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K Awadzi

Publications and source records attributed to K Awadzi.

66 records · Page 4Linked to original sources
PubMed1981

Diethylcarbamazine disposition in patients with onchocerciasis.

Diethylcarbamazine (DEC), 0.5 mg/kg, was taken orally by six patients being treated for onchocerciasis. Blood samples were taken at timed intervals for 48 hr and urine and feces collected for 4 days. Plasma and urinary concentrations of DEC and DEC N-oxide were measured by gas-liquid chromatography. DEC appeared to be rapidly absorbed, with a peak plasma concentration of 150 to 250 ng/ml reached in 2 to 3 hr. There was a secondary rise in plasma DEC concentration at 5 to 6 hr in all patients. In contrast to the way the drug is eliminated in rats, in man it was by both renal and extrarenal routes, with small amounts (+/- 10%) being excreted as an N-oxide metabolite. DEC kinetics were also investigated in five normal subjects and the result were much the same. Clinical implications are discussed.

Adult↗
PubMed1981

Studies of metrifonate in onchocerciasis.

Metrifonate has been studied in the treatment of infections with Onchocerca volvulus in West Africa. In doses of 10 mg/kg daily for six days, metrifonate was effective against the microfilariae but produced unpleasant reactions due both to the death of the microfilariae and to the muscarinic effects of the drug. In a comparison of 10 mg/kg metrifonate, for 3 doses at 10 day intervals, with diethylcarbamazine (D.E.C.) in a total dose of 6.6 g, metrifonate was significantly less effective than D.E.C. in killing microfilariae but produced significantly fewer adverse effects. In a final study comparing metrifonate 10 mg/kg/day given for 3 or for 6 days there was little difference in their therapeutic effect. However, metrifonate 10 mg/kg given for 6 days produced more severe adverse reactions due largely to the muscarinic and nicotinic effects of acetylcholine and these effects were not prevented by the administration of belladonna alkaloids. Metrifonate 10 mg/kg given for 3 doses at 10 day intervals is effective in the treatment of onchocerciasis but is unlikely to replace diethylcarbamazine. Metrifonate has no action on the adult worms.

Acetylcholine↗
PubMed1980

The chemotherapy of onchocerciasis II. Quantitation of the clinical reaction to microfilaricides.

A method of quantitation of the clinical reaction to microfilaricides has been devised at the Onchocerciasis Chemotherapeutic Research Centre at Tamale, in the savanna area of Northern Ghana. The method employs commonly occurring reactions--pruritus, rash, glandular reactions, musculoskeletal, febrile and cardiovascular--and a scoring system with a built-in weighting factor. Although the method is time-consuming and requires close, continuous observation of patients, it should permit more specific statements to be made about the severity of clinical reactions in individual patients or in groups of patients taking similar or different doses of the same drug or taking different drugs of the same drug or taking different drugs on a comparative basis. It is recommended that quantitative methods of the clinical reaction to microfilaricides form a basic part of the assessment of any drug used in the control of onchocerciasis.

Adolescent↗
PubMed1980

The chemotherapy of onchocerciasis iii. A comparative study of diethylcarbamazide (DEC) and metrifonate.

In a single-blind comparative study of diethylcarbamazine (DEC) and metrifonate against onchocerciasis, 20 patient received a total dose of 6.6 g DEC over a two-week period and 20 patients each received one dose of metrifonate 10 mg/kg body weight at ten-day intervals, three times. Both the efficacy and the severity of reaction to treatment were measured. DEC proved the more effective, destroying 98.9% of the microfilarial load while metrifonate destroyed only 75.4% (assessed one week after completion of treatment). The reaction to treatment was much more severe in patients treated with DEC. The persistence of significant postural cardiovascular effects for two weeks after the completion of DEC needs to be considered in mass therapy. The pattern of re-emergence of skin microfilariae indicated no difference between the two drugs over a six-month period. It is concluded that DEC is more effective than metrifonate and remains the 'reference' microfilaricide although its effects are more severe than those of metrifonate.

Adolescent↗
PubMed1980

The chemotherapy of onchocerciasis IV. Further trials with metrifonate.

Thirty-four healthy adult males, moderately to heavily infected with Onchocerca volvulus, were treated daily with metrifonate at 10 mg/kg body weight for either three or six days. The patients' reactions and the effects on the microfilariae were measured on a 'single-blind' basis. Muscarinic effects of acetylcholine were prominent despite the use of belladonna alkaloids, and nicotinic effects--leading to a proximal muscle weakness--occurred in one patient after the fifth dose. A syndrome of polyarthritis, fever and elevated erythrocyte sedimentation rate occurred in 11 patients, in two of whom microfilariae were demonstrated in the joint fluid. The six-day regime destroyed 83% of the microfilarial load and the three-day regime destroyed 72%, but the difference was not statistically significant (as assessed one week after the completion of treatment). It seems unlikely that metrifonate will replace DEC as the 'reference' microfilaricide and attempts to improve its efficacy by employing higher dosage must employ an intermittent dose regime.

Acetylcholine↗
PubMed1980

The chemotherapy of onchocerciasis V. A standard method for the determination of microfilarial density in skin snips.

The microfilarial density in 400 skin snips from 100 patients was determined using the standard technique of the Onchocerciasis Chemotherapeutic Research Centre (OCRC method), the method used by the Onchocerciasis Control Programme (OCP method), and also after collagenase digestion. The OCRC method was fairly consistent and detected 84% of the total microfilariae. The OCP method gave a density which was consistently 20% less than the OCRC method, indicating that the increase in weight in skin snips following incubation in saline was fairly predictable. It is concluded that collagenase digestion is not worthwhile as a routine technique in chemotherapeutic trials, for which the OCRC method is recommended.

Humans↗
PubMedDate not supplied

Comparison of the sensitivity of different geographical isolates of Onchocerca volvulus microfilariae to ivermectin: effects of exposure to drug on development in the blackfly Simulium ornatum.

Four geographical isolates (Ghana forest, Ghana savannah, Cameroon forest, Guatemala) of Onchocerca volvulus microfilariae (mf) and O. lienalis mf (UK) were examined for their sensitivity to ivermectin by incubation in vitro in drug followed by assessing their ability to develop in the blackfly Simulium ornatum after intrathoracic injection. Parasites were incubated for 30 min in ivermectin (10(-6) to 10(-9) M), which resulted in a concentration dependent decrease in the numbers of parasites surviving and developing in the insect; there were significant reductions in parasite recoveries from all isolates in the 10(-6) M to 5 x 10(-8) M ivermectin groups, but no significant effect was seen following incubation in concentrations of 10(-8) M and below. Experiments consistently demonstrated that the 4 isolates of O. volvulus were similarly sensitive to ivermectin (in the 10(-7) M ivermectin groups there was a reduction of 76.3% to 85.1% in numbers of infective larvae, and 60.9% to 85.5% in numbers of all larval stages, compared to controls); O. lienalis mf were significantly more sensitive (100% reduction in infective larvae, 98.7% reduction in all larval stages). This baseline information on drug sensitivity and techniques should prove useful for examining populations of O. volvulus for possible development of drug resistance in the future.

Animals↗
PubMedDate not supplied

Comparison of the sensitivity of different geographical races of Onchocerca volvulus microfilariae to ivermectin: studies in vitro.

This study was designed to provide baseline information on the sensitivity of 4 geographical isolates of Onchocerca volvulus microfilariae (mf) (Ghana forest, Ghana savanna, Cameroon forest and Guatemala) to ivermectin, and to develop an in vitro system with which to examine parasites for the possible development of drug resistance. Drug effects were best visualized in the presence of monkey kidney (LLCMK2) feeder cells in the culture system (MEM medium+20% serum), since mf maintained in the absence of cells declined in condition rapidly. Incubation of Ghana forest mf (+cells) in ivermectin (10(-5)-10(-10) M) caused a decrease in motility index (MI) scores in a concentration-dependent fashion; drug effects could be observed as early as 6 h, but cultures maintained for up to 8 d showed greater differences between control and drug groups with increasing time. All 4 O. volvulus isolates and O. lienalis (bovine) were compared for their response to ivermectin (10(-7) M): O. lienalis mf were significantly more sensitive (78%) reduction in MI scores on day 8) than the O. volvulus isolates (33.4-47.7% reduction). O. volvulus microfilariae ex utero generally displayed lower levels of motility and were slightly less inhibited by ivermectin than were skin mf. The in vitro system described can distinguish between the populations of mf studied on the basis of differing MI responses to ivermectin and, when combined with assays to test the infectivity of mf to blackflies following exposure to drug, will provide methods with which to examine parasites for the possible development of resistance.

Animals↗
PubMedDate not supplied

The effects of high-dose ivermectin regimens on Onchocerca volvulus in onchocerciasis patients.

Ivermectin, at the standard dose of 150 micrograms/kg bodyweight, does not kill the adult worms of Onchocerca volvulus and does not disrupt embryogenesis or spermatogenesis. Repeated standard doses, if maintained, arrest microfilarial production but result in only a mild-to-modest macrofilaricidal effect. We investigated whether high doses would effectively kill the adult worms, and whether cessation of microfilarial production could be reproduced by an equivalent, single, high dose. One hundred men participated in a double-blind placebo-controlled trial and received increasing doses of ivermectin from 150 micrograms/kg to 1600 micrograms/kg bodyweight. Nodules were excised at day 180 and examined by histopathology. Total doses of ivermectin up to 1600 micrograms/kg were not significantly more effective than 150 micrograms/kg. Moreover, they did not reproduce the marked inhibitory effects of the repeat standard-dose regimens on embryogenesis, nor the modest effect on adult worm viability, at comparable total doses. These effects may be functions of multiplicities of dosages rather than of the total dose. Our findings also suggest that repeated high-dose regimens are unlikely to be more effective than a similar number of 150 micrograms/kg doses. This deficiency of ivermectin requires that the search for macrofilaricides remains a top priority.

Animals↗