Presentation on theme: "Bioterrorism and medical countermeasures"— Presentation transcript:
1 Bioterrorism and medical countermeasures Dr. Marwan Jabr AlwazzehAssoc. Prof. of MedicineConsultant Internist/Infectious DiseasesUniversity of Dammam
2 What is Biological Warfare? The use, for hostile purposes, of living organisms, whatever their nature, or infective material derived from them, which are intended to cause disease or death in man, animal, or plants
3 Bioweapens recent history Bioweapons have a long history. Recent uses include:U.S, Canada, Great Britain, Japan, and the Soviet Union with anthrax during World War IIPost World War II, NATO and the Warsaw Pact nations had bioweapons programsOther countriesBioterrorism
4 The threat of biological warfare Biologic agents are likely to be used as weapons because:Relatively easy to procurePotentially inexpensive to produceUnless the terrorists announced the release of agent, detection of the attack would be challenging (odorless, colorless and tasteless)Can be used to attack people, economies and food suppliesCause fear, panic and social disruption
5 Biological warfare arsenal of the Cold Ware Superpowers (U.S) Anticrop weaponsIncapacitating agentsLethal agentsWheat-stem rustRye-stem rustRice-blast sporeVenezuelan equine encephalitisStaphylococcal Enterotoxin BBrucella suisCoxiella burnetiiBacillus anthracisBotulinum toxinFrancisella tularensis
6 Biological warfare arsenal of the Cold Ware Superpowers (Soviet Union) SmallpoxYersinia pestisBacillus anthracisBotulinum toxinVenezuelan equine encephalitis virusFrancisella tularensisCoxiella burnetiiMarburg virusInfluenza virusBurkholderia malleiRickettsia typhi
7 The Ideal Bioweapon Contagious Virulent Robust Difficult to detect Drug-resistantUser-controllable
8 Characteristics of biological attacks Incubation periodsA delay is likely between the release of the agent and the knowledge that the occurrence is a sinister actA short window of opportunity exists between the first wave and the second waveSeveral inherent differences that make biological weapons different than conventional or chemical.Covert attack most likely – Perpetrators will be long gone. May be weeks before the attack is detected. No “scene” where victims will be treated or decontaminated.Because of covert attack and incubation – victims may very widely spread out geographically anthrax attack showed that agent may be widely dispersed as well.One of the few disasters/terrorist events where primary healthcare providers are first respondersWe may be discovering new cases/outbreaks for days, weeks, even monthsHoaxes have potential to cause significant impact on healthcare system, law enforcement. (and panic)The potential for casualties is massive (staggering) – especially with agents that spread person to personAnn EM 34: 221
9 Characteristics of Biological attacks Victims widely dispersed and likely to present for days to weeksPotential for many casualties“First responders” may be health care providers
10 Hypothetical dissemination of some infectious agents Total casualtiesDeathsDownwind carriageAgent12500095000>>20 kmAnthrax1000005500010 kmPlague30000>20 kmTularemia3500095001 kmTick-borne encephalitis85000190005 kmEpidemic typhus500Brucellosis150Q-fever400Venezuelan equine encephalitisCasualty figures assume 50 kg of dried agent, disseminated along a 2-km line upwind of a population center of
11 Critical agents for public health preparedness Category CCategory BCategory AEmerging threat agents (e.g., nipah virus, hantaviruses, pandemic influenza viruses)Coxiella burnetiiBrucellaeBurkholderia malleiBurkholderia pseudomalleialphavirusesRickettsia prowazekiiCertain toxins (e.g., ricin, SEB)Chlamydia psittaciFood safety threat agents(e.g., salmonellae, E. coli O 157:H7)Water safety threat agents(e.g., vibrio cholera)Variola virusBacillus anthracisYersinia pestisBotulinum toxinFrancisella tularensisFiloviruses and arenaviruses
12 CDC CATEGORY A AGENTS Ease of dissemination Agents that would have maximum impact on population:Ease of disseminationPerson-to-person transmissionHigh mortalityNeed for public health preparednessThe CDC has developed lists of agents that have the potential for use as biologic weapons. The agents are divided into category A,B,C. The different categories are based mostly on public heath impact of the different bioagents and to some degree likelihood of use.Category A agents have the highest potential for impact. These agents have a high potential for mortality. Several may be spread person to person. Easy to disseminate. Highest priority for public health preparedness!All of these agents have already been weaponized, some of them have actually been used.Category A Variola major (Smallpox), Bacillus anthracis (Anthrax),Yersinia pestis (Plague), Clostridium botulinum (botulinum toxins), (Botulism), Francisella tularensis (Tularemia), Filoviruses and Arenaviruses (e.g., Ebola virus, Lassa virus)--Viral hemorrhagic fevers.
14 ANTHRAXBacillus anthracis has characteristics that make it attractive as biological weapon:Easy to obtainGrows readily in easily prepared mediaCan be easily induced to form sporesSpore size and durability
16 CLINICAL FORMS OF ANTHRAX Cutaneous form:7 days after exposure to infected hides or meat, a painless or mildly pruritic papule formsThe lesion rapidly enlarges and ulcerates, often accompanied by significant surrounding edema and regional lymphadenopathyThe case fatality rate of cutaneous anthrax is 20% without antibiotic treatment, and <1% with antibiotics.
17 CLINICAL FORMS OF ANTHRAX Gastrointestinal formRare natural occurrenceResults from consumption of insufficiently cooked meat of infected animalsTypically develop massive gastrointestinal bleeding and sepsisFatal outcome in 50% of casesOropharyngeal anthrax
18 CLINICAL FORMS OF ANTHRAX Inhalational formPresent within 1-6 days of exposure (but perhaps up to several month later)Person-to-Person spread extremely rareNonspecific febrile prodromePneumonia is rare, but there is usually mediastinitis and plural fusionFatal outcome in 45-85% of casesAnthrax Meningitis manifests in 50% of Inhalational Anthrax patients
19 CLINICAL FORMS OF ANTHRAX CXR classically shows mediastinal widening with clear lung fieldsNon-contrast chest CT was useful in leading to a presumptive diagnosis in some patients
20 DiagnosisBlood culture (on blood agar) is the gold standard and is very specific (100% before antibiotic initiation)Culture from the cutaneous lesion (from vesicle)Stool cultureImmunohistochemical stainsPCR
21 Treatment Cutaneous form Systemic and route unknown: Initial empirical should be include ciprofloxacin or doxycycline plus one or tow additional effective antibioticsHuman anthrax immune globulin (in clinical trials)
22 Postexposure prophylaxis Oral ciprofloxacin, levofloxacin or doxycycline for at least 60 daysAnthrax Vaccine Adsorbed (AVA) (under investigation)Contact precautions
23 SMALLPOX Two forms: Variola Major and Variola Minor Variola virus - Orthopox virusTwo forms: Variola Major and Variola MinorGlobal eradication was in 1980, but remaining viral stocks existSmallpox caused by the virus Variola major. Two forms: Variola major = 20-40% mortality in unvaccinated. Variola minor = 1% mortality in unvaccinatedNo non-human reservoirs. Has survived through history by continual human to human transmission. Probably responsible for 100 million deaths during the 20th century alone.WHO declared smallpox eradicated in 1980 – vaccination in U.S. ceased shortly thereafter.Researchers estimate that vaccinated individuals retain immunity for approximately 10 years.Currently there are two WHO-approved repositories of variola virus: CDC in Atlanta and the Russian State Research Center of Virology and Biotechnology in Koltsovo (former Soviet Union). According to the former deputy director of the biological weapons program in the Soviet Union (Ken Alibeck), massive amounts of smallpox were produced since 1980.Notice that for most of these agents the incubation period runs around 1-2 weeks. May present with nonspecific febrile prodrome.
24 SMALLPOX Droplet-borne infection Person-to-person spread very rapid and would likely infect 35-50% of unvaccinated case contactsIncubation period: 7-17 daysNonspecific influenza-like symptoms of prodromal phaseThe rash appears in centrifugal patternMortality: less than 1% in the minor form and 20 to 50 % in the major form
25 SMALLPOX RASHThese photos show different stages of the smallpox rash DIFFERENCE BETWEEN VARICELLA AND VARIOLAMaculopapular => vesicular => pustular => scabs => scarsStarts in mouth/face then hands/forearms then legs then trunk.Synchronous = all same stage.Becomes distinctive when pustular – umbilicated.
26 SMALLPOX RASHThese photos show different stages of the smallpox rash DIFFERENCE BETWEEN VARICELLA AND VARIOLAMaculopapular => vesicular => pustular => scabs => scarsStarts in mouth/face then hands/forearms then legs then trunk.Synchronous = all same stage.Becomes distinctive when pustular – umbilicated.
27 SMALLPOX RASHThese photos show different stages of the smallpox rash DIFFERENCE BETWEEN VARICELLA AND VARIOLAMaculopapular => vesicular => pustular => scabs => scarsStarts in mouth/face then hands/forearms then legs then trunk.Synchronous = all same stage.Becomes distinctive when pustular – umbilicated.
28 SMALLPOX RASHThese photos show different stages of the smallpox rash DIFFERENCE BETWEEN VARICELLA AND VARIOLAMaculopapular => vesicular => pustular => scabs => scarsStarts in mouth/face then hands/forearms then legs then trunk.Synchronous = all same stage.Becomes distinctive when pustular – umbilicated.
31 Treatment There is no specific treatment Supportive care Antiviral drugs (Cidofovir)Vaccina immune globulin
32 Postexposure prophylaxis Strict contact and respiratory isolation until all scabs have separatedSmallpox vaccine (within 4 days of exposure)Near complete protection lasting at least 5-10 yrsVaccinia immune globulin is also effectivethe antiviral drug cidofovir
33 PlagueInfectious agent: Yersinia pestis – a non-motile, Gram-neg., coccobacillus
34 Plague Plague is primarily a zoonotic disease In nature, fleas living on rodents spread infection to humansAs a bioterrorist weapon – inhalation of aerosol leads to pneumonia and sepsis
36 Bubonic Plague Incubation period: 2-6 days Bite of infected flea Characteristic “bubos” grossly enlarged, extremely tender lymph nodesSuppurative lymphadenopathy and fever
37 Bubonic PlagueIf untreated, can lead to pneumonic or septicemic forms of plague
38 Pneumonic Plague Short incubation: 2 to 3 days Aerosolized bacilli Short, febrile prodromeRapid progression to severe pneumoniaFatality: 100% if untreated within 24 hours of symptom onsetPneumonic plague is caused by inhalation of aerosolized Yersinia pestis bacilli.Presents within about a week. Short febrile prodrome with rapid progression to severe pneumonia. Death occurs by respiratory failure and circulatory collapse. Can also spread to CNS and cause plague meningitis in about 6%.Mortality of untreated bubonic plague is about 60%, less than 5% with prompt treatment. In untreated pneumonic plague mortality is nearly 100% - survival unlikely if treatment delayed beyond 18 hours of infection.Person to person spread is possible by droplet transmission
39 Often fatal even when treated “Black Death” Septcemic PlagueRare, usually seen secondary to pneumonic or bubonic forms of plagueProgression:PurpuraDisseminated intravascular coagulation (DIC)Acral necrosisOften fatal even when treated “Black Death”
40 Diagnosis Wayson, Wright’s, Giemsa stains Blood, sputum and CSF cultureSerologic tests provide a diagnosis retrospectively
41 Treatment Rapid antibiotic therapy Streptomaycin or Gentamycin Alternative ciprofloxacin or doxycyclineBeta-lactams,rifampin, and macrolides are ineffective
42 Postexposure prophylaxis Strict respiratory isolation until 48 hrs of effective antibiotic therapyCiprofloxacin or doxycycline for 7 days after exposure
43 TularemiaA zoonotic, bacterial infection caused by Francisella tularensis, a tiny, pleomorphic, poorly staining Gram-negative coccobacillus
44 TularemiaCommonly found in ticks living on rabbits and transmitted by handling the animal or by tick bite
45 Tularemia Inhalation of aerosol leads to pneumonia and sepsis Incubation period: 3 to 5 days (range 1 to 14)Person-to-person transmission is unusualSudden onset with influenza-like symptoms such as fever, chills, malaise, profuse sweating, headache and nauseaPulse-temperature dissociation
46 Tularemia CLINICAL FORMS Ulceroglandular (Most common form in naturally occurring cases)GlandularOcculoglandularOropharyngealThese are the forms of Tularemia recognized by the CDCUlceroglandularMost common form in naturally occurring casesCutaneous ulcer with regional lymphadenopathy—progresses to pneumonia in approximately 30% of casesGlandularRegional lymphadenopathy with no ulcerOropharyngealStomatitis or pharyngitis or tonsillitis and cervical lymphadenopathyIntestinalIntestinal pain, vomiting, and diarrheaPneumonicPrimary pleuropulmonary diseaseTyphoidalFibrile illness without early localizing signs and symptomsPathophysiology: Humans become infected after introduction of the bacillus by inhalation, intradermal injection, or oral ingestion. The clinical form of disease reflects the mode of transmission. Some authors classify the disease as typhoidal (predominance of systemic symptoms), pneumonic (pulmonary findings), or ulceroglandular (regional symptoms). ( Tularemia: Kerry O Cleveland, MD, et al.)Multiple forms of tularemia depending on route of transmission. In naturally occurring disease the most common form is ulceroglandular which occurs after inoculation of skin (bite of deer fly). This form causes a skin ulcer and regional lymphadenopathy.UG tularemia progresses to pneumonia in approx 30% cases.Primary clinical forms vary in severity and presentation according to virulence of the infecting organism, dose, and site of inoculum.The onset of tularemia is usually abrupt, with fever (38oC–40oC), headache, chills and rigors, generalized body aches (often prominent in the low back), coryza, and sore throat. A pulse-temperature dissociation has been noted in as many as 42% of patients. A dry or slightly productive cough and substernal pain or tightness frequently occur with or without objective signs of pneumonia, such as purulent sputum, dyspnea, tachypnea, pleuritic pain, or hemoptysis. Nausea, vomiting, and diarrhea may occur.Sweats, fever, chills, progressive weakness, malaise, anorexia, and weight loss characterize the continuing illness.In general, tularemia would be expected to have a slower progression of illness and a lower case-fatality rate than either inhalational plague or anthrax. Milder forms of inhalational tularemia would be indistinguishable from Q fever; another potential bioterrorism agent; establishing a diagnosis of either would be problematic without reference laboratory testing. (CDC website)
47 Tularemia CLINICAL FORMS Pneumonic (Primary pleuro-pulmonary disease) TyphoidalAbrupt onset of febrile illness in 3-5 daysRapid progression to life-threatening pneumonitis in 80% of typhoidal casesCase fatality rate for typhoidal tularemia is 35% in untreated patients
49 Diagnosis Sputum Gram’s stain is invariably negative Culture of Blood, sputum or plural fluid is slow and insensitiveSerologic tests more sensitivePCR available
50 TreatmentRapid antibiotic therapy (Mortality rate > 60% in untreated cases)Streptomaycin or GentamycinAlternative ciprofloxacin or doxycyclineCefteriaxone is ineffective
51 Postexposure prophylaxis Strict contact precautionsCiprofloxacin or doxycycline for 14 days after exposureA live attenuated vaccine available, but not recommended for postexposure prophylaxis
52 BotulismClostridium botulinum – a spore forming, anaerobic Gram-positive bacillusNo person-to- person transmissionIncubation period: 12 to 72 hours
53 Botulism There are 7 neurotoxins (A-G) LD50 =0.001 µg/kg (the most potent chemical warfare agent)Affect the motor nerve terminus with irreversibly blocks the release of acetylcholineMuscle paralysis lasts until axonal branches regenerate
54 Botulism Food-born botulism (ingested toxin) Gastrointestinal and Infant botulism (Clostridium botulinum)Wound botulism(Clostridium botulinum)Iatrogenic botulism (Botox)Pulmonary botulism(inhaled aerosolized toxin)Infant = caused by infants who ingest C. botulinum spores. Infants have no gut flora and spores can germinate liberating large amounts of botulinum toxin. Classic association is with infants getting contaminated honey. Babies present with poor feeding, poor muscle tone. In texts this is reported as most common form.Wound = seen usually in injection drug users who inject themselves with contaminated drug. Spores are able to germinate in an abscess cavity and liberate toxin. Patients most commonly present with bulbar symptoms – like diplopia or difficulty swallowing. Frequently the contaminated wound can’t be found. At UC Davis this is the most common form we see. In fact, in California, stores of botulinum antitoxin are kept at LAX, SFO, and at UC Davis (we have our own store because of the number of cases we see).Iatrogenic = newest form. Caused by iatrogenic injection of Botox. May cause unwanted paralysis of individual muscles (the case I saw was neck muscle paralysis – patient couldn’t hold head up). I don’t think systemic poisoning from iatrogenic injection has been reported (?).Food-born = from contaminated canned foods. Spores in can germinate and release toxin into food. This is why food must be properly heated in a pressure cooker when home canning.GI = Occurs in patients with surgically altered gut physiology. Allows botulinum spores to germinate in gut and liberate toxin.Pulmonary = Due to inhalation of aerosolized botulinum toxin. This is what we are concerned about with weaponized botulinum toxin. Only a few cases have occurred – some lab workers were accidentally exposed.
55 Botulism Classic triad: Lack of fever Clear sensorium Symmetric descending flaccid paralysisSymptoms include ptosis, diplopia, dysarthria, dysphagia, dry mouth, and Muscle weakness
56 DiagnosisCases presenting with the classic syndrome can be diagnosed clinicallyMouse bioassay (confirmatory test)
57 Treatment Supportive care particularly ventilatory support Botulinum antitoxins (IV)
58 Postexposure prophylaxis Asymptomatic persons: Botulinum antitoxin is not recommended for prophylaxis (10% hypersensitivity reactions)Symptomatic persons: Botulinum antitoxin and carefully monitoring
59 Viral Hemorrhagic Fevers (VHFs) Virus FamilyDisease (Virus)Natural DistributionUsual Source of Human InfectionRespiratory transmissionIncubation (Days)ArenaviridaeArenavirusLassa feverAfricaRodentyes5-16Argentine HF (Junin)South America7-14Bolivian HF (Machupo)9-15Brazilian HF (Sabia)Venezuelan HF (Guanarito)BunyaviridaePhlebovirusRift Valley feverMosquito2-5NairovirusCrimean-Congo HFEurope, Asia, AfricaTick3-12HantavirusHemorrhagic fever with renal syndrome, hantavirus pulmonary syndromeAsia, Europe, worldwide9-35FiloviridaeFilovirusMarburg and EbolaUnknown3-16FlaviviridaeFlavivirusYellow feverTropical Africa, South America3-6Dengue HFAsia, Americas, AfricaUnknown for dengue HF, 3-5 for dengue
60 Viral Hemorrhagic Fevers (VHFs) All share the potential for severe disruption of vascular permeability (vascular endothelial damage) and bleeding diathesis (DIC)Think at VHF in every case with unexplained leukopenia, thrombocytopenia and hepatitis
61 Viral Hemorrhagic Fevers (VHFs) Sudden onset of fever, muscle aches, headache, followed by vomiting, diarrhea, rash and bleeding
62 Viral Hemorrhagic Fevers (VHFs) Progresses rapidly to hypotension, shock, mucosal and GI bleeding, edema and end-organ failure
63 Viral Hemorrhagic Fevers (VHFs) Confirmed diagnosis can be made for most VHFs serologicallySome viruses can be culturedSupportive therapy is crucial for all patientsAntiviral therapy (Ribavirin IV) has been used experimentally for Crimean-Congo HF, Lassa, Rift Valley fever and HF caused by hantaviruses
64 Postexposure prophylaxis All patients should be placed in respiratory and contact isolationOral Ribavirin can be used after high-risk exposure to Crimean-Congo HF, Lassa, Rift Valley fever and HF caused by hantavirus
65 Horses or Zebras? Outbreak of rare disease Seasonal disease at wrong timeUnusual age distributionUnusual clinical symptomsUnusual epidemiologic featuresOutbreak in region normally not seen
66 Horses or Zebras?Rapidly increasing disease incidence in a healthy populationMultiple diseases in one patientDead animals (especially multiple species)History of visible cloudClaims by aggressorsFulminant disease presentationsTravel history
67 The Ideal Bioweapon Contagious Virulent Robust Difficult to detect Drug-resistantUser-controllable