SEARCH · PubMed Health

Results for “Onchocerca volvulus”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources

PubMed2004

Ov-ASP-1, the Onchocerca volvulus homologue of the activation associated secreted protein family is immunostimulatory and can induce protective anti-larval immunity.

Vaccination of mice with a recombinant protein, Ov-ASP-1, the Onchocerca volvulus homologue of the activation associated secreted gene family stimulated very high titres of both IgG1 and IgG2a without adjuvant. rOv-ASP-1 was also immuno-reactive with IgG isotypes from both O. volvulus-infected (INF) and putatively immune (PI) humans, with higher IgG4 in the former group. The protein also stimulated IFN-gamma secretion by PBMC from INF and PI and IL-5 only in INF. Using a mouse diffusion chamber model, vaccination with rOv-ASP-1 resulted in partial but significant protection against challenge with infective third-stage larvae (L3) but only when formulated with Freund's complete adjuvant (FCA) or alum. Protection was Th1-dependent (highly elevated IgG2a) with FCA and contingent on a strongly Th2-skewed (IgG1) response with alum. IgE responses to rOv-ASP-1 with or without adjuvant were weak or absent. When immunization using rOv-ASP-1 in adjuvant failed to induce adequate Th1 (FCA) or Th2 (alum) responses, protection efficacy was compromised. The recombinant protein appears to stimulate a mixed Th1/Th2 response but the outcome in terms of protective immunity is the result of a subtle interplay of its intrinsic and adjuvant-augmented properties. Ov-ASP-1 is potentially secreted based on its localization in the secretory granules of L3.

Adjuvants, Immunologic↗

PubMed2005

Evidence for macrofilaricidal activity of ivermectin against female Onchocerca volvulus: further analysis of a clinical trial in the Republic of Cameroon indicating two distinct killing mechanisms.

During a 3-year trial of the effects of ivermectin (Mectizan) on adult worms and microfilariae of Onchocerca volvulus in the Republic of Cameroon, comparison was made between the percentages of calcified and uncalcified moribund (M) and dead (D) adult female worms dying following (a) the standard dose (150 microg/kg) given annually; (b) high doses (400, then 800 microg/kg) given annually; and (c and d) these same doses given at 3-monthly intervals. In the killing of adult female O. volvulus worms, the relative rôles of (a) natural causes; (b) a presumed, direct, anthelminthic, macrofilaricidal action of ivermectin; and (c) a potentially fatal pleomorphic ovarian neoplasm (PN), of which the incidence is increased by ivermectin treatment, are herein further investigated and discussed. It is concluded that ivermectin per se has a considerable direct macrofilaricidal action against female worms and that this lethal effect is supplemented by the drug's ability in some worms to increase the incidence, and the spread throughout the body of the worm, of the potentially fatal PN ovarian tumour. In moribund and dead ivermectin-treated female worms that were heavily invaded by PN, it is probable that the neoplasm was chiefly responsible for their death, but the additional direct anthelminthic action of the drug, which by itself has been responsible for the death of many other female worms, cannot be excluded as having played a supplementary lethal rôle. Similar problems as to the exact means by which adult female worms are killed may arise now that ivermectin is used in Africa for the mass treatment of lymphatic filariasis; or if and when the macrofilaricidal actions on O. volvulus of other drugs, which are closely related to ivermectin, come to be investigated.

Administration, Oral↗

PubMed1975

Factors influencing the passage of Onchocerca volvulus microfilariae into the urine.

The effect of various substances on the output of Onchocerca volvulus microfilariae in the urine was investigated in volunteers infected with the Cameroon forest and Sudan-savanna strains of the parasite. Output of microfilariae in the urine tended to be higher during periods of normal activity than during sleep. During waking hours, the rate of output remained generally steady, but in some patients occasional showers of microfilariae appeared in the urine, possibly associated with the intake of food and drink. Drinking 1.2-2.5 litres water produced a shower of microfilariae in the urine of some subjects. This began within an hour of drinking and its onset preceeded that of the diuresis. Thiazide diuretics, acting on the convoluted tubules, produced no increase in microfilaruria. In savanna subjects intravenous injection of DT TAB vaccine caused pyrexia, and simultaneously large numbers of microfilariae appeared in the urine. There was no associated diuresis, and no increase in the concentration of microfilariae in the venous blood. In forest subjects DT TAB caused no increase in microfilaruria. In all subjects 25-50 mg diethylcarbamazine (DEC) caused large numbers of microfilariae to appear in the urine on day 0, within a few hours of the first dose; and there was an increased output of urine over the first 24 hours. Microfilaruria declined sharply on day 1 of treatment, but in subjects developing a high microfilaraemia, it rose again on day 2, and declined more slowly thereafter. Betamethazone, given in conjunction with DEC, appeared to slow the rate of destruction of microfilariae in the skin and lymph glands, and to prolong the duration of microfilaraemia and microfilaruria. The findings suggest that there is a reservoir of microfilariae in the glomerular capillaries, which fills slowly by accumulating microfilariae from the circulating blood. The microfilariae probably enter the urine by penetrating the glomerular capillary.

Adult↗

PubMed1976

Fundus lesions in the rabbit eye following inoculation of onchocerca volvulus microfilariae into the posterior segment. II. Pathology.

The injection of living microfilariae of Onchocerca volvulus into the vitreous or immediately beneath the retina of rabbits gave rise to a variable degree of choroiditis. Uveal inflammation was most marked in eyes inoculated directly into the retina and subretinal tissue. The choroiditis was characterised by lymphocytic, plasma cell and eosinophil infiltration and was associated in many instances with degeneration of the overlying retina and pigment epithelium. In the eyes of animals killed more than 40 days after inoculation with microfilariae the leucocytic infiltration was usually mild or even absent, and the predominant finding was circumscribed atrophy and degeneration of the retina. It is concluded that the pathogenesis of the lesions in posterior segment onchocerciasis is basically inflammatory with, possibly, a direct toxic action of the microfilariae on the retina.

Animals↗

PubMed2002

Onchocerca volvulus glycolytic enzyme fructose-1,6-bisphosphate aldolase as a target for a protective immune response in humans.

To identify potential vaccine candidates for the prevention of infection with the filarial nematode Onchocerca volvulus, we screened an O. volvulus L3 stage cDNA library with sera from putatively immune (PI) subjects, and a prominent immunogenic clone of 1,184 nucleotides was identified. It contained an open reading frame of 363 amino acids encoding the glycolytic enzyme fructose 1,6 bisphosphate aldolase (Ov-fba-1). Immunolocalization experiments demonstrated that the protein was most abundantly expressed in metabolically active tissues, including body wall muscle and the reproductive tract of adult female worms. Immunoelectron microscopy of L3 demonstrated binding in the region where the cuticle separates during molting, in the channels connecting the esophagus to the cuticle, and in the basal lamina surrounding the esophagus and the body cavity. Among subjects from areas where this organism is endemic specific humoral and cellular immune responses to recombinant protein were observed in both PI and infected subjects, whereas responses were not observed among subjects who had not been exposed to O. volvulus. Despite the absence of differential responsiveness in parasite-exposed human populations, when the recombinant was tested for protective efficacy in a mouse chamber model, a reduction in survival of larvae by ca. 50% was seen. This observation provides support for the further study of this parasite enzyme as a vaccine candidate in larger animal models.

Amino Acid Sequence↗

PubMed2004

Crystallization of the major cytosolic glutathione S-transferase from Onchocerca volvulus.

Glutathione S-transferases (GSTs) are a family of detoxification enzymes that catalyse the conjugation of glutathione to xenobiotic and endogenous electrophilic compounds, thus facilitating their elimination from cells. The recombinant Onchocerca volvulus GST2 has been expressed in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion technique. Two different crystal forms were grown under identical conditions. They belong to space groups P2(1)2(1)2 and P2(1), respectively. The unit-cell parameters obtained are a = 112.6, b = 84.3, c = 45.1 A for the P2(1)2(1)2 crystal form and a = 51.6, b = 82.3, c = 56.7 A, beta = 95.89 degrees for the P2(1) form. Complete data sets to 2.6 and 1.5 A, respectively, have been collected at 100 K with synchrotron radiation.

Animals↗

PubMed1988

Vascular perfusion of Onchocerca volvulus nodules.

Perfusion of the vascular bed was achieved in 24 freshly excised nodules of Onchocerca volvulus varying from 0.5 to 2 cm in diameter. India Ink, Microfil polymer, or acrylate perfusates were passed through the vascular supply via cannulation of superficial capsular vessels. After clearing in glycerol or methyl salicylate, or KOH corrosion in the case of the acrylate, nodules were examined microscopically. Small nodules had an extensive blood supply, diffusely distributed throughout the nodule matrix, and in close association with the coils of the worms. In bigger nodules the central area appeared more dense, and intense vascularization appeared to be more peripheral; in the largest nodules the central core was not well vascularized, but a band of heavy vascularization was seen at the margin of the core, fed by superficial vessels and in close contact with worm coils. Very fine branches of the vascular tree were perfused by all three contrast media, but histologically there was evidence of incomplete filling of the smallest vessels. However, there was no extravasation of per-fusates around parasites, even where the approximation between between vessels and parasite surfaces was close. The possibility is considered that O. volvulus may control blood vessel proliferation by release of angiogenesis factors, analogous to rapidly growing solid tumors.

Animals↗

PubMed2006

Ivermectin selection on beta-tubulin: evidence in Onchocerca volvulus and Haemonchus contortus.

Ivermectin resistance is common in trichostrongylid nematodes of livestock, such as Haemonchus contortus. This anthelmintic is the only drug approved for mass administration to control onchocerciasis caused by the nematode parasite, Onchocerca volvulus. In parts of West Africa up to 18 rounds of ivermectin treatment have been administered to communities and there are reports of poor parasitological responses to treatment. Understanding ivermectin resistance and ivermectin selection is an important step to reduce selection pressure for resistance, and to develop molecular markers which can be used to monitor the development of resistance and its spread. Here we report evidence that ivermectin selection changes the frequency of beta-tubulin alleles in both the sheep parasite, H. contortus, and the human parasite, O. volvulus. In O. volvulus we have been able to look at the frequency of beta-tubulin alleles in O. volvulus obtained before any ivermectin was used in humans in Africa, and following its widespread use. In H. contortus, we have been able to look at the frequency of beta-tubulin alleles in a strain which has not seen any anthelmintic selection and in an ivermectin selected strain derived from the unselected strain. We have found ivermectin selects on beta-tubulin in both of these nematode species. In the case of O. volvulus, we had previously reported that ivermectin selects for specific single nucleotide polymorphisms in the O. volvulus beta-tubulin gene. This polymorphism results in three amino acid changes in the H3 helix of beta-tubulin, as well as deletions in an associated intron. We report a simple PCR assay to detect the amplicon length polymorphism, resulting from these intronic deletions, which can be used to monitor the frequency of the beta-tubulin allele selected for by ivermectin in O. volvulus.

Africa, Western↗

PubMed1997

The anterior central nervous system of male Onchocerca volvulus (Nematoda:Filarioidea) as a target for chemotherapy: results of an electron microscopy study.

An electron microscopy study was performed to evaluate the feasibility of the use of the anterior nerve ring of male Onchocerca volvulus for the assessment of early drug effects. Worms were exposed to new and known compounds at reasonable concentrations of 1 microM and less for 6, 12, 18, and 36 h in an established in vitro system. The anterior end of the filariae up to a length of 1 mm was examined and the morphological findings were compared with motility and reduction of a tetrazolium sat to formazan by live but not dead worms. The nerve fibers were more susceptible to the chemotherapeutic intervention then the other tissues in the anteriormost part of the worms. The alterations depended on the duration of exposure and the chemical nature of the compounds used. Morphological changes in the nervous tissue and the inhibition of motility and formazan production corresponded well for the arsenical mel w, used as an active standard, two pyrimidinyl-guanidines (PD 105482 and PD 105666), and an imidazolinylhydrazone (WR 251993).

Animals↗

PubMed2005

Protective immunity to the larval stages of onchocerca volvulus is dependent on Toll-like receptor 4.

Toll-like receptor 4 (TLR4) has been shown to be important for the induction of Th2-dependent immune responses in mice. Protective immunity against larval Onchocerca volvulus in mice depends on the development of a Th2 immune response mediated by both interleukin-4 (IL-4) and IL-5. In addition, O. volvulus contains the rickettsial endosymbiont Wolbachia, which has molecules with lipopolysaccharide-like activities that also signal through TLR4. We therefore hypothesized that protective immunity to O. volvulus would not develop in C3H/HeJ mice which have a mutation in the Tlr4 gene (TLR4 mutant), either because of a decreased Th2 response to the larvae or because of the absence of a response to Wolbachia. TLR4-mutant mice were immunized against O. volvulus with irradiated third-stage larvae, and it was observed that Th2 responses were elevated based on increased IL-5 production, total immunoglobulin E (IgE) levels, antigen-specific IgG1 response, and eosinophil recruitment. Protective immunity, however, did not develop in the TLR4-mutant mice. The Th1 response, as measured by gamma interferon production from spleen cells, was comparable in both wild-type and TLR4-mutant mice. Furthermore, antibody responses to Wolbachia were absent in both wild-type and TLR4-mutant mice. Therefore, the defect in the development of a protective immune response against O. volvulus in TLR4-mutant mice is not due to loss of Th2 immunity or the response to Wolbachia but is due to an unidentified TLR4-dependent larval killing mechanism.

Animals↗

PubMed2003

Epidemiology of concomitant infections due to Loa loa, Mansonella perstans, and Onchocerca volvulus in rain forest villages of Cameroon.

An epidemiological survey was conducted in 16 remote villages of the rain forest of southern Cameroon to ascertain the prevalence and intensity of three species of filariae: Loa loa, Onchocerca volvulus, and Mansonella perstans. We examined 1458 individuals for blood-dwelling microfilariae and 1255 of these were also for the presence of palpable nodules. All the villages surveyed were found highly endemic for onchocerciasis and mansonellosis with prevalence ranging from 28.44% to 87.17% for O. volvulus and 52.48% to 100% for M. perstans. The intensities of infection were also found high for M. perstans with arithmetic means of microfilaremia ranging from 280.94 to 4947.57 mf/ml. The loiasis prevalence was relatively low with value from 2.22% to 19.23%. Males were found more infected than females for the three species of filariae, and the prevalence and intensities of microfilaremia vary differently in males and females at different ages. The three species of filariae displayed different degrees of association in the inhabitants with a low prevalence of co-occurrence between L. loa/O. volvulus and between L. loa/M. perstans. In contrast, there was a high prevalence of co-occurrence between M. perstans and O. volvulus. The implications of the co-occurrence of the three species of filariae in the populations of these remote villages on the intervention programs based on mass treatment with mectizan are discussed.

Adolescent↗

PubMed1988

In vitro maintenance of Onchocerca volvulus for harvest of excretory and secretory products.

Recommendations are given for maintenance of female Onchocerca volvulus; conditions as standardized here for drug screening and harvest of secreted-excreted products resulted in survival of worms in culture medium for up to four and six weeks in absence and presence of serum, respectively. As parameter for viability of worms lactate excretion was determined beside control of motility.

Animals↗

PubMed2001

Characterisation of nuclear ribosomal DNA sequences from Onchocerca volvulus and Mansonella ozzardi (Nematoda: Filarioidea) and development of a PCR-based method for their detection in skin biopsies.

The internal transcribed spacer region (ITS1, 5.8S gene and ITS2) of the two filarial nematodes Onchocerca volvulus and Mansonella ozzardi was sequenced, and two species-specific primers designed in the ITS2 to develop a PCR-based method for their specific detection and differentiation. When used with a universal reverse primer, the two species-specific primers gave amplification products of different size, which were readily separated in an agarose gel. The PCR was tested on skin biopsies from 51 people from three localities in Brazil where M. ozzardi is present, and results have been compared with those of parasitological examination of blood. The species-specific PCR gave a higher percentage of detection of infection by M. ozzardi than the parasitological examination of blood. No infection with O. volvulus was detected by PCR. This PCR-based assay may assist in determining the nature of infection in areas where both filarial species exist in sympatry.

Animals↗

PubMed1997

pOVEX vector: prokaryotic expression and purification of onchocerciasis vaccine candidate antigens as fusion proteins with the 24 kD Onchocerca volvulus glutathione S-transferase.

An expression vector, pOVEX, has been designed and constructed, combining the advantages of the expression vectors pGEX-3X and pJC2o. The pOVEX vector produces a fusion protein with the 24 kD Onchocerca volvulus glutathione S-transferase (OvGST2) which is easy to purify in one step from bacterial extracts under non-denaturing conditions using glutathione-sepharose chromatography. High yields of fusion protein were produced from this T7 RNA polymerase-dependent expression vector, which were then cleaved by digestion with the factor Xa protease to separate the OVGST2 polypeptide from the expressed protein of interest. This vector will be particularly useful to O. volvulus investigators for the production of O. volvulus antigens for the analyses of host humoral and cellular responses to these proteins and for immunization studies.

Animals↗

PubMed1999

Onchocerca volvulus: immunolocalization of the extracellular CuZn superoxide dismutase using antibodies raised against a 15-mer epitope of this enzyme.

The study describes the immunohistological localization of the extracellular CuZn superoxide dismutase (SOD2) in the parasitic nematode Onchocerca volvulus. Using specific antiserum raised against a 15-amino-acid peptide from the N-terminal region of the mature protein, this enzyme is detected primarily in the intestinal epithelium of the adult worms and to a lesser extent in the muscle cells of the uterine wall. A blocking experiment with the SOD2 peptide reduced the staining significantly, confirming specificity. The localization profile of SOD2 correlates extremely well with the localization of iron deposits in the gut and uterine muscle cells of adult O. volvulus. The detection of SOD2 in the functional intestine of O. volvulus, together with the evidence that it is a secreted protein, indicates that this enzyme in parasitic nematodes is in a position to interact with host molecules. It also demonstrates the accessibility of the parasite enzyme to an inhibitor or blocking antibody.

Amino Acid Sequence↗

PubMed1988

Histological examination of adult Onchocerca volvulus and comparison with the collagenase technique.

The methods used for the assessment of adult Onchocerca volvulus by histology are described. Based on the results of several studies, mainly in Liberia and Burkina Faso, the morphology of the adult filariae in histological sections is represented as far as it is relevant for the evaluation. Especially are described the morphological alterations due to old age of the worms, to chronic hyperreactivity of the human host (sowda) and effects of the macrofilaricidal suramin and of microfilaricidal drugs. Quantitative results are reported on untreated adult O. volvulus from various countries, the changes of the worm population during 12 years of vector control in Burkina Faso and the effects of suramin, diethylcarbamazine, metrifonate, and ivermectin. The data from the histological examinations are compared with those gained from the examination of worms isolated by the collagenase technique in the same studies.

Aging↗

PubMed2003

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 activity. In the absence of an activator, the O. volvulus enzyme exhibits an extremely low specific activity. This fact, together with the unspecificity of activator binding, was thought to be useful for a new strategy to inhibit nematode AdoMetDC activity. Therefore, different polyamine analogues were tested as competitive inhibitors towards the stimulatory effect putrescine has on the O. volvulus and, in comparison, on the Caenorhabditis elegans and human AdoMetDC. Bis(aralkyl)- and bis(alkyl)-substituted polyamine analogues with a 3-7-3 backbone were found to inhibit AdoMetDC activities, however, probably without interfering with the putrescine stimulation. The best inhibitor, BW-1, was about 10-fold more effective against O. volvulus AdoMetDC than against the human enzyme. Unexpectedly, BW-1 was determined to be a competitive inhibitor with respect to AdoMet, having a Ki value of 310 microM for the putrescine-stimulated human AdoMetDC. Furthermore, we show for the O. volvulus and the human enzyme that the degree of inhibition by BW-1 depends on the actual putrescine concentration.

Adenosylmethionine Decarboxylase↗

PubMed2002

An internal control for the detection of Onchocerca volvulus DNA by PCR-ELISA and rapid detection of specific PCR products by DNA Detection Test Strips.

We developed a polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA) for the detection of Onchocerca volvulus DNA. To standardize the PCR and to avoid false-negative results, an internal control DNA was co-amplified by the same set of primers. We differentiated the wild-type PCR product of the O-150 DNA sequence from the internal control by specific DNA probes. Detection of biotinylated PCR products by DNA probes was performed by ELISA to quantify the PCR product or by DNA Detection Test Strips as a rapid field technique. The methods were evaluated on skin biopsies from individuals living in an area endemic for O. volvulus in Uganda, but with low microfilaria densities because of ivermectin treatment. Microfilaria density was assessed by a single skin snip and a second skin snip was examined by PCR. Among 69 samples from microfilaria carriers, 47 (68%) were positive by ELISA and 55 (80%) by test strip detection of PCR products. When 39 samples of microfilaria-negative individuals from the same area were tested, 10 (27%) were positive by ELISA and 12 (31%) by test strips. None of the 19 samples obtained from persons living in an area not endemic for O. volvulus but endemic for Mansonella streptocerca was positive in either test. Although the ELISA is theoretically more sensitive than the test strips for the detection of PCR products, examination of field samples revealed that the test strip method had a higher operational sensitivity and was more convenient to perform. Thus, the DNA Detection Test Strips are a rapid and low-tech tool for identification of PCR products in laboratories of countries endemic for onchocerciasis.

Animals↗