Assessing and controlling health risks from animal husbandry

NJAS - Wageningen Journal of Life Sciences 66 (2013) 7–14

Contents lists available at SciVerse ScienceDirect

NJAS - Wageningen Journal of Life Sciences journal homepage: www.elsevier.com/locate/njas

Review

Assessing and controlling health risks from animal husbandry Tjeerd Kimman a,∗ , Maarten Hoek a , Mart C.M. de Jong b a b

Central Veterinary Institute, Lelystad, The Netherlands Quantitative Veterinary Epidemiology, Wageningen University Wageningen, The Netherlands

a r t i c l e

i n f o

Article history: Received 28 September 2012 Received in revised form 13 May 2013 Accepted 15 May 2013 Available online 3 July 2013 Keywords: Health risks Animal husbandry Public health Safety Intensive livestock farming Zoonoses Antibiotics

s u m m a r y A fierce debate is going on about the risks of animal husbandry for human health and the quality of control measures to reduce such risks. Risks include the occurrence of infectious diseases, in particular zoonoses, and the high antibiotic use in livestock production contributing to emergence of antibiotic resistance and its spread from animals to humans. On the other hand, many infectious diseases of animals and humans have been eliminated, including brucellosis, tuberculosis, leptospirosis, and BSE, resulting in an animal husbandry that perhaps has never been as safe as nowadays. So while many health risks have been brought under control, the public opinion appears to reflect a feeling of anxiety and mistrust in authorities and producers to deal with the potential and remaining public health risks associated with animal husbandry. These risks, often associated with the intensification of animal production, are nonetheless indeed real. An animal husbandry that is “completely” safe and healthy for humans and animals requires a central role for disease prevention in the design and management of animal husbandry systems. It also requires that rapid and adequate responses are taken by veterinary and medical authorities on both perceived and real risks. Communication on health risks must be complete and open. Because actions to protect the health of animals often also benefit human health, there is usually no conflict of interests between humans and animals regarding their health needs. We emphasize the need to use the precautionary principle in matters of human and animal health. This implies that there must not be a “clash of cultures” between medical and veterinary professionals and policy makers. © 2013 Royal Netherlands Society for Agricultural Sciences. Published by Elsevier B.V. All rights reserved.

Contents 1. 2. 3. 4. 5. 6. 7.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nature of the risks for human and animal health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Risk assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Possibilities for intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Perception, acceptance and communication of risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Guaranteeing safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion and future perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction From time to time severe outbreaks of infectious diseases in animals occur. Sometimes such diseases spread from animals to humans and may impair human health and even cause fatalities. A recent and dramatic example is the Q fever epidemic

∗ Corresponding author. Central Veterinary Institute, P.O. Box 65, 8200 AB Lelystad, The Netherlands. Tel.: +31 3202 38069. E-mail address: [email protected] (T. Kimman).

7 8 9 10 11 12 12 13

from 2007–2010 in the Netherlands during which approximately 10 people died. The epidemic was eventually stopped by massive culling of goats [1]. Other examples include human cases of avian influenza (AI), bovine spongiform encephalopathy (BSE), hemolytic-uremic syndrome (HUS), caused by certain Escherichia coli strains (O157:H7), and “old diseases”, such as trichinellosis, toxoplasmosis, brucellosis, tuberculosis, and leptospirosis [2,3]. These are all zoonoses, infectious diseases that are able to spread from animals to man. Recently many emerging and re-emerging infectious diseases of humans have originated from animals, but the phenomenon is not new. Indeed many of

1573-5214/$ – see front matter © 2013 Royal Netherlands Society for Agricultural Sciences. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.njas.2013.05.003

8

T. Kimman et al. / NJAS - Wageningen Journal of Life Sciences 66 (2013) 7–14

the present-day human pathogens (measles, respiratory syncytial virus) originated from domesticated animals and evolved during their co-evolution with humans [4]. From the 18th till the 20th centuries, increased general hygiene (sewerage), better food production and handling (meat inspection, cooling, pasteurization), specific disease control and eradication programs, and development of vaccines and antibiotics have strongly reduced infectious diseases in humans and animals. Take for example brucellosis and tuberculosis, diseases that can be contracted following the consumption of unpasteurized milk or cheese products made from unpasteurized milk and that may result in a chronic “wasting” illness. These diseases have been largely eliminated by specific test and cull protocols of animals and the pasteurization of milk. Yet, while many infectious diseases, including zoonoses, have been brought under control (not necessarily by eradication), the recent occurrence of serious human cases of zoonotic diseases appeared to have caused strong feelings of anxiety and even mistrust in authorities and producers whose task it is to practice safe animal husbandry and provide safe products of animal origin. More recently the occurrence of infections in humans with resistant bacteria of animal origin, such as Methicillin-Resistant Staphylococcus aureus (MRSA) and bacteria producing Extended Spectrum Beta-lactamases (ESBLs), have fueled new and growing concerns among scientists, public health officials and the general public on the wide use of antibiotics in livestock production that may lead to the emergence of resistant bacteria in animals and their transfer to humans [5,6]. In addition to MRSA and ESBLs, an increasing number of bacteria are becoming resistant against a wide range of antibiotics, for example Enterobacteriaceae and Staphylococci. In addition, other problems have added to create an image–not per se wrong - that there are risks for both human and animal health associated with intensive animal production. These are the occurrence of large outbreaks of–often non zoonotic- epidemic diseases, such as highly pathogenic avian influenza, foot-and-mouth disease, swine vesicular disease, and classical swine fever. These diseases are brought under control by large scale culling of both infected and susceptible animals. In addition, the up scaling and the intensification of animal production has led to the widespread occurrence of so-called “production diseases”, animal pathologies that are linked to intensive production systems and management practices. These may lead to an increase in the occurrence of health risks for both humans and animals. For example, the intensification of production has likely led to an increase in the occurrence of a wide range of diseases, such as coccidiosis, salmonellosis, bacterial and viral respiratory tract diseases, cryptosporidiosis, and mastitis, together resulting in a high use of antibiotics. Factors in intensive animal husbandry that affect the occurrence of infectious disease and its control include population density, animal movements, poor management and hygiene practices, and genetic constitutions that are one-sided directed at economic parameters. Thus while many public and veterinary health risks associated with livestock production have been brought under control and have even been eradicated in some countries, one could call into question whether there is a misconception between the current perception of risks among the general public and the presence of real risks, and whether risks indeed have increased due to the intensification of production processes. Or is it, perhaps, that our society increasingly demands complete elimination of all remaining risks? In this paper we reflect on several aspects concerning the health risks associated with animal production, including their nature, transmission of threats from animals to humans, public awareness and perception, and possible actions that can be taken to safeguard both animal and human health. We especially would like to emphasize two key points. Firstly, there is most often no conflict of interests between humans and animals regarding their

health needs. It is clear that actions which protect the health of animals often also protect human health. Thus actions to promote human health mostly coincide with actions to promote animal heath, and vice versa. Hence there is an absolute interconnectivity (or, in Dutch, “lotsverbondenheid”) between the health of humans and that of animals1 . Secondly, we promote the use of the precautionary principle in matters of human and animal health. This implies that precautionary actions are taken proactively when an activity may raise threats of harm to human or animal health, even if some cause and effect relationships have not been fully established scientifically. 2. Nature of the risks for human and animal health Traditionally health hazards for man and animals are divided in infectious and non-infectious diseases. The daily circumstances in intensive livestock production systems, where many animals, often without pre-existing immunity to specific microorganisms, go through stressful transition moments (weaning, movements, changing microbial environments) and live closely together, clearly facilitate the occurrence, spread, and severity of many infectious diseases. These diseases are often designated as endemic or production diseases. The risk of such diseases may be further increased by unfavourable genetic, nutritional and management factors. Examples include neonatal mortality, weaning diarrhoea, and gut and respiratory disorders caused or facilitated by a range of microbial factors. While the impact on the health and well-being of animals is clear, their risk for human health is usually more indirect, i.e. mainly caused by the extensive use of antibiotics to prevent or treat these disorders resulting in the emergence of resistant bacteria, and transfer of such bacteria or the genetic elements carrying resistance to humans. This may eventually give rise to untreatable infections among humans. While this scenario is now widely recognized to be real and proven, and has resulted in a strong impetus to reduce the use of antibiotics in animal husbandry, it must be emphasized that the relation between animal consumption of antibiotics and occurrence of resistant bacteria among humans is not simple. For example, not using antibiotics will not immediately make the resistant bacteria disappear from the farm [7], and we do not know what extent of use will or will not lead to the development of resistance. Another important sub-category of infectious diseases are the zoonoses. These are common, which is biologically explained by the close genetic and environmental relationship between humans and animals causing that they may share and exchange their pathogens. Indeed the majority of pathogens known to affect humans are zoonotic [8]. This category of diseases is wide, and hence their risks for humans vary widely, from currently very infrequent (tuberculosis) to frequent (campylobacteriosis), and from severe (BSE, Escherichia coli O157:H7, listeriosis) to mild (rotavirus) [9,10]. In the Netherlands the number of confirmed human zoonotic infections is estimated to be at least 1,000 persons/year and estimated to rise due to increased human-animal contacts, tourism, expanding trade, and growing consumption of animals and their products [11]. This number comprises frequent zoonoses as Q fever, toxoplasmosis, toxocariosis, psittacosis and dermatomycoses, but not the very frequently occurring foodborne infections due to Salmonella and Campylobacter spp. Many of these zoonoses originate from animal husbandry: 44% of 86 zoonotic microorganisms identified in the Netherlands occur in farm animals [12].

1 There may be rare exceptions in which the health and wellbeing of animals and humans are not per se in parallel. For instance, the welfare of chickens may be more optimal under free-range conditions, which however increases the risk of introduction of avian influenza virus from wild birds, their mutation towards highly pathogenic strains of AI, and their subsequent transfer to other poultry and humans.

T. Kimman et al. / NJAS - Wageningen Journal of Life Sciences 66 (2013) 7–14

Some infectious animal diseases, such as foot-and-mouth disease, classical swine fever, African swine fever, and avian influenza, have serious consequences for animal health, as well as considerable negative economic impact, and are therefore controlled under national and international regulations. Often these diseases are controlled by the large-scale culling of infected animals and the massive pre-emptive culling of animals at risk of spreading the disease. Due to trade restrictions placed on vaccinated animals and their products, vaccination against such diseases is often not allowed and under strict control of EU regulations. Some of these diseases (avian influenza, Q fever and BSE) are zoonotic, in contrast to foot-and-mouth disease, swine vesicular disease, and classical swine fever. While these diseases are not zoonotic and pose no direct threat to public health, the large-scale culling campaigns may cause stress, fear, disgust and disapproval among the general public. They may also evoke psychological stress among those charged with destroying so many–often healthy–animals, as well as the farmers involved. Depression and even suicide among those involved in this process have been documented [13,14]. Farmers on affected farms may further be anxious about the effects of these dramatic events on their economic future. It is known that livestock farmers and farm employees are at higher risk of contracting some zoonotic diseases than the general public because of their frequent and direct contact with animals. The same is true for veterinarians and slaughterhouse personnel. Concerns are growing, apparently associated with the increasing of herd sizes, whether people living nearby intensive livestock farms are at increased risk of contracting zoonotic diseases. However, at present there are insufficient data available on the risk of contracting zoonotic diseases for residents living in the vicinity of farms [15]. Likewise it is unknown what the influence is of risk factors, such as distance to the farm, the type of farming and the size of the farming enterprise, on the chance of acquiring bird flu, psittacosis, campylobacteriosis, livestock-associated MRSA, and ESBL-producing bacteria. The only disease for which there are strong indications that people living nearby infected farms are at an increased risk of contracting it is Q fever [16]. Also, possible links between the presence of micro-organisms in the surrounding environment of livestock farms and the degree to which zoonotic infections occur in neighbouring residents are unknown. Bacteria resistant to one or more antibiotics may more easily emerge in intensive livestock production systems because they occur in higher frequencies in populations that are characterized by a high antibiotic usage. This will lead to selection of resistance among pathogens. Furthermore, a high density of individuals with close contacts and poor hygienic conditions are circumstances that facilitate the dissemination of resistance traits to different bacteria. Resistant bacteria from animals may reach humans, for example through the consumption of meat, colonize the human gut, and they may then transfer plasmids carrying resistance genes (for example the vanA resistance gene cluster) to the commensal human bacterial microbiome or other pathogenic bacteria. The degree of resistance among the commensal microbiome, such as E. coli, Campylobacter spp., and enterococci, is a good indicator of the selection pressure caused by antibiotics and for resistance among pathogenic bacteria [17]. This is because the commensal microbiome of humans and animals is a reservoir of resistance genes for pathogenic bacteria [18]. The degree of resistance in the commensal microbiome is therefore monitored regularly in many countries, including the Netherlands [19]. A special remark needs to be made about the risk of animal diseases as a source of completely new emerging diseases in humans [20]. These interspecific transmissions from animal to man are difficult to predict and an event for which we have no idea of how to prevent it. An example is the anticipated next pandemic of human influenza. Although we know about transmission to

9

humans of avian and mammalian strains of influenza, we have no idea when and what will trigger the next pandemic of influenza among humans [21,22]. Thus, we conclude that infectious diseases in livestock can have an impact on (1) the general public and those living in the vicinity of farms, which has up to now only clearly been proven to occur for Q-fever, (2) consumers of animal products, which has been shown for many zoonoses such as EHEC, contaminated food, and antibiotic resistance, (3) professionals working in the livestock industry that are at risk for contracting diseases that require close contact with animals, for example avian influenza, MRSA and listeriosis, and (4) the animals themselves, who may suffer and produce less favourably. Finally, there is a range of–often less well–characterized noninfectious hazards that may threaten the health of animals and humans working or living on or nearby farms. Also consumers of animal products may be affected by non-infectious health hazards. This hazard category includes intoxications, for example dioxin, gaseous emissions (such as ammonia), and emissions of small-sized particulate matter (incl. endotoxins) in and around stables. The extent of the public health impact of such hazards is still not yet fully understood and is now subject of many studies and debates. It seems evident however that the negative effects of gaseous emissions are larger for the animals and workers in the farm than for surrounding residents. 3. Risk assessment Risk assessments analyses may help in judging health hazards from the livestock industry and their consequences in an objective and measurable way. Risk assessment may thus be instrumental in pointing the way where to intervene, in allocating funds for control activities, as well as in identifying knowledge gaps to which research activities should be directed. Evidently people tend to be risk adverse with the ultimate aim to avoid harm, and they appear to do so more and more often. The process of a risk assessment comprises of several steps, beginning with identifying and characterizing the hazard, including the specifics of its life cycle. Next steps are an entry assessment (how can the hazard come into contact with an animal or a human, how many different entry pathways exist, and which are the most likely to occur?), an exposure assessment (how frequent and in what quantities does exposure occur?), and a consequence assessment (what is the impact of exposure?). Such assessments result in a risk estimation, which can either be qualitative or quantitative, telling whether the hazard poses a risk for animal or human health and whether or not mitigating or control measures need to be taken. Evidently, risk assessments cannot identify hazards for us, or predict the emergence of yet unidentified hazards. Neither can they tell us how to intervene to mitigate the risk or impact associated with a hazard. It can merely tell us where to intervene and what the goal of the intervention needs to be, e.g. a reduction in Salmonella growth of x-% on chicken breasts during packaging. Neither can risk assessments reduce the variability surrounding a hazard identified. Nature, and all living things, is unpredictable, and no matter how much data were collected and used for the risk assessment, at some point we will always be left with variability in the outcome. The usefulness of risk assessments therefore stands or falls with the correct identification of a hazard, its parameters and collected data, the model build to include the parameters, and the interpretation of the outcomes of the risk assessment. Thus the biggest uncertainty in risk analysis is whether we started off analysing the right thing and in the right way [23]. The final stage, risk communication, is perhaps the most underestimated aspect of a risk assessment (see below). The results need to be presented in an easy understandable way, particularly for those responsible for the implementation of control measures.

10

T. Kimman et al. / NJAS - Wageningen Journal of Life Sciences 66 (2013) 7–14

A good example of the use of risk analysis concerns the Bovine Spongiform Encephalopathy (BSE) epidemic in Europe during the 1980’s, a disease that was until then unknown. This serious disease for cattle was newly detected in the UK in the eighties of the last century [24] had been shown to be zoonotic and cause a quickly progressing and fatal new variant of Creutzfeldt–Jakob disease in humans [25]. Disease eradication proved to be the strategy of choice for BSE in cattle. Results or risk assessments indicated that transmission of BSE occurred through the feed chain: brains of diseased animals ended up (processed) in the extra protein feed that was given to high producing dairy cattle. The risk of contracting the disease after consumption of meat from affected animals was very low, but neither heating nor freezing had little, if any, risk mitigating effect. These studies also helped identifying animals most at risk of having the disease and therefore being able to transmit the disease. Diagnostic methods for live animals were not available and thus all slaughtered animals were tested and diseased animals were kept out of the human food and the cattle feed chain. In combination with other measures, such as keeping all ruminant material out of the ruminant feed chain, this has led to eradication of BSE and new variant of Creutzfeldt–Jakob disease in humans. The example of BSE illustrates that special attention for health risks is needed when major changes in husbandry systems are introduced. Such periods pose a risk for the occurrence of unknown risks or the enhanced expression of previously unknown risk factors. In the case of BSE changes in the handling of cadavers led to the BSE crisis. Another example is the fast and strong expansion of the milk goat husbandry in the Netherlands leading to the largest human Q fever outbreak ever. Another, more recent example is the risk analysis of Schmallenberg virus for humans. The virus had not been detected in Europe before 2011. The virus adversely affects the unborn lambs and calves. A quick risk analysis estimated the risk for humans, and in particular pregnant women, to be negligible. Evidently, a different outcome would have had a major impact on the control measures taken. In the Netherlands risk assessments are primarily used to inform policy makers on the risks and desirability of control measures concerning exotic diseases, such as Rift Valley fever virus, Crimean Congo haemorrhagic fever and West Nile virus, and to assess the risk of re-introduction of highly contagious notifiable diseases such as classical swine fever and foot-and-mouth disease. Some examples are illustrated in Table 1. 4. Possibilities for intervention For interventions in the occurrence of infectious diseases it is important to set a clear goal, to consider beforehand whether or not these goals can be achieved, and to check that these goals are achieved after implementation. The most stringent intervention is that we attempt to eradicate the infectious agent from the animal population. Often this is only possible when there is no wildlife reservoir and it is only considered when the impact of the disease on humans or animals is very severe. Eradication is mostly done in a certain area (e.g. a country) and trade restrictions are used to isolate the free area(s) from infected areas. In the past, eradication of bovine tuberculosis (bTb, caused by Mycobacterium bovis) from cattle in developing countries, including the Netherlands, has been achieved by a test and cull strategy. This implies that infected animals are identified and are then removed from the population before they can infect more than one other animal. For infections with slow dynamics and good diagnostic tools this approach is possible. Whereas bTb may have been the first eradicated disease in farmed animals there have been other diseases where this has been done successfully. For example also Brucella abortus and Leptospira Hardjo have been eradicated from the cattle population in

The Netherlands using this test and cull strategy. Currently, there are increasing problems with countries that fail to progress with bTb eradication due to wildlife reservoirs: badgers in Europe, possums in New Zealand, and elk and deer in North America [26]. In these circumstances additional control measures seem necessary to achieve eradication. As culling wildlife is not popular or feasible, other possibilities are examined such as vaccinating wildlife [27], either with or without vaccinating cattle. Several countries have started programs to reduce other zoonotic bacteria such as certain species and variants of Salmonella spp, Campylobacter spp and Escherichia coli. Often eradication is not mentioned as the target because this target does not seem attainable. The target that is mentioned is risk mitigation for consumers of animal products [28]. This is achieved by detecting elevated levels of these bacteria and excluding farms or production groups with higher levels of infection from the food production chain. Vaccination is another possibility to eradicate infectious diseases in animals. If effective vaccines are available, they can be used to stop outbreaks of animal diseases. This is the case for classical swine fever virus [29,30], foot-and-mouth disease virus [31–34], or highly pathogenic avian influenza virus [35]. Also for endemic diseases vaccination has been used in combination with other control measures to eradicate them. The prominent examples for where it has succeeded are pseudorabies virus (PRV or Aujeszky’s disease virus) in the Netherlands [36,37], and rinderpest worldwide [38]. After a recent introduction of blue tongue virus type 8 in North West Europe it is attempted to control this epidemic by vaccination also. Vaccination of goats against Q fever has also been used, not with the target of eradication, but to prevent abortions and therewith largescale shedding during lambing in order to prevent transmission to humans. For animal diseases that are a public health threat vaccination tends to be viewed with suspicion as it might be that vaccination only reduces clinical symptoms (which otherwise might be a justified goal of using vaccines), but does not stop transmission of the pathogen. Furthermore vaccination may interfere with possibilities to diagnose the infection. Therefore, vaccines nowadays are mostly developed together with a diagnostic test that can detect infection in vaccinated animals [39]. In the example of PRV we were able to show that even when virus replication is not completely stopped in individual hosts we can quantify transmission [36] and are able to eradicate the virus from a country using these vaccines. Mathematical modelling has been a useful tool in this process because progress in the field could be compared to the expected progress calculated by extrapolating results from transmission experiments and field observations. However, up to now eradication by vaccination has not been attempted for diseases that pose a public health treat. As mentioned above in the case of bTb, vaccination of cattle may be necessary to maintain a bTb free status in cattle in the face of bTb infection in wildlife. Antibiotic treatment, either of the whole population or of the infected animals, could be a possibility to deal with zoonotic infectious agents. However, this is not a preferred option because of the development of antibiotic resistance. Also it seems rational to reserve those antibiotics that work in humans for humans and not to use them in animals. From a theoretical point of view it can be said that any set of measures that effectively controls an infectious agent will also preclude the development of resistance against these control measures. Development of vaccine escape, i.e. resistance against vaccination, will only occur when transmission occurs in spite of vaccination. This could be the case when the vaccination misses part of the population or when vaccination is suboptimal in some animals only, for example because of quality issues, e.g. a not properly maintained cold-chain. The same principle may apply to antibiotics. Use of antibiotics should be restricted as much as possible because it always, but in particular when application is

T. Kimman et al. / NJAS - Wageningen Journal of Life Sciences 66 (2013) 7–14

11

Table 1 Examples in which risk-analysis has contributed to the protection of animal and human health. Hazard identified

Potential consequences

Risk assessment

Measures taken

Q-fever

Serious illness in humans

Medium risk

Antibiotic (multi-) resistance Bacterial foodborne diseases (salmonellosis, campylobacteriosis, listeriosis) Products from vaccinated animals, vaccinated against a former OIE list A disease, for example classical swine fever Rift Valley fever, a mosquito borne zoonosis.

Emergence of untreatable illnesses Mild to serious illness in humans

High risk Variable risk

Vaccination, testing and culling of affected animals Antibiotic reduction strategy Various control strategies

Spread of disease due to trade in animals with subclinical wild virus infections

Negligible risk

Discussion on implementing emergency vaccination instead of culling

Serious illness in farm animals and humans

Low risk (for the Netherlands)

Serious illness in humans

Low risk (for the Netherlands)

Mosquito surveillance in the Netherlands, control of identified imported exotic mosquitos Tick surveillance in the Netherlands

Serious illness in humans

High risk through international air-travel

Fumigation of aircrafts, uptake of prophylactic medication by travellers

Crimean Congo haemorrhagic fever, a tick borne zoonosis Malaria

suboptimal (for example low dosages), may result in development of antibiotic resistance. In humans it cannot be avoided to apply antibiotics that eventually do not work, as everything possible will be attempted to help the patient. In farm animals antibiotic use should be avoided as much as possible, especially whenever it is not fully effective, as eventually we are better off when only effective control measures are applied and resistance development is avoided.

•

5. Perception, acceptance and communication of risks The actual number of fatal human cases due to, for example BSE and avian influenza, is very limited. However, the financial and logistic efforts to combat these and other notifiable diseases have been very high in for example The Netherlands and the UK. The economic damage due to the Dutch avian influenza epidemic in 2003 was excessive. A total of 255 infected poultry herds were culled, and 1,255 commercial and 17,000 hobby farms were culled as a prevention measure. Together 31 million chickens, ducks and turkeys were killed. The economic losses were estimated to approximate hundreds of millions of euros. Evidently such disease outbreaks cause considerable public concern. In contrast, the public’s concerns on the risks associated with common foodborne infections, such as salmonellosis and campylobacteriosis, appear somewhat less prominent. However, such diseases cause a considerable and regular number of human infections and fatalities. In the Netherlands the number of fatal cases of salmonellosis and campylobacteriosis amounts to an estimated number of 80-90 persons per year [9,10,40]. In the absence of systematic research on the perceptions of citizens on the risks associated with living in the vicinity of farms or consuming animal products, such anecdotal observations may evoke some thoughts on the perception of public health threats originating from animal husbandry. • It appears that there are discrepancies between the real risks associated with animal husbandry and their perception in the public opinion. Emerging and re-emerging infectious diseases of animals appear to frighten the public. Citizens no longer want to accept the threat of infectious diseases, in particular when TV broadcasts show images of the large scale culling of animals. Such TV broadcasts appear to frighten and anger people, even when there is no immediate public health risk or when healthy animals are killed for prevention because vaccination is not allowed. Thus media appear to magnify emotions. • For experts the perception and acceptance of risks by the general public does not always appear logical. Perhaps the nearness

•

•

•

or unfamiliarity with events (‘fear of the unknown’), play critical roles in the public’s perception and acceptance of risks. Also risks that are out of self-control appear to be valued stronger and more negative and hence less accepted (e.g. compare airplane travel and car travel). Likely, the acceptance of livestock-associated health risks may be related to the appreciation of livestock farming. Nowadays citizens, consumers of animal products, and neighbours of farms simply demand that they do not become ill of farms in their vicinity, that their health is not adversely affected following the consumption of products from animal origin or from the way in which they are produced. In earlier times infectious diseases originating from animals may have been regarded as normal “facts-of-life”. Nowadays the public appears to accept fewer of such risks than before, demands quick and drastic measures to control and prevent real and perceived threats, and wants to identify and blame culprits. Foremost the public demands complete and open communication [41,42]. So demands are shifting and contextual. For example, the culling of goats for Q fever control appeared better accepted in the public’s opinion (because it constituted a real public health threat) than the culling of swine to control an outbreak of classical swine fever (no danger for man). The attitude towards livestock-associated risks may differ between persons (including veterinary experts) working in livestock industry or elsewhere, for example in public health. Perhaps–according to contemporary demands - the attitude towards risks associated with livestock production is sometimes even somewhat too lax or too little among professionals working in the livestock industry. For example, veterinary experts and authorities involved in the control of the Dutch Q fever outbreak who were inclined to support farmers, appeared to respond somewhat slower and less adequate than public health experts [42]. Otherwise, veterinarians may have more knowledge on zoonoses than medical professionals. These observations may point to a “clash of cultures” between those who approach these matters from the animal production or the public health perspective [42,43]. If true, this demands actions to be taken to improve the conscientiousness and attitude of those working in the livestock industry regarding public health risks, as well as knowledge on zoonoses among medical professionals. Government authorities and producers can no longer rely on blind faith from a more and more critical public in these matters. Society demands that both structural public health threats and calamities are managed adequately and that communication in these matters is open and fair. The public also wants to be included in discussions on intensive livestock production and

12

T. Kimman et al. / NJAS - Wageningen Journal of Life Sciences 66 (2013) 7–14

their associated risks. Without doubt, knowledge on factual risks and the public’s perception of risks may help enabling a balanced discussion on the risks associated with animal production in relation to other public health risks. Clearly there are uncertainties regarding both infectious diseases and the public’s opinion about their risks. Evidently communication should be clear on aspects where knowledge of risks is still insufficient, take for example the unknown burden of disease of animal hepatitis E infections and its zoonotic risk, or the threat of antibiotic resistance in humans due to antibiotic use in animals. Producers, experts and authorities have to take these concerns seriously. Thus, both experts and the public need sufficient and objective knowledge to be able to assess the health risks of livestock production. 6. Guaranteeing safety A frequently expressed wish from consumers and producers of animal products is “guaranteed safe”. Although safety can never be guaranteed completely due to failures or the inherent variability associated in everything and anything alive, producers can strive to attain maximal safety by reducing the probability of unacceptable risks occurring. Therefore consensus is needed on the risks that are considered unacceptable, what costs we are willing to make in order to reduce these risks, and what responsibility consumers are willing to take in order to further reduce the risks associated with the preparation and consumption of animal products. To reduce the risk to health to currently acceptable levels, producing, processing and storing protocols have been made for all foodstuffs. An example of this is the development of HACCP. This stands for Hazard Analysis and Critical Control Points. Common interventions at critical control points include freezing, cooling, heat treatment, chemical treatment and radiation treatment of spices. It is clear, however, that in animal production safety protocols must not be restricted to the later stages of animal production (when the animals have been slaughtered or milk collected), but must be operative in the whole production chain (thus “from seed to feed”). One way to establish public trust and a means to assure the health of animals on farms and the safety of their products is by certification programs. However, at present, consumers in supermarkets are confronted with a proliferating array of certification programs and quality marks. Each has their own aims and characteristics, but they are often aimed at demonstrating animal welfare and environmentally responsible production. We consider this plethora of certificates undesirable, and pledge for one single certification program for products of animal origin, like the certification program of the Marine Stewardship Council [44] for fish, to recognise and reward sustainable farming. Such a single program may promote the best choices regarding the protection of human and animal health, animal welfare and environmental protection. Such a program may also be invaluable in promoting a responsible attitude towards public health issues among workers in the livestock production sectors. In the establishment of such a program, dilemmas between several aspects may arise and have to be resolved. Willingness to compromise is necessary here. Whatever choices in establishing such a program are made, the minimum requirement is that both the way of producing and the product itself are safe for public health according to current standards. Preferably such a certification program should be available on an European or even global level. 7. Discussion and future perspectives Responsibility for safeguarding health of humans and animals from the risks associated with animal husbandry lies obviously

with a variety of actors, especially with the producers in the whole production chain, as well as with government and the state run veterinary services. However, consumers also have their responsibilities. They need to get accurate information on the safety of animal husbandry and its products, including information about safe product handling and consumption habits. Finally, the media need to be helpful in reporting accurately and informatively. Transmission of pathogens from animals to man and vice versa, and the transmission of genetic elements (carrying resistance or virulence between pathogens) is a fact of life. This applies to all animals and their pathogens, i.e. wild animals and pets also, and not only to farmed animals [20]. Such exchange events therewith pose a natural risk for humans living and working on farms or in the vicinity of farms, for consumers of products of animal origin, and the human population in general. However, circumstances in modern livestock production practices may favour such events, and they should thus be controlled. The intensification of animal husbandry and the close contacts between humans and farmed animals and their products warrant special attention to the safety of farm animal production. Very many of such public health threats have already been brought under control in most developed countries, for example anthrax, tuberculosis, listeriosis, brucellosis, BSE, etc. [3]. Therewith one could say that livestock production nowadays is “safer than ever”. Nonetheless, intensification of production, associated “production diseases”, high use of antibiotics, emergence of antibiotic resistance, new and re-emerging diseases and zoonoses (Q fever), and remaining old problems such as foodborne infections (salmonellosis, campylobacteriosis) are strong incentives to strive towards an animal production sector that is both “safe and healthy” for man and animals. Public trust in animal production is clearly needed to assure its “license–to-produce”, particularly in a densely populated country. This will be challenging to achieve because people appear to accept fewer and fewer risks while their perception of risks is subject to strong emotions. As mentioned, we strongly like to argue that the interconnectivity between the health of humans and that of animals excludes contrasting views regarding health issues or a clash of cultures between veterinary and medical professionals and policy makers. In matters where human health is at stake, we consider that the right attitude towards livestock-associated risks demands the precautionary principle, which implies that there is a social responsibility to protect the public from exposure to harm when scientific investigation has found a plausible risk. Following this principle we need to take, for example, action to control livestock-associated MRSA infections. Not because we know all the risks, their magnitudes and modes of action associated with this infection, but because the presumed risks are real and the circumstances in livestock production may favour the emergence of similar and more resistant bacteria. Thus, in order to restore public confidence in the safety of livestock production and to safeguard its “license-toproduce” we are obliged to take the safe side. The role and position of the primary producers justifies special attention. Their position in providing a safe animal husbandry producing safe products in a clean environment is both central and precarious because of their economic risks. Society’s demands on primary producers needs to be supported with an earnest income and other means of support, for example a system of “blame-free” reporting of diseases. Criteria and standards, for example used in a certification program aimed at safeguarding human health, need to be clear and unambiguous. However, such criteria and standards are subject to discussion and dynamic change. Not only pathogens evolve, but also animal husbandry systems (more or less favouring pathogens and certain risk factors), the public’s perceptions and demands regarding risks, and the scientific knowledge regarding health risks and their control strategies. Furthermore, on many aspects more

T. Kimman et al. / NJAS - Wageningen Journal of Life Sciences 66 (2013) 7–14

knowledge is needed, for example on the human health risks of certain pathogens (hepatitis E virus, toxoplasmosis, Chlamydia infections), on the transmission routes of resistant bacteria and the genetic elements carrying resistance from animals to man, on the design of safe husbandry systems, on the role of genetic and nutritional factors in promoting animal health, on vaccine development, etc. [6]. We propose to develop livestock production systems that are intrinsically designed to limit the occurrence and severity of infectious diseases, the transfer of pathogens from animals to man, and the need to use antibiotics. This requires not only crisis management of acute disease outbreaks, but also design of “disease-free” systems with genetically resistant animals, systematic prevention of production-associated diseases, and adequate early warning systems. Risk assessment studies may help to identify, characterize and quantify livestock-associated health hazards and factors favouring their occurrence, and so help identifying ways for preventing them. A more widespread design and use of systems aimed at preventing the occurrence and severity of diseases, such as specificpathogen-free (SPF) or minimal disease systems, may be a good approach to reach many of these goals [45,46]. Furthermore, these systems may also have a favourable impact on feed conversion, the carbon footprint and economic results of farms. In addition to eliminating specific pathogens, disease-preventive measures and systems need to be further developed. These may comprise of, for example, systematic vaccination schedules, timely and adequate medical treatments (also aimed at prevention of pathogen transmission and emergence of resistance), good housing, a high level of biosecurity, adequate feeding and clean drinking water, animal transport and contact structures aimed at reducing pathogen transmission, adequate management of transition moments (such as weaning), breeding for disease-resistance, etc. Evidently, proof of effectiveness of such measures needs to be delivered, which may not always be easy and may require new research [47–49]. Thus, all measures aimed at disease reduction should, as much as possible, be cost-effective and “evidence-based”. In conclusion, improving animal health goes hand in hand with improving human health. Conscientious managing animal health in modern, intensive livestock farming will give the animal all essential care it requires. Eventually this will benefit the public’s health and its confidence in livestock production. References [1] H.J. Roest, J.J. Tilburg, W. van der Hoek, P. Vellema, F.G. van Zijderveld, C.H. Klaassen, D. Raoult, The Q fever epidemic in The Netherlands: history, onset, response and reflection, Epidemiol. Infect. 139 (2011) 1–12. [2] D.J. Alexander, Avian influenza viruses and human health, Dev. Biol. (Basel) 124 (2006) 77–84. [3] P. Verhoef (Ed.), Strenge wetenschappelijkheid en practische zin. Een eeuw Nederlands Centraal Veterinair Instituut 1904-2005, Erasmus Publishing, Rotterdam, 2005. [4] J. Pearce-Duvet, The origin of human pathogens: evaluating the role of agriculture and domestic animals in the evolution of human disease, Biological Reviews 81 (2006) 369–382. [5] I. van Loo, X. Huijsdens, E. Tiemersma, A. de Neeling, N. van de Sande-Bruinsma, D. Beaujean, A. Voss, J. Kluytmans, Emergence of methicillin-resistant Staphylococcus aureus of animal origin in humans, Emerg. Infect. Dis. 12 (2007) 1834–1839. [6] White paper on research enabling an antibiotic-free animal husbandry, Editor: T.G. Kimman, Lelystad (2010) (http://www.cvi.wur.nl/NR/rdonlyres/ E8288614-D024-41BE-928D-2AD7503DB42F/108061/Whitepaper.pdf). [7] E.M. Broens, E.A.M. Graat, A.W. van de Giessen, M.J. Broekhuizen-Stins, M.C.M. de Jong, Quantification of transmission of livestock-associated methicillin resistant Staphylococcus aureus in pigs, Vet. Microbiol. 155 (2012) 381–388. [8] L.H. Taylor, S.M. Latham, M.E.J. Woolhouse, Risk factors for human disease emergence, Philosophical Transactions of the Royal Society B 356 (2001) 983–989. [9] W. van Pelt, W.J.B. Wannet, A.W. van de Giessen, D.J. Mevius, M.P.G. Koopmans, Y.T.H.P. van Duynhoven, Trends in gastro-enteritis van 1996 tot en met 2004, Infectieziekten Bulletin 16 (2005) 250–256.

13

[10] W. van Pelt, M.A.H., Braks, B., Schimmer, O.F.J., Stenvers, M.F.M. Langelaar, Staat van zoönosen, 2007-2008, RIVM rapport 330131001, Bilthoven (2009). [11] H.E. de Melker, M.A.E. Conyn-van Spaendonck, M.J.W. Sprenger, Infectieziekten in Nederland: Epidemiologie, diagnostiek en bestrijding, Bilthoven, Rijksinstituut voor Volksgezondheid en Milieu (1997). [12] Emzoo report: Emerging zoonoses: early warning and surveillance in the Netherlands. Editors: Van der Giessen, JWB, van de Giessen, AW, Braks, MAH. RIVM-report 330214002, Bilthoven (2010). [13] A. Bosman, Y.M., Mulder, J.R.J. de Leeuw, A., Meijer, M. Du Ry van Beest Holle, P.A., Kamst, P.G. van der Velden, M.A.E. Conyn-van Spaendonck, M.P.G., Koopmans, M.W.M.M., Ruijten, Vogelpest Epidemie 2003: Gevolgen voor de volksgezondheid, RIVM report 630940001 (2004). [14] D.F. Peck, Foot and mouth outbreak: lessons for mental health services, Advances in Psychiatric Treatment 11 (2005) 270–276. [15] Gezondheidsrisico’s rond veehouderijen. Report, Gezondheidraad, The Hague (2012), http://www.gezondheidsraad.nl/sites/default/files/201227 Gezondheidsrisicoveehouderijen.pdf [16] C.B.M. Maassen, E. van Duijkeren, Y.T.H.P. van Duynhoven, A., Dusseldorp, P., Geenen, A.A. de Koeijer, M.P.G., Koopmans, F., Loos, W.F. Jacobs-Reitsma, R. de Jonge, A.W. van de Giessen, Risk of infections from livestock farming for people living nearby, RIVM Report 609400004 (2012). [17] S.C. Leste, M. del Pilar Pla, F. Wang, I. Perez Schael, H. Jiang, T.F. O‘Brien, The carriage of Escherichia coli resistant to antimicrobial agents by healthy children in Boston, in Caracas, Venezuela, and in Qin Pu, China, N. Engl. J. Med. 323 (1990) 285–289. [18] A.E. van den Bogaard, Volksgezondheidsrisico’s door antibioticumgebruik in de veehouderij, Geneesmiddelenbulletin 35 (2001) 83–88. [19] MARAN 2012/NETHMAP 2012. Consumption of antimicrobial agents and antimicrobial resistance among medically important bacteria in the Netherlands. Monitoring of antimicrobial resistance and antibiotic usage in the Netherlands (2013). [20] K.E. Jones, N.G. Patel, M.A. Levy, A. Storeygard, D. Balk, J.L. Gittleman, P. Daszak, Global trends in emerging infectious diseases, Nature 451 (2008) 990–994. [21] S. Herfst, E.J.A. Schrauwen, M. Linster, S. Chutinimitkul, E. de Wit, V.J. Munster, E.M. Sorrell, T.M. Bestebroer, D.F. Burke, D.J. Smith, G.F. Rimmelzwaan, A. Osterhaus, R.A.M. Fouchier, Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets, Science 336 (2012) 1534–1541. [22] C.A. Russell, J.M. Fonville, A.E.X. Brown, D.F. Burke, D.L. Smith, S.L. James, S. Herfst, S. van Boheemen, M. Linster, E.J. Schrauwen, L. Katzelnick, A. Mosterin, T. Kuiken, E. Maher, G. Neumann, A. Osterhaus, Y. Kawaoka, R.A.M. Fouchier, D.J. Smith, The potential for respiratory droplet-transmissible A/H5N1 Influenza Virus to evolve in a mammalian host, Science 336 (2012) 1541–1547. [23] C. Vose, Risk Analysis A Quantitative Guide, 2nd edition, (2000) ISBN: -13: 9780471997658. [24] J.W. Wilesmith, J.B.M. Ryan, M.J. Atkinson, Bovine spongiform encephalopathy - epidemiologic studies on the origin, Vet. Rec. 128 (1991) 199–203. [25] R.G. Will, J.W. Ironside, M. Zeidler, S.N. Cousens, K. Estibeiro, A. Alperovitch, S. Poser, M. Pocchiari, A. Hofman, P.G. Smith, A new variant of Creutzfeldt-Jakob disease in the UK, Lancet 347 (1996) 921–925. [26] A. Gortazar, R.J. Delahay, R.A. McDonald, M. Boadella, G.J. Wilson, D. GavierWiden, P. Acevedo, The status of tuberculosis in European wild mammals, Mammal. Review 42 (2012) 193–206. [27] I. Aznar, G. McGrath, D. Murphy, L.A.L. Corner, E. Gormley, K. Frankena, S.J. More, W. Martin, J. O‘Keeffe, M.C.M. de Jong, Trial design to estimate the effect of vaccination on tuberculosis incidence in badgers, Vet. Microbiol 151 (2011) 104–111. [28] L. Alban, F.M. Baptista, V. Mogelmose, L.L. Sorensen, H. Christensen, S. Aabo, J. Dahl, Salmonella surveillance and control for finisher pigs and pork in Denmark - A case study, Food Research International 45 (2012) 656–665. [29] J. Dortmans, W.L.A. Loeffen, K. Weerdmeester, W.H.M. van der Poel, M.G.M. de Bruin, Efficacy of intradermally administrated E2 subunit vaccines in reducing horizontal transmission of classical swine fever virus, Vaccine 26 (2008) 1235–1242. [30] C. Klinkenberg, R.J.M. Moormann, A.J. de Smit, A. Bouma, M.C.M. de Jong, Influence of maternal antibodies on efficacy of a subunit vaccine: transmission of classical swine fever virus between pigs vaccinated at 2 weeks of age, Vaccine 20 (2002) 3005–3013. [31] T.J. Hagenaars, A. Dekker, M.C.M. de Jong, P.L. Eblé, Estimation of foot and mouth disease transmission parameters, using outbreak data and transmission experiments, Revue Scientifique et Technique-Office International Des Epizooties 30 (2011) 467–481. [32] K. Orsel, A. Dekker, A. Bouma, J.A. Stegeman, M.C.M. de Jong, Vaccination against foot and mouth disease reduces virus transmission in groups of calves, Vaccine 23 (2005) 4887–4894. [33] K. Orsel, M.C.M. de Jong, A. Bouma, J.A. Stegeman, A. Dekker, Foot and mouth disease virus transmission among vaccinated pigs after exposure to virus shedding pigs, Vaccine 25 (2007) 6381–6391. [34] K. Orsel, A. Dekker, A. Bouma, J.A. Stegeman, M.C.M. de Jong, Quantification of foot and mouth disease virus excretion and transmission within groups of lambs with and without vaccination, Vaccine 25 (2007) 2673–2679. [35] J.A. van der Goot, G. Koch, M.C.M. de Jong, M. van Boven, Quantification of the effect of vaccination on transmission of avian influenza (H7N7) in chickens, Proceedings of the National Academy of Sciences of the United States of America 102 (2005) 18141–18151. [36] M.C.M. de Jong, T.G. Kimman, Experimental quantification of vaccine-induced reduction in virus transmission, Vaccine 12 (1994) 761–766.

14

T. Kimman et al. / NJAS - Wageningen Journal of Life Sciences 66 (2013) 7–14

[37] A. van Nes, M.C.M. de Jong, J. Buijtels, J.H.M. Verheijden, Implications derived from a mathematical model for eradication of pseudorabies virus, Prev. Vet. Medic. 33 (1998) 39–58. [38] J. Anderson, M. Baron, A. Cameron, R. Kock, B. Jones, D. Pfeiffer, J. Mariner, D. McKeever, C. Oura, P. Roeder, P. Rossiter, W. Taylor, Rinderpest eradicated; what next, Veterinary Record 169 (2011) 10–11. [39] J.T. van Oirschot, Diva vaccines that reduce virus transmission, J. Biotech. 73 (1999) 195–205. [40] A.H. Havelaar, J.A. Haagsma, M.J. Mangen, J.M. Kemmeren, L.P. Verhoef, S.M. Vijgen, M. Wilson, I.H. Friesema, L.M. Kortbeek, Y.T. van Duynhoven, W. van Pelt, Disease burden of foodborne pathogens in the Netherlands 2009, Int. J. Food Microbiol. 156 (2012) 231–238. [41] Rampensite.nl (http://rampensite.nl/). [42] Evaluatiecommissie Q koorts, Van verwerping tot verheffing. Q-koorts beleid in Nederland 2005–2010, (2011). [43] M.J. Poen, De GGD, die is toch voor mensen? Tijdschr, Diergeneesk. 137 (2012) 474–475. [44] M.J. Kaiser, G. Edwards-Jones, The role of ecolabeling in fisheries management and conservation, Conserv. Biol. 20 (2006) 392–398.

[45] J. Benschop, M.A. Stevenson, J. Dahl, N.P. French, Towards incorporating spatial risk analysis for Salmonella sero-positivity into the Danish swine surveillance programme, Prev. Vet. Med. 83 (2008) 347–359. [46] A. Boklund, L. Alban, S. Mortensen, H. Houe, Biosecurity in 116 Danish fattening swineherds: descriptive results and factor analysis, Prev. Vet. Med. 66 (2004) 49–62. [47] G.K. Hybschmann, A.K. Ersbøll, H. Vigre, N.P. Baadsgaard, H. Houe, Herd-level risk factors for antimicrobial demanding gastrointestinal diseases in Danish herds with finisher pigs: A register-based study, Prev. Vet. Med. 98 (2011) 190–197. [48] G. van Schaik, Y.H. Schukken, M. Nielen, A.A. Dijkhuizen, H.W. Barkema, G. Benedictus, Probability of and risk factors for introduction of infectious diseases into Dutch SPF dairy farms: a cohort study, Prev. Vet. Med. 54 (2002) 279–289. [49] Q. Zhuang, K. Barfod, H. Wachmann, S. Mortensen, D.T. Lavritsen, B. Ydesen, P. Willeberg, Risk factors for Actinobacillus pleuropneumoniae serotype 2 infection in Danish genetic specific pathogen-free pig herds, Vet. Rec. 160 (2007) 258–262.