock: cows, sheep and horses. Natural infection of Anthrax presents in its cutaneous, gastrointestinal & pulmonary forms. Inhalational anthrax is the form most likely to be spread by terrorist attack. This form is almost uniformly and rapidly fatal. Its destructive capacity is enormous. It is estimated that 100 Kg of Anthrax spores dispersed in aerosolized form by a plane over Washington DC would cause after an incubation period of 1 -5 days upto 3 million deaths. The victims present with a non- specific prodrome resembling Influenza with malaise, dry cough and mild fever. This is followed 2 days later by dyspnea, stridor and cyanosis. Many patients will have hemorrhagic mediastinitis and roughly half will have meningitis. Septic shock and death will occur 24 -36 hrs after the onset of respiratory distress. On CXR wide mediastinum, pleural effusions are late & not universal findings. Gm stain and blood culture will demonstrate the organism-Bacillus anthracis late in the disease when treatment is not effective. ELISA for toxin exists but is not available in most Labs. Mainstay of treatment is an antibiotic but to be effective it should be started before significant symptoms appear. Respiratory distress victims are most certainly going to die despite treatment. Antibiotics include penicillin, doxycline and ciprofloxacin. Bioterrorists are likely to use resistant strains. Supportive treatment includes IV fluids, airway support and treatment of shock. Does not spread from person to person. Antibiotics to be given to individuals exposed but not symptomatic. Vaccine consists of 6 s/c injections over 18 months. Course of antibiotics is 4 weeks with vaccine and 8 weeks without vaccine. Individuals coming in contact with spores should bathe with soap and water and the clothes should be stored in plastic bags.
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16. Plague presents in three forms naturally bubonic, pneumonic and septicemic. It is spread from rodents to man by bite of infected fleas. In the event of a terrorist attack with aerosolized bacillus pneumonic form will be the common presentation. As with Anthrax the pneumonic form is the more dangerous. Left untreated it is nearly always fatal within two days of the onset of symptoms. After an incubation period of two - three days patients with pneumonic plague suffer fulminant pneumonia. CXR shows typical findings of pneumonia. The disease progresses rapidly leading to dyspnea, cyanosis, stridor and septic shock. Diagnosis is made by identification of Y.pestis in gram stain of blood, sputum and lymph node aspirate. Culture is confirmatory. ELISA exists but is not universally available. Pulmonary plague is very contagious & so strict isolation is necessary until infected individuals receive treatment for at least three days. Early treatment within 24 hrs is crucial to the survival of pneumonic plague victims. Streptomycin is the antibiotic of choice but doxicycline and chloramphenicol are also effective. Quinolones have not been evaluated in humans as yet.
17. Viral hemorrhagic fevers include Ebola, Marburg disease, Lassa fever and Bolivian hemorrhagic fever. Mortality rates for some of them are very high. Lassa fever is spread through ingestion of food contaminated with rodent's urine. Person to person transmission may occur via contact with urine, feces or saliva. Terrorist attacks would take place through dispersal of aerosol containing causative agents. Incubation period varies between 4- 21 days. Severe fevers such as lassa fever have shorter incubation periods. Patients present with a non-specific prodrome that includes fever, malaise and prostration. Physical findings include petechiae, hypotension, flushing and conjunctival injection. Lab tests include thrombocytopenia; evidence of DIC; elevated liver enzymes and creatinine. Few hrs or days later pt will suffer deterioration in clinical status with mucous bleed, shock, often with signs of neurologic, pulmonary and hepatic involvement. Specific tests exist but are not available in most labs. In most instances clinical suspicion will enable you to make the diagnosis. Hospital staff can prevent transmission to themselves by simply wearing gloves, gowns and masks. Good supportive care is the mainstay of treatment. Ribavirin is effective against Lassa fever Bolivian hemorrhagic fever, Congo-Crimean fever and Rift-valley fever.
18. Smallpox fever: Because of its propensity for secondary human-to-human transmission, variola virus is one of the most feared biologic agents. Because of eradication vaccination is no longer given leaving most persons susceptible to infection. Incubation is approximately 12 days. The prodrome lasting for two to four days consists of fever malaise and aches. The characteristic rash develops over the extremities and spreads central. It starts as papules that progresses to vesicles, and pustules that scab over approximately 1-2 weeks. Mortality is 30% among the unvaccinated. Diagnosis can be confirmed by electron microscopy or gel diffusion on vesicular scrapings. All efforts to stop secondary exposures should be undertaken. Exposed individuals should undergo quarantine with respiratory isolation for 17 days. Cidofovir used to treat CMV infections is active against variola virus in-vitro. A vaccine based on vaccinia virus is effective.
19. Botulism is a syndrome caused by exposure to one or more of the seven neurotoxins produced by the bacillus Clostridium botulinum. Botulinum toxins are among the most potent toxins in existence. They are more than 100,000 times more toxic then the nerve agent sarin that was used by the cult Aum Shinrikyo in the terrorist attack in the Tokyo sub-way in 1995. Most cases of naturally occurring botulism results from the ingestion of improperly prepared or canned food; it may rarely result from infected wounds or abscesses related to i/v drug use. Although terrorist may contaminate food supplies with the toxin they are more likely to disperse the toxin via aerosol over a vast area. Botulism has a fairly characteristic presentation. It blocks the cholinergic synapses interfering with neurotransmission. Incubation period is 1-5 days. Bulbar palsies are extremely common with such ocular signs as diplopia and mydriasis. Other bulbar effects include dysarthria and dysphagia. Patients will suffer progressive skeletal muscle paralysis. The cause of death is respiratory failure. Patients are afebrile, alert and oriented.
Diagnosis must be made on clinical and epidemiologic grounds. Decontamination of skin is by discarding clothes and bathing with soap and water. Mainstay of treatment is Ventilatory support. Recovery will take several weeks to months - a long time to be on a ventilator-because new synapses must grow to replace the ones damaged by botulinum toxin. In the event of a terrorist attack the meager supply of ventilators will get exhausted. Proper care for many victims will be impossible. Botulinum antitoxin a horse serum product is available in the US -it prevents further deterioration but does not reverse muscular weakness.
20. Q Fever unlike other agent's produces a mild but long lasting illness. It has a long incubation period and is very rarely fatal. Q fever is a zoonotic illness most commonly spread through inhalation of air contaminated with the rickettsial organism- Coxiella burnetti. The organisms natural reservoirs are domesticated animals especially sheep, cattle and goats. Terrorist attack victims of Q fever will resemble naturally occurring infection. Patients typically present with fever, headache, myalgias, and malaise. CXR 50 % of patients will show patchy infiltration suggestive of pneumonia. Lab tests: WBC counts are usually normal. LFT's are often abnormal. Hepatitis is common when Q fever persists for a prolonged period. The prognosis is good for most patients but the malaise lasts for several months. C. burnetti is difficult to culture & so diagnosis is based on clinical grounds. IFA, ELISA or CFT can detect antibodies in the patient's serum. Acute and convalescent sera may be required for the diagnosis.
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Although Q fever resolves on its own without treatment, antibiotics are recommended to shorten the course of disease. Tetracycline is preferred in adults whereas chloramphenicol is the traditional agent for children. Other antibiotics that have proved effective are erythromycin, azithromycin, quinolones and trimethoprim- sulfamethoxazole.
21. Brucellosis is caused by four species of Brucella which are slow growing zoonotic gram -negative ,rod-shaped bacteria. The disease can affect the lungs, liver spleen, bone marrow, and central nervous system. The disease spreads by direct contact with livestock, or by ingestion of contaminated milk and other products from infected animals. The organism is highly infectious when aerosolized. Inhalaton will be the most likely route of infection during a terrorist attack.
After an incubation period of 5 to 60 days most patients present with fever headache, sweats, malaise and myalgias; cough and pleuritic chest pain may also be present. GI symptoms such as anorexia nausea, vomiting, diarrhea, and constipation are also common. The intermittent fever phase lasting for several weeks and is followed by a period of remission during which symptoms may wane or disappear. The fever and other symptoms then recur. This pattern of fever and remission may last for several years.
Other features of the disease include joint pain, hepatomegaly and splenomegaly. Serious complications include endocarditis, meningitis and encephalitis. Chronic disease can be very debilitating but is rarely fatal.
Lab tests may demonstrate leukopenia, anaemia or thrombocytopenia. The serum agglutination test documents both IgM and IgG antibodies. Titers of 1:160 or greater are signs of active disease. The organism can sometimes be identified in bone marrow and blood cultures.
Standard universal precautions should be followed. The preferred treatment is a combination of antibiotics usually doxicycline and rifampin or doxicycline plus trimethoprim Sulfa-methaxozole. In severe cases such as endocarditis or CNS infection streptomycin must be added. Most patients will recover even without antibacterial therapy.
22. Tularemia is contracted after contact with infected animals or from bite of infected deer flies, mosquitoes, or ticks. It can also be caused by ingestion of contaminated food and water or inhalation of contaminated air. The causative organism Francisella tularensis is a small intra-cellular gram- negative coccobacillus.
Clinical manifestations depend on the route of infection. Ulcer-glandular type is the most common form resulting from contact with infected animals accounting for 85% of natural infection cases. Typhoidal tularemia caused by aerosol inhalation would be the form seen in a terrorist attack. Incubation period is 2 to 10 days. Most victims present with fever, headache, myalgias, nausea, vomiting and diarrhea. They may also have cough and other respiratory symptoms. A small percentage will have pneumonia.
Diagnosis is difficult due to non-specific signs and symptoms. Isolation of organism from sputum and culture is difficult. Diagnosis is confirmed by serological tests but only after the patient has been ill for more than one week.
The traditional treatment is a 10 to 14 day course of streptomycin. Other agents that have proved effective against the disease include gentamicin, tetracycline and chloramphenicol.
Standard universal precautions should be followed.
Finally what steps should one take to prepare for a biological attack? First we should familiarize our staff and ourselves with potential biologic agents and their presentations. This will result in early recognition of an attack when medical treatment is still effective. Possibility of a biological terrorist attack should be incorporated in the hospitals disaster plan. Change in the background epidemiological pattern of disease will be the main tip- off to a biological attack. Ensuring that your staff remains healthy and working is crucial. Therefore you should ensure that sufficient decontamination equipment and protective gear should be available.
Masks should be equipped with high efficiency particulate air (HEPA) filters. The disaster plan should address security and crowd control. The hospital will be suddenly confronted with a host of frightened if not hysterical patients and their relatives. Effective crowd control is critical to your staff's ability to focus on the considerable medical challenges at hand.
Rapid implementation of a post attack prophylaxis program is the single most important means of reducing these losses.
Guidelines on Handling Mail suspected to Carry Bio-terrorism Agent
Q. What do I do if I get a suspicious package or letter?
A. Common sense is critical in dealing with this unfamiliar situation. Unopened envelopes or packages present a low risk. The risk of exposure is greatest after a suspicious package or letter is opened.
Q. What constitutes a suspicious letter or parcel?
A. Some typical characteristics which ought to trigger suspicion include letters or parcels that:
Have any powdery substance on the outside. Are unexpected or from someone unfamiliar to you. Have excessive postage, handwritten or poorly typed address, incorrect titles or titles with no name, or misspellings of common words. Are addressed to someone no longer at your workplace or home or are otherwise outdated. Have no return address, or have one that can't be verified as legitimate. Are of unusual weight, given their size, or are lopsided or oddly shaped. Have an unusual amount of tape. Are marked with restrictive endorsements, such as "Personal" or "Confidential." Have strange odors or stains.
Q. What should I do if I receive an anthrax threat by mail?
A. Do not handle the mail piece or package suspected of contamination. Make sure that damaged or suspicious packages are isolated and the immediate area cordoned off. Ensure that all persons who have touched the mail piece wash their hands with soap and water. List all persons who have touched the letter and/or envelope. Include contact information and have this information available for the authorities. Place all items worn when in contact with the suspected mail piece in plastic bags and have them available for authorities. As soon as practical, shower with soap and water. Notify your local health officials.