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At least 1,063 records · Page 59Linked to original sources
PubMed1989

pH-dependent uptake and macrofilaricidal effects of chloroquine on adult filarial parasites in vitro.

Uptake and macrofilaricidal effects of chloroquine (CQ) and other aminoquinolines were found to be highly pH dependent in Brugia pahangi, Acanthocheilonema viteae, Onchocerca volvulus, and Dirofilaria immitis. Using [3H]CQ, it was found that all of the parasites took up more drug under alkaline conditions (RPMI 1640 at pH 8.4) than in neutral (pH 7.4) or acidic (pH 6.8) media. Differences were seen in the amount of drug taken up among the filariae studied. B. pahangi and A. viteae took up 7 times more chloroquine per milligram of tissue than did O. volvulus, and 30 times more than D. immitis during a 60-min incubation period at pH 8.4. Sensitivity to the aminoquinolines also increased with increasing media pH, and was measured using parasite motility as an indicator of drug efficacy. Potency of chloroquine against B. pahangi increased 100-fold at pH 8.4 compared to pH 7.4. A. viteae and O. volvulus showed similar sensitivity to chloroquine compared to B. pahangi; D. immitis was less sensitive. While uptake of chloroquine was linear from pH 6.8 to 8.4, B. pahangi was unaffected by 32 microM of the drug below pH 7.6; at any pH above this, motility of this parasite was completely inhibited. Calculations of the internal pH of this parasite indicated that it shifted upwards significantly with changes in media pH. It was concluded that these shifts in internal pH may render parasites more sensitive to the effects of chloroquine.

Animals↗
PubMed1991

Hallucinogenic and neuroleptic drug interactions with potential neurotransmitter receptors in parasitic nematodes.

Receptors potentially involved in neurotransmitting have been characterised in the muscle tissue and in whole worms of the nematodes Ascaris suum and Onchocerca volvulus, respectively. Binding studies revealed a high affinity for LSD with apparent KD values of 94 nM for A. suum and 120 nM for O. volvulus, whereas those of the neuroleptics haloperidol, spiperone and mianserin were found to be in the micromolar range. A variety of neurotransmitter antagonists, known to bind with high affinities either to mammalian D1/2 or to 5-HT1/2 receptors, were tested for their ability to bind to the nematode receptor. Results from these displacement experiments using tritiated LSD, mianserin, spiperone and haloperidol show distinct specificities of the nematode receptors compared to known receptor classes of mammals. With respect to this novel specificity, the nematode receptors seem to be unique and clearly distinct from those of the hosts.

Animals↗
PubMed1985

The onchocercal nodule: interrelationship of adult worms and blood vessels.

This study of onchocercal nodules reveals an intimate relationship between the cuticle of Onchocerca volvulus and the capillaries of the host. Perfusion of blood vessels with India ink and other special techniques reveal a proliferation of capillaries around the worms and communication between small vessels and the spaces around the worms. The space around the worm is continuous with the central fibrin lake. These findings, together with the fact that the worm's gut contains hemosiderin, suggest that the worm subverts the vascular reaction and causes within the nodule a controlled hemorrhage that serves the worm's nutritional needs. We believe this explains, in part, how worms survive in fibrous nodules for many years.

Animals↗
PubMed1985

Double-blind study of ivermectin and diethylcarbamazine in African onchocerciasis patients with ocular involvement.

In a randomised double-blind study, ivermectin was compared with diethylcarbamazine (DEC) and placebo in the treatment of onchocerciasis in 30 male patients from Mali with moderate to heavy Onchocerca volvulus infections and ocular involvement. 10 patients received a single oral dose of ivermectin, 12 mg, 10 received DEC daily for eight days (total dose 1.3 g), and 10 received matching placebo. Patients were examined periodically for twelve months. Punctate keratitis disappeared in 6 of 7 ivermectin patients but increased in DEC patients. Numbers of O volvulus microfilariae (mf) in the anterior chamber decreased slowly and eventually disappeared in most ivermectin patients during the six months following treatment; anterior chamber mf disappeared more rapidly in some patients after DEC, but reappeared within six months of stopping treatment. Both ivermectin and DEC caused a prompt decrease in mean skin mf density; density then increased in both groups over the twelve month observation period, reaching 9% of pretreatment values in ivermectin patients and 45% in the DEC group. Analysis of adult O volvulus from nodules excised at three and twelve months post treatment showed no effect of either drug on viability; however, there was evidence of degeneration of intra-uterine developing mf in the ivermectin group. Side-effects were less frequent and less severe in ivermectin patients than in DEC patients. Ivermectin as a single oral dose appears to be a more effective microfilaricidal drug than DEC in onchocerciasis.

Adolescent↗
PubMed1988

Microfilarial surface carbohydrates as a function of developmental stage and ensheathment status in six species of filariids.

The lectin-binding properties of microfilariae of Onchocerca volvulus, O. lienalis, Brugia pahangi, Wuchereria bancrofti, Dirofilaria immitis, and Monanema (= Ackertia) marmotae share a number of characteristics. Carbohydrates specific for lectins are associated with the egg shell or sheath. N-acetyl-D-glucosamine is the predominant carbohydrate associated with the ensheathed forms with lesser quantities of D-galactose and/or alpha-lactose and D-galactosamine. The density of these carbohydrates on the sheath surface diminishes as the larvae undergo normal growth and development. Similar carbohydrates are not found on the cuticle as exsheathed microfilariae show virtually no ability to bind lectins.

Animals↗
PubMed1991

Immunohistological and electron microscopic studies of microfilariae in skin and lymph nodes from onchocerciasis patients after ivermectin treatment.

Microfilariae were studied in skin and lymph node biopsies from Liberian patients with generalised onchocerciasis 12-78 hours after administration of a single dose of 150 micrograms/kg body weight using histology, transmission electron microscopy and immunocytological staining with antibodies against an immunodominant antigen of Onchocerca volvulus. Most microfilariae in the skin appeared morphologically intact and beginning signs of degeneration were seen only on the ultrastructural level. The densities of microfilariae in the lymph nodes were about thousandfold higher in ivermectin treated patients. More than 90% of the microfilariae in the lymph nodes showed distinct signs of degeneration. Early changes were seen in the muscle cells. The disintegrating microfilariae in the lymph nodes were always encircled by eosinophils or macrophages or both cells. Immunohistological staining with antifilarial antibodies increased the detection of small and disintegrating pieces of microfilariae considerably.

Animals↗
PubMed1994

Molecular phylogenetic studies on filarial parasites based on 5S ribosomal spacer sequences.

This paper is the first large-scale molecular phylogenetic study on filarial parasites (family Onchocercidae) which includes 16 species of 6 genera: Brugia beaveri Ash et Little, 1962, B. buckleyi Dissanaike et Paramananthan, 1961; B. malayi (Brug, 1927) Buckley, 1960; B. pahangi (Buckley et Edeson, 1956) Buckley, 1960; B. patei (Buckley, Nelson et Heisch, 1958) Buckley, 1960; B. timori Partono et al, 1977; Wuchereria bancrofti (Cobbold, 1877) Seurat, 1921: W. kalimantani Palmieri. Purnomo, Dennis and Marwoto, 1980: Mansonella perstans (Manson, 1891) Eberhard et Orihel, 1984; loa loc, Stiles, 1905; Onchocerca volvulus (Leuckart, 1983) Railliet er Henry, 1910; O. ochengi Bwangamoi, 1969; O. gutturosa Neumann, 1910; Dirofilaria immitis (Leidy, 1856) Railliet e Henry, 1911; Acanthocheilonema viteae (Krepkogorskaya, 1933) Bain, Baker et Chabaud, 1982 and Litomosoides sigmodontis Chandler, 1931. 5S rRNA gene spacer region sequence data were collected by PCR, cloning and dideoxy sequencing. The 5S rRNA gene spacer region sequences were aligned and analyzed by maximum parsimony algorithms, distance methods and maximum likelihood methods to construct phylogenetic trees. Bootstrap analysis was used to test the robustness of the different phylogenetic reconstructions. The data indicated that 5S spacer region sequences are highly conserved within species yet differ significantly between species. Spliced leader sequences were observed in all of the 5S rDNA spacers with no sequence variation, although flanking region sequence and length heterogeneity was observed even within species. All of the various tree-building methods gave very similar results. This study identified four clades which are strongly supported by bootstrap analysis the Brugia clade; the Wuchereria clade; the Brugia-Wuchereria clade and the Onchocerca clade. The analyses indicated that L. sigmodontis and A. viteae may be the most primitive among the 16 species studied. The data did not show any close relationship between Loa loa and D. immitis presently classified in the same subfamily, and the constitution of the Dirofilariinae subfamily is questionable.

Algorithms↗
PubMed1990

The chemotherapy of onchocerciasis. XIV. Studies with mebendazole citrate.

Twenty patients from an area of vector control in the savannah region of northern Ghana with moderate to heavy infection with Onchocerca volvulus were randomised to receive two priming doses of levamisole 150 mg on two occasions followed either by mebendazole-citrate (500 mg) given daily or twice daily for 14 days. The two dose levels produced a similar effect on skin microfilariae (80-88% reduction) with a very mild systemic clinical reaction: low levels were maintained over 42 weeks. Both regimes were embryotoxic for O. volvulus; an effect which was transient in the single dose group but persisted for more than three months in the twice daily dose group. Mebendazole-citrate appeared to be absorbed more predictably than has been observed previously for mebendazole. The degree of systemic exposure as determined by measurement of AUC (0-24 h) was 2.5 times greater for the twice daily dose as compared to the single dose and this fact was reflected in the efficacy of the two dose regimes against the adult female worms at three months.

Adult↗
PubMed1975

Onchocerciasis in Guatemala. II. Microfilariae in urine, blood, and sputum after diethylcarbamazine.

Guatermalan volunteers with onchocerciasis were given a dose of diethylcarbamazine to learn if this caused migration of microfilariae of Onchocerca volvulus into urine, blood, and sputum. In 5 of the 10 volunteers, the num0ers of microfilariae in the urine increased considerably following the drug. In the same 5, relatively large numbers of microfilariae were observed in the blood and sputum specimens. Response in the remaining 5 was negligible. Four controls given a placebo did not respond. Interestingly, however, 2 control subjects had onchocercal microfilariae in their concentrated blood specimens and 3 control subjects had microfilariae in the sputum. Therefore, we believe that microfilariae, if searched for, may be found in other parts of the patient not normally associated with the infection.

Administration, Oral↗
PubMed1980

Circulating immune complexes in onchocerciasis.

Circulating immune complexes were detected in sera of patients with both localized and generalized onchocerciasis by a 125I-Clq binding assay but not by the IgG latex agglutination inhibition method. Gel filtration of sera demonstrated high molecular weight Clq-reactive material(greater than 2 x 10(6) Daltons) which contained IgM but no IgG. Antibody titres to Onchocerca volvulus antigen were higher in patients with generalized disease than in those with the localized form. The lack of correlation between antibody titres and levels of immune complexes suggests that these immune complexes contain antigens other than those derived exclusively from the parasite. Although few of the symptoms of this disease are likely to be due to deposition of circulating immune complexes, the depression of delayed hypersensitivity reactions to the parasite found in patients with generalized onchocerciasis may be due to IgM immune complexes exerting an immuno-regulatory role on T cell function.

Adolescent↗
PubMed1990

Population decline of Simulium woodi and reduced onchocerciasis transmission at Amani, Tanzania, in relation to deforestation.

To investigate an apparent decline of the onchocerciasis vector Simulium woodi, in the Simulium neavei group, weekly 12-hour biting catches on man were carried out for 13 months near Amani and compared with those obtained 22 years earlier. The results showed a marked fall in biting S. neavei s.l. females and supported earlier findings on the aquatic stages. The mean biting-catch in 1985/6 was only 13% of that in 1963/4 and comprised 91% S. woodi and 9% the more common, but largely zoophilic, Simulium nyasalandicum (Amani form). The infection rate of S. woodi with Onchocerca volvulus larvae had also fallen markedly from 17% to 3% of parous flies; no S. nyasalandicum females were infected. Recent onchocerciasis surveys indicate that reduced transmission has resulted in lower infection rates in man. Exposure by deforestation of the breeding sites of S. woodi in small shaded streams seems to have caused the simuliid's population decline. Reduced populations of S. neavei group vector species have been reported in other deforested parts of eastern Africa. Our long-term quantitative data on declining numbers of biting females without control measures, help to corroborate such reports. Control may no longer be necessary in some areas allowing a greater concentration of limited resources.

Animals↗
PubMed1989

The efficacy of 22,23-dihydroavermectin B1 (Ivermectin) acting singly or in combination with a benzodiazepine on microfilariae of Onchocerca species and Brugia pahangi (an in vitro study).

An in vitro study of the antinematodal action of two groups of compounds which act on the receptor complex of the inhibitory neurotransmitter, Gamma-aminobutyric acid (GABA) in mammalian systems is described. The compounds, Ivermectin and two benzodiazepines, Diazepam and a water soluble Midazolam were tested singly or in combination against two microfilarial parasites Onchocerca lienalis (closely related to Onchocerca volvulus) and Brugia pahangi. The combination of ivermectin and diazepam at a concentration of 0.1 microgram/ml and 33 micrograms/ml respectively achieved the same effect on microfilarial motility as when ivermectin was given at 1 microgram/ml alone or diazepam at 66 micrograms/ml alone. Similarly when the combination of ivermectin at 0.1 microgram/ml and midazolam at 10 micrograms/ml was used it achieved the same effect as ivermectin at 1 microgram/ml alone or midazolam at 33 micrograms/ml alone. This showed that both benzodiazepines had a synergistic effect on the activity of ivermectin. The microfilariae of B. pahangi were insensitive to both groups of compounds at all concentrations used.

Animals↗
PubMed1989

Onchocerciasis endemic in the State of Bolivar, Venezuela.

Microfilariae of Onchocerca volvulus were demonstrated by single shoulder-skin biopsy in 42.8% of inhabitants of seven Amerindian villages in an area of approximately 10,000 km2, near the Brasilian Roraima Territory. The highest prevalence was found among the Yanomama Indians of Chajuraña (84.6%, with a mean of 61.3 microfilariae per mg of skin). The six other communities were affected, but with lower prevalence and microfilaria skin densities. The absence of lymphoedema and the few subcutaneous nodules and eye lesions found among the infected individuals suggest a relatively recent introduction of the disease to the region. Mansonella ozzardi infections were also detected in the area.

Adult↗
PubMed1975

Onchocerciasis: prevalence of microfilaruria and other manifestations in village of Cameroon.

Onchoecercal microfilaruia was studied in the course of an epidemiologic investigation of diseases, infections, and general health conditions in a rural village on the Adamaoua Plateau in northern Cameroon. Microfilariae of Onchocerca volvulus were observed in nearly one half of the skin snips taken from the village residents. The prevalence of onchocerciasis as diagnosed from skin snips increased with age, and was greater for males than females. The number of microfilariae per skin snip also increased wth age. The presence of subcutaneous nodules, inguinal lymphadenopathy, microfilariae in the urine, ocular lesions and prolonged itching all were related to both age and the presence of microfilariae in skin biopsy specimen, as well as to intensity of infection. Microfilaruria was not restricted to individuals with severe onchocerciasis.

Adolescent↗
PubMed1990

Developmentally regulated expression and secretion of a polymorphic antigen by Onchocerca infective-stage larvae.

In order to analyse the developmental biology of Onchocerca spp. with a view to identifying molecules with specialised functions, we have devised a novel method for labelling proteins synthesised by larvae during growth in the vectors. Pulse labelling of Onchocerca lienalis by micro-injections of [35S]methionine into blackflies have revealed a major acidic protein of 23 kDa which is developmentally expressed almost exclusively by infective, third-stage larvae. The protein appears to be antigenically conserved between O. lienalis and Onchocerca volvulus, but exhibits size polymorphisms both among species and among individual organisms. It continues to be elaborated after terminal differentiation of the parasite in flies, but not by post-infective larvae entering the phase of development in the vertebrate host. A shift in temperature from 26 degrees C to 37 degrees C triggers secretion of the 23-kDa molecule as a discrete event 24-72 h after transmission. The labelling technique has been successfully employed with filarial species that develop in mosquitoes, and in principle should be widely applicable to the study of endoparasite gene expression within arthropods.

Animals↗
PubMed1990

Ivermectin treatment of ocular onchocerciasis.

Ivermectin, a recently developed macrocyclic lactone with broad antiparasitic activity, has been shown by a series of clinical trials to be safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction as is seen with diethylcarbamazine treatment. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/Kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement, although ivermectin has no known long-lasting effects on the adult worms. With treatment there is no significant exacerbation of either anterior or posterior segment eye disease even in those with severe ocular disease. Treatment leads to a marked and prolonged improvement in ocular status. Because of its safety and efficacy, ivermectin can be used on a mass scale and promises to revolutionize the treatment of onchocerciasis.

Animals↗
PubMed1988

Evaluation of skin biopsies from different body regions of onchocerciasis patients in Central Nigeria.

The diagnostic potential of skin snips from different body regions was evaluated in 97 onchocerciasis patients of Central Nigeria. Biopsies from the iliac crest had the greatest diagnostic potential followed by those of the calf and shoulder with 95% of Onchocerca volvulus carriers being diagnosed from these sites. However, 23.7% of microfilarial carriers in the skin of the outer canthus, shoulder, calf and ankle were negative in the iliac crest. The probability of diagnosing onchocerciasis in microfilarial positives from the 5 sites was, 0.76 for the iliac crest; 0.63 for the calf; 0.31 for the shoulder; 0.27 for the ankle; and 0.08 for the outer canthus. The concentrations of microfilariae in skin snips were significantly associated with the probability of a positive diagnosis especially with regard to those of the shoulder, iliac crest and calf.

Adolescent↗
PubMed1999

Chemoprophylaxis of Onchocerca infections: in a controlled, prospective study ivermectin prevents calves becoming infected with O. ochengi.

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.

Animals↗