Bioaerosols and Disease Donald E Gardner PhD

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6 The Health Effects of Bioaerosols in the Workplace

Of the many diseases that have been associated with airborne contaminants in the workplace, the contribution of biological agents to total illness is presumed to be large. But to date, the attributable risk is not known with certainty. The frequency and severity of such diseases vary, depending on the particular work environment, types of organisms present, and the individual's susceptibility to the agent. Experimental and epidemiological studies have been used to evaluate the health effects of bioaerosols. Respiratory infections, it has been estimated, cause 50-60% of all acquired illnesses (49). In the United States about two million people get pneumonia each year. It ranks sixth among all disease categories as a cause of death and is the most frequent lethal hospital-acquired infection (14). The economic impact from the standpoint of health-care cost and loss of productivity in the workplace is in the millions of dollars. A few examples of infectious diseases that are transmitted via inhalation are discussed later. This section addresses the potential for workplace exposure to biological agents, provides examples illustrating various mechanisms of action of different microbes, and identifies the great variety of illnesses that are associated with a broad range of diverse biological agents. Rather than attempt to list and discuss all organisms that might pose a threat within the workplace environment, this section uses a few examples to illustrate the principles involved in airborne infectious diseases. A broad base of understanding the basic concepts of the potential health risk of airborne microbes can aid in preventing and controlling such diseases. Excellent texts and handbooks on infectious diseases are readily available in most research and medical libraries for a more detailed discussion of specific types of organisms and the pathogenesis of their disease (4, 37, 50, 51). 6.1 Bacteria

6.1.1 Bacillus Anthracis As a disease of great antiquity, anthrax occupies an important place in the history of infectious diseases because it was the first human disease attributed to a specific pathogen (52). This organism is a large rod-shaped microbe that occurs frequently in chains. The bacterium can maintain itself in a spore state under severe adverse environmental conditions for many years. Anthrax is primarily a disease of farm animals (e.g., sheep, goats, cattle, and horses). The infected animal becomes a living reservoir from which the pathogens are dispersed. Human pulmonary anthrax, also called "woolsorter's disease" is rare but can be deadly. It is primarily an occupational disease among workers who come in contact with infected animals and/or their products (e.g., hides, hair, or meat) (53). It occurs occasionally in textile mills where imported animal products (goat, camel, sheep hair) are incorporated into fabrics. Such an occurrence can call for an immediate shutdown and disinfection of the entire plant, which is difficult and expensive. Pulmonary anthrax develops after aerosolized cells, usually spores, gain entry into the body through the respiratory system. The virulence of this organism results from the production of an exotoxin which allows this organism to spread rapidly through the circulation, and death can occur suddenly, usually as a result of cardiac failure (52, 54, 55).

Anthrax is a major military threat facing the armed forces and a biological agent that could be used in a terrorist attack. It has been estimated by the Department of Defense that more than ten countries may possess or are suspected of having anthrax as a biological warfare agent. The Department of Defense has plans to vaccinate more than 2.4 million military members against this organism by the year 2005.

6.1.2 Brucella The Brucella organisms are obligate parasites that can persist intracellularly in an infected host. Infected animals, typically cattle, swine, and goats are the reservoirs from which humans acquire brucellosis. In naturally acquired brucellosis, the organism usually enters the body through broken skin, the conjunctivae, or via the gastrointestinal tract. However, the organism may also enter the body via inhalation when contaminated dust becomes airborne. The symptoms are quite nonspecific, and the diagnosis may be overlooked unless a high degree of suspicion exist. Brucellosis has been associated with farm workers, packing house employees, livestock workers, and veterinarians and has been identified as one of the bacteria most infectious to laboratory personnel, probably by aerosols. In some developing countries, brucellosis is a reemerging communicable disease (56-58).

6.1.3 Klebsiella Pneumoniae This bacillus belongs to an enteric group of organisms whose natural habitat is the intestinal tract. The organism was initially described in 1882 by Friedländer who believed that it was the exclusive cause of pneumonia. These organisms are nonspore forming and are closely related to coliform bacilli. Klebsiella pneumonia can be found in the nose, mouth, and intestinal tract of healthy persons and is the etiologic agent responsible for about 5% of bacterial pneumonias. These pneumonias are usually very serious and are characterized by the production of sputum and frequently the formation of lung abscesses which can be highly fatal. Klebsiella has a large mucoid capsule that surrounds the organism and is effective in protecting it against phagocytosis. It can be a secondary invader in the lungs of patients with bronchiectosis or chronic pulmonary diseases. Health-care workers are at risk of infection with these agents from daily exposure to patients who are admitted with this illness. It accounts for a significant proportion of pneumonias acquired in hospitals (59, 60).

6.1.4 Legionella Pneumophila The outbreak of this respiratory illness at the 1976 American Legion convention in Philadelphia focused attention on a common source of exposure to a bacterium later classified as Legionella pneumophila. Although morbidity rates are generally less than 5% for exposed individuals, the mortality rates may approach 10-15% (61). Legionella infections are not transmitted by respiratory droplets from one infected person to another but instead result from inhaling contaminated water droplets from sink outlets, shower sprays, humidifiers, water cooling towers, and air conditioners. Ingestion of contaminated water has not been implicated. The initial symptoms of the disease include malaise, headache, fever, chills, cough, and changes in mental status. At least 23 different species of Legionella have been implicated in human disease. This microorganism is very difficult to recover from air and usually detection depends on collecting and analyzing of water specimens (62-65).

6.1.5 Mycobacterium Tuberculosis Tuberculosis (TB) is caused by a rod-shaped bacterium and is a highly contagious disease easily passed from one person to another in the airborne droplets formed when a person with active tuberculosis sneezes or coughs. The causative agent (Mycobacterium tuberculosis) usually persists in the body long after the primary infection is over but can be reactivated, especially if immunosuppression occurs. Tuberculosis is a significant hazard to hospital personnel, medical students, and physicians who have two to three times the incidence of infection compared to nonmedical personnel. The AIDS epidemic has increased the likelihood that health-care workers will come in contact with active pulmonary tuberculosis because this organism is often one of the opportunistic infections seen in patients with AIDS. The TB incidence rate among people infected with HIV is nearly 500 times the rate for the general population. After a decline in rates of TB during the last several decades, the United States is experiencing a disturbing increase in such infections. The number of cases has gone from 22,200 in 1985 to more than 26,000 in 1991 or 10.4 per 100,000 population (7). Even more alarming is the rise of multidrug-resistant strains (14). Because of the importance of this highly communicable disease, a separate chapter (Chapter 21) has been dedicated to it (66-68).

6.1.6 Mycoplasma Pneumoniae These organisms are the smallest known free-living bacteria that, unlike most bacteria, do not possess cell walls. Mycoplasma are widespread in nature, commonly in pooled water and soils. This organism is associated with primary atypical pneumonia, an acute, febrile disease that usually begins in the upper respiratory tract and spreads to the lungs. The manifestations of the disease, including fever, cough, headache and malaise, can be fairly severe. Although the disease is transmitted by oral or nasal secretions, it is generally not considered very contagious. Mycoplasma pneumoniae can be recovered from sputum or pharyngeal swabbing. This disease typically occurs in young adults and children and also in institutions and among military personnel (69-71).

6.1.7 Neisseria Meningitis This organism causes meningococcus meningitis. Meningitis is a general term for inflammation of the meninges (membranes covering the brain and spinal cord). The cells may be either kidney-shaped or spherical, about 0.6 to 1.0 mm in diameter. They are nonmotile and nonspore forming. Early symptoms are excessive nasal secretions, sore throat, headache, fever, neck and back pain, and loss of mental alertness. Like most respiratory infections, the meningococcus organism is disseminated by direct contact through droplet infections from secretions of the nose, mouth, and throat. Some persons are temporary carriers, whereas others may discharge the organism continuously or sporadically. After being deposited in the nasopharynx, the organism directly invades the blood stream. This bacteremia is followed by the onset of acute purulent meningitis. The virulence of this organism is related, in part, to the antiphagocytic properties of its capsule. In addition, these organisms produce an endotoxin that can cause extensive vascular damage. These organisms can withstand drying and other adverse physical conditions. Epidemics of meningoccus meningitis are prone to occur in military populations probably related to reduced overall resistance of the individual due to conditions of military life, fatigue, and exposure to inclement weather. It seems that with the relatively high carrier rate and the rather low rate of morbidity, there must be a high degree of normal resistance to this organism in the general population (72, 73).

6.1.8 Streptococcus Infections This organism is the commonest cause of community-acquired bacterial pneumonia and is also responsible for sore throats, bronchitis, meningitis, sinusitis, otitis, scarlet fever, rheumatic fever, and septicemia (55, 74). Streptococcal infection of the upper respiratory tract does not usually progress to involve the lungs. The various disease-causing strains of Streptococcus are grouped by their behavior, chemistry, and appearance. Group A streptococci are the most virulent species for humans. The ultimate source of these infections is usually a person who harbors these organisms. Such an individual may have a demonstrable or subclinical infection or may be a carrier. Nasal discharges of the organism are the most dangerous source of transmission of this disease. Although all streptococci are similar in cellular morphology, these organisms are extremely variable in pathogenicity. The high virulence of this organism is associated with its ability to produce several kinds of extracellular products, such as hemolysins, hyaluronidase, leukocidin, streptokinase, streptodornase, and erythrogenic toxins. Many of these products aid in spreading the organism within the host. The most virulent streptococci (beta-streptococci) produce hemolysins capable of destroying red blood cells. The less virulent organisms (alpha-streptococci) may also produce hemolysins but are characterized by their lack of complete lysis of the red blood cells. Of special concern is that a "new" form of highly virulent streptococcus has been identified (10, 75). The British tabloids have coined the term "flesh-eating bacteria" to describe this invasive, necrotizing infection. This new strain, like other streptococci, is transmitted by inhalation. However, the resulting infection is especially insidious. Its early symptoms are easily mistaken for signs of the flu. The infection is extremely difficult to treat even with massive doses of antibiotics, and there is no treatment for the deadly toxin produced which actually causes the pneumonia. Resistance against the streptococci is type-specific. Thus, a host who has recovered from infection by one Group A type is fully susceptible to infections by another type. Epidemics can occur in workplaces and institutions where large numbers of people are close together. Certain irritants (i.e., SO2, NO2, phosgene, and

NH3) in the workplace can increase the risk and incidence of this bacterial infection.

6.3 Fungi

A fungus infection is known as a mycosis. Environmental factors that can influence fungal growth in the workplace include outdoor air concentrations, type and rate of ventilation, and indoor moisture levels. Many of the diseases caused by these organisms occur in agricultural workers and workers exposed to contaminated air handling systems and open water spray chambers. The fungi that cause systemic mycoses are generally saprophytes in soil. Inhalation of these spores initiates the infection in humans. The spores germinate and develop vegetative organisms that initiate a localized infection. The earliest pulmonary infections are usually acute, consisting of self-limited pneumonitis that can be often overlooked or ascribed to a bacterial or viral disease. The infection subsequently begins to spread progressively to other tissues and often results in the development of granulomatous lesions that clinically resemble tuberculosis. Many fungi can spread by way of the bloodstream and can attack almost any tissue in the body. Because these organisms are not transmitted from human to human, they are not contagious. The organisms appear in infected tissue as small, oval cells (15 mm in diameter) frequently located within macrophages and/or reticuloendothelial cells. Miliary lesions appear throughout lung parenchyma, and the lymph nodes become enlarged. The disease may occur either in an acute or chronic state and may be localized or disseminated. Workers without adequate respiratory protection, who are exposed to atmospheres that have been contaminated with quantities of bird or bat droppings, are especially at risk of these types of respiratory diseases. The full range of health effects due to fungal exposure include allergic disease (e.g., allergic rhinitis, asthma, and hypersensitivity pneumonitis) and infectious diseases (e.g., histoplasmosis, blastomycosis, aspergillosis, coccidioidomycosis, and acute toxicosis). Fungi that cause these diseases are frequently opportunistic organisms that produce disease in compromised hosts, such as those with reduced pulmonary defenses (e.g., from corticosteroids, X irradiation, medication), some concurrent disease, or a coexposure with some other air pollutants (76-79).

Of the more than 100,000 fungal species in our environment, only about 150 are pathogenic and of these only about 40 affect the lung. Of these, the two most pathogenic are Histoplasma capsulatum and Coccidioides immitis.

6.3.1 Histoplasma Capsulatum Histoplasmosis, sometimes called Darling's disease, is an infection resulting from inhalation of the fungus Histoplasma capsulatum. It was discovered in 1906 by Darling who observed it in sections of tissue taken from post-mortem cases. H. capsulatum is the most common endemic fungal disease in the United States, and it has been estimated that about 500,000 new cases of histoplasmosis occur each year (80). About 90-95% of these cases represent asymptomatic, self-limited pulmonary infections. The remaining 5-10% of patients may develop an acute pulmonary form, a disseminated form or a chronic pulmonary form of the disease (80).

Histoplasma capsulatum has been isolated from soil in more than 50 countries. In the United States, the most heavily endemic area includes Ohio, Kentucky, Indiana, Illinois, Tennessee, Arkansas, and Missouri. In these areas, up to 75% of the population has had primary pulmonary histoplasma infection before the age of 20, based on positive skin tests for the organism (80). Like other fungi that cause systemic mycoses, these organisms can be found as saprophytes in soil. Soil constitutes the reservoir from which infections with H. Capsulatum occur. These organisms are commonly found in areas heavily contaminated with the droppings of chickens and keratonaceous material, as well as in the soil beneath areas where pigeons, starlings, and other birds nest (80). Bats are implicated as carriers, and outbreaks of this disease have been traced to the inhalation of dust from bat guano found in caves. In these cases, the disease has been referred to as "cave fever" or "speleonosis" Another source of soil contamination comes from decaying bodies of small rodents and excreta from a variety of wild and domesticated animals (81). Besides man, a variety of domesticated and wild animals are naturally infected (e.g., cats, fox, opossum; and dogs). Although chickens are heavily exposed, they do not develop the disease, nor do other birds, presumably because the fungus does not thrive at their high body temperature. No intermediate host has been identified, and the disease is not transmitted directly from one human to another or from an animal to a person.

Workers other than farmers who may be at risk include construction crews, operators of heavy equipment, such as bulldozers and graders, and maintenance workers. Any type of industrial activity that results in disturbing contaminated soil can disperse and scatter the infectious spores into the air, which then can be carried by prevailing winds to residents of adjacent areas who may also be at risk

(81). Outbreaks of histoplasmosis have been associated with excavation of infected soil for construction of buildings and roads, working in soil fertilized by chicken manure, and breathing dust from silo towers or derelict houses where starlings have congregated or in caves inhabited by bats

(82). Like all highly pathogenic fungi, these organisms are dimorphic, capable of changing their growth characteristic from a mycelial form normally found in nature and in laboratory culture, to a budding, oval, yeast-like structure found in infected tissue.

The pathogenesis of H. capsulatum has been clearly established. When soil or other contaminated matter is disturbed, aerosolized fungal spores called conidia are inhaled and they are transformed within the respiratory system, into yeast forms by the heat of the body. Most often, the infection remains localized within the lungs perhaps producing patchy areas of interstitial pneumonitis, but it is usually self-limiting (83). The host response to this infection varies with the dose of inoculum and the age and immunologic status of the host (84-86). In the lung, the spores are engulfed by macrophages and multiply intracellularly in the yeast phase with a generation time of about 4 h. The draining lymph nodes become quickly involved, and hematogenous spread of the organisms occurs. This fungemia is generally self-limited but results in seeding of reticuloenothelial organs throughout the body with this organism. Specific lymphocyte-mediated cellular immunity develops in 7-14 days that results in rapid limitation of the infection both in the lung and at distant sites with necrosis and granuloma formation in involved areas. The lymphocytes of patients with healthy immune systems produce cytokines that activate macrophages and induce formation of granulomas. In a small number of individuals, an effective cell-mediated immune response may not develop, the infection becomes progressive and widely disseminated, and lesions occur in practically all tissues and organs. Ulcerating lesions may be found in the nose, tongue, and mouth. Fever, wasting, and enlargement of liver, spleen, and lymph nodes may occur, and the disease may closely simulate miliary tuberculosis. Histoplasmosis is also occasionally seen as a chronic pulmonary disease with cavitation that simulates chronic pulmonary tuberculosis.

Factors that may increase one's susceptibility to this infection include aggressive immunosuppressive therapy in organ transplant recipients and in AIDs patients and the presence of chronic debilitating diseases such as cancer, diabetes, Hodgkins disease, leukemia, and tuberculosis (83). Because this is an "opportunistic" organism, children and old and debilitated patients are also predisposed.

A provisional diagnosis of histoplasmosis is based upon clinical manifestations, serological tests, and a positive skin response to histoplasmin. The latter has virtually no value in those localities where the fungus is so prevalent that most persons have positive reactions to histoplasmin.

No treatment is needed for most patients with acute mild pneumonitis, but treatment is recommended for patients with severe, persistent, or progressive disease and for immunosuppressed patients. Amphotericin B remains the drug of choice (85).

6.3.2 Coccidioides Immitis This fungus causes the second most common endemic infection in the United States and is the cause of coccidioidomycosis (84). Coccidioides immitis was first observed in Argentina in 1892 when the causative agent was thought to be a protozoan but later was cultured and shown to be a fungus. This disease also goes by names of "valley fever," "Joaquin fever," or "desert rheumatism." Approximately 100,000 cases occur annually in the United States and about 70 of these cases per year are fatal (84).

The fungus has a predilection for growth in desert soils and occurs endemically in the southwestern United States, especially in the San Joaquin Valley of California, and in areas around Tucson and Phoenix and western Texas, where the soil is arid and alkaline and the ambient temperature is usually higher than 26°C (84). In these areas, the majority of residents give evidence of past infection by a positive skin test. Both man and animals (e.g., wild rodents, dogs, and cattle) are infected by the inhalation of airborne spores contained in dust (82). The disease is not communicable, and there is no evidence that infected animals contribute directly to the spread of this disease.

In these endemic areas, the people who are particularly at risk include those individuals who work in agriculture and allied pursuits as well as oil field workers, highway maintenance and construction crews, operators of graders, bulldozers, and other heavy equipment, and occasionally train crews who pass through. Repair workers, mechanics, and those involved with handling the organism in a laboratory may also be exposed (81, 87). A high incidence has also been found in American Indian tribes who live in reservations in these dusty, desert areas (85).

Like other pathogenic fungi, C. immitis is dimorphic, that is, the infective stage within the tissue is morphologically different from that observed in nature and in culture. In body exudates and in histological sections, the organism appears as spherules or a mixture of spherules and hyphae (84, 88). The spherules are thick-walled structures as small as 5 mm in diameter but at maturity may be 20-60 mm. They are filled with hundreds of irregularly shaped endospores varying from 2 to 5 mm in diameter. These large spherules eventually rupture, and the endospores are released and develop into new spherules. In culture, growth is rapid, and fluffy white mycelia appear within about 5 days. A characteristic feature of the hyphae is the cast-shaped arthrospores, which alternate with smaller clear hyphal cells. When the hyphae fragment, they release huge numbers of arthrospores, which are easily airborne and highly infectious.

Coccidioides immitis can be both an acute, benign respiratory infection or a chronic disease, fatal if untreated. In about 60% of infected persons, the disease is not clinically apparent; infection is revealed only by the acquisition of delay-typed hypersensitivity (positive coccidioidin skin test reaction) in about three weeks. The rest of the individuals may develop a spectrum of symptoms ranging from a flu-like syndrome to frank pneumonia following an incubation period of 1-4 weeks. Symptoms include cough, fever, headache, chest pain, dyspnea, and malaise, often with pleurisy and skin eruptions. About 5% of infected persons ultimately develop chronic pulmonary cavitary disease resembling pulmonary TB. Dissemination occurs in less than 1% of the infected persons, producing infected granulomatous lesions that are indistinguishable from tuberculosis, unless spherules can be detected in numerous organs (84, 85). Death from disseminated coccidioidomycosis is usually attributed to meningitis (58%) or pulmonary disease.

Host factors associated with high risk of disseminated infection include race, sex, age, pregnancy, and immunosuppression. Dissemination occurs ten times more frequently in dark-skinned than light-skinned individuals. Men are 1.5 to 6 times more susceptible to disseminated infection than nonpregnant females. Pregnant females are more susceptible, especially during the second and third trimesters (84, 85). In endemic areas, this fungus is the third most frequent opportunistic infection of HIV-infected individuals. Many of these cases probably result from reactivation of latent infection rather than a recent primary infection.

Diagnosis is made by finding the fungi in the lesions. The organism can be found by direct microscopic examination of pus, sputum, gastric washings, spinal fluid, and biopsy specimens. The cocidioidin test, a test of skin sensitivity to an extract of the organism, is of value; however, cross reactions with other fungal infections such as histoplasmosis and blastomycosis may occur.

In endemic areas, infection can be diminished by dust control measures. Repeated spraying with oil has been used to reduce the incidence of C. immitis infections in very arid, dusty environments (81). No treatment is needed for most patients with acute pulmonary Coccidioides immitis but amphotericin B is the drug of choice for chronic or cavitary disease (85). 6.4 Viruses

Several hundred different viruses may infect humans. Examples of viruses found in indoors include rhinoviruses, influenza, parainfluenza, variola, adenoviruses, varicella zoster, paramyxoviruses, poliovirus, and cytomegalovirus (10, 23). The viruses that occur primarily in humans are transmitted chiefly by humans, mainly via the respiratory route. Diseases caused by viruses vary considerably in their effects on susceptible individuals, mild or moderate in some cases and extremely dangerous in others. Epidemics caused by viruses present formidable challenges to public health officials responsible for preventing and controlling the spread of such diseases. Infectious diseases caused by viruses are many and varied. This discussion focuses on viral infections such as influenza and the common cold that are associated with crowded working conditions.

6.4.1 Influenza Virus The 1918-1919 influenza pandemic is recognized as one of the most serious and devastating outbreaks of an infectious disease known. It was estimated that more than 20 million people died of this disease during that period (7, 78). Later, in the pandemics of 1957 and 1968, it was estimated that influenza killed 90,000 people in the United States alone and the direct cost of medical care exceeded $3.4 billion. Outbreaks have been associated with crowded working conditions and military posts. Influenza is an acute infection that enters the respiratory tract by direct contact with the mucus of an infected person. The virus can persist for hours in dry mucus. It is an RNA virus that possesses an unusual degree of genetic variability. As a result of this property, the virus frequently undergoes major antigenic shifts, and new variants emerge. Thus, individuals with immunity to prior strains have limited protection to the newly emerged strains. The infectious strain enters the body through the mouth and nose and replicates in the upper respiratory tract. Normally, the disease is self-limiting. However, serious effects may occur when the virus destroys the cells of the respiratory tract and secondary bacterial infection develops. The incubation period is short, only 1-2 days. The symptoms of infection include chill, fever, malaise, muscular aches, cough, and general respiratory symptoms. Individuals with immunosuppression or chronic respiratory diseases have the greatest risk (89).

6.4.2 Common Cold The common cold is aptly named because it is one of the most common human maladies; it has been recognized since earliest recorded history. There are more than 200 agents that are etiologically responsible for clinical syndromes associated with pharyngitis or the common cold. These include certain bacteria and a wide host of viral agents, including respiratory syncytial virus, rhinovirus, adenovirus, influenza, parainfluenza virus, and certain echo- and coxsackieviruses. About 90% of colds stem from viral infections. Serological testing or viral isolation is necessary to establish the specific etiologic agent. Most colds develop in the nose and throat but then can spread to the trachea and larynx (laryngitis), the sinuses (sinusitis), or the lungs (bronchitis). Colds account for more time lost from work than any other cause. Although self-limiting, colds can lead to secondary infections. Health-care workers are at risk from these agents due to frequent exposure to infected individuals. Infection may be facilitated by excess fatigue, allergic nasopharyngeal disorders, or inhalation of certain noxious fumes in the workplace (90, 91).

6.5 Rickesttsial and Chlamydial Infections

Both chlamydia and rickesttsiae rely on host cells to compensate for their own metabolic deficiencies; thus they are obligate intracellular parasites. Although rickettsial infections in humans usually begin in the vascular system following the bite of an infected arthropod, an important rickettsial disease is acquired by inhaling contaminated dust particles, resulting in Q fever. Q fever is an acute febrile illness that affects veterinarians, farmers, dairy workers, and abattoir employees. Animals shed the organism (Coxiella burnetii) in their nasal and salivary secretions, and it can be inhaled by individuals who work in this environment. The organism remains viable in a dried state for long periods of time (92, 93).

Chlamydial infections are occupational diseases in the poultry industry. However, veterinarians, workers in pet bird industries, and bird owners may be infected. Psittacosis or ornithosis is the term used for human infections. At highest risk are workers engaged in plucking and eviscerating chickens and turkeys. Most infections are transmitted through inhalation. Because the symptoms resemble the "flu," misdiagnoses are common (94).

6.6 Hypersensitivity Diseases

Microorganisms in the workplace may also affect the immune system. Allergic respiratory diseases may develop in response to inhaling aerosols of both viable and nonviable organisms and their antigens, as well as microbial products such as glucans, endotoxins, and mycotoxins. Fragments of microbial cells, including cell wall segments, flagella, genetic material, and by-products of metabolism that are transported as bioaerosols can cause health problems (95). Such allergic respiratory illnesses produce acute symptoms, including malaise, fever, chills, shortness of breath, and coughing. They can often be serious diseases possibly leading to permanent lung dysfunction. Individuals can become hypersensitive to the inhalation of thermophilic actinomycetes in heating, ventilating, and air conditioning systems (19, 96).

Potential allergens include dust mite wastes, mold spores, fungal hyphal fragments, and macromolecular organic dust deposited on floors and surfaces. Exposure to such allergens is an important cause of asthma and chronic allergic rhinitis in certain occupations. Worldwide, the incidence of asthma is increasing, and occupational asthma has become more prevalent. Various factors have been suggested to explain this increase, including increased exposure to allergens, possible adjuvant effects of environmental chemicals, and improved diagnoses. Occupational asthma, a common respiratory ailment, may be defined as a disease characterized by variable airflow limitations and/or hyperresponsiveness due to conditions in an occupational environment and not to certain stimuli outside the workplace. Symptoms include recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. About 200 agents have been implicated in causing workplace asthma (97). Examples include baker's asthma in workers exposed to Aspergillus and Alternaria, workers exposed to mites found in grain dusts, handlers of animal, workers involved in the manufacture of detergents where certain proteolytic enzymes are added; and workers exposed to wood dusts, especially red cedar.

6.7 Diseases Related to Bacterial Toxins

Microorganisms that cause disease may produce certain toxins. Airborne endotoxins are ubiquitous in nature and may be distributed throughout the workplace. Given appropriate moisture content and temperature, organic substrates furnish the necessary nutrients to promote the growth and reproduction of a wide variety of microorganisms (gram-negative) capable of producing endotoxins. Adverse human reactions to these endotoxins have been associated with a number of occupational settings including agriculture (e.g., swine/poultry shelters, composting, rice hulling and silo unloading, animal feed), manufacturing (e.g., machining oils, bioengineering, and mattress making), and textile production (e.g., cotton spinning mills, flax and textile processing, cotton garnetting, and carpet weaving). Although most of the settings in which high aerosol levels of endotoxins may occur are occupational, bacterial endotoxins have also been implicated in nonoccupational exposures as well. Endotoxin exposure is a possible cause of humidifier fever and is related to SBS (20, 98-100). A very important type of reservoir for such organisms is recirculated water-based fluids that are found in many home and office humidifier systems and possibly in areas where humans live downwind from sewage outfalls, solid waste processing centers, or wastewater treatment plants (98, 99). Endotoxin inhalation may cause an acute illness with fever, sweating, muscle aches, and headaches; sometimes rhinitis, asthma, and breathlessness may occur. Symptoms usually start within hours after exposure and may resolve in a day; however, they can reappear again with repeated exposures.

Mycotoxins, such as aflatoxins, are products of fungal metabolism that can lead to respiratory distress and severe systemic toxicosis. Some mycotoxins may be immunosuppressive and increase the likelihood of opportunistic and secondary bacterial infections. Inhalation of such toxin-containing spores may lead to "pulmonary mycotoxicosis" due to the absorption of toxin through the mucous membranes of the respiratory tract (100).

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