Related Experiment Videos
The entry of ivermectin and suramin into Onchocerca ochengi nodules
H F Cross1, B M Bronsvoort, G Wahl
1Liverpool School of Tropical Medicine, U.K. h.f.cross@liv.ac.uk
Abstract:
No currently available drug, which is safe for mass treatment, effectively kills adults of Onchocerca volvulus, the causal agent of onchocerciasis in humans, or of O. ochengi, a cattle parasite used as a model of O. volvulus. Since adults of both of these filarial nematodes are found in well developed nodules, the lack of efficacy of these drugs may be a result of their poor penetration into the nodules. To check if this was the problem, the distributions of the microfilaricide, ivermectin, and the partial macrofilaricide, suramin, in plasma, skin, nodule capsules and nodule contents were determined in cattle naturally infected with O. ochengi in Cameroon. The cattle were treated with either a single, subcutaneous injection of 500 micrograms ivermectin/kg, or with intravenous injections of [14C]-labelled suramin, each of 10 mg/kg, given one a day for 6 days. Concentrations of ivermectin and suramin in various tissues were then assayed by high-pressure liquid chromatography and scintillation counting, respectively. On day 7 post-treatment (pt), suramin concentrations were consistently highest in the nodule, contents and capsule wall (11.0 and 8.9 nCi/g, respectively) and significantly less in skin and plasma (1.2 and 1.4 nCi/g, respectively; P < 0.05). The distribution of ivermectin on day 7 pt was similar, with the highest concentrations in the capsule wall, nodule contents and plasma (58.4 ng/g, 43 ng/g and 48.6 ng/ml, respectively; P > 0.05) and the concentration in the skin (6.4 ng/g) significantly lower than those in the capsule or plasma (P < 0.05). High intra-nodular concentrations of both drugs were maintained for 5-7 days at least and those of ivermectin would be expected to kill nematodes other than filariae. It is apparent that failure of ivermectin and suramin to kill adult Onchocerca spp. is not because the drugs penetrate nodules inadequately.
Insights
Drug penetration into nodules is not the reason for the ineffectiveness of onchocerciasis treatments. Both ivermectin and suramin reach high concentrations within nodules, suggesting other factors limit their efficacy against adult Onchocerca parasites.
Area of Science:
- Veterinary Parasitology
- Pharmacokinetics
- Tropical Medicine
Background:
- Onchocerciasis treatment faces challenges due to the lack of drugs effectively killing adult Onchocerca parasites.
- Adult filarial nematodes reside within nodules, raising questions about drug penetration as a limiting factor.
Purpose of the Study:
- To investigate the distribution of ivermectin and suramin in cattle infected with Onchocerca ochengi, a model for human onchocerciasis.
- To determine if inadequate drug penetration into nodules explains the limited efficacy of current treatments.
Main Methods:
- Cattle infected with O. ochengi were treated with subcutaneous ivermectin or intravenous [14C]-labeled suramin.
- Drug concentrations were measured in plasma, skin, nodule capsules, and nodule contents using HPLC and scintillation counting.
- Tissue and plasma samples were collected on day 7 post-treatment.
Main Results:
- Both suramin and ivermectin achieved high concentrations within nodule contents and capsules.
- Skin concentrations of both drugs were significantly lower than those found in nodules.
- High intra-nodular drug levels were sustained for at least 5-7 days post-treatment.
Conclusions:
- The failure of ivermectin and suramin to eliminate adult Onchocerca spp. is not due to poor drug penetration into nodules.
- High concentrations of these drugs within nodules suggest alternative mechanisms limit their macrofilaricidal activity.