Diagnosis and extirpation of nodules in human onchocerciasis.

The clinical search for onchocercal nodules, and their preferred sites on the body in different geographic areas are described and illustrated. The differential diagnosis of onchocercomata is discussed and figures on the frequency of false diagnoses are reported. The prevalence of adult Onchocerca volvulus in relation to the endemicity of infection, the age and sex of the patients, the localisation of nodules on the body, and the measures used to control onchocerciasis are discussed.

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.

Histological examination of onchocercomata after therapy with ivermectin.

During chemotherapy trials in hyperendemic onchocerciasis areas in West Africa 15 adult nodule carriers in Liberia and 24 patients in Mali received single doses of ivermectin (150 or 200 micrograms/kg). Nodules were extirpated two, six and ten months after therapy and examined histologically. No macrofilaricidal effect of ivermectin was observed.

Effects of high doses of diethylcarbamazine on adult Onchocerca volvulus examined by the collagenase technique and by histology.

Thirty adult male nodule carriers from a hyperendemic onchocerciasis area in the Liberian rain forest were treated with high doses of diethylcarbamazine (30 mg/kg/d) over one week. Another ten patients received placebo tablets and served as a control. All detectable nodules were removed from half of the patients at two months and from the remaining patients at ten months after chemotherapy.

Chemotherapy of onchocerciasis with high doses of diethylcarbamazine or a single dose of ivermectin: microfilaria levels and side effects.

Fifty adult male subjects with moderate to heavy onchocerciasis from the Liberian rain forest were selected for a double-blind placebo-controlled chemotherapy study. The effects of high doses of diethylcarbamazine (DEC) - 30 mg/kg/d - over one week preceded by a one week initial treatment with normal oral doses of DEC or DEC lotion were compared with a single dose of ivermectin (150 micrograms/kg) and placebo. During the initial treatment DEC tablets or lotion caused distinctly more frequent and severe reactions than did invermectin.

Distribution pattern of peripheral lymphocyte subsets in localized and generalized form of onchocerciasis.

The relationship of peripheral lymphocyte subpopulations to the generalized and localized form of onchocerciasis has been studied in 43 Liberian (West African) patients. Typing revealed a significantly increased proportion of lymphocytes expressing interleukin 2 or transferrin receptors in the localized form of onchocerciasis (African sowda) when compared to subjects with a generalized form and those without signs of onchocerciasis. Patients with African sowda showed a higher number of helper/inducer T cells, a greater ratio of helper/inducer: suppressor/cytotoxic T cells, and an increased number of DR antigen-positive cells and lymphocytes with a natural killer cell phenotype.

A DNA sequence specific for forest form Onchocerca volvulus.

Onchocerciasis, or river blindness, is caused by infection with Onchocerca volvulus, a filarial parasite which infects about 40 million people in Africa and Latin America. Epidemiological, clinical, entomological and serological studies of African onchocerciasis led to the hypothesis that Onchocerca volvulus exists in different forms in the forest and savannah. It is uncertain if these differences are due to genetic differences within O.

Ivermectin effect on microfilariae of Onchocerca volvulus after a single oral dose in humans.

Ivermectin is a broad spectrum anti-helminthic agent which is currently being tested for use in human onchocerciasis. Its activity is believed to result from its effect on GABA-mediated neurotransmission. We examined the effects of ivermectin on motility of microfilariae of O.

The Testryp CATT (Card Agglutination Test for Trypanosomiasis): a field study on gambiense sleeping sickness in Liberia.

The inhabitants of three Liberian villages in a known gambiense sleeping sickness area with a low prevalence were examined comparatively with the haematocrit centrifugation technique (HCT), the miniature anion exchange centrifugation technique (m-AECT), the indirect fluorescent antibody test (IFAT) and the Testryp CATT (Card Agglutination Test for Trypanosomiasis). Among 418 persons examined was one individual from whom trypanosomes could be isolated with the HCT and m-AECT. This positive case and another 21 individuals had positive titres of 1:40 and more in the IFAT.

Phosphoenolpyruvate carboxykinase from Onchocerca volvulus and O. gibsoni.

Phosphoenolpyruvate carboxykinase, a rate-limiting enzyme at the branchpoint of phosphoenolpyruvate (PEP), was demonstrated in Onchocerca volvulus and O. gibsoni. The activity of PEP-carboxykinase from both filarial worms depends absolutely on the presence of divalent cations; in addition to Mg2+ the enzyme activity was strongly activated by Mn2+.

Differences in the distribution of HLA antigens in localized and generalized form of onchocerciasis.

Fifty-nine unrelated Liberians have been studied for human leukocyte antigens (HLA). Twenty-three individuals were classified as localized and 24 as generalized onchocerciasis, and the remaining 12 subjects showed no signs of the infection. HLA-typing documented differences in phenotype frequencies for class I (A, B, C) and class II (DR) antigens between the 3 groups of tested subjects.

Detection of serum antibodies and circulating antigens in a chimpanzee experimentally infected with Onchocerca volvulus.

The course of the humoral immune response was followed in a chimpanzee experimentally infected over 27 weeks with a total of 168 Onchocerca volvulus 3rd-stage larvae obtained from naturally infected wild-caught blackflies. Antibodies against an adult worm extract could be detected by ELISA from week 16 onwards (after the inoculation of 44 larvae). Peak antibody levels were observed between weeks 66 and 74 (about one year after the last larval injection).

Prevalence of Paragonimus uterobilateralis infection in children in a Liberian village.

Stool and sputum samples from 127 children in an endemic paragonimiasis area in Liberia, West Africa, were examined for the presence of lung fluke eggs. Samples from nine children (7%) were positive. The eggs were identified as those of Paragonimus uterobilateralis.

Onchocerca volvulus: enzyme polymorphism in relation to the differentiation of forest and savannah strains of this parasite.

Isozyme analysis was carried out on Onchocerca volvulus worms collected from Liberia, Ivory Coast, Burkina Faso and Sudan to see whether this technique could detect differences between forest and savannah populations of this parasite. A total of 243 forest and 189 savannah individual female worms were electrophoresed and stained for seven enzymes. Four showed some polymorphism, LDH, MDH, PGM and MPI and the other three, GAPDH, PEP and GPI were invariant.

Humoral and cellular immune responses to Onchocerca volvulus infection in humans.

Onchocerciasis is one of the major filarial diseases affecting humans and a leading cause of blindness. Control of the disease by chemotherapy and by elimination of the vector is not feasible in most areas of endemicity. The host immune response is thought to play a major role in the pathogenesis of complications.

Calcification in adult Onchocerca volvulus.

Calcified worm fragments of adult Onchocerca volvulus from patients in West Africa were collected for a chemical analysis. The material contained predominantly calcium carbonate. Some results of investigations on the occurrence of calcified worms in untreated populations are reported on.

Parasite-specific inhibition of 5'-nucleotidase from Onchocerca volvulus and Dirofilaria immitis by the amoscanate-derivative CGP 8065.

The presence of 5'-nucleotidase was demonstrated in Onchocerca volvulus and Dirofilaria immitis; the bulk of activity was found in the particulate fraction. The enzyme of filarial worms exhibited a broad pH-optimum between 6.4 and 8.

Onchocerca volvulus: transplantation of adult worms into chimpanzees.

Adult Onchocerca volvulus were transplanted into chimpanzees with or without complete or partial digestion of associated nodule tissue. Survival of adults worms was limited, but low level microfilarial densities remained detectable in skin over partially digested nodule transplants for 12 months. Human nodule tissue transplanted with adult worms showed enhanced survival as compared to subcutaneous tissue transplanted without worms.

Effects of a single complete nodulectomy on nodule burden and microfilarial density two years later.

In hyperendemic onchocerciasis areas of the Liberian rain-forest it was possible to re-examine 210 microfilaria carriers two years after a first examination. At the first examination of these patients 143 had presented with palpable nodules, and 110 nodule carriers had been completely nodulectomized. Two-thirds of the operated patients had an average of one newly detected nodule two years later, and their microfilarial densities were slightly increased.

Dolichol kinase in Ascaris suum and Onchocerca volvulus.

Dolichol kinase was demonstrated in the microsomal fraction of Ascaris suum and Onchocerca volvulus. The enzyme from nematodes exhibited specificity for CTP as phosphoryl donor and was found to be inhibited by the reaction product CDP. Enzyme activity was optimal at pH 7.

Development of onchocerca lienalis and O. volvulus from the third to fourth larval stage in vitro.

Third-stage larvae of Onchocerca volvulus and O. lienalis were observed to molt to the fourth stage in various cell-free in vitro systems. The percentage of O.

Studies on nodules and adult Onchocerca volvulus during a nodulectomy trial in hyperendemic villages in Liberia and Upper Volta. II. Comparison of the macrofilaria population in adult nodule carriers.

In the Liberian rain-forest and the savanna of Upper Volta 189 adult nodule carriers were operated on. From 2231 extirpated nodules 3327 male and 5713 female macrofilariae were isolated. About 98% of the male worms and 88% of the female worms were found alive.

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.

Long-term treatment of onchocerciasis patients from the Liberian rain-forest with low doses of diethylcarbamazine citrate after complete nodulectomy.

60 completely nodulectomized volunteers from the Liberian rain-forest were given an initial treatment with diethylcarbamazine citrate (DEC-C) for one week with gradually increasing doses up to a total of 1.1 g per patient. A long-term treatment followed with 50 mg DEC-C per week for 12 months.