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Many virulent animal diseases, especially in livestock, are very contagious and can be economically devastating, especially in developing tropical countries. Livestock are susceptible to many types of dysentery and diseases such as African horse sickness, bovine leukosis, bovine infectious rhinotracheitis, brucellosis, and Rift Valley fever, to name just a few. Developing countries often have no way of coping with the widespread outbreak of disease.
Most biotechnologies related to health focus on the needs of the developed world, meaning that 90% of health research is devoted to the health problems of 10% of the world’s population. Two main approaches are being used to develop vaccines using recombinant DNA technology.
The first involves deleting genes that determine the virulence of the pathogen, thus producing attenuated organisms (non-pathogens) that can be used as live vaccines. Currently, this strategy is more effective against viral and bacterial diseases than against parasites.
Attenuated live vaccines have been developed against the herpes viruses that cause pseudorabies in pigs and infectious bovine rhinotracheitis in cattle. A number of candidate Salmonella vaccines have also been produced. The second approach is to identify protein subunits of pathogens that can stimulate immunity.
The International Livestock Research Institute (ILRI) used this approach to develop a vaccine against Theileria parva, the parasite that causes East Coast fever in African cattle. A novel strategy for developing vaccines against bloodsucking parasites involves using, components of the gut wall of the parasite that are not usually exposed to the immune system of the host.
When the parasite feeds, it ingests antibodies induced by the vaccine, which destroy the gut wall and, consequently, kill the parasite. This strategy has been used successfully to develop a vaccine against the one-host tick Boophilus microplus.
Vaccination is one of the most effective and sustainable methods of controlling disease. Vaccines against parasitic diseases in Africa and viral diseases in Asia have been shown to control disease effectively and increase livestock productivity. A recent approach has been to use vaccines based on DNA.
The use of DNA in vaccines is based on the discovery that injecting genes in the form of plasmid DNA can stimulate an immune response to the respective gene products. This immune response is a result of the genes being taken up and expressed by cells in the animal after injection. The live-vector and DNA vaccination systems could be manipulated further to enhance the immunity conferred by the gene products.
Experimental studies have demonstrated that these vaccines can potentially induce appropriate and enduring immune responses. This technology is, in principle, one of the simplest and yet most versatile methods of inducing both humeral and cellular immune responses, as well as protecting against a variety of infectious agents.
However, although immune responses have been induced in a number of larger species, most of the information on the efficacy of DNA immunisation comes from studies of mice. An exhaustive review of the information available on the use of DNA vaccines in farm animals, including cattle, pigs and poultry, has identified the areas that need specific attention before this technology can be used routinely.
These areas include the delivery, safety and compatibility of plasmids in multivalent vaccines and the potential for using immune stimulants as part of a DNA vaccine. Korean scientists have developed a combined vaccine against pleuropneumonia, pneumonic pasteurellosis and enzootic pneumonia in swine.
Molecular biology has been used to produce an improved vaccine against swine fever. In the Philippines, a vaccine has been developed that protects cattle and water buffalo against haemorrhagic septicaemia, which is the leading cause of death in these animals. The new vaccine provides improved protection at a very low cost.
Advanced diagnostic tests that use biotechnology enable the agents causing disease to be identified and the impact of disease control programmes to be monitored more precisely than was previously possible. Molecular epidemiology characterises pathogens (viruses, bacteria, parasites and fungi) by nucleotide sequencing, enabling their origins to be traced.
This is particularly important for epidemic diseases, in which pinpointing the source of the infection can significantly improve disease control. For example, the molecular analysis of rinderpest viruses has been vital in determining the lineages circulating in the world and instrumental in aiding the Global Rinderpest Eradication Programme.
Enzyme-linked immunosorbent assays have become the standard means of diagnosing and monitoring many animal and fish diseases worldwide, and the PCR technique is especially useful in diagnosing livestock disease. Many diagnostic techniques currently used in developing countries are cumbersome and unsuitable for low-resource settings.
Molecular diagnostic technologies that are either already in use or being tested in low-income regions include polymerase chain reaction (PCR), monoclonal antibodies and recombinant antigens. These technologies can be modified to facilitate their application in the developing world.
Simple hand-held devices that rely on the binding specificity of monoclonal antibodies or recombinant antigens to diagnose infection may be easily adapted for use in settings without running water, refrigeration or electricity. Molecular characterisation of the virus serotypes causing foot and mouth disease has helped in the vaccination and control programmes in Asia.
In Japan and Taiwan, DNA testing is being used to diagnose hereditary weaknesses of livestock. One test looks for the presence of the gene responsible for porcine stress syndrome in pigs. Pigs with this gene tend to produce pale poor-quality meat because of their reaction to the stress of transport and slaughter.
Pigs with this gene can now be excluded from breeding programmes, so the gene will become less common. In addition, DNA testing is being used in Japan to check for the gene that causes leucocyte adhesion deficiency in Holstein cattle. Cattle with this condition suffer from gum disease, tooth loss and stunted growth.
They usually die before they are one year old. By using DNA testing, carriers can be identified and eliminated from breeding herds. Bulls used for breeding can also be tested to make sure that they are not carriers. Another DNA test identifies a gene that leads to anaemia and retarded growth in Japanese Black cattle.
Detection of Pathogen:
New diagnostic tests will increase the sensitivity with which parasites can be detected in animals. Serological tests of livestock populations have proven inadequate for detecting exposure to infectious disease causing organisms.
The presence of antibodies does not always indicate current infection, since antibodies can remain in an animal for long periods of time. Instead of detecting the antibodies produced in response to an infection, new diagnostic methods are needed for detecting parasite proteins or antigens and DNA.
Parasite antigen detection kits are available for detecting trypanosome proteins and tick-borne protozoan parasites. Mouse monoclonal antibodies raised against specific parasite proteins are used to identify parasite antigens in animals. These assays are highly sensitive and specific. Often, specific strains or species of an infectious organism produce different responses in an infected animal.
The infecting strain determines which treatments are used. Not only can these assays detect current infections, they can also distinguish between different strains or species of parasite (for example, between the major tsetse-transmitted species of trypanosomes). Parasite-specific DNA assays are desirable because of their sensitivity and because the DNA is stable. Samples can be collected in the field and delivered to a laboratory for DNA analysis.
Polymorphic DNA sequences and their probes allow different parasites, such as tickbome parasites and trypanosomes, to be detected and distinguished. These sequences are detected in both animals and vectors by hybridisation or the polymerase chain reaction. These methods allow animal and vector populations (such as ticks) to be monitored to determine the extent of parasite infection.
Animal Genome:
The availability of animal genome sequences using high -throughput sequencing technologies will provide a battery of new tools to study disease. Genomic research will provide new insight into pathogenesis, evolution, diagnostics, vaccines, epidemiology, and therapeutics.
A well-developed bioinformatics approach to genome sequence analysis will yield valuable information for molecular epidemiology of disease outbreaks, for identification of virulence and host range factors and for development of new diagnostics and control approaches.
Current Methods of Treatment:
Examples of current methods of treatment for a few important animal diseases are presented below. In many cases, biotechnology is only beginning to offer effective treatments. Developing countries in particular have special needs because of climate (often high temperatures), lack of modern facilities (e.g. refrigeration), and a need for low- cost treatments.
Foot-and-Month Disease:
This highly contagious disease is one of the most devastating to livestock and very costly to the industry. Worldwide, approximately 30% of cloven- hoofed animals are affected. Although only about 5% of adult animals die from the disease, young cattle and pigs are most affected and approximately 50% of those afflicted die from myocarditis. Infected females abort their calves and rarely produce young. Usually infected animals are killed to avoid spreading the disease and their milk and meat cannot be used.
The most common way of protecting animals against foot-and-mouth disease is by vaccination with inactivated virus vaccine (when available). However, thermal instability, short-term protection (four to six months), and virus strain specificity present problems for treatment and prevention with vaccines. Experimental vaccines include a single inactivated antigen and a mixture of two strains of inactivated antigen for cross protective activity to different viral strains.
Coccidiosis:
Nine parasitic protozoan species in the genus Eimeria invade epithelial cells of the digestive tract and associated glands in livestock such as cattle, sheep, and poultry. Coccidiosis can be extremely costly to the poultry industry, where overcrowded, stressful conditions promote the spread of disease and make treatment very difficult. Developmental problems are found in the young, and 20% of those infected die. In industrialised countries, many feeds contain a coccidiostat to prevent the disease.
Several drugs are available both for treatment and prevention of coccidiosis. A gene for a particular protein produced by the oocysts of the protozoan has been cloned so that purified antigen can be prepared for an effective vaccine. In vivo trials have been ongoing to determine the appropriate mixture of purified antigens for a vaccine that will boost immunity to coccidiosis.
Trypanosomiasis:
More than 60 million cattle, as well as humans, pigs, domestic buffaloes, camels, horses, and small ruminants, in sub-Saharan Africa are susceptible to trypanosomiasis, a disease transmitted by the tsetse fly. Trypanosomiasis is difficult to treat since the single celled trypanosomes continually change their surface antigens during infection and can escape detection by the host’s immune system. The most common method of preventing this disease is the routine use of chemical sprays or dips.
Research is focusing on ways to prevent infection by preparing vaccines from trypanosome components involved in the pathological process, such as the proteolytic enzymes used to degrade host molecules or proteins responsible for the suppression of the cattle immune system.
Researchers are trying to isolate trypanosome-resistance genes in West African cattle so that transgenic trypanotolerant cattle can be produced. Host genes that inhibit parasite cell division may one day be identified and, through their increased expression, used to prevent the spread of the parasite within the host.
Theileriosis:
Theileriosis, or East Coast fever, a deadly disease of cattle prevalent in 12 countries of east, central and southern Africa, is caused by several strains of tick- transmitted protozoans. Losses to African farmers exceed $170 million U.S. dollars. Once ingested by the tick, the parasite develops and finally forms sporozoites in the tick’s salivary gland that are released into cattle bitten by infested ticks. Infected lymphocytes in the cattle become leukemic and eventually lympholysis occurs, usually causing death within one month of infection.
Ticks feeding on the blood of cattle infected with the protozoan transmit the disease to other cattle. At least 24 million cattle are at risk of infection, and high yielding exotic breeds are especially susceptible. Spraying or dipping cattle in a chemical insecticide has traditionally been used to control the disease.
However, even if insect resistance can develop, the milk and meat may become contaminated with the pesticide, and chemicals can harm the environment. A crude preparation of live, infected ticks with an antibiotic has been used to stimulate cattle immune systems, but immunity is not always obtained and the antibiotic may not inhibit development of the parasite.
Recombinant DNA technology offers a means of producing new drugs for treatment, synthesising monoclonal antibodies for typing strains in geographical areas, and producing sporozoite antigen for vaccination in large quantities. If specific proteins expressed in the sporozoite stage of the parasite can be cloned and expressed in bacteria and insect cultures, these recombinant proteins in vaccine form may offer immunity in cattle.
Feed Utilisation and Nutrition:
The shortage of feed in most developing countries and the increasing cost of feed ingredients mean that there is a need to improve feed utilisation. Aids to animal nutrition, such as enzymes, probiotics, single-cell proteins and antibiotics in feed, are already widely used in intensive production systems worldwide to improve the nutrient availability of feeds and the productivity of livestock.
Gene-based technologies are being increasingly used to improve animal nutrition, either through modifying the feeds to make them more digestible or through modifying the digestive and metabolic systems of the animals to enable them to make better use of the available feeds.
Feeds derived from GM plants (a quarter of which are now grown in developing countries), such as grain, silage and hay, have contributed to increases in growth rates and milk yield. Genetically modified crops with improved amino acid profiles can be used to decrease nitrogen excretion in pigs and poultry.
Increasing the levels of amino acids in grain means that the essential amino acid requirements of pigs and poultry can be met by diets that are lower in protein. Metabolic modifiers have also been used to increase production efficiency (weight gain or milk yield per feed unit), improve carcass composition (meat-fat ratio), increase milk yield and decrease animal fat.
The use of recombinant bovine somatotropin (rBST) in dairy cows increases both milk yield and production efficiency and decreases animal fat. In the USA, the use of rBST typically increases milk yield by 10% to 15%. Although trials conducted in developing countries have reported a similar percentage increase, this increase is not significant because of the low milk yields and the high cost-benefit ratio.
However, rBST is being used commercially in 19 countries where the economic returns make its use worthwhile. A porcine somatotropin has been developed that increases muscle growth and reduces body- fat deposition, resulting in pigs that are leaner and of greater market value.