natural history of select agents

Natural history of select agentsNatural history of select agents

The world is awash in The world is awash in microorganismsmicroorganisms

Mostly they go about their businessMostly they go about their businessMany we needMany we needOblivious to mostOblivious to mostA few get crosswiseA few get crosswise

Some of these bad guys we’ve known for thousands of years

Some are newSome used or researched as weaponsSelect Agents

We love to categorize We love to categorize Select agents HHS/FDA/USDA ~ 70

"potential to pose a severe threat to public health and safety”

CDC regulates labs within the U.S.

EU and most developed countries have their own lists

Some researched for bioweapons

Bacillus anthracis-anthrax

Coxiella burnetii-Q fever

Francisella tularensis-tularemia

Variola major-small pox

Yesinia pestis-plague

Brucella suis-brucellocis

Botulinum toxin

Burkholderia mallei-glanders

Ricin toxin

Some other nasty guys out there

Ebola virus

Lassa virus

Marburg Virus

Typhus Rickettsia prowazekii

Crimean-Congo hemorrhagic fever

Vibrio cholerae

Nipah Virus

USDA lists agents with tremendous potential economic impact

Virulent Newcastle Disease

Foot and Mouth Disease

Bovine spongiform encephalopathy (Mad Cow)

Phakopsora pachyrhizi (Asian soybean rust)

Phoma glycinicola (red leaf blotch)

Puccinia triticina (wheat leaf rust)

Natural history of select agentsNatural history of select agents

Did they always have it in for us?Did they always have it in for us?What do they do in their spare time?What do they do in their spare time?Where are new ones coming from?Where are new ones coming from?How do we detect the ones we know How do we detect the ones we know

and identify new ones?and identify new ones?Any special challenges to water systems?Any special challenges to water systems?

Bacillus anthracis

Traits for success in nature make BA dangerous to us

Spore formingAerosolizesReaersolizes

Three infection routesInhalationCutaneousgastrointestinal

Cholera-one of the most feared diseases on earth.

Caused by the bacteria Vibrio cholera

The natural habitat of Vibrio, isn’t our insides, but estuaries

Monsoons bring changes in salinity Monsoons bring changes in salinity and temperature in estuariesand temperature in estuaries

Leading to increased encounters Leading to increased encounters between between VibrioVibrio and copepods and copepods

Filter feeders come in nextFilter feeders come in next

Understanding Understanding VibrioVibrio ecology ecology has broader implicationshas broader implications

How did Vibrio acquire enterobacteriaciae-like toxin?

The ocean is teeming with The ocean is teeming with phages (1-10 million/ml)phages (1-10 million/ml)

Acanthamoeba are everywhereAcanthamoeba are everywhereSoil, freshwater, dirty contact lens, thing the dentist uses to rinse your mouth out

Life cycle includes two stages, a feeding “trophozoite” a dormant cyst.

Trophozoite feeds on bacteria, Trophozoite feeds on bacteria, algae, yeasts, fungi.algae, yeasts, fungi.

Franciscella tularensis Franciscella tularensis (Ft) is the (Ft) is the causative agent of Tularemia.causative agent of Tularemia.

Several select agents are obligate or Several select agents are obligate or facultative intracellular bacteria.facultative intracellular bacteria.

• Coxiella multiplies strictly inside the amoeba,

• Brucella, Francisella, and Yersinia are facultative intracellular bacteria

• The ability to survive within host cells originated as a defense mechanism against predation. It now is a pathway to pathogenicity.

Emerging Infectious Diseases Emerging Infectious Diseases

Global emergence of a zoonotic Global emergence of a zoonotic pathogen needs 3 steps. pathogen needs 3 steps.

1.1. Successful transit between a wild reservoir Successful transit between a wild reservoir and humans or domestic animalsand humans or domestic animals

2.2. Direct transmission between humans. Direct transmission between humans. 3.3. Local epidemics into the global population. Local epidemics into the global population.

Many agents move between animal and Many agents move between animal and humans but fail steps 2 and 3humans but fail steps 2 and 3

Environmental changes aid Environmental changes aid emergence of new diseasesemergence of new diseases

Urban centers Urban centers Bush meat economyBush meat economyVillage, town, cityVillage, town, cityHuman behavior Human behavior Global travel Global travel

Known and emerging agents Known and emerging agents challenge our response capability challenge our response capability

How do we detect them

How do we treat them

• How do we respond to them

Detection is built on timescalesDetection is built on timescales

• Detect to intercept-prevent exposure

• Detect to warn-minimize exposure

• Detect to treat- treat exposed people

Three methods of detectionThree methods of detection

• “White powder”

• Epidemiological surveillance

• Widgets

White powder HazMat responseWhite powder HazMat response

• >150,000 anthrax hoaxes 2001-2002

• 2008 >50 white powder letters mailed to JP Morgan Chase bank facilities

Epidemiological surveillanceEpidemiological surveillance

• Traditional surveillance– Background rates of disease. Trends in mortality and

morbidity; disease occurrence – Laboratory confirmation

• Syndromic surveillance in real-time – Computer/internet based– Capture and analyze health data– Identifying abnormal conditions– Early detection of outbreaks

An EPI monitoring systemAn EPI monitoring system

Early detection is criticalEarly detection is critical

Faster and faster widgetsFaster and faster widgets• Culture

• Immunoassay

• PCR

• Particle detection

• Autonomous Systems

Challenges for widgetsChallenges for widgets

Time to an answerTime to an answer

Resources to run the systemResources to run the system

False positive-False negativeFalse positive-False negative

SpecificitySpecificitynear neighborsnear neighborsenvironmental positives and gunkenvironmental positives and gunk

Response and return to serviceResponse and return to service

Economic costs of being wrongEconomic costs of being wrong

Threats to water systemsThreats to water systemsYou guys are lucky!

The path aheadThe path ahead