Sustainable control of zoonotic pathogens in wildlife: how to be fair to wild animals?

Wildlife may harbour infectious pathogens that are of zoonotic concern. However, culling such reservoir populations to mitigate or control the transmission of these pathogens to humans has proved disappointingly inefficient. Alternatives are still in an experimental stage of development. They include vaccination, medication, contraception and environmental manipulation, including fencing and biosecurity measures. This review examines the general concepts involved in the control of wildlife diseases and presents relevant case studies. Since wildlife disease control inevitably involves interfering with wildlife ecology, this is a complex goal whose attempts at realisation should be supervised by a scientific organisation. Most approaches within natural ecosystems should first be carefully tested in trials that are progressively extended to a larger scale. Finally, all measures that aim to prevent infection in humans (such as personal hygiene or vaccination) or that encourage us to avoid infectious contacts with wildlife should be recommended.

The control of rabies in Eurasia: overview, history and background.

After a short overview of the present and past epidemiological situation regarding animal and human rabies in Eurasia, the general characteristics of the disease are described in each vector. Three main rabies cycles are presently established in Eurasia: in dogs, wild carnivores and insectivorous bats. Because of the strong barrier that exists between species-adapted rabies viruses and various potential hosts, these cycles are quite independent. They are perceived in many countries in Eurasia not to have a significant impact on animal health or the rural economy in general; the loss of dogs (or cattle) is not a priority animal health issue at the national level. Wildlife rabies has almost been eliminated in Western Eurasia by oral vaccination campaigns. Bats do not represent a real threat for a well informed public. Rabies is thus essentially a public health issue. Human rabies of canine origin has continued unabated for centuries in Eastern Eurasia, despite the Pasteur treatment and subsequent improvements of rabies post-exposure prophylaxis and biological products. Dog rabies, which is the main source of human contamination, remains practically uncontrolled. The Ministries of Health of all infected countries of Eurasia should focus their attention on canine rabies first, as it incurs endless expenses for treating humans that have been exposed to dog bites. These Ministries should use the competence of Veterinary Services and all other national bodies involved in dog rabies control, and contribute all necessary resources to support them to control this reservoir. This goal seems achievable in less than five years in a country, provided that cost-shared and well-planed mass canine oral vaccination campaigns are organised and coordinated at the regional and international levels. The conditions for the success of such campaigns are presented.

A history of the traceability of animals and animal products.

The author presents a review of the history of traceability as applied to live animals and animal products from antiquity to the 19th Century. The evidence shows that livestock farmers, owners, and those in charge of animal production and health were concerned with traceability from a very early stage. With regard to live animals, individual identification by means of body markings has been practised for over 3,800 years (Code of Hammurabi). Branding with a red-hot iron, with or without a written record of animal characteristics, was employed in most ancient civilisations. This branding technique was principally used on valuable animals, in particular horses, in which case a written record was kept. Individual indelible branding was used on other species over the following centuries, for example, on swans belonging to the Kings of England as early as the 13th Century. Branding for disease control purposes commenced later, prompted by the major epizootics (rinderpest, contagious bovine pleuropneumonia, glanders and rabies). Marking of animals formed part of a series of very pragmatic measures, and the penalties in the event of violation were much more severe than is currently the case. Although modern traceability techniques were not available, our ancestors, as early as the 17th Century, practised indelible branding and strict health certification. Animal products were likewise closely monitored, particularly during the epidemics of human plague during the 14th Century. Some animal products could not be traded internationally unless accompanied by a certificate of origin guaranteeing safety. During the major epizootics of the 18th Century, some contaminated products (meat, hides) were cut up, slashed or covered with lime to indicate that the product was unfit for trade or consumption.

History of trichinellosis surveillance.

The origin of trichinellosis, which existed in ancient times as testified by the discovery of parasite larvae on an Egyptian mummy, unfolded in several stages: discovery of encapsulated larvae (in the 1820s), identification and scientific description of these larvae (Paget & Owen, 1835), followed by experimental infestations of animals (dogs, pigs, rabbits, mice) or of humans as from 1850. The main occurrences of trichinellosis were followed with particular attention in Europe (Germany, Denmark, France, etc.) and in the United States of America at the end of the XIXth century. They affected numerous domestic animal species (pigs, horses, etc.) or wildlife and humans. Germany paid the heaviest toll with regard to the disease in humans, between 1860 and 1880, with several thousands of patients and more than 500 deaths. Different trichinellosis surveillance systems were set up in the relevant countries in the 1860s. In humans, this surveillance was carried out on affected living patients by a biopsy of the biceps muscles and subsequently by an analysis of eosinophilia (1895). In animals, surveillance was for a long time solely based on postmortem examination of the muscles of the affected animals. This method was used for the first time in 1863 in Germany, and from the 1890s, on several hundreds of thousands of pigs in Europe or in the United States of America.

[Brief review of the history of zoonoses]. / Brefs rappels sur l'histoire des zoonoses.

By studying the surviving documents describing surveillance and methods of control of zoonoses in the distant past, the history of the fight against these diseases can be retraced. Prior to the 20th Century, the best known zoonoses were, amongst others, rabies, anthrax, glanders, tuberculosis, plague, yellow fever, influenza, and certain zoonotic parasitic diseases. An analysis of historical events yields a number of lessons as to the positive and negative influences of past theories regarding the aetiology, contagiousness and control of these diseases. These lessons serve as a reminder, to all those involved in the fight against emerging zoonoses, of the urgent need for extensive research on the aetiology and mode of transmission of these zoonoses, in addition to the need for timely application of the findings of such research to disease control activities.

[Surveillance and prevention of animal rabies in the world]. / Surveillance et prophylaxie de la rage animale dans le monde.

The author examines in turn methods and results for surveillance and control of rabies in animals. Surveillance is essentially carried out by collecting laboratory results from diagnoses of rabies in animals through direct immunofluorescence in the sample or after mouse inoculation or inoculation in cell cultures. Due to technical and financial constraints, the results collected are usually insufficient in number, particularly in developing countries. Surveillance of rabies is thus often based on data obtained from a non-target species (human beings). Disease prophylaxis varies according to whether rabies is found in wildlife or domestic animals. In both cases, there is at present a tendency to abandon methods of sanitary prophylaxis by reducing the number of vector-animals (fox, stray dogs, cats, bats, etc.), and instead to introduce medical prophylaxis by preventive vaccination. As a result, oral vaccination has already given spectacular results in the fight against rabies in foxes, and could also be used for dogs. The author specifies the conditions for applying this vaccination.

[Transmission of rabies virus: importance of the species barrier]. / Transmission du virus de la rage: importance de la barrière d'espèce.

The authors describe experimental inoculations of different animal species with either the wild-type rabies virus or the modified one through in vivo or in vitro passages. With these experiments, it was possible to determine the 50% lethal dose of these viruses for these species, and to thus quantify the importance of the species barrier that opposes, in particular, the transmission of vulpine rabies to cats and dogs (respectively 10(5) and 10(6) times more resistant than foxes). Studies were also undertaken on the influence of the inoculation route and that of serial passages of the virus in vivo or in vitro on the importance of resistance to rabies. The epidemiological consequences of the existence of a species barrier, its nature and variability, are discussed.

[International organization of the campaign against anthropozoonoses]. / Organisation internationale de la lutte contre les anthropozoonoses.

After briefly defining the scope of his presentation, the author will describe the respective roles of the different international, national and regional organization in the surveillance of anthropozoonoses. He will then restate the objectives of international control of anthropozoonoses, i.e. limit spread by strictly restricting exportations of animals and animal products (International Animal Health Code of the International Epizooties) and reduce disease incidence by coordinating the application of regional regulatory measures. The presentation will be fully illustrated by tables and examples from the field. In conclusion the author will emphasize the need for standardization of international control of anthropozoonoses to prevent possible spread as a result of greater free trade in the world.

Early methods of surveillance and control for contagious bovine pleuropneumonia.

From the many existing documents on the history of contagious bovine pleuropneumonia, it is possible to describe the practical measures adopted for disease surveillance and control from ancient times until the 19th century. Surveillance was based on diagnosis, post-mortem examination, animal inoculation and also on knowledge of the conditions under which infection occurred: aetiology, pathogenesis, mode of infection, susceptible species, virulent material, incubation period, etc. The historical facts are assembled and compared, with comments on each of these points. Control was based upon the application of health control measures or vaccination. A study of these two procedures makes it possible to compare their efficacy and to describe the principal steps in their implementation.

[Vaccines against anthrax in animals, from Louis Pasteur to our day]. / Les vaccins contre la fièvre charbonneuse des animaux, de Louis Pasteur à nos jours.

The authors outline the history of vaccination against anthrax in animals, from the end of the 19th century to the present time. The three main steps in the production of specific vaccines are described in detail: production of vaccines from live, encapsulated bacteria, followed by vaccines from live, unencapsulated bacteria and, finally, subunit vaccines. Advantages and disadvantages of these three types of vaccine, some of which are still in use today, are described and discussed.

[Infectious pathology of Canidae and Felidae in zoological parks]. / Pathologie infectieuse des Canidés et Félidés des parcs zoologiques.

The Canidae (36 species) and Felidae (34-37 species) are two families of carnivores represented by numerous exotic species in zoos or wildlife reserves. To some extent, the diseases of these species are similar to those of dogs and cats, and are therefore relatively well known. However, there are differences in sensitivity to infectious agents, treatments and vaccines. Canidae and Felidae may also act as carriers or even vectors of zoonoses, such as leptospirosis, rabies, salmonellosis, toxoplasmosis and tuberculosis. Due to their behaviour patterns and morphological adaptations, these species are capable of transmitting various opportunistic infections by biting or scratching. These characteristics mean that Canidae and Felidae are difficult to keep in captivity, and require special health precautions, particularly protection from contact with stray carnivores.

Experience with veterinary vaccines in warm climates.

After a short description of the African laboratories manufacturing veterinary vaccines, the authors explain the main constraints for the use, in the field, of veterinary vaccines in warm climates. The need to respect the cold chain from the supplier of vaccines to the recipient animal is emphasised. In the Ivory Coast, during national vaccination campaigns, it has been proved that the quality of the rinderpest and contagious bovine pleuropneumonia vaccines is satisfactory when there is no disruption in the cold transport services. The data of this survey are exposed. In the framework of a project entitled "Thermostable rinderpest Vaccine, Transfer of Technology", a thermostable vaccine has been developed. It is manufactured in different African laboratories and integrated in some Pan African Rinderpest Campaign (PARC) vaccination programmes. On the other hand, the prospects offered by new thermotolerant attenuated vaccines against Newcastle disease are exposed. Finally, the authors present an outlook on the development of thermoresistant veterinary vaccines, such as those produced by genetic engineering, in particular with pox virus vectors.

The role of international and regional organisations in the regulation of veterinary biologicals.

The authors discuss the role played by international and regional organisations in the registration and testing of veterinary biological products. International organisations which contribute significantly to this field include the Office International des Epizooties (OIE)--through the work of the Standards Commission and the publication of the Manual of standards for diagnostic tests and vaccines--, the Food and Agriculture Organisation of the United Nations (FAO) and the World Health Organisation (WHO)--through the work of the Joint FAO/International Atomic Energy Agency (IAEA) Division of Nuclear Techniques in Food and Agriculture in standardising enzyme-linked immunosorbent assay (ELISA) techniques, as well as through WHO Expert Committees. In Europe, the most important regional organisations are the European Commission and the European Pharmacopoeia. In the Americas, the most significant contribution is made by the two specialised institutes of the Pan American Health Organisation (namely INPPAZ [Pan American Institute for Food Protection and Zoonoses] and PANAFTOSA [Pan American Foot and Mouth Disease Centre]), and by the Inter-American Institute for Cooperation in Agriculture. In Africa, PANVAC (the Pan-African Veterinary Vaccine Centre) continues to perform valuable work in testing veterinary vaccines. For the industrialised countries, the Organisation for Economic Co-operation and Development (OECD) is involved in the regulation of biotechnology products and in standardising "good laboratory practice' for vaccine manufacture. A table is presented which summarises and compares the respective roles of these organisations in the harmonization of licensing and testing procedures, the distribution of reference reagents, vaccine testing and the creation of vaccine banks.

[Efficacy of the administration of serum amd vaccine for the antirabies treatment of experimentally-infected sheep]. / Eficacia de la administración de suero y vacuna en el tratamiento antirrábico de ovinos infectados experimentalmente.

The objectives of this study were to examine the humoral immune response of sheep to experimental infection with an isolate of rabies virus from a fox, to analyse the efficacy of vaccination as a method of post-infection treatment, and to find a suitable animal model to evaluate new procedures for human vaccination following infection. A total of 47 sheep were used. Initially, 26 sheep received an intramuscular injection of a suspension of virus (titre: 10(6.8) 50% lethal dose for mice by the intracerebral route). Half of the sheep were subsequently treated using a vaccine on the day of infection and at 3, 7, 14 and 30 days post-infection. The remaining half comprised the unvaccinated controls. This vaccination protected seven of thirteen sheep, while nine of the thirteen controls died. Subsequently, 21 sheep were inoculated under the same conditions as in the previous trial. The animals were divided into three groups of seven animals each. The first group was vaccinated in the same way as described above. The second group received an injection of anti-rabies immunoglobulin of human origin (26.3 IU/kg of body weight), followed by the course of vaccine treatment 24 hours later. The remaining group acted as unvaccinated controls. Of the seven sheep given vaccine alone, four were protected, while all seven animals given immunoglobulin and vaccine were protected. Six of the seven untreated controls died. In this study, no apparently-healthy carriers of rabies virus were created by any of the treatments used, nor was there any shortening of the incubation periods. Additional observations were made concerning incubation periods and the course of the disease, as well as symptoms, lesions and the presence of rabies virus in various nerve centres and salivary glands of the experimental sheep.

History of disinfection from early times until the end of the 18th century.

The author describes and analyses the methods of disinfection in use until the end of the 18th century, i.e. before the scientific demonstration of the role of pathogenic microorganisms. These methods are classified into three categories: chemical (by derivatives of sulphur, mercury, copper, and also by alkalis and acids), physical (heating, fumigation, filtration, etc.) and biological (burial). The author concludes that, despite their empiricism, these methods were of great value to those responsible for controlling diseases of animals, as in some cases they were able to eradicate diseases while still ignorant of the causal mechanisms.

Early methods for the surveillance and control of rabies in animals.

From the many existing documents on the history of rabies in animals, it is possible to describe with precision the practical measures adopted for the surveillance and control of rabies in animals from antiquity until the 18th century. Surveillance is based on clinical diagnosis, post-mortem examination, animal inoculation and knowledge of the conditions under which infection occurred: aetiology, pathogenesis, susceptible species, virulent material, mode of infection, incubation period, etc. The historical data are assembled and compared, with comments on each of these points. Control is based on the application of general disease control measures and attempts at vaccination and treatment. A study of these procedures enables a comparison of their efficacy and a description of the major steps which led to (or delayed) the work of Louis Pasteur.

Early methods for the surveillance and control of glanders in Europe.

From the many existing documents on the history of glanders, it is possible to detail the practical measures adopted for disease surveillance and control from antiquity until the 19th century, principally in European countries. Surveillance is based on clinical diagnosis, post-mortem examination, animal inoculation and knowledge of the conditions under which infection occurred: aetiology, pathogenesis, susceptible species, virulent material, mode of infection, incubation period, etc. The historical data are assembled and compared, with comments on each of these points. Control is based on the application of general disease control measures and attempts at vaccination and treatment. A study of these procedures enables a comparison of their efficacy and a description of the major steps in their implementation.

Assay of oral vaccination of dogs against rabies in Tunisia with the vaccinal strain SADBern.

The possibility of immunizing dogs orally against rabies, using SADBern, an attenuated strain, was tested on dogs in the field in Tunisia. This strain induced high neutralizing antibody titres and conferred to all vaccinated dogs total resistance against a challenge with a Maghrebian strain. However, an excretion of virus of vaccinal origin was observed in one dog, hampering the use of SADBern in dogs. Nevertheless, this work demonstrates for the first time that dogs in developing countries, especially those which are inaccessible to parenteral vaccination, could be efficiently immunized against rabies by the oral route.