US20050226897A1 - Method of protecting against coccidiosis - Google Patents

Method of protecting against coccidiosis Download PDF

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US20050226897A1
US20050226897A1 US11/149,157 US14915705A US2005226897A1 US 20050226897 A1 US20050226897 A1 US 20050226897A1 US 14915705 A US14915705 A US 14915705A US 2005226897 A1 US2005226897 A1 US 2005226897A1
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animal
eimeria
vaccine
infectious
cycle
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Eng-Hong Lee
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/002Protozoa antigens
    • A61K39/012Coccidia antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • A61P33/02Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin

Definitions

  • the present invention is directed to a method of protecting poultry against coccidiosis.
  • diseases which are caused by infectious agents which have multiple stages in their life cycle and/or may go through more than one life cycle during the infection are common amongst many animal species and are generally caused by infectious agents of various genus and species of protozoa, although in some circumstances, agents of bacterial origin may also cause multiple infectious cycles.
  • a number of multiple life stage or multiple infectious cycle diseases are prevalent among animals of agriculturally economic significance, such as cattle, swine and poultry. Many of these diseases are of financial importance to the owner of the animals, as many such diseases can cause effects to the animals which may not be apparent until the animal is prepared for market. In some cases, the disease may render the animal unmarketable and the animal may have to be destroyed.
  • Such infections are of particular importance to animals which have a short time for growing out prior to market. For example, poultry are generally marketed within weeks after hatching and this short time period does not permit the animals sufficient time to recover from a infection prior to market if not treated in time.
  • Coccidiosis is a very common disease of poultry and there are several species of Eimeria which are known to cause such disease. The symptoms and severity of the disease are dependent upon the species of Eimeria with which the bird is infected with E. tenella, E. acervulina and E. maxima being three of the most prevalent species.
  • poultry flocks are protected against coccidiosis by either immunization or the use of anti-coccidial chemotherapeutic agents with the most commonly utilized method for controlling coccidial infections being the use of anti-coccidial agents.
  • anti-coccidial agents are commonly ionophores, a class of antibiotics of complex structure although other chemotherapeutic agents are also used. Many such ionophores exhibit anti-coccidial activity, although the relative degree of activity varies from one agent to another.
  • the ionophores which are commonly utilized for commercial control of coccidiosis include monensin, narasin, lasalocid and salinomycin. If anti-coccidial agents such as ionophores are utilized for control of coccidiosis in animals, it is necessary that the agent be continuously administered to the animal typically by being mixed with the feed used for raising the animal.
  • Another problem associated with the use of anti-coccidial therapeutic agents is the possibility of resistant strains of Eimeria developing as a result of exposure to the anti-coccidial agent. There have, in fact, been reports of such resistant strains developing in the field.
  • Coccidiosis vaccines are at present comprised of live virulent strains of coccidia in a suitable carrier for administration, the coccidia being capable of causing a mild form of the disease and selected to be very anticoccidial susceptible.
  • Immunization does have some drawbacks, in that there may be antigenic diversity amongst species of the infectious agent as well as amongst strains of a particular species of the infectious agent. Thus, depending upon the antigenic diversity displayed in a field strain of the organism, immunization may not be quite so effective against that particular strain. In addition, organisms may undergo antigenic mutation to the point where the immunological response induced as a result of the immunization will not have sufficient specificity against the antigens present on the field strain to protect the animal against infection by the field strain.
  • Live vaccines present the best chance of success for conferring protective immunity against infectious agents.
  • the live vaccine should mimic the action of the native organism. In many case, this requires that the live vaccine induce a sub-clinical infection in the host. For many diseases which are only minimally lethal and their causitive agents, this may not present a major problem if the infection caused by the vaccine should progress beyond the sub-clinical stage. For other disease this may be unaccepatable.
  • the present invention is directed to a method of protecting a poultry bird against coccidiosis.
  • the method comprises:
  • the present invention is directed to a kit for treating poultry to prevent coccidiosis.
  • the kit comprises a live vaccine containing a sufficient number of Eimeria sp. to develop an immunological response in the poultry and a therapeutic amount of a narasin ionophore for administration to the poultry for a period of time corresponding to at least one life cycle or infectious cycle of the Eimeria after the poultry has been maintained free from the chemotherapeutic agent for a period of time corresponding to about one life cycle or infectious cycle of the Eimeria.
  • the method of the present invention is practiced by first immunizing the poultry bird by administering to the bird a live vaccine containing sufficient organisms to develop an immunological response in the bird. This administration is carried out at a suitable time in the life of the bird, preferably shortly after birth or hatching. In general, for most poultry species the administration will be carried out within the first 24 hours after birth or hatching.
  • the chicks may be administered live vaccine by means of the watering system, by means of on-feed spray or through the use of a gelled vaccine.
  • Aqueous-based live vaccines are generally particulate in nature and if administered in the watering system, the vaccines should be provided in a composition which will maintain a relatively uniform suspension of the organisms in the vaccine.
  • Coccidiosis vaccines which consist of relatively large oocysts of Eimeria species.
  • Coccidiosis vaccines are usually administered orally for immunizing domestic animals of the avian species from coccidiosis, the vaccine having oocysts of at least one coccidium in relation to which the immunization is desired.
  • a vaccine comprising oocysts of Eimeria species in a water based carrier is sprayed onto the feed to be provided to the hatchlings.
  • the use of on-feed spray administration requires large doses of oocysts and uniform exposure of the flocks to the vaccine cannot always be achieved.
  • Vaccine may also be administered through the use of water proportioning systems including automatic fountains and automatic water medicator or proportioners.
  • water proportioning systems including automatic fountains and automatic water medicator or proportioners.
  • the vaccine may actually make it to the end of the water line, resulting in uneven exposure of the flock.
  • administration of the vaccine through the water proportioning system requires that after administration of the vaccine, the proportioning system be thoroughly cleaned to remove any residual vaccine.
  • the present invention in a preferred embodiment utilizes a gel form of a coccidiosis vaccine as described in my previous patent application WO 96/25951, published Aug. 29, 1996.
  • This form of a vaccine contains the oocysts of the coccidium diluted and suspended in a gel form which results in maintaining a uniform suspension of the oocysts and consequently, relatively uniform infection of the flock by the oocysts.
  • the gel form of the vaccine is particularly useful with Eimeria species, more particularly with Eimeria tenella or other species such as Eimeria necatrix, Eimeria acervulina, Eimeria maxima, Eimeria brunetti, Eimeria proecox , and Eimeria mitis are also useful.
  • the method of obtaining each of these species is well-known by those skilled in the art. Two or more species of Eimeria can be used simultaneously and in the practice of the present invention, it is generally not necessary to use more than six species together in the same
  • the gel form vaccine provides for an easy to handle method of vaccinating poultry hatchlings in the hatchery and is, therefore, suitable for general hatchery workers without any special expertise required.
  • the gel form is produced utilizing an edible polysaccharide gel, preferably a low temperature setting alginate or carrageenan gel, most preferably the kappa carrageenan gel sold as refined carrageenan Bengel MB 910, a water soluble kappa-type carrageenan extracted from the red algae Eucheuma cottonii.
  • the gel form of the vaccine is prepared by dissolving the gel powder in water at a suitable temperature to effect complete dissolution of the polysaccharide powder.
  • the powder is added to the water at a concentration such that, when mixed with the oocyst suspension and allowed to gel, a relatively soft gel results.
  • the dissolved gel powder and organism suspension are mixed in volumes such that the temperature of the resultant mixture is within the tolerant temperature of the organism.
  • the dissolved gel powder and oocyst suspension are mixed in a ratio of about 1:1(v:v) to prepare the gel form of the vaccine.
  • the gel form vaccine has sufficient levels of the oocysts to provide immunization to the flock. It has been found that each hatchling will consume about 0.5 to 1.5 ml of the gel within a few hours and the concentration of the oocysts in the gel should be such as to provide sufficient organisms in this typical volume to immunize the hatchling. It has been found that between about 50 and 1,000 oocysts per bird provides adequate protection and so it is preferred if the gel form of the vaccine has between about 100 and 500 oocysts per ml of gel, to provide for proper immunization of the flock.
  • the gel form of the vaccine contains between about 200 and 300 oocysts per ml of gel, most preferably about 250 oocysts per ml of gel.
  • the gel form is prepared by mixing the dissolved polysaccharide powder with the oocyst suspension in equal volumes, preferably one volume of a 2 to 5% polysaccharide gel solution is mixed with an equal volume of oocyst suspension containing between about 200 and 1,000 oocysts per ml, more preferably one volume of a 2 to 4 percent polysaccharide solution with an equal volume of oocyst suspension containing between about 400 and 600 oocysts per ml, most preferably a 2.5 percent solution of polysaccharide is mixed with an equal volume of oocyst suspension containing about 500 oocysts per ml.
  • the use of the edible polysaccharide gels results in a gel which forms very rapidly, usually in less than an hour and preferably within about 3 to 5 minutes at 40° C., maintains the vaccine organisms in uniform suspension and allows for more uniform exposure of the poultry hatchlings to the vaccine organisms.
  • the low content of the edible gum in the gel form means that approximately 95 percent or more of the gel form is water which can aid in the hydration of the bird and induce the feeding response.
  • the gel form has other advantages over liquid suspensions in that the gel form will not wet the bird and therefore will not affect the health of the chicks, particularly in winter when, if the hatchling becomes wet through exposure to aqueous solution, the exposure may cause death of the hatchling.
  • the use of the edible polysaccharide gel which gels at a relatively low temperature is also suitable for adding nitrogen nutrients and other additives such as vitamins to the gel form or competitive exclusion products such as BROILACT sold by Orion Corp., Finland. This is especially useful with heat sensitive nutrients which, if exposed to temperatures over about 50° C., are denatured.
  • the use of the gel form vaccine also realizes a saving in the hatchery in that as the gel form is 95 percent or more water, additional watering systems are not needed such as a built-in watering system. This reduces the likelihood of the spilling of water and wetting of the chicks which can affect the health of the birds.
  • a gel is a soft flowable gel capable of being administered through a spray droplet apparatus such that the flat of chicks is sprayed with sufficient amount of the gel vaccine to provide immunization for the chicks in the flat.
  • treatment of diseases caused by an infectious organism may have involved multiple doses of the vaccine. Although it is possible that the administration of the organisms may be in more than one dose, when practising the present invention, for most organisms there are no advantages to multiple dosing and a single dose is generally sufficient.
  • the exact number of infective organisms to be administered in the vaccine should be such to be effective to develop an immunological response in the animal.
  • the number should be sufficient to provide a uniformly low level exposure to all animals without causing severe disease. This number would vary, depending upon the nature of the infective organism and the animal to be treated. Such factors may include the species and size of the animal, the relative immunogenicity of the infective organism being administered in the vaccine, the nature of the vaccine, whether the organism is developed from a wild strain or an attenuated strain, and other factors known to those of skill in the art.
  • the suitable number of organisms sufficient to develop the immunological response in the animal may be easily determined by those of ordinary skill in the art through the use of common techniques for vaccine development.
  • the animal After the infectious organism is administered to the animal, the animal is left to be exposed to the entire antigenic complement of the organism to enable it to develop the full immunological response to the infective organism before the commencement of the narasin chemotherapy.
  • the period of time between administration of the infective organism and the commencement of narasin chemotherapy would correspond to about one life cycle or infectious cycle of the infective organism. This will enable the animal to be exposed to the full antigenic complement of the infective organism, particularly for those infective organisms which go through various stages in the life cycle. Eimeria will go through a number of stages in the life cycle such as sporulated oocysts, sporozoites and sporocysts.
  • the antigenic complement presented to the animal during each of these stages may be different and it is of advantage to the development of the immunological response that the animal be exposed to the full antigenic complement.
  • the administration of the narasin chemotherapeutic agent is commenced during the early part of the second life cycle or infectious cycle and continued to the end of the third life cycle or infectious cycle.
  • one life cycle takes approximately 5 to 9 days, with major species having life cycles of 5 to 7 days, E. tenella having a life cycle of 6 to 7 days.
  • chemotherapy is begun by administering the narasin chemotherapeutic agent effective against the infective organisms.
  • the narasin ionophore as the chemotherapeutic agent has been found to be of particular usefulness.
  • the narasin ionophore is generally administered to the animal for a period of time corresponding to at least about one life cycle or infectious cycle of the infectious organism.
  • the main function of the administration of the narasin ionophore is to limit the effects to the animal from the live vaccine, particularly, effects evident after the first cycle of the infectious organism.
  • the second and subsequent cycles which generally are not as uniform in exposure in terms of time and dose of exposure are controlled. Such subsequent cycles may also cause cumulative effects which may cause more damage to the animal. This enables mitigation of any possible side effects of vaccination, while permitting the full immunological response of the animal to the vaccination to develop.
  • the animals are being exposed to a particularly virulent field strain, it is preferable to maintain the animals on the narasin ionophore for a period of time corresponding to about two life cycles of the organism.
  • the birds will be maintained on the narasin ionophore for a period of about 20 to 30 days. After this period of time, the chemotherapy is discontinued and the animals are maintained on a non-medicated feed.
  • narasin ionophore follows the methods of administration commonly employed in the art. Typically, for animals such as cattle, swine, poultry, etc., the narasin ionophore is administered to the animal as an additive to the feed on which the animal is raised, i.e. by using a medicated feed.
  • the method of the present invention also has particular utility for replacement of the naturally occurring strains of organism in the field by a particularly selected organism.
  • a live vaccine for at least the first life cycle of the organism, viable organisms will be shed from the animals into the environment in which the animal is located. Over a period of a number of generations of the animal in the same location, the proportion of such organisms shed as a result of the immunization scheme in the total population of organisms present in the environment will increase until substantially most or all of the organisms in the environment are present as a result of the immunization process. In this way, the nature of the organisms in the environment may be controlled to select for organisms having a particular property, such as increased susceptibility to chemotherapeutic agents.
  • the method of the present invention is also adaptable to the nature of the organism found in the natural environment in which the animals are located.
  • the organisms native to the environment may be isolated and identified.
  • vaccines specific for the organisms and the particular strains present in the environment may be prepared to maximize the protection of the animal to the organisms found in the environment. For example, if it is found that on a particular poultry farm, E. tenella is the major species of Eimeria present, then the vaccine could be adjusted to have E. tenella as the major component of the vaccine.
  • the particular strain of the E. tenella present on the local farm could also be utilized for the preparation of the specific vaccine.
  • the organisms utilized in the vaccine could also be modified to provide for increased susceptibility to chemotherapeutic agents. In this way, the protection of the animal is maximized as the animal is being immunized against the species and strains of organisms found in the natural environment as well as over a number of generations the wild type strain present in the environment will be gradually replaced by the strain utilized in the vaccine.
  • the vaccine may also contain organisms which have been genetically engineered to optimize the protection of the animal to the organisms to which the animal would be exposed in the natural environment.
  • organisms which have been genetically engineered to optimize the protection of the animal to the organisms to which the animal would be exposed in the natural environment.
  • the organism for the vaccine could be engineered to utilize a less virulent species or strain of the organism, the less virulent species or strain of the organism in the vaccine also being capable of expressing antigens on its surface which cross-react with, or are specific for the more virulent strain found in the natural environment. This would optimize the protection of the animal to the strain found in the natural environment while minimizing the effects of the vaccine on the animal.
  • the present invention also provides for a kit for treating the poultry for coccidiosis.
  • the kit comprises a vaccine containing a sufficient number of live oocysts of one or more Eimeria sp. to develop an immunological response in the animal.
  • the vaccine is described above.
  • the kit also contained a therapeutic amount of a narasin ionophore for treating the animals for a period of time corresponding to at least one life cycle or infectious cycle of the Eimeria .
  • the kit also contains instructions for the use of the kit to administer the live vaccine to the poultry, maintain the poultry free from the chemotherapeutic agents for a period of time corresponding to about one life cycle or infectious cycle of the Eimeria and thereafter administer to poultry a therapeutic amount of the narasin ionophore for a period of time corresponding to at least one life cycle of infectious cycle of the Eimeria.
  • the method and kit of the present invention is illustrated in the following examples using coccidiosis in poultry but the invention is not limited thereto.
  • the vaccine being the oocysts in the gel form was not fed to the bird manually, the birds were simply placed in the same area as the gel form vaccine during the time period and were allowed to consume the vaccine voluntarily.
  • a gel form vaccine was prepared by first adding 200 ml of hot tap water to 5 gm of kappa carrageenan Bengel MB 910 in a container and mixing until the MB 910 had dissolved. To this solution was added 200 ml of a solution containing 500 oocysts per ml of a mixture of Eimeria acervulina, E. maxima and E. tenella and the combined solution was mixed. The solution was then poured into a plastic watering dish and allowed to cool and gel at 4° C. This resulted in a gel form of the vaccine containing 1.25 percent MB 910 and 250 oocysts per ml.
  • a kit was prepared containing a sufficient amount of a vaccine as prepared in Example 1 for treating at least 100 poultry hatchlings.
  • the kit also contains a sufficient amount of the narasin ionophore to provide 70 mg per kilogram of feed for feeding the 100 poultry hatchlings for 10 days.
  • the kit also included instructions for the administration of the vaccine and ionophore in accordance with the method of the present invention.
  • the present invention provides for a method and kit for treating poultry flocks against coccidiosis infection.
  • the method of the present invention helps to overcome some of the drawbacks of each of the individual methods namely, immunization and/or chemotherapeutic therapy by providing a means of controlling the exposure of the animal to the organism and in the preferred embodiment by controlling the nature of the organism which is found in the natural environment. This is accomplished through wild type field strain replacement by the strain utilized in the vaccine used as part of the method of the present invention.

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Abstract

In one aspect, the present invention is directed to a method of protecting a poultry bird against coccidiosis. The method comprises:
    • a) administering to the bird a live vaccine containing sufficient number of Eimeria sp. to develop an immunological response in the animal;
    • b) maintaining the animal free from chemotherapeutic agents effective against the Eimeria sp. for a period of time corresponding to about one life cycle or infectious cycle of the Eimeria sp.; and
    • c) thereafter administering to the animal a therapeutic amount of a narasin ionophore for a period of time corresponding to at least one life cycle or infectious cycle of the Eimeria sp.

Description

    CROSS-REFERENCE TO RELATED APPLICATIONS
  • This application is a continuation-in-part of U.S. Ser. No. 09/971,359 filed Oct. 5, 2001 which is a continuation-in-part of Ser. No. 09/062,316, filed Apr. 20, 1998 now U.S. Pat. No. 6,306,385 issued Oct. 23, 2001.
  • FIELD OF THE INVENTION
  • The present invention is directed to a method of protecting poultry against coccidiosis.
  • BACKGROUND OF THE INVENTION
  • There are many diseases which are caused by infectious agents which have multiple stages in their life cycle and/or may go through more than one life cycle during the infection. Such diseases are common amongst many animal species and are generally caused by infectious agents of various genus and species of protozoa, although in some circumstances, agents of bacterial origin may also cause multiple infectious cycles. A number of multiple life stage or multiple infectious cycle diseases are prevalent among animals of agriculturally economic significance, such as cattle, swine and poultry. Many of these diseases are of financial importance to the owner of the animals, as many such diseases can cause effects to the animals which may not be apparent until the animal is prepared for market. In some cases, the disease may render the animal unmarketable and the animal may have to be destroyed.
  • Such infections are of particular importance to animals which have a short time for growing out prior to market. For example, poultry are generally marketed within weeks after hatching and this short time period does not permit the animals sufficient time to recover from a infection prior to market if not treated in time.
  • One particular infectious agent which is of importance to the management of poultry flocks is coccidiosis caused by a protozoa of the genus Eimeria. Coccidiosis is a very common disease of poultry and there are several species of Eimeria which are known to cause such disease. The symptoms and severity of the disease are dependent upon the species of Eimeria with which the bird is infected with E. tenella, E. acervulina and E. maxima being three of the most prevalent species. Presently, poultry flocks are protected against coccidiosis by either immunization or the use of anti-coccidial chemotherapeutic agents with the most commonly utilized method for controlling coccidial infections being the use of anti-coccidial agents.
  • Such anti-coccidial agents are commonly ionophores, a class of antibiotics of complex structure although other chemotherapeutic agents are also used. Many such ionophores exhibit anti-coccidial activity, although the relative degree of activity varies from one agent to another. The ionophores which are commonly utilized for commercial control of coccidiosis include monensin, narasin, lasalocid and salinomycin. If anti-coccidial agents such as ionophores are utilized for control of coccidiosis in animals, it is necessary that the agent be continuously administered to the animal typically by being mixed with the feed used for raising the animal. Another problem associated with the use of anti-coccidial therapeutic agents is the possibility of resistant strains of Eimeria developing as a result of exposure to the anti-coccidial agent. There have, in fact, been reports of such resistant strains developing in the field.
  • As noted above, another method of controlling chronic infections, especially within poultry, is the use of immunization. At the present time, poultry hatchlings, within the first few days of life, are immunized against various diseases and the type of vaccine used for each disease dictates its method of administration. Attenuated vaccines are usually administered in the hatchery by injection at the time of sorting and/or sexing of the hatchlings from the hatching incubator into holding or transporting trays. Live vaccines are more commonly administered once the hatchlings are established in their brooding trays in the form of aqueous suspensions either sprayed on feed, added to the drinking water or the use of gelled form of vaccines such as taught in my PCT Application WO 96/25951 published Aug. 29, 1996.
  • Coccidiosis vaccines are at present comprised of live virulent strains of coccidia in a suitable carrier for administration, the coccidia being capable of causing a mild form of the disease and selected to be very anticoccidial susceptible.
  • Immunization does have some drawbacks, in that there may be antigenic diversity amongst species of the infectious agent as well as amongst strains of a particular species of the infectious agent. Thus, depending upon the antigenic diversity displayed in a field strain of the organism, immunization may not be quite so effective against that particular strain. In addition, organisms may undergo antigenic mutation to the point where the immunological response induced as a result of the immunization will not have sufficient specificity against the antigens present on the field strain to protect the animal against infection by the field strain. Use of live vaccines also results in the induction of a mild disease state in the animal from which the animal would normally recover, however, in immunosuppressed or immunoincompetent animals the degree of the disease state induced by the immunization may become significant. In such circumstances the uniformity of the therapy is affected with resultant variation in weight gain and feed conversion of the animals.
  • There have been attempts to overcome the above difficulty by the use of a combination of immunization and chemotherapy. U.S. Pat. No. 4,935,007, issued Jun. 19, 1990 to Eli Lilly and Company describes a method for control of coccidiosis involving both immunization and ionophore chemotherapy. The method of this patent involves orally administering to the animal at a neonate stage sufficient coccidial organisms of an ionophore resistant strain to generate an immunological response while maintaining the animal free of any chemotherapeutic anti-coccidial. After the sporozoites have penetrated the host cells, an anti-coccidially effective dose of an ionophore is administered substantially continuously throughout the life of the animal.
  • While the method as described in U.S. Pat. No. 4,935,007 attempts to overcome the difficulties of the two methods of controlling coccidiosis, there are drawbacks associated with that method. The ionophore is administered to the animals commencing within 24 hours of immunization and continued throughout the life of the animal. Thus, the use of the method of U.S. Pat. No. 4,935,007 does not result in any significant savings over the traditional use of a chemotherapeutic agent alone. In addition, the commencing of the use of the chemotherapeutic agent within 24 hours of the immunization may not permit the full immunological response to occur, particularly if there are antigens which may not be expressed until later stages of the life cycle.
  • Live vaccines present the best chance of success for conferring protective immunity against infectious agents. However, to be most effective, the live vaccine should mimic the action of the native organism. In many case, this requires that the live vaccine induce a sub-clinical infection in the host. For many diseases which are only minimally lethal and their causitive agents, this may not present a major problem if the infection caused by the vaccine should progress beyond the sub-clinical stage. For other disease this may be unaccepatable.
  • There thus remains a need for an improved method of controlling diseases caused by infectious agents which undergo multiple life cycles or multiple infectious cycles in animals, and in particular, a method of providing effective immunity to the animal while controlling any side effects of the use of live vaccines.
  • SUMMARY OF THE INVENTION
  • In one aspect, the present invention is directed to a method of protecting a poultry bird against coccidiosis. The method comprises:
      • a) administering to the bird a live vaccine containing sufficient number of Eimeria oocysts to develop an immunological response in the animal;
      • b) maintaining the animal free from chemotherapeutic agents effective against the Eimeria sp. for a period of time corresponding to about one life cycle or infectious cycle of the Eimeria sp.; and
      • c) thereafter administering to the animal a therapeutic amount of a narasin ionophore for a period of time corresponding to at least one life cycle or infectious cycle of the Eimeria sp.
  • In another aspect, the present invention is directed to a kit for treating poultry to prevent coccidiosis. The kit comprises a live vaccine containing a sufficient number of Eimeria sp. to develop an immunological response in the poultry and a therapeutic amount of a narasin ionophore for administration to the poultry for a period of time corresponding to at least one life cycle or infectious cycle of the Eimeria after the poultry has been maintained free from the chemotherapeutic agent for a period of time corresponding to about one life cycle or infectious cycle of the Eimeria.
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • Many warm blooded animals of importance to animal husbandry are susceptible to coccidiosis caused by Eimeria such as for example swine or poultry. Of these animals, it is found that poultry suffer most from coccidiosis, with chickens and turkeys being the species most commonly needing protection. Because of the prevalence of coccidiosis in chickens and turkeys and because of their economic importance, the present invention is particularly useful for controlling coccidiosis in such animals. The present invention may also be utilized with other poultry species such as duck, geese, quail, pheasants and the like, or other warm blooded animals important in animal husbandry, such as cattle, sheep, swine and the like.
  • The method of the present invention is practiced by first immunizing the poultry bird by administering to the bird a live vaccine containing sufficient organisms to develop an immunological response in the bird. This administration is carried out at a suitable time in the life of the bird, preferably shortly after birth or hatching. In general, for most poultry species the administration will be carried out within the first 24 hours after birth or hatching.
  • In a poultry hatchery, at the time of emergence of the hatchlings from their shells in the incubation trays, they are generally examined for defects, immunized with poultry vaccines by injection and then sorted by sex and placed into holding or transporting trays. Once in the brooding trays, the chicks may be administered live vaccine by means of the watering system, by means of on-feed spray or through the use of a gelled vaccine. Aqueous-based live vaccines are generally particulate in nature and if administered in the watering system, the vaccines should be provided in a composition which will maintain a relatively uniform suspension of the organisms in the vaccine. This is particularly true for coccidiosis vaccines which consist of relatively large oocysts of Eimeria species. Coccidiosis vaccines are usually administered orally for immunizing domestic animals of the avian species from coccidiosis, the vaccine having oocysts of at least one coccidium in relation to which the immunization is desired.
  • One common method of immunization against coccidiosis involves the use of on-feed spray administration while the birds are feeding from flats or other containers. A vaccine comprising oocysts of Eimeria species in a water based carrier is sprayed onto the feed to be provided to the hatchlings. The use of on-feed spray administration requires large doses of oocysts and uniform exposure of the flocks to the vaccine cannot always be achieved.
  • Vaccine may also be administered through the use of water proportioning systems including automatic fountains and automatic water medicator or proportioners. However, given the particulate nature of coccidiosis vaccines, it is doubtful that the vaccine may actually make it to the end of the water line, resulting in uneven exposure of the flock. Additionally, administration of the vaccine through the water proportioning system requires that after administration of the vaccine, the proportioning system be thoroughly cleaned to remove any residual vaccine.
  • The present invention in a preferred embodiment utilizes a gel form of a coccidiosis vaccine as described in my previous patent application WO 96/25951, published Aug. 29, 1996. This form of a vaccine contains the oocysts of the coccidium diluted and suspended in a gel form which results in maintaining a uniform suspension of the oocysts and consequently, relatively uniform infection of the flock by the oocysts. The gel form of the vaccine is particularly useful with Eimeria species, more particularly with Eimeria tenella or other species such as Eimeria necatrix, Eimeria acervulina, Eimeria maxima, Eimeria brunetti, Eimeria proecox, and Eimeria mitis are also useful. The method of obtaining each of these species is well-known by those skilled in the art. Two or more species of Eimeria can be used simultaneously and in the practice of the present invention, it is generally not necessary to use more than six species together in the same suspension.
  • The gel form vaccine provides for an easy to handle method of vaccinating poultry hatchlings in the hatchery and is, therefore, suitable for general hatchery workers without any special expertise required. The gel form is produced utilizing an edible polysaccharide gel, preferably a low temperature setting alginate or carrageenan gel, most preferably the kappa carrageenan gel sold as refined carrageenan Bengel MB 910, a water soluble kappa-type carrageenan extracted from the red algae Eucheuma cottonii.
  • The gel form of the vaccine is prepared by dissolving the gel powder in water at a suitable temperature to effect complete dissolution of the polysaccharide powder. The powder is added to the water at a concentration such that, when mixed with the oocyst suspension and allowed to gel, a relatively soft gel results. The dissolved gel powder and organism suspension are mixed in volumes such that the temperature of the resultant mixture is within the tolerant temperature of the organism. Typically, the dissolved gel powder and oocyst suspension are mixed in a ratio of about 1:1(v:v) to prepare the gel form of the vaccine.
  • The gel form vaccine has sufficient levels of the oocysts to provide immunization to the flock. It has been found that each hatchling will consume about 0.5 to 1.5 ml of the gel within a few hours and the concentration of the oocysts in the gel should be such as to provide sufficient organisms in this typical volume to immunize the hatchling. It has been found that between about 50 and 1,000 oocysts per bird provides adequate protection and so it is preferred if the gel form of the vaccine has between about 100 and 500 oocysts per ml of gel, to provide for proper immunization of the flock. Preferably, the gel form of the vaccine contains between about 200 and 300 oocysts per ml of gel, most preferably about 250 oocysts per ml of gel. As the gel form is prepared by mixing the dissolved polysaccharide powder with the oocyst suspension in equal volumes, preferably one volume of a 2 to 5% polysaccharide gel solution is mixed with an equal volume of oocyst suspension containing between about 200 and 1,000 oocysts per ml, more preferably one volume of a 2 to 4 percent polysaccharide solution with an equal volume of oocyst suspension containing between about 400 and 600 oocysts per ml, most preferably a 2.5 percent solution of polysaccharide is mixed with an equal volume of oocyst suspension containing about 500 oocysts per ml.
  • The use of the edible polysaccharide gels results in a gel which forms very rapidly, usually in less than an hour and preferably within about 3 to 5 minutes at 40° C., maintains the vaccine organisms in uniform suspension and allows for more uniform exposure of the poultry hatchlings to the vaccine organisms. The low content of the edible gum in the gel form means that approximately 95 percent or more of the gel form is water which can aid in the hydration of the bird and induce the feeding response. The gel form has other advantages over liquid suspensions in that the gel form will not wet the bird and therefore will not affect the health of the chicks, particularly in winter when, if the hatchling becomes wet through exposure to aqueous solution, the exposure may cause death of the hatchling. The use of the edible polysaccharide gel which gels at a relatively low temperature is also suitable for adding nitrogen nutrients and other additives such as vitamins to the gel form or competitive exclusion products such as BROILACT sold by Orion Corp., Finland. This is especially useful with heat sensitive nutrients which, if exposed to temperatures over about 50° C., are denatured. The use of the gel form vaccine also realizes a saving in the hatchery in that as the gel form is 95 percent or more water, additional watering systems are not needed such as a built-in watering system. This reduces the likelihood of the spilling of water and wetting of the chicks which can affect the health of the birds.
  • Another version of a gel based coccidiosis vaccine has been described in my Canadian Patent Application No. 2,213,385. In this version of the gel vaccine, a gel is a soft flowable gel capable of being administered through a spray droplet apparatus such that the flat of chicks is sprayed with sufficient amount of the gel vaccine to provide immunization for the chicks in the flat.
  • In the past, treatment of diseases caused by an infectious organism may have involved multiple doses of the vaccine. Although it is possible that the administration of the organisms may be in more than one dose, when practising the present invention, for most organisms there are no advantages to multiple dosing and a single dose is generally sufficient.
  • When practising the method of the present invention with organisms that cause multiple infectious cycles, it is possible to rely on recycling of the organism to provide for multiple exposures of the animals to the organism. Thus for coccidiosis in chickens where the oocysts are shed into the feces at the end of every life cycle, the chicks are exposed to the shed oocysts at the end of the first life cycle, and thus are given a second dose of the organisms. A chemotherapeutic thereapy is commenced just after the start of the second life cycle, or just after the animals have been exposed to the organisms which have been shed at the end of the first life cycle.
  • The exact number of infective organisms to be administered in the vaccine should be such to be effective to develop an immunological response in the animal. The number should be sufficient to provide a uniformly low level exposure to all animals without causing severe disease. This number would vary, depending upon the nature of the infective organism and the animal to be treated. Such factors may include the species and size of the animal, the relative immunogenicity of the infective organism being administered in the vaccine, the nature of the vaccine, whether the organism is developed from a wild strain or an attenuated strain, and other factors known to those of skill in the art. The suitable number of organisms sufficient to develop the immunological response in the animal may be easily determined by those of ordinary skill in the art through the use of common techniques for vaccine development.
  • After the infectious organism is administered to the animal, the animal is left to be exposed to the entire antigenic complement of the organism to enable it to develop the full immunological response to the infective organism before the commencement of the narasin chemotherapy. Generally, the period of time between administration of the infective organism and the commencement of narasin chemotherapy would correspond to about one life cycle or infectious cycle of the infective organism. This will enable the animal to be exposed to the full antigenic complement of the infective organism, particularly for those infective organisms which go through various stages in the life cycle. Eimeria will go through a number of stages in the life cycle such as sporulated oocysts, sporozoites and sporocysts. The antigenic complement presented to the animal during each of these stages may be different and it is of advantage to the development of the immunological response that the animal be exposed to the full antigenic complement. In a preferred embodiment of the present invention, the administration of the narasin chemotherapeutic agent is commenced during the early part of the second life cycle or infectious cycle and continued to the end of the third life cycle or infectious cycle. By commencing the narasin treatment during the second life or infectious cycle, this allows recycling to occur in the animal, such that they are exposed to the organisms shed at the end of the first life or infectious cycle. However, the subsequent stages in the recycling, such as the exposure at the end of the first life or infectious cycle may not be as uniform as the exposure to the controlled dosages of the vaccine. Consequently, the effects of such exposure are more variable.
  • For Eimeria species, one life cycle takes approximately 5 to 9 days, with major species having life cycles of 5 to 7 days, E. tenella having a life cycle of 6 to 7 days. Thus, in practicing the present method for controlling coccidial infections in poultry, within about 10 days after administering the vaccine, chemotherapy is begun by administering the narasin chemotherapeutic agent effective against the infective organisms.
  • For the control of coccidiosis in poultry using the method of the present invention, the narasin ionophore as the chemotherapeutic agent has been found to be of particular usefulness.
  • The narasin ionophore is generally administered to the animal for a period of time corresponding to at least about one life cycle or infectious cycle of the infectious organism. The main function of the administration of the narasin ionophore is to limit the effects to the animal from the live vaccine, particularly, effects evident after the first cycle of the infectious organism. By administering the narasin ionophore at this time, the second and subsequent cycles which generally are not as uniform in exposure in terms of time and dose of exposure are controlled. Such subsequent cycles may also cause cumulative effects which may cause more damage to the animal. This enables mitigation of any possible side effects of vaccination, while permitting the full immunological response of the animal to the vaccination to develop.
  • For control of coccidiosis in poultry, in most circumstances, it is only necessary to maintain the animals on the narasin ionophore for a period of time corresponding to at least one life cycle of the coccidial organism, preferably for a period of 10 to 14 days. After this time, the birds are immunized and the ionophore is no longer needed for protection.
  • In some circumstances, such as for example where the birds are being exposed to a particularly virulent field strain, it is preferable to maintain the animals on the narasin ionophore for a period of time corresponding to about two life cycles of the organism. Thus, for example when the method is used to control coccidioisis in poultry, the birds will be maintained on the narasin ionophore for a period of about 20 to 30 days. After this period of time, the chemotherapy is discontinued and the animals are maintained on a non-medicated feed.
  • The administration of the narasin ionophore follows the methods of administration commonly employed in the art. Typically, for animals such as cattle, swine, poultry, etc., the narasin ionophore is administered to the animal as an additive to the feed on which the animal is raised, i.e. by using a medicated feed.
  • The method of the present invention also has particular utility for replacement of the naturally occurring strains of organism in the field by a particularly selected organism. As the method of the present invention utilizes a live vaccine, for at least the first life cycle of the organism, viable organisms will be shed from the animals into the environment in which the animal is located. Over a period of a number of generations of the animal in the same location, the proportion of such organisms shed as a result of the immunization scheme in the total population of organisms present in the environment will increase until substantially most or all of the organisms in the environment are present as a result of the immunization process. In this way, the nature of the organisms in the environment may be controlled to select for organisms having a particular property, such as increased susceptibility to chemotherapeutic agents.
  • The method of the present invention is also adaptable to the nature of the organism found in the natural environment in which the animals are located. By utilizing standard techniques, the organisms native to the environment may be isolated and identified. Once the organism is isolated and identified, vaccines specific for the organisms and the particular strains present in the environment may be prepared to maximize the protection of the animal to the organisms found in the environment. For example, if it is found that on a particular poultry farm, E. tenella is the major species of Eimeria present, then the vaccine could be adjusted to have E. tenella as the major component of the vaccine. The particular strain of the E. tenella present on the local farm could also be utilized for the preparation of the specific vaccine. The organisms utilized in the vaccine could also be modified to provide for increased susceptibility to chemotherapeutic agents. In this way, the protection of the animal is maximized as the animal is being immunized against the species and strains of organisms found in the natural environment as well as over a number of generations the wild type strain present in the environment will be gradually replaced by the strain utilized in the vaccine.
  • In addition, the vaccine may also contain organisms which have been genetically engineered to optimize the protection of the animal to the organisms to which the animal would be exposed in the natural environment. For example, if a particularly virulent strain of the organism is present in the natural environment, the organism for the vaccine could be engineered to utilize a less virulent species or strain of the organism, the less virulent species or strain of the organism in the vaccine also being capable of expressing antigens on its surface which cross-react with, or are specific for the more virulent strain found in the natural environment. This would optimize the protection of the animal to the strain found in the natural environment while minimizing the effects of the vaccine on the animal.
  • The present invention also provides for a kit for treating the poultry for coccidiosis. The kit comprises a vaccine containing a sufficient number of live oocysts of one or more Eimeria sp. to develop an immunological response in the animal. The vaccine is described above. The kit also contained a therapeutic amount of a narasin ionophore for treating the animals for a period of time corresponding to at least one life cycle or infectious cycle of the Eimeria. The kit also contains instructions for the use of the kit to administer the live vaccine to the poultry, maintain the poultry free from the chemotherapeutic agents for a period of time corresponding to about one life cycle or infectious cycle of the Eimeria and thereafter administer to poultry a therapeutic amount of the narasin ionophore for a period of time corresponding to at least one life cycle of infectious cycle of the Eimeria.
  • The method and kit of the present invention is illustrated in the following examples using coccidiosis in poultry but the invention is not limited thereto. In all of the examples where it is stated that the animals were exposed to oocysts, it should be understood that the vaccine being the oocysts in the gel form was not fed to the bird manually, the birds were simply placed in the same area as the gel form vaccine during the time period and were allowed to consume the vaccine voluntarily.
  • EXAMPLE 1
  • A gel form vaccine was prepared by first adding 200 ml of hot tap water to 5 gm of kappa carrageenan Bengel MB 910 in a container and mixing until the MB 910 had dissolved. To this solution was added 200 ml of a solution containing 500 oocysts per ml of a mixture of Eimeria acervulina, E. maxima and E. tenella and the combined solution was mixed. The solution was then poured into a plastic watering dish and allowed to cool and gel at 4° C. This resulted in a gel form of the vaccine containing 1.25 percent MB 910 and 250 oocysts per ml.
  • EXAMPLE 2
  • A comparison was conducted between use of vaccine dose and the method of the present invention for protecting poultry against coccidiosis in a paired barn trial. 35,000 birds split between 2 barns were administered the vaccine prepared in accordance with Example 1 on Day 1 and maintained on feed with no medication for 10 days. The birds were then divided into two groups with one group maintained on non-medicated feed and the other group given 70 mg per kilogram of narasin in the feed for a further 10 days after which all the animals were maintained on non-medicated feed until shipping. A virginiamysin based growth promotant STAFAC (SmithKline Beecham) at a level of 11 mg per kilogram of feed was used as a growth promotant in both groups. The results for both groups are shown in Table 1.
    TABLE 1
    B3 (Immucox Gel) B2 (Immucox Gel + Monteban)
    Age (days) 45 44
    weight (Kg) 2.79 2.88
    FCR 2.11 1.85
    Mortality 5.37 6
    Condem. 2.1 1.1
    EEF 278 333

    EEF = European Efficiency Factor
  • From the above, it can be seen that the use of the combined vaccination and the narasin treatment resulted in a significantly and unexpectedly higher efficiency as measured by the European Efficiency Factor which is related to the percent liveability, average market weight, feed conversion rate and market age of the birds.
  • EXAMPLE 3
  • A kit was prepared containing a sufficient amount of a vaccine as prepared in Example 1 for treating at least 100 poultry hatchlings. The kit also contains a sufficient amount of the narasin ionophore to provide 70 mg per kilogram of feed for feeding the 100 poultry hatchlings for 10 days. The kit also included instructions for the administration of the vaccine and ionophore in accordance with the method of the present invention.
  • The present invention provides for a method and kit for treating poultry flocks against coccidiosis infection. The method of the present invention helps to overcome some of the drawbacks of each of the individual methods namely, immunization and/or chemotherapeutic therapy by providing a means of controlling the exposure of the animal to the organism and in the preferred embodiment by controlling the nature of the organism which is found in the natural environment. This is accomplished through wild type field strain replacement by the strain utilized in the vaccine used as part of the method of the present invention.
  • Although various preferred embodiments of the present invention have been described herein in detail, it will be appreciated by those skilled in the art, that variations may be made thereto without departing from the spirit of the invention or the scope of the appended claims.

Claims (3)

1. A method of protecting poultry against a coccidiosis caused by Eimeria sp., the method comprising:
a) administering to the animal a live vaccine containing sufficient Eimeria sp. organisms to develop an immunological response in the animal;
b) maintaining the animal free from chemotherapeutic agents effective against Eimeria sp. for a period of time corresponding to about one life cycle or infectious cycle of the Eimeria sp.; and
c) thereafter administering to the animal a therapeutic amount of narasin ionophore for a period of time corresponding to at least one life cycle or infectious cycle of the Eimeria sp.
2. A method as claimed in claim 1 wherein the animal is maintained free from chemotherapeutic agents effective against the Eimeria sp. for a period of time corresponding to about two to five days beyond one life cycle or infectious cycle of the Eimeria sp.
3. A method as claimed in claim 2 wherein the narasin ionophore is administered to the animal for a period of time corresponding to about 1.5 to 2.5 life cycles or infectious cycles of the Eimeria sp.
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US09/971,359 US20020061314A1 (en) 1997-08-20 2001-10-05 Method for protecting against chronic infections
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