Acta Leidensia最新文献

To determine the natural filarial infections in east african nonhuman primates, we initiated a screening study at the Institute of Primate Research (IPR) in 1985. We report the findings of this study for the period between 1985 and 1988. Animals screened were wild-caught from different geographical regions of Kenya for various biomedical studies at IPR. We have recovered three dermal filariae from the animals. Two of these parasites are new and have never been described before. Based on demonstratable microfilariae (mf) there was a total infection rate of 67.10%. The adult stages of these filariae are dermal while the free-living mf live in the skin. Our attempts to transmit these infections to tick vectors have been unsuccessful inspite of tick attachment and engorgement. A susceptible vector remains to be determined.

The viability of adult Onchocerca volvulus and the effect of 12 known anthelmintic compounds on the parasites have been evaluated in an in vitro culture system. Three different parameters, a colorimetric assay, using NADH-dependent reduction of a tetrazolium salt to dark blue formazan by living adult worms, motility indices of male worms and lactate excretion of female worms were used to determine worm viability. The experiments showed that over a short term period of six days the viability of the worms did not decline significantly. The use of males isolated by dissection of whole nodules for the evaluation of drug effects in vitro is preferable to collagenase isolated worms. Mel W, milbemycin a and d, ivermectin, levamisole, CGP 6140 and, to a lesser extent, suramin immobilized male worms or significantly reduced the motility indices at a concentration of 10 microM. The tetrazolium reduction by male worms was not affected by levamisole, whereas the other active compounds demonstrated significant inhibitory effects. Diethylcarbamazine, mebendazole, flubendazole, metrifonate and CGP 20376 had no significant effect on male viability. Comparable activity was seen with the intact female worms isolated by collagenase digestion. Mel W, the milbemycins and ivermectin significantly inhibited tetrazolium reduction, whereas suramin and the other compounds had only slight or no inhibitory effects on female O. volvulus. Although one still has to aim at an improvement of the culture conditions, the in vitro test system using adult O. volvulus provides a basis for further research on potential antifilarial compounds.

After more than 13 years of aerial larviciding, the Onchocerciasis Control Programme in West-Africa (OCP) is considering the future of its control activities. In the original OCP-area the prevalence of infection has been brought down to very low levels and cessation of larviciding is being contemplated. The introduction of ivermectin has broadened the spectrum of available control measures. Countries outside the OCP are also planning chemotherapy-based onchocerciasis control. The prediction of the epidemiological impact of the different control options is difficult in view of the many factors which affect the dynamics of a chronic infectious disease like onchocerciasis. We developed the computer simulation model ONCHOSIM, which takes these many factors and their interrelationships into account. The program has a broad spectrum of uses of which some examples are given. It is explained how the model is used to simulate endemic situations and epidemiological trends during vector control. These trends can be explained in terms of longevity of the parasite and other model parameters. Secondly, predictions are made about the risk of recrudescence after stopping larviciding. Finally, the possible role of ivermectin to control recrudescence after interruption of vector control and to reduce disease symptoms in an endemic situation is explored. The latter application is also important outside the OCP-area. This shows the usefulness of ONCHOSIM as a means for transferring the OCP-knowledge about onchocerciasis control to other countries. From our experience with ONCHOSIM, it is concluded that model based prospective evaluation of control measures is useful in synthesizing existing knowledge, in steering applied research, in interpreting the results of experimental studies, and last but not least, in aiding the policy-making process.

This study compiles observations on the reproductive capacity of O. volvulus. Adult parasites enzymatically isolated from excised onchocercomata of untreated and chemotherapeutically treated patients, and from inhabitants living in areas with long vector control, were investigated to assess their fecundity. Changes of microfilaria development in utero and microfilaria release were assessed or estimated after treatment of patients with micro-filaricidal drugs that interfered with the development of intra-uterine stages. Intra-uterine production of microfilariae: After treatment of patients with ivermectin a daily development of 2500 to 4000 uterine microfilariae per female worm was observed. Actual output of microfilariae: Microfilariae left actively the female worms. The daily microfilaria release in vivo was 700 to 900 microfilariae, assessed after treatment of patients with mebendazole. In vitro most worms isolated from untreated patients shed between 500 to 1500 microfilariae per day.-The microfilarial load of 56 adult patients calculated from microfilarial skin counts was 12 million on the average. Taken for granted a mean life span of a microfilaria of 1.0 to 1.5 years, 22 to 47 female worms per patient would suffice to maintain this microfilarial load on a constant level. Excision of all palpable nodules showed a geometric mean of 15.9 female worms in these patients. It is suggested that factors intrinsic in the host and the adult worms partially operate together to regulate and maintain a stable microfilarial density.

The control of onchocerciasis through reduction of its vector Simulium damnosum depends on highly effective insecticide treatments directed against the larvae. As these treatments must be applied weekly over wide areas for many years, ideal conditions for the development of resistance have been created. Resistance to organophosphate compounds has occurred. To maintain effective vector control, an intense operational research effort has been necessary. Close and constant monitoring of susceptibility, combined with cytotaxonomic identification of the tested larvae, has revealed the pattern of spread of the resistance by migration and apparently by hybridization between populations. These studies have helped indicate when it might be possible to contain or eliminate a resistant population. Screening of all available appropriate compounds has led to the selection of replacement compounds in the microbial (Bacillus thuringiensis H14), pyrethroid (permethrin), and carbamate (carbosulfan) groups. Laboratory studies have revealed esterase and multi-function oxidase mechanisms for the existing organophosphate resistance. Cross-resistance tests have shown no cross-resistance to carbamate insecticides with these mechanisms, but negative correlations with most pyrethroids. These considerations, along with estimated risk of future resistance, effects on non-target organisms, and costs have led to a complex alternation pattern of insecticides, with Bacillus thuringiensis H14 being used in the dry season and a series of classical chemical compounds in the wet season. Through these measures, vector control remains a viable method of onchocerciasis control for the WHO Onchocerciasis Control Programme in West Africa.