Introductory Review
Cellscience Reviews Vol 2 No.1
ISSN 1742-8130


Assessing the role of transmissible agents in human disease by studying meat workers


Eric Johnson

Department of Epidemiology, Tulane University

Received 6th July © Cellscience 2005


Introduction

A lot of attention has been paid to the chemical composition of animal food, naturally or from contamination, or its chemical composition after preparation, as these are possible sources of human diseases such as heart disease and diabetes (Mann, 2002), and various cancers including cancer of the kidney, colon, breast, lung, etc (Gago-Dominguez et al, 2002, Chao et al, 2005, Willett, 2005, Alavanja et al, 2001). However, there is reason to suspect that the chemical composition of animal food alone may not explain the association with these diseases completely. For example, the findings of many of the case-control studies reporting a positive association between dietary fat and some of these cancers, or a protective effect of fruits and vegetables for breast cancer, have not been confirmed in large well conducted prospective studies or randomized trials (van Gills et al, 2005; Willett, 2005). Also, it has been shown that an observed association between the consumption of red meat and lung cancer risk persisted even after controlling for total fat, saturated fat, cholesterol, and tobacco smoking (Alavanja et al, 2001). The situation therefore begs for alternative hypotheses to explain the underlying causes of most of these diseases.
Animal food can be the source of disease in humans not only because of the chemical composition of some of its constituents prior to cooking such as heme (Sesink et al, 1999; Cross et al, 2003), fat or cholesterol (Introduction to Lipid Peroxidation), dioxins (Inter Agency Working Group, 2003) or because of substances formed during its preparation such as polycyclic aromatic hydrocarbons (International Programme on Chemical Safety, 1998), heterocyclic amines (National Cancer Institute, Cancer Facts, 2004), or N’-nitroso compounds (International Programme on Chemical Safety, 1978), but also because it acts as a carrier for disease-causing biological agents that can be transmitted from food animals to humans, and could conceivably be involved in the etiology of these diseases. Historically, there is precedence for this - once common human infectious diseases such as gastrointestinal tuberculosis, brucellosis, and anthrax that resulted from the ingestion of animal food have been successfully transformed to very rare occurrences through control measures instituted decades ago. But there are many transmissible biological agents present in food animals whose role in the occurrence of especially chronic human disease has not been investigated.
The purpose of this review is to call attention to the following: 1) To date there are still many common malignant and non-malignant diseases in humans of undetermined etiology. 2) There is a myriad of biological agents that are present and cause disease in animals used for food and can be transmitted to humans. 3) The vast majority of epidemiological studies showing a link between various types of human malignant and non-malignant diseases, and ingestion of meat, have not adequately investigated the possible role of these transmissible agents present in animal food products, that may well be the underlying cause in some of these situations. It is therefore hypothesized that some of these agents may play a role in the etiology of some of the chronic or sub-acute human diseases of unknown cause, and a study of health risks in meat workers presents an excellent model for investigating this hypothesis.
Traditionally, the risk posed to the general population from environmental exposure to important chemicals such as asbestos, benzene, aniline dyes, polycyclic aromatic hydrocarbons (PAH), have been identified and assessed from the study of subjects with occupational exposure to these substances. Because exposures to pollutants in the general environment are relatively low and widespread, it is difficult to observe risks arising in the general population from such exposures in epidemiological studies. On the other hand, studies of exposed occupational groups are more rewarding and frequently the preferred method used to identify or detect such risks, because occupational exposures are additional to those engendered in the general population and are substantially higher, and therefore much easier to detect any associated risks. It is therefore proposed that any potential health risk posed by the myriad of biological agents present in food animals to human health could also be investigated by studying exposed workers in the meat industry.
There is a well-defined exposure gradient among these workers, the highest exposure occurring in slaughterhouses, with much lower exposures expected in workers in the meat department of supermarkets or canned meat industries. Meat workers have the highest human exposure to these transmissible agents, because for example in a typical large abattoir, they may come into contact with hundreds or several thousands of animals that are slaughtered daily. Also, contact with the animals is very intimate involving contact with secretions, blood and other body fluids, droppings, and internal organs. Moreover, abrasions and cuts from piercing wounds from sharp bone splinters and knives, and breaches in the skin from dermatitis due to contact with irritant enzymes are frequent, making it easy for agents to enter directly into the circulatory system. Power saws used on large carcasses, slicing, mixing, mincing and tenderizing machines, falls from slippery floors, and burns and scalds from the use of steam-heated fat-rendering vessels, are all further sources of injury that facilitate entry of agents into the body and make the industry one of the most dangerous of all industries (Copplestone & Kaplan, 1972; Antonev et al, 1978; Women’s Occupational Health Resource Center, 1979). Aerosol transmission occurs continuously (Harris et al, 1962; Rahkio & Korkeala, 1997), and exposure can even occur through ingestion (for example, it is not uncommon for workers in the kill floor in cattle abattoirs to drink blood from the animals. No other human group has such potential for high exposure to these transmissible agents.
In this paper, the strategy therefore is to identify and highlight those diseases that epidemiologic studies have thus far detected increased risks of in workers in the meat industry. If any chronic disease that occurs in the human general population is caused by transmissible agents present in animal food products, then such diseases would be identifiable among those observed to be occurring in excess in meat workers who have the highest exposures. This paper is therefore a review of disease risk and mortality in workers in the meat industry, and an evaluation of the relevance to the general population. The review will be restricted to studies that have purposefully investigated workers in the meat industry.

A. Transmissible Agents in Food Animals

Cattle, pigs, sheep and poultry are provide the main source of food for the vast majority of mankind, and they are naturally infected with a plethora of transmissible agents that include prions, viruses, bacteria, protozoa, etc., that are known to cause disease in these animals, including cancer and neurologic diseases.

1. Oncogenic Agents

Bovine Leukemia Virus (BLV) commonly infects and causes lymphosarcoma in cattle and sheep (Burny and Mammerickx, 1987). Bovine papilloma virus (BPV) causes tumors of the alimentary and urinary tracts in cattle (Campo, 1987, Lancaster & Olson, 1982). Lung cancer in sheep is caused by the Jaagsiekte Sheep Retrovirus (JSRV, Palmarini & Fan, 2001; Wooton et al, 2005). In addition, several viruses such as Marek’s disease virus (MDV), avian leukosis/sarcoma viruses (ALSV) and reticuloendotheliosis viruses (REV) cause a wide variety of tumors such as leukemia, lymphoma, sarcoma, kidney cancer, etc., and neurologic diseases in poultry, (Witter, 1984; Payne, 1985; Payne, 1987). Some of these viruses are the most potent cancer-causing agents known. For example, infection with certain strains of ALSV or REV that carry an oncogene can induce tumors in chickens within days (Payne, 1987), and JSRV can cause lung cancer in a sheep in as little as two weeks (Palmarini & Fan 2001).

2. Non-oncogenic Agents

Transmissible agents also cause an inestimable variety of non-malignant diseases in cattle, pigs, sheep and poultry, which are well-described in standard veterinary textbooks. Selected agents include prion agents that cause the sub-acute severe neurologic disease known as bovine spongiform encephalopathy (BSE) or ‘mad cow’ disease in cattle, and scrapie in sheep (Handbook of Veterinary Neurology, 1993), bacteria such as the anthrax bacillus, leptospira, coxiella, brucella, listeria monocytogenes, and viruses such as vesicular stomatitis virus, influenza virus, foot-and-mouth disease virus, etc. Some of these agents cause acute or latent disease of the nervous system in animals with associated disturbances in gait, loss of consciousness, paralysis, tremors, seizures, coma, and depression. These include BSE, pseudorabies virus of pigs, malignant catarrhal fever virus of cattle, porcine paramyxovirus, visna virus, the louping ill flavivirus of sheep, the enteroviral encephalomyelitis virus in swine, listeria moncytogenes, clostridium tetani, clostridium botulinum, and several bacterial agents that cause meningitis, etc.. Similarly, a variety of fungal, protozoal, ricketsial, chlamydial and parasitic agents cause diseases of the central nervous system in these animals such as crytococcosis, histoplamosis, neosporosis, trypanosomiasis, aspergillosis, phaeomycosis, toxoplasmosis, babesiosis, encephalitozoonosis, etc.

B. Malignant Disease Mortality and Incidence in Meat Workers

1. Record-Linkage Analysis of National Occupational Mortality Data and Census.

Interest in mortality among workers in the meat industry surfaced in 1982 with reports from several countries of excess risk of lung cancer in meat workers (Fox et al, 1982; Griffith, 1982; Doerken & Rehpenning, 1982; Johnson & Fischman, 1982). Fox et al (1982) reported on mortality and cancer incidence in three countries from the examination of national occupational mortality statistics and census data - in England & Wales the risk of death from lung cancer among butchers was between 1.2- to 1.3-fold higher than expected for 1966 to 1970. In Denmark for the period 1970-1975, a 2.5-fold increased risk was reported for butchers in slaughterhouses, and a 1.7-fold risk for other butchers, while unskilled workers in slaughterhouses had no excess risk. In Sweden lung cancer incidence was 80% higher than expected in slaughterhouse butchers, 30% higher in other butchers, and 50% higher in other slaughterhouse workers. Griffith (1982) noted that the excess lung cancer mortality in butchers and meat cutters in England & Wales for the period 1959 to 1963 was 30%, and in 1951 it was 30% also for slaughterhouse workers and twice the expected rate for meat and fish curers. Doerken & Rehpenning (1982) observed an increased risk of cancer the respiratory tract in butchers in Hamburg, Germany compared to bakers. Lynge et al (1983) reported that for the period 1975-1980, the risks for self-employed and skilled butchers in butchers shops were 1.8-fold and 0.9-fold respectively, while for slaughterhouse workers they were 1.5 and 1.1 for skilled and unskilled workers respectively; smoking history was similar for both skilled butchers and unskilled workers in slaughterhouses. Chow et al (1995) in a record linkage study in Sweden reported increased risk of esophageal cancer in butchers. Coggon et al (1995) linked 4,018 butchers identified nationwide from the 1961 census in England & Wales with mortality data; increased risks were observed for cancers of the rectum, prostate and melanoma, but over 16% of subjects were not traced. Bofetta et al (2000) linked national census data with cancer registry data in Sweden to investigate cancer incidence in 25,049 butchers and meat workers. Increased relative risks (RR) were observed for cancers of the oral cavity & pharynx (RR= 1.6), stomach (RR=1.6), larynx (RR=1.4), and lung (RR=1.4). In separate reviews of the literature, Kristensen & Lynge (1993) and McLean & Pearce (2004) concluded that butchers and meat workers have an excess risk of lung cancer that is not all explained by tobacco smoking, and is probably related to biological exposures.

2. Proportional Cancer Mortality Study & Cohort Cancer Mortality and Incidence Studies of Workers Exposed to Cattle, Pigs & Sheep.

In a proportional mortality ratio (PMR) analysis of all 223 death certificates of white males available at a local meat cutters’ union in Baltimore, Maryland, increased risks of cancers of the lung (RR=1.5), bladder, kidney, and ureter (RR= 1.6), myeloid leukemia (RR=3.8), lymphosarcoma and reticulosarcoma (RR=2.7), multiple myeloma (RR=2.7), were observed (Johnson & Fischman, 1982).
Four cohort studies have been conducted in workers exposed to cattle, pigs, and sheep in the meat industry. 1) Johnson et al studied mortality in the United States of 28,900 members of the local meat cutters union in Baltimore, Maryland for whom they had previously reported PMR results (Johnson & Fischman, 1982). Increased risks were observed among workers exposed to cattle, pigs and sheep for cancers of the lung, buccal cavity & pharynx, esophagus, colon, kidney, bladder, and bone, and tumors of the hemopoietic/lymphatic (H&L) systems (Johnson et al 1986a, Johnson et al, 1986b, Johnson, 1987, Johnson, 1989, Johnson et al, 1994b; Johnson et al, 1995a). High risks were observed in relation to slaughtering activities, and risks were higher in butchers who killed than in meat cutters who did not. In the subgroup of workers in pig processing plants, increased risks were observed for cancers of the lung, colon, and esophagus. (2) Coggon et al (1989) studied cancer mortality in 1,610 workers employed in bacon factories, abattoirs and meat distribution centers in the north and south of England that slaughtered pigs or handled pork, beef and lamb – increased risks of cancers of the stomach, liver, lung, and tumors of the H&L systems were observed; risk was higher for workers exposed to warm meat than for those exposed to chilled meat. 3) Guberan et al, (1993) reported on mortality and cancer incidence in 552 self-employed butchers and 310 pork butchers in Geneva, Switzerland. Elevated risks were observed for cancers of the lung, larynx, buccal cavity & pharynx, esophagus, stomach, colon and rectum, prostate, liver, pancreas, prostate, and tumors of the H&L systems. Excess risks of cancers of the esophagus, stomach, liver, gall bladder, kidney, cervix, brain and tumors of the H&L systems were also observed in the wives. 4) McLean et al (2004) studied mortality and cancer incidence in 6,647 workers in one meat processing plant handling mutton and beef, and two plants handling only sheep meat, in New Zealand. Excess risks of cancers of the lung, larynx, oral cavity & pharynx, oral cavity, esophagus, stomach, colon, rectum, bone, gall bladder, bladder, thyroid, female genital organs, testis, and non-Hodgkin’s lymphoma were observed. The findings in these cohort studies from four different countries are remarkably consistent with each other and with those of record-linkage analyses of national data in several countries mentioned above, and from case-control studies reporting an association between working in the meat industry and cancers of the lung and H&L systems, (Dubrow and Wegman, 1984; Pearce et al, 1986; Pearce et al, 1988; Reif et al, 1989; Mallin et al, 1989; Johnson (1991), Loomis & Savitz, 1991; Siemiatycki, 1991; Whittaker, 1991; Metayer et al 1998; Bethwaite et al, 2001).

3. Case-control Studies Nested Within Cohorts.

Gustavsson et al (1987) observed in a nested case-control study of the lung cancer excess observed in a cohort of butchers only a very modest elevation of lung cancer risk in association with slaughtering, an activity expected to have one of the highest exposures to oncogenic viruses within the industry. However, the failure to have observed a much higher risk could have resulted from comparing workers who kill with other workers in the cohort who were all probably also exposed to oncogenic viruses. Also, not all histologic types of lung cancer were included. Johnson (1991) in a nested case-control study of lung cancer within the Baltimore cohort observed a very strong association with slaughtering and exposure to live animals that persisted even after controlling for tobacco smoking. In a similar study of tumors of the hemopoietic and lymphatic systems, highest risks were again observed to be associated with slaughtering activities and exposure to live animals (Metayer et al, 1998).

4. Cohort Cancer Mortality Studies of Workers Exposed to Poultry.

Only two cohort studies have reported on poultry workers (Johnson et al, 1997; Netto & Johnson, 2003). Statistically significant excess risks were observed for cancers of the esophagus, liver, pancreas and tumors of the H & L systems and non-significant risks of cancers of the buccal cavity & pharynx, stomach, colon, rectum, lung, cervix, kidney, brain and other CNS, and H&L systems (Johnson et al, 1997; Netto & Johnson, 2003).
The evidence overall from all these studies indicates that occupational exposure to each of the food animals (cattle, pigs, sheep, poultry) is associated with excess cancer risk in workers, and strongly suggests that occupational exposures within the industry, particularly exposure to oncogenic viruses, are probably responsible for some of the increased risks observed, especially given the consistent higher risks observed for working in slaughterhouses versus elsewhere within the industry, or with slaughtering versus other activities, or the higher risks in butchers who kill versus meat cutters who do not.

C. Non-Malignant Disease Mortality in Meat Workers

Very little information is present on the long-term effects in workers resulting from exposure to the large number of non-carcinogenic transmissible agents in the industry. Many of these agents cause chronic severe neurologic diseases like scrapie and visna in sheep, and BSE (also known as “mad cow disease”) in cattle (Handbook of Veterinary Neurology, 1993). The experience with the prion that causes BSE in animals provides an example of a transmissible agent that naturally causes a neurologic disease in food animals which also causes a similar type disease in humans, with significantly much higher risks in meat workers. It is now believed that the prion that causes BSE is responsible for a variant form of the severe neurologic disease known as Creutzfeldt-Jakob disease (vCJD) in persons who had eaten beef contaminated with BSE (Weihl & Roos, 1999; Belkin, 2003). vCJD affects younger ages than classical CJD. It is believed that a cluster of 5 cases of vCJD in a town in Leicestershire, England, was caused by exposure to beef contaminated with infected brain tissue during butchering (Editorial, 2001). A review of the literature revealed high risks for associations between exposure to various types of animal meat and CJD, and instances of suspected human to human transmission have occurred (Hillier & Salmon, 2000). Occupational contact with animals such as deer, monkeys, and squirrels was associated with a 9-fold risk that was not statistically significant because of small numbers, while the excess risk of similar degree associated with non-occupational contact with deer or rabbits was statistically significant. Exposure to animal organs was also significantly associated with CJD (OR=20.9; p<0.005, Davanipour et al, 1986). In a case-control study of 636 deaths from CJD in the United States and occupation (Cocco et al, 2003) the relative risk as measured by the odds ratio (OR) for butchers was 6.8 (95% CI 1.5, 30.1), and the OR for food preparation occupations was 3.2 (95% CI, 0.9, 10.7); the odds ratio for physicians was 4.6, and the odds ratio for working in offices of physicians was also 4.6, but neither was statistically significant; the OR for meat products industry was 3.8 (95% CI, 0.8, 17.3). In a review of the literature in that same article, it was noted that reports of sCJD in livestock farmers and butchers have been repeatedly published; in one case-control study of 662 sCJD cases a significant increased risk was observed in livestock farmers based on 6 cases – four of the 6 cases (0.6 expected) occurred in farms where BSE cases had been reported; in another case-control study, the OR for occupational contact with animal products was 1.6 (95% CI, 1.2, 2.2). In a re-analysis of three case-control studies combined, borderline statistically significant odds ratios for risk of CJD from exposure to cows and sheep were 1.7 and 1.6, respectively (Wientjens et al, 1996).
Multiple sclerosis developed in four out of seven research workers exposed to lambs affected by the swayback, a disease of the central nervous system in sheep (Dean et al, 1985). Suspected cases of congenital myasthenia gravis were recently diagnosed for the first time in cattle (Thompson, 1998). These examples raise the possibility that many of the neurologic diseases in humans presently of unknown etiology, such as multiple sclerosis, amyotrophic lateral sclerosis (Lou Gehrig’s disease), Alzheimer’s disease, and some forms of Parkinson’s disease may well be due to zoonotic infectious agents originating from these animals.
Reports of mortality from non-malignant diseases in the cohort, and record-linkage studies of meat workers have unfortunately been limited to the study of diseases grouped into very broad categories based on major systems such as circulatory, respiratory, or gastrointestinal, rather than specific individual causes, because of limitations in the various software used to analyze these studies. In spite of this, statistically significant elevated risks have been reported in certain subgroups within the industry for endocrine, nutritional & metabolic diseases (Coggon et al, 1995); benign neoplasms; diabetes; diseases of the circulatory system; atherosclerotic heart disease and coronary heart disease; diseases of the digestive system; cirrhosis of the liver; and diseases of blood forming organs in men, but not in women (Johnson, 1987a; Johnson, 1987b). In a more recent analysis using more detailed causes of death, Johnson et al (unpublished) have additionally observed increased risks of nephritis, stroke, and functional diseases of the heart in meat workers; circulatory disease; ischemic heart disease; cirrhosis of the liver (Guberan et al, 1993). Non-significant elevated risks were reported for benign neoplasms; diseases of the circulatory system; and diseases of the digestive system (McLean et al, 2004). Again these findings, though limited, raise the possibility that transmissible agents in food animals may be responsible for some of these diseases in the general population.

Biological Plausibility of, and Other Evidence for the Hypothesis

This is best illustrated by using oncogenic retroviruses that cause cancer in cattle, sheep and poultry as examples:

1. Cattle & Bovine Leukemia Virus (BLV)

Early serologic studies of BLV infection in humans have been mostly negative (Donham et al, 1977; Ferrer, 1980), but this could have been due to use of insensitive assays and other technical problems (Ferrer et al, 1981). Only very recently have currently available and highly sensitive assays such as Western blot and ELISA been employed in testing human sera. Buehring et al (2003) detected antibodies against BLV p24 capsid antigen in 74% of human sera tested using Western blot, while none of the samples that had given the most intense reaction was positive when tested with one of the earlier techniques. BLV has been shown to be present in unpasteurized milk and colostrom from infected cows (Miller et al, 1979; Ferrer et al, 1981), and can remain viable in refrigerated blood for up to nine days (Bovine Leukemia Virus Workshop, 1983). It has been shown blood from BLV-infected cows can transmit the infection to other cows by parenteral inoculation (Evermann et al, 1986). Perhaps more poignantly, BLV infects human and simian cells in vitro, and causes erythroleukemia in chimpanzees (McClure et al, 1974).

2. Sheep & Jaagsiekte Sheep Retrovirus (JSRV)

Human serological studies of JSRV that naturally causes bronchioloalveloar adenocarcinoma of the lung in the sheep have not been conducted, but JSRV can infect and replicate in human cells (Palmarini & Fan, 2001). Also, the oncogenicity of this virus has been recently determined to be a direct effect of its envelope protein (Wootton et al, 2005). Moreover, it is evident that a significant proportion of human lung cancer cases including bronchioloalveloar carcinomas are not due to tobacco smoking (Morabia & Wynder, 1992), and the etiology of some of these cases remains unknown. Interestingly, 30.2% of human bronchioloalveolar lung tumors and 26% of pulmonary adenocarcinomas were found to be positive for JSRV capsid protein, as compared with 0% of squamous cell lung carcinomas and normal lung tissues (De Las Heras et al, 2000).

3. Pig and Pig Endogenous Retrovirus (PERV)

A variety of cancers are known to occur naturally in pigs. Lymphosarcoma for example occurs worldwide, and is the single most common type of cancer, found with an incidence rate typically of between 0.3 and 2.5 per 100,000, although rates as high as 64 per 100,000 have been reported in some areas in France. In the United States and in the United Kingdom, porcine lymphosarcoma has been reported to account for between 23% and 66% of all condemnations for neoplasms in abattoirs (Bostock & Owen, 1973; Hejazi & Danyluk, 2005). A definite etiologic agent has not been established for any of these cancers in pigs, possibly because of inadequate investigation, and infection in humans has also not been adequately studied if at all. However, there have been reports of the presence of C-type particles associated with porcine lymphosarcoma or leukemia that were not antigenically related to the viruses of bovine, murine or feline leukemia (Skavlen et al, 1986; Hayashi et al, 1988). Pigs are naturally infected with the retrovirus known as PERV (pig endogenous retrovirus) and it is worth noting that infectious viral particles are present in the blood of pigs, and in Factor VIII used to treat hemophiliacs (Heneine et al 2001). It was recently shown that human cells can spontaneously fuse with pig cells, and that the hybrid cells contain PERV and are able to transmit this virus to uninfected human cells in vitro (Ogle et al, 2004). It is worthwhile to note that any infection with retroviruses is potentially harmful, as integration into the genome of the recipient (a requirement for infection) would invariably be associated with damage to the recipient’s DNA. This type of information suggests that exposure to animal host cells (such as those of chicken and pig) that naturally carry endogenous retrovirus is tantamount to exposure to the retrovirus as well, thus it will not be unexpected if PERV or the endogenous retrovirus of the ALSV group is later found to be integrated within the human host genome in vivo, and causing disease. The public health impact of this would be immense because of the widespread human exposure to pigs and chickens. Thus the recent finding that all stocks of measles and mumps vaccines in current use in the US are contaminated with endogenous ALSV, portends an ominous prediction if these viruses are confirmed to be capable of infecting humans as evidence so far suggests.

4. Poultry & Avian Leukosis/Sarcoma Viruses (ALSV) and Reticuloendotheliosis Viruses (REV)

Potential human exposure to ALSV and REV may occur principally in four ways: 1) exposure of the general population through contact with, and/or consumption of, chickens and turkeys or their products (including eggs). In one study (Spencer et al, 1976), infectious ALSV were isolated from 45% of commercial eggs that had been previously stored at 8°, for 0 to 6 days, and from 21% of eggs stored for 7 to 34 days; 2) occupational - persons involved in the production, i.e. raising, tending, slaughtering, processing, and preparation of, chickens or their products for food consumption; veterinarians, and laboratory workers; 3) exposure of the general population, from inoculation with vaccines prepared from chicken embryo cells contaminated with these viruses; and 4) potential use of some of these viruses to transport genes into cells, or to activate specific host genes, in future gene therapy.
Human exposure to these viruses is widespread, and may be virtually universal in all populations which consume chicken and eggs or their products. The viruses have been shown to be present in commercial eggs in supermarkets at a prevalence rate of at least 14% (Pham et al 1999a; Pham et al, 1999b), and in otherwise apparently healthy chickens and turkeys destined for human consumption, and their products. In addition, these and related viruses may be present as contaminants in vaccines grown on chicken cells such as measles, mumps and yellow fever vaccines - virtually all the yellow fever vaccines used during World War II were contaminated with ALSV (Waters et al 1972). A recent study by the Centers of Disease Control report that virtually all stocks of measles and mumps vaccine currently in use in the United States are contaminated with the endogenous forms of ALSV (Tsang et al, 1999).
Exposure also occurs occupationally among subjects exposed to poultry such as poultry farmers, poultry breeders, laboratory workers, veterinarians, workers in poultry slaughtering/processing plants, egg handlers, workers who handle raw chickens and turkeys such as cooks, and workers in the meat department of supermarkets.
Experimentally, ALSV and REV can infect and transform human cells in vitro (Stenkvist and Ponten, 1976; Koo et al, 1991; Johnson & Griswold,1997), and ALSV can infect and induce tumors in mammals, including primates, in vivo (see review by Johnson, 1994a). Moreover, recently two studies have reported that poultry workers as well as a high proportion of subjects in the general population with no known occupational exposure to poultry, have antibodies in their blood directed against ALSV, REV and MDV, indicating widespread exposure to these viruses (Johnson et al 1995a; Johnson et al, 1995b; Choudat et al, 1996), although another study did not detect antibodies (Hussain et al, 2001). It is interesting that the possible link between the occurrence of cancers in the general population and transmissible agents originating from animal food would be consistent with the report that dietary sources are the single most important cause of cancer occurrence in humans, possibly accounting for as many as 35% of all cancers in the US (Doll & Peto, 1981).

5. Non-oncogenic Transmissible Agents

The example of emerging non-oncogenic transmissible agents that cause disease in animals also being able to cause severe disease in humans such as neurological diseases is perhaps best illustrated by the prion agent that causes BSE in cattle. This agent is now known to give rise to a new variant of Creutzfeldt-Jakob disease in humans (Belay & Schonberger, 2005). Gibbs et al (1980) demonstrated that kuru, Creutzfekdt-Jakob disease and scrapie can be transmitted orally to non-human primates. Also, the prion protein that causes scrapie in sheep has recently been found to be present in the tongues of infected sheep thus expanding possible modes of transmission other than through primary nervous tissue for these types of agents (Casalone et al, 2005). Furthermore, it has now been demonstrated that infectious scrapie prions can be generated in vitro (Castilla et al, 2005).
In summary, this review has attempted to call attention to the fact that while some risk factors such as red meat, animal fat, or chemical contaminants in meat have been suggested to be causally related to the occurrence of some of the more common chronic diseases that occur in humans such as cancer, diseases of the circulatory and neurological systems, etc., the etiology of at least a proportion of cases of these diseases still remains unknown. It is hypothesized that for some, the cause may originate from transmissible agents present in food animals and their products. It is suggested that the conduct of epidemiologic, serologic and molecular studies that aim to link these agents with the occurrence of human disease in high risk groups such as workers in the meat industry provides the best opportunity of investigating this hypothesis, and that future research efforts should be directed in this area.

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