Acta Leidensia最新文献

Ivermectin, a recently developed macrocyclic lactone with broad antiparasitic activity, has been shown by a series of clinical trials to be safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction as is seen with diethylcarbamazine treatment. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/Kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement, although ivermectin has no known long-lasting effects on the adult worms. With treatment there is no significant exacerbation of either anterior or posterior segment eye disease even in those with severe ocular disease. Treatment leads to a marked and prolonged improvement in ocular status. Because of its safety and efficacy, ivermectin can be used on a mass scale and promises to revolutionize the treatment of onchocerciasis.

The primary objective of the Wellcome Foundation/World Health Organisation Onchocerciasis Chemotherapy Project, which began in July 1982, was the discovery and development of a safe and effective macrofilaricide for the treatment of onchocerciasis in man. A multidisciplinary Team of biologists, biochemists and medicinal chemists was assembled. They investigated a variety of potential targets in filariae and carried out in-depth lead optimisation studies on a number of different chemical series. A valuable contribution was made to our understanding of filarial biology and biochemistry and the susceptibility of filariae to various metabolic inhibitors. However, the ultimate goal of identification of a compound worthy of evaluation in man was not achieved and the programme was closed at the end of June 1989. Factors that contributed to this situation and some overall conclusions are discussed.

Suitable drugs for the elimination of adult Onchocerca volvulus are still needed since ivermectin, the new microfilaricide, appears to be ineffective against this parasite stage. Herein we report on the identification of filaricides in three medicinal plants. The compounds carapolide A, mexicanolide-methylangolensate mixture from Carapa procera and oliverine from Polyalthia suaveolens or Pachypodanthium staudtii when tested at 10-100 micrograms.ml-1 were found to exhibit considerable microfilaricidal activity after 24 hours of incubation. Oliverine was found to be filaricidal when tested against adult female worms at 100 micrograms.ml-1. Preliminary toxicity studies in mice showed carapolide A and the mexicanolide-methylangolensate mixture to be relatively non-toxic, whereas, oliverine had a minimal lethal dose of 8 mg.Kg-1 of body weight. Based on the above results further pharmacologic studies are recommended to determine, the potential application of the active compounds on the treatment of onchocerciasis.

To investigate an apparent decline of the onchocerciasis vector Simulium woodi, in the Simulium neavei group, weekly 12-hour biting catches on man were carried out for 13 months near Amani and compared with those obtained 22 years earlier. The results showed a marked fall in biting S. neavei s.l. females and supported earlier findings on the aquatic stages. The mean biting-catch in 1985/6 was only 13% of that in 1963/4 and comprised 91% S. woodi and 9% the more common, but largely zoophilic, Simulium nyasalandicum (Amani form). The infection rate of S. woodi with Onchocerca volvulus larvae had also fallen markedly from 17% to 3% of parous flies; no S. nyasalandicum females were infected. Recent onchocerciasis surveys indicate that reduced transmission has resulted in lower infection rates in man. Exposure by deforestation of the breeding sites of S. woodi in small shaded streams seems to have caused the simuliid's population decline. Reduced populations of S. neavei group vector species have been reported in other deforested parts of eastern Africa. Our long-term quantitative data on declining numbers of biting females without control measures, help to corroborate such reports. Control may no longer be necessary in some areas allowing a greater concentration of limited resources.

The impact of 10-11 years of successful vector control on ocular onchocerciasis was evaluated in the population of 13 villages in the central part of the Onchocerciasis Control Programme area. The prevalence of ocular microfilariae was found to have reduced remarkably and loads over 20 microfilariae in the anterior chamber of the eye or the cornea which was rampant before the start of vector control, were rare. Whilst limited change in the age specific prevalence of lesions of the posterior segment of the eye was recorded, significant reduction in the prevalence of lesions of the anterior segment of the eye was found. The small decrease in the age specific prevalence of lesions of the posterior segment of the eye was partly explained by a reduced occurrence of the type of lesions of the anterior segment of the eye which previously obstructed the effective view of the fundus during examination. The prevalence of blindness was found to have reduced by 40% and onchocercal blindness was no longer found below the age of 20 years. It was concluded that 10-11 years of successful vector control has effectively reduced the incidence of onchocercal eye lesions, the deterioration of the existing eye lesions and the risk of developing an onchocercal eye lesion as well as going blind to virtually nil.

Following our report on onchocherciasis among the Ikyov and Nanev clans, we initiated a survey of the prevalence and distribution on onchocerciasis in some villages in Benue State, Nigeria. Out of the 1,558 inhabitants (619 males and 608 females) examined, 1,227 (78.8%) were found to carry microfilariae (mf) of Onchocerca volvulus (mean density: about 20/skin snip). The presence and number of mf from the right and left iliac crests were comparable. The findings indicate that clinical manifestations in onchocerciasis remain vital indices for rapid prospection.