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Showing papers in "Advances in Parasitology in 2008"


Book ChapterDOI
TL;DR: Canine, feline and ferret heartworm disease are updated with regard to the clinical presentation, diagnosis, prevention, therapy and management of the disease, with special emphasis on the recently described Heartworm Associated Respiratory Disease (HARD) Syndrome in cats.
Abstract: Heartworm disease due to Dirofilaria immitis continues to cause severe disease and even death in dogs and other animals in many parts of the world, even though safe, highly effective and convenient preventatives have been available for the past two decades. Moreover, the parasite and vector mosquitoes continue to spread into areas where they have not been reported previously. Heartworm societies have been established in the USA and Japan and the First European Dirofilaria Days (FEDD) Conference was held in Zagreb, Croatia, in February of 2007. These organizations promote awareness, encourage research and provide updated guidelines for the diagnosis, treatment and prevention of heartworm disease. The chapter begins with a review of the biology and life cycle of the parasite. It continues with the prevalence and distribution of the disease in domestic and wild animals, with emphasis on more recent data on the spreading of the disease and the use of molecular biology techniques in vector studies. The section on pathogenesis and immunology also includes a discussion of the current knowledge of the potential role of the Wolbachia endosymbiont in inflammatory and immune responses to D. immitis infection, diagnostic use of specific immune responses to the bacteria, immunomodulatory activity and antibiotic treatment of infected animals. Canine, feline and ferret heartworm disease are updated with regard to the clinical presentation, diagnosis, prevention, therapy and management of the disease, with special emphasis on the recently described Heartworm Associated Respiratory Disease (HARD) Syndrome in cats. The section devoted to heartworm infection in humans also includes notes on other epizootic filariae, particularly D. repens in humans in Europe. The chapter concludes with a discussion on emerging strategies in heartworm treatment and control, highlighting the potential role of tetracycline antibiotics in adulticidal therapy.

499 citations


Book ChapterDOI
TL;DR: Examples in which anisakid nematodes recognized genetically at the species level in definitive and intermediate/paratenic hosts from various geographical areas of the Boreal and Austral regions and their infection levels have been used as biological indicators of fish stocks and food-web integrity in areas at high versus low levels of habitat disturbance are presented.
Abstract: The application of molecular systematics to the anisakid nematodes of the genera Anisakis, Pseudoterranova and Contracaecum, parasites of aquatic organisms, over the last two decades, has advanced the understanding of their systematics, taxonomy, ecology and phylogeny substantially Here the results of this effort on this group of species from the early genetic works to the current status of their revised taxonomy, ecology and evolutionary aspects are reviewed for each of three parasitic groups It has been shown that many anisakid morphospecies of Anisakis, Contracaecum and Pseudoterranova include a certain number of sibling species Molecular genetic markers provided a rapid, precise means to screen and identify several species that serve as definitive and intermediate and or/paratenic hosts of the so far genetically characterized species Patterns of differential distribution of anisakid nematodes in various definitive and intermediate hosts are presented Differences in the life history of related species can be due both to differential host-parasite co-adaptation and co-evolution, and/or to interspecific competition, that can reduce the range of potential hosts in sympatric conditions Phylogenetic hypotheses attempted for anisakid nematodes and the possible evolutionary scenarios that have been proposed inferred from molecular data, also with respect to the phylogeny of their hosts are presented for the parasite-host associations Anisakis-cetaceans and Contracaecum-pinnipeds, showing that codivergence and host-switching events could have accompanied the evolution of these groups of parasites Finally, examples in which anisakid nematodes recognized genetically at the species level in definitive and intermediate/paratenic hosts from various geographical areas of the Boreal and Austral regions and their infection levels have been used as biological indicators of fish stocks and food-web integrity in areas at high versus low levels of habitat disturbance (pollution, overfishing, by-catch) are presented

402 citations


Book ChapterDOI
TL;DR: The search for a definition of 'strain', how the data and discussion shaped current understandings of many aspects of malaria and a number of specific connections with perspectives from the past 30 years are suggested.
Abstract: From the 1920s to the 1970s, a large body of principles and evidence accumulated about the existence and character of 'strains' among the Plasmodium species responsible for human malaria. An extensive research literature examined the degree to which strains were autonomous, stable biological entities, distinguishable by clinical, epidemiological or other features, and how this knowledge could be used to benefit medical and public health practice. Strain theory in this era was based largely on parasite phenotypes related to clinical virulence, reactions to anti-malarial drugs, infectivity to mosquitoes, antigenic properties and host immunity, latency and relapse. Here we review the search for a definition of 'strain', suggest how the data and discussion shaped current understandings of many aspects of malaria and sketch a number of specific connections with perspectives from the past 30 years.

55 citations


Book ChapterDOI
TL;DR: A causal association between geohelminth infection and atopic disorders has not been established but some helminthic substances, especially the cytokines, have respiratory and anti-allergic effects, and may therefore become useful as therapeutic modalities for many atopic and allergic disorders.
Abstract: This chapter examines the relationship between atopic disorders and parasitic infections. Atopy is an exaggerated IgE-mediated Type-1 immune response in predisposed individuals. Conflicting information exists in regard to the relationship of parasitic infections and the classic allergic diseases, that is, atopic dermatitis, allergic rhinitis and asthma. Attention is paid to the explanations for these discrepancies in the literature found within both human and animal studies on atopy with particular emphasis on helminthic infections. The factors that cause only a proportion of atopic individuals to develop clinical disease have not been defined although helminths confer protection in many studies examined. Early childhood infections help induce a Th1-biased immunity and prevent the induction of the Th2 system that causes atopy. Acute parasitic infections may increase manifestations of allergy, whereas chronic infections with parasites decrease atopic predisposition. Nonetheless, a causal association between geohelminth infection and atopic disorders has not been established. Some helminthic substances, especially the cytokines, have respiratory and anti-allergic effects, and may therefore become useful as therapeutic modalities for many atopic and allergic disorders.

18 citations


Book ChapterDOI
TL;DR: This chapter discusses de novo synthesis of pyrimidines and folates in malaria parasites and finds that UMP may be formed from uracil via salvage by the action of UPRT or by the sequential action of uridine phosphorylase (UP) and uridine kinase.
Abstract: Publisher Summary This chapter discusses de novo synthesis of pyrimidines and folates in malaria parasites. Early experimental findings of two pyrimidine biosynthetic enzymes (OMPDC and TS) in Plasmodium lophurae suggested that, unlike the duckling host, malaria parasites synthesized pyrimidines de novo from precursors such as CO2, glutamine, and aspartic acid. Malaria parasites, unlike their hosts, synthesize folates de novo using a pathway that in other organisms is mediated by five enzymes: GTP cyclohydrolase (GTPCH), dihydroneopterin aldolase (DHNA), hydroxymethyl dihydropterin pyrophosphokinase (PPPK), dihydropteroate synthase (DHPS), and dihydrofolate synthase (DHFS). The interconversion amongst the various forms involves four other enzymes: DHFR, TS, serine hydroxymethyl transferase (SHMT), and folylpolyglutamate synthase (FPGS). In malaria parasites, the synthesis of thymidylate from UMP requires the enzyme TS because plasmodia lack the enzyme thymidine kinase and they cannot salvage preformed thymidine from the host. Thymidine cannot be salvaged, but recent studies show that UMP (which can be produced de novo) may be formed from uracil via salvage by the action of UPRT or by the sequential action of uridine phosphorylase (UP) and uridine kinase.

2 citations


Book ChapterDOI
TL;DR: Experimental studies to analyze shock and clock processes in malaria infections, which found that initially asynchronous cultures became synchronized when exposed to 40°C on alternate days of the 48-h growth cycle, suggesting that this was due to “periodic disruption of the latter part of the erythrocytic cycle” by elevated temperature.
Abstract: Publisher Summary This chapter discusses experimental studies to analyze shock and clock processes in malaria infections. In one experiment study, the chicken embryos were injected with Plasmodium lophurae and at 12-h intervals shifted the incubator temperature from 38°C to 43°C. It was found that the heat shocks lengthened the period of asexual development by 8-10 h with the schizont stage being most susceptible. The length of the asexual cycle was same in the chick embryos as in the duckling. The infection was highly synchronous in the duckling, but when adapted to the chicken embryos it became asynchronous. After 1976 and with the continuous in vitro culture of Plasmodium falciparum , it became possible to eliminate the use of chick embryos for heat shock experiments since temperature changes could be carried out in vitro . In 1989, it was found that initially asynchronous cultures became synchronized when exposed to 40°C on alternate days of the 48-h growth cycle, suggesting that this was due to “periodic disruption of the latter part of the erythrocytic cycle” by elevated temperature. The other experiments are discussed that were conducted to study the rhythmicity of gametocytes in a variety of malarias by measuring infectivity for mosquitoes, exflagellation rates, and morphology of gametocytes.

1 citations


Book ChapterDOI
TL;DR: This chapter discusses the early experimental studies on pyrimidines and the mitochondrion in malaria research and the finding of a minor deoxyribonucleic acid (DNA) component, in addition to a major component in Plasmodium knowlesi and P. falciparum.
Abstract: Publisher Summary This chapter discusses the early experimental studies on pyrimidines and the mitochondrion in malaria research. Electron microscopic studies of asexual parasites from a variety of malaria species have shown mitochondria with a sac-like appearance and very few cristae. The mitochondria of sexual stages, in contrast, had a more conventional appearance. Based on these observations, it was assumed that in the asexual stages the mitochondrion did not function as an energy-yielding metabolic pathway involving a Krebs tricarboxylic acid (TCA) cycle in conjunction with oxidative phosphorylation, whereas in the sexual and mosquito stages it would function in the same manner as in most aerobic eukaryotes. The isolation of intact, contaminant-free mitochondria from Plasmodium had been a major obstacle in understanding the function of this organelle until Fry and Beesley (1991) working in the Wellcome Research Laboratories were able to isolate the functional mitochondria from Plasmodium yoelii and Plasmodium falciparum . They found the reduction of cytochrome c by dihydronicotinamide adenine dinucleotide (NADH), α-glycerophosphate and succinate, as well as low rates of oxidation of proline, dihydroorotate and glutamate. This chapter also discusses about Win Gutteridge and Peter Trigg finding of a minor deoxyribonucleic acid (DNA) component, in addition to a major component in Plasmodium knowlesi and P. falciparum . Some properties of the electron transport chain in case of metazoans are also described.

1 citations


Book ChapterDOI
TL;DR: This chapter discusses the early years of research and development of malaria parasites in biochemistry, when work on the biochemistry of malaria was initiated at several universities in the United States including Harvard, Johns Hopkins, and the University of Chicago.
Abstract: Publisher Summary This chapter discusses the early years of research and development of malaria parasites in biochemistry. The search for the mode of action of atabrine stimulated the earliest biochemical studies on malaria parasites. The first such study was conducted at the London School of Hygiene and Tropical Medicine, by Christophers and Fulton (1938) using Plasmodium knowlesi, discovered in 1932 in a Malayan kra monkey that had been sent to the Calcutta School of Tropical Medicine via Singapore. In 1898, Sir Rickard Christophers (1873-1978) was appointed to study the relationship of quinine therapy to blackwater fever; his long career in malaria continued with Colonel H. E. Shortt in India (1904-1932). James D. Fulton (1899-1974), trained in chemistry and medicine (1934), worked on antiprotozoan chemotherapy with Warrington Yorke at the Liverpool School of Tropical Medicine. During this same period, work on the biochemistry of malaria was initiated at several universities in the United States including Harvard, Johns Hopkins, and the University of Chicago. Studies in the United States with bird and monkey malarias also used the then current techniques of manometry, photometry supplemented by spectrophotometry.

1 citations


Book ChapterDOI
TL;DR: Microarray analysis of the P. falciparum transcriptome shows that most of the apicoplast-related genes reach maximal levels of messenger ribonucleic acid (mRNA) transcription as the parasite develops from the late trophozoite to the early schizont stages in the erythrocytic cycle.
Abstract: Publisher Summary This chapter provides an overview of the apicoplast structure in Plasmodium falciparum . The apicoplast in asexual trophozoite stages of P. falciparum is a tubular structure measuring 0.35 mm × 1.6 mm that has a triple-membraned wall and is closely adherent to the mitochondrion; the interior matrix contains ribosome-like granules and a network of fine-branched filaments. Most of the proteins in the apicoplast are now encoded by genes in the nucleus. The nuclear-encoded apicoplast proteins include housekeeping enzymes involved in DNA replication and repair, transcription, post-translation modifications, cofactor synthesis, protein and metabolite import, and protein turnover. Despite the progress in identifying the apicoplast proteins, the functions of about 60% of the putative apicoplast-targeted proteins remain unknown. In addition to the nuclear-encoded proteins, there are 23 proteins encoded by the apicoplast genome itself. In P. falciparum , the apicoplast includes genes for three subunits of a bacteria-like RNA polymerase, 17 ribosomal proteins, the translation factor Tuf, a likely chaperone Clp, and SufB . Microarray analysis of the P. falciparum transcriptome shows that most of the apicoplast-related genes reach maximal levels of messenger ribonucleic acid (mRNA) transcription as the parasite develops from the late trophozoite to the early schizont stages in the erythrocytic cycle.

1 citations


Book ChapterDOI
TL;DR: This chapter analyzes the purine salvage pathway in malaria parasites and indicates that in vivo, the plasma-supplied nucleoside for the parasites is hypoxanthine.
Abstract: Publisher Summary This chapter analyzes the purine salvage pathway in malaria parasites. Intraerythrocytically, adenosine, inosine, and hypoxanthine are the purines available for salvage by the Plasmodium, and these may be supplemented by that present in plasma. Because the plasma levels of adenosine are quite low whereas hypoxanthine levels are much higher, it is indicated that in vivo, the plasma-supplied nucleoside for the parasites is hypoxanthine. The support for the critical role of hypoxanthine in purine salvage can be found in the reports of increased levels in the plasma of ducklings infected with Plasmodium lophurae, the increased severity of Plasmodium chabaudi, Plasmodium berghei, and Plasmodium vinckei infections by adding allopurinol to the drinking water of infected rats and mice, the inhibition of Plasmodium falciparum growth when xanthine oxidase was added to in vitro cultures, and its favoring effect when present in the culture media for P. lophurae, P. knowlesi, and P. falciparum. The salvage of hypoxanthine through hypoxanthine-guanine phosphoribosyl transferase (HGPRT) is described. Evidence for the presence of adenylosuccinate synthetase that catalyses the condensation of IMP with aspartate to form adenylosuccinate is also discussed.

1 citations


Book ChapterDOI
TL;DR: To counter the problem associated with the treatment by atovaquone alone, it has been combined with proguanil hydrochloride (Malarone) and the combination is found to be more effective than either component alone or mefloquine, chloroquines, or sulphadoxinepyrimethamine in areas where parasites are resistant to these drugs.
Abstract: Publisher Summary This chapter discusses the history of development of atovaquone and its effectiveness in the treatment of malaria. Experimental studies have shown that atovaquone has structural similarity to ubiquinones. Studies with BW58C demonstrated that the inhibition of respiration of mitochondria isolated from plasmodia was 1000-fold more sensitive than were mammalian and avian mitochondria. It was also shown that atovaquone acts on the cytochrome bc 1 complex to block either ubiquinol oxidation or ubiquinone reduction. When it was used as a monotherapy for Plasmodium falciparum infections, there was a 30% treatment failure rate with atovaquone-resistant parasites emerging 28 days after the treatment. Resistance appeared to involve mis-sense mutations in a region of cytochrome b especially near the highly conserved PEWY sequence, a peptide sequence important for the way ubiquinone fits into the binding site of the malaria cytochrome bc 1 complex. To counter the problem associated with the treatment by atovaquone alone, it has been combined with proguanil hydrochloride (Malarone) and the combination is found to be more effective than either component alone or mefloquine, chloroquine, or sulphadoxinepyrimethamine in areas where parasites are resistant to these drugs.

Book ChapterDOI
TL;DR: This chapter presents an overview of the research work conducted to analyze the invasion of erythrocytes in case of malaria, with an elegant series of studies using both videomicroscopy and electron microscopy.
Abstract: Publisher Summary This chapter presents an overview of the research work conducted to analyze the invasion of erythrocytes in case of malaria. In 1969, the invasion of erythrocytes by merozoites was described in electron microscopic studies. With improvements in electron microscopy techniques and membrane sieving methods that allowed for isolation of large numbers of Plasmodium knowlesi merozoites, a detailed description of the morphological characteristics of invasion was achieved. As other electron microscopic studies have shown similar structural characteristics for erythrocytic merozoites, it is assumed that the steps in invasion are similar for all the species of malaria parasites including Plasmodium falciparum and Plasmodium vivax. In an elegant series of studies using both videomicroscopy and electron microscopy, the dynamics of the entry process have been described in considerable detail. The earliest light microscopic investigations, as well as the visualization of the steps in invasion that suggest the presence of parasite ligands and red cell receptors are discussed. The experimental study using in vitro short-term culture system to study invasion is described. An overview of the human Duffy antigen is also presented.