AIHce Sauri 2007 Infectious Aerosols ... · PDF fileLegionella Outbreaks in Open Markets and Water Parks ... Live bird market employees ... An aerosol must be of fine enough particle

AIHce Roundtable

Emerging Infectious Hazards and Exposure Control

Part AJune 7, 2007

Infectious AerosolsMichael A. Sauri, MD, MPH&TM, FACP, FACPM

Medical DirectorOccupational Health Consultants

Rockville, Maryland301-738-6420

[email protected]

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Infectious AerosolsOutline

IntroductionDefinition of AerosolsDefinition of BioaerosolsSampling for BioaerosolsBioaerosols Containment

Engineering and Environmental ControlsAdministrative Controls and Work PracticesPersonal Protective EquipmentTest Model: SARS

Challenges in Containment of Infectious AerosolsValidation of StandardsNanotechnology Avian Flu PandemicNatural Disasters/PandemicsBioterrorism

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Non-Infectious Aerosols

Fibers: silica, asbestos, nylon, etc.Metals: lead, titanium dioxide, chromium,

cadmium, etc.Carbon: coal dust, combustion dusts, diesel

fume, asphalt fumes, smoke particulates, etc.

Organic Solvents: metal working fluids, etc.Synthetics: isocyanates (styrofoam), methyl

ethly ketone, acetoin, diacetyl, 1-nonanone (artificial butter flavoring), pesticides, etc.

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Severe Respiratory IllnessesExtensively Drug Resistant (XDR) Tuberculosis

(Mycobaterium tuberculosis hominis)

Severe Acute Respiratory Syndrome; SARS (Coronavirus)

Avian Influenza (H5N1 Influenza virus)

BioterrorismSmallpox (Variola major)Inhalational Anthrax (Bacillus anthracis)?

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Infectious Aerosols of Recent Public Health Concern

Acute Respiratory Outbreaks in Military Traineesin Russia and Malaysia

Legionella Outbreaks in Open Markets and Water ParksResearch Pathogens and Allergens

Anthrax Incident in Veterinary Research LabAnimal Caretakers and Cage WashersFermentation Operations (e.g. in-process sampling)

In-Door Mold (Stachybotrys)Post-Katrina New Orleans homes and Temporary Classrooms

Haatan Virus Risk in Camping/Hiking Shelters in Public Parks; Cabins in West Virginia

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Institute of Medicine’s 2002 List of Candidate Infectious Aerosols

for Biological Terrorism/Warfare

SmallpoxMonkeypoxNipah (Paramyxovirus)Viral encephalitides (VEE, WEE, Chikungunya)Tick-borne encephalitis virus“Eradicated” polio and measlesInfluenza A 1918 strain (Avian Flu)Hong Kong H5N1Others (Plague, Q Fever, Anthrax, Brucella)

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Infectious Aerosols: Population At Risk

Health Care Workers (Tbc, SARS, Avian flu, Ebola, Smallpox)

Laboratory Workers(Clinical Labs, Research Labs (Laboratory Animal Workers)

Patient Population (Hospital, Nursing Homes, Institutional)

First Responders (Police, Fire, EMS, Hazmat; FEMA; National Guard; Relief Volunteers )

Certain Occupations (Poultry Industry, Animal/Animal Product Handlers; Nano-technicians)

The General Public (Legionellosis; Plague; Histoplasmosis; Coccidioidomycosis; Avian Influenza, bioterrorist attacks)

Special Populations (Airline Passengers; Students in Temporary Classrooms; Water Park visitors; Prisoners)

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Occupational Risks For Highly Pathogenic H5N1 (Asian Strain)

Poultry producers / industry workersBackyard hobby farmers (free-range birds)Live bird market employeesBird fighting groupsEmployees involved in disease control and

eradication activities VeterinariansMedical professionals treating H5N1-infected

humans

Since the days of the cave man, the Earth has never been a Garden of Eden,

but a Valley of Decisionwhere resilience is essential to survival…

to grow in the midst of dangers is thefate of the human race.

Rene Dubos“Mirage of Health”

1901 -1982Microbiologist, Environmentalist

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The Garden of Eden

Our grandparents and great grandparents lived their daily lives with the constant threat of an untimely death due to host of deadly infectious diseases. Epidemics and their attendant losses were a reality of life for them.

The current generations have grown unaccustomed to human loss due to any cause and have found it very difficult to accept the threat of any global pandemic (even that of HIV) and, as a result, tend to not prepare.

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Global UrbanizationNearly half of the world's people now live in urban centers. The number of cities with a population greater than 1 million(agglomerations) has increased sharply over the past half century.

1955 1995# of Agglomerations (> 1M) 90 336

(26% Pop) (36% Pop)

# of Agglomerations 1970 1996In Developed Countries 82 115In Developing Countries 83 221

1950 1995 2001 2015Megacities (> 10 M) 1 14 18 (21)Sources: United Nations Population Division: World urbanization prospects: the 1999 revision. Key Findings. UN, New York 2001.World Health Organization: Life in the 21st century: A vision for all. World Health Organization, Geneva 1998 Melinda Moore, Philip Gould, Barbara S. Keary, 2003, Int. J. Hyg. Environ. Health 206, 269 ± 278 (2003)

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GLOBAL TRAVEL STATISTICS

In 1997, 30-35 million persons travel annually to developing countries from industrialized countries

80% are tourists

Origin of Travel:50% travel from Europe to Africa and Asia40% travel from US and Canada to Mexico and Caribbean10% travel from Australia, New Zealand, & Japan

Source: Dupont, HL and Steffen, R, “Textbook of Travel Medicine and Health,” 1997, BC Decker, Inc.

By 2015, ICAO projects 2.5 billion passengers will travel by airannually

Outlook for Air Transport to the year 2015,, Montreal, Intl. Civil Aviation Org.( ICAO), 2004, (Circular 304 AT/127, 2004)

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Air Travel Statistics (USA)(in Millions)

Type of Travel 1994 2005

All Airline trips 480 660 (2006)

Departures to Foreign country 20 86

Arrivals into USA 18 25 (2000) 18 (2003)

Cruise trip 5 10

Immigration into USA 1 1

Sources:Bureau of Transportation Statistics, T-100 International Market and Segment, March 2004 Plunkett's Airline, Hotel & Travel Industry Almanac 20072005 Yearbook of Immigration Statistics, Homeland SecurityU.S. Department of Commerce, ITA, Office of Travel and Tourism Industries: Statistics

Canada; & Secretaria de Turismo (Mexico)

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Serious Airborne Or Droplet-spread Infections Encountered During Air Travel

Mycobacterium tuberculosis Measles (Rubeola)Meningococcal (Neisseria meningitidis)SARS (coronavirus)Influenza virus

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Respiratory Protection’sCompeting Standards

ACGIH TLV’s vs OSHA Limits (Air Quality)ACGIH TLV's vs NIOSH REL's (Safe Level)ACGIH vs DOE (Falling efficiency)CDC Biohazard vs Animal Biosafety (NHP)Res. Laboratory vs Hospital (BBP)JCAHO vs OSHA (Tbc) OSHA vs EPA (Katrina Relief)ASHRAE vs FAA (A/C Cabin)ASHRAE vs CDC (ACH)

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Definition of an Aerosol

An aerosol is any system of liquid or solid particlesdispersed in a finely divided state through a gas,usually air, and in a stable aerial suspension.

An aerosol must be of fine enough particle size andconsequent low settling velocity to possessconsiderable stability as an aerial suspension.

- smaller particles acquire the properties of a true solution.

- larger particles settle so rapidly that the system cannot properly be called a true aerosol.

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Aerosol Particle Size

Range in diameter from a few nanometers (millimicrometers) to about 1 micron (micrometer; 10-4 cm).

Particles with a diameter of less than 0.1 micron are referred meteorologically to as Aitken nuclei and generally produced by combustion processes.

In the case of fog or cloud droplets and dust particles, particles can have diameters of over 100 micron

Aerosols composed of particles larger than about 50 micron are unstable unless the air turbulence is extreme, as in a severe thunderstorm (note: hair width is 80 microns).

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Bioaerosol Sizes

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Special Case of Fibers

Fiber deposition is a special case with regard to site of deposition.

Fiber settling velocity, as with other particles, is largely dependent on its diameter.

Fibers in a moving air stream tend to align their length parallel to the direction of air flow and behave much the same as a spherical particle of the same cross-sectional diameter.

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Liquid Aerosols Particulates

Liquid aerosols are generally classified as fogs or mists.

Liquid aerosols are normally formed by condensation from a gaseous to a liquid state (fog), or by dispersion of a liquid due to splashing or foaming, by atomization , and by gas entrainment of a liquid (mists).

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Solid Aerosol Particulates

Solid particulates are subdivided according to particle size and method of evolution:

dusts (by crushing , drilling, grinding,blasting and pulverizing),

fumes (by combustion or condensationafter volatilization and formation ofmetal oxides), and

smokes (by incomplete combustion oforganic materials).

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Pathophysiology of Aerosol particles

Particulates causing respiratory diseases are those suspended in air which can be inhaled (respirable).

This includes all particles, solid or liquid, in a size range capable of being:

inhaled and deposited in the nasopharyngealand /or tracheobrochial region, or

penetrating the tracheobronchial tree and beingdeposited in the alveolar regions of the lung

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Transmissibility of Aerosols

Reservoir sufficient to promote growth

Ability of agent to escape from the reservoir Humans and animals generate large particles (aerosols)Laboratory operations generate smaller, respirable

particles (2-8um)

Ability to transport through environment Downwind, upwind, air currents, ventilationHumidification Increases collection by impinger,Viruses with structural lipids survive best in low humidityViruses without structural lipids prefer higher humidity

Entry point into host

Susceptibility of Host

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“Respirable”

ACGIH’s focus is on the “respirable” dust fraction of any cloud that penetrates to the non-ciliated portions of the lung

That fraction of “respirable” dust is defined by a sampling efficiency curve which depends on the falling velocity of the particles( ACGIH standards).100% efficiency at 2 micron and below50% efficiency at 3.5-5 microns and zero efficiency 0% efficiency for particles of 7-10 microns or more

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Deposition-Size Distribution of Aerosol Particles in Lung

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Aerodynamics of Aerosol Particles

determine the particle’s mobility regardless of its apparent size and shape (e.g. a relatively large, loose aggregate of particles may behave aerodynamically the same as a much smaller dense particle).

determine the relative ease with which the particles are removed by the physical mechanisms of inertial impaction, sedimentation and diffusion.

is an important factor in selecting the method of sampling.

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a substance of biological origin that is capable of producing an adverse effect

e.g. an infectione.g. a hypersensitivity, irritant,

inflammatory, or other response)

Source: American Conference of Governmental Industrial Hygienist(ACGIH)

Definition of Biological Agent

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Biological Agents

Around 1200 Infectious disease or toxins identified

Biological Agents included prions, microorganisms (viruses, bacteria and fungi) and some unicellular and multi-cellular eukaryotes (parasites) and their associated toxins.

Examples: Anthrax, avian influenza, botulism, foodborneillness (e.g. Staph. toxin), hantavirus, Legionnaires’ disease, molds, and fungi,pneumonic plague, smallpox, tularemia andviral hemorrhagic fevers

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Biologically Derived Airborne Contaminants

Ubiquitous in nature

modifiable by human activity.

Humans are constantly exposed to a wide variety of such materials.

Source: American Conference of Governmental Industrial Hygienist (ACGIH)

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1. Bioaerosols = airborne particles composed of or derived from living organisms

Microorganisms (culturable, non-culturable, dead)FragmentsToxinsParticular waste products

2. Volatile organic compounds


Biologically Derived Airborne Contaminants

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Bioaerosols Categories

A. Toxigenic: classic “poisons”B. Allergenic: a non-infectious adverse event

(e.g. dead microorganisms, fragments,toxins, and particulate waste products from all varieties of living things; “bad building syndrome”)

C. Proliferative: classic “infectious aerosols”

Note: All can cause mortality and morbidity


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Bioaerosol Poisons (Microbial, Plant, Animal or Synthetic toxins)

SolidLead sulphate; arsenic trioxide

LiquidMany liquids an exist as liquid aerosols

GasCarbon monoxide

Vapor (i.e. the gas phase of liquid @ RT)Benzene (highly volatile); furfural (volatile and

lipophilic)Aerosol

Fibers and dust are solid aerosolsLow volatility liquids (e.g. Inorganic liquids)

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Bioaerosol Allergens(e.g. Indoor Mold-related Stachybotrys illness)

Many studies suggest a fungus-disease association relationship between Stachybotrys and human disease, these studies nearly uniformly suffer from significant methodological flaws, making their findings inconclusive.

However, to date, there is no supportive evidence for serious illness due to Stachybotrys exposure in the contemporary environment.

There is a need for studies using objective markers of illness, relevant animal models, proper epidemiologic techniques, and careful examination of confounding factors (e.g. bacteria, endotoxin, man-made chemicals, and nutritional factors).

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Indoor Biological Contamination

is defined as the presence of: a) biologically derived aerosols, gases, and vapors of a

kind and concentration likely to cause disease or predispose humans to disease:

b) inappropriate concentrations of outdoor bioaerosols, especially in buildings designed to prevent their entry: or

c) indoor microbial growth and remnants of biological growth that may become aerosolized and to which humans may be exposed.

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Proliferative Bioaerosols:The “Classic” Infectious Aerosols

Tuberculosis (the Prototypical Infectious Aerosol)Avian InfluenzaeInfluenzaeSARS (Coronaviruses)Aspergillus spp.Legionella spp.Varicella-zoster virusPlague (Yersinia pestis)Weaponized Infectious agents (Bioterrorism)

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Sources for Infectious Aerosols

Naturally Occurring Infectious Aerosols

Occupational Exposure

Man-Made or Man-Amplified

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Naturally Acquired Infectious Aerosols

BacterialTuberculosis, Psittacosis, Q Fever, Anthrax,

Brucellosis, Leptospirosis, Tularemia, RMSF, Legionella, Plague

ViralInfluenza, Avian Influenza, SARS, Monkey Pox,

Hemorrhagic Viral Infections, Haatan Virus Fungal

Histoplasmosis, Aspergillosis, Candidiasis, Coccidiodomycosis

ParasiticDust Mites

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Occupationally Acquired Infectious AerosolsHospital workers (patients) Conjunctivitis, UTI, Surgical Wounds,

Skin, Respiratory, Hepatitis

Microbiology lab workers Any agent studied (Human or Animal (Clinical/Research)

Lab animal care Any agent studied; incl. B virus

Construction site workers & Histo, Blasto, Apergillosis Ventilations system repair men

Stock handler Glanders, Brucellosis, Tularemia, EEEHair and hides handlers Anthrax, TetanusRendering Plant worker Q-feverPet shops Operators PsittacosisMeat packing plant workers BrucellosisPoultry Packers Psittacosis,Ornithosis, Avian FluFarmers Anthrax, Brucellosis, Q-fever, RMSF,

Newcastle Dis., Coccidiodomycosis, Plague, Ornithosis, Farmers’ lung

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Ideal Sampler for Bioaerosols

Concentrate the aerosol provide some particlesize discrimination ranging from 0.1 to 50 microns

Work with minimal energy input

Work with minimal noise output

Utilize a variety of collection media

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Workplace Sampling for Infectious Aerosols

Samplers historically sample microbial aerosols by

a. impaction onto nutrients

b. impingement into fluid

c. combination of electrostatic and impaction into fluids.

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Sampling Methods

ImpactionMulti-stage sieve-typeSlit samplerMembrane FilterElectrostatic impaction

SettlingOpen petri dishUncoated surface

ImpingementRaised jet all-glass impingerMulti-stage liquid impinger

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Environmental Sampling of Bioaerosols

1. Culturable bioaerosols (e.g.. total bacteria or fungi grown in laboratory culture and reported as the number of colony-forming units (CFU):

Aspergillus fumigatusLegionella pneumophilaMycobacterium tuberculosis;

orassayable biological contaminants (e.g. endotoxin,

mycotoxin, antigens, or microbial volatile organic compounds)

2. Countable bioaerosols are those pollen grains, fungal spores, bacterial cells, and other material that can be identified and counted by microscope.

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Recommended Sampling Methodology for Microbial Aerosols (AFGIH)

Spores: filters through impaction or on water-free surfacese.g. Aspergillus

Bacteria: collected onto nutrient medium or in fluids e.g. Coliformse.g. Mycobacterium Tuberculosise.g. Legionella

Viruses: slit samplers (12% gelatin), impingers (tissue culture nutrient w/ additives) and Anderson samplers (3% gelatin)

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Outdoor Sampling for Infectious Aerosols

Particles are of a wide variety and from ill-defined sources

Counts tend to be from the hardy fractions of cell populations that have undergone relative humidity (RH) stress, ultraviolet (UV) irradiation and exposure to air pollutants.

Particles heterodispersed

Collection during an unknown variety of meteorological conditions.

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Limitation of Workplace Sampling for Infectious Aerosols

Generally, we are currently not able to sample the air of a workplace and define hazardous conditions (since type and conc. of pathogen is often unknown)

Specific TLVs have not been established to prevent hypersensitivity irritant or toxic responses.

Viable vs. non-viable counts? Bioaerosol sources and mechanisms by which workers may

be exposed to bioaerosols are often unclearEnvironmental monitoring commonly detects a mixture of

many biologically derived materials, reflecting the diverse and interactive nature of indoor microenvironments.

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Limitations of Sampling for Infectious Aerosols

It is not possible to collect and evaluate all bioaerosol components using a single sampling method.

Different methods of sample collection and analysis may result in different estimates of culturable and countable bioaerosol concentrations.

Deficiencies in Instrumentation and Sampling Procedures often:

do not yield data on particle size of the aerosol and/ordo not provide time-concentration data

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Environmental variables difficult to control Desiccation and osmotic shock affects viabilityRelative humidity affects viabilityOutdoor sampling variables: wind, UV radiation

(e.g. Legionella)For particles less than 8 microns, sampling is

significantly affected by airflow directions if the wind is greater than 5 MPH.

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No exposure TLV limits since, in theory, one microorganism may cause disease (e.g Inhalation of a single tubercle bacillus (10-12 to 10-13 gram) can initiate an active tuberculosis lesion).

Human responses to bioaerosols range from innocuous effects to serious, even fatal diseases, depending on the specific material involved and workers susceptibility to it.

Therefore, an appropriate exposure limit for one bioaerosol may be entirely inappropriate for another.

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Culturable microorganisms and countable biological particles do not comprise a single entity, e.g. bioaerosols in occupational settings are generally complex mixtures of many different microbial animal and plant particles.

At present, information relating culturable or countable bioaerosol concentrations to health effects consists largely of case reports and qualitative exposure assessments.

The data available are generally insufficient to describe exposure-response relationships

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Epidemiological Limitations of Sampling for Infectious Aerosols

Most data on concentrations of specific bioaerosols are derived fromindicator measurements rather than from measurements of actual effector agents.

Most measurements are from either area or source samples rather than from personnel sampler for the actual effector agents.

Low statistical power common and limits evaluations of cause-effect relationships between exposures to specific biological agents and building-related health complaints.

Bioaerosol components and concentrations vary widely within and among different occupational and environmental settings; consequently, measurements from single, short-term grab samples are unlikely to represent workplace exposures accurately.

Data from different studies can seldom be combined to reach meaningful conclusions.

Human dose-response data are available for only a few infectious bioaerosols; at present, air-sampling protocols for infectious agents are limited and suitable primarily for research endeavors.

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Trend in the Sampling of Infectious Aerosols

Miniaturization of samplers with single stage sieve collector and timing devices without the need for external pumps or power sources.

Monitoring in the Respirable Zone (e.g. Button Aerosol Sampler of Inhaled Air)

A shift to utilizing ELISA and PCR-based detection methods for rapid identification as eliminated the need and risk of culturing the agents and the reduced viability of certain agents in extramural air sampling.

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The Future of Sampling of Infectious Aerosols

Innovative molecular assay methods and field validation are steadily improving for certain biologically derived contaminants (e.g., endotoxin, mycotoxins, antigens, and volatile organic compounds)

Dose-response relationships for some assayable bioaerosols have been observed in experimental studies and occasionally in epidemiologic surveys.

Eventually, exposure limits for certain assayable, biologically derived, airborne contaminants may be possible.

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Bioaerosols Containment

Engineering and Environmental ControlsAdministrative Controls and Work PracticesPersonal Protective EquipmentTest Model: SARS

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Engineering and Environmental Controls of Bioaerosols

In most routine exposure settings:public health measures, such as immunization, active case finding, and medical treatment, remain the primary defenses against infectious bioaerosols.

In High-risk facilitiesemploy engineering controls to minimize air

concentrations of infectious agents.consider the need for administrative controls and

personal protective equipment to prevent the exposure of workers to these bioaerosols.

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Bioaerosol Generating Sources/Procedures

in Hospitals

Patients >> HCWsRoutine and Emergency IntubationsRespiratory Therapy (Inducing Sputum)Surgical Laser ablationsSurgery on extrapulmonary tbcHospital Construction ActivitiesAutopsy Procedures (electric saw and opening

sites/containers of infectious materials whose internal pressures may be different from ambient pressures

Decorative fountains and fish tanks in Patient Areas

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Sneeze = 100,000 particles (traveling at 200 mph)

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A Cough (1000 particles) in a Typical Isolation Room First 60 Seconds

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Positive PressureIsolation Room

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Negative PressureIsolation Room

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Airborne Infection Isolation (AII) with Anteroom

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Isolation Room DesignASHRAE Goal

Reduction in the number of particles inhaled per minute by HCW to 1 bacilli / minute.

Dilute the HCW breathing space (10 L/min or 0.04ft3/min) with 10,000 fold quantity of that volume in fresh air.

Principles of Isolation Room Design

The basic design philosophy of tbc patient isolation rooms is relatively straightforward.

ASHRAE (2003) utilizes a high ventilation rate within a room to dilute and flush the aerosol contaminants.

Consequently, the objective is maximizing air mixing effectiveness and dilutional ventilation.

Note: CAN/CSA Standard Z 317.2-01 requires bidirectional airflow, flow across the infection source and non-aspirating diffusers.

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ACH EquationAir Changes / Hour

Air Changes / Hour (ACH) = Q/VQ = air flow rate in cuft/hrV = room volume in cubic feet

ACH Equation:t2 – t1 = -[ ln (C2 / C1) / ((Q/V)] X 60where T1 = initial timepoint in minutes = 0T2 = final timepoint (min)C1 = initial [contaminant]C2 = final [contaminant]C1/C2 = 1 – (removal efficiency/100)

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Isolation Room Design ASHRAE Calculation of ACH

ACH

= Air Exchanges / Hour

= (0.04ft3 /min X 10,000) X 60 min/hr 1,600ft3

= 24,0001,600

= 15/hr

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Air Exchanges/Hour Table

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Isolation Room Design ASHRAE Assumptions

Infective particle = 1-5 microns (prolonged airborne time)

Infective Dose = 1-10 particlesNumber of Tbc bacilli per particle = 10 bacilliNumber of particles per cough = 1000 Cough volume = 0.5 liter (0.02ft3 )Number of coughs per min = 1Room Dimensions = 47m3 or 1,600 ft3

(10’X16’X10’)HCW inhalation vital capacity = 10 liters/min

(0.04ft3 /min)

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Isolation Room Design ASHRAE Limitations

ACH equation applies to an empty room with no aerosol-generating source (e.g. patient).

Although there are ACH equations available for a constant generating source; certain diseases (e.g Tbc) are not likely to be aerosolized at a constant rate.

ACH equation assumes perfect mixing of the air within the space; not all regions of room are ventilated at a high rate (stagnant zones).(usually areas of air stagnation exists).

Patients cough often more than 1/min Sneezing produces 100,000 particlesNumber of Tbc bacilli per particle may exceed 10

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Isolation Room – Laminar Flow (ASHRAE Design

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Isolation Room Design Conclusion

Despite maintaining 15 air exchanges per hour; ASHRAE approach of rapid mixing does not negate the CDC recommendation that all HCW treating Tuberculosis patients wear respiratory protection.

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Bioaerosol Containment in High-Risk Facilities

Microbiology laboratories

Biomedical Research Laboratories

Animal-handling facilities

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Infectious Aerosols Exposures in Laboratories

In the 1930’s and 1940’sbacterial, fungal anRickettsial

Between 1950 -1975BrucellosisQ fevertyphoid feverviral hepatitistuberculosis.

Note: Of these infections, only 20% of cases were attributedto mouth pipetting and needle sticks; 80% considered due to exposure to infectious aerosols

In the 1970’s and 1980’smarked decline due to bacterial and rickettsiallesser decline due to viruses and fungi

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Infectious Aerosols Exposures in Laboratories

In the 1980’s and 1990’sblood and blood byproducts (e.g. Hepatitis B virus and HIV) non-human primates viruses

(Marburg virus, B virus, simian retroviruses).

In the 1990’sSimian Retroviruses, recombinant DNA, carcinogenic material/tissueschimeric virus vaccine development (Vaccinia and adenovirus)

In the first decade of the 21st century hypersensitivity in laboratory animal handlersdisease agents without antidotes

bioterrorism agents (e.g. ricin, hemorrhagic viruses)prionsnanotechnology

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BioSafety Level ?

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Infectious Aerosols in Laboratories

Procedures with a potential for creating infectious aerosols or splashes must be conducted in a certified Biosafety Cabinet (BSC).

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Aerosol Generating Procedures in Laboratories

CentrifugingGrindingBlendingVigorous Shaking Or Mixing Sonic DisruptionOpening Containers Of Infectious Materials

Whose Internal Pressures May Be Different From Ambient Pressures

Inoculating Animals Intranasally Harvesting Infected Tissues From Animals Or

Embryonate Eggs

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Laboratory ContainmentBiosafety Level 3

Biosafety Level 3 practices, safety equipment, and facilities are applicable to clinical, diagnostic, teaching, research, or production facilities in which work is done with indigenous or exotic agents with a potential for respiratory transmission, and which may cause serious and potentially lethal infection.

Mycobacterium tuberculosis (TBC), St. Louis encephalitis (SLE) virus, and Coxiella burnetii (Q-fever) are representative of microorganisms assigned to this level.

Primary hazards to personnel working with these agents relate to autoinoculation, ingestion, and exposure to infectious aerosols.

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Laboratory ContainmentBiosafety Level 3

At Biosafety Level 3, more emphasis is placed on primary and secondary barriers to protect personnel in contiguous areas, the community, and the environment from exposure to potentially infectious aerosols.

For example, all laboratory manipulations should be performed in a BSC or other enclosed equipment, such as a gas-tight aerosol generation chamber.

Secondary barriers for this level include controlled access to the laboratory and a specialized ventilation system that minimizes the release of infectious aerosols from the laboratory.

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Animal Facilities10-15 fresh air changes per hour has been used for

secondary enclosures for many years and is considered an acceptable general standard

However, the guidelines do not take into consideration:

Range of possible heat loadsSpecies, size and number of animals involvedRoom dimensionsEfficiency of air distribution from the secondary to the

primary enclosureEfficiency of the HEPA filters used from recycled air;Control of odors (e.g. ammonia), allergens and metabolically

generated gases Particle generation due to sanitation procedures (bedding

changes and cage cleaning) and husbandry practices (e.g. temperature, humidity)

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Agents by Biosafety Levels

BSL 1Bacillus subtilis, Canine Hepatitis, E. Coli, Varicella

BSL 2Hepatitis B, Hepatitis C, Influenza, Lyme Disease, Salmonella,

HIV, scrapieBSL 3 (~ 60 operational in USA)

Anthrax, BSE, mumps, WNV, SARS, Smallpox, TBC, typhus, Yellow Fever

BSL 4 (~12 operational in USA)Bolivian Fever, Dengue Fever, Marburg virus, Ebola, Hanta

virus, Lassa virus or other hemorrhagic diseases.BSL 5 (fictional)

“Andromeda Strains;” “Wildfire;” NASA extra-terrestial samples

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BSL 4 Containment LaboratoriesWorldwide

Australia (3) Brazil (1)Canada (1) France (1)Gabon (1) Germany (1)Japan (1) India (1)Italy (1) Russia (1)Singapore (1) South Africa (1)Sweden (1) Switzerland (1)Taiwan (1) United Kingdom (3)United States (12+)

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BSL 4 Containment Facilities in USA Operational Facilities

USAMRIID in Fort Detrick, MD ("old building") CDC in Atlanta, GA (two buildings operational) NIAID’s Integrated Research Facility in Fort Detrick, MD NAIIDs Rocky Mountain Laboratories in Hamilton, MTNIH’s BSL-4 lab in Building 41A on the NIH Campus in Bethesda, MD

sometimes operates at BSL-3) (NIH’s BSL-4 lab in Bulding 33 (new) on the NIH Campus in Bethesda, MD NIH’s BSL-4 lab 12735 Twinbrook Pkwy, Rockville, MD Southwest Foundation for Biomedical Research in San Antonio, TX UTMB's Shope Laboratory in Galveston, TX Georgia State University in Atlanta, GA (smaller "glovebox" facility) The Division of Consolidated laboratory Services lab (part of the

Department of General Services of the Commonwealth of Virginia) in Richmond, VA (so-called "surge" BSL-4 capacity)

The Infectious Disease Unit (IDU) of the Oklahoma Animal DiseaseDiagnostics laboratory (OADDL) at Oklahoma State Univ, Stillwater, OK.

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BSL 4 Containment Facilities in USAUnder Construction

USAMRIID in Fort Detrick, MD ("new building“)

Boston University s National Emerging Infectious Diseases Laboratory (NEIDL) in Boston, MA

UTMB’s National Biocontainment Facility in Galveston, TX

DHS's National Biodefense Analysis and Countermeasures Center (NBACC) in Fort Detrick, MD

DHS’s National Bio- and Agro-defense Facility (NBAF)

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NIH/NIAID Bldg 33Hardened Level 3 Facility at NIH

• Bact Vacc (non-cGMP)• Poxvirus• Drug resistant TB• Tularemia• Food and Waterborne Pathogens• Viral Hemorrhagic Fevers (Ebola,

etc)• Avian Influenza• SARS (Coronavirus)

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Biosafety Level 4 Laboratory

• Source: NEJM, 1-12-06, 254:2, pg 110

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Engineering and Environmental Controls

Administrative Controls and Work PracticesPersonal Protective EquipmentTest Model: SARS

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Administrative Controls and Work Practices Control of Bioaerosol Exposure

Host-directed ActionsDeficiencies in Host DefensesVaccines (e.g. flu, anthrax, smallpox)

Containment Criteria DevelopmentStandard Precaution/Good Laboratory PracticeIsolation (Ill Patient and Exposed)Quarantine vs Reduced Socialization

Reservoir-directed (e.g. culling, rodenticides, etc)

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Administrative Controls and Work Practices Control of Bioaerosol Exposures

ACGIH approach to assessment and control:

Visually inspecting buildingsAssessing occupant symptomsEvaluating building performanceMonitoring potential environmental sources, and Applying professional judgment.

88

ACGIH provides background information on:

the major groups of bioaerosols, on the assessment, control, remediation, and

prevention of biologically derived contamination their sources and health effects, and describes methods to collect, analyze, and interpret

bioaerosol samples from potential environmental sources.


89


TLVs exist for certain substances of biological origin, including:cellulose some wood cottonflour and grain dustsnicotinepyrethrumstarchsubtilisins (proteolytic enzymes)sucrosevegetable oil mistvolatile compounds produced by living organisms (e.g., ammonia, carbon

dioxide, ethanol, and hydrogen sulfide).

However, there are no TLVs against which to compare environmental air concentrations of most materials of biological origin.

90


Engineering and Environmental ControlsAdministrative Controls and Work Practices

Personal Protective EquipmentTest Model: SARS

91

Which is best PEP during Pandemic Flu?

N-95 Mask or Surgical Mask

92

What PEP is the right one?

Answer: A risk assessment process should review the key factors in the pathophysiology of the disease in question before any specific recommendations are made.

Factors:Transmissibility of agent Characterisitics of specific job functions

e.g. respiratory technicianSusceptibility of Host

(e.g neonates; cancer patients; etc)Facility characteristics

(e.g. patient flow, isolation rooms, ventilation)

93

Bacterial Filtration Efficiency (BFE)

"Standard Test Method” for Evaluating the Bacterial Filtration Efficiency (BFE) of Medical Face Mask Materials is found in ASTM F2101-01

BFE test uses a biological aerosol of Staphylococcus aureus", and Military Specification MIL-STD 36954C-Section 1.4 of the standard states

Results of these BFE tests evaluates the effectiveness of the medical face mask materials as an item of protective clothing to filter aerosols of ~3.0µ in size.

94

BFE vs NIOSH Certification

The BFE test method does not evaluate materials for regulatory approval as respirators.

The BFE test method does not address design, performance or facial fit.

Meeting BFE specifications does not necessarily apply to respiratory protection, therefore, a NIOSH-certified respirator should be used (i.e. meeting the requirements of 42 CFR Part 84)

In order to make claims against specific organisms (e.g. avian flu virus, nano-particles) there will need to be data with the appropriate regulatory agency to back up those claims.

95

Validation of the Assigned Protection Factoris contingent upon:

The respirator user must adhere to program requirements (OSHA’s Respiratory Protection Standard 29 CFR1910.134)

NIOSH certified respirators must be used in their approved configuration

The use of individual fit testing to rule out those respirators that cannot achieve a good fit on individual workers

96

Assigned Protection Factor for Particulate Respirators (in multiples of PEL)

5 Filtering Mask (Disposable; Dust mask)5 Quarter Mask respirator

10 Elastomeric Half-Mask25 PAPR (Powered HEPA filtered Air

Purifying Respirator with hood or helmet)50 Elastomeric Full Mask respirator with

N-100, R-100, P-100 filter1,000 Powered, Pressure demand Half-Mask2,000 Powered, Pressure demand Full-Mask

10,000 Powered, Pressure demand SCBA &/or Supplied Air Respirator (SAR) Full Mask

The assigned protection factors are only effective when the employerimplements a continuing, effective respirator program as required by thissection (29 CFR 1910.134), including training, fit testing, maintenance, anduse requirements. Reference: NIOSH Pub. No. 2005-100 (Oct 2004)

97

Does a half mask with particulate filters give a higher APF than a similar

specification disposable respirator?

Purely based on the protection factor, and not taking into account other factors such as user acceptability and cost effectiveness, there is no difference in APF between disposable particulate respirators and a half mask fitted with the same specification filters.

98

Why are there APFs and NPFs?

A respirator’s Nominal Protection Factor (NPF) is the theoretical protection level based on laboratory measured performance data.

An Assigned Protection Factor (APF) is the level of respiratory protection that can realistically be achieved in the workplace by 95% of adequately trained and supervised wearers. The APF should be used when selecting a respirator.

99

The Effect of Breathing Resistance onPulmonary Function and Work Capacity

Half face air purifying respirator with 2 HEPA/organic vapor/acid gas cartridges cartridge airflow resistance = 36 mm H20 @ 42.5 L/min

Source: Mead, Z, Sharkey, B, and Townsend, T; University of Montana Human Performance Laboratory, and USDA/FS Missoula Technology and Development Center, 1991. http://www.fs.fed.us/eng/pubs/htmlpubs/htm91672848/page03.htm

100

NIOSH CERTIFICATION OF MASK

The procedure for a NIOSH N95 certification is available at the following website address:

http://www.cdc.gov/niosh/npptl/resources/certpgmspt/default.html

The following tests are required for pre-qualification:

1) filtration efficiency2) inhalation resistance3) exhalation resistance, and 4) exhalation valve leak (when applicable).

101

Filtration Efficiency Test

Neutralized NaCl aerosol through the sample at 85 L/min. This aerosol has a particle size distribution with a count median diameter of 0.075± 0.02µ, a mass median diameter of 0.26µ, and a geometric standard deviation not exceeding 1.86µ as determined by the manufacturer with a scanning mobility particle sizer (SMPS).

Masks are loaded with the NaCl until 200 mg contacts the filter.

The maximum filter penetration that can occur to maintain a N95 rating is =5% (=95 % efficiency).

102

Inhalation Airflow and Exhalation AirFlow Resistance Test

Initial breathability of the mask, in both directions of exhalation and inhalation (42 CFR Part 84.180).

Measurements are made with a 6 inch slant manometer.

Initial Inhalation resistance cannot exceed 35 mm water

Initial exhalation resistance cannot exceed 25 mm water.

103

Exhalation Valve Leak Test

Exhalation valve is removed from the respirator

The leakage across the valve is determined according to 42 CFR Part 84.182.

Measurements are made with a digital soap film flowmeter

Leakage cannot exceed 30 mL/min.

104

An N-95 respirator is one of nine types of disposable particulate respirators.

Particulate respirators are also known as “air-purifying respirators” because they protect by filtering particles out of the air as you breathe.

These respirators protect only against particles—not gases or vapors. Since airborne biological agents such as bacteria or viruses are particles, they can be filtered by particulate respirators.

105

Respirators in this family are rated for protection against oils.

This rating is important in industry because some industrial oils can degrade the filter performance so it doesn’t filter properly.* Respirators are rated “N,” if they are not resistant to oil, “R” if somewhat resistant to oil, and “P” if strongly resistant (oil proof). Thus, there are nine types of disposable particulate respirators:

N-95, N-99, and N-100 R-95, R-99, and R-100P-95, P-99, and P-100

Those that filter out at least 99% receive a “99” rating. And those that filter at least 99.97% (essentially 100%) receive a “100”rating.

The N-series will be tested against a mildly degrading aerosol of sodium chloride (NaCl). The R- and P-series filters will be tested against a highly degrading aerosol of dioctylphthalate (DOP)

106

N95 respirators

The N95 designation indicates that under the test methods in the laboratory, 95% of particles are captured with a GMD (Geometric Mean Diameter) of 1.6 micron (or 5% will pass through).

Face seal leakage in N95 respirators can be estimated at 1% when properly fit tested. This value corresponds to a fit factor of 100, which is OSHA’s criterion for an acceptable fit.

This is in addition to the large leakage that will result in the practical environment where face fit is not possible and where no training in respiratory protection has been carried out.

A NIOSH certified N-95 rated respirator will filters out at least 95% of airborne particles during a 0.3 micron sized particle challenge.

Other respirators (e.g surgical mask) are allowed to transmit greater than 20% particles through the respirator, but in practice much greater leakage of particles will result due to face fit factors

107


Engineering and Environmental ControlsAdministrative Controls and Work PracticesPersonal Protective Equipment

Test Model: SARS

108

SARS (Coronavirus) SARS (lobar pneumonia)

SARS (CHINA 2003) SARS (Civet Cat)

109

SARS

Nonspecific presentation: fever & respiratory symptoms (dyspnea & cough); FLS

No rapid diagnostic test: case definition usedDefinitive mechanism of transmission remains

unclear (droplet, fomite, airborne)No specific medication or vaccine available

110

SARS (Nosocomial Epidemic)

Nov 2002 to July 20038427 probable cases29 counties (29 in USA; no deaths)813 Deaths3-12% Case Fatality Rate (45% CFR if > 60 years old)

Primarily a nosocomial (hospital associated) epidemicHong Kong 62% HCWsVietnam: 57% HCWsCanada: 51% HCWs

111

SARS EPIDEMIC FEB 2003

Index Case (Chinese Physician visiting Hong Kong after treating SARS patients) infected: 4 HCW2 Family members

12 Hong Kong Hotel guests2 stayed in Hong Kong:

1 infected 3 HCWs1 infected 99 HCWs

3 went to United States: infected unknown number1 went to Ireland: infected unknown number2 went to Canada and infected

4 family members; 10 HCWs2 close contacts

1 went to Hanoi and infected 37 HCWsone HCW went to Thailand and infected unknown number

3 went to Singapore: infected 37 close contacts 34 HCWsone HCW went to Germany and infected 2 family members

This index case resulted in infections of 53 family members/close contacts and 187 HCWs.

112

SARS Transmission In Commercial Aircraft 2003

113

Classic Hierarchy of Controls1. Engineering and Environmental Controls

(e.g. physical barriers, general and local ventilation, filtration, anterooms, negative pressure isolation, and temporary structures (triage tent ER facilities)

2. Administrative Controls and Work Practices(e.g early identification and separation of cases; SOPs to reduce duration, frequency and severity of exposures to HCW, patients and visitors; education, drills)

3. Personal Protective Equipment(e.g. gloves, gowns, goggles/eye shields, masks & respirators)

Important Caveat: In infectious disease outbreak, AdministrativeControls (i.e. early identification of cases) is critical prior to theeffective implementation of Engineering and Environmental Controls.

114

1. Engineering And Environmental Controls

Dedicated SARS treatment Unit with their own ventilation system

Single rooms for suspected SARS patientsExternally exhausted HEPA filtersHeated Tents outside the Hospital for screening

Hierarchy of Controls Application in combating a

SARS Outbreak

115

2. Administrative Controls

Assignment of dedicated staff to the SARS unitStrict screening program for everyone entering a

healthcare facility – patients, visitors, staffCancellation of ambulatory clinics and elective surgeriesPreventing inter-facility patient and staff transfersRestriction of hospital visitors10 day voluntary home quarantine for exposed patients,

visitors and staff


SARS Outbreak

116


SARS Outbreak

3. Personal Protective Equipment (PPE)

Routine use of gowns, gloves, eye protection, & N-95 masks for all visitors and staff

Double gowns, double gloves, and hair & shoe covers in high-risk areas such as ED, ICU & SARS unit.

117

Effectiveness of a N-95 Respirator

N-95 Mask only 85% effective

Based on transmission in epidemicsituations with SARS and TBC, simplyputting a surgical mask on the patientand regular hand washing may be moreeffective than simply using a N-95 mask.

118

Challenges in Containment of Infectious Aerosols

Validation of StandardsNanotechnology Avian Flu PandemicNatural Disasters/Pandemics Bioterrorism

119

Respiratory Protection’sCompeting Standards

ACGIH TLV’s vs OSHA Limits (Air Quality)ACGIH TLV's vs NIOSH REL's (Safe Level)ACGIH vs DOE (Falling efficiency)CDC Biohazard vs Animal Biosafety (NHP)Res. Laboratory vs Hospital (BBP)JCAHO vs OSHA (Tbc) OSHA vs EPA (Katrina Relief)ASHRAE vs FAA (A/C Cabin)ASHRAE vs CDC (ACH)

120

42 CFR Part 11Purpose: to certify the N-95 respirator filtration efficiency using

the most penetrating aerosol size (0.30 µ) with either degrading or non-degrading particulates to challenge the respirator at 95, 99, or 99.97% filtration efficiency.

NIOSH StandardNeutralized NaCl aerosol: a median mass diameter of 0.26µ(0.075± 0.02µ)

Other standards used to screen new respirator material (as per Military Specification MIL-STD 36954C)

Bacterial Filtration Efficiency (BFE) Aerosol of Staphylococcus aureus with a MPS of approximately 3.0µ.

Viral Filtration Efficiency (VFE) phiX174 bacteriophage at 0.027µ(27 nm) in size (one of the smallest known viruses, has no envelope, and has icosahedral morphology)

121

Recent Controversies in Respiratory Protection

ICPA vs OSHA (standard of care issues)

AOHN vs CDC (fit testing)

Rescinding of the OSHA 1995 Guidelines for Tuberculosis (based on the realization that the standard would not prevent its most common method of transmission (i.e. undetected reactivation of disease)

Effectiveness of N-95 respirators during the SARS Epidemic in Hong Kong, China and Canada

Reliance on fit-tested N95 respirators during an Avian Influenza epidemic.

122

Research in Infectious Aerosols

Early Detection of Infectious AerosolsEnvironmental Detectors

MicroscopyEndotoxin assaysImmunoassaysGene Probes

Syndromic Surveillance

Primate Aerobiology

Bioweapon Research

123


Validation of Standards

NanotechnologyAvian Flu PandemicNatural Disasters/Pandemics Bioterrorism

NanotechnologyThe next pneumoconiosis?

125

A Nanometer

Like comparing a marble to the earthLike comparing an inch to 400 milesThe tinted coating on a pair of sunglasses is one-

tenth of a nanometer thickOne-billionth of a meter 100-nanometer-wide wire would span about 500

atoms of siliconA human hair is about 50-80,000 nanometers thickA dollar bill is 100,000 nanometers thickA head of a pin is 1 million nanometers wide

126

THE AGE OF NANOSCIENCE10µ Visible to unaided eye = 10,000 nm

2µ - 8µ “RESPIRABLE PARTICLES” - 2,000 – 8,000 nm

1.0µ 1 micrometer = 1 micron = 1 millionth of a meter = 1000 nm

BACTERIA0.40µ = 400 nm = 400 billionths of a meter - Qual. Fit Test (Bitrex or Saccharin) 0.3µ = 300 nm = 300 billionths of a meter - Staph aureus0.26µ = 260 nm = 260 billionths of a meter - N95 Respirator test particle (NaCl)

VIRUSES0.2µ = 200 nm = 200 billionths of a meter - Smallpox (large, enveloped) 0.027µ = 27 nm = 27 billionths of a meter - smallest virus (non-enveloped)

0.1µ = 100 nm = aerosol particles are referred to meteorologically as Aitken nuclei and generally produced by combustion processes.

NANOSTRUCTURES0.01µ = 10nm = 10 billionths of a meter (10 Hydrogen atoms line up)

MINI-NANOSTRUCTURES0.001µ = 1 nm = 1 billionths of a meter = 10 Angstroms

127

NANOTECHNOLOGY RESEARCH

BIOTECHNOLOGYMicroarrays – gene expression studiesDNA sequencing through micropores

(sequence the entire human genome in 2 hrs instead of 3 years)MEDICINE

Personalized medicineMicrofluidics ( a miniaturized laboratory)Synthesis of extremely small probes that can examine individualsstrands of DNA for disease detectionMan-made capillary systems to bring nutrients to artificial organs

ENGINEERINGNanoelectronics with transistors 100 nm in sizeManufacturing extremely strong fibers atom by atomVery small valvesAerospace engineering

Source : Dr. Albert Lozano, Nanotechnology Program, Commonwealth College, PSU

128

NANOTECHNOLOGY RESEARCH

HOMELAND SECURITYNanostructures as incredibly sensitive chemical and biological

substance detectors (nanosensors)Information Technology

DAILY LIFETextile (antibacterial treatments)Food bacteria detectionPollution detectorsFlat picture-like TVs and Computer screensAutomotive / Transportation

Source : Dr. Albert Lozano, Nanotechnology Program, Commonwealth College, PSU

129

NANOFABRICATION FACILITYNANOFABRICATION FACILITY

130


Validation of StandardsNanotechnology

Avian Flu PandemicNatural Disasters/PandemicsBioterrorism

131

So what happens when the chicken crosses the road?

132

“Bird Flu” in Florida

133

Avian

Influenza

134

Requirement for a Pandemic

• A new virus emerges for which the population has no immunity (i.e. resistant)

• The new virus must be able to replicate in humans and cause disease (i.e. virulent)

• The new virus must be efficiently transmitted from human to human (i.e. infectious)

135

Nations with confirmed cases of avian influenza A (H5N1) as of July 7, 2006

Source: http://www.pandemicflu.gov

136

Wild Bird Migration Paths

Ducks, swans, geese carry influenza south in the fallShorebirds carry influenza north in the spring

137

The original 1918 Spanish Influenza virus is recovered by Dr. Johan Hultin in 1999!

In 2005, Dr. Jeffery Taubenberger reconstructs the influenza virus isolated from the lung of an Alaskan eskimo victim of the 1918 Spanish Flu buried in the permafrost.

90% (72) of Village inhabitants died in 5 days and was buried in a mass grave in the permafrost in Brevig Mission, Alaska near the Bering Strait.

138

Avian Influenza Pandemic: Clear and Present Danger

We do not yet know if H5N1 will develop into a pandemic

However, the virus isolated in Alaska in 1999 from a victim of the 1918 Spanish Flu Pandemic was found to be pure avian (not a recombinant)

In 2005, the current circulating H5N1 was only two mutations away from becoming the 1918 Spanish Flu.

139

“Red Sky in Morning ….”

Circulating strains of H5N1 becoming more pathogenic

Ducks, infected with H5N1 virus, shedding more virus for longer periods without showing symptoms of illness (an ideal vector)

140

H5N1 has “broken the rule.”

H5N1 went back from the domestics into the wild birds.

Is it going to be perpetuated there as a killer? (That’s the million dollar question!)

141

Starlings, Pigeons, & Sparrows—Threat To Domestic Poultry

Experimental highly pathogenic H5N1 infection Sparrows, starlings and pigeons

All birds shed H5N1 virus in their feces Did not infect their own kindSparrows died—less likely threat to domestic poultry.

The bigger threats are the starling and the pigeon; especially the starling since it doesn’t die of A.I., but shed plenty of virus (i. e. an efficient vector between chicken houses)

142

Pandemic Flu: The Perfect Storm

Mismatch of Supply and Demand

Medical Surge Spectrum of Care:Home Care > “Main Street Triage” > Alternate

Care Sites “Surge Hospitals” > Hospitalized Patients

Medical Surge Communication>Pier2Pier Network > Phone Bank > Community

“Local AM Radio” > National (TV/Radio)

143

2004 WHO Executive Summary Pandemic Influenza

“Never before has an avian influenza virus with documented ability to infect humans caused such widespread outbreaks in birds in so many countries. This unprecedented situation has significantly increased the risk for the emergence of an influenza pandemic.”

144

Avian Influenza Transmission

145

Timeline of Pandemic Influenza

Source: Gerberding, N Engl J Med 2004;350:1236-1247.

146

Timeline of Avian (H5N1) Influenza

Source: Fauci, AS, EIN Jan 2006 Vol 12 No 1.

147

Combined Influenza- and pneumonia-specific death rates for the interpandemic years (1911 to 1917, dashed line) and for the

pandemic year (1918, solid line)

“Cytokine Storm”

Reprinted from Grove RD, Hetzel AM. Vital Statistics Rates in the United States: 1940-60. Washington: U.S. Government Printing Office, 1968, and Linder FE, Grove RD. Vital Statistics Rates in the United States: 1900-1940. Washington: U.S. Government Printing Office, 1943.

148

Mortality Rate For H5N1

As of June 1, 2007188 Deaths/310 Cases

60% Mortality Rate

Note: 1918 Spanish Flu Pandemic2.5%Mortality Rate

149

“Under 40” Group Most Affected

Source: Smallman-Raynor M, et al. Emerg Infect Dis, Mar 2007 http://www.cdc.gov/EID/content/13/3/510.htm

150

Impact Today of an Avian Pandemic on USA

Based on the 1918 pandemic:30 percent of the population (90 million) ill 2.5 percent (2.25 million) of those ill would dieThe U.S. Gross Domestic Product (GDP) could drop between over 5.5% (approximately $683 Billion loss)

Source: http://healtyamericans.org/reports/flurecession/

151

Poultry Industry

152

Poultry Farm BiosecurityKeep an “all-in, all-out” philosophy of flock managementProtect poultry flocks from contact with migratory birdsPermit only essential workers and vehicles to enter the farmEducate on symptoms and signs of avian influenza in poultry

and humans and provide clean clothing and disinfection facilities for employees

Thoroughly clean and disinfect equipment and vehicles entering and leaving the farm

Do not loan to, or borrow equipment from , other farmsAvoid visiting other poultry farms; If you do visit other farms

or live-bird markets, change footwear and clothing before working with your own flock

Do not bring birds from slaughter channels, especially liver-bird markets, back to the farm.

Source: APHIS FACTSHEET, Feb 2004 Avian Influenza : Protecting Poultry Workers at Risk SHIB 12-13-2004http://www.osha.gov/dts/shib121304.html

153

When H5 or H7 Is Detected In Poultry Operation In The United States

State Animal Industry Board & USDA take over so that these birds do not enter the food chain

Birds are immediately depopulatedCarcasses destroyed on the farm Burying / composting / or renderingFacilities are cleaned and disinfected CDC is notified to watch for human cases in poultry

workers

154

Control measures already applied in USA

Movement control inside the countryQuarantineStamping outVaccination prohibitedNo treatment of affected animalsIncreased surveillance on all flocks

within a 6-mile radius

155

Disposal of Carcasses

Composting Burial or Incineration

156

CompostingComposting Ratio: 1 part poultry carcasses, 2-

3 parts poultry litter, 0.1 parts wheat straw, 0.5 parts water.

A composting bin of 10-12 feet wide by 6-7 feet high can used for poultry, swine and one or two large animals.

Large bales of hay or straw could be used to create a bin but a cover is necessary in area with high precipitation rates to maintain a moister content of 40-60%.

157

Precautions to the General Public:

Do not swim in lacks or ponds used by wild birds

Do not feed pond or lack ducks or geeseTry not to walk in areas heavily

contaminated wit bird feces.Special precautions exists for owners of

bird feeders and bird baths.

158

H5N1 & Food Safety

Proper cooking will inactivate the virusFDA will compile a list of foods and dietary supplements

at high risk of contamination with avian influenza “Ready-to-eat'' foods that require little or no cooking

might be contaminated with virus by workers who have bird flu

Cooking food at or above 165 F safe to eat H5N1 is not killed by freezing/refrigerationVirus can survive for >35 days @ 39FVirus can survive, at cool temperatures, in contaminated

manure for at least 3 months.Home slaughtering & preparation of sick or dead poultry

is extremely hazardous

159

H5N1 & Food SafetyDO NOT EAT SICK OR DEAD BIRDS Separate raw meat from cooked foods Do not use the same chopping block or utensils for raw meat

and other foods Do not put cooked meat back on the raw meat platter Wash your hands with soap and hot water after handling raw

meatNo pink meatH5N1 virus can be on the inside &/or outside of eggs

Fully cooked or pasteurized eggs are safe to eat Do not consume raw or partially cooked eggs No runny yolks

Notice: these are the same recommendations on food preparation that protect consumers against Salmonella and other food-borne pathogens

160

AI: Personal Protective EquipmentMinimum equipment:

N95 face maskDisposable glovesDisposable/washable gownEye protection—only during procedures

When proper personal protective equipment is worn risk of exposure to H5N1 from sick patients is low

However, infections despite wearing PPE have been reported

Source: Lye, DCB, et al. Singapore Med J 47(6): 471-475, 2006Liem N et al. Emerg Infect Dis 11(2):210-215, Feb 2005Buxton C et al. J Infect Dis 181:344-348, Jan 2000http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/mar300

7doctor.html

161

Influenza Virus

RNA virus, 2 major types cause disease in humans (A and B)

Antigenic drift: point mutations → slight variations in surface proteins

Antigenic shift: genetic re-assortment of genes from different strains, some from animal reservoirs

162

Sneeze = 100,000 particles (traveling at 200 mph)

163

Particle Sizes of in a SneezeInfluenza Virus

Large Droplets (50 – 100 microns)Do not remain suspended in airBallistic trajectory of a few feetInfect by direct contact with mucous membranes of mouth, eyes, upper

nasal passages

Intermediate size particles (10 – 50 microns)Transmission of these particles influenced by temperature, humidity, air

currents and air velocityReach upper respiratory tract

Small particles aerosols and droplet nuclei (< 10 microns)Droplet nuclei – Intermediate size particles that have dessicated and

shrunkTransmission primarily influenced by air currentsReach lower respiratory tract

164

Transmissibility of Influenza A

Virus introduced into a

Home: 50% Attack RateEnclosed space outside Home: 50% Attack RateNaval Cruiser: 42% Attack RateAirplane with failed Air Circulation System: 73% Attack

Rate

165

Survival of Influenza on Environmental Surfaces

On cloth or paper – 8 – 10 Hours

On non-porous surface – 24 48 Hours(stainless steel)

On porous surfaces - Unknown

166

Gauze Mask used in 1918 Spanish Flu

Philadelphia police

167

1918 Influenza Epidemic U.S. Army Camp Hospitals (Hollerich, Luxembourg ; Aix-Les-Bains, France; USA)

National Museum of Health and Medicine, Armed Forces Institute of Pathology, Washington, D.C.,

168

1918 Influenza Epidemic

Emergency hospital Sneeze ScreensCamp Funston, Kansas San Francisco Naval Ctr

National Museum of Health and Medicine, Armed Forces Institute of Pathology, Washington, D.C.,

169

Sufficiency of Care (aka Altered Standards of Care)

Hospital StaffingThink Essential “Function:”Not Essential “Job”

Hospital Staff Education (K.I.S.S.)“Anthrax is like HIV”“Smallpox is like Tuberculosis”“Influenza is like Measles or Chickenpox”

170

“Sufficiency of Care”(aka Altered Standards of Care)

In the USA, during a Pandemic Flu epidemic, it is foreseen that scare hospital ventilators will be limited to only surgical patients.

Currently in a Pediatric Hospital in the Philippines, the shortage of hospital ventilators is so severe that, during influenza season, patients are limited to 48 hours on a ventilator. After that, their family is expected to manually ventilate the them.

171

Hanes Heavy Weight T-shirt 100% Pre-shrunk

(Fit Factor 67)

Source: Dato, VM, et al, “Simple Respiratory Mask,” Emerging Inf. Dis., June 2006, Vol. 12, No. 6

172

Policies developed after the fact often caused more harm than good.

173

Straight Whiskey Kills Flu Virus!Bartenders now required to have pharmacy degree

174

New Emerging Threats?

175

The Providence Journal. December 10, 2003. B4

No Oxycontin, but I scored some dynamite Flu vaccine!

176

The Human Factor

177

Smallpox Epidemic in NYC 1947

People waited 24 hours in line for vaccination1 HCW gave 8 vaccinations / minute

178

Polio Epidemic 1916

179


Validation of StandardsNanotechnology Avian Flu Pandemic

Natural Disasters/PandemicsBioterrorism

180

“WHEN YOUR UP TO YOUR ASSIN ALLIGATORS

IT’S OFTEN HARD TO REMEMBERTHAT THE FIRST THING YOU

NEED TO DO IS DRAIN THE SWAMP.”

ANNONYMOUS

181

Hurricane Katrina Sept 2005 Jefferson Parish

182

Hurricane Katrina 2005 Houston Astrodome

183

Hurricane Katrina 2005 Houston Reliant Center

400 Patient Norovirus Ward (closed)

184

Camp ArmstrongHurricane Katrina

Mississippi HCWs Accommodations

185

Post Katrina CleanupNew Orleans

186

Public Health Controversies in Infectious Aerosols

Adequacy of N-95 respirators and fit-testing in epidemic situations

Definition of exposure in relation to containment of disease in epidemics

The increasing demand and the associated hazard of blood and blood products in biotechnology research

The increasing demand but inherent limitations of environmental monitoring

Defining indoor air quality (e.g. “bad building syndrome)

The future challenges of nanotechnology

187

The Challenge during Disasters (Natural or Man-Made)

EPA is the lead agency for the Katrina Relief effort

EPA emphasis in the past has been on: On population exposure and not specifically

worker healthOn warehousing data rather than getting data to

physicians

188

Denominator Problems

The post-disaster recovery process usually involves a huge number of independent contractors and health care providers

Most monitoring programs are usually employer-based:

Health ProfessionalsUtility Workers

“Free lancers” (e.g. tree cutters) are often ICS or FEMA financed (i.e. “federalized”) and therefore entitled to future federal program

For other “volunteers,” there exists no structure to monitor this group (e.g. the Red Cross volunteers)

189

Katrina Relief Astrodome Sept 2005

190

Respiratory Infections

191

N = 845-912 Police FirefighterRespiratory Symptoms

Upper Respiratory* 28% 32%Cough w/ or w/o phlegm 21% 23%Lower Respiratory** 9% 11%

Gastrointestinal SymptomsN, V, D, Abdominal Pain <6% <8%

Skin SymptomsRash 54% 49%

Psychological SymptomsPTSD 19% 22%Major Depression 26% 27%InjuryLaceration 20% 24%Sprain/.Strain 13% 25%Animal Bite/Sting 11% 8%Fall 9% 10%Other injury <4% <5%

* Head/sinus congestion, nose/throat irritation, or both** Shortness of breath, wheezing, and/or chest tightnessSource: MMWR, 4-28-06; Vol. 55, No. 16, pg 457

Illness Symptoms and Injuries in Police Officers and Firefighters after Hurricane Katrina New Orleans, Louisiana,

10-17-05 to 10- 28-05 and 11-30 to 12-4-05

192

Serious Airborne Or Droplet-spread Infections Encountered During Air Travel

Mycobacterium tuberculosis Measles (Rubeola)Meningococcal (Neisseria meningitidis)SARS (coronavirus)Influenza virus

193

2007 Global Reporting of XDR Mycobacterium tuberculosis

194

Cabin Air Filtration and Circulation

Since the late 80’s, all aircraft re-circulate the cabin air; 10-50% of the cabin air is filtered and mixed with the outside conditioned bleed air from the engine compressors and then reintroduced into the passenger cabin.

Aircraft Pre-Filter and High Efficiency particulate Air (HEPA) Filter capture 99.99% of particles between 0.1 and 0.3 micron. Note: the tubercle bacillus is approximately 0.5 to 1 micron in size

To date, no evidence that recirculation of cabin air facilitated TBC transmission.

Source: Miller, MR, et al, Tuberculosis risk after exposure on airplanes. Tubercle and Lung Disease, 1996, 77: 414 -419.

195

Cabin Air Exchange Rate

At Cruising Level, there are 20 air exchanges per hour (3 minute clearing rate)

When Throttle below 80%, the is significantly lower amounts during descent and by APU on the ground

An Influenza outbreak in aircraft was greatly facilitated by a ground delay lasting 3 hours, during which the ventilation system did not operate and the passengers did not receive outside air.

Consequently, passengers should not stay aboard planes without adequate ventilation for greater than 30 minutes during ground delays (DOT Report)

Source: Moser, MR, et al An outbreak of influenza aboard a commercial airliner, Am J of Epid, 1979, 110: 1-6Nagda, NL, “Airline cabin environment: contaminant measurements, health risks and mitgation options. USDOT, 1989 (Report No. DOT-P-15-89-5)

196

Cabin Airflow Patterns

Source: Tuberculosis and Air Travel, Guidelines for Prevention and Control,2006, Second Edition, WHO

http://www.who.int/tb/publications/2006/who_htm_tb_2006_363.pdf

Global Statistics Myocbacterium tuberculosis

TBC is the leading cause of death in adults

4 Million new and relapse TBC cases annually

1.9 Million of these cases had positive sputum smears

95% of these cases occurred in developing countries

Note: 2.5 Billion air passengers/year projected by 2015 (ICAO)

Source: Raviglione, MC, etal, JAMA 1995, 273, 220-226Global TBC control: surveillance, planning, financing, WHO Report 2005

(WHO/HTM/TB/2005.349)Outlook for Air Transport to the year 2015,, Montreal, Intl. Civil Aviation Org.

( ICAO), 2004, (Circular 304 AT/127, 2004)

Resistant Myocbacterium tuberculosisMDR-TBC XDR-TBC

First Line drugs:Isoniazid X XRifampin X XEthambutol XPyrazinamide XStreptomycin (IM Drug) Rifabutin

Second Line Drugs:Aminoglycosides (IM Drug)

Capreomycin, Amikacin, Kanamycin, Viomycin XQuinolones XPara-aminosalicylic acidCycloserineEthionamideThiacetazone

Source: Mandell, GL, Bennett, JE, Dolin, R,; Principles and Practice of Infectious Diseases, 2005, Chapter 36, Antimyocobacterial Agents, Sixth Edition, Churchill Livingstone

199

Transmission of TBC on board Aircraft

Transmission probably rare: based on 6 highly infectious passengers on a total of 191 flights involving nine different aircraft and 2600 passengers and cabin crew between 1992 and 1994 (2/6 had MDR TBC)

Two possible skin test conversions occurred during prolonged (>8hours) air flights: first, in a crew member from another crew member; second, in a passenger from a nearby passenger.

No case of active TBC has been identified as a result of exposure on a commercial aircraft

Risk appears to be limited to close personal contact and/or close proximity as previously observed during train trips, bus trips,and gatherings in enclosed spaces (e.g. classrooms)

Source: MMWR, 1995, Exposure to passengers and flight crew to MTC on commercial aircraft,

1992 -1995, Vol. 44,, 112-113.Kenyon TA, et al, Transmission of MDR TBC during a long airplane flight, NEJM, 1996,

334, 933-938.

200

SARS (also) Broke the Rules

Report of SARS cases among passengers were:

seated much further apart and

on flights lasting considerably < 8 hours

Source: Olsen SJ et al, “Transmission of severe acute respiratory syndrome on aircraft,” NEJM, 2003, 349: 2416 – 2422.

201


Validation of StandardsNanotechnology Avian Flu PandemicNatural Disasters/Pandemics

Bioterrorism

202

“A good plan today is better than a perfect plan tomorrow.”

General George S. Patton

203

Characteristics of Bioterrorist Agents

Agent Person-person Infective dose Incubation pd (days) VaccinePersistence

Smallpox Smallpox HighHigh <100 <100 77--1717 + + Very stableVery stablePlague Plague High High <500 <500 22--33 –– Stable Stable VHF VHF Mod.Mod. <10 <10 44--2 2 –– UnstableUnstableBotulism Botulism No No 0.001 (0.001 (µµg/kg) g/kg) 11--5 5 +/+/-- StableStableAnthrax Anthrax No No <10,000 <10,000 11--6 6 + + Very stableVery stableTularemia Tularemia No No <50 <50 22--10 10 + + StableStable

204

Inhalational Anthrax Bacillus anthracis

205

USA Smallpox Cases 1913

206

TOPOFF: Aerosol of Y. pestis released at Denver Performing Arts

207

BIOSENSE

208

Medical Clues Highly Suggestive of a Bioterrorist Attack in the USA

Three or more cases of:“mediastinitis”“non-menstrual” Toxic Shock Syndrome (TSS)“necrotizing” pneumoniavesicular exanthem / Varicella pneumonia in “immune” individuals“unexplained” Disseminated Intravascular Coagulation (DIC)“Red” measles“viral” encephalitis“atypical” Guillain Barre SyndromeLeptospirosisYellow FeverDengue “Hemorrhagic” Shock Syndrome

209

1) Upper/Lower Respiratory with fever URT/LRTURT/LRT2) Diarrhea/Vomiting/Abdominal pain(Gastroenteritis) N/V/DN/V/D3) Suspected Meninigitis, encephalitis, encephalopathy Mn/EnMn/En4) Unexplained bilat. paralysis; C.N. impairment,botulism-like Paralaral5) Rash and fever RashRash6) Sepsis or non-traumatic shock S/SS/S7) Unexplained death with history of fever D/F/F8) Unspecified infection (new) INFINF9) None of the above (No box check on form) N/AN/A

ENCOMPASS SYNDROMIC SURVEILLANCE SYSTEM

210

((F/C/S Jts/Msc LA) H/A N/V/D Skin URT/LRT ARDS NeuroF/C/S Jts/Msc LA) H/A N/V/D Skin URT/LRT ARDS Neuro Bleed DeadBleed Dead

N/A (N/A ( INFINF ) Mn/En N/V/D Rash ( URT/LRT ) P) Mn/En N/V/D Rash ( URT/LRT ) Para S/S D/Fara S/S D/F________________________________________________________________________________________________________________________________________________________________________________

9 ( 89 ( 8 ) 3) 3 2 5 ( 1 ) 4 6 2 5 ( 1 ) 4 6 77

Bacterial AgentsBacterial Agents

AnthraxAnthrax ++ + + + + + + ++BrucellosisBrucellosis + ++ + ++ ++ + ++ + ++CholeraCholera ++ ++ ++GlandersGlanders + + + + + + + + + ++ +PlaguePlague ++ ++ ++ ++ ++ ++ + ++ +TularemiaTularemia ++ ++ ++ + + ++ + +Q feverQ fever ++ ++ ++

VirusesViruses

SmallpoxSmallpox + ++ + ++ + + + + + ++ +VEEVEE + ++ + ++ + ++ + ++ + ++ +VHF VHF + ++ + ++ + ++ + + ++ +

Biological ToxinsBiological Toxins

BotulinumBotulinum ++ ++SEBSEB + ++ + ++ ++RicinRicin ++ ++ + ++ + ++ ++Myxotoxins Myxotoxins + ++ + + ++ +

Emergency Room Code Sheet for Bioterrorist AttackEmergency Room Code Sheet for Bioterrorist Attack

211

Infection Control Practices for Patient Management

Bacterial Agents Viruses Biological Toxins1 Anthrax 6 Smallpox 10 Botulism2 Brucellosis 7 VEE 11 Ricin3 Plague 8 Viral Encephalitis 12 Staph EB4 Tularemia 9 Viral Hemorrhagic Fever5 Q Fever

Bacterial Viruses BiologicAgents Toxins

1 2 3 4 5 6 7 8 9 10 11 12Isolation PrecautionInitial decontamination required x x x Standard Precautions x x x x x x x x x x x x Contact Precautions (gloves, gowns) x xAirborne Precautions (N95 respirator) x xDroplet Precautions (surgical mask) x xWash hands with antimicrobial soap x x x x x x x x x x x xPatient PlacementNo restrictions x x x x x xCohort "like" patients x x x x x xPrivate Room x x x x xNegative Pressure xDoor closed at all times x x xPatient TransportNo restriction x x x x x x xLimit movement x x x x xPlace mask on patient x x x x

212

“Hope is an expensive commodity ..... it makes better

sense to be prepared”

Thucydides Greek Historian; 5th Century BC

History of the Peloponnesian War

213

References (continued)InfluenzaeCDC. Influenza vaccination of Health-Care Personnel:

Recommendations of the Health Care Infection Control Practices Advisory Committee (HICPAC) and the Advisory Committee on Immunization Practices (ACIP), MMWR 2005, 55 (No RR-10), pp1-16.

CDC. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR 2005, 54 (No RR-8), 1-40.

Garner JS, Hospital Infection Control Practices Advisory Committee. Guideline for isolation precautions in hospitals. Infect Control Hosp Epidemiol, 1996; 17: 53-80.

CDC. Guidelines for preventing health-care-associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR 2003; 53 (No. RR-3): 1-36.

Bradely, SF. The Long Term-Care Committee of the Society of Healthcare Epidemiology of America. Prevention of influenza in long-term care facilities. Infect Control Hosp Epidemiol 1999; 20 629-37.

214

References (continued)

InfluenzaeCDC. Respiratory hygiene/cough etiquette in health-care settings.

Atlanta, GA: Dept of Health Human Services CDC; 2003. http://www.cdc.gov/flu/professionals/infectioncontrol/resphygiene.htm

Sneller V-P, Izurieta H, Bridges C, et al. Prevention of vaccine-preventable diseases in long-term care facilities. Journal of the American Medical Directors Association 2000; 1 (Suppl): S2-37.

Bridges CB, Kuchnert MJ, Hall CB. Transmission of influenza: implications for control in healthcare settings. Clin Infect Dis 2003; 37: 1094-1010.

CDC. Detection and control of influenza outbreaks in acute care facilities. Atlanta, GA: US Dept of Health and Human Services, CDC; 2001. Available at http://www.cdc.gov/ncidod/hip/INFECTFluBook2001.pdf

Talbot TR, Bradley SE, Cosgrove SE, Ruef C, Siegel JD, Weber DJ. Influenza vaccination of healthcare workers and vaccine allocation for healthcare workers during vaccine shortages. Infect Control Hosp Epidemiol 2005; 26: 882-90.

CDC. Guidelines for Environmental Infection Control in Health-Care Facilities: Recommendations of the CDC and the Health Care Infection ControlPractices Advisory Committee (HICPAC), MMWR 2003, 52 (No RR-10, 1-44.

215


Isolation Room Design References

Duguid, J. P, “The Size and The Duration of Air-carriage of Respiratory Droplets and Droplet-nuclei, J. Hygiene, 1945, Vol. 54: pp 471-479.

ASHRAE, 2003: HVAC Design Manual for Hospitals and Clinics, Atlanta: American Society of Heating Refrigerating and Air Conditioning Engineers (ASHRAE).

CSA Z2317.2 (2003) Special requirements for Heating, Ventilation and Air Conditioning (HVAC) Systems in Healthcare Facilities, Mississauga, Ontario; Canadian Standards Association.

MWWR, Guidelines for Preventing the transmission of mycobacterium tuberculosis in health-Care Facilities, CDCP, 1994, 43, (No. RR-13).

Gammaitoni, L and Nucci, MC, 1997, Using a mathematical model toevaluate the efficacy of tb control measures, Emerging Infectious Diseases, Vol. , No. 3, pp 335-341.

Kowlaski, W, etal, Filtration of Airborne Microorganisms: Modeling and Prediction, 1999, ASHRAE Transactions, Vol. 104, part 2.

216

References (continued)SamplingAmerican Conference of Governmental Industrial Hygienists:

Bioaerosols: Assessment and Control. .JM Macher, Ed; KM Ammann, HA Burge, DK Milton, and PR Morey, Asst. Eds. ACGIH, Cincinnati, OH (1999)

American Conference of Governmental Industrial Hygienists, Air Sampling Instruments Committee, air Sampling Instruments for Evaluation of Atmospheric Contaminants, 5th Edition, 1978

Biosafety in Microbiological and Biomedical Laboratories, US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention and National Institutes of Health, 4th Edition

Occupational Diseases: A guide to Their Recognition, June 1977 DHHS (NIOSH Publication No. 77-181

2006 TLVs and BEIs (ACGIH Worldwide)Lighthart B, Mohr AH, 1994, Atmospheric microbial aerosols: Theory

and applications, New York, MMY, Chapman & HallJensen PA, Schafer, MP, Sampling and Characterization of

Bioaerosols, NIOSH/DPSE, Manual Of Analytic Methods, 1-15-98Merchant, JA, Occupational Respiratory Diseases, NIOSH, September

1986, Pub No. 86-102

217

References

Personal Protective Equipment

29 CFR 1910.134 OSHA Respiratory Protection Standard; updates 9-98 and 10-01

Interim Recommendations for the Selection and Use of Protective Clothing and Respirators Against Biological Agents SHHS (NIOSH) Publication No. 2002-109 (2001)

NIOSH Respirator Selection Logic 2004, Oct 2004, NIOSH Publ No 2005-100

DHHS (NIOSH) Publication No. 2005-109 (2004)Aerosols Program Assessment Committee Report, Final Report 4-7-2003;

http://www.cdc.gov/nioshs/topics/aerosols/aerosols_gaps.htmlInformation on personal protective equipment, manufacturers of

protective clothing, respirators, eye protection listed in the Buyer's Guide of the International Safety Equipment Association at http://www.safetyequipment.org.

Avian Influenza (Bird Glu) (CDC); http://www.cdc.gov/flu/avian/Guideance for Portecting Workers Against Avian Flu (OSHA)

http://osha.gov.dsg/guidances/avian-flu.htmlAvian Influenza, Protecting Poulty Workers at Risk (OSHA);

http://www.osha.gov.dts.shib.shib121304.html

218

References (continued)SARs Olsen SJ et al, “Transmission of severe acute respiratory

syndrome on aircraft,” NEJM, 2003, 349: 2416 – 2422Mandell GL, Bennett JE, Dolin RD., SARS (Coronaviruses),

Principles and Practices of Infectious Diseases 5th Ed. Churchhill Livingstone, New York. 2005. p. 19901997.

NIOSH SARS Web site: http://www.cdc.gov/niosh/topics/SARS/CDC SARS Web site: http://www.cdc.gov/ncidod/sars/WHO SARS Web site: http://www.who.int/en/

Information for health care providers wishing to test for or report cases of influenza A (H5N1) and SARS can be found at this website http://www.cdc.gov/flu/han020302.htm

MoldKuhn, D. M. and Ghannoum, M. A., 2003 January, Indoor Mold,

Toxigenic Fungi, and Stachybotrys chartarum: Infectious Disease Perspective,* Clin Microbiol Rev. 16(1): 144–172.

219


Disaster Medicine

Medical Management of Biological Casualties Handbook, USAMRIID, Fort Detrick, Feb 2001, Fourth Edition

Burkle, F. M, Disaster Medicine – Application for the Immediate Management and Triage of Civilian and Military Disaster Victims, 1984, Medical Examination Publishing Co., Inc

Manual of Disaster Medicine: Civilian and Military, Reis, ND and Dolev, E, (Israel), 1989,Springer-Verlag

Military Aspects of Medical Care: Operational & Emerg. Med., 1975, USUHS

Chemical and Radiological Operations and Biological Defense, The Army Institute for Professional Development, 7th Edition, Pam 221-1, Feb 1977 (AR 220-58)

NATO Handbook on the Medical Aspects of NBC Defensive Operations, AmedP-6, Aug 1973

Biological Warfare and Terrorism, The Military and Public HealthResponse, Sept 1999, CDC Publication

Dato, VM, et al, “Simple Respiratory Mask,” Emerging Inf. Dis., June 2006, Vol. 12, No. 6

220


Avian Influenzae

US Department of Agriculture, Animal and Plant Health inspectionService, http://www.aphis.usda.gov/lpa/issues/ai_us/ai_us.html

Nicholson KG, et al, "Influenza," The Lancet, Vol 362, November 22, 2003, p 1733.

World Health Organization, "Avian influenza frequently asked questions," http://www.who.int/csr/disease/avian_influenza/avian_faqs/en/

World Health Organization, "Avian influenza – fact sheet" http://www.who.int/csr/don/2004_01_15/en/

Centers for Disease Control and Prevention, http://www.cdc.gov/flu/avian/index.htm


221


Avian Influenzae

Information for health care providers wishing to test for or report cases of influenza A (H5N1) and SARS can be found at this website http://www.cdc.gov/flu/han020302.htm

US Department of Agriculture, Animal and Plant Health inspectionService, http://www.aphis.usda.gov/lpa/issues/ai_us/ai_us.html

Nicholson KG, et al, "Influenza," The Lancet, Vol 362, November 22, 2003, p 1733.


World Health Organization, "Avian influenza – fact sheet" http://www.who.int/csr/don/2004_01_15/en/

Centers for Disease Control and Prevention, http://www.cdc.gov/flu/avian/index.htm

222


Avian Influenzae

HHS Pandemic Influenza Plan, 2005, supplement 4, Infection control, outpatient medical offices

http://www.hhs.gov/pandemicflu/plan/http://www.pandemicflu.gov/plan/healthcare/maskguidancehc.htm

lMusher, D., “How Contagious are common respiratory tract

infections? NEJM, 348:13, Mar 27, 2003Tellier, R. Review of Aerosol transmission of influenza A virus,

Emerging Infectious Diseases, 12: 11, Nov, 2006DVD “Why Don’t We Do It In Our Sleeves?, Maine Medical

Association, PO Box 190, 30 Association Dr, Manchester, ME 04351; 207-622-3374; Fax 207-622-3332. www.mainemed.com.

223


Avian Influenzae

WHO and International Food Safety Authorities Network (INFOSAN)

Information Note No. 7/2005 (Rev 1. 5 Dec) –Avian Influenza. Available from http://www.fao.org/ag/againfo/subjects/documents/ai/Foodsafety

.pdfThomas C, et al. Journal of Food Protection. 70(3):675-680,

March 2007EFSA Journal 74:1-29, 2006http://www.fsis.usda.gov/News_&_Events/NR_040506_01/index.a

sphttp://www.fsis.usda.gov/PDF/Use_a_Food_Thermometer.pdfhttp://www.who.int/csr/disease/avian_influenza/avian_faqs/en/in

dex.htmlhttp://www.newsday.com/news/health/nyhsflu155130802mar15,0

,7255982.story?coll=ny-health-print

224

References (continued)Tuberculosis

CDC. MMWR, Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005, December 30, 2005, Vol 54, No. RR-17, pp1-102.

CDC. MMWR, Controlling Tuberculosis in the United States, 2005, November 4, 2005, Vol 54, No. RR-12, pp1-81.

CDC. MMWR, Guidelines for Investigation of Contacts of Persons with Infectious Tuberculosis and Guidelines for using QuantiFERON-TB, 2005, December 16, 2005, Vol 54, No. RR-15, pp1-55.

CDC. MMWR, Tuberculosis in Imported Nonhuman Primates –United States, June 1990 – May 1993, July 30, 1993, Vol 42 (29); 572-576.

Mandell GL, Bennett JE, Dolin RD. Mycobacterium tuberculosis, Principles and Practices of Infectious Diseases 5th Ed. Chapter36, Antimycobacterial Agents, Churchhill Livingstone, New York. 2005. p. 2852-2886.

225


Tuberculosis

Tuberculosis and Air Travel, Guidelines for Prevention and Control, 2006, Second Edition, WHO, found at: http://www.who.int/tb/publications/2006/who_htm_tb_2006_363.pdf

Olsen SJ et al, “Transmission of severe acute respiratory syndrome on aircraft,” NEJM, 2003, 349: 2416 – 2422

MMWR, 1995, Exposure to passengers and flight crew to MTC on commercial aircraft, 1992 -1995, Vol. 44,, 112-113.

Kenyon TA, et al, Transmission of MDR TBC during a long airplane flight, NEJM, 1996, 334, 933-938.

Raviglione, MC, etal, JAMA 1995, 273, 220-22

226


Tuberculosis

Global TBC control: surveillance, planning, financing, WHO Report 2005 WHO/HTM/TB/2005.349)

Outlook for Air Transport to the year 2015,, Montreal, Intl. Civil Aviation Org.( ICAO, 2004, (Circular 304 AT/127, 2004)

Raviglione, MC, etal, JAMA 1995, 273, 220-226Global TBC control: surveillance, planning, financing, WHO

Report 2005 (WHO/HTM/TB/2005.349)Outlook for Air Transport to the year 2015,, Montreal, Intl. Civil

Aviation Org.( ICAO), 2004, (Circular 304 AT/127, 2004)Miller, MR, et al, Tuberculosis risk after exposure on airplanes.

Tubercle and Lung Disease, 1996, 77: 414 -419.

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