Safe Handling, Packaging & Shipping of Infectious Substances Utah Department of Health November 21, 2002 Kim Christensen

Objectives Information on possible organisms Information on possible organisms Why these organisms? Why these organisms? Safety Safety Samples Samples Packaging Packaging Transport/Shipping Transport/Shipping

Agents of Highest Concern Bacillus anthracis (Anthrax) Francisella tularensis (Tularemia) Yersinia pestis (Plague) Botulinum toxin (Botulism) Variola major (Smallpox) Viral Hemorrhagic Fevers

Other Possible Agents Brucella spp. – Brucellosis Brucella spp. – Brucellosis Coxiella burnetti – Q-fever Coxiella burnetti – Q-fever Arboviruses (West Nile) – encephalitis Arboviruses (West Nile) – encephalitis Mycotoxins Mycotoxins Ricin Toxin – Castor beans Ricin Toxin – Castor beans SEB – Staphylococcus Enterotoxin B SEB – Staphylococcus Enterotoxin B

Why these organisms? Can cause disease via aerosol route Can cause disease via aerosol route Fairly stable in aerosolized form Fairly stable in aerosolized form Susceptible civilian population Susceptible civilian population High morbidity and mortality rates High morbidity and mortality rates Difficult to diagnose and/or treat Difficult to diagnose and/or treat Some can be transmitted person-to-person Some can be transmitted person-to-person

Bacillus anthracis Anthrax Bacillus anthracis –   Gram-positive, spore-forming bacillus (rod)

Bacillus anthracis Anthrax Cutaneous Exposure-   A skin lesion evolving during a period of 2-6 days from a papule, through a vesicular stage, to a depressed black eschar.

Cutaneous Anthrax Intense itching Painless skin sore Incubation 1-5 days (up to 60) 20% fatality if untreated (may spread to blood) Direct contact with skin lesion may result in cutaneous infection

Inhalation Anthrax Inhalation Anthrax-   A brief prodrome resembling a viral respiratory illness with radiograph evidence of mediastinal widening

Inhalation Anthrax Flu-like symptoms –   Fever, fatigue, muscle aches, difficulty breathing, headache, chest pain & non-productive cough   1-2 day improvement followed by respiratory failure, meningitis may develop No person-to-person spread

Francisella tularensis Tularemia Humans become infected by: Humans become infected by:  Handling infected animal carcasses  “Rabbit Fever”  Bites of ticks, deer flies, or mosquitoes No person-to-person transmission No person-to-person transmission Endemic in Utah Endemic in Utah

Tularemia Clinical Presentations Pneumonic- Pneumonic-  Incubation 3-5 days  Flu-like symptoms  Mortality –  30% untreated  <10% treated Ulceroglandular Ulceroglandular  Ulcer w/adenopathy Glandular  Adenopathy w/o lesion Oculoglandular  Painful, purulent conjunctivitis Typhoidal  Possible presentation for BT  Septicemia

Yersinia pestis Plague Transmission – Transmission –  Inhalation  Direct contact  Fleas

Plague Clinical Presentations Bubonic Bubonic  Flu-like with painful buboes (lymph nodes) Septicemic  Similar to bubonic  No swelling of lymph nodes

Plague Clinical Presentations Pneumonic Pneumonic  Highest mortality  Rapid transmission  Fever  Hemoptosis  Lymphadenopathy  Cough

Plague Distribution Distribution  Highest in 4 corners area – Western states  Prairie dog population

Botulism Clostridium botulinum Clostridium botulinum  Organism – gram positive, spore- forming, anaerobic bacilli Botulinum toxin Botulinum toxin  Neurotoxin A, B, C1, D, E, F, G

Botulism Foodborne Foodborne  Diplopia (double vision), blurred vision, flaccid, symmetric paralysis (rapid progression) Infant Infant  Constipation, poor-feeding, “failure to thrive”, weakness, impaired respiration and death Wound Wound  Same symptoms as foodborne w/infection through a wound Other Other  Non-infant patient with no suspect food or wound

Botulism Foodborne Foodborne  Most likely presentation for BT event  Mortality  Currently 5-10%  Previously 60% Wound Wound  Mortality 15%  Emerging problem of drug users  Injecting Black Tar Heroin

Variola major Smallpox Orthopox virus Orthopox virus DNA virus DNA virus Brick-shaped structure 200 nm in diameter Brick-shaped structure 200 nm in diameter Incubation 8-16 days Mortality 30% Clinical symptoms  Acute  Fever  Headache  Vomiting  Backache

Variola major Smallpox 4 Types 4 Types  1. Ordinary – most frequent  2. Modified MildMild Occurring in previously vaccinated personsOccurring in previously vaccinated persons  3. Flat  4. Hemorrhagic Much shorter incubationMuch shorter incubation Not likely to be recognized as Smallpox (initially)Not likely to be recognized as Smallpox (initially)

Variola major Smallpox Disease Progression Disease Progression  Incubation Period  Initial Symptoms – Prodrome  Rash Development & Distribution Variola minor Variola minor  Less common clinical presentation  Much less severe disease

Variola major Smallpox Rash Rash  Begins on face, hands, forearms & spreads to lower extremities within 7 days  Lesions on palms & soles of feet

Variola major Smallpox Rash Rash  Synchronous progression: macules  vesicles  pustules  scabs

Smallpox Spread by infected droplets Spread by infected droplets Most infectious after onset of rash Most infectious after onset of rash Contagious until the last scab falls off Contagious until the last scab falls off Vaccine given within 4 days of exposure can prevent disease or lessen symptoms Vaccine given within 4 days of exposure can prevent disease or lessen symptoms 70% recovery rate 70% recovery rate Chicken pox vs. Smallpox Chicken pox vs. Smallpox

Viral Hemorrhagic Fevers Ebola Ebola Lassa Lassa Marburg Marburg Hanta Hanta Dengue Dengue Yellow fever Crimean-Congo Rift Valley fever Other

Viral Hemorrhagic Fevers High Fever with: High Fever with:  Mucous membrane bleeding  Petechiae  Malaise  Muscle-aches  Headaches  May have diarrhea or vomiting Fatality depends on virus – 90% Ebola Fatality depends on virus – 90% Ebola

Viral Hemorrhagic Fevers Mosquito or tick vectors Mosquito or tick vectors Person-to-person transmission through body fluids/blood Person-to-person transmission through body fluids/blood Vaccine available for Yellow Fever Vaccine available for Yellow Fever People can be infected but show no signs or symptoms of disease People can be infected but show no signs or symptoms of disease

Protection of First Responders & Health Care Workers Knowledge Universal Precautions Communication Vaccination Prophylaxis

Safety First First Responders First Responders  Personal Protective Equipment  Established protocols Transporters Transporters  Regulations Lab Personnel Lab Personnel  Personal Protective Equipment  Established protocols  Biosafety Containment  Vaccinations Use Universal Precautions – treat everything as if it were contaminated Use Universal Precautions – treat everything as if it were contaminated

Safety First Responders First Responders  Know what you “might be” dealing with  Protect yourself  Protect the community  Protect the next in line (transporter)  Recommendations for the Selection and Use of Protective Clothing & Respirators Against Biological Agents: asp asp

Safety Transporter/Shipper Transporter/Shipper  Know what you “might be” dealing with  Protect yourself  Protect the public  Follow rules and regulations  IATA, USPS, DOT, Etc.

Safety Laboratory Personnel Laboratory Personnel  Handle & process according to Biosafety Level Classifications (Level 1, Level 2, Level 3, Level 4)  Biosafety in Microbiological & Biomedical Laboratories CDC/NIH, 4 th Edition.  Protect yourself  Protect other laboratorians  Protect the public

Samples Clinical specimens Clinical specimens Non-clinical Non-clinical Environmental Environmental Evidentiary Materials Evidentiary Materials

Specimen Clinical Specimen Selection All clinical specimens should go directly to a Level A Laboratory for processing

Bacillus anthracis Anthrax Cutaneous Cutaneous  Vesicular Stage  Fluid from intact vesicles on sterile swab  Eschar Stage  Without removing eschar, rotate swab beneath edge of eschar & collect lesion material Gastrointestinal  Stool  5-10 grams  Sterile, leakproof container  Rectal swab  Blood  Institution’s procedure  Routine blood cultures

Bacillus anthracis Anthrax Inhalational Inhalational  Sputum  > 1 mL expectorated sputum  Sterile, leakproof container  Blood  Institution’s procedure  Routine blood cultures

Yersinia pestis Plague Pneumonic Pneumonic  Bronchial Wash/Transtracheal Aspirate  > 1 ml  Institution’s procedure  Sputum/Throat  Routine throat culture (swab)  Expectorated sputum – sterile, leakproof container Septicemic  Blood  Institution’s procedure  Routine blood culture Bubonic  Biopsied Specimen  Liver, spleen, bone marrow, lung  Tissue aspirate  May yield little material

Francisella tularensis Tularemia Biopsied tissue Biopsied tissue  Scraping of an ulcer - preferred  Swab of an ulcer – alternate Tissue Aspirate Tissue Aspirate Bronchial/Tracheal Wash Bronchial/Tracheal Wash  Institution’s procedure Sputum/Throat Sputum/Throat  Routine throat culture  Sputum expectorated into sterile, leakproof container Blood Blood

Clostridium botulinum & Botulism Toxin Foodborne Foodborne  Clinical Material  Serum  Gastric contents  Vomitus  Stool  Enema fluid  Autopsy Samples  Intestinal & Gastic contents  Serum  Food Samples Infant  Stool  Enema fluid  Post-mortem samples (intestinal contents)  Food samples  Environmental Samples

Clostridium botulinum & Botulism Toxin Wound Wound  Serum  Wound tissue, exudate, swab  Anaerobic transport  Stool  Enema fluid  Isolate Bioterrorism – Intentional Release  Serum  Stool  Enema fluid  Gastric aspirate  Nasal swab  Food samples  Environmental samples

Variola major Smallpox Report immediately to UDOH Report immediately to UDOH UDOH contacts CDC & FBI UDOH contacts CDC & FBI

Variola major Smallpox Biopsy Specimen Biopsy Specimen  2-4 portions of tissue  Sterile, leakproof, freezable container Scabs Scabs  Scrapings/material  Sterile, leakproof, freezable container Vesicular fluid Vesicular fluid  Separate lesions  Include cellular material

Viral Hemorrhagic Fever Specific handling conditions are currently under development at the CDC. Specific handling conditions are currently under development at the CDC. Serum Serum  10-12cc of serum

Chemical Exposure Specimens to be collected from each individual Urine Urine  At least 25 mL  Screw-cap plastic containers  Freeze ASAP Whole Blood Whole Blood  Two – 5 or 7 mL purple-top (EDTA) tubes – vacuum-fill only (unopened) Whole Blood  One 5 mL or 7 mL gray-top or green-top tube (unopened)  One empty tube Whole Blood  Two 10 mL red-top tubes  no anticoagulant  Do not separate serum from cells

Non-Clinical Specimens To be delivered directly to the UDOH - Lab Animal Animal  Carcass, tissue, blood, bone, skin Vector Vector  Fleas, mosquitoes, ticks, flies Human Human  Post-mortem specimens

Environmental Samples To be delivered directly to the UDOH - Lab Water Water  At least 500 mL Soil/Mud Soil/Mud Plant Material Plant Material Food Food

Evidentiary Materials To be delivered directly to the UDOH - Lab Non-organics Non-organics  Powder  Paper  Containers Organics Organics  Hair  Wood  Liquids Example procedure for collecting environmental samples: Example procedure for collecting environmental samples:  sampling-apr2002.asp

Chain of Custody Always observe a Chain of Custody Always observe a Chain of Custody Evidence Evidence Collector  Transporter  Laboratory Collector  Transporter  Laboratory  Each person to touch the sample must sign for it. Laboratory – Laboratory –  Signed for each time the sample is manipulated

Environmental Samples Please Pre-screen Sample should be determined to be a credible threat Sample should be determined to be a credible threat  Determined by FBI/Local law enforcement  Directly related to an event FBI or HAZMAT should pre-screen samples for:  Bombs  Incendiary Devices  Radiological Materials  Chemicals

Specimen Packaging Clinical- Clinical-  Containers:  Sterile  Leak-proof  Blood collection tubes  Sterile swabs  Labeled, individually, with patient ID  According to institution’s protocols

Specimen Packaging Non-clinical- Non-clinical-  Original containers – if possible 1. Sample placed in sealed, clean, dry container – Ziplock bags okay 2. Change gloves 3. Sample placed in 2 nd container a. In a clean area a. In a clean area b. Seal 2 nd container b. Seal 2 nd container 4. Change gloves 5. Decontaminate outer container with 10% bleach solution OR add a 3 rd container. bleach solution OR add a 3 rd container.

Packaging & Shipping Commercial Carriers & Local Transfer

Regulations Protect! Protect!  Postal personnel  Airline personnel  Industry personnel Made by: Made by:  Federal government  Private industry associations

Regulations Responsibility is given to the SHIPPER! Responsibility is given to the SHIPPER!  Shipper must CORRECTLY:  Classify  Package  Label  Prepare documentation  For all Diagnostic & Infectious Materials  MUST be Trained & Certified!!!

Regulations Training & Certification Training & Certification  Anyone directly involved with the shipping of diagnostic materials or infectious substances.  1 individual per institution must be trained.  By certified training authority  That person trains others

Regulations Training & Certification Training & Certification  Saf-T-Pak, Inc  1-day course – Spring 2003 – SLC  

Classification Diagnostic Specimen vs. Infectious Substance Diagnostic Specimen vs. Infectious Substance  Diagnostic Specimen  Not considered hazardous  Poses negligible threat  Low probability of containing pathogens  Testing other than for presence of pathogens  Have not been tested yet

Classification Diagnostic Specimen vs. Infectious Substance Diagnostic Specimen vs. Infectious Substance  Infectious Substance:  Same as Hazardous Material  Contains or Suspected to contain agent that may cause infection (bacteria/virus)  Human/Animal samples likely to contain an infectious agent

Shipment by Commercial Carrier

Planning Planning Packaging Packaging Labeling Labeling Documenting Documenting Shipping Shipping

Planning Call Recipient: Call Recipient:  Verify shipping address  Obtain contact name & phone  Verify when to ship

Packaging Includes: Includes:  Classification  Packing  Labeling  Documentation Must withstand:  Leakage  Shocks  Pressure Changes  Other conditions  Transport

Packaging Primary Sample Container Primary Sample Container  Waterproof & Leak-proof  Seal plates/tubes with tape  Wrap specimen container in absorbent material  Enough to absorb entire liquid contents  Ziplock Biohazard bag  Solids – 1 bag  Liquids – 2 bags  Pre-freeze specimens if shipping frozen

Packaging Secondary Container Secondary Container  Complete Packaging System  Unbreakable  Water-proof  Leak-proof  Biohazard Label  Commercial Suppliers of Certified Packaging Systems  i.e. Saf-T-Pak, EXAKT-PAK

Packaging Certified Outer Shipping Package Certified Outer Shipping Package  Strong enough to hold capacity & mass  Indicated on the bottom of box  Choose appropriate package  Must meet UN Class 6.2 Specs  Must bear the UN Packaging Specification Marking 4G CLASS 6.2 / 99 4G CLASS 6.2 / 99 CAN / 8-2 SAF-T-PAK UNUN

Packaging Certified Outer Shipping Package Certified Outer Shipping Package  Each comes with:  Inner Packaging  Labels  Do NOT make any substitutions  UN-certification becomes invalid  Refurbishment kits may be used

Packaging Certified Outer Shipping Package Certified Outer Shipping Package  Closing instructions included  Over-packs?  Shipping packs & over-packs Marked & Labeled identicallyMarked & Labeled identically Additional Label:Additional Label: “Inner packages comply with prescribed specifications”

Labeling Apply to flat surface w/o overlap or corner wrap Apply to flat surface w/o overlap or corner wrap HAZARD Labels for Dangerous Goods HAZARD Labels for Dangerous Goods  Must be displayed on packages containing:  Infectious substances  Dry ice

Labeling Hazard Class 6.2 Infectious Substances Hazard Class 6.2 Infectious Substances Etiologic agents Biomedical material In case of damage or leakage Notify Director CDC, Atlanta, Georgia (404) Apply on the blank diamond marked on outside package

Labeling Miscellaneous Hazard Class 9 Dry Ice Miscellaneous Hazard Class 9 Dry Ice  Weight of dry ice in kg  Handwritten on label  Apply on side opposite Hazardous Substance label  UN Shipping Name Label for Dry Ice  Carbon dioxide, solid (Dry Ice) (Dry Ice)UN1845_______kg Next to Dry Ice Hazard Label

Labeling Orientation Labels Orientation Labels  Opposite sides of shipping container  Do not cover the hazard labels UN Shipping Name Label UN Shipping Name Label  Required for EACH Infectious Organism Infectious substances, Affecting humans (Escherichia coli) UN2814 X _________mL Apply next to Hazard Class 6.2 label

Labeling Address Label Address Label  One side of outer box  Must include:  Receiver’s name, shipping address (No PO boxes) & phone (with area code)  Shipper’s name, address & phone  Temperature/Storage requirements (optional)

Documenting Complete forms & letters (enclose w/sample) Complete forms & letters (enclose w/sample)  Memo  All infectious substance shipments  Letterhead  Insert on top of 2 nd container  Test request

Documenting Shipping Record File Shipping Record File  Copies of all forms  Keep 2 years Shipping Documents Shipping Documents  Provided by Commercial Carrier

Documenting Shipping Documents Shipping Documents  Commercial Air Shipments require:  Air Waybill Name & telephone # responsible personName & telephone # responsible person Person should bePerson should be –Knowledgeable –Accessible 24/7 Shipping pouch (address window)Shipping pouch (address window) –Top surface of closed package

Documenting Shipping Documents Shipping Documents  All infectious substance shipments require: Dangerous Goods Declaration  To avoid a LARGE fine (> $1000) Forms in shipping pouch & apply pouch to bottom of packageForms in shipping pouch & apply pouch to bottom of package Edges of pouch cannot overlap any of the labels or markings on the sideEdges of pouch cannot overlap any of the labels or markings on the side

Shipping Some commercial carriers will NOT ship Some commercial carriers will NOT ship  Call local carrier to see FedEx – will ship FedEx – will ship  Computer program – document preparation

Local Transport of Diagnostic Specimens & Infectious Substances

Local Transport Usually courier service Usually courier service Transfer of specimens from: Transfer of specimens from:  Dr.’s office/hospital  Laboratory  Laboratory  Laboratory As important as air transport As important as air transport No possibility of contents escaping under normal transport conditions No possibility of contents escaping under normal transport conditions

Packaging Primary Sample Container Primary Sample Container  Water-proof  Leak-proof  Seal plates/tubes with tape  Wrap absorbent material around specimen container and secure  Ziplock Biohazard bag  Solids – 1 bag  Liquids – 2 bags

Labeling Label with: Label with:  Name, address & phone of recipient  Storage requirements ID form/test request ID form/test request  Outside pocket of biohazard bag  Do NOT put forms inside with the specimen!!

Transporting Sample containers placed in leak-proof, unbreakable Sample containers placed in leak-proof, unbreakable  Transport Box  Secure, tight-fitting cover  Biohazard label Frozen specimens Frozen specimens  Labeled, insulated box w/dry ice

Transporting Transport box  Transport box   Carried to courier vehicle  Secure in position for transport  VERY IMPORTANT!! Courier Vehicle Courier Vehicle  Should carry a spill kit with:  Absorbent material  Disposable gloves  Chlorine disinfectant  Leak-proof waste disposal container

Regulations Public Health Service 42 CFR Part 72. Interstate Transportation of Etiologic Agents. Public Health Service 42 CFR Part 72. Interstate Transportation of Etiologic Agents.  Department of Transportation. 49 DFR Parts Hazardous Materials Regulations. Applies to the shipment of both biological agents and clinical specimens. Department of Transportation. 49 DFR Parts Hazardous Materials Regulations. Applies to the shipment of both biological agents and clinical specimens.   New regulations just established

Regulations United States Postal Service. 39 CFR Part 111. Mail ability of Etiologic Agents. From the Domestic Mail Manual United States Postal Service. 39 CFR Part 111. Mail ability of Etiologic Agents. From the Domestic Mail Manual  Occupational Health and Safety Administration (OSHA). 29 CFR Part Provides minimal packaging and labeling requirements for transport of blood and body fluids within the laboratory and outside of it. Occupational Health and Safety Administration (OSHA). 29 CFR Part Provides minimal packaging and labeling requirements for transport of blood and body fluids within the laboratory and outside of it. 

Regulations Dangerous Goods Regulations (DGR). International Air Transport Association (IATA). These regulations followed by the airlines provide packaging and labeling requirements for infectious substances and materials as well as for diagnostic specimens. Dangerous Goods Regulations (DGR). International Air Transport Association (IATA). These regulations followed by the airlines provide packaging and labeling requirements for infectious substances and materials as well as for diagnostic specimens.  Guidelines for the Safe Transport of Infectious Substances and Diagnostic Specimens. World Health Organization (WHO), Guidelines for the Safe Transport of Infectious Substances and Diagnostic Specimens. World Health Organization (WHO), 

Other Websites CDC – Centers for Disease Control CDC – Centers for Disease Control  ASM – American Society for Microbiology ASM – American Society for Microbiology  Utah Department of Health (Microbiology) Utah Department of Health (Microbiology) 

Additional Comments Call ahead of time Call ahead of time  Clinical/Environmental  Let lab know sample is on its way Clinical Specimens Clinical Specimens  Go to Level A Labs for rule-out Environmental Specimens Environmental Specimens  Go to UDOH Lab UDOH has 24/7 coverage UDOH has 24/7 coverage

Contact Information Utah Department of Health Lab Response Utah Department of Health Lab Response  Kim Christensen –  June Pounder –  Barbara Jepson –  Emergency Pager – FBI FBI