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 is commonly known as River Blindness and affects about 18 million people around the world. It is transmitted by black flies that breed in river and stream rapids and transmit the parasitic microfilariae, Onchocerca volvulus, to people who live and work near such rivers. Infection with the microfilariae results in blindness or visual impairment for 1 or 2 million people. The microfilariae migrate to superficial tissues and may invade any part of the eye and ocular structure. Living worms cause little damage, however, their death triggers a localized inflammation which can lead to blindness. Sclerosing keratitis, a severe corneal involvement, is the major cause of blindness from the disease. The World Health Organization (WHO) Expert Committee on Onchocerciasis has estimated that 9% of the disease is found in Africa, the rest occur in Yemen and Latin America. Treatment with ivermectin is contraindicated for pregnant and lactating women, children under 5 years of age, asthmatics, and people with other diseases. The WHO Onchocerciasis Control Program in 11 countries of West Africa has eliminated the risk of onchocerciasis by aerial spraying of black fly breeding sites only from 1 country. A single annual oral dose (150 mg/kg) of ivermectin can reverse early lesions in the cornea. Ivermectin must be taken annually to sustain protection against blindness, thus its incorporation into primary health care along with malaria, AIDS, trachoma, xerophthalmia, and cataract is most cost effective. Nigeria and Tanzania have optometry schools, and optometrists can play a significant role in onchocerciasis control and blindness prevention programs by training local health care workers to distribute invermectin in vision screening programs.
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PMID:Onchocerciasis and other eye problems in developing countries: a challenge for optometrists. 824 90

To identify potentially protective Ag of the filarial nematode Onchocerca volvulus on the molecular level we screened a cDNA library of O. volvulus with a human serum raised against radiation-attenuated infective larvae of O. volvulus. A cDNA clone of 218 bp (OvL3-1) was selected for further studies. It was expressed in Escherichia coli and affinity purified recombinant polypeptide was tested for its ability to stimulate in vitro PBMC from African onchocerciasis patients and PBMC from chimpanzees experimentally infected with O. volvulus. An enhanced cell proliferation by PBMC was observed in many patients after stimulation with the recombinant OvL3-1 polypeptide. In addition, some patients' PBMC responded to OvL3-1 stimulation with enhanced IL-2 production. Infected chimpanzees also showed an increase in T cell proliferation. Onchocerciasis patients had variable levels of specific antibodies directed to the recombinant polypeptide when sera were tested by ELISA. A mAb directed against the recombinant protein located the native target Ag in the muscles of the adult worm. The molecular mass of native OvL3-1 was found to be 50 kDa on immunoblots. Polymerase chain reaction analysis of RNA from different life stages of the parasite showed that OvL3-1 is transcribed in all parasite stages within the mammalian host. A homologous gene is also present in other filarial parasites. The protein corresponding to OvL3-1, therefore, represents an immunogen present during the whole life-span of the parasite, and because of its B and T cell stimulatory properties, it may be a candidate for a protective Ag in human filariasis.
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PMID:Characterization of a recombinant T cell and B cell reactive polypeptide of Onchocerca volvulus. 845 65

Onchocerciasis is associated with blindness and gross skin changes, believed to be a consequence of the immune response to antigens released from the offspring of the female worm of Onchocerca volvulus, the microfilariae (mf). An effective microfilaricidal drug is now available which quickly reduces the mf burden without affecting the adult worm. There exist foci in onchocerciasis endemic areas where some of the patients have many mf in their skin but relatively few clinical symptoms. This state of hyposensitivity is believed to be due to immunosuppression. The aim of this study was to address the question of the basis of, and the effect of ivermectin treatment on this immunosuppression. Female adult worms of O. volvulus were used as whole or fractionated antigens to stimulate peripheral blood mononuclear cells. Microfilariae are found in the reproduction tract of the female worms, and thus an antigen preparation of the female adult O. volvulus contains both exclusive adult antigens as well as antigens from microfilariae. Cells were obtained from onchocerciasis patients, individuals of similar socio-economic status living in the same Ghanaian village, but who showed no parasitological or clinical evidence of onchocerciasis (exposed endemic controls), healthy Ghanaians living in areas where transmission of onchocerciasis does not seem to occur (non-exposed endemic controls) and unexposed healthy Swedish donors. As a group, cells from onchocerciasis patients proliferated to a lesser degree than cells from the exposed endemic control and the non-exposed endemic control groups to the whole worm antigen, whereas the phytohaemagglutinin (PHA) response was strongest in the patients. Proliferative responses of above 1000 ct/min to fractions of the worm extract were only evident in the cells from a few individuals in each of the various groups. However, 28 days following ivermectin treatment, cells from all onchocerciasis patients were able to mount significantly enhanced proliferation to a fraction of approximately 96 kD (fraction 3), while only four of nine of this group showed an increased response to the whole worm antigen. The proportional increase in the response to the whole organism in these individuals was of a much lower magnitude than the increased response to fraction 3. The O. volvulus antigen-specific immunosuppression observed in these onchocerciasis patients appears to be due to suppressive antigens which have the capacity to mask the potential response to selected antigens of O. volvulus, and ivermectin treatment possibly modulates the immune response, allowing for stepwise recognition of such antigens. Since ivermectin treatment kills only the microfilariae and not the adult worm, the putative suppressive antigens would be expected to be from the microfilariae.
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PMID:Ivermectin-induced immunopotentiation in onchocerciasis: recognition of selected antigens following a single dose of ivermectin. 856 7

The prevalence of the apathogenic filaria Mansonella perstans was studied in four parishes in western Uganda as part of an onchocerciasis control programme to avoid futile treatment. Blood samples from 1543 persons aged over 14 years from 19 villages were examined for the presence of microfilariae using a modified Knott method. The prevalence of microfilaraemic persons ranged between the parishes from 39% (95% CI 35.9-42.0%) to 81% (95% CI 76.2-84.8%). With exception of single microfilariae of Onchocerca volvulus no other filaria species was detected. Onchocerciasis mass treatment campaigns did not reduce the prevalence of M. perstans infection, since 6-12 months after treatment with a single dose of 150 micrograms/kg ivermectin the prevalence in 124 persons was about the same as before treatment. The QBC-fluorescence technique was employed for the detection of microfilariae in samples from outpatients of the government hospital in Fort Portal: in 16% of 120 children and 24% of 369 adults microfilariae of M. perstans were detected.
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PMID:Prevalence of Mansonella perstans in western Uganda and its detection using the QBC-fluorescence method. 857 45

A recently developed polymerase chain reaction (PCR)-based assay is significantly more sensitive than current methods for diagnosing Onchocerca volvulus infection, and it overcomes many difficulties in identifying active onchocerciasis. Since chemotherapy is widely used to treat onchocerciasis, the utility of PCR in assessing responses to treatment and in predicting recrudescence is important. Twenty-eight patients who had skin snips positive for microfilariae (Mf) were studied 120 days after receiving amocarzine, when each was negative for Mf: 16 (57%) were positive for O. volvulus DNA in the PCR-based assay. Of these, 14 (88%) were Mf positive when reassessed parasitologically on day 240, and all were Mf positive on day 365. Equally important was the finding that 12 patients had cleared both Mf and Mf DNA; only 1 was Mf positive at day 240. This suggest that the PCR-based assay provides a sensitive means assessing infection status after macrofilaricidal chemotherapy and is an early predictor of persons likely to have a recurrence of Mf.
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PMID:Polymerase chain reaction-based assessment after macrofilaricidal therapy in Onchocerca volvulus infection. 862 52

The diagnostic value of ELISAs based on recombinant Onchocerca volvulus antigens OC 3.6 and OC 9.3 was evaluated with sera from endemic areas in West Africa, Guatemala and Ecuador. IgG assays were slightly more sensitive than those that detected IgG4, and the antigen combination was significantly more sensitive than either antigen alone (OC 3.6, 93%; OC 9.3, 84%, combined 98%). These assays were also evaluated with sera from 2 villages in the Onchocerciasis Control Programme area of West Africa including one village (Pendie) with recent recrudescence of infection and one (Niarba) where transmission had been interrupted for 15 years by vector control. The OC 3.6 IgG antibody assay was sensitive for new infections and exposure in Pendie; 24/24 (100%) of people with positive skin snips and 15/74 (20%) of sera from MF negative people had IgG antibodies to this antigen. In addition, antibodies to OC 3.6 often preceded the onset of skin snip positivity in Pendie. In contrast, IgG antibodies to OC 3.6 and OC 9.3 were rarely seen in children born during the 15 years since transmission was interrupted by vector control in Niarba. These encouraging results suggest that antibody assays based on OC 3.6 and OC 9.3 may be valuable tools for surveillance of onchocerciasis and also for monitoring the efficacy of control programmes.
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PMID:Use of recombinant Onchocerca volvulus antigens for diagnosis and surveillance of human onchocerciasis. 891 41

Onchocerciasis is a chronic infectious disease caused by the filarial nematode Onchocerca volvulus. A minor population of human gammadelta T cells expressing Vdelta1 chains is preferentially stimulated by O. volvulus ligands in vitro. Therefore, the nature of the parasite ligand and the effector functions of Vdelta1+ T cells stimulated by O. volvulus was investigated. A 5- to 30-kDa ligand from the adult parasite lysate that is sensitive to proteinase treatment was identified. Presentation for preferential stimulation of Vdelta1+ T cells required processing. After in vitro stimulation with O. volvulus in the presence of interleukin-2, Vdelta1+ T cells produced interferon-gamma but not interleukin-4 and exhibited NK cytolytic activities. It is concluded that somatic 5- to 30-kDa protein ligands from O. volvulus stimulate Vdelta1+ T cells and that Vdelta1+ T cells play a role in immunity to O. volvulus.
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PMID:Low-molecular-weight protein ligands from Onchocerca volvulus preferentially stimulate the human gammadelta T cell Vdelta1+ subset. 894 Feb 23

Corneal inflammation (keratitis) is a major cause of visual impairment in Onchocerca volvulus infection. Previous studies showed that onchocercal keratitis can be induced in mice following s.c. immunization and intracorneal injection with soluble O. volvulus Ags (OvAg), and that the inflammatory response is dependent on T cells and IL-4. Since recombinant IL-12 impairs IL-4-dependent, Th2-mediated responses in other parasitic infections and in models of allergic asthma, the present study was undertaken to determine the effect of IL-12 on onchocercal keratitis. Mice were injected i.p. with IL-12 or saline at the time of initial sensitization to OvAg. Surprisingly, IL-12 treatment caused significant exacerbation of corneal pathology, which was associated with increased eosinophil and mononuclear cell infiltration into the corneal stroma. Consistent with the well-documented effect of IL-12 on Th1 cell development, corneas of IL-12-treated animals had elevated expression of the Th1 cytokine IFN-gamma and diminished expression of the Th2 cytokines IL-4, IL-5, IL-10, and IL-13. However, corneas from these animals also had marked elevation of alpha- and beta-chemokines known to be active on eosinophils and mononuclear cells, including IFN-gamma-inducible protein (IP)-10, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, JE/monocyte chemotactic protein-1, RANTES (regulated upon activation, normal T expressed and secreted), and eotaxin. Together, these data indicate that IL-12 exacerbates OvAg-mediated corneal pathology by enhancing chemokine expression and recruitment of inflammatory cells.
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PMID:IL-12 exacerbates helminth-mediated corneal pathology by augmenting inflammatory cell recruitment and chemokine expression. 899

This study examined the development and persistence of immunity in humans presenting defined states of Onchocerca volvulus infection, i.e. in exposed endemic control individuals without microfilaridermia and clinical disease, in patients with patent or post-patent onchocerciasis, and in patients concurrently infected with Mansonella perstans. Onchocerca volvulus antigen (OvAg)-specific cellular reactivity was significantly diminished in microfilariae (mf)-positive patients, while the highest reactivity was measured in exposed but mf-negative endemic controls, those being free of any clinical signs of onchocercal disease. In patients who became post-patent, responses to OvAg were significantly augmented, but did not approach entirely the magnitude observed in endemic controls. In onchocerciasis patients with concurrent mansonelliasis, cellular unresponsiveness to OvAg persisted, even when mf of O. volvulus were eliminated permanently by repeated ivermectin therapy. Cells from mf-positive onchocerciasis patients produced significantly less interferon-gamma (IFN-gamma) (P < 0.01) and interleukin-5 (IL-5) (P < 0.05) in response to OvAg than those taken from endemic controls or post-patent individuals in whom IFN-gamma and IL-5 production was similarly high. In contrast, both OvAg-driven as well as spontaneous IL-10 secretion was higher in mf-positive patients than in endemic controls or post-patent cases. In all individuals examined, serological recognition of OvAg by immunoglobulins was dominated by IgG4; in mf-positive patients OvAg of 205,000-12,000 molecular weight (MW) were strongly bound. In post-patent individuals, and similarly in endemic controls. OvAg recognition by IgG4 varied from intense (with numerous antigens being recognized) to weak or absent antigen binding. Significantly elevated OvAg-specific IgG isotypes were measured in mf-positive onchocerciasis patients in comparison with endemic controls or post-patent individuals (with the exception of IgG3). IgG1, IgG2 and IgE were higher, but IgG4 was lower in endemic controls compared with post-patent onchocerciasis patients. The ratios of IgG4/IgG1 differed (P < 0.001) between endemic controls and mf-positive or post-patent onchocerciasis patients, with IgG4/IgG1 ratios of R < 3.0 being characteristic for endemic controls and post-patent O. volvulus infection. In conclusion, this cross-sectional immunoepidemiological investigation showed that distinct states of O. volvulus infection correlate with a particular cellular and humoral immune response. The mf-free condition appeared to be associated with a vigorous parasite-specific cellular reactivity and a particular cytokine production profile, while concurrent M. perstans infection depressed OvAg-specific cellular responsiveness. Antibody responses, in all likelihood, reflected the intensity and state of infection, and not the degree of acquired immunity protective against parasite aggregation.
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PMID:The diverse expression of immunity in humans at distinct states of Onchocerca volvulus infection. 917 14

The prevalence of onchocerciasis infection was determined in communities on 7 rivers located in the northern area of the canton San Lorenzo, province of Esmeraldas. Diagnosis of the infection was obtained by skin biopsies and recombinant-antigen based-serology. No evidence of infection was detected in 9 communities studied along the Rio Mataje, which forms the frontier between Ecuador and Colombia, nor in 10 adjacent communities located on 5 interior rivers. Evidence for Onchocerca volvulus infection was found in 4 communities on the Rio Tululvi with the following prevalence: La Boca (3.5% by biopsy and 3.9% by serology), Guayabal (9.1% by both biopsy and serology), La Ceiva (51.5% by biopsy and 53% by serology), and Salidero (4% by biopsy and 7.7% by serology). A few individuals in these communities were seropositive for O. volvulus in the absence of detectable dermal microfilariae: these might harbor very light or prepatent infections. No clinical disease attributable to onchocerciasis was found. The infected communities will be included in the ivermectin-based National Control Program for the disease, with no evidence of the infection having extended north of the Ecuadorian-colombian border.
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PMID:Onchocerciasis in Ecuador: prevalence of infection on the Ecuador-Colombia border in the Province of Esmeraldas. 933 82


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