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Biomedical subjects

H Schulz-Key

Publications and source records attributed to H Schulz-Key.

At least 37 records · Page 2Linked to original sources

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

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

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

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

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

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

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

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

Observations on adult Onchocerca volvulus maintained in vitro.

Adult Onchocerca volvulus were enzymatically isolated with collagenase from excised nodules and kept in TC medium 199 with Hank's salts supplemented with various sera. Male and female worms survived in the culture medium and 10% human serum on average for about 11 days (maximum 28 days) and 14.5 days (maximum 42 days). Up to 4,000 microfilariae were expelled by each female per day, but the production of new oocytes or development of embryos could not be observed in vitro.

Animals

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. The sex ratio of the live male and female worms was 1:1.5 in Liberia and 1:1.6 in Upper Volta. Less than 1% of all live macrofilariae were immature in both countries. 22% of the live male worms in Liberia were regarded as old. The percentage of old male and female worms in Upper Volta and that of the old female worms in Liberia were similar (5-7%). The portion of old worms was independent of the age of the patients in Liberia. Dead worms were found in 66% of the Liberians and in 85% of the Voltaics. The percentage of patients with dead worms increased with the age. About 0.5% of all male and 8% of all female worms were calcified. In Liberia the percentage of calcified worms increased with the age of the patients. In both countries the highest number of live and dead worms were found on the pelvic girdle. On the thorax many more macrofilariae were found in Upper Volta than in Liberia. This may contribute to the severe eye lesions in this savanna area. The presented findings provide some basic information for the planning and performance of trials with macrofilaricidal drugs in hyperendemic areas of West Africa. However, the striking differences between individual worm burdens have to be considered.

Adolescent

The transmission of Onchocerca tarsicola (Filarioidea: Onchocercidae) by Odagmia ornata and Prosimulium nigripes (Diptera: Simuliidae).

Onchocerca tarsicola is a subcutaneous filariid of the red deer living on the tendons of the radial-carpal and tibial-tarsal joints. Its microfilariae concentrate mainly in the external ears. The extrinsic cycle of this parasite was investigated. In a hyperendemic area wild-caught Odagmia ornata were dissected, as well as samples which had fed on a tame deer and been kept in the laboratory after the infecting blood-meal. About 3 to 5% of the flies were infected with larval stages of Onchocerca tarsicola. More than 40% of Odagmia ornata induced to feed on the ears of the deer became infected and about 30% of the flies which survived more than 18 days contained third-stage larvae. The larval development in the vector is described. Prosimulium nigripes appears to be a second natural vector of Onchocerca tarsicola. Observations concerning the potential vectors of O. flexuosa, O. tubingensis and Cutifilaria wenki living in red deer are discussed.

Animals

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

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

Analysis of enzymatically isolated adults of Onchocerca volvulus after treatment of patients with suramin or metrifonate.

The application of a new technique is described permitting a better recognition of activities of drugs on macrofilariae of Onchocerca volvulus. In two villages of a hyperendemic focus in Liberia onchocercomata were excised from untreated persons and from patients treated with conventional doses of suramin or metrifonate. The adult worms were enzymatically isolated with collagenase and microscopically examined for degenerative alterations including calcifications and for the presence of eggs and embryos in the female parasites. Six weeks after the last dose of suramin the degenerative alterations could not be distinguished qualitatively from those in untreated worms, but a statistically significant macrofilaricidal efficacy could be shown by quantitative analyses, although more than half of the parasites were still alive at this early date. Metrifonate did not show any macrofilaricidal effect.

Animals