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Results for “Onchocerca volvulus”

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PubMed1983

Non-specific suppression of antigen-induced lymphocyte blastogenesis in Onchocerca volvulus infection in man.

Lymphocyte blastogenic responses to O. volvulus antigen (Oncho Ag), SKSD, and the mitogen PHA were tested in three groups of persons: light to moderately infected persons (INF); previously exposed but uninfected persons (EXP) and normal controls (NC). The exposed group showed significant responsiveness to Oncho Ag (delta ct/min = 6,002 +/- 1,375), while the infected (delta ct/min = 943 +/- 418) and normal control (delta ct/min = 428 +/- 418) groups did not. The mean blastogenic response to SKSD were EXP, 8,644 +/- 5,249; NC 6,039 +/- 2,880; INF, 2,619 +/- 1,012. The reduced reactivity in the INF group to Oncho Ag showed a significant correlation with reactivity to SKSD (P less than 0.05). To elucidate the mechanism of hyporesponsiveness in the infected group rigorous adherent cell depletion, by adherence to plastic followed by a nylon wool column, was utilized. When 20% plastic adherent cells were added back to the T cells prepared in this fashion, the mean blastogenic response to SKSD was significantly augmented (P less than 0.01). In contrast, the responsiveness to Oncho Ag was not significantly altered. The addition of indomethacin (1 microgram/ml) or autologous plasma had no significant effect on reactivity to either SKSD or Oncho Ag. There were no significant differences in the mean reactivity of the three groups to PHA-M (delta ct/min EXP 78,514 +/- 12,564; INF 62,393 +/- 14,447; NC 61,423 +/- 4,465). These results suggest that O. volvulus infection is associated with decreased lymphocyte reactivity to both parasite related and unrelated antigens, and imply that the mechanism for the two types of hyporesponsiveness may be distinct. While a weakly adherent suppressor cell may account for non-specific hyporesponsiveness, the mechanism of parasite specific decreased reactivity remains unknown.

Adolescent↗

PubMed1988

Phylogeny of Onchocerca volvulus and related species deduced from rRNA sequence comparisons.

A rapid, direct method for determining the partial nucleotide sequence of large subunit ribosomal RNA was adapted and applied to a group of helminth parasites. Small samples of total, unfractionated cellular RNA isolated from each organism were analysed and the nucleotide sequences of equivalent portions of the large subunit ribosomal RNA compared. The data obtained were used to construct a phylogenetic tree showing the evolutionary relationships within this group of organisms.

Animals↗

PubMed1978

A simple technique to assess the total number of Onchocerca volvulus microfilariae in skin snips.

A technique for the assessment of the total number of microfilariae in skin snips from onchocerciasis patients is described. For the digestion of the skin tissue the biopsies are incubated at room temperature for 24 hours in medium 199, containing 3 mg/ml collagenase and antibiotics. This process leaves the microfilariae unharmed. A comparative study of the emergence of the microfilariae in different media showed that only 20% of the total number were released after 30 minutes in distilled water. After 24 hours incubation in isotonic saline 80% were found.

Humans↗

PubMed1988

Molecular cloning of an immunodominant antigen of Onchocerca volvulus.

We have cloned and characterized the gene for an immunodominant antigen of O. volvulus that is recognized by the sera of 96% of patients with onchocerciasis. Its 1.2-kb mRNA constitutes 0.3% of adult worm poly(A)+ RNA and its cDNA sequence reveals that it is not a highly conserved structural protein such as actin or tubulin. Similar but not identical genes occur in the genomes of related filarie, Brugia malayi and Dirofilaria immitis. The recombinant antigen has both immunodiagnostic and immunoprophylactic significance.

Amino Acid Sequence↗

PubMed1978

Small-scale trials of six drugs against Onchocerca volvulus.

Six drugs in common use for the treatment of parasitic infections of man were given to 18 adult patients suffering from onchocerciasis. None of the six (metronidazole, tinidazole, mebendazole, trichlorophone, oxamniquine and pyrantel pamoate) showed any evidence of substantial activity against the microfilariae or adult worms of O. volvulus. The mean reduction in skin microfilarial counts a week after drug treatment (a measure of microfilaricidal action) was highest in patients treated with trichlorophone (47.0%) and mebendazole (40.0%). The rate of build-up of microfilariae over a follow-up period of 24 months after treatment with the drug under test followed by DEC (a measure of macrofilaricidal action) was slowest in the groups treated with metronidazole and trichlorophone (22.9% and 27.0% of the pre-treatment counts respectively). These results fall short of those expected of drugs with potential value in the treatment of onchocerciasis.

Adult↗

PubMed1979

Effect of diethylcarbamazine on the concentration of Onchocerca volvulus microfilariae in hydrocoele fluid and urine.

The effect of graded doses of diethylcarbamazine on the concentration of microfilariae in the hydrocoele fluid, urine and skin of patients suffering from onchocerciasis was studied. The results showed that a significant number of microfilariae migrated into hydrocoele fluid and urine immediately after the drug was given and thereafter returned to pre-treatment levels rather more quickly in the former than the latter. The increase was found to be roughly directly proportional to the intensity of infection in the skin. By contrast the skin concentration of microfilariae fell sharply after treatment and remained significantly lower than pre-treatment levels for over four weeks. The potential use to which these observations could be put with respect to clinical screening of drugs in onchocerciasis is discussed.

Adult↗

PubMed1984

Interaction of amoscanate with the cyclic AMP-phosphodiesterases from Schistosoma mansoni, Onchocerca volvulus and bovine heart.

The anthelmintic compounds amoscanate (4-isothiocyanato-4'-nitrodiphenylamine) and its derivatives CGP 6140 and CGP 8045 are potent inhibitors of the activities of cyclic AMP-phosphodiesterases from schistosomal and filarial worms as well as from both the calmodulin-dependent and the -independent enzyme of bovine heart. As shown for CGP 8045 the type of inhibition is non-competitive with respect to the substrate and the inhibition constants were determined to be in the range of 50 micrograms/ml for the enzymes of parasites and mammalian. It is proposed that the inhibition of cyclic AMP-phosphodiesterase-activity by amoscanate and derivatives - resulting in accumulation of cyclic AMP - might subsequently lead to disturbances in the regulation of metabolic areas like glycogen metabolism which are controlled by cyclic AMP-dependent protein kinases.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1980

Onchocerca volvulus: effect of suramin on lactate dehydrogenase and malate dehydrogenase.

Lactate dehydrogenase and malate dehydrogenases were partially purified and characterized from adult O. volvulus. The molecular weight of lactate dehydrogenase was determined to be 130 000, those of malate dehydrogenase I and II to be 120 000 and 65 000, respectively. The activities of both malate dehydrogenases and of the lactate dehydrogenase were strongly inhibited by suramin. The inhibition constants were determined to be in the range of 2 microM to 5 microM. The type of inhibition was found to be competitive with respect to the coenzyme NADH and to be non-competitive to the substrates. It is suggested that the mode of action of suramin in the therapy of Onchocerciasis might depend on the blokkade of reoxidation of NADH produced within the glycolytic pathway.

Animals↗

PubMed1982

The fine structure of adult Onchocerca volvulus. I. The cuticle, the hypodermis and the muscle cell of the male worm.

The fine structure of the cuticle, the hypodermis and the muscle cells of five male worms from Liberia and of two male worms, at least five years old, from Upper Volta is described. The cuticle in the lateral regions is thicker and consists of more layers than in the dorsal and ventral regions. The innermost zone of the hypodermis contains a wide labyrinth of extracellular clefts. The muscle cells are of the shallow coelomyarian type. Bacteria were found in the hypodermis of worms from Liberia and Upper Volta. The hypodermis and the muscle cells contained various other inclusions and particles. Some of them were formed by aggregations of regularly arranged membranes and lamellae. Although all the worms had been alive at the moment of fixation, severe degenerative alterations of the hypodermis and the muscle cells could be observed. Only the cuticular morphology was more or less constant in all seven worms.

Animals↗

PubMed1982

The fine structure of adult Onchocerca volvulus. II. The intestine and the reproductive system of the male worm.

The morphology of the gut and the genital duct of five male worms from Liberia and two male worms at least five years old, from Upper Volta are described. The lumen of the intestine can be distended vesicularly or it can be reduced to a cleft which is filled with microvilli. The intestinal epithelium contains concentric spherules or dense bodies with piles of lamellae. In parts of the intestine of a live worm the cells can be completely disintegrated. The wall of the testis consists of a squamous epithelium which contains numerous dense bodies on the luminal side. The wall of the vas deferens is a squamous or cuboid epithelium which contains glycogen and various particles. In the ejaculatory duct the epithelial cells are linked together by desmosomes at their luminal side. The brownish appearance of some organs under the light microscope is related to the accumulation of iron containing particles.

Animals↗

PubMed1983

The fine structure of adult Onchocerca volvulus. III. The cuticle, the interchordal hypodermis and the muscle cells of the female worm.

The morphology of the cuticle, the interchordal hypodermis and the muscle cells of three mature but not full-grown worms, one worm less than five years old, two worms at least five years old and seven worms of unknown age are described. The cuticle in the anterior region is very similar to that of the male worm, however, in the midbody region the cuticular structure is more simple. The length of the folds of the surface membrane and the thickness of the coat vary considerably. The outer surface of the hypodermis is increased by lamellae, the inner surface by a labyrinthine system of folds. The structure of the muscle cells is simpler than in the male worm: degenerative alterations are found frequently comprising reduction of the afibrillar portion, separation of the filaments from the septa, disintegration of the filaments, and separation of the plasma from the laminae and finally total disintegration of the cell, leaving the empty laminal coverings behind.

Animals↗

PubMed1983

The fine structure of adult Onchocerca volvulus IV. The hypodermal chords of the female worm.

The morphology of the hypodermal chords in the anterior, midbody and posterior region and in worms of different ages are described and the amphids, the cephalic papillae and the nerve ring are demonstrated. At the anterior end, the hypodermal cap comprises the sensory organs. Close behind, the hypodermal chords are differentiated, and several cell margins are found in all of them. Four sublateral chords are differentiated, and several cell margins are found in all of them. Four sublateral chords are also found in the anterior region. A row of median cells is found between the dorsal and ventral syncytia further behind and at the posterior end. In the midbody region, the lateral chords are very large but without central cells. Various particles and inclusions such as bacteria, dense bodies and fibrils are found in the plasm of the hypodermal chords. A large multilayered inclusion was found in the degenerating chord of a female worm at least five years old.

Animals↗

PubMed1990

Effect of ivermectin on the vertical distribution of Onchocerca volvulus microfilariae in the skin.

A new technique for assessing vital and degenerative microfilariae (mf) in different skin layers of onchocerciasis patients is described. Vertical sections at least 5 mm deep were collected from the surgical nodulectomy wounds before and 2, 4 and 28 days after treatment with ivermectin and fixed in ethanol. Skin biopsies were punched horizontally with trephines and digested enzymatically with collagenase. In untreated biopsies 80% of the mf were located in the uppermost layer of 1 mm and only 1.2% were degenerated. After treatment with ivermectin the total number of mf was significantly reduced, and the distribution of living and remnant mf in the different skin layers had changed. The proportion of degenerated mf had increased markedly, but did not exceed 6% of the total pre-treatment mf level, i.e., the vast majority of the mf had actually disappeared from the skin. It is suggested that ivermectin reduces microfilarial motility slightly, and that mf are then attacked by adhering immunocompetent cells of the host and cleared by the lymphatic drainage.

Animals↗

PubMed1989

Dynamics of microfilariae of Onchocerca volvulus over the first 72 hours after treatment with ivermectin.

Changes in microfilaria (mf) densities in skin, blood and urine were followed over 72 hours in 8 Guatemalan patients who received invermectin (150 mcg/kg po in a single dose). After an initial increase at 6 hours, the significance of which is not clear, mf densities in skin snips decreased rapidly to reach 13% of their pre-treatment level by 48 hours and then fell much more slowly over the next 24-hour period. The fall in mf concentrations is thought to be mainly a result of movement away from the subepidermal layer. In contrast to what happens after DEC, it was not accompanied by any marked wave of microfilaraemia or microfilaruria, nor by the appearance of a papular rash, although brawny oedema of the skin sometimes developed. Reactions that occurred after ivermectin could not be correlated with the initial density of microfiladermia. It is hypothesized that the movement of mfs may be 1) into the deeper layers of the dermal collagen, 2) the subcutaneous fat, or 3) the lymphatic system.

Adult↗

PubMed1988

The morphology of adult Onchocerca volvulus based on electron microscopy.

The fine structures of male and female O. volvulus are described. The sexual dimorphism and the age dependent modifications are mentioned in particular. The cuticle of the male worm consists of more layers than that of the female. The epicuticle of the male is wrinkled, whereas the epicuticle of the female forms protuberances. The outer membrane of the hypodermis is folded to form lamellae, which are associated with a layer of mitochondria. The female worms have only small somatic muscle cells. The intestinal cells are filled with concentric spherules, and the intestinal lumen is reduced. Various types of age dependent alterations of the fine structures are observed. The electron density of the cytoplasm changes. The interspace between basal lamina and cell membrane increases, the number of organelles is reduced and specific structures are decomposed whereas the number of granules, vacuoles and lipid droplets increases with age and the laminae and the cuticle thicken. These age dependent modifications might resemble drug induced alterations.

Aging↗

PubMed1983

The fine structure of adult Onchocerca volvulus. V. The digestive tract and the reproductive system of the female worm.

The morphology of the oesophagus, the intestine, the ovary, the uterus, the vagina and some inclusions in the body cavity are described in worms of different ages. The oesophagus wall comprises mostly muscle fibrils and a few glandular regions located only in the posterior portion. In the lumen, some material was found. From the anterior to the posterior end, the lumen of the intestine is reduced. The plasm of the intestinal cells of older worms is filled with concentric spherules containing iron, which are absent in mature but not full-grown worms. The ovarial cells contain in their outer region some fibrils and in the inner region some dense bodies. The ring-muscles of the uterine wall run in clefts of the basal lamina. They usually have accumulated iron containing bodies. In the final portion of the uterus and in the vagina the muscles are very thick. A comparison of the general morphology of the midbody regions of young, not full-grown worms, one less than five years old worm and some worms at least five years old is given.

Aging↗

PubMed1980

Investigations on female Onchocerca volvulus for the evaluation of drug trials.

Females of O. volvulus show several typical morphological alterations during their ontogenesis. In order not to attribute such natural findings to the efficacy of drugs in drug trials female worms isolated from untreated patients in Liberia and Togo were examined by light microscopy. Local incrustations could be found regularly on the surface of the female parasite. Different inclusions are described which could often be found. They partially lead to degeneration and calcification. For the evaluation of ovocidal or embryocidal efficacy of drugs the developmental stages of 290 untreated female worms were quantitatively assessed, normal and pathologically altered forms were distinguished. Embryos were obviously not produced continuously but in intervalls of unknown length and frequency. Two third of the females contained embryos and microfilariae, one third showed eggs only or had empty uteri. The number of the developmental stages per female varied considerably. On the average more than 200,000 stages per female were found.

Animals↗

PubMed1987

In vitro study on the effect of the new chemotherapeutic agents CGP 6140 and CGP 20376 on the microfilariae of Onchocerca volvulus.

The effect of two new filaricidal compounds, CGP 6140 and CGP 20376, on the microfilariae of O. volvulus was tested in vitro. Culture medium consisted of a 1:1 mixture of IMDM/NCTC 135 supplemented with 20% heat-inactivated foetal calf serum and gentamycin. For pulse experiments the microfilariae were exposed to the drugs for one or three hours in medium without serum and then replaced to serum supplemented medium. In the continuous cultures the microfilariae were exposed to the drugs fur up to 72 hours without a change of medium. The effect of the drugs was assessed by their ability to reduce the larval motility. A reduction of motility of 98-100% after 24 hours of exposure occurred at levels of 1 micron/ml CGP 20376 or 10 mu mg/ml CGP 6140. After exposure for one hour CGP 20376 immobilized 100% of the microfilariae irreversibly at a drug level of 1 microgram/ml. Whereas no significant immobilization was seen with CGP 6140 after one hour. After exposure for three hours CGP 6140 immobilized up to 100% of the microfilariae at drug levels of 10 and 5 micrograms/ml.

Animals↗