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Onchocerca volvulus is a filarial parasite that is transmitted by the bite of black flies. The disease, onchocerciasis, is primarily manifest by fibrous nodules in the skin and the subcutaneous tissue under the skin. Microfilaria may migrate from nodules on the head into the cornea of the eye and produce blindness, known as river blindness. Ivermectin is a new anti-helminthic drug that has shown significant promise in the treatment of onchocerciasis by substantially reducing the microfilarial load (number of parasitic worm embryos). The Onchocerciasis Control Program (OCP) previously utilized vector (insect) control and larvicides as ways of controlling the disease. Only 1,209 volunteers were involved in the clinical trials of ivermectin prior to the drug's acceptance. Additional evidence of safety for large-scale use in endemic areas was essential, especially in areas with limited emergency care facilities for dealing with adverse reactions to the medication. A study was undertaken in the form of eight trials, in different areas of West Africa, between August 1987 and May 1988; the combined results on the incidence of side effects are reported. The disease prevalence varied by study site. Sixty percent of the population in the trial areas, totalling 50,929 persons, was treated with a single oral dose of ivermectin, based on body weight, and followed for 72 hours for the development of any adverse reaction. The remainder of the population was not treated for various exclusionary reasons. The reactions included pain, swelling, glandular reaction, skin reactions, ocular (visual) reactions, severe symptomatic postural hypotension (SSPH-the inability to stand for 2 minutes due to dizziness and a sudden drop in blood pressure), and breathing difficulties. Of the 9 percent showing adverse reactions, the SSPH reaction (49 cases) was the most severe, and occurred principally in persons with high skin microfilarial loads. The OCP recommended the use of ivermectin in large-scale programs with the presence of nurse monitors for at least 36 hours. The benefits of the drug overshadow the generally mild adverse reactions. (Consumer Summary produced by Reliance Medical Information, Inc.), Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: combined results from eight community trials Introduction Ivermectin, a new microfilaricide for the treatment of human onchocerciasis [1], has been shown [...]

Older driver safety is a complex phenomenon, extending beyond the person level to multiple system characteristics, such as epidemiologic, environment, and policy. Studying multiple factors in older driver safety requires the use of an integrated socioecological approach. In a cross-sectional design, we used a public health model and the 2003 General Estimates System database to determine main risk factors and their measures of association in the presence or absence of injury among older adults involved in motor vehicle accidents. Compared to the findings of the existing literature, participants demonstrated similar person-level crash-related injury characteristics. However, the socioecological model elucidated the importance of environment-level and vehicle-level factors as significant determinants of older driver safety. [ABSTRACT FROM AUTHOR]

The biology of Episimus utilis Zimmerman, a natural enemy of Brazilian peppertree, Schinus terebinthifolius Raddi, was investigated in a quarantine laboratory as part of a classical biological control program against this invasive weed in Florida. Adults lived on average 6.8 ± 0.8 d, and a generation was completed in 43.6 d at a temperature of 22.0°C and a photoperiod of 12:12 (L:D) h. Peak egg production occurred 2 d after females eclosed from the pupal stage. Females deposited a maximum of 172 eggs, with an average daily maximum of 13.6 eggs. The durations of the egg, larval, and pupal stages were 5.9, 23.7 (five instars), and 12.0 d, respectively. Stage-specific life tables were constructed to calculate basic population statistics. Under laboratory conditions where predation and food supply were not limiting factors, a population of E. utilis was capable of multiplying its population by 1.17 times per day, and a doubling of the population would occur every 4.4 d. To date, 10 consecutive generations of E. utilis have been produced on potted Brazil peppertree plants in the laboratory. The potential effectiveness of F. uulis as a biological control agent of Brazilian peppertree in Florida was examined using Goeden's revision of the Harris scoring system. [ABSTRACT FROM AUTHOR]

Two randomized, double-blind, placebo-controlled trials, in which levamisole (2.5 mg/kg) was given alone or co-administered with ivermectin (200 μg/kg) or albendazole (400 mg), were conducted. In Trial 1, safety and drug– drug interaction were explored in 42 healthy male volunteers. During Trial 2, the safety of the same treatment regimens and their efficacy against the adult worms and microfilariae of Onchocerca volvulus were investigated in 66 infected subjects of both sexes. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. The pharmacokinetic parameters for levamisole alone and the combinations were determined in Trial 1 and then compared with historical data for ivermectin and albendazole, given as single agents, to determine if drug–drug interaction had occurred. The level of efficacy against the adult worms was determined by the examination of histology sections of nodules excised 6 months posttreatment and from the changes seen in the levels of microfilaridermia within a year of treatment. Microfilaricidal efficacy was estimated from the reductions in the levels of microfilaridermia between day 0 (1 day pre-treatment) and day 30. Although the regimens were generally well tolerated, there were unexpected adverse effects in both healthy volunteers and infected subjects. Clinically significant drug–drug interactions resulted in an increase in the bio-availability of ivermectin but a reduction in that of albendazole when these drugs were co-administered with levamisole. Levamisole given alone or with albendazole had little effect on O. volvulus . The combination of levamisole with ivermectin was neither macrofilaricidal nor more effective against the microfilariae and the adult worms than ivermectin alone. The pathogenesis of the adverse events and the drug–drug interactions are discussed. [ABSTRACT FROM AUTHOR]

A randomized, double-blind, placebo-controlled trial was conducted, to determine whether the co-administration of ivermectin with albendazole is safe and more effective against Onchocerca volvulus than ivermectin alone, and whether a significant pharmacokinetic interaction occurs. Forty-two male onchocerciasis patients received ivermectin (200 mug/kg) alone, albendazole (400 mg) alone or the combination. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. Microfilaricidal efficacy was estimated from the reductions in skin counts between day 0 (pretreatment) and day 30. To determine efficacy against the adult worms, two independent observers examined histology slides prepared from nodules excised on day 180; changes in the skin counts of skin microfilariae between days 30 and 365 provided additional indicators of the level of adulticidal activity. Pharmacokinetic parameters for ivermectin and albendazole sulphoxide were defined over 72 h post-treatment. The co-administration of ivermectin with albendazole did not produce more severe adverse effects than ivermectin alone. Both nodule examiners found that the combination was not macrofilaricidal and that it was not clearly superior to ivermectin alone in the effects on reproductive activity; this was supported by the similar efficacy of the two regimens in the suppression of skin microfilariae. There was no significant pharmacokinetic interaction. Although the co-administration of ivermectin with albendazole appears safe, it offers no advantage over ivermectin alone in the control of onchocerciasis. The combination does not require an alteration in the dosage of either component. [ABSTRACT FROM AUTHOR]

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 < 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 slate, as shown by increased expression of Class M MHC antigens (P < 0.02, conjunctiva; P < 0.05, iris). These concomitant findings of lymphocyte infiltration and resident ceil 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]