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Biomedical subjects

H Schulz-Key

Publications and source records attributed to H Schulz-Key.

At least 55 records · Page 3Linked to original sources
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

Ophthalmological results from a placebo controlled comparative 3-dose ivermectin study in the treatment of onchocerciasis.

One hundred and ninety eight patients with moderate to heavy infection with Onchocerca volvulus and with eye involvement in most, were allocated randomly to treatment with 100, 150 or 200 mcg/kg body weight of ivermectin or placebo given as a single oral dose in a double-blind dose finding study. The patients were drawn from an area under over ten years of vector control in Northern Ghana by the Onchocerciasis Control Programme, OCP. They underwent detailed clinical, laboratory and ophthalmological examination before treatment and in the review period of one year in hospital. Ivermectin given in a dose of 100, 150 or 200 mcg/kg eliminated microfilariae similarly slowly over 3-6 months and was associated with inflammatory reaction in the anterior segment which resolved without treatment. No changes in the fundus of the eye was detected by fluorescein angiography and no no-table other adverse eye reaction was observed. The ceiling of therapeutic activity of ivermectin in the eye is therefore put at 100 mcg/kg which is lower than the level fo 150 mcg/kg found in the skin. The apparent discrepancy may be due to different dose requirements on account of different mechanisms of action of ivermectin at the two sites. In the skin there is active killing while in the eye it is presumed there is a passive elimination of microfilariae.

Adolescent↗
PubMed1988

Characterization of an immunodominant Onchocerca volvulus antigen with patient sera and a monoclonal antibody.

Adult Onchocerca voluvlus and infective larvae, but not microfilariae contain an immunodominant antigen (33,000 and 21,000 Mr in females, 39,000, 33,000, and 21,000 Mr in males, 133,000 Mr in infective larvae) which is recognized by an Onchocerca-specific mAb. The component is part of the reproductive organs and muscles. 96.2% of onchocerciasis sera contained antibodies detectable by immunoblotting against it. Antigen purified by immunoaffinity chromatography was specifically recognized in immunoblots by onchocerciasis sera, but not by sera from other filarial infections. The high immunogenicity, the specificity, and the occurrence in infective larvae of this antigen indicate an immunodiagnostic potential and a possible role in the immunobiology of the parasite.

Animals↗
PubMed1988

Ingestion of microfilariae from different sources by Culicoides nubeculosus (Diptera: Ceratopogonidae) through an artificial membrane.

Laboratory-hatched Culicoides nubeculosus midges were membrane-fed on cattle blood containing various Onchocerca microfilariae which had been isolated from the hides of red deer (Cervus elaphus) and from Australian and native German cattle. All microfilariae were ingested through the membrane except those of O. tarsicola, which were too large. Onchocerca gibsoni and O. lienalis reached the thoracic musculature, but no further development occurred. Microfilariae of O. flexuosa developed to the "sausage" stage. Microfilariae of O. gutturosa developed to the infective larval stage within 9 days at a temperature of 25 degrees C.

Animals↗
PubMed1988

The collagenase technique: how to isolate and examine adult Onchocerca volvulus for the evaluation of drug effects.

The collagenase technique developed more than twelve years ago has successfully been applied to isolate living and intact O. volvulus from excised onchocercomata for various biological, morphological, biochemical, immunological and in vitro studies. The experience gained with this technique and its modifications is critically reviewed giving practical advice for the selection, preservation and treatment of nodules for different purposes, especially for the evaluation of antifilarial drug effects. The composition of the worm load, the morphology of adult worms found in untreated patients, signs of degeneration and ageing of worms are described to show the broad morphological spectrum of the worm population in endemic areas to avoid false conclusions in drug trials. When these parameters are carefully considered, the collagenase technique provides a reliable method for examination of onchocercomata. An immediate answer can be obtained concerning the viability of the parasite. The qualitative and quantitative assessment of reproduction (embryogram) can give further valuable information on any changes in the reproductive dynamics and provide a sensitive indicator of any disturbances in the adult worms which may explain the early or late reinvasion of microfilariae into the skin after treatment with microfilaricidal drugs.

Animals↗
PubMed1988

Emergence of Onchocerca volvulus microfilariae from skin snips before and after treatment of patients with ivermectin.

As ivermectin is supposed to have a paralyzing effect, the emergence of Onchocerca volvulus microfilariae from skin snips before and after treatment was examined. Before treatment 79.8% of the microfilariae emerged from the skin snips. Three days after treatment the microfilarial skin density had dropped to 83% (placebo), 28% (100 microgram/kg ivermectin), 19% (150 micrograms/kg) and 14% (200 micrograms/kg) of the pretreatment values but the microfilarial emergence was not altered distinctly. The majority of the remaining microfilariae were mobile and able to leave the biopsy. Only a slight, but significant, dose-dependent trend of reduced emergence could be shown. From our results no direct support is derived for the hypothesis that O. volvulus microfilariae are paralyzed or immobilized by ivermectin.

Analysis of Variance↗
PubMed1987

Electron-microscopic observations on the female worms of six Onchocerca species from cattle and red deer.

The midbody regions of female worms of six Onchocerca species (O. flexuosa, O. tarsicola, O. lienalis, O. gutturosa, O. armillata, O. gibsoni) were studied by transmission electron microscopy. The cuticular layering was rather similar in all species with the ridges built up by the cortical layers and the inner cuticular striations by the median or basal layers. Differences in the epicuticular morphology were considerable. O. flexuosa and O. lienalis had a thin epicuticle without protuberances, the epicuticle of O. armillata carried small knobs, and O. tarsicola, O. gutturosa, and O. gibsoni had a thick trilaminar epicuticle with long protuberances. Extreme hypertrophy of hypodermis and reductions of somatic musculature were observed in O. flexuosa and O. gibsoni. Less extended thickenings of the hypodermis were observed in the other species. No degenerative alterations were found in the muscle cells of O. gutturosa and O. lienalis. The intestinal lumen of most of the species was in a central position, but in O. tarsicola and O. gibsoni the lumen was reduced to small clefts between the intestinal cells. In these species, numerous electron-dense, concentric granules were observed in the cytoplasm of the intestinal cells. The proportions of the various organs differed considerably from species to species, e.g., the uteri contained the embryos filed one behind the other in O. tarsicola, whereas 50 or more embryos were found beside one another in cross-sections of the uterus of O. gibsoni. The comparative study showed that O. gibsoni and O. volvulus have many derived morphological characteristics in common and that in the other species more primitive stages of development of these morphological marks can be observed.

Animals↗
PubMed1987

Ocular findings in a double-blind study of ivermectin versus diethylcarbamazine versus placebo in the treatment of onchocerciasis.

The effect of ivermectin, a new microfilaricide, was assessed in a double blind trial against diethylcarbamazine citrate (DEC) and placebo. Fifty-nine adult males with moderate to heavy infection with Onchocerca volvulus and with eye involvement were recruited from an area under Onchocerciasis Control Programme (OCP) vector control in Northern Ghana. They were randomly assigned to an eight-day treatment with ivermectin as a single dose of 12 mg on day 1 followed by placebo for the remaining seven days, or DEC, total dose 1.3 g, or placebo, and ophthalmological review was undertaken over a period of one year. DEC acted quickly to eliminate microfilariae from the eye and was associated with reactive ocular changes and in a few cases functional deficit. Ivermectin eliminated microfilariae slowly from the anterior chamber of the eye over a period of six months. The ocular inflammatory reaction was minimal and no functional deficit occurred. It is postulated that the observed slow action of ivermectin on the eye may be attributed in part to its instability to cross the blood-aqueous humour barrier because of its molecular size as a macrocyclic lactone causing microfilariae to leave the eye gradually along a newly created gradient. Ivermectin is an effective microfilaricide with minimal ocular adverse effect and could therefore be suitable for widespread application without strict supervision.

Adolescent↗
PubMed1987

Population dynamics of Onchocerca volvulus after 7 to 8 years of vector control in West Africa.

In an attempt to describe the changing population dynamics of Onchocerca volvulus during a period of vector control, nodulectomies were undertaken in 256 patients from ten villages in the Onchocerciasis Control Programme (OCP) and in 74 patients from two villages in an area with ongoing transmission. A total of 1198 nodules were excised and 4350 adult worms were isolated and examined for viability and productivity. In the OCP villages, the worm population is ageing and dying without replacement by new generations of parasites and various findings signal a breakdown of the worm population after about 12 years interruption of transmission. The sexual activity of the worms was significantly reduced. A Productivity Index was developed to measure the microfilariae production at the nodule level. The reduction in this index for the OCP villages correlates closely with the decline over the control period in the community microfilarial loads in the skin. The results show that it is not only the longevity of the parasite which will determine the duration of vector control, but that the reduced productivity of the ageing parasite population is of equal importance.

Africa, Western↗
PubMed1986

A double-blind comparison of the efficacy and safety of ivermectin and diethylcarbamazine in a placebo controlled study of Senegalese patients with onchocerciasis.

Ivermectin (MK-933) has been compared with diethylcarbamazine (DEC) and placebo in a double-blind study in 30 adult male Senegalese patients with Onchocerca volvulus infection. 10 patients were randomly assigned to each treatment group. Ivermectin was administered as a single oral dose of 12 mg and DEC as 50 mg daily for two days and 100 mg twice daily for the following six days, total 1.3 g in eight days. Skin O. volvulus microfilaria densities remained near pre-study values in the placebo patients, but decreased rapidly with both active drugs to mean values about 2% of pretreatment (Day 8) and then increased slowly, reaching in 12 months about 4% of pre-treatment (ivermectin) and 18% (DEC). This difference is statistically significant. Clinical adverse reactions were recorded in four ivermectin, ten DEC and three placebo patients. One ivermectin and six DEC patients received steroid treatment for relief of these reactions. Serious adverse ocular changes were not seen in any patients, possibly because of the steroid therapy in the DEC patients. Adult O. volvulus from onchocercal nodules one and six months after treatment showed no effect of either drug on viability. Intra-uterine developing forms of the microfilariae appeared normal in all three treatment groups at the one month examination but deformed and degenerated forms were evident at six months in the ivermectin group but not in the DEC and placebo patients. Ivermectin as a single oral dose appears to be a safer and more effective microfilaricidal drug in human onchocerciasis than DEC in the standard multi-dose regimen.

Adolescent↗
PubMed1986

The chemotherapy of onchocerciasis. XI. A double-blind comparative study of ivermectin, diethylcarbamazine and placebo in human onchocerciasis in northern Ghana.

Fifty-nine onchocerciasis patients with ocular involvement were randomly assigned to receive either 12 mg of ivermectin in a single dose or 1300 mg of diethylcarbamazine over eight days or matching placebo capsules. Detailed standardized follow-up examination was carried out for one year. Both ivermectin and diethylcarbamazine rapidly reduced skin microfilarial counts to a similar extent over six months, after which counts increased significantly more with diethylcarbamazine. Diethylcarbamazine rapidly eliminated microfilariae from the eye, while ivermectin did so over six months. Reactions to treatment were more severe with diethylcarbamazine, which also produced clinical ocular deficiency in two patients. Ivermectin produced intra-uterine sequestration and degeneration of microfilariae in adult worms, which may account for its ability to produce prolonged suppression of skin microfilariae. Ivermectin proved superior to diethylcarbamazine in safety, tolerance and efficacy, but further work is needed to assess fully its effects in patients with heavy intraocular microfilarial loads.

Adolescent↗
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↗
PubMed1985

Comparison of ivermectin and diethylcarbamazine in the treatment of onchocerciasis.

We compared ivermectin with diethylcarbamazine for the treatment of onchocerciasis in a double-blind, placebo-controlled trial. Thirty men with moderate to heavy infection and ocular involvement were randomly assigned to receive ivermectin in a single oral dose (200 micrograms per kilogram of body weight), diethylcarbamazine daily for eight days, or placebo. Diethylcarbamazine caused a significantly more severe systemic reaction than ivermectin (P less than 0.001), whereas the reaction to ivermectin did not differ from the reaction to placebo. Diethylcarbamazine markedly increased the number of punctate opacities in the eye (P less than 0.001), as well as the number of dead and living microfilariae in the cornea over the first week of therapy. Ivermectin had no such effect. Both ivermectin and diethylcarbamazine promptly reduced skin microfilaria counts, but only in the ivermectin group did counts remain significantly lower (P less than 0.005) than in the placebo group at the end of six months of observation. Analysis of adult worms isolated from nodules obtained two months after the start of therapy showed no effect of either drug on viability. Ivermectin appears to be a better tolerated, safer, and more effective microfilaricidal agent than diethylcarbamazine for the treatment of onchocerciasis.

Adult↗
PubMed1985

Fluorescein angiographic studies of mebendazole treatment for onchocerciasis.

Mebendazole was compared to placebo treatment in a prospective double-masked study of the treatment of onchocerciasis. Twenty Ghanaian men were randomly assigned to one of two groups and received either mebendazole 2 G per day for 14 days preceded by 300 mg of levamisole in 2 doses or placebo vitamin tablets for 14 days. They were then followed for 12 months. Systemic side effects during the first 2 weeks of treatment were uncommon in each group. Similarly, ocular changes associated with a microfilaricidal action were infrequent. No fluorescein angiographic changes attributable to treatment appeared during the one-year follow up although there was progression of ocular disease in some men in each group. Skin microfilarial (mf) counts fell significantly in both groups at 1 week but returned toward pretreatment levels at 3 months and fell again by 12 months. At no time was there a difference between the placebo-treated control group and the mebendazole/levamisole group in terms of mf counts, ocular changes, clinical changes, biochemical parameters, nor was there a difference in the status of adult worms or embryogenesis assessed in nodules excised at 5 months. These results suggest that, in this study at least, mebendazole/levamisole was no more effective than placebo in treating onchocerciasis. Why mebendazole, which has been previously reported to both suppress embryogenesis and lower skin mf counts, had no effect in this study is unknown.

Adult↗
PubMed1985

Suramin in the treatment of onchocerciasis: the efficacy of low doses on the parasite in an area with vector control.

In a village hyperendemic for onchocerciasis in Burkina Faso, where the vector had been controlled by the Onchocerciasis Control Programme since 1976, 65 patients were treated with doses of 37 to 71 mg/kg suramin in 1979. The viability and fertility of the adult parasites were studied in 217 nodules excised from 42 patients one month to four years after treatment using the collagenase technique. Most of the worms had survived the treatment. Male worms were more susceptible to suramin than female worms. The development of intrauterine stages initially continued, but was completely suppressed after several months. The female worms remained sterile in those patients who had received more than 60 mg/kg suramin. In other ones 11 and 13% of the female worms showed new embryonic stages in the uteri during two follow-up examinations in the second year. In a final examination in 1983 the reproduction had declined again. However, the reproductivity of the superannuated worms had considerably decreased in the untreated patients as well. All patients had shown a very high microfilardermia in 1979. After treatment the microfilarial densities dropped to levels near zero depending on the dose of suramin administered, but in none of the patients was the reduction complete during the first year of the treatment. Microfilariae gradually reappeared in the second year in several patients who had received less than 60 mg/kg suramin. In the final follow-up in 1983 most of the treated patients had become negative in skin counts, although they still harboured viable worms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗