Koi Herpes Virus (KHV) under suitable environmental conditions results in heavy mortalities of populations of Koi and carp (Cyprinus Carpio). Koi are traded on a continuous basis in the worldwide ornamental fish market and the common carp is an important protein source, especially in many developing countries. During the last decade KHV has spread rapidly throughout the world and has resulted in significant economic losses to the carp and 0rnamental fish industries in some countries. KHV outbreaks have been documented in Israel since 1998. Production of carp and Koi on farms throughout Israel were considerably reduced during the initial surge of disease, with massive fish kills. Three active approaches to the restoration of economic production were implemented by Israeli fish farmers, all claiming to assist in the containment and eradication of KHV.
1. Initially, farms in Israel performed natural immunisation (NIS) of the carp and koi as a solution to viable production.
2. A vaccine has recently been developed and is used in some koi and carp producing farms in Israel.
3. Certain farms in Israel destroyed all infected or compromised stock and continue production in indoor or outdoor virus free, Biosecure facilities.
This paper will present the case for Biosecure production and stocking of virally uncompromised carp on farms and facilities around the world, in the context of a strategy of worldwide eradication and containment of KHV as well as future pathogenic threats.
It is estimated that by the end of 2008, about 15% of Israel''s Koi exports will originate from biosecure facilities where the fish are never exposed to the virus. The rest will come from facilities that vaccinate their Koi. The percentage of virally uncompromised Koi exported from Israeli Koi suppliers by the end of 2009 is expected to increase to about 40%, as existing facilities are expanded and new ones built.
Most members of the Koi and Carp industry in Israel, including this author, are aware of and have a high regard for the achievements of those involved in saving and resurrecting the carp industry in Israel which faced extinction in the early years of the virus. It is important that a safe vaccine for KHV be developed as an integral tool in the effort for global eradication of the virus, and as a protective measure for the continued existence of the trade by helping containment in the event of localised breakdowns in bio-security.
This paper is not a scientific and/or empirically based manuscript. Much of it is based on the lessons learned from the production of Koi Carp in Israel. The paper will also quote from existing research and documentation of the use of vaccines in animal disease eradication and containment and it will present the view that worldwide containment, eradication and prevention of KHV cannot be carried out using only vaccination, but necessitates the production and distribution of carp that have not been virally compromised. Eradication and prevention of diseases and security against the eventuality of new pathogens is not possible without the encouragement and gradual implementation of biosecurity in all parts of our industry, but especially in production, on a world wide scale.
Dealing with KHV as a Global Threat
KHV threatens not only the livelihood of a large number of Koi producers, dealers and hobbyists. It also threatens the angling community, which, in many countries is far larger than the number of Koi Hobbyists. However, the overriding concern of responsible authorities around the world is the fact that the common carp is the third most important farmed freshwater fish species in the world (FAO World aquaculture production statistics for 2005) and fish are the major protein source of many communities worldwide. FAO statistics on world aquaculture for 2006 show that aquaculture provides about half of the total fish consumption of humanity. Fish provide 2.6 billion people with more than 20% of their total protein diet. The stakes are much higher than an ornamental or angling hobby for the wealthy of our planet.
Measures for the prevention and/or eradication of KHV that are recommended or enforced by authorities must therefore take all the above facts into account. In order for them to be effective and enforceable, measures must lend themselves to methods and means available to carp producers in both developed as well as developing countries. They should not only be easily available to and applicable by farmers, exporters, importers, wholesalers and retailers, but should also be enforceable in practice by local authorities from the UK to China, from Israel to Bangladesh and from the USA to Vietnam.
At the time of writing there is no evidence indicating that worldwide Carp production is directly endangered by KHV. Most of the reported incidences of KHV have been in the ornamental fish industry – in Koi farms, trade facilities or private ponds - where containment and prevention of further contamination can be relatively easily achieved. There have also been a few reports of KHV in natural waters in some parts of the world but this has usually only affected the angling community. Almost all the Carp produced for human consumption is grown on farms and in aquaculture facilities, few of which, to date, have been affected by KHV. (Israel is one exception to this and the Israeli Carp industry was severely damaged by the spread of KHV). However, steps need to be taken to ensure that the situation regarding this important food source remains unchanged, and that Carp farms around the world remain, as far as possible, uncompromised.
The fundamental premise for a worldwide effort in the prevention and control of any disease is the ability to impose restrictions and regulatory measures that are viable and that can be implemented with relative ease and low cost around the globe. In the case of the carp, this includes food carp producers as well as growers, importers, distributors, retailers and consumers in the ornamental trade. These measures should be applicable and feasible not only in countries or areas like the US, the EU and Israel but also in developing countries with lower standards of living, meagre national budgets and very different national priorities.
A few facts about KHV
1. To date, at least three known strains of KHV exist, each with differing symptoms and differing rates and percentages of mortality. The number of variants is most likely much higher. (Takashi Aoki et al, 2007)
2. KHV is highly contagious and can result in high (over 80%) mortality in diseased populations of Koi and common carp (A. Dishon et al., 2005)
3. Neither the "immunisation" process nor the present vaccine that is used in Israel has categorically been proven to be effective for all three strains of KHV.
4. There is to date, no definitive test that proves whether a fish is an active carrier of KHV.
5. The virus can remain persistent and dormant in the organs of the host, without any expression of viral pathology for long periods of time. (A. Dishon et al. 2005)
6. Survivors of KHV are potential carriers of KHV. (S. St-Hilaire et al, 2005)
7. Recent research has shown the presence of asymptomatic KHV in goldfish and other aquatic species, leading to conjecture that these may also be hosts and/or carriers of KHV. (J. Sadler et al, 2008, M. El-Matbouli et al, 2007, Kirsten Meyer, 2007).
Past and present use of vaccines in disease eradication
Vaccination is without doubt the single most useful measure available to prevent infectious diseases, and numerous examples of successful vaccines exist. However, in every single case there were other extremely important factors which contributed to this success. The most successful case of virus eradication in history is that of the smallpox virus. This campaign was effective because the variola virus (i) produced acute illness in humans, (ii) had no carrier stage or unmanageable non-human reservoirs, and (iii) sensitive and specific tools were available for diagnosis and surveillance. In addition, an effective vaccine was available and could be used in combination with political commitment, international surveillance and public education. (Annals of the New York Academy of Sciences 894:83-91 (1999) The Cost of Disease Eradication: Smallpox and Bovine Tuberculosis A. M. Nelson. Considerations for Viral Disease Eradication: Lessons Learned and Future Struggles. Washington, DC: National Academies Press; 2002)
There seems to be apparently increasing disagreement in medical and scientific circles regarding the negative, long term side effects of vaccines and their ability to completely eradicate a pathogen. Notwithstanding this controversy, the principle generally accepted is that the use of a vaccine is not the only ingredient for disease eradication. The contrary is true: while it reduces the prevalence/incidence of outbreaks, a vaccine usually guarantees the persistence of the pathogen and its associated disease. In almost every scenario of disease prevention or eradication, a vaccine is only one of a number of measures put in place. Other measures usually include sanitation and, in the case of animal diseases, stamping out. (Killing off all infected or potentially infected animals). Often, the vaccine is only a part of an eradication program as in the case of Bovine Tuberculosis. (Recommendation by UK House of Commons Environment, Food and Rural Affairs Committee - Bovine TB . Government reply to Committee''s report – 17th Special Report – October 2004). In some cases a vaccine could hinder eradication programs, as in the case of Hog Cholera Virus (Agricultural Research Magazine, USA, March 1978).
A survey of literature available on the subject shows that for most animal diseases, programmes are implemented combining stamping out, biosecurity and restriction of movement. In some of these programmes, for example, Brucellosis, where the vaccine allowed tracking of infection among vaccinated animals, vaccination was permitted in specific areas and for a defined period of time. (W.H.O. website: http://www.who.int/zoonoses/diseases/brucellosis/en/). In other instances, for example, FMD or Bovine Tuberculosis, the use of a vaccine was prohibited or partly prohibited. In cases where the use of certain vaccines is allowed for a limited time the reason is usually an economic one. Although it is clear that the vaccine contributes little to the eradication of the disease; it is sometimes unreasonable to enforce stamping out (killing off all animals suspected of infection) and thus bring financial ruin upon the farmers involved.
The rationale for disallowing the long-term use of veterinary vaccines is based on the fact that, besides the compromisation of diagnostic tools (for example in Bovine Tuberculosis), vaccination is employed on a vast number of individuals (tens of millions in the case of fish). In every case of mass vaccination there are always individuals that are "low responders” or "vaccine escapers” and these create reservoirs for the persistence of the disease. What matters is not the large numbers of immunised individuals, but the potential danger of small numbers of non-immune individuals that persist in the vaccinated stock. For herpetic diseases, or where a carrier state is known to exist, the likelihood of viral persistence among vaccinated stock is much higher. Since it is impossible to round up and vaccinate all the fish existing in natural waters, these potential carriers may come into contact with and infect naïve populations of fish in nature, thus spreading the virus even further.
In summary, vaccination is of limited use as a measure of control or eradication for any infectious disease if the following factors exist:
1. There is a high transmission rate of disease between susceptible hosts.
2. The vaccine efficacy is less than 100 per cent.
3. Occult disease is manifest and transmitted sub clinically before diagnosis.
4. A low frequency and low level of challenge exists against susceptible pools in given geographical regions.
Points 1 to 3 above are definitely true for KHV and these characteristics have been cited in almost every scientific paper published on the disease (M. Haimi. 2003. KV3 – KHV Koi Herpes Virus Vaccine – Kovax).
Regarding the frequency (point 4), statistics on the number of outbreaks exist in almost every Koi producing country and in some Carp producing countries. Before debating whether these comprise high or low incidences, whether many incidences go unreported, or whether KHV exists everywhere or not, a number of facts should be considered:
1. Most of the outbreaks are on ornamental farms, trade facilities or private ponds where containment and sterilisation can be carried out relatively easily.
2. Outbreaks in natural waters cannot be controlled, either by vaccine or any other method, because of the fact that 100% of the fish cannot be vaccinated and because the disease is occult and transmission cannot be prevented.
3. In light of the fact that the common carp is the third most commonly farmed food fish in the world, even limited incidences of KHV could cause food shortages and economic damage to producing countries. This is obviously not the case at the present time . The conclusion can therefore be made that the level of challenge for KHV is low and does not warranty a solution involving vaccination except in cases (similar to that of the countrywide KHV outbreak in Israel between 1998 and 2001) where infection has reached levels where containment and stamping may not be viable or economical.
Due to the unique structure of the aquaculture industry, (millions of fish, shared water, world wide trade), there is a natural hesitation to establish eradication programmes. However, recent history tells us that these fears can be overcome if a decisive, co-ordinated and well-structured programme is implemented. This is demonstrated by the success of the European Union policy for the eradication of VHS. Any such programme will inevitably be based on measures of basic biosecurity that are required to be put in place at all points in the supply chain.
First hand testimony demonstrating the value of Biosecurity in KHV eradication.
Following the KHV outbreak in Israel in 1998, the Hazorea Koi farm was the last commercial koi farm in Israel to be infected (in the spring of the year 2000). The production of koi in open air ponds at the Hazorea farm was immediately discontinued. Production continued in an indoor biosecure pilot facility which was enlarged and intensified. Since 2001 Hazorea has been producing Koi in intensive indoor biosecure facilities. The outdoor ponds are now used exclusively for the production of goldfish. Periodic challenges for KHV are made by the controlled introduction of uncompromised naïve Koi into various outdoor ponds for extended periods of time during the time of the season when water temperatures are most suitable for KHV infection. Since 2001 KHV has never been found at the Hazorea farm and the disease seems to have disappeared completely. A safe, KHV free environment was achieved in one season without the use of natural immunisation or vaccination.
The case study detailed here shows that it could be relatively simple to achieve a basic biosecure status on any Koi or Carp farm in the world. In some cases a co-ordinated effort is required for farms adjoining each other or when water sources could be compromised by run-offs from other farms.
Looking beyond KHV
The past decade has seen a marked increase in the aquaculture industry around the world. From statistics published by the FAO in 2004 it is clear that aquaculture is by far the fastest growing sector of world food production. Fish are the most rapidly increasing commodity produced and/or traded globally and among commodities, account for the largest export earnings of the developing countries. In fact fish exports from developing countries earn more for these countries than all the other commodities put together! The ornamental fish industry is seeing a similar trend of movement from traditional open water "natural" farming to intensive controlled farming with the increased use of regulated and enhanced breeding programs using limited genetic pools. Increased intensification results in an increased risk of infectious disease outbreaks, and crowding increases the vulnerability of a population of animals to disease and death from opportunistic and obligate pathogens. (Julie Bebak, 1998). The combined result of this orientation is the increased risk of disease, and of the emergence of new and as yet unknown pathogens. The new pathogen may be far more deadly and have dangerous, far-reaching implications on the future of this industry which has become so important to the lives of millions of people around the world. Vaccination usually provides an induced immunity that hopes to prevent recurring infections of a specific pathogen. Rather than waiting for new pathogens to appear, and then spending 5 or 10 or 20 years and thousands of dollars developing another vaccine, we should act now to safeguard ourselves and the future of our food sources. Rather than waiting for new pathogens to spread to our rivers and lakes to organise a worldwide scientific effort to find applicable solutions, an approach is needed whereby we start today to put in place the systems that will help us protect ourselves tomorrow from what is an almost certain eventuality. KHV is a sample of what may be in store for us around the corner. Our reaction needs to be one that helps us in the containment and eradication of KHV, while reinforcing our defences against dangerous new pathogens.
Biosecurity – the solution for the Present and for the Future
Medication and vaccination have traditionally played a major role in treating diseases but it is now widely accepted that they cannot, in isolation, prevent losses due to disease. Modern farming demands a holistic approach. Unless the background challenge from disease causing organisms can be controlled, and good management practices strictly followed, medication and vaccination alone are not capable of adequately protecting fish stocks. Fish must be given an environment in which the level of infection is controlled to the point where vaccination and medication can achieve beneficial effects. Biosecurity is the key to achieving this. (DuPont Animal Health Solutions)
Biosecurity consists of practices and procedures that:
• reduce the risk that pathogens will be introduced to a facility
• reduce the risk that pathogens will spread throughout the facility
• reduce conditions that can increase susceptibility to infection and disease
(Fish Health Management, Julie Bebak-Williams et al).
As aquaculture systems become more and more intensive the Biosecurity measures put in place need to be more rigid and detailed. However, in a traditional open-air, mud-pond fish farm, there are certain basic measures that can be practiced with relative ease by any fish farmer in any part of the world and although these may have limited efficacy, they can be intensified and expanded as and when needed or according to the level of safeguards required. One of the greatest impediments to achieving a safer, more biosecure environment is the "all or nothing” attitude that is based on the argument that it is not possible to achieve complete Biosecurity in many facilities and especially in outdoor farms. This is like saying that there is no point in locking our houses as it is impossible to make them completely burglar proof, or not telling our children to wash since they are going to get dirty anyway. With Biosecurity, every step we take to make our premises, our stocks and our production safer, is a step in the right direction. Put schematically, the key to achieving Biosecurity lies in the way we way we think, behave and work. "Thinking Biosecurity” means being constantly conscious of what we are doing and with whom and with what we are interacting. "Behaving Biosecurely” means acting responsibly in a way that ensures the biosecure environment and reacting immediately to actual or potential threats. "Working Biosecurely” means putting in place and using procedures that ensure biosecurity in every aspect of our work - from our clothes and our equipment to our daily routines. Basic Biosecurity is as much a state of mind and behaviour as keeping our children safe and healthy. It is a concept that anyone, anywhere can appreciate, learn and emulate.
The importance of Biosecurity in an ever shrinking world where diseases have no borders and new strains or mutations of pathogens are being discovered regularly cannot be emphasised enough.
It is not the intention of this author to provide more than an overview of basic biosecurity that can be easily implemented in almost any production facility or farm anywhere in the world. Extensive and comprehensive literature on the subject has been published by many, and special mention should be given to material published by OATA. (Ornamental Aquatic Trade Association). Basic measures are usually implemented by treating, controlling and monitoring the following elements in ways that reduce the risk of infection and the risk of the introduction and/or spread of pathogens:
• Incoming and outgoing water
• Eggs, fry, new fish or broodstock brought in from other locations.
• Fish feed
• Equipment used
• Movement of staff and visitors and their vehicles
• Protection against wild animals and birds
• Removal of dead fish
• Monitoring and reporting of unusual mortalities
• Sterilisation procedures
It is clear that not every farmer in every location can carry out and/or practice a strict regime of biosecurity that includes all of the above factors. However, awareness will always provide better results than ignorance, and achieving partial biosecurity is better than relying solely on medication and luck. The education of fish producers, exporters, wholesalers, and retailers as well as anglers and hobbyists on the basic rules of biosecurity and how to practice them will do more for disease prevention, eradication and control than the traditional methods of medication and vaccination. This education may prevent the farmer in rural China from losing his entire stock to disease and it may help stop the spread of a dangerous disease from a wholesaler of Koi to retailers around the country. If all the links in the chain of supply use simple-to-follow and easy-to-implement rules of biosecurity, a reduction in the danger of the spread of disease will naturally follow.
Summary and Conclusions
1. Producing KHV compromised carp under a regime of either natural immunisation or vaccination is at present no guarantee that the disease will ever be controllable. Historical evidence proves that while vaccination can be an important aid in the eradication of certain diseases, it does not completely stop the carrying and distribution of a virus, especially where numerous strains exist or are liable to mutate. For a vaccine to be deemed effective in a worldwide eradication program there needs to be a rigorous and tested appreciation of its side effects and long term consequences, as well as an in-depth analysis of its cost efficiency in poor and developing countries, prior to its universal application. Even then, a vaccine can, at best, play only a small part in an eradication effort.
2. Vaccination is at best, of limited use in the control of KHV (i) since the disease is highly infectious, (ii) the vaccine does not provide a 100% efficacy, (iii) the disease is transferred sub-clinically by means as yet not fully understood or known and (iv) there is to date a low frequency of occurrences in most geographical regions.
3. It is the belief of the author of this paper that at present the only way to be absolutely sure that a population of carp is KHV free is if it is bred, maintained and transported under bio-secure conditions that do not allow cross infection with potential carriers of the virus. The key to maintaining a disease free population of carp is the implementation of easy-to-learn and easy-to-follow pragmatic guidelines for the maintenance of basic biosecurity on production sites of all kinds and in all areas.
4. The control and/or eradication of KHV as a threat can only be achieved by adopting a "back-to-basics" policy of prevention and stamping out, while immunisation by vaccine can and should be carried out in extreme cases as a back up, in a limited and restricted area and then only with a vaccine that has undergone exhaustive testing and proved effective against the relevant strain of KHV.
5. Furthermore, the use of biosecurity as a preventative measure provides a solution not only for the present KHV problem but prepares us for the predicted eventuality of developing pathogens that will undoubtedly appear as aquaculture becomes more and more intensive. More importantly, by introducing the concepts of biosecurity on a production level whether on a carp farm in rural China, or on a highly intensive RAS facility in the US, we are sowing the seeds that will grow to help protect our planet from poverty, disease and food shortage. It would be fitting to sum up this view of biosecurity with the three truisms so aptly stated in the booklet produced by OATA "Biosecurity and the Ornamental Fish Industry":
• If a pathogen isn’t present on a site it can’t cause a disease on that site
• If a pathogen isn’t present on a site it can’t be transmitted from that site.
• If the pathogen is present at a supplier’s site then better it remains there: curative treatment to eradicate the pathogen prior to fish leaving that site may be required
KHV (as well as other equally dangerous fish pathogens) should serve as a wake-up call for the aquaculture fraternity. The responsibility for all those involved, farmers, scientists and policymakers, goes beyond this specific virus and has applications to developing diseases and the way we deal with them as a global community.
References & Bibliography:
Aoki, Takashi, Hirono, Ikuo, Kurokawa, Ken, Fukuda, Hideo, Nahary, Ronen, Eldar, Avi, Davison, Andrew J., Waltzek, Thomas B., Bercovier, Herve, and Hedrick, Ronald P. (2007) Genome sequences of three koi herpesvirus isolates representing the expanding distribution of an emerging disease threatening koi and common carp worldwide. Journal of Virology 81, 5058-5065– American Society for Microbiology
Dishon, A, Davidovich, M, Ilouze, M, Kotler, M (2007). Persistence of cyprinid herpes virus 3 (CyHV-3) in infected cultured carp cells. Journal of Virology 02188-06- American Society for Microbiology
St-Hilaire, S., Beevers, N., Way, K., Le Deuff, R. M., Martin, P., Joiner C., (2005). Reactivation of koi herpesvirus infections in common carp Cyprinus carpio, Diseases of Aquatic Organisms
Sadler, J, Marecaux, E and Goodwin, A E.; (2008) Journal of Fish Diseases
El-Matbouli, M., Saleh, M., Soliman, H. (2007) Detection of cyprinid herpesvirus type 3 in goldfish cohabiting with CyHV-3-infected koi carp (Cyprinus carpio koi). The Veterinary Record
Nelson, M. E. (1999) The Cost of Disease Eradication: Smallpox and Bovine Tuberculosis. Annals of the New York Academy of Sciences 894:83-91
Institute of Medicine, Forum on Emerging Infections. Considerations for Viral Disease Eradication: Lessons Learned and Future Struggles. Washington, DC: National Academies Press; 2002. March 1978 issue of Agricultural Research Magazine - USA
House of Commons Environment, Food and Rural Affairs Committee. Bovine TB: Government Reply to the Committee’s Report. Seventeenth Special Report Published on 20 October 2004
World Health Organisation website: http://www.who/int/en/
March 1978 issue of Agricultural Research Magazine - USA
Haimi, M. (2003) KV3 – KHV Koi Herpes Virus Vaccine – Kovax
Josupeit, H., (2002) Aquaculture production and Trade World Wide Survey, Fisheries Dept. – FAO
Bebak-Williams, Julie; Noble, Alicia; Bowser, Paul R.; and Wooster, Gregory A. (2006). Fish Health Management. Chapter 16.
Julie Bebak, (1998). The Importance of Biosecurity in Intensive Culture.
Aquaculture Biosecurity Program, Aquaculture Leaflet – Bradan Ltd. DuPont Animal Health Solutions
Biosecurity and the Ornamental Fish Industry – OATA (2006)