Companion animal parasitology: a clinical perspective

In recent years there have been many changes to the ways that clinical veterinary science is conducted and nowhere is this more evident than in companion animal practice. Veterinarians working with pet dogs and cats are facing new challenges associated with the emergence and re-emergence of parasitic diseases. Some, such as Neospora caninum, have been recently recognised; others like Giardia and Cryptosporidium have been reported with increasing frequency, in part as a result of laboratory tests with improved sensitivity and specificity. In many regions, the emergence of parasitic diseases has been a consequence of pet travel and exotic diseases pose a unique diagnostic challenge for the veterinarian, as the index of suspicion for these conditions may be absent. The ranges of certain vector-borne diseases such as babesiosis, hepatozoonosis, ehrlichiosis, leishmaniasis and dirofilariasis are extending due to ecological and climatic changes and enhanced by animals with subclinical infection returning home from endemic areas. In companion animal practice, veterinarians have the additional responsibility of providing accurate information about the zoonotic transmission of parasite infections from pets, especially to those most vulnerable such as children, the elderly and the immunocompromised. Effective education is vital to allay public concerns and promote responsible pet ownership.     

Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling

Parasitic diseases, caused by protozoa, helminths and arthropods, rank among the most important problems in human and veterinary medicine, and in agriculture, leading to debilitating sicknesses and loss of life. In the absence of vaccines and with the general failure of vector eradication programs, drugs are the main line of defence, but the newest drugs are being tracked by the emergence of resistance in parasites, sharing ominous parallels with multidrug resistance in bacterial pathogens. Any of a number of mechanisms will elicit a drug resistance phenotype in parasites, including: active efflux, reduced uptake, target modification, drug modification, drug sequestration, by-pass shunting, or substrate competition. The role of ABC transporters in parasitic multidrug resistance mechanisms is being subjected to more scrutiny, due in part to the established roles of certain ABC transporters in human diseases, and also to an increasing portfolio of ABC transporters from parasite genome sequencing projects. For example, over 100 ABC transporters have been identified in the Escherichia coli genome, but to date only about 65 in all parasitic genomes. Long established laboratory investigations are now being assisted by molecular biology, bioinformatics, and computational modelling, and it is in these areas that the role of ABC transporters in parasitic multidrug resistance mechanisms may be defined and put in perspective with that of other proteins. We discuss ABC transporters in parasites, and conclude with an example of molecular modelling that identifies a new interaction between the structural domains of a parasite P-glycoprotein.     

Parasitic diseases in marine cage culture--an example of experimental evolution of parasites?

Rapid development of fish culture in marine cages has been associated with an emergence of parasitic diseases. There is a general trend to an increase in infections with ectoparasites with direct life cycles and a reduced diversity of parasites in aquaculture. Some mariculture creates conditions that are similar to serial passage experiments, which are used to study adaptation during experimental evolution of pathogens. In particular, increased density of fish, repeated introduction of naive hosts, homogenous host populations, fast growth and a potential decrease in genetic diversity are attributes of both aquaculture and serial passage experiments. Some free-living organisms, for example Neoparamoeba spp. and Uronema spp. parasitise fish in culture, but have not been reported from wild populations. Farming fish in marine cages can increase the risk of outbreaks of parasitic diseases, including those caused by opportunistic parasites. However, aquaculture has the potential to control parasitic diseases through selective breeding, vaccination and general fish health management.     

HIV-1/parasite co-infection and the emergence of new parasite strains

HIV-1 and parasitic infections co-circulate in many populations, and in a few well-studied examples HIV-1 co-infection is known to amplify parasite transmission. There are indications that HIV-1 interacts significantly with many other parasitic infections within individual hosts, but the population-level impacts of co-infection are not well-characterized. Here we consider how alteration of host immune status due to HIV-1 infection may influence the emergence of novel parasite strains. We review clinical and epidemiological evidence from five parasitic diseases (malaria, leishmaniasis, schistosomiasis, trypanosomiasis and strongyloidiasis) with emphasis on how HIV-1 co-infection alters individual susceptibility and infectiousness for the parasites. We then introduce a simple modelling framework that allows us to project how these individual-level properties might influence population-level dynamics. We find that HIV-1 can facilitate invasion by parasite strains in many circumstances and we identify threshold values of HIV-1 prevalence that allow otherwise unsustainable parasite strains to invade successfully. Definitive evidence to test these predicted effects is largely lacking, and we conclude by discussing challenges in interpreting available data and priorities for future studies.     

Severe and fatal central nervous system disease in humans caused by Baylisascaris procyonis, the common roundworm of raccoons: a review of current literature

Baylisascaris procyonis, a parasitic infection of raccoons, causes severe neurologic disease in humans when infective eggs from raccoon feces are ingested. Definitive diagnosis is challenging, but can be made by isolation of larvae in brain biopsy or exclusion of other potential causes of eosinophilic meningoencephalitis. Prevention efforts are critical due to the lack of effective treatment.     

Fish-borne parasitic zoonoses: status and issues

The fish-borne parasitic zoonoses have been limited for the most part to populations living in low- and middle-income countries, but the geographical limits and populations at risk are expanding because of growing international markets, improved transportation systems, and demographic changes such as population movements. While many in developed countries will recognize meat-borne zoonoses such as trichinellosis and cysticercosis, far fewer are acquainted with the fish-borne parasitic zoonoses which are mostly helminthic diseases caused by trematodes, cestodes and nematodes. Yet these zoonoses are responsible for large numbers of human infections around the world. The list of potential fish-borne parasitic zoonoses is quite large. However, in this review, emphasis has been placed on liver fluke diseases such as clonorchiasis, opisthorchiasis and metorchiasis, as well as on intestinal trematodiasis (the heterophyids and echinostomes), anisakiasis (due to Anisakis simplex larvae), and diphyllobothriasis. The life cycles, distributions, epidemiology, clinical aspects, and, importantly, the research needed for improved risk assessments, clinical management and prevention and control of these important parasitic diseases are reviewed.     

The role of amino acid electron-donor/acceptor atoms in host-cell binding peptides is associated with their 3D structure and HLA-binding capacity in sterile malarial immunity induction

Plasmodium falciparum malaria continues being one of the parasitic diseases causing the highest worldwide mortality due to the parasite’s multiple evasion mechanisms, such as immunological silence. Membrane and organelle proteins are used during invasion for interactions mediated by high binding ability peptides (HABPs); these have amino acids which establish hydrogen bonds between them in some of their critical binding residues. Immunisation assays in the Aotus model using HABPs whose critical residues had been modified have revealed a conformational change thereby enabling a protection-inducing response. This has improved fitting within HLA-DRβ1¹ molecules where amino acid electron-donor atoms present in β-turn, random or distorted α-helix structures preferentially bound to HLA-DR53 molecules, whilst HABPs having amino acid electron-acceptor atoms present in regular α-helix structure bound to HLA-DR52. This data has great implications for vaccine development.     

Control and prevention of emerging parasitic zoonoses

Emerging zoonoses have been defined as zoonoses that are newly recognised or newly evolved, or that have occurred previously but show an increase in incidence or expansion in geographical, host or vector range. Among parasitic zoonoses, protozoa are particularly likely to emerge. Control and prevention of emerging parasitic zoonoses are complex tasks that require an integrative and multidisciplinary approach. Reduction of parasite burden is certainly a major objective but cannot be set alone. Therefore, environmental and ecological modifications need to be implemented to reduce not only the parasitic load, but also the risk of parasite transmission. Finally, education and behavioral changes are critical for the success of both control and prevention of these diseases. However, without appropriate financial resources specifically allocated at the local and national levels as well as through international cooperation, control and prevention of these emerging parasitic diseases will not be possible.     

The future impact of societal and cultural factors on parasitic disease -- some emerging issues

A variety of societal and cultural factors will increase host exposure or susceptibility to infectious agents, particularly parasites. Such factors have already had a major impact on the emergence of infectious diseases and the situation is likely to worsen further as we enter the new millennium. The changes that are enhancing the spread and transmission of parasitic diseases, as well as those which are adversely affecting host responsiveness, are examined with reference to specific parasites.     

Emerging viral infections in a rapidly changing world

Emerging viral infections in both humans and animals have been reported with increased frequency in recent years. Recent advances have been made in our knowledge of some of these, including severe acute respiratory syndrome-associated coronavirus, influenza A virus, human metapneumovirus, West Nile virus and Ebola virus. Research efforts to mitigate their effects have concentrated on improved surveillance and diagnostic capabilities, as well as on the development of vaccines and antiviral agents. More attention needs to be given to the identification of the underlying causes for the emergence of infectious diseases, which are often related to anthropogenic social and environmental changes. Addressing these factors might help to decrease the rate of emergence of infectious diseases and allow the transition to a more sustainable society.     

Diamine derivatives with antiparasitic activities

There are a lack of effective chemotherapies for many parasitic diseases. Polyamine pathways have been reported as potential targets for the development of new chemotherapies against parasitic diseases. In the present study, different libraries of substituted diamines totalling 78 compounds have been synthesized on solid support and their activities against malaria and leishmania parasites have been determined. Most active compounds demonstrated submicromolar activities against both organisms and their structure-activity relationships are discussed.     

Side effects of insecticides on aphidius rhopalosiphi (Hym.: Aphidiidae) In laboratory

The toxicity of bifenthrin, cyfluthrin, λ-cyhalothrin, cypermethrin, deltamethrin, esfenvalerate, fluvalinate, phosalon and pirimicarb have been assessed in laboratory on the parasitic hymenoptera Aphidius rhopalosiphi. A strong toxic effect was found with every tested product when adult parasitoids were exposed to freshly applied residues on both glass plates and maize leaves for 24 hours. Only two products, fluvalinate and esfenvalerate, did not kill all the insects. No differences were observed between mortalities on glass plates and leaves. Applied on aphids mummies, cyfluthrin and deltamethrin slightly reduced the emergence of young parasitoids, but not their reproductive performance. The other tested products had no effects on adult emergence. On basis of these results, the insecticides are of comparable toxicity to A. rhopalosiphi in laboratory.     

Microorganisms and man. Various characteristics of their coexistence at present

Modern data of literature on microbial associations and their role in human health and diseases are presented. As pointed out in this work, the characteristic feature of the XX century is the emergence and the re-emergence of 36 new infections. The emergence of many infections is associated with such factors as the increased migration of the population, ecological environmental disasters, etc. Grounds for a new view on the etiology of a number of chronic somatic diseases are given. The task of preparation development for the immunoprophylaxis of 25-30 infections has been set by WHO as its target for the year 2025. Prospects of new approaches to the development of new generation vaccines against bacterial, viral and parasitic infections, including HIV/AIDS, tuberculosis, virus hepatitides, malaria, etc., are shown.     

Changing patterns of parasitic disease: old enemies and new invaders--the battle wages on

• 1.A. The classic parasitic diseases—malaria, schistosomiasis, the filariases, and many other familiar “old enemies”—continue to be the major parasitic causes of morbidity and morality and the continuing objects of our research and control efforts. Although all have been receptive to control interventions under certain circumstances, most of these infections continue to be transmitted without apparent restrictions in the rural, developing regions where nearly one-half of all the world's people live. New technologie achievements will improve the chances for treatment and control of these infections, but more important, may be improved administrative capacity and the commitment of political will and economic resources toward these goals.
• 2.B. The emergence of resistance to drugs and chemical control agents as a result of selection of resistant strains in the face of exposure to the chemical is a growing phenomenon among parasites with very serious public health implications. Strains of Plasmodium falciparum resistant to most drugs formerly effective for prophylaxis and treatment have appeared in Africa, Asia and parts of South and Central America at a faster pace than new compounds can be made available. Similar problems have been reported with gastrointestinal nematodes of livestock animals and many insect vectors.
• 3.C. Cryptosporidiosis emerged dramatically as a human disease when it appeared as one of the many opportunistic infections suffered by patients with AIDS. Increased clinical awareness and improved diagnostic procedures have now implicated Cryptosporidium as an important worldwide cause of diarrheal illness in persons with normal immunologic function. Zoonotic and various forms of person-to-person transmission are now recognized as important modes of spread for this protozoan.
• 4.D. Development and widespread use of specific serodiagnostic tests for human toxocariasis has revealed that zoonotic transmission of the common dog and cat ascarids is widespread in populations in industrialized societies. Serologic studies suggest that human Toxocara infection is even more common in tropical, developing areas but the health impact of this has not yet been measured. New nematode agents of larva migrans have been identified recently. One of them, the racoon ascarid, Baylisascaris procyonis, may increase in importance as its host extends its range as a commensal resident.
• 5.E. In developed countries where social and environmental conditions limit opportunities for transmission of most protozoal and helminthic disease agents, parasitic diseases are seen often as imported infections in returning tourists or immigrants who became infected in foreign endemic areas. One of these, imported malaria, has been exacerbated in the past decade by the resurgence of malaria transmission in Asia, the resettlement, in many countries, of refugees from Southeast Asia, and the spread of chloroquine-resistant P. falciparum in Africa.
• 6.F. Other special problems of parasitic diseases in developed countries include the increase in opportunistic parasitic pathogens (Pneumocystis, Toxoplasma, Strongyloides and others) in patients with AIDS and iatrogenically-caused immunodepression and the occurrence of infections resulting from changing dietary preferences and “fads”, e.g. diphyllobothriasis from “Shushi” and “Sashimi” (Japan, United States and Canada) and gnathostomiasis from imported fish (Japan).

     

Parasitic disease in humans: the extent in Canada.

Much is being said, often dramatically, about the potential hazards of parasitic diseases in Canada, but little or no attempt has been made to determine the true extent of the problem. Indigenous parasite pathogens are recognized in resident Canadians, and pathogens are acquired by travellers abroad or reported from immigrants. The role of each of these categories is important in the characterization of the problem of parasitic diseases in Canada. From data provided by provincial laboratories and hospitals it is estimated that 1 person in 1000 will spend 1 day per year in hospital because of intestinal parasites, and 1 in 100 each year will have a diagnosis of intestinal parasitic infection made from examination of a stool sample.     

Bioinformatic tools for DNA methylation and histone modification: A survey

Epigenetic inheritance occurs due to different mechanisms such as chromatin and histone modifications, DNA methylation and processes mediated by non-coding RNAs. It leads to changes in gene expressions and the emergence of new traits in different organisms in many diseases such as cancer. Recent advances in experimental methods led to the identification of epigenetic target sites in various organisms. Computational approaches have enabled us to analyze mass data produced by these methods. Next-generation sequencing (NGS) methods have been broadly used to identify these target sites and their patterns. By using these patterns, the emergence of diseases could be prognosticated. In this study, target site prediction tools for two major epigenetic mechanisms comprising histone modification and DNA methylation are reviewed. Publicly accessible databases are reviewed as well. Some suggestions regarding the state-of-the-art methods and databases have been made, including examining patterns of epigenetic changes that are important in epigenotypes detection.     

Years of life lost due to Huntington disease.

Many genetic diseases shorten the lives of people who have them. Hence, it makes sense to speak of years of life lost due to cystic fibrosis or sickle-cell anemia or numerous other genetic disorders. In conventional practice, years of life lost is calculated for causes of death only, but a genetic disease is better understood as a risk-altering state or condition: it acts not at the time of death only but from birth onwards. Therefore, we must reformulate the concept of years of life lost before applying it to genetic conditions. This has already been done for congenital genetic diseases. This paper extends the reformulation to diseases with delayed onset. Huntington disease (HD) is used as an example.     

The bright side of parasitic plants: what are they good for?

Parasitic plants are mostly viewed as pests. This is caused by several species causing serious damage to agriculture and forestry. There is however much more to parasitic plants than presumed weeds. Many parasitic plans exert even positive effects on natural ecosystems and human society, which we review in this paper. Plant parasitism generally reduces the growth and fitness of the hosts. The network created by a parasitic plant attached to multiple host plant individuals may however trigger transferring systemic signals among these. Parasitic plants have repeatedly been documented to play the role of keystone species in the ecosystems. Harmful effects on community dominants, including invasive species, may facilitate species coexistence and thus increase biodiversity. Many parasitic plants enhance nutrient cycling and provide resources to other organisms like herbivores or pollinators, which contributes to facilitation cascades in the ecosystems. There is also a long tradition of human use of parasitic plants for medicinal and cultural purposes worldwide. Few species provide edible fruits. Several parasitic plants are even cultivated by agriculture/forestry for efficient harvesting of their products. Horticultural use of some parasitic plant species has also been considered. While providing multiple benefits, parasitic plants should always be used with care. In particular, parasitic plant species should not be cultivated outside their native geographical range to avoid the risk of their uncontrolled spread and the resulting damage to ecosystems.

Advances

• Parasitic plants may act as highways for transferring systemic signals among host plants.
• Harmful effects of parasitic plants on individual hosts suppress community dominants including invasive species, reduce competitive pressure, and may increase biodiversity.
• Parasitic plants enhance nutrient cycling and provide resources for other organisms thus contributing to facilitation cascades in ecosystems.
• Many parasitic plants are recorded to have medicinal values against a broad range of diseases.
• There is a long tradition of worldwide human use of parasitic plants, which have been cultivated for their products and aesthetic values.

     

Effects of environmental change on emerging parasitic diseases

Ecological disturbances exert an influence on the emergence and proliferation of malaria and zoonotic parasitic diseases, including, Leishmaniasis, cryptosporidiosis, giardiasis, trypanosomiasis, schistosomiasis, filariasis, onchocerciasis, and loiasis. Each environmental change, whether occurring as a natural phenomenon or through human intervention, changes the ecological balance and context within which disease hosts or vectors and parasites breed, develop, and transmit disease. Each species occupies a particular ecological niche and vector species sub-populations are distinct behaviourally and genetically as they adapt to man-made environments. Most zoonotic parasites display three distinct life cycles: sylvatic, zoonotic, and anthroponotic. In adapting to changed environmental conditions, including reduced non-human population and increased human population, some vectors display conversion from a primarily zoophyllic to primarily anthrophyllic orientation. Deforestation and ensuing changes in landuse, human settlement, commercial development, road construction, water control systems (dams, canals, irrigation systems, reservoirs), and climate, singly, and in combination have been accompanied by global increases in morbidity and mortality from emergent parasitic disease. The replacement of forests with crop farming, ranching, and raising small animals can create supportive habitats for parasites and their host vectors. When the land use of deforested areas changes, the pattern of human settlement is altered and habitat fragmentation may provide opportunities for exchange and transmission of parasites to the heretofore uninfected humans. Construction of water control projects can lead to shifts in such vector populations as snails and mosquitoes and their parasites. Construction of roads in previously inaccessible forested areas can lead to erosion, and stagnant ponds by blocking the flow of streams when the water rises during the rainy season. The combined effects of environmentally detrimental changes in local land use and alterations in global climate disrupt the natural ecosystem and can increase the risk of transmission of parasitic diseases to the human population.     

Protein network prediction and topological analysis in <Emphasis Type="Italic">Leishmania major</Emphasis> as a tool for drug target selection

Background  

Leishmaniasis is a virulent parasitic infection that causes a worldwide disease burden. Most treatments have toxic side-effects and efficacy has decreased due to the emergence of resistant strains. The outlook is worsened by the absence of promising drug targets for this disease. We have taken a computational approach to the detection of new drug targets, which may become an effective strategy for the discovery of new drugs for this tropical disease.