Bioterrorism-Related Disease and Method of Outbreak Investigation

8/6/2019 Bioterrorism-Related Disease and Method of Outbreak Investigation

1/51


2/51

` Our world must take bio-security much moreseriously [] It would be comparatively easy for

terrorists to cause mass death by using agents such as

anthrax or weaponized smallpox. Lets not wait until

something has gone terribly wrong to act collectivelyto meet this threat

` Kofi Annan, UN Secretary General, February 13, 2005


3/51

BIOTERRORISM

` "Bioterrorism refers to the intentional release ofbiological agents or toxins for the purpose of harming orkilling humans, animals or plants with the intent to

intimidate or coerce a government or civilian population

to further political or social objectives."` (Bioterrorism Incident Pre-planning and response guide, ICPO

INTERPOL, 2007)


4/51

BIOTERRORISM

CLASSIFICATION

OVERT COVERT

ImmediateEarly recognition of event

More challengingClinical microbiologist & physician

First to suspect the attackDelayed recognition & response


5/51

BIOLOGICAL WAREFARE

` The use of bacteria, viruses, fungi, or toxins to injurepeople, animal, or crops to gain a military advantage

` WWI: Germany

` Human: Vibrio cholerae & Yersenia pestis

` Animal:Bacillus antracis & Burkholderia mallei

` Geneva protocol


6/51

Bio-safety Level (BSL)

` Classification of microorganism based on diseasepotential

` Combination of standard procedures and technique,safety equipment, and facilities designed to minimize the

exposure of workers and the environment to infectiousagents


7/51

Bio-safety Level (BSL)

BSL-1 BSL-2 BSL-3 BSL-4

Do not ordinarilycause disease inhuman

Cause humandisease

But not readily

transmitted

Many are recovered

in clinical lab

Biological safetycabinet required[culture included]

Transmission: respiroute

Produce seriousillness

Transmission: respiroute

High risk of serious

disease

No available

treatment

Very strict

precautions

Bacillus subtillis HBVSamonellaBacillus anthracis[clinical specimen]

Bacillus anthracis[grown in largeconcentration]

Ebola virusCongo Crimeanhemorrhagic virus

Table 1.Bio-safety Level Classification


8/51

Bio-threat Level/Bio-terrorism Agent

Category

` CategoryAAgents` Highest Priority Agent

` Easily disseminated or transmitted person-to-person causing secondary and tertiary cases

` Cause high mortality with potential for majorpublic health impact including the impact onhealth care facilities.

` May cause public panic and social disruption

` Require special action for public healthpreparedness.


9/51


Category

` Category BAgents

` 2nd highest priority

` Moderately easy to disseminate

` Cause moderate morbidity and low mortality

` Require specific enhancement of CDC's diagnostic

capacity and enhanced disease surveillance


10/51


Category

` Category CAgents

` 3rd highest priority

` Emerging pathogens that could be engineered for mass

dissemination

` Availability

` Ease of production and dissemination

`

Potential for high morbidity and mortality and majorhealth impact


11/51

Bio-threat Level/Bio-terrorism Agents

Category

Category B Category C

Coxiella burnetti (Q fever)

Brucella species (brucellosis)

Burkholderia mallei (glanders)

Burkholderia pseudomallei (Melioidosis)

*alphaviruses,Venezuelan encephalomyelitisEastern andWestern equine

Encephalomyelitis

Ricinus communis (Castor bearns)

Clostridium perfringens

Staphylococcal enterotoxin B

Salmonella speciesShigella dysenteriae

Escherichia coli 0157:H7

Vibrio cholerae

Cryptosporidium parvum*Rickettsia prowaken (Typhus fever)

Chlamydia psittaci (Psittacosis)

Nipah virus

Hantaviruses

Tickborne

hemorrhagicfever viruses

Tickborne

encephalitisviruses

Yellow Fever

Multidrug

resistanttuberculosis

CategoryA

Variola major (small pox)Bacillus anthracis (anthrax)Yersinia pestis (plague)Clostridium botulinum toxin

(botulism)Francisella tularensis

(tularaemia)Filoviruses,Ebola hemorrhagic feverMarburg hemorrhagic

feverArenaviruses,

Lassa (Lassa fever)Junin (Argentine

hemorrhagic fever)And related viruses

Table 2.Bio-terrorism Agents Category


12/51

General Characteristics of Bioterror Agent

` Cost less than conventional and other weapon` Culturing: No required training or expertise

` Mobile laboratories housed in large vans/semitrailers

` Produce large amount of bio-weapon in small laboratory,release the agent, and move on before the attack wasnoticed [COVERT]

` Wide scope of MOT

`

Efficient transmission: Aerosol` Dilution may occur in food/water

` Person-to-person spread

` Use of SPORES [Disadvantage: Out-of-target]


13/51

Laboratory Response Network (LRN), 1999

` Established by CDC, Association of Public HealthLaboratories (APHL), Federal Bureau of Investigation(FBI) & USAMRIID

` Goal: To decentralize testing capabilities and to link stateand local laboratories with advanced-capacity clinical,military, veterinary, agricultural, water, and food testinglaboratories


14/51

Laboratory Response Network (LRN), 1999

Recognize

Rule outRefer

Confirmatory testing

Definitive characterizationNational

Labs

Reference Labs

Sentinel Labs

Figure 1. The structure of LRN


15/51

Bio-terror Agents

` Bacillus anthracis` Yersenia pestis

` Francisella tularensis

` Brucella Species

` Burrholderia Species` Coxiella burnetii

` VariolaVirus

` Viral hemorrhagic Fevers

` Clostridium botulinumToxin` Staphylococcal Enterotoxis

` Ricin


16/51

Bacillus anthracis

` Anthrax` Aerobic Gram positive bacilli

` Disease of herbivores

` Forms

` Cutaneous anthrax lesion [common]

` Gastrointestinal anthrax nausea & vomiting

` Inhalation of spores

Figure 1. Bacillus anthracis in Grams stain


17/51

Bacillus anthracis

Figure 4. Inhalation of anthrax sporesdevelops intomediastinitis shown inchest radiograph

Figure 3. Necrotic lesion ofcutaneous anthrax characterized by

blackeschar


18/51

Bacillus anthracis

` Specimen Collection` Cutaneous = Vesicular fluid

` GI = blood; {culture} stool & rectal swab

` Inhalation = blood

` Direct Examination` Gram positive bacilli; may be evident for capsule

` Culture

` Rapid growth (8 hours)

` Nonhemolytic colonies (SBA)

` Medusa-head colonies


19/51

Yersenia pestis

` History Pandemic Plague1. EGYPT: 541AD

2. ASIA: 1330 & EUROPE: 1347 BLACK DEATH

` 1894:AlexandreYersinBubonic plague

` 1st to describe the agent

` Xenopsylla cheopis (rat flea) - vector

` Rattus rattus (black rat) most responsible in urban outbreak


20/51

Yersenia pestis

` Bubonic plague (most common form)` Bite of infected flea (MOT)

` S&S: Fever, chills, headache, malaise

` Multiply in the lymph node = BUBO

` Leads to disseminated intravascular coagulation (DIC) withpetichae & gangrene

Figure 5. Clinical manifestation ofYersenia pestis:Bubo on the leg (left) & Gangrene(right). Media from Center for Disease Control and Prevention.


21/51

Yersenia pestis

` Specimen Collection` Sputum,Bronchial wash, Tracheal aspirate

(specimen of choice)

` w/ sepsis & fever: blood

` w/ bubo: aspirated lesion

` Direct Examination` Gram negative bacilli, singly or short chain

(long in liquid med.)

` Bipolar staining characteristic/ Safety pinappearance

` Culture` Slow (48 hours)

` Nonhemolytic (SBA)

` Fried egg appearance

Figure 6. Yersenia pestis in Gramsstain. Safety pin appearance. Media

from Center for BiologicCounterterrorism and Emerging

Diseases.


22/51

Francisella tularensis

` 1911: 1st isolated & described` Outbreak of ground squirrels in Tulare County, CA

` Tularemia/Oharas disease

` Accidental contact on the infected organism

` Common reservoir: Several tick species

` Most common mammal-associated: Rabbit

` Recognized as potential bioweapon


23/51


` Ulceroglandular tularemia (most common)` Inoculation on the dermis/Bite of infected organism

` Incubation: 3-10 days = febrile w/ chills, headaches, cough, chestpain

` May manifest bubonic plague-like buboes` Develops among outdoor-related work

` Pneumonic tularemia

` Inhalation

` Fever and LRTI (influenza-like illness)Figure 7. Cutaneous lesion of tularemia onthe right hand. Media from Center forDisease Control and Prevention


24/51


` Specimen Collection` Blood & Biopsies

` Direct Examination

` Pleomorphic gram negative coccobacilli

` Culture

` Growth not rapid (36-48 hours)

` Cystine-dependent

` Grows well CAP, Thayer-Martin, Buffered charcoal yeast-

extraxt


25/51

BrucellaSpecies

` Malta fever, undulant fever, Mediterranean fever, Cyprusfever,Bangs disease` Associated with human

` Brucella melitensis (sheep & goats)

` Brucella suis (swine)

` Brucella abortus (cattle)` Not associated with human

` Brucella ovis (sheep)

` Brucella neotomae (desert wood rat)

` Brucella canis (dogs)

` Potential aerosol waepon


26/51

BrucellaSpecies

` Brucellosis` MOT:Breaks in skin, ingestion of

contaminated food, inhalation

` Respiratory tract or Occupationalexposure

` Hematogenous dissemination(seeding of multiple organ)

` Lung, Liver, Spleen, CNS

` Malaise, Night swear, Relapsing

fever, Chills, Myaglia` Relapse may occur after

medicationFigure 8. Exposure to infected animals maytransmit Brucella virus to human. Media

from ADAM


27/51

BrucellaSpecies

` Specimen Collection` Biosafety cabinet

` Blood,BM, tissues and fluid from affected organ, abscess


` Small Aerobic Pleomorphic Gram negative coccobacilli

` Culture

` Blood culture bottles: retain up to 10 days (slow)

` Grows in aerobic - CAP & SBA (48 -72 hours)

` Small, circular, smooth, convex, nonpigmented, nonhemolytic

` Catalase, Oxidase, Nitrate reduction, Urease positivity, Motility


28/51

BurkholderiaSpecies

` 2 potential agent:

` B. mallei (Glanders)

` B. pseudomallei (Meliodosis)

` Endemic: SE Asia, South Pacific, Africa, India, Middle East

` Found in soil & water

` Equids (horses, mules, donkeys)

`

Direct contact with infected animals` 2Cases (human-human transmission): Sexual or direct contact

` S&S: Fever, Myaglia, Headache, Chest pain


29/51

BrucellaSpecies

` Specimen Collection` Blood,BM, Sputum,Bronchial alveolar lavage, Abscess, Urine,

Sputum


` Gram negative coccobacilli (B. mallei); positive (B. pseudomallei)` Culture

` Incubation: 35C, 5%CO2 5 days

` SBA: small, circular, butyrous colony after 24-48 hours

` MAC


30/51

Coxiella burnetii

` Q(uery) fever` Outbreak: slaughterhouse workers, Australia 1935

` Reservoir: cattle, sheep, goats, dogs, cats, deer, fowl(asymptomatic)

` Risk: Occupational exposure` Develops to PNEUMONIA or HEPATITIS (chronic)

Figure 9. A possible reservoir ofCoxiellabrunetii, a goat.


31/51

Coxiella burnetii

` Specimen Collection` Blood, Serum, Tissue, Body fluids


` Obligate intracellular Gram negative coccobacilli

` Culture` Grow in the cell monolayer (not in plated media)

` Serological testing

` High titer: Phase 1 Phase II


32/51

Variola Virus

` Family Poxviridae, Genus Othropoxviridae[smallpox]

` Brick-shaped double-stranded DNA virus

` MOT: Respiratory droplets/Directcontact/Fomite

` Replicates at oropharynx/respiratory mucosathen to lymph nodes` TRANSIENT ASYMPOTMATIC VIREMIA

` Fever & malaise, influenza-like syndrome in 8-10 days

` Oral lesions

` Light macular rash > Vesicular rash


33/51

Viral hemorrhagic Fevers

` All viruses: single stranded RNA viruses` Ebola

` Marburg viruses (family Fioviridae)

` Lassa fever virus (familyArenaviridae)

` Crimean-Congo hemorrhagic fever virus

` Rift Valley virus

` Hantaviruses (family Bunyaviridae)

` Dengue` Yellow fever

` Omsk hemorrhagic fever viruses (family Flaviviridae)


34/51

Viral hemorrhagic Fevers

` Incubation: 2-3 weeks` Fever, Rash, Myglia,Arthalgia, Nausea, Conjunctivitis, Diarrhea, CNS

symptoms {not all viruses}

` Infection: Varying degree of bleeding

Ranging from DIC, petichiae, hemorrhage of mucousmembrane, to blood in urine and vomitus

` Specimen Collection

` Should not collect from patient with suspected viralhemorrhagic fever until after consultation

` [compatible to disease] Serum, Heparinized plasma.Wholeblood, Respiratory aspirates, Tissue & Urine


35/51

Clostridium botulinum Toxin

` Botox/Botulinum toxin` Recovered from soil species throughout the world

` Food-borne botulinum: ingestion of toxin

` Incubation: (vary) 2 hours 8 days

` Develop trouble in speaking, swallowing, and seeing

` Respiratory paralysis = Death

`

Specimen Collection` Feces, gastric aspirate/vomitus, Serum, Tissues/exudates & food

specimen >>> LRN reference laboratory


36/51

Staphylococcal Enterotoxins

` Small molecular wt. polypeptides` BACTERIAL SUPERANTIGEN family

` Mild exposure resembles CMI response

` Approx. 18 staphylococcal enterotoxins identified

` Symptoms vary: enterotoxin & route of entry

` SEB: Staphylococcal enterotoxin B` Category B bioterrorism agent

` Fever, Respiratory complaints (cough, dyspnea, and chest pain),GI symptoms

` Severe: Pulmonary edema, respiratory distress syndrome,shock, & possibly death


37/51

Ricin

` Category B bioterrorism agent` From castor beans (Ricinus

communis)

` Potent biologic toxin that inhibits

protein synthesis` Inhalation: mist/powder

` Ingestion: Profuse vomiting &diarrhea

` Multisystem organ failure

` Possibly death within 36 -72 hours

Figure 10. Castor beans

Figure 11.

Image of Georgi

Markov, a

Bulgarian writer

& journalist in

London, died

after injected

with ricin pellet.


38/51


39/51

Outbreak

` CDC:

` Occurrence of more cases of disease

than normally expected within a specific

place or group of people over a givenperiod of time


40/51

Outbreak vs Epidemic vs Pandemic

Outbreak / Epidemic Pandemic

` Epidemiologist samemeaning

` Epidemic > Outbreak

` Serious connotation

` Widespread diseaseepidemic

` Global


41/51

Why investigate???

` To understand & ultimately control and prevent spread ofdisease

` Collecting information

` Identifying the source

` Make recommendations` To facilitate development of new vaccines, drugs and

changes in human behavior as well as legislation for theimprovement of public health


42/51

STEPS in OUTBREAK INVESTIGATION

1. Prepare for field work` Investigators should be:

FAMILIARWITH THE DISEASE

SHOULD HAVE A PLAN OF ACTION

Supplies needed

Division of tasks among members

Administrative and Travel arrangement


43/51


2. Establish the existence of an outbreak` Investigators can examine health department surveillance

records, hospital records, and other disease registries.

***IF

INFORM

ATION

IS UN

AVAILABL

E:Interview with the doctor or people within the community


44/51


3. Verify the diagnosis` Review clinical findings and lab tests

` Determine the specific nature of disease

For example:

In infectious disease outbreaks, additional lab tests may be necessary to

determine the specific strain of microbe implicated in the outbreak.


45/51


4. Define and identify cases` Investigator is responsible for establishing what

constitutes a case.

-Information about disease

-Characteristics of the patient

-Information about the location

-Specific range in time


46/51


5. Describe and orient the data in terms of time, place andperson.

` Investigator understand more about the outbreak bycompiling a comprehensive description of its trens over

time, place, and kinds of people (age, race, sex) affectedby the disease.


47/51


6. Develop hypotheses` Making educated guess about the source of disease,

mode of transmission, and/or exposures that caused thedisease based on available information


48/51


7. Evaluate hypotheses` Evaluation of hypotheses by looking at the facts

` Crunching numbers to get actual statistics


49/51


8. Refine hypotheses and carry out additional studiesADDITIONAL STUDIES:

Lab tests

Environmental studies


50/51


9. Implement control and prevention measures` Control and prevention methods are usually aimed

toward:

Source of disease

Interrupting transmission

Limiting exposure


51/51


10. Communicate findings` Findings of the investigation should be communicated to

local health authorities

-IMPLEMENATION OF CONTROL MEASURES

` Make written that will provide legal record of thefindings and contribute to public awareness

Bioterrorism-Related Disease and Method of Outbreak Investigation

Documents

Transcript of Bioterrorism-Related Disease and Method of Outbreak Investigation