resistance and susceptibility in human onchocerciasis--beyond th1 vs. research progress has led to programs for the elimination of onchocerciasis as a public health problem, research must now be intensified to protect elimination efforts. a profound understanding of the immunology in the human-parasite relationship is required for predicting the impacts of an altered immune response in a population post-microfilaricide treatment, and for the development of a vaccine against onchocerciasis, a highly desirable tool to guarantee sustained elimination success. this ...200211850011
human onchocerciasis: the essential partnership between research and disease control efforts.twenty years ago onchocerciasis was a disease generally ignored by the medical world, except by those who actually worked with the affected people in africa and latin america. now, largely as a result of the success of mass vector control and drug treatment programs, this is a disease management model for developing countries. the recent literature on onchocerciasis has, not surprisingly, mainly focused on various aspects of control. investigation into the more basic questions is needed to ensur ...200011964814
[human onchocerciasis and "sowda" in the republic of yemen].the geophysics of the north yemen, associating a north-south directed mountainous fish bone (rising in more of 2,000 meters), to numerous rivers or "wadis" is convenient to the development of simulium shelters, main vectors for cutaneous filariasis to onchocerca sp. following several missions of bio-clinical and epidemiological evaluations in neighbouring villages of wadis, it has been possible to study different clinical aspects: one reminding the classical african onchocerciasis with generaliz ...200111974966
human onchocerciasis in brazil: an overview.human onchocerciasis was recently discovered in brazil among yanomámi indians living along the border region with venezuela in the states of amazonas and roraima. the article reports on the history of the disease's discovery, its distribution, and incrimination of vector simuliid species. the literature that has been generated on the parasite, its vectors, and control of the disease is critically analyzed as well as the organization of epidemiological surveys and the control program developed by ...200212244349
antigen-specific t regulatory-1 cells are associated with immunosuppression in a chronic helminth infection (onchocerciasis).different mechanisms underlie the phenomenon of peripheral tolerance. recently, a new subset of cd4+ t cells, called t regulatory-1 (tr1) cells, was described which show suppressor functions in vitro and in vivo and are characterized by a predominant production of il-10 and/or tgf-beta. tr1 cells have so far been generated experimentally in an il-10-rich environment and hold promise for exploitation in the suppression of alloreactions and inflammatory or allergic dispositions. however, these cel ...200212443893
final report of the conference on the eradicability of onchocerciasis.sixty-four experts from a variety of disciplines attended a conference on the eradicability of onchocerciasis at the carter center, in atlanta ga, held january 22-24, 2002. the conference, which was organized by the carter center and the world health organization, with funding from the bill & melinda gates foundation, addressed the question: "is onchocerciasis (river blindness) eradicable with current knowledge and tools?" former us president jimmy carter attended part of the final plenary proce ...200312605722
human immune responses to infective stage larval-specific chitinase of filarial parasite, onchocerca volvulus, ov-chi-1.background: ov-chi-1 is a chitinase specifically expressed in the infective stage larvae of the human filarial parasite onchocerca volvulus. evidence has show that it could be a vaccine candidate, however, there is no data available regarding the immunological status of people naturally exposed to infective stage larvae and thus provoked by this antigen. method: we analysed the ov-chi-1-specific immune response present in four endemic foci of human onchocerciasis (ecuador, nigeria, togo and came ...200312685941
doxycycline in the treatment of human onchocerciasis: kinetics of wolbachia endobacteria reduction and of inhibition of embryogenesis in female onchocerca worms.recently, experts have warned that mass treatment with ivermectin alone may not interrupt the transmission of onchocerca. hence, additional drugs are needed, such as antibiotics acting on symbiotic endobacteria of the filariae, the causative agents of onchocerciasis. based on animal experiments, human onchocerciasis was treated with doxycycline, and preliminary observations published in 2001 in the lancet showed sterility in female worms by depletion and marked reduction in symbiotic wolbachia e ...200312706439
wolbachia in the inflammatory pathogenesis of human filariasis.filarial nematodes cause some of the most debilitating diseases in tropical medicine. recent studies, however, have implicated the parasites' endosymbiotic wolbachia bacteria, rather than the nematode, as the cause of inflammatory-mediated filarial disease. soluble extracts of a variety of filarial species stimulate innate inflammatory responses, which are absent or reduced when using extracts derived from species either devoid of bacteria, or those cleared of bacteria by antibiotics. characteri ...200312860672
the activator-binding site of onchocerca volvulus s-adenosylmethionine decarboxylase, a potential drug target.s-adenosylmethionine decarboxylase (adometdc) is a key enzyme in polyamine biosynthesis. in many eukaryotes its activity is stimulated specifically by putrescine. the adometdc of the filarial parasite onchocerca volvulus, however, is not only stimulated by putrescine but also by the naturally occuring polyamines spermidine and spermine. several diamines, acetylated polyamines and polyamine analogues were used to analyse what molecular prerequisites are needed to stimulate nematode adometdc activ ...200312974388
the movement of microfilariae of onchocerca volvulus in the human eye from lid to retina. 195913647617
density-dependent parasite establishment suggests infection-associated immunosuppression as an important mechanism for parasite density regulation in onchocerciasis.the modulation of human immune response by filarial parasites has yielded contradictory experimental findings and attracted much controversy. we address the unresolved question of acquisition, establishment and accumulation of onchocerca volvulus by using a modelling approach that relates computer simulations to cross-sectional data concerning parasite burdens in 913 west african onchocerciasis patients. it is shown that the acquisition of o. volvulus is not constant with host age; instead, the ...200314584385
wolbachia endosymbionts of onchocerca volvulus express a putative periplasmic htra-type serine protease.wolbachia are intracellular bacteria of many filarial nematodes. a mutualistic interaction between the endobacteria and the filarial host is likely, because the clearance of wolbachia by tetracycline leads to the obstruction of embryogenesis and larval development. databases were searched for exported molecules to identify candidates involved in this mutualism. fragments of a wolbachia serine protease from the human filarial parasite onchocerca volvulus were obtained (wol-ov-htra) by the use of ...200414998511
an investigation of persistent microfilaridermias despite multiple treatments with ivermectin, in two onchocerciasis-endemic foci in ghana.if ivermectin-based programmes for the control of human onchocerciasis are to be successful, the drug must remain effective for as long as necessary. in an open, case-control study, an attempt was made to determine if the persistent, significant, onchocerca volvulus microfilaridermias seen in some individuals who had received at least nine treatments with ivermectin were the result of the development of drug resistance in the parasite. twenty-one of these 'sub-optimal' responders (cases) were ma ...200415119969
the major surface protein of wolbachia endosymbionts in filarial nematodes elicits immune responses through tlr2 and tlr4.more than 150 million humans in tropical countries are infected by filarial nematodes which harbor intracellular bacterial endosymbionts of the genus wolbachia (rickettsiales). these bacteria have been implicated in adverse effects of drug treatment in filariasis. the present study provides evidence that purified major wolbachia surface protein (rwsp) acts as an inducer of the innate immune system through tlr2 and tlr4: 1) recombinant, stringently purified rwsp elicited the release of tnf-alpha, ...200415210803
experimental onchocercal individuals with onchocerciasis, severe visual impairment (river blindness) occurs as a result of corneal inflammation induced by antigens released from dead and dying onchocerca volvulus microfilariae. to characterize the underlying immune response, animal models have been developed that partially reproduce many of the clinical features of human onchocercal keratitis, eric pearlman here discusses how these studies have identified systemic and local immune responses associated with keratitis, ...199615275190
onchocerciasis control programme-the human perspective.the west african onchocerciasis control programme (ocp), launched in 1974, seeks to interrupt transmission o f onchocerca volvulus (fig. i) over a vast area now encompassing 11 countries. the main strategy has been vector control using larvicides (particularly temephos) against blockfly larvae in fast-flowing rivers and streams. more recently, the programme has also begun to implement large-scale chemotherapy using ivermectin. the ocp has an operational budget approaching us$25 million a year. t ...198815463024
development and evaluation of an antigen detection dipstick assay for the diagnosis of human improve on the diagnosis of onchocerciasis, especially light infections, we developed and evaluated an oncho-dipstick test based on the detection of onchocerca volvulus specific antigens in urine and tears. the test was able to detect as little as 25 ng/ml of parasite specific antigens in samples and took as little as 3 h. evaluation of the assay on 456 residents of an onchocerciasis hyperendermic area in cameroon resulted in 408 (89.5%) positives in urine and 374 (82%) positives in tears. th ...200515730506
characterization of a novel filarial serine protease inhibitor, ov-spi-1, from onchocerca volvulus, with potential multifunctional roles during development of the parasite.a novel filarial serine protease inhibitor (spi) from the human parasitic nematode onchocerca volvulus, ov-spi-1, was identified through the analysis of a molting third-stage larvae expressed sequence tag dataset. subsequent analysis of the expressed sequence tag datasets of o. volvulus and other filariae identified four other members of this family. these proteins are related to the low molecular weight spis originally isolated from ascaris suum where they are believed to protect the parasite f ...200516186127
differential display of genes expressed in the filarial nematode litomosoides sigmodontis reveals a putative phosphate permease up-regulated after depletion of wolbachia endobacteria.mutualist symbiotic wolbachia endobacteria are found in most filarial nematodes. wolbachia are essential for embryogenesis and for larval development into adults, and thus represent a new target for anti-filarial drug development. tetracycline antibiotics deplete wolbachia in animal model filaria litomosoides sigmodontis and brugia pahangi, as well as in the human parasites brugia malayi, onchocerca volvulus and wuchereria bancrofti. very little is known about the molecular details of the symbio ...200616616613
modeling targeted ivermectin treatment for controlling river blindness.there is considerable host heterogeneity in exposure to onchocerciasis. we incorporate this heterogeneity into a model of onchocerciasis transmission that we use to evaluate intervention strategies targeting specific portions of the human population for treatment with ivermectin. our model predicts that targeted allocation of ivermectin in a highly heterogeneous population will reduce the public health burden of onchocerciasis using 20-25% of the doses of untargeted allocation. targeted allocati ...200617123988
towards the elimination of onchocerciasis.human onchocerciasis is a severely disabling filarial disease that is endemic in 28 african countries, six latin american countries and yemen. the disease causes a high burden of blindness and visual loss, along with itching and other severe dermal manifestations. it constitutes a significant obstacle to socio-economic development in highly endemic riverine areas, where the simulium blackflies that act as vectors breed. onchocerciasis has been subject to control efforts for more than 50 years, i ...200617227651
natural death of adult onchocerca volvulus and filaricidal effects of doxycycline induce local foxp3+/cd4+ regulatory t cells and granzyme expression.immunosuppression in human filarial disease involves regulatory t cells. we hypothesized that natural or worm antigen-induced foxp3 regulatory t cells could be involved locally, suppressing effector cells via granzymes. natural and treatment-induced death of worms implies enhanced exposure to worm antigens. therefore, we examined foxp3+t cells and granzyme expression in onchocercomas harbouring adult onchocerca volvulus worms, with respect to worm viability, productivity, the patient's immune st ...200818339571
of mice, cattle, and humans: the immunology and treatment of river blindness.river blindness is a seriously debilitating disease caused by the filarial parasite onchocerca volvulus, which infects millions in africa as well as in south and central america. research has been hampered by a lack of good animal models, as the parasite can only develop fully in humans and some primates. this review highlights the development of two animal model systems that have allowed significant advances in recent years and hold promise for the future. experimental findings with litomosoide ...200818446236
the complete mitochondrial genomes for three toxocara species of human and animal health significance.studying mitochondrial (mt) genomics has important implications for various fundamental areas, including mt biochemistry, physiology and molecular biology. in addition, mt genome sequences have provided useful markers for investigating population genetic structures, systematics and phylogenetics of organisms. toxocara canis, toxocara cati and toxocara malaysiensis cause significant health problems in animals and humans. although they are of importance in human and animal health, no information o ...200818482460
efficacy of 2- and 4-week rifampicin treatment on the wolbachia of onchocerca volvulus.the microfilaricidal and temporarily sterilizing drug ivermectin is used for mass treatment of filarial infections. filariae containing wolbachia endobacteria can also be treated by the antibiotic doxycycline. the loss of wolbachia results in sterilization of onchocerca volvulus and macrofilaricidal effects. besides doxycycline, other antibiotics may be effective in depleting wolbachia. a preliminary study on the effects of rifampicin on the endobacteria, embryogenesis and microfilariae producti ...200818679718
transmission dynamics of simulium damnosum in rural communities of akwa ibom state, nigeria.onchocerciasis is endemic in some parts of akwa ibom state, nigeria. this study describes the entomological parameters of transmission in three rural communities of akwa ibom state, prior to ivermectin intervention in 2004.200818807379
immunoglobulin kappa chain locus on chromosome 2p12 and onchocerciasis. 200919115983
onchocerca-simulium interactions and the population and evolutionary biology of onchocerca volvulus.parasite-vector interactions shape the population dynamics of vector-borne infections and contribute to observed epidemiological patterns. also, parasites and their vectors may co-evolve, giving rise to locally adapted combinations or complexes with the potential to stabilise the infection. here, we focus on onchocerca-simulium interactions with particular reference to the transmission dynamics of human onchocerciasis. a wide range of simuliid species may act as vectors of onchocerca volvulus, e ...200919289198
recombinant ov-asp-1, a th1-biased protein adjuvant derived from the helminth onchocerca volvulus, can directly bind and activate antigen-presenting cells.we previously reported that rov-asp-1, a recombinant onchocerca volvulus activation associated protein-1, was a potent adjuvant for recombinant protein or synthetic peptide-based ags. in this study, we further evaluated the adjuvanticity of rov-asp-1 and explored its mechanism of action. consistently, recombinant full-length spike protein of sars-cov or its receptor-binding domain in the presence of rov-asp-1 could effectively induce a mixed but th1-skewed immune response in immunized mice. it a ...200919299698
successful interruption of transmission of onchocerca volvulus in the escuintla-guatemala focus, guatemala.elimination of onchocerciasis (river blindness) through mass administration of ivermectin in the six countries in latin america where it is endemic is considered feasible due to the relatively small size and geographic isolation of endemic foci. we evaluated whether transmission of onchocerciasis has been interrupted in the endemic focus of escuintla-guatemala in guatemala, based on world health organization criteria for the certification of elimination of onchocerciasis.200919333366
the elimination of the vector simulium neavei from the itwara onchocerciasis focus in uganda by ground larviciding.the itwara focus of onchocerciasis covers an area of approximately 600 km(2) in western uganda about 20 km north of fort portal. the vector is simulium neavei, whose larvae and pupae live in a phoretic association on freshwater crabs. the phoretic host in the itwara focus is the crab potamonautes aloysiisabaudiae. before any onchocerciasis control, atps were estimated to reach between 4500 and 6500 infective larvae per person per year. s. neavei was found to be a very efficient vector with 40% o ...200919446785
the nematode parasite onchocerca volvulus generates the transforming growth factor-beta (tgf-beta).transforming growth factor-beta (tgf-beta) is a highly conserved cytokine that has a well-known regulatory role in immunity, but also in organ development of most animal species including helminths. homologous tgf-b genes and mrna have been detected in the filaria brugia malayi. the in situ protein expression is unknown for filariae. therefore, we examined several filariae for the expression and localization of latent (stable) tgf-beta in adult and larval stages. a specific goat anti-human laten ...200919452170
the heme biosynthetic pathway of the obligate wolbachia endosymbiont of brugia malayi as a potential anti-filarial drug target.filarial parasites (e.g., brugia malayi, onchocerca volvulus, and wuchereria bancrofti) are causative agents of lymphatic filariasis and onchocerciasis, which are among the most disabling of neglected tropical diseases. there is an urgent need to develop macro-filaricidal drugs, as current anti-filarial chemotherapy (e.g., diethylcarbamazine [dec], ivermectin and albendazole) can interrupt transmission predominantly by killing microfilariae (mf) larvae, but is less effective on adult worms, whic ...200919597542
immunohistological studies on onchocerca volvulus paramyosin.paramyosin is a muscular protein exclusively found in invertebrate species, which has been proposed as a vaccine candidate against infections with schistosoma mansoni and brugia malayi. here, we report the studies on the distribution of onchocerca volvulus paramyosin, designated ovpmy, in different o. volvulus stages by immunohistochemistry using rabbit antibodies raised against the recombinant ovpmy protein as well as the induction of the human humoral immune response to ovpmy. to conduct the s ...200919629524
a putative nuclear growth factor-like globular nematode specific protein.expressed sequence tags (ests) are an effective approach for discovery of novel genes. in the current study, approximately 250 ests of the cattle parasitic nematode setaria digitata were examined and a cdna clone identified whose coding sequence could not be functionally annotated by searching over publicly available genome, protein, est and sts databases. here, we report the extensive characterization of this orf (up) and its homologues using a bioinformatic approach. uncharacterized protein (s ...200919759810
immunisation with a multivalent, subunit vaccine reduces patent infection in a natural bovine model of onchocerciasis during intense field exposure.human onchocerciasis, caused by the filarial nematode onchocerca volvulus, is controlled almost exclusively by the drug ivermectin, which prevents pathology by targeting the microfilariae. however, this reliance on a single control tool has led to interest in vaccination as a potentially complementary strategy. here, we describe the results of a trial in west africa to evaluate a multivalent, subunit vaccine for onchocerciasis in the naturally evolved host-parasite relationship of onchocerca och ...200919901988
strong expression of tgf-beta in human host tissues around subcutaneous dirofilaria repens.dirofilaria repens and other dirofilaria species are widely distributed parasitic nematodes of carnivores, which occasionally are transmitted to men, causing subcutaneous nodules. in humans, it usually occurs only as single male or female filariae without production of microfilariae. the non-productive living or dead dirofilaria worms in subcutaneous biopsies from 15 human patients permitted us to study the role of the pleiotropic and immunoregulatory cytokine transforming growth factor beta (tg ...201120809419
onchocerca armillata contains the endosymbiotic bacterium wolbachia and elicits a limited inflammatory response.human onchocerciasis, also known as river blindness, is a debilitating disease caused by the filarial nematode onchocerca volvulus. many, but not all, filarial nematodes carry within their tissues endosymbiotic, rickettsia-like bacteria of the genus wolbachia. onchocerca spp. infections in cattle offer the most relevant, analogous host-parasite model system. west african cattle are commonly co-infected with four onchocerca spp.; two of these are wolbachia-positive (onchocerca gutturosa and oncho ...201020850932
toward molecular parasitologic diagnosis: enhanced diagnostic sensitivity for filarial infections in mobile populations.the diagnosis of filarial infections among individuals residing in areas where the disease is not endemic requires both strong clinical suspicion and expert training in infrequently practiced parasitological methods. recently developed filarial molecular diagnostic assays are highly sensitive and specific but have limited availability and have not been closely evaluated for clinical use outside populations residing in areas of endemicity. in this study, we assessed the performance of a panel of ...201020980560
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