Emergency Preparedness

Emergency Preparation: Theoretical and Practical Perspectives

Frank Paloucek, PharmD

MODERN CHICAGO ◆

Tyl enol m urders

– 9/ 29-10/ 1/ 82, seven deaths from cyanideladen T ylenol capsules

◆ ◆

◆

Nev er sol ved, appear s pur ely random act of poi soni ng Af ter publ ici ty of cas e, fol lowi ng month had 270 reports of product tamper ing, 36 were proven true in the U.S. Lead to dev el opm ent of two innovations – Dosage for m? – Packaging?

Emergency Preparedness Case ◆

You are part of the team that is called to respond to a natural outbreak or possible terrorist attack involving an infectious agent.

◆

Multiple attendees of an outdoor concert festival have presented in the 1-3 days following with “flu-like” symptoms, black rashes on finger and toes and painful swellings in their groin and armpits

Responsibilities Your team is assigned to mass dispensing of prophylactic antibiotics to other attendees of the concert which took place over 3 days and had an estimated 350,000 visitors and staff What team is this anyway?

◆

2.

• 3.

And who took take of them before this?

So what are you dispensing and where does it come from? • A Stockpile, right?

Question 1) Answer: Medical Outreach Team ◆ ◆ ◆ ◆ ◆

Alerted and formed from locally organized disaster plans. Composed of physicians, nurses, EMT, preventive medicine staff and pharmacists Drug info / dispensing / distribution Patient education Non-traditional clinical functions during an emergency – – – –

Triage and physical assessment Taking histories to exclude contraindications Medication administration Collection of epidemiological data; screening surveys

Question 2) Answer: “Pills to the People” ◆

The Problem with Stockpiling – Antidotes and treatments are expensive – Have limited shelf-lives – Unlikely to be used in large quantities ❖ ❖ ❖ ❖

◆

350,000 for prophylaxis 2 doses daily for > 7 days of Cipro or Doxycycline 4.9 million doses Clearly exceeds local supply

What plans currently exist for such a disaster?

Terrorism or Large Scale Natural Disaster ◆

Require rapid access to large quantities of pharmaceuticals and medical supplies

TIMELINE ◆

◆

◆

CDC formed an antidote/antibiotic depot for 1996 Summer Olympics in Atlanta Congressional charge to Health and Human Services and to Centers for Disease Control and Prevention in 1999 created National Pharmaceutical Stockpile (NPS) – Re-supply of large quantities of essential medical materiel to states and communities during an emergency within 12 hours of the federal decision to deploy. Plans subsequently updated in 2002

Strategic National Stockpile (Homeland security act of 2002) ◆

DHS defines goals and performance requirements and manages deployment. – March 1 2003, NPS became the strategic national stockpile (SNS). – The SNS program upgrades federal public health capacity to respond to a national emergency. – Critical is ensuring capacity to receive, stage, and dispense SNS assets ❖ Federal,

state, and local levels

Strategic National Stockpile ◆

Repository of – – – – – – – – –

Antibiotics Vaccines Immunoglobulins Chemical antidotes Antitoxins Life-support medications IV administration Airway maintenance supplies Medical/surgical items

Containers designed to facilitate shipping by highways, railways and…

SNS: Push Packages ◆

◆

◆ ◆

Strategically located throughout US Supplement and re-supply state and local public health agencies in the event of a national emergency When: Anywhere and Anytime Where: Within the U.S. or its territories

Push Package “Deployment” ◆

◆ ◆ ◆ ◆

Local emergency management and public health authorities determine that the demand for pharmaceuticals will exceed local supply. They will notify their respective central offices Decision is made to discuss with governor. If appropriate, the governor will request the push package from CDC or DHS. DHS, HHS, CDC, and other federal officials will evaluate the situation and determine a prompt course of action. – Short turn around time expected.

SNS Program Delivery and Transport ◆

◆

◆

Push packages can be delivered within 12 hours of a federal decision to deploy. – Authority for material will transfer upon arrival Once package is on the tarmac, responsibility shifts from federal to local authorities SNS technical advisory response unit (TARU) staff will arrive and remain – Coordinate with state and local officials for efficient delivery and distribution

Supplementing State and Local Resources ◆

The SNS is not a first response tool but a resupply tool – Significant exposure to nerve agents will require an antidote within minutes ❖

◆ ◆

What would we do then?

Chempack

During a national emergency, state, local, and private stocks of medical material will be depleted quickly State and local first responders and health officials can use the SNS to bolster their response with a 12hour push package, VMI, or both

SNS: Follow up (Not necessarily second line response) ◆ ◆

Vendor managed inventory (VMI) supplies Arranged contractually with major manufacturers – ie, Bayer had agreed to supply 300 million Cipro to U.S. government (100 now 200 on re-supply) – Shipped to arrive within 24 to 36 hours. – Can be tailored to the suspected or confirmed agent(s). – Could act as the first option for immediate response from the SNS if agent is known.

Chempacks ◆

Will be placed in preselected areas within the state and contain: – MARK-1 autoinjectors ❖

2mg atropine & 600mg 2-PAM

– Bulk atropine sulfate – Bulk 2-PAM – Pediatric atropine auto injectors ❖

0 .5mg and 1.0mg

– Diazepam (CANA kits) – Bulk diazepam – IV fluids and catheters

Chempack

2 Types of Chempack

Determining and Maintaining SNS Assets ◆

Factors for considerations: – – – –

◆

Current threats Availability of medical material Ease of dissemination Medical vulnerabilities

Stock is rotated – Quarterly QA and quality control checks – Annual 100% inventory of all package items – Inspections of environmental conditions, security, and overall package maintenance

•350,000 “patients” •Local supply now • 3400 Cipro • 1 b.i.d. x 7 days • Can only treat 200? •Maybe 3 days

Supplementing State and Local Resources ◆

The SNS is not a first response tool but a re-supply tool – Significant exposure to nerve agents will require an antidote within minutes Chempack

◆

So can’t we have something faster for biologicals? Hosp APT Kits

Hosp APT kits ◆

Will be placed in preselected areas within the state and contain: – – – – –

◆

Antibiotics Epinephrine and immunosuppresants morphine Airway maintenance supplies Medical/surgical items

Intended to treat 100 patients for 3 days – Resupply via HAN or other local networking

◆

Local Health Department determines need for case reporting surveillance

But there still might not be enough so….we should also be able: ◆

Provide appropriate messages to convey to the public about the use of essential pharmaceuticals after an attack – – – – –

Effectiveness of alternatives Delivery/administration problems Contraindications Adverse effects Potential for development of drug interactions, bacterial resistance and drug ineffectiveness

Effectiveness of alternatives – We are out of drug, what do we do? Expired? Veterinary?

Same drug class

Change routes

Effectiveness of alternatives – We are out of vials, what do we do?

Delivery Administration problems Dosage forms for adults or older children only ◆ Oral route unavailable and no parenteral dosage exists ◆

Availability Issues

When alternatives are available, normally contraindicated agents should be avoided However, acts of bioterrorism shift the benefit such that these agents should NOT be excluded as viable treatments if the accepted alternatives are not available.

What about contraindications? 1. 2. 3.

Isn’t ciprofloxacin bad for kids? Isn’t same true for doxycycline? What if patient is pregnant? Or breastfeeding

Special Populations Issues Pregnancy ◆

◆

Concerns of teratogeneticity with quinolones or tetracyclines (arthroparthies) must be weighed against risk of severe life-threatening infections by Class A agents Tetracyclines may cause teeth discoloration when given for prolonged periods during late pregnancy (such as anthrax prophylaxis)

Special Populations Issues Pediatrics Quinolones are indicated for treatment of anthrax and for post exposure prophylaxis in children < 18 y/o ◆ Doxycycline is indicated for treatment of anthrax and for post exposure prophylaxis in children < 8 y/o – Use with sensitivity indications, allergy, exhaustion of supplies of cipro or penicillin ◆

Adverse effects -Long term impacts ◆

Persistent symptoms

3 6 13 20 41 62

Long term impacts Persistent symptoms or… ◆ Continued exposure ◆

If this patient had children who became secondarily infected when would the children appear ? ◆ ◆ ◆ ◆

◆ ◆

Anthrax Smallpox Plague Viral Hemorrhagic Tularemia Botulinum

If this patient had children who became secondarily infected when would the children appear ? ◆ ◆ ◆ ◆

◆ ◆

Anthrax Smallpox Plague Viral Hemorrhagic

◆

Tularemia Botulinum

◆

◆ ◆ ◆

◆

They wouldn’t, not transmissible 2 weeks 1-4 days (P), 2-10days (B) 2days – 4 weeks Not transmissible Not transmissible

Rashes and other cutaneous signs of bioterrorism - timelines ◆ ◆ ◆ ◆

◆

Cutaneous Anthrax Small Pox Plague Viral hemorrhagic fevers Tularemia

3-5 days 3-5 days (sick) 1-4 (days) varies 2-5 days (painful)

Long term impacts Persistent symptoms or… ◆ Continued exposure ◆

◆

Adverse effects of treatment ❖ Rare

events-

– what if an ADR has an incidence of 0.1-1.0% ❖ “Allergies” ❖ Microbial

resistance

Special Issues Geriatrics ◆

◆

Quinolones are potent inhibitors of CYP 3A4 and 1A2 and doses need adjust for renal insufficiency Doxycycline undergoes CYP 3A4 interactions as a substrate and inhibitor

Antidote ◆

Atropine - Blocks the effects of neurotransmitter - Dosing is symptomatic and often exceeds “normal” - Eyedrops effective for ocular symptoms (also provide easy source for a lot of drug – but homatropine not as potent) 2-PAM (Pralidoxime) - Removes nerve agent from the enzyme

◆

Military Autoinjector – MARK I

“Aging” Name

Synonym

Aging T1/2

Sarin

GB

~5 hours

Soman Tabun VX

GD GA None

~2 min >40 hours >40 hours

Treatment ◆ ◆ ◆

Adult atropine dose: “enough” Give atropine regardless of heart rate Pediatric Considerations – 0.01mg/kg ❖ ❖ ❖

◆

0.5mg for 15-40 lbs 1mg for 40-90lbs 2mg for > 90lbs

Atropine used until endpoint achieved (resolution of secretions) – In Iran doses between 100-1000 mg/daily were used

Cyanide Treatment ◆

◆ ◆

Remove from source Oxygen Cyanide antidote kit

NO ONE able to walk and talk is in immediate danger of loss of life

So take a breath

Outbreaks with Class “A” agents have actually occurred over days

And lets not forget

2004 Indian Ocean Tsunami: Health-Related Infrastructure Loss in Banda Aceh

Damage to the lab equipment at the Provincial Hospital

Damage outside Meuraxa Hospital

2004 Indian Ocean Tsunami

Mass fatalities: preserved with dry ice on grounds of Wat (temple) Yan Yao in Takuapa, Thailand.

U.S. Drinking Water Our drinking water supply is normally safe. Diseases are spread when: • there’s a water main break or interruption • travel • lakes, streams, pools, or waterparks? Majority of problems: Cryptosporidium, Giardia, Toxoplasma CDC estimates 2.5 million cases annually

Cryptosporidium parvum • • • •

•

First described in 1907 In 1976, two cases of human diarrhea AIDS epidemic by 1986; 4% of AIDS patients symptomatic, with 61% fatality rate In 1993 - Milwaukee over 400,000 cases – Las Vegas – 32 deaths in 1994 – Over 3000 cases in NY’s Seneca Lake Park (also at Coon Lake MN) CDC states at least 30,000 cases of Cryptosporidium annually

Cryptosporidium in Human Disease •   • • • • •

Transmission is fecal/oral: outbreaks associated with faulty water purification   1­2 week incubation with PROFUSE watery  diarrhea (12L/day) Resistant to chlorination,  must boil Self­limiting except in immunocompromised  patients No effective drugs HIV patients must drink boiled or Bottled water

Cholera • Cholera prevalent in U.S. in 1800s, virtually eliminated by modern sewage and water treatment • Currently it is common in Asia, Africa, and Latin America (especially the former Soviet Union, Iran, and Pakistan • Current outbreak in Africa (110 new cases per day) • Over 100,000 cases with 2345 deaths in 2004

Cholera • Vibrio cholerae- serogroups O1 (El Tor) or O139 (Bengal) produce cholera toxin • Asymptomatic to profuse watery diarrhea with vomiting, circulatory collapse and shock • 25-50% of cases fatal if untreatedtreatment is oral rehydration therapy (sugar and salt mixed with clean water) • Virtually no risk for persons in the U.S.

Post-Hurricane Vibrio • 7 people in the area affected by Hurricane Katrina have been reported to be ill from Vibrio vulnificus, 4 have died • 1 case of Vibrio cholerae • "It's a non-epidemic cholera”

EMERGING INFECTIOUS DISEASES SINCE 1970 ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆

1975 - Parvovirus B-19 1973 - Rotavirus 1976 - Cryptosporidium 1977 - Ebola 1977 - L. pneumophilia 1977- Hantaan virus 1977 - C. jejuni 1980 - HTLV-1 1981 - S. aureus - Toxic Shock 1982 - E. coli O157:H7 1982 - HTLV-2 1982 - B. burgdorferi 1983 - HIV 1983 - H. pylori

◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆

1986 - Cyclospora cayatanensis 1988 - HHV-6 1988 - Hepatitis E 1989 - Erlichia chafeensis 1989 - Hepatitis C 1991 - Guanarito virus 1991 - Babesia species 1992 - Vibrio cholerae O139 1992 - Bartonella henselae 1993 - Sin nombre virus 1993 - Encephalitozoon cuniculi 1994 - Sabia virus 1995 - HHV-8 1995 - vCJD

EID Threats of the New Millennium “Mother Nature is the Ultimate Bioterrorist” 10. Norovirus – “The cruise ship virus” 9. Human Metapneumovirus 8. CWD 7. Anthrax, ricin and other bioterrorism agents 6. West Nile Virus 5. BSE - “Mad Cow Disease” 4. Monkeypox 3. SARS 2. Pertussis (“Whooping Cough”) 1. Influenza A (H5N1) – “Avian Flu”

Helpful Links CDC Bioterrorism – www.bt.cdc.gov ◆ Radiation Emergency Assistance Center & Training Site (REAC/TS) http://www.orau.gov/reacts/default.htm ◆ Medical management of radiological casualties handbook www.afrri.usuhs.mil ◆

•www.epr-education.net

Name the worst serial killer ?

Do You Know? ◆

Jack the Ripper

◆

Jeffrey Dahmer

◆

John Wayne Gacy

◆

Ted Bundy

Do You Know? ◆

Jack the Ripper (7)

◆

Jeffrey Dahmer (31)

◆

John Wayne Gacy (33)

◆

Ted Bundy (20+)

Harold Shipman, M.D.

Mercy Killers ◆

Nurses – – – – –

◆

K Gilbert (4+) 96-7 NC epinephrine Richard Diaz (12+) CA succinylcholine Orville Majors (70-130) 1993-5 Indiana epi, KCL Don Harvey (37-80+) 1970-1987, Edson Guimares (5-131) Sao Paulo RN tech KCL, C Malevre (4-30 Paris 1997-8) Queen of euthanasia, W. Wagner gang Austria (45-200) 1983 MSO4/water

Others – E Saldivar resp therapist (6-50) Glendale 19891997pancuronuim, – A Nessitt nursing home administrator Norway 22+ curare – Midwife (36 women) gang, Hungary (80-300 men) 19141929 arsenic

Charles Cullen

Risk of Dying ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆

Smoking 10 cig/day Road accident Playing soccer Homicide Terrorist attack (2001) Hit by lightening Terrorist attack (1990’s) Anthrax (2001) Smallpox (2001)

1 in 200 1 in 8,000 1 in 25,000 1 in 100,000 1 in 100,000 1 in 10,000,000 1 in 50,000,000 1 in 50,000,000 < than 1 in 50,000,000

• Being rescued from terrorists in 8

1

Beslan middle school hostage crisis