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Parasite,
1994]
Two genes coding for cuticlin components of Coenorhabditis elegans have been cloned and their structure is described. Recombinant proteins have been produced in E. coli and antibodies raised against them. Nucleic acid and specific antibodies are being used to isolate the homologues from the parasitic species Ascaris lumbricoides and Brugia pahangi.
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Rev Infect Dis
]
This report summarizes the findings of the 17 published studies involving humans who have been experimentally infected with filarial parasites. Over the past 60 years, 45 individuals have been deliberately infected with Wuchereria bancrofti, Brugia malayi, Brugia pahangi, Loa loa, Mansonella perstans, Mansonella ozzardi, and/or Onchocerca volvulus. The findings from these experimental infections of humans have helped define microfilarial survival and periodicity within human hosts, the prepatent period for the causative agents of lymphatic filariasis, etiologic agents for particular clinical syndromes, immunologic and hematologic consequences of filarial infection, and the role of chemotherapeutic agents in the prevention and treatment of filarial infections.
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Curr Opin Insect Sci,
2014]
As a function of size, migration trajectory through the body and developmental site, filarial worm parasites inflict significant damage on the mosquito host. Some mosquitoes are equipped with physical and physiological barriers that confer a refractory state to parasite infection. In a susceptible host, parasites migrate to a developmental site and achieve an intracellular existence; during this process, worms elicit canonical mosquito immune response elements, particularly melanization and antimicrobial peptide (AMP) production. It is clear now that the response to infection also involves mitigating stress and manipulation of host cell machinery to delay necrosis. This review focuses on mechanisms of refractoriness and resistance to Brugia malayi, Brugia pahangi, and Dirofilaria immitis, with emphasis on infection in the mosquito, Aedes aegypti.
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Parasitology,
2014]
Nematodes are amongst the most successful and abundant organisms on the planet with approximately 30 000 species described, although the actual number of species is estimated to be one million or more. Despite sharing a relatively simple and invariant body plan, there is considerable diversity within the phylum. Nematodes have evolved to colonize most ecological niches, and can be free-living or can parasitize plants or animals to the detriment of the host organism. In this review we consider the role of heat shock protein 90 (Hsp90) in the nematode life cycle. We describe studies on Hsp90 in the free-living nematode Caenorhabditis elegans and comparative work on the parasitic species Brugia pahangi, and consider whether a dependence upon Hsp90 can be exploited for the control of parasitic species.
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Biochem Soc Symp,
1987]
Human lymphatic filariasis is a chronic, potentially debilitating disease caused by Brugia and Wuchereria species of parasitic nematodes. The spectrum of clinical manifestations appears to be related to the immune response of individuals to invasive larvae, adult worms and circulating first-stage larvae (microfilariae). Potential immunopathological outcomes place constraints on vaccine development, emphasizing the need to understand the basis of immunity and pathology. Clones coding for a number of distinct antigenic proteins of Brugia pahangi and Brugia malayi have been isolated via immunological screening of a cDNA expression library. A small number of these expressed peptides show exclusive reactivity with antibody from amicrofilaraemic, potentially immune individuals. Surprisingly, a dominant immunogen isolated with human antibody is the filarial parasite homologue of heat shock protein (hsp) 70. This protein is constitutively expressed in both insect- and mammalian-dwelling parasitic stages, but does not appear to presented to the host immune system in intact worms.
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Parasitol Int,
2009]
Filarial nematode parasites, the causative agents of elephantiasis and river blindness, undermine the livelihoods of over one hundred million people in the developing world. Recently, the Filarial Genome Project reported the draft sequence of the ~95 Mb genome of the human filarial parasite Brugia malayi - the first parasitic nematode genome to be sequenced. Comparative genome analysis with the prevailing model nematode Caenorhabditis elegans revealed similarities and differences in genome structure and organization that will prove useful as additional nematode genomes are completed. The Brugia genome provides the first opportunity to comprehensively compare the full gene repertoire of a free-living nematode species and one that has evolved as a human pathogen. The Brugia genome also provides an opportunity to gain insight into genetic basis for mutualism, as Brugia, like a majority of filarial species, harbors an endosybiotic bacterium (Wolbachia). The goal of this review is to provide an overview of the results of genomic analysis and how these observations provide new insights into the biology of filarial species.
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Dermatol Clin,
1989]
It is apparent that there are many similarities among the various filariae. Besides a common life cycle, with an arthropod vector and human hosts, there are similarities in the diseases that they produce. This clinical picture takes one of two main courses: (1) characteristic disease produced by the presence of adult nematodes in their target tissue, which distinguishes typical cases for each of the filariae, and (2) the systemic hypersensitivity reactions to the circulating microfilaria, which tend to be similar. The characteristic feature of Wuchereria bancrofti is genital disease with funiculitis and hydrocele and less often elephantiasis. For Brugia malayi it is elephantiasis of the distal leg or arm, usually leaving the knee or elbow uninvolved with normal contours. Brugia timori, restricted to just a few islands of Indonesia, produces elephantiasis similar to that of Brugia malayi, but with its characteristic descending lymphadenitis. Loa loa is best known for the Calabar swelling, or angioedema, that it produces, although other filariae can induce similar reactions. Both Loa loa and Dirofilaria tenuis cause macroscopic, subconjunctival eyeworms. Clinical disease from onchocerciasis takes four predominant forms: eye disease, lymphadenitis, subcutaneous nodules (onchocercomata), and a pruritic, hypopigmented, or hyperpigmented papular dermatitis.
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Future Med Chem,
2010]
Filariasis is caused by thread-like nematode worms, classified according to their presence in the vertebrate host. The cutaneous group includes Onchocerca volvulus, Loa loa and Mansonella streptocerca; the lymphatic group includes Wuchereria bancrofti, Brugia malayi and Brugia timori and the body cavity group includes Mansonella perstans and Mansonella ozzardi. Lymphatic filariasis, a mosquito-borne disease, is one of the most prevalent diseases in tropical and subtropical countries and is accompanied by a number of pathological conditions. In recent years, there has been rapid progress in filariasis research, which has provided new insights into the pathogenesis of filarial disease, diagnosis, chemotherapy, the host-parasite relationship and the genomics of the parasite. Together, these insights are assisting the identification of novel drug targets and the discovery of antifilarial agents and candidate vaccine molecules. This review discusses the antifilarial activity of various chemical entities, the merits and demerits of antifilarial drugs currently in use, their mechanisms of action, in addition to antifilarial drug targets and their validation.
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Ann Trop Med Parasitol,
1991]
An intense global collaborative effort under the leadership of the Steering Committee of the Filariasis Scientific Working Group of the Tropical Diseases Research Programme, World Health Organization, has brought together researchers, pharmaceutical chemists and clinicians in the development and search for antifilarial compounds which are more effective and more convenient to administer than diethylcarbamazine citrate, the current drug of choice for lymphatic filariasis. The Brugia spp.-rodent model has been used extensively for the primary screening and B. pahangi infections in the dog or cat for the secondary screening, of potential filaricides. Recently, the leaf-monkey (Presbytis spp.) infected with subperiodic B. malayi or Wuchereria kalimantani has been used for the tertiary evaluation and pharmacokinetic studies of compounds which have shown effectiveness in the primary and secondary screens. Both P. cristata and P. melalophos are extremely susceptible to subperiodic B. malayi infection, but the former is a better host as a higher peak microfilaremia and adult worm recovery rate were obtained. Although more than 30 potential filaricides have been evaluated in the tertiary screen, only a few compounds have shown some promise against lymphatic filariasis. CGP 20376, a 5-methoxyl-6-dithiocarbamic-S-(2-carboxy-ethyl) ester derivative of benzothiazole, had complete adulticidal and microfilaricidal activities against the parasite at a single oral dose of 20 mg kg-1. However, as the compound or its metabolites caused hepatotoxicity, its clinical use in the present formulation is not recommended.(ABSTRACT TRUNCATED AT 250 WORDS)
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Parasitol Today,
1999]
Four years ago, a WHO/United Nations Development Programme/World Bank-sponsored genome project to study the filarial lymphatic nematode parasite Brugia malayi was initiated. The project took as its aims gene discovery for drug target and vaccine candidate identification, genome mapping, dissemination of genomic data to the world community and training of endemic country partners in genomic research. In this article, the principal investigators in the laboratories behind the project describe the background to the project, the data now emerging and goals for the future. Open access to filarial genome data is emphasized.