WHAT WHAT IS IS A A HAZARDOUS HAZARDOUS BIOLOGICAL BIOLOGICAL AGENT AGENT (HBA)? (HBA)? OVERVIEW OVERVIEW OF OF HAZARDOUS HAZARDOUS BIOLOGICAL BIOLOGICAL AGENTS AGENTS IN IN THE THE WORKPLACE WORKPLACE –– LEGAL LEGAL AND AND PRACTICAL PRACTICAL ISSUES ISSUES Any cell (plant, animal, human), micromicro-organism or cell culture of natural origin or genetically engineered that constitutes a risk to human health Prof Mohamed Fareed Jeebhay Occupational and Environmental Health Research Unit School of Public Health and Family Medicine University of Cape Town, South Africa MAIN MAIN PRINCIPLES PRINCIPLES OF OF THE THE PREVENTIVE PREVENTIVE LEGISLATION LEGISLATION HBA-RELATED HBA-RELATED LEGISLATION LEGISLATION MAJOR LAWS RELATING TO HAZARDOUS BIOLOGICAL AGENTS Preventive Compensation 1. OHSA - Hazardous Chemical Substances Regs. - Regs. Hazardous Biological Agents 2. MHSA HCS Regs - grain, cotton, wood - rubber (?latex) Regs HBA - micro-organisms, cells, - pathogens, cell cultures - human endoparasites 1. Compensation for Occupational Injuries and Diseases Act 2. Occupational Diseases in Mines and Works Act COIDA - Infectious/parasitic disease - high risk work - Toxic/inflammatory syndromes - exposure to endotoxins,mycotoxins,glucans, VOCs - Upper airways disorders, byssinosis, occupational asthma, extrinsic allergic alveolitis (organic dust, moulds, proteins/enzymes, animals/insects) - Allergic/irritant contact dermatitis • Identify sources of high-risk exposure/risk assessment (inspections, record keeping) • Control the hazard: substitution, isolation, engineering controls (eg. exhaust ventilation), administrative controls (eg. universal infection control procedures), personal protective equipment • Exposure monitoring: industrial hygiene surveillance and evaluation of bioaerosols and allergens (approved inspection authority: AIA) • Medical surveillance programmes (skin prick testing, serum antibodies, target organ tests) • Information, education and training, and counseling programmes (reporting, hazard awareness, safe procedures for handling/ decontamination) PARADIGM PARADIGM FOR FOR EVALUATING EVALUATING BIOLOGICAL BIOLOGICAL HEALTH HEALTH RISKS: RISKS: A A REQUIREMENT REQUIREMENT UNDER UNDER HBA/HCS HBA/HCS REGULATIONS REGULATIONS HOST (worker, occupant) - immunity - atopy - genetic (HLA) - smoking HEALTH EFFECTS Route (air/skin) Dose (level/duration) AGENT (biological agent) - name - physical state - properties (virulence, allergenic potency) - particle size AGENT AGENT ENVIRONMENT (workplace, building) - work process - control measures 1 MAJOR MAJOR CATEGORIES CATEGORIES OF OF BIOLOGICAL BIOLOGICAL AGENTS AGENTS OF OF NATURAL NATURAL ORIGIN ORIGIN CATEGORY Microorganisms • Viruses • Bacteria • Fungi Plants • Lower plants • Higher plants Animals • Invertebrates • Arthropods • Vertebrates COMMON COMMONOCCUPATIONAL OCCUPATIONALSETTINGS SETTINGS WITH WITH EXPOSURE EXPOSURE TO TO HBA HBA EXAMPLES SECTOR Agriculture EXAMPLES Cultivating, harvesting, forestry • Breeding and tending animals, fishing • Abattoirs, food processing plants Agricultural products • Storage facilities: grain silos, tobacco • Processing animal hair, leather, silk • Textile plants, sawmills, paperpaper-mills • Veterinary facilities, pet shops Animal care Biotechnology/research labs • Production, microbiology, animal units • Metal working, soldering Metal • Gold and coal mining Mining • Hospitals, clinics, nursing homes Health care • Production of drugs, herbal products Pharmaceutical Sewage and waste disposal • Waste removal, treatment plants Influenza, Rabies, Hepatitis A, HIV Brucella, Anthrax, Leptospira, Thermophilic bacteria, Tetanus, Mycobacteria (TB) Aspergillus, Alternaria Lichens, liverwarts, ferns Grain, cotton, wood, coffee, tobacco, spices Shistosoma (bilharzia), Anisakis, Plasmodium (malaria) Arachnids (spiders, storage mites, ticks), Insects (cockroaches, beetles, moths, bees), Crustaceans Fish, Amphibians, Reptiles, Birds, Mammals (cattle, sheep) REGULATIONS REGULATIONS FOR FOR HAZARDOUS HAZARDOUS BIOLOGICAL BIOLOGICAL AGENTS AGENTS (HBA): (HBA): SCOPE SCOPE HBA HBA REGULATIONS REGULATIONS –– Risk Risk Group Group Categories Categories for for HBA HBA Scope: Every employer and self-employed person where: z z • CATEGORY DEFINITION - unlikely to cause human disease Group 1 Group 2 - can cause severe human disease - might be a hazard to workers - unlikely to spread to community - effective prophylaxis/treatment HBA is deliberately produced, processed, used, handled, stored or transported Incident or high risk exposure to a HBA in the following work situations: - food production plants - contact with animals and/or products of animal origin - health care, including isolation and post mortem units - clinical, veterinary and diagnostic laboratories - sewage purification installations - general workplace Group 3 Group 4 EXAMPLE E Coli K10, yeast Legionella pneum. Leptospira Influenza A/B (V) Hepatitis A (V) Ascaris (A) - can cause severe human disease Mycobacterium TB (V) - serious hazard to workers Bacillus anthracis (V) - may spread to community Hepatitis B (V) - effective prophylaxis/treatment HIV, Shigella (T) - causes severe human disease Congo haem. fever - serious hazard to workers Ebola pox - high risk of spread to community - no effective prophylaxis/treatment Symbols: A-allergenic, T-toxic effects, V-vaccine available PARTICLE PARTICLE DEPOSITION DEPOSITION IN IN RELATION RELATION TO TO AERODYNAMIC AERODYNAMIC DIAMETER DIAMETER DETERMINES DETERMINES HEALTH HEALTH EFFECTS EFFECTS Particles (MMAD 5 -10 microns) deposited in tracheotracheo-bronchial region as airway defences become less efficient (thoracic (thoracic fraction) z Maximal lung deposition occurs with particles MMAD < 5 microns (respirable fraction) 1000 z Spearman r = 0.74 (p<0.001) 500 Particles (MMAD >10 microns) trapped in nose or mucomuco-ciliary escalator in tracheotracheo-bronchial tree not retained (inhalable (inhalable fraction) 0 z Pilchard antigen concentration 1500 Cross-reactive Cross-reactive allergens: allergens: Pilchard Pilchard and and anchovy anchovy environmental environmental antigen antigen concentrations concentrations in in seafood seafood processing processing workplaces workplaces (n=198) (n=198) 0 2000 4000 Anchovy antigen concentration Fitted values 6000 8000 ng/m3 Jeebhay et al, Annals Occup Hyg, 49(5):423-37, 2005 2 MECHANISMS MECHANISMS BY BY WHICH WHICH HBA HBA CAUSE HEALTH EFFECTS CAUSE HEALTH EFFECTS HAZARDOUS BIOLOGICAL AGENT HEALTH HEALTH EFFECTS EFFECTS OCCUPATIONAL OCCUPATIONAL DISEASES DISEASES DUE DUE TO TO HBA HBA Microbial infection 1. Infectious material 2. Opportunist pathogens 3. Zoonoses Allergic response 1. Micro-organisms 2. Proteinaceous material 3. Chemical compounds Toxic response 1. Endotoxins (gram neg. bacteria) 2. Mycotoxins (fungi) Carcinogenic 1. Wood dust 2. Mycotoxins (aflatoxin) Examples 1. C. Tetanus, Leptospira 2. Legionella Pneumophilia 3. B. Anthracis, Brucella Examples 1. Mould e.g. Aspergillus 2. Pollen, dust, animal secretions 3. Plicatic acid, gums, resins Examples 1. Stored grain, hay, cotton, swine and poultry confinement units 2. Stored fodder, grain, nuts Examples 1. Hardwood (Beech, oak), Softwood 2. Stored nuts INFECTIONS/ZOONOSIS INFECTIONS/ZOONOSIS OCCUPATIONAL DISEASES Inhalation fever (fever, myalgia, fatigue) - Toxic pneumonitis - Organic toxic dust syndrome (fever, myalgia, headache, respiratory symptoms) Infections (including zoonosis) - Rhinitis, conjunctivitis, urticaria - Asthma - Asthma-like syndrome (acute functional respose) - Contact irritant dermatitis - Contact allergic dermatitis - Protein contact dermatitis Hypersensitivity pneumonitis (extrinsic allergic alveolitis) Carcinoma (eg. nasopharynx, liver, lung) - Chronic bronchitis - Chronic obstructive lung disease Anthrax: Anthrax:skin skin“eschar” “eschar” Malaria Malaria--mosquitoe mosquitoebite bite EXTRINSIC EXTRINSIC ALLERGIC ALLERGIC ALVEOLITIS/ ALVEOLITIS/ HYPERSENSITIVITY HYPERSENSITIVITY PNEUMONITIS PNEUMONITIS OCCUPATIONAL ASTHMA Allergy Allergyto toflour flourdust: dust:wheat, wheat,rye, rye, corn cornflour flourallergens allergensin inaabaker baker 3 SKIN SKIN ALLERGY ALLERGY ENVIRONMENT: ENVIRONMENT: Dermatitis/eczema Dermatitis/eczema Urticaria/”bommels”/wheals Urticaria/”bommels”/wheals -- high high risk risk populations: populations: multiple multiple exposures exposures -- route route of of exposure: exposure: inhalation, inhalation, direct direct skin skin contact, contact, (ingestion) (ingestion) -- dose dose and and duration duration of of exposure exposure Latex allergy prevalence studies in teaching hospitals in the Western Cape __________________________________________________________ Hospital Overall latex allergy (%) prevalence __________________________________________________________ Sheep Sheepworkers: workers:bacteria bacteria Health Healthcare careworkers: workers: --viruses/bacteria: viruses/bacteria: hepatitis, HIV, hepatitis, HIV,TB; TB; --allergens: allergens:latex, latex,drugs drugs Sewer Sewerworkers: workers:bacteria bacteria Number surveyed No. with WRS Groote Schuur, Schuur, 2001 2300 712 (31%) 9%* Red Cross, 2001 302 142 (47%) 5% Tygerberg, Tygerberg, 1999 250 180 (72%) 21% ________________________________________________________________________________________________________________________________ ___________________________________________ ___________________________________________________________________________________________________________________________________________________________________________ * 25% = latex +, 7% = asthma, 15% urticaria, urticaria, 17% conjunctivitis Potter, ACI, 2002 EPIDEMIOLOGICAL EPIDEMIOLOGICAL STUDIES STUDIES OF OF OCCUPATIONAL OCCUPATIONAL ALLERGY ALLERGY AND AND ASTHMA ASTHMA IN IN SOUTH SOUTH AFRICAN AFRICAN FOOD FOOD INDUSTRIES INDUSTRIES Exposure group SPT/ WRS Asthma Specific agents RAST + Prevalence Grain mill (n=111) 26% 23% 24% 17% 16% 11% (Jeebhay et al, 2004) 15% 29% 7% Vineyards (n=207) 23% 26% 7% spider mite: Tetranychus species 8-11% 47% - fungi: Alternaria sp. Mucor sp., pollen (Dactylis sp.) 4% 32% - chicken feed, serum, feathers, faeces Fish processing (n=594) 7% (Jeebhay et al, 2001) 9% 16% 3% fish: pilchard, anchovy fish parasite: Anisakis sp. (Jeebhay et al, 1997) Bakeries (n= 517) (Jeebhay et al, 2002) Maize farm (n= 101) (van Niekerk et al, 1989) Poultry farm (n=134) (Rees et al, 1998) grains: wheat and rye; storage mites: Tyrophagus sp; Lepidoglyphus sp., beetles: weevil, mealworm cereal flours: wheat, rye, alpha-amylase Bird Birdhandlers: handlers:feathers, feathers,droppings, droppings, mites, mites,bacteria, bacteria,volatile volatileorganic organic compounds compounds(e.g. (e.g.ammonia) ammonia) 4 Cotton Cottonworkers: workers:cotton cottondust dust contaminated contaminatedwith withendotoxin endotoxin Fruit Fruitfarm farmworkers: workers:spider spidermite, mite, predator predatormites, mites,storage storagemites, mites,pollen pollen 3 (Current (CurrentOEL OEL0.5 0.5mg/m mg/m3)) Mites Mites are are major major determinants determinants of of work-related work-related asthma asthma symptoms symptoms among among table table grape grape farm farm workers workers in in the the Western Western Cape Cape (n=207) (n=207) (Jeebhay (Jeebhayet etal, al,Curr CurrAllerg AllergClin ClinImmunoI, ImmunoI,2003) 2003) _________________________________________________________________________________________ Outcome Predictor Prevalence Confidence p-value Odds Ratio Interval _________________________________________________________________________________________ Skin (urticaria) Pesticide crop sprayers* 3.42 1.00 – 11.66 0.050 Ocular-nasal Male gender Pesticide crop sprayers* House dust mite (SPT)* 1.93 3.49 3.17 1.01 – 3.72 1.31 – 9.31 1.37 – 7.33 0.048 0.012 0.007 Wheeze Age 1.03 1.00 – 1.06 0.031 Spider mite (ELISA)* 5.78 1.75 – 19.05 0.004 Storage mite (RAST)* 2.39 1.02 – 5.59 0.044 _________________________________________________________________________________________ *Adjusted for age and gender Grain Grainharvesting harvestingand andmilling milling workers: workers:grain graindust, dust,storage storage mites, mites,beetles, beetles,mealworm, mealworm,mould mould 3 (Current (CurrentOEL OEL10 10mg/m mg/m3)) Grain Grain mill mill workers workers can can become become sensitised sensitised to to aa broad broad spectrum spectrum of of allergens allergens (n=106) (n=106) (Jeebhay (Jeebhayet etal, al,Curr CurrAllerg AllergClin ClinImmunoI, ImmunoI,2005 2005)) 45 Significant determinant of work-related wheeze (OR:6.2) 40 35 30 25 20 15 10 High risk work processes associated with exposure to sensitising agents in flour dust in bakery workers Storage mites Grains Cockroaches Bread Breaddough doughmixing mixing Beetles Mould Dough Doughhandling handling 0 T. B. Pu Tr tr op L. es ica D ce lis es nt tr iae uc B to .G r P. e r m A an m B e ic . O ri a rie can nt a al S. is G ra na T. ri (m mo us ea lit lw or o W rm he ) at R M ye ou ld m ix 1 5 Cleaning/Sweeping Cleaning/Sweeping 5 Flour Flour dust dust exposures exposures among among supermarket supermarket bakers: bakers: proportion proportion of of inhalable inhalable dust dust samples samples 3* above per job job category category (n=211) (n=211) above 0.5mg/m 0.5mg/m3*per (Baatjies, (Baatjies,Jeebhay Jeebhayet etal, al,Curr CurrAllerg AllergClin ClinImmunoI, ImmunoI,2005 2005)) Prevalence Prevalence of of allergic allergic sensitsation sensitsation among among supermarket supermarket bakers bakers according according to to employment employment (Baatjies, duration (Baatjies,Jeebhay Jeebhayet etal, al,2005 2005)) duration (n=517) (n=517) 90 Prevalence of sensitisation by jobtitle for total population and short and long duration of employment 80 45 40 60 50 35 40 Percentage Percentage 70 30 20 10 0 Baker Confectioner Supervisor Manager Counterhand Job title 30 Total 25 Less than 3 years 20 More than 3 years 15 10 5 0 Counterhand Manager Supervisor Confectioner Baker *The American Conference of Government Industrial Hygienists (ACGIH) 8-hr TWA-OEL = 0.5mg/m3 Wheat allergen results 100% of samples above 0.2 µg/m3 (Houba R, 1998) ROUTES ROUTES OF OF EXPOSURE EXPOSURE AND AND HIGH HIGH RISK RISK WORK WORK PROCESSES PROCESSES IN IN THE THE SEAFOOD SEAFOOD INDUSTRY INDUSTRY Seafood category Sources of occupational exposure to seafood product/s Fishermen Fishermenand andfish fishprocessing processing workers: workers:fish fishprotein protein(blood, (blood,guts, guts, muscle), muscle),Anisakis Anisakisparasite, parasite, fishmeal fishmealdust dust - inhalation of wet aerosols from lobster "tailing", crab "cracking", butchering and degilling, boiling, prawn "blowing" (water jets, compressed air) - dermal contact from unprotected handling of prawn; hand immersion in water containing fish juice Molluscs Oysters, mussels - inhalation of wet aerosols from oyster "shucking" - dermal contact from unprotected handling Finfish Salmon, pilchard, anchovy - inhalation of wet aerosols from fish heading, degutting, boiling - inhalation of dry aerosols from fishmeal milling, bagging - dermal contact from unprotected handling Jeebhay et al, Occup Env Med, 2001 Environmental exposures among fish processors in the Western Cape (n=198) (Jeebhay et al, Ann Occup Hyg 2005) Work process Thoracic particulate conc. GM(range) (mg/m3) Protein conc. Pilchard antigen conc. GM(range) GM(range) 3 (ug/m ) (ng/m3) Anchovy antigen conc. GM(range) (ng/m3) Fishmeal productn Jetty, canning, pick-ups, stores Admin, boiler, labeling, w/shop 0.447 (0-1.570) 0.504 (0-9.846) 0.118 (0-0.439) 0.064 (0-0.593) 220 (0-563) 132 (0-898) 456 (0-1485) 292 (0-795) 0.472 (0-7.725) 0.096 (0-1.150) 68 (0-68) 98 (0-128) GM: geometric mean Crustaceans Crabs, prawns Detection limit of antigen assay: 0.5 µg/ml Dose-response Dose-response relationship relationship between between pilchard pilchard fish fish 3 antigen antigen exposures exposures (log (log ng/m ng/m3)) and and onset onset of of workworkrelated related asthma asthma symptoms symptoms among among fish fish processors processors (n=594) ((Jeebhay Jeebhayet etal, al,Ann AnnOccup OccupHyg Hyg2005) 2005) (n=594) Pilchard antigen conc. at time of onset of symptoms >30 (categ 2) vs <30 (cat 1) >60 (categ 3) vs <30 >90 (categ 4) vs <30 Hazard ratio 95% CI 2.25 2.20 2.47 1.06 – 4.75 0.034 1.03 – 4.69 0.042 1.15 – 5.31 0.021 Exposure entered as a time varying covariate (months) Models adjusted for age (at start of employment), gender, atopy, smoking status pvalue Probability: absence of work-related asthma 1.00 concat 1 concat 2 concat 3 0.75 concat 4 0.50 0.25 0.00 0 200 Time: months 400 600 6 MEASURING MEASURING AND AND INTERPRETING INTERPRETING EXPOSURE EXPOSURE DATA DATA FROM FROM BIOLOGICALLY BIOLOGICALLY DERIVED DERIVED AIRBORNE AIRBORNE CONTAMINANTS CONTAMINANTS CATEGORY Total culturable/countable bioaerosols EXPOSURE EXPOSURE ASSESSMENT ASSESSMENT Specific bioaerosols Infectious agents EXAMPLE total bacteria, fungi, pollen Aspergillus fumigatus Legionella Pneumophilia Mycobacterium tuberculosis endotoxin, mycotoxin, allergens, volatile organic compounds (ammonia, SO2, CO2, ethanol) Assayable biological contaminants INTERPRETING INTERPRETING EXPOSURE EXPOSURE MEASUREMENTS MEASUREMENTS –– HCS HCS STANDARDS STANDARDS ARE ARE NOT NOT PROTECTIVE PROTECTIVE AGENT Cellulose Cotton Flour Grain (oat, wheat, barley) ACGIH TWA 10 mg/m3 0.2 mg/m3 0.5 mg/m3 (Inhal) 4 mg/m3 HCS OELS 0.5 mg/m3 10 mg/m3 Natural rubber latex (total protein) 0.001 mg/m3 (Inhal) 8 mg/m3CL Nicotine 0.5 mg/m3 - Pyrethrum 5 mg/m3 - Rosin core solder (colophony) Low as possible - Subtilisins (proteolytic enzymes) 0.00006 mg/m3STEL - Starch/sucrose 10 mg/m3 - Vegetable oil mists (metal working) 0.2 mg/m3 - HOST HOST FACTORS FACTORS -- atopy atopy -- smoking smoking -- genetic genetic (e.g. (e.g. HLA-type) HLA-type) Wood 0.5-1 mg/m3 (Inhal) 10 mg/m3 Endotoxins, (1-3)B,D-glucans Under study - 3 Relationship Relationshipbetween betweeninhalable inhalabledust dust(log (logmg/m mg/m3)/wheat )/wheat 3 allergens allergens(log (logµgEQ/m µgEQ/m3)) and andallergic allergicsensitization sensitizationamong among Dutch bakers and flour mill workers according to Dutch bakers and flour mill workers according toatopic atopicstatus status (Peretz (Peretzet etal, al,Sc ScJJWork WorkEnv EnvHealth, Health,2005) 2005) Table 3: The effect of smoking on sensitisation: prevalence ratios and population attributable fractions in 4 factories for all workers and for atopic workers separately PR 0.4 1.0 1.7 1.7 2.3 0.7 Total 1.1 95%CI AFp 0.5-2.2 1.0-3.0 1.0-2.8 1.0-4.9 1.3% 15% 21% 42% 0.8-1.6 5.3% 0.6 Probability Probability 0.3 0.8 Pine sawmill Maize mill Soybean plant Fish plant 0.2 0.1 Atopic workers 0.5 0.4 0.2 0.1 0 -4 -3 -2 -1 0 1 2 3 4 Exposure levels to inhalable dust(logged) Non-atopic (n=193) 5 PR 95%CI AFp Pine sawmill Maize mill Soybean plant Fish plant 1.2 1.3 2.4 1.8 0.4-3.6 0.8-2.1 1.3-4.4 0.6-4.8 6.5% 9.8% 75% 31% Total 1.3 0.9-2.0 15% 0.3 0 -5 -4 -3 -2 -1 0 1 2 3 4 Exposure to inhalable dust (logged ) 5 6 Atopic (n=77) Rees D, Bartie D, Fox F, Jeebhay M, Mansoor N, Occ H SA, 2005 7 ACKNOWLEDGEMENTS University of Cape Town, South Africa Andreas Lopata Roslynn Baatjies THANK YOU Univ. of Washington, USA Noah Sexias Cape Peninisula Univ. Technology, South Africa Raymond Beukes Dashwill George Emmanuel Rusford BGFA, Ruhr Univ. Bochum, Bochum, Germany Monika Raulf-Heimsoth Ingrid Sander Univ. of Michigan, USA Thomas Robins Xihong Lin Tulane Univ., USA Samuel Lehrer Joshua Fernandez Funded by: - NIOSH R01 Grant - MRC (South Africa) - Fogarty - ALLSA IRAS, Univ. Utrecht, Neth. Neth. Dick Heederik Gert Doekes Hans Kromhout Tim Meijster 8
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