Animal Health - Research Update

Advances in Control of Parasitic Diseases Continue to Rely on Biotechnology

Parasitic disease continues to be a major health problem worldwide in humans and domestic animals. Applying biotechnology has led to progress in prevention and control in many areas, particularly in regard to diagnosis.

Parasites, like most organisms, carry repetitive sequences in their genomes. These are sometimes tandem repeats (back-to-back in a chromosome), or they may be located at random throughout the genome. Often, repetitive sequences are intergenic and noncoding, and are thus far more subject to evolution and change, increasing the likelihood that they will be genus or even species specific. Since detection of these sequences is not dependent upon gene expression, which may vary over time, repetitive sequence-based assays allow detection of the parasite at any life stage. The effectiveness of repetitive sequence-based polymerase chain reaction (PCR) methods of identification has been demonstrated for parasites of several clinically important genera (1). A PCR assay has also been developed to differentiate two closely related nematode species that are virtually indistinguishable by morphologic examination (2), as well as for diagnosis of Toxoplasma and Cryptosporidium infections (3).

Attempts to develop anti-parasite vaccines have met with multiple failures. The problems often result from lack of post-translational modification by currently used vector-host systems and the inability to regenerate the secondary and tertiary structure of the native immunogens. Antigen presentation in recombinant parasite vaccines has also been thought to be a problem resulting in failed efficacy. There is now some evidence to indicate that cloning of genes for antigens of interest to yield chimeric molecules expressed in the BCG strain of Mycobacterium bovis may provide improved antigen presentation to stimulate both humoral and cellular responses (4); however, it is unlikely that future applications of this technology will be simple. Nonetheless, work is proceeding on the application of biotechnology to the development of vaccines against parasites in most food animals.

A particularly striking exception to the marginal successes reported in other systems has been a recombinant vaccine for a parasitic helminth of sheep (5). This product yielded greater than 94% protection in experimental work and is now available as a commercial product.

A further possibility is the application of anti-idiotypic monoclonal antibodies. When monoclonal antibodies are prepared against a monoclonal antibody, it is possible to obtain, in a very small number of cases, an antibody which mimics the original antigen. Results of work with Cryptosporidium perfringens epsilon toxin suggest that animals immunized with anti-idiotype monoclonals can be protected against toxin challenge.

1. Christensen CM et al.1994. Experimental Parasitol. 78:93-100.
2. Zarlenga DS et al. 1994. Experimental Parasitol. 78:28-36.
3. Savva D et al. 1990. J Med Microbiol 32: 25-31; Laxer MA et al. 1991. Am J Trop Med Hyg 45:688-694.
4. Zarlenga DS. 1994. J Amer Vet Med Assoc 204: 1616-1621.
5. Johnson KS et al. 1989. Nature 338: 585-587.

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