Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Onchocerciasis ('River Blindness'), caused by the filarial nematode Onchocerca volvulus is of major public health importance in West Africa. Ivermectin, a drug originally developed for veterinary use, is now being incorporated in control strategies but whilst it has potent efficacy against L1 larvae (microfilariae), ivermectin is not lethal to adult (L5) O. volvulus, nor to adults of the related cattle parasite O. ochengi. We have exploited this model to determine if ivermectin has prophylactic activity against naturally transmitted, O. ochengi infections in a controlled, prospective study in northern Cameroon. Calves were treated monthly with ivermectin at either 200 micrograms/kg or 500 micrograms/kg for 21 months. None of 15 treated calves developed adult worm infection, whereas 5/6 untreated controls became infected (P < 0.001) with a total of 54 O. ochengi nodules, and all 5 developed patent microfilaridermia. These results have significant implications for the use of ivermectin in humans, and suggest that strategic chemotherapy at times of maximal transmission will confer prophylactic as well as therapeutic benefits.
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PMID:Chemoprophylaxis of Onchocerca infections: in a controlled, prospective study ivermectin prevents calves becoming infected with O. ochengi. 1002 34

Ivermectin, at the standard dose of 150 micrograms/kg bodyweight, does not kill the adult worms of Onchocerca volvulus and does not disrupt embryogenesis or spermatogenesis. Repeated standard doses, if maintained, arrest microfilarial production but result in only a mild-to-modest macrofilaricidal effect. We investigated whether high doses would effectively kill the adult worms, and whether cessation of microfilarial production could be reproduced by an equivalent, single, high dose. One hundred men participated in a double-blind placebo-controlled trial and received increasing doses of ivermectin from 150 micrograms/kg to 1600 micrograms/kg bodyweight. Nodules were excised at day 180 and examined by histopathology. Total doses of ivermectin up to 1600 micrograms/kg were not significantly more effective than 150 micrograms/kg. Moreover, they did not reproduce the marked inhibitory effects of the repeat standard-dose regimens on embryogenesis, nor the modest effect on adult worm viability, at comparable total doses. These effects may be functions of multiplicities of dosages rather than of the total dose. Our findings also suggest that repeated high-dose regimens are unlikely to be more effective than a similar number of 150 micrograms/kg doses. This deficiency of ivermectin requires that the search for macrofilaricides remains a top priority.
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PMID:The effects of high-dose ivermectin regimens on Onchocerca volvulus in onchocerciasis patients. 1045 Apr 48

Onchocerciasis, or river blindness, is a parasitic infection caused by the filarial nematode, Onchocerca volvulus. It infects 18 million people worldwide, but is rarely seen in the United States. It is one of the leading causes of blindness in the developing world. Although onchocerciasis is also known as river blindness, it is not just a disease of the eyes, but rather a chronic multisystem disease. Clinically, onchocerciasis takes three forms: 1) eye disease; 2) subcutaneous nodules; and 3) a pruritic hypopigmented or hyperpigmented papular dermatitis. We present an 18-year-old African female with a 5-year history of asymptomatic, hypopigmented, slightly atrophic macules on her anterior tibiae. Pathology revealed a scant perivascular inflammatory infiltrate with mononuclear cells, eosinophils, and rare microfilariae in the papillary dermis. Ivermectin is the treatment of choice for onchocerciasis and was initiated in this patient. We present this interesting patient with onchocerciasis to expand our differential of hypopigmented macules, especially in the African population. In addition, we discuss both the diagnosis and the treatment of onchocerciasis in expatriate patients living in nonendemic areas.
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PMID:Onchocerciasis presenting with lower extremity, hypopigmented macules. 1082 90

A pleomorphic neoplasm (PN) is described from sections of Onchocerca volvulus worms in nodules excised from Cameroonian patients. PN is confined to older, non-fecund, female worms, and those classed as moribund/dead. It is mainly composed of small, roundish, basophilic cells of diverse sizes, often forming a 'rosette' pattern around amorphous eosinophilic centres. The cells have a high nuclear/cytoplasmic ratio and up to 2-3 mitoses/high-power field; some become grossly enlarged, highly polymorphic and contain large, irregular blocks of chromatin. The eukaryotic PN cells first appear posteriorly in the pseudocoelom, probably from ovarian cells; they spread anteriorly, invading or compressing the uteri. Ivermectin treatment increased the prevalence PN from 3.7% of 1422 female worms in 637 patients before treatment to 17.5% of 1134 worms in 511 patients after 3 years treatment. Ivermectin at 400-800 microg/kg annually, or at 150 microg/kg or 400-800 microg/kg 3-monthly, over 3 years, did not increase the PN prevalence significantly, as compared with standard doses of 150 microg/kg annually. In other small series of African patients, PN prevalence increased in worms 2, 4, 6 and 10 months after ivermectin treatment; but there was no increase after treatment with amocarzine, albendazole or diethylcarbamazine and suramin. PN may partly account for the increased macrofilaricidal action of ivermectin on female O. volvulus in patients treated for 3 years at 3-monthly intervals.
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PMID:Neoplastic change in Onchocerca volvulus and its relation to ivermectin treatment. 1245 27

The induction of pathological changes in Onchocerca volvulus infections is directly related to the presence of the microfilarial stage of this filarial nematode. Patients with either of the 2 major forms of the clinical disease (i.e., asymptomatic/mild [n=12] and severe [n=16] dermatopathology) were studied. The cellular immune responses (cell proliferation) of those with severe disease were stronger (stimulation index [SI], 12.3+/-1.9) than those with mild dermatopathological effects (SI, 2.9+/-0.6) or control patients (SI, 4.5+/-0.4). Cytoadherence antibody responses were greatest (grade 4) in the clinically severe group and only weak (grades < or = 1) in the mild group or the control patients. Ivermectin treatment was followed by an increase in immune responsiveness in those with initially poor responses. Thus, the degree of dermatopathological effect is related to the host's immune response against microfilariae, and ivermectin augments such responses.
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PMID:Immune responses directed against microfilariae correlate with severity of clinical onchodermatitis and treatment history. 1259 94

Onchocerciasis is an infestation caused by the nematode, Onchocerca volvulus, and characterized by eye manifestations, skin lesions and troublesome itching. Although partially controlled by international mass treatment programs, onchocerciasis remains a major health hazard in endemic areas in Africa, Arabia, and the Americas. Onchocerciasis is spread by bites from infested blackflies which transmit larvae that subsequently develop into adult filariae. Skin findings are commonly non-specific, and include severe pruritus, acute and chronic dermatitis, vitiligo-like hypopigmentation and atrophy. Onchocercal ocular disease has a large spectrum of manifestations and may even lead to blindness. Diagnosis is usually made by direct visualization of the larvae emerging from superficial skin biopsies, "skin snips". In some cases, the microfilariae can also be directly observed with a slit lamp when they migrate into the anterior chamber of the eye. Ivermectin is highly microfilaricidal, and is the current drug of choice for both skin and ocular manifestations.
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PMID:[Onchocerciasis]. 1275 35

Ivermectin (or Mectizan trade mark ) is widely used by onchocerciasis and lymphatic filariasis control programs worldwide. Generally, Mectizan trade mark is both safe and well tolerated. An exception to this general pattern is in some areas co-endemic for Onchocerca volvulus and Loa loa, where a number of severe adverse reactions to Mectizan trade mark have been noted in L. loa infected individuals. The vast majority of these severe adverse events have occurred in Southern Cameroon. This suggested the hypothesis that the parasites endemic to Southern Cameroon might form a distinct population that exhibited a phenotype of eliciting severe adverse reactions in Loa-infected individuals upon Mectizan trade mark exposure. To test this hypothesis, the DNA sequences of three potentially polymorphic loci were compared among L. loa parasites from Southern Cameroon and other endemic foci in Sub-Saharan Africa. Analysis of these data suggested that parasites from Southern Cameroon were at least as genetically diverse as those from other foci. Furthermore, no polymorphisms were noted that were unique to and shared among the parasite isolates from Southern Cameroon. Although a limited number of parasite isolates were tested, these results do not appear to support the hypothesis that L. loa parasites from Southern Cameroon represent a unique, genetically isolated population.
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PMID:Genetic heterogeneity in Loa loa parasites from southern Cameroon: A preliminary study. 1522 48

Ivermectin administration is now the major tool in the control of human onchocerciasis (caused by Onchocerca volvulus) based on its suppression of microfilariae and hence the prevention of disease. However, in Africa, transmission is not eliminated and treated populations continue to be exposed to infective larval (L(3)) challenge, albeit at reduced levels. We have investigated whether protective immunity might develop under such conditions using the analogous host-parasite system Onchocerca ochengi in cattle, based on our previous findings in cattle exposed to challenge, that in vivo ivermectin attenuates the development of adult infections and that irradiation-attenuated L(3) induce significant protection. In a two-phase prospective study over 4 years, groups of cattle were exposed to severe natural challenge. In the first phase, 38/40 animals treated either with ivermectin or with moxidectin at either monthly or 3-monthly intervals had not developed detectable infections after 22 months of exposure whereas, in a non-treated control group (n = 14) nodule prevalence was 78.6% and the geometric mean (range) nodule load was 4.8 (0-33). In the second phase, all drug treatments were withdrawn, a new control group (n = 8) introduced, and exposure continued at the same site. After 24 months, all groups had developed patent infections, with geometric mean (range) nodule loads of 17.4 (4-99), 38.4 (10-111), 50.7 (26-86), 14.3 (0-69) and 14.7 (0-55) for the control, monthly-ivermectin, 3-monthly ivermectin, monthly moxidectin and 3-monthly moxidectin groups, respectively. There was no evidence of protection-indeed the 3-monthly ivermectin group was significantly (P < 0.05) hyper-susceptible. In addition, microfilarial densities and the rate of increase in microfilarial load were significantly higher (P < 0.05) in the ivermectin-treated groups than in control animals. These results have important implications for ivermectin-based control of human onchocerciasis and suggest that humans exposed to ongoing transmission in endemic areas whilst receiving ivermectin are unlikely to develop immunity and will be highly susceptible should drug distribution cease.
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PMID:Cattle protected from onchocerciasis by ivermectin are highly susceptible to infection after drug withdrawal. 1531 33

Ivermectin is a semi-synthetic derivative of a macrocyclic lactone. It causes paralysis in many nematodes and arthropodes because of its effect on ion-channels in cell membranes. Ivermectin was first used in veterinary medicine. In man, it was shown to be microfilaricid against Onchocerca volvulus. Most of the adverse reactions following treatment were mild, without the systemic and ocular side effects usually complicating diethylcarbamazine therapy. In endemic areas after repeated administration of ivermectin, a dramatic reduction in dermal microfilarial load was observed, resulting in a decrease in transmission. There was a significant decrease in the prevalence of anterior segment lesions in the eyes and acute onchocercal skin disease. Moreover, ivermectin also exhibited microfilaricidal activity against Wuchereria bancrofti and Brugia malayi. Annual mass treatment with a single dose of diethylcarbamazine alone, or associated with ivermectin, was initiated in endemic areas for lymphatic filariasis. The preliminary results showed a decrease in the reservoir of microfilariae and rate of transmission, a reduction in the frequency of clinical lymphatic abnormalities due to bancroftan filariasis. In Loa loa infections ivermectin decreases microfilaremia, but serious adverse events such as encephalopathy can be induced in patients with high rate of microfilaremia. Ivermectin appears to be the drug of choice in Strongyloides stercoralis infections, a single dose is highly effective with less frequent side effects than thiabendazole. Oral ivermectin is an alternative to topical scabicides, it appears as effective as local treatment for common scabies, but there are few comparative studies. The best indications for ivermectin in this ectoparasitic infection could be the outbreak in institutions and crusty scabies, but in association with topical treatment. The precise position of this agent in the treatment of scabies remains to be specified. Ivermectin is also affective in the treatment of ascariasis and cutaneous larva migrans. It could also be a promising treatment for head lice.
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PMID:[Ivermectin]. 1531 39

Human infection with Onchocerca volvulus was investigated in 13 rural communities in the Upper Imo River basin, Imo State, Nigeria between March 1997 and December 2000 using the skin snip method. Of the 3,311 persons examined, 889 (26.8%) had microfilariae. There were significant differences between communities in microfilariae prevalence and intensity of infection (P<0.05). Sex infection was similar in males (26.8%) and females (26.9%); whereas farmers (46.6%) and fishermen (28.4%) were more affected than people in other occupations. The proportion of infected persons increased with age coinciding with the period when most clinical signs manifest. A significant proportion of the 889 persons with positive microfilariae skin biopsy had musculoskeletal pain (57.1%). Thirty-four (47.2%) of the 72 epileptics identified had positive skin biopsy in addition to other manifestations. The present findings show that onchocerciasis is a public health problem in the area. The use of ivermectin has reduced the incidence of the disease when compared with data from the pre-ivermectin era. This shows that Community Directed Treatment with Ivermectin (CDTI) campaign is successful and should be sustained until onchocerciasis is eliminated as a public health problem in the area.
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PMID:Onchocerciasis in Imo state, Nigeria (2): the prevalence, intensity and distribution in the upper Imo river basin. 1538 15


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