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Biologic Weapons in War The use of germs to kill, immobilize or demoralize the Enemy. It WILL happen. Again. Vicken Y. Totten MD, MS FACEP 1.

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Presentation on theme: "Biologic Weapons in War The use of germs to kill, immobilize or demoralize the Enemy. It WILL happen. Again. Vicken Y. Totten MD, MS FACEP 1."— Presentation transcript:

1 Biologic Weapons in War The use of germs to kill, immobilize or demoralize the Enemy. It WILL happen. Again. Vicken Y. Totten MD, MS FACEP 1

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3 Warfare agents Projectiles and explosives – physical injuries incompatible with life Chemical and nuclear – poisoning incompatible with life Eco devastation – the environment will no longer sustain human life Carthage Genetic imperialism Rape and forced impregnation change a genome “Germ Warfare” 3

4 Purpose of bioterrorism To instill fear, change lifestyles Immobilize populations Waste resources Occupy trained personnel Weaken the Enemy 4

5 Germ Warfare (BioWar) Different agents have different infectious dose, germ survival in the environment, effectiveness, availability & LD-50, but: all should be feared. Psychological impact almost as lethal as their physical effects. Hot zones where contracting these germs means sure but slow! and contagious! death. 1 to 2 weeks turn your body into liquefied, virus - infected tissue culture. You Hemorrhage virus infected blood: potential to wipe out 20-99% of population 5

6 The Salt Lake Tribune (5/12, May)Salt Lake Tribune “ if "a killer flu strikes, with several thousand sick or injured and no room to spare in understaffed hospitals, care will be denied to the sickest adults and children." Individuals "who are severely burned, have incurable and spreading cancer, fatal genetic diseases, end-stage multiple sclerosis or severe dementia will be turned away. They can be sent elsewhere for comfort care, such as painkillers, but they will not be treated for the flu, according to the guidelines. 6

7 BioWeapons = Germ Warfare Not new: used for thousands of years What’s new is “Weaponizing” increases virulence Assists in spread by technology Biologic capability is relatively inexpensive and widespread. Risk of a serious bioterrorism incident. 7

8 Serendipitous and deliberate Zoonoses in the “New World” Deliberate small pox in the New World Actual infection is not even required: post attack, US anthrax hoaxes had many of the effects hoped-for from actual infections: Disrupting business, life styles and demoralizing the Enemy. 8

9 Ashdod of the Philistines BC I Samuel: The Philistines stole the Israelites’ Ark of the Covenant. Rats (mice) appeared, then “the Lord’s hand on the people of Ashdod and its vicinity, throwing [the city] into a great panic. He afflicted the people of the city, both young and old, with an outbreak of tumors (emerods) in the groin.” As a result, the Philistines returned the Ark of the Covenant with “five golden emerods and five golden mice.” 9

10 Plague of Athens ( BCE) Thucydides’ “The Peloponnesian War” attributed the success of the war to the plague. The plague arrived in the first days of summer, during the second year of the war, at the same time as Archidamus, son of the king of Lacedaemon. 10

11 Plague of Athens Spartans besieging the city were not affected by the disease. Many Athenians died, and eventually capitulated. Plague probably came by boat with the alleys up from Egypt, with immune soldiers. 11

12 14th and 15th century Europe. Armies would fling diseased and decaying cadavers (especially of slaughtered enemy soldiers) over protective town walls to demoralize and sicken the besieged cities Tartars defeated Genoese army by catapulting plague-dead soldiers over the walls into Kaffa (Caffa), by the Black Sea Lithuanians flung dead soldiers and 2000 cart loads of excrement into Carolstein. These battles contributed to the 25 million victims of the European Black Plague 12

13 THE BLACK DEATH PANDEMIC Worst from 1346 and 1352 with outbreaks till 1800s Killed 25 million people(1/3 of the world’s population at that time) 30-60% of the populations of large cities died from the disease final “foray” occurred in Marseilles in Still around 13

14 World War II British tested anthrax in Gruinard Island off the coasts of Scotland. Anthrax can live decades in soil. Cleaning the Island years later was very costly. 14

15 United States, Post WWII 1950, Germany accuses US of releasing Colorado beetles over German crops. China, North Korea, and the Soviet Union accused the US of using biological weapons during the Korean War. 15

16 Second Sino-Japanese War The Imperial Japanese Army bombed Ningbo with fleas carrying bubonic plague More plague-contaminated fleas airdropped by 40 planes onto Changde. These operations caused epidemic plague outbreaks. 16

17 United States 1980s September 1984, The Dalles, OR, dozens got food poisoning: Salmonella enterica typhimurium. 1 st : Shakey’s Pizza. Later, 10 more restaurants. More than 700 ill; the only hospital ran out of beds. CDC involved. Deliberate contamination was proved; the Rajneesh cult was suspected but never convicted. 17

18 Weaponized Super-Germs vs common organisms Small inoculums will infect large populations (highly infectious) Easily transmitted from person to person: airborne better than contact. Either lethal or prolonged illness with lasting morbidity (ties up Enemy resources and diverts them from War Effort; demoralizes) Treatment: none 18

19 Properties for “Maximum Credible Threat” highly lethal & toxic easily produced in large quantities. environmental & aerosol stability Dispersal capability to (1 mm to 5 mm particle size) person to person communication no treatment or vaccine. 19

20 Potential human biological pathogens. NATO handbook lists 39 agents including bacteria, viruses, rickettsiae, and toxins. Biologic agents spread on their own; therefore, the “dose” needed is less. Highly toxic poision, Ricin: 8 metric tons vs 1 kg anthrax for same number casualties 20

21 Comparison Agent TypeUntreated Mortality % Relative Infectivity Dose Incubatio n Period Treatment AnthraxBact- eria Spores 1-4 DaysPre Exposure Antibiotics* BotulismVirus40-90Moderate2-7 DaysSome Antibiotics PlagueBact- eria 9010 Organisms 2-3 DaysAntibiotics SmallpoxVirus75High7-14 DaysVaccine Tular- emia Bact- eria 3025 Organisms 2-4 DaysAntibiotics V.H.F.Virus50-90High2-7 DaysAntibiotics * Not effective after symptoms develop 21

22 Anthrax, Plague and Smallpox: best candidates Highly lethal: Anthrax, untreated anthrax > 80% die; Variola Major: 30% of unvaccinated patients die; Septicemic Plague 100% All can be produced in quantity Plague available world wide; no need to raid containment facilities Anthrax & Smallpox stable for aerosol transmission; Anthrax spores survive for decades; smallpox can be freeze-dried. 22

23 All Weaponized. Iraq produced anthrax for use in Scud missiles; former Soviet Union produced smallpox virus by the ton; Japanese weaponized plague All uncommon diseases with non-specific initial presentation Delayed recognition will allow for secondary spread Vaccines poor or limited in availability. 23

24 Treaties: honored in the breach 1972 Biological Weapons Convention Soviet Union in 1979 accidentally released anthrax Iraq in 1995 had anthrax, botulinum toxin, and aflatoxin 24

25 United States 1969 stockpile: Bacillus anthracis, botulinum toxin, Francisella tularensis, Brucella suis, Venezuelan equine encephalitis virus, staphylococcal enterotoxin B Coxiella burnetti (9). 25

26 Soviet Union stockpile: smallpox, plague, anthrax, botulinum toxin, equine encephalitis viruses, tularemia, Q fever Marburg melioidosis Typhus 26

27 More details about: Plague (Yersinia pestis), Smallpox (Variola major and minor) Anthrax (Bacillus anthracis), Tularemia (Francisella tularensis) Influenza is seldom mentioned but would be an excellent BioWeapon Many diseases have been accused of being BioWeapons, including SARS, Swine Flu and HIV 27

28 Plague 28

29 Plague (Yersinia pestis), gram-negative, anaerobic coccobacillus. transmitted to humans through fleas, rodents, or droplet infection. Human-to-human transmission quick Called “Black death” because the septic shock causes cyanosis, & peripheral gangrene “Blackening” 29

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31 Rodents and fleas Endemic in rodents; fleas transmit but don’t sicken. The next mammal is the next victim. 10,000 years of human garbage attracting flea-ridden rats. Less a disease of nomads. 31

32 Plague – mode of transmission Natural: Fleas from infected rodents BioWar: aerosolized Large aerosol droplets contain organisms Person-to-person transmission 32

33 Plague Worldwide: one of most feared diseases throughout history As many as 200 million deaths in last 1000 years. Not gone! India had outbreak in Endemic in US Southwest in rodents 33

34 Plague: Clinical Manifestations Cervical buboEcchymosis, septicemiaGangrene, septicemia Inglesby T, et al. JAMA 2000;383:

35 Plague 3 forms: bubonic, pneumonic and septicemic; Bubonic is classic. infected individuals die within 2 -3 days Bubonic has a mortality of %; pneumonic & septicemic forms have mortality of % respectively Septicemic plague usually occurs secondary to bubonic or pneumonic plague. 35

36 Plague: Black lesions & bubos (fingers & toes, penis & nose) 36

37 Symptoms: Bubonic Plague AMS: Hallucinations, headache, fever, chills. semiconscious to lethargic. " Madness” (agitated delirium) Hematemesis, bloody diarrhea Lymphadenopathy: swollen, tender lymph nodes (buboes) in armpits, groin; even supra-clavicular and cervical buboes rupture & suppurate Black blisters and hematemesis Recovered victims disabled: muscular tremors, “withered thighs and tongues“ 37

38 Plague bubo 38

39 Plague Septicemia Non-specific gram-negative septicemic symptoms: Flu-like illness rapidly progresses to pneumonia, hemoptysis. Blood cultures +, but no lymphadenopathy; respiratory contagion at 2 to 5 feet. Pneumonic plague is 100% fatal unless treatment is given with 24 hours of the onset of symptoms. 39

40 Pneumonic Plague Most contagious and deadly: pneumonic plague Airborne person-to-person airborne spread. Y. pestis is not spore forming, and is viable for only 60 minutes as an aerosol. Doesn’t live long on surfaces. 40

41 Pneumonic Plague: CXR 41

42 Plague Diagnosis and Treatment CXR nonspecific Suspicion, setting, environment Standard treatment of bubonic, septicemic, or pneumonic plague is streptomycin, 30mg/kg IM q 12 h x 10 days. alternatives: chloramphenicol, gentamicin, or doxycycline. Chemoprophylaxis includes treatment with tetracycline or doxycycline. 42

43 Plague Vaccine Not a generally viable option The Greer vaccine is an inactivated form of the disease, and requires a course of injections over 6 months. A recombinant sub-unit vaccine is being investigated. Outbreak would spur vaccine development – too late 43

44 Smallpox 44

45 Smallpox Communicability Contact: fomites, person to person Aerosol: communicability by aerosol requires negative-pressure isolation. One single case -> 10 to 20 others. No more than 20% of the population has any immunity from prior vaccination No acceptable treatment 45

46 Smallpox: Mode of transmission Patient-to-patient transmission likely Droplets, Large & Small More infectious if coughing or bleeding 46

47 Smallpox – the Virus 2 Wild types Variola major Variola minor Variola called "smallpox" to distinguish it from Syphilis, the "great pox" Smallpox is believed to have emerged in human populations about 10,000 BC. human populations 47

48 Pustules up close. Note: thick covering of skin. not like typical blisters. 48

49 Small Pox Symptoms: Maculopapular rash, then Raised fluid-filled blisters characteristic scars, commonly on the face, which occur in 65–85% of survivors. Blindness resulting from corneal ulceration and scarring; Limb deformities due to arthritis and osteomyelitis are less common complications, 2–5% of cases. 49

50 Variola Diseases V. major produces a more serious disease than V. minor V. major mortality 30–35% V. minor causes a milder form of disease (also known as alastrim, cottonpox, milkpox, whitepox, and Cuban itch; kills about 1% of its victims. ?Protective immunity? 50

51 Smallpox versus chicken pox 51

52 Smallpox Lesions progress simultan- eously; in Chicken pox they come in crops 52

53 Biological Warfare Using Smallpox Ravaged Europe; surviving population relatively immune Frequently used against American Indians: The British: June , William Trent, a local trader, wrote, “…we gave them two Blankets and an Handkerchief out of the Small Pox Hospital. I hope it will have the desired effect.“ 53

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55 Diagnosis Clinical setting: classic syndrome & rash is enough to make the diagnosis Electron Microscopy of vesicle; see Orthopox virus; does not prove variola Culture definitive but SLOW. Chick membrane or cell culture PCR (ref lab) is faster 55

56 Treatment Isolation!! Supportive care Fluid balance Electrolytes Hemodynamic support Respiratory support if needed No proven effective antivirals Antibiotics for secondary infections 56

57 Smallpox Infection Control Strict Universal Precautions Prevent inhalation of particles 5µ or smaller Transfer to appropriate isolation room In large epidemic, may cohort patients Limit transportation (but use mask on patient if necessary) 57

58 Post-Exposure Prophylaxis Vaccine Partially effective up to 3 days s/p exposure Reduces incidence 2-3 fold Decreases mortality by ~50% Plus Vaccinia immune globulin (VIG) 3 fold decrease in incidence and mortality Passive immunity for 2 weeks (?) Cidofovir – antiviral agent is effective in animals against other poxviruses 58

59 Smallpox prevention No more wild smallpox Vaccine available Last case 20 years ago Immunization may NOT confer lifelong immunity. CDC has 10-15M doses of vaccine, can produce more fairly quickly 59

60 Reactions to Smallpox Vaccine 60

61 More reactions 61

62 Anthrax and tularemia (rabbit fever) Most infectious in aerosol cause the highest number of dead and incapacitated greatest downwind spread 62

63 Anthrax & Tularemia (rabbit fever) These are the most infectious aerosols Aerosols cause the highest number of dead and incapacitated Spread downwind & person to person Available in the wild Weaponized versions are Abx resistant 63

64 Anthrax 64

65 Anthrax history Biblical Egyptian plague. Bacillus anthracis, a gram-positive, spore forming bacillus. Transmission by inhalation, ingestion, or skin breaks from infected animals or their products, or from terror attack. Often associated with sheep and wool 65

66 Cutaneous lesions are black 66

67 Anthrax as BioWeapon Anthrax as a Biological Weapon, 2002: Updated recommendations for management JAMA. 2002;287(17): (doi: /jama ) Thomas V. Inglesby; Tara O'Toole; Donald A. Henderson; et al. assn.org/cgi/content/full/287/17/

68 Lesion of Cutaneous Anthrax Associated With Microangiopathic Hemolytic Anemia and Coagulopathy in a 7-Month-Old Infant 68

69 Infant w Cutaneous Anthrax Previous slide photo was from hospital day 12, when 2-cm black eschar was present in the center of the cutaneous lesion. Reprinted from Freedman et al. 69

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71 BioWar Anthrax not new Aerosol technologies for large-scale dissemination are developed and tested Brits weaponized Anthrax pre-WWII 1995, Iraq acknowledged producing weaponized Anthrax Soviet Union & at least 13 other countries: Clear evidence of offensive biological weapons programs. 71

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73 US: 2001 Anthrax Attacks Powder containing Anthrax spores in at least 5 letters to Florida, New York City, and Washington, DC. 22 confirmed or suspected Anthrax cases B anthracis spores in all the letters were “Ames strain” a research strain Aerosol release of B anthracis would be odorless and invisible and would have the potential to travel many kilometers before dissipating. 73

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75 Types of Anthrax cutaneous, (Woolsorter's disease), gastrointestinal inhalational CNS (meningitis) Anthrax invades the lymphatic system and causes hemorrhages, sepsis, produces necrotizing toxins & death 75

76 Cutaneous anthrax stemming from wearing contaminated wool scarf 76

77 Cutaneous anthrax inoculation of spores through open skin lesions. Painless, pruritic papules appear w/i 5 d. Papules develop into vesicles By 7 days, central necrosis develops Necrosis progresses to black eschar that eventually sloughs off. Cutaneous: Not usually fatal Half the victims of mailed powdered anthrax 2001 got cutaneous anthrax. 77

78 Cutaneous Anthrax Eschar Raised, vesiculated edge, inflamed, and with a black base to the ulcer 78

79 Cutaneous anthrax ulcer Antibiotics reduce systemic symptoms Antibiotics don’t alter lesion course 79

80 Gastrointestinal Anthrax Seen in poor, developing countries with food shortages or inadequate food inspection. Sub- Saharan Africa, Central Asia, Russia, India, and Thailand Usually have concurrent cutaneous cases from butchering the affected animal or handling the infected meat Probable frequency: one outbreak per 64 infected animals eaten. 80

81 Gastrointestinal anthrax From eating contaminated meat: Starts with pharyngeal ulcers and edema. Hemorrhagic mesenteric adenitis, ascites, hematemesis, and melena may occur. Morbidity from loss of blood, fluids, electrolytes. Subsequent shock. Death from intestinal perforation or anthrax toxemia. Symptoms subside in 10 to 14 days in survivors 81

82 Inhalational Anthrax Sudden, severe, acute febrile illness in persons at risk following a specific attack Fulminant course and death or acute febrile illness Example: from 2001 attacks: postal workers, members of the news media, and politicians and their staff Half got inhalational anthrax 82

83 Inhalation anthrax Usually fatal. Infective dose is 8,000-15,000 spores. Flu-like symptoms for 4 days. Primary pulmonary infection rare. Endospores are engulfed by alveolar macrophages, get transported to the mediastinal and hilar lymph nodes, germinate and multiply in lymph nodes. Hemorrhagic mediastinitis, peribronchial hemorrhagic lymphadenitis, Lymphatic drainage blocked. Pulmonary edema. Toxin released into circulation. Death from septicemia, toxemia, or pulmonary bleeding/edema. 83

84 Anthrax CXR CXR: widened mediastinum (classic but not so common), infiltrates, pleural effusion Chest CT: hyperdense hilar and mediastinal nodes, mediastinal edema, infiltrates, pleural effusion Hemorrhagic mediastinitis, hemorrhagic thoracic lymphadenitis, hemorrhagic meningitis; 84

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86 Diagnostic tests Toxin: ELISA Peripheral blood smear & culture: gram- positive bacilli CXR: classically, “widened mediastinum” pleural effusion, mediastinal edema (boards question) Chest CT scan: hyper-dense mediastinal and hilar lymph nodes Thoracocentesis: hemorrhagic pleural effusions 86

87 Diagnosis DFA stain of infected tissues Thoracentesis: hemorrhagic pleural effusions Peripheral blood smear: gram- positive bacilli on blood smear Blood culture: large gram-positive bacilli with preliminary identification of “Bacillus species” 87

88 Treatment: Natural strains sensitive to penicillin Doxycycline (preferred) of tetracyclines Fluroquinolones should have equivalent efficacy; Penicillin, doxycycline, & ciprofloxacin are FDA approved for inhalational anthrax. Other drugs: clindamycin, rifampin, imipenem, aminoglycosides, chloramphenicol, vancomycin, cefazolin, tetracycline, linezolid, and the macrolides. 88

89 Anthrax Prophylaxis Natural anthrax is PCN & TCN sensitive; weaponized Anthrax is resistant. CDC recommends: Oral ciprofloxacin 500 mg q 12 hours. Prophylaxis for 60 days (unless exposure has been excluded) because disease can present 50 days or more after exposure. 89

90 Anthrax Vaccine Poor, many side effects & limited availability. 1997: all U.S. military personnel are required to receive it. Anthrax vaccine adsorbed (AVA): inactivated cell-free product, produced by Bioport Corp, Lansing, Mich. 6-dose SC series: 0, 2, & 4 weeks; then 6, 12, & 18 months; annual boosters. Peacetime / civilian safety has been questioned. 90

91 Weaponizing Anthrax B anthracis engineered to resist tetracycline and penicillin study induced in vitro Ofloxacin resistance Assume PCN & TCN resistance if terrorist attack Fluroquinolones 1 st choice. Maybe. Once susceptibility known, use most widely available, efficacious, and least toxic antibiotic 91

92 Francisella tularensis aerobic, gram-negative, intracellular coccobacillus found in the water, soil, and vegetation. Natural reservoir: small mammals such as rabbits, squirrels, and mice In many ways, similar to Plague 92

93 Tularemia Disease 3 types: Ulcero-glandular, Oro-glandular, Pneumonic. Usual humans infections from insect bites, contact with (skinning) infected rabbits or other small mammals, inhalation, & contact with contaminated environments The last 2 modes of transmission are what makes F. tularensis an ideal agent for BioWar. 93

94 Ulceroglandular Tularemia Most common. It occurs after a bite from an infected arthropod or from handling an infected mammal. Symptoms begin as flu-like and an ulcer appears at the site of infection. Regional lymph nodes enlarge and may resemble buboes. The patient may become bacteremic. Low mortality rate, but may take quite a long time for recovery. 94

95 Oro-glandular Tularemia Usually after ingestion of contaminated raw meat, contaminated water; occasionally from inhalation. Symptoms: stomatitis, exudative Pharyngitis or tonsillitis. Cervical or retropharyngeal lymphadenopathy will occur and also may resemble buboes. Bacteremic possible; low mortality rate, but long recovery. Immunity ? 95

96 Pneumonic Tularemia Most severe form Inhalation of aerosolized bacteria. Or secondary to hematogenous spread from cutaneous or oral lesions. Symptoms: fever, non-productive cough, pleuritic chest pain, chills, headache, and malaise. It may resemble community-acquired pneumonia. No person to person spread; no isolation needed. Mortality rate of 30-60%. 96

97 Tularemia Chest x-ray May show infiltrates, hilar adenopathy, or pleural effusion. Can have TB-like miliary infiltrates. Sometimes caseating granulomas found on lung biopsy. Culture of F. tularensis will grow in about hours, and can make the definitive diagnosis PCR or ELISA may also be used to aid in the diagnosis. 97

98 Treatment of Tularemia Streptomycin 30mg/kg IM q 12 h x days. Alternative gentamicin 5mg/kg IM or IV q day x days. Vaccination is not recommended as a post- exposure prophylaxis. No live attenuated vaccine against tularemia yet. Weaponised Tularemia: oral doxycycline or ciprofloxacin are recommended as post- exposure prophylaxis. 98

99 Viral Hemorrhagic Fevers RNA viruses: highly lethal, high infectivity by aerosol route % mortality Sx: febrile illness, liver failure, DIC, hypotension, death. Highly contagious. Dx: Setting, environment, H&P Confirm: viral serologies or culture (difficult) Available in the wild; hard to handle. Weaponizable when techniques for tissue culture mature. 99

100 The Viral Hemorrhagic Fevers Ebola Hemorrhagic Fever and Marburg Disease from the Filoviridae family. Lassa Fever from the Arenaviridae family Rift Valley Fever & Crimean Congo Hemorrhagic Fever, from the Bunyaviridae family 100

101 Clinical Hallmarks of Ebola Bleeding everywhere: DIC, capillary leaks, “bleeding eyes” Nose, GI tract… Highly Infective 101

102 VHR Patient Isolator 102

103 Treating in Isolator Difficult 103

104 VHF - Treatment Mostly supportive and ineffective In a mass casualty situation, Triage (in the harshest sense of the word) For lesser numbers, consider antivirals Ribavirin for Lassa, CCHF, Rift Valley 104

105 Personal Protective Equipment (PPE) No universal standard of PPE for health care providers in BioWar. Health Care workers will be among the first infected secondarily Fear of contamination or infection may prevent some physicians from going to work At a minimum: mask, gown, gloves. Complete change of clothes and shower BEFORE LEAVING FACILITY. HCW may be isolated into workplace 105

106 Decontamination in hospital Decontamination PRIOR TO patient arrival, and AWAY from hospital ventilation ducts. Do you know where the UH decon room is? BioAgent: undress, & mask the patient. For most agents, this would be enough. Anthrax: washing the patient with soap and water reduces the likelihood of secondary aerosolization of the spores. 106

107 Mass Casualty Wet decontamination (undress completely, shower & with soap/detergent, contain effluent.) Isolate & decontaminate all clothing & patient goods Dilute bleach solution: hypochlorite can render a biological agent harmless, is safe for equipment and most fabrics (hypochlorite is contraindicated for open wounds) Heat and radiation for durable equipment: Autoclaving and dry heat at 100 C x 2 hours Solar UV radiation and desiccation to inactivate biological agents. 107

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