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Biomedical subjects

K Awadzi

Publications and source records attributed to K Awadzi.

At least 55 records · Page 3Linked to original sources
PubMed1989

Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: combined results from eight community trials.

Eight community trials were carried out by the Onchocerciasis Control Programme in West Africa to determine the safety of the new microfilaricide ivermectin during large-scale treatment of onchocerciasis. The trial areas were located in eight different countries and varied greatly in endemicity level; a total of 50,929 persons were treated and monitored for 72 hours. Overall treatment coverage was 60% of the census population, the main reasons for non-treatment being the exclusion criteria. Of those treated, 9% reported with adverse reactions, 2.4% with moderate reactions, and 0.24% with severe reactions. Most reactions were reported during the first day of follow-up, the most frequent severe reaction being severe symptomatic postural hypotension (in 49 cases). Three cases of severe dyspnoea were life-threatening but their relationship with ivermectin treatment is uncertain. The incidence of adverse reactions was directly related to skin microfilarial load and was highest in the foci with the highest endemicity levels. Treatment resulted in 98% reductions in mean microfilarial loads at all endemicity levels. The benefit of treatment largely compensated for the discomfort due to adverse reactions, which were all transient and managed successfully. Ivermectin thus appears to be sufficiently safe for large-scale treatment but monitoring by resident nurses for at least 36 hours is recommended.

Africa, Western↗
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↗
PubMed1989

The chemotherapy of onchocerciasis. XIII. Studies with ivermectin in onchocerciasis patients in northern Ghana, a region with long lasting vector control.

One hundred and ninety eight patients with moderate to heavy infections with Onchocerca volvulus were randomly assigned to receive single doses of 100, 150 or 200 mcg/kg of ivermectin or matching placebo capsules. Detailed systemic, ocular and parasitological examinations were carried out at intervals over a period of one year. Nodules were excised twelve months after treatment to evaluate the effect of the treatment with ivermectin in adult O. volvulus. The three ivermectin-treated groups produced massive reductions in skin microfilariae (over 97%) with low levels being maintained over one year. The 150 and 200 mcg/kg doses were however superior to the 100 mcg/kg dose in achieving a greater reduction in skin microfilarial counts initially and in maintaining significant lower levels throughout the period of observation. There was no difference between the 150 and 200 mcg/kg doses at anytime. The three ivermectin doses were equally effective in the clearance of ocular microfilariae. The proportion of dead adult worms was very high in all treatment groups, which is effected by the successful ten years lasting vector control in northern Ghana. In spite of this superannuation of the worm population, an impact of the treatment with ivermectin on the reproductivity of the parasite could be shown. Systemic total clinical reaction was mild and was similar in the ivermectin treated groups. However, severe symptomatic postural hypotension (SSPH) was limited to patients treated with 150 or 200 mcg/kg of ivermectin. Ocular reactions were mild in all patients and no ocular deficiency occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Immunopathology of ocular onchocerciasis. I. Inflammatory cells infiltrating the anterior segment.

Ocular tissue (conjunctiva and iris) was obtained from 12 adult African men with active ocular onchocerciasis and from nine age-matched persons from the same endemic region but without onchocercal infection. These tissues were examined immunohistologically and two major findings were noted. First, mild-to-moderate chronic inflammatory cellular infiltration was present in the conjunctiva of the onchocerciasis patients. T lymphocytes (CD3+) were the major inflammatory cells, and the T suppressor/cytotoxic (CD8+) subset was significantly increased in the ocular onchocerciasis patients (P less than 0.03). Second, in the onchocerciasis patients, non-lymphoid cells of the conjunctiva and iris, such as vascular endothelium, pericytes and fibroblasts were in an activated state, as shown by increased expression of Class II MHC antigens (P less than 0.02, conjunctiva; P less than 0.05, iris). These concomitant findings of lymphocyte infiltration and resident cell activation indicate a dynamic state of localized host responsiveness presumably to the microfilarial parasites and their products in the anterior segments of the eyes of patients with ocular onchocerciasis.

Aged↗
PubMed1987

Immunopathology of ocular onchocerciasis. 2. Anti-retinal autoantibodies in serum and ocular fluids.

Ocular fluids and sera from 12 onchocerciasis patients and nine age-matched controls living in Tamale, Ghana, were examined for the presence of anti-retinal autoantibodies by the indirect immunoperoxidase technique. Antibodies directed against autoantigens of the inner retina (nerve fiber, ganglion cell, and Müller cell) were found in the sera of 10 of 12 patients, but in only three of nine controls (P less than 0.003). Autoimmune antibodies against the outer segment of the photoreceptor were noted in 7 of 12 patients, in contrast to only one of nine controls (P less than 0.02). Findings with the ocular fluids generally mirrored those with the sera. These autoantibodies could not be absorbed by conventional techniques using either retinal S-antigen (S-Ag) or the interphotoreceptor retinoid binding protein, an observation suggesting that other ocular antigens are involved. Such anti-retinal antibodies, especially those directed against the inner retina, may play a significant role in the pathogenesis of the retinal degeneration and optic atrophy that occur as a consequence of onchocerciasis.

Adult↗
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

The chemotherapy of onchocerciasis. XII. The prediction of microfilarial loads in patients with onchocerciasis after treatment with diethylcarbamazine in northern Ghana.

This paper presents some statistical problems of analysing changes in patterns of microfilarial loads in onchocerciasis patients after chemotherapeutic treatment. Analyses are made of a pooled set of data from ten separate studies of diethylcarbamazine (DEC) conducted at the Onchocerciasis Chemotherapeutic Research Centre, Tamale, between 1978 and 1983. Regression models of microfilarial load at different intervals post-treatment are fitted with initial microfilarial load, total dose of DEC, duration of treatment and age of the patient as the independent variables. Appropriate transformations of the variables are chosen by examination of plots of residuals for violations of the assumptions underlying the regression models. A dose response curve for DEC is produced.

Adult↗
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↗
PubMed1986

The effect of moderate urine alkalinisation on low dose diethylcarbamazine therapy in patients with onchocerciasis.

Twenty-one patients with moderate to heavy infections with O. volvulus were treated with 25 mg of diethylcarbamazine (DEC) citrate twice daily for 10 days. In 11 patients the urine was made alkaline with sodium bicarbonate, 2 g, administered 6 hourly for three doses daily beginning 1 day before DEC was started and continued throughout the DEC therapy. Ten patients served as controls. The mean pre-dose plasma DEC concentration during treatment and the mean plasma DEC half-life were significantly higher in bicarbonate treated patients as compared to controls. Total urinary excretion of DEC was significantly less in the bicarbonate treated group than in controls. Mean overall total reaction was higher in bicarbonate-treated patients but the difference was not significant. The bicarbonate-treated group achieved a significantly greater reduction in skin microfilarial counts than the control group as assessed 1 week after completion of therapy, but there was little difference at 1 month. Microfilarial killing was associated with microfilarial mobilisation, alteration in peripheral leucocytes and elevation in serum aminotransferases in both groups. There was no effect of DEC on the number of adult worms recovered in nodules removed at the end of the therapy. This study indicates that moderate urinary alkalinisation alters the kinetics of DEC and the therapeutic response. However the severity of clinical reaction coupled with the inadequate level of microfilarial killing achieved make it unlikely that manipulation of urinary pH will be of practical value in onchocerciasis chemotherapy.

Adolescent↗
PubMed1985

The Mazzotti reaction following treatment of onchocerciasis with diethylcarbamazine: clinical severity as a function of infection intensity.

To determine definitively whether or not the severity of the Mazzotti reaction was correlated with infection intensity, as determined by skin snip quantification, 21 infected Ghanian patients were evaluated during 7 days of treatment with 200 mg/day of diethylcarbamazine. Serial blood, urine and skin biopsy samples were collected during the progression of the Mazzotti reaction. Hypotension, fever, adenitis and pruritus were all correlated with infection intensity in these patients while arthralgia and tachycardia were not. Peripheral blood eosinopenia and neutrophilia also correlated with intensity of infection and appeared to reflect the accumulation of degranulating eosinophils around "mobilized" microfilariae that migrated from the dermis to the epidermis after diethylcarbamazine (DEC). Other mobilized microfilariae apparently were cleared by the liver and resulted in abnormal liver enzyme levels in the serum which, again, were directly correlated with the patients' microfilarial density. Though the severity of the Mazzotti reaction clearly correlated with intensity of infection, the different times of onset of symptoms, and cellular and serum chemistry changes indicate that there are probably multiple infection intensity-dependent mechanisms responsible for mediating this complex reaction.

Adolescent↗
PubMed1985

The chemotherapy of onchocerciasis X. An assessment of four single dose treatment regimes of MK-933 (ivermectin) in human onchocerciasis.

Nineteen patients from an area of vector control in the savanna region of Northern Ghana, all with moderate to heavy infections with Onchocerca volvulus and some with ocular involvement, were treated with 50, 100, 150 or 200 micrograms kg-1 of ivermectin. Detailed monitoring of clinical and ocular reactions and of alterations in skin microfilarial counts and laboratory indices were carried out during the first 28 days. Microfilarial counts in skin snips and detailed ocular examinations were then repeated at intervals over a period of nine months. Ivermectin slowly eliminated microfilariae from the skin and eye without serious adverse clinical or ocular reactions in all treated groups. There was little difference in efficacy between doses of 100, 150 and 200 micrograms kg-1, and these were more effective than the 50 micrograms kg-1 dose. Very low levels of skin microfilariae were maintained for nine months. Microfilariae were not eliminated from the eye for at least three months. The drug was neither macrofilaricidal nor embryotoxic. However, it produced a dose-dependent stimulation of embryogenesis manifest at one month and succeeded by a suppression of embryogenesis at three months after therapy. In areas where transmission of onchocerciasis has been interrupted, ivermectin may need not be given more often than once a year. The efficacy of the drug on single dosage and the mild adverse reactions produced, if confirmed in subsequent controlled studies, would greatly simplify the treatment of onchocerciasis and would reintroduce new concepts of the role of chemotherapy in the control of onchocerciasis.

Adolescent↗
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↗