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Comparison between two common methods for measuring Giardia lamblia susceptibility to antiparasitic drugs in vitro.

2017-05-17

We measured ivermectin in plasma, urine, and saliva of nine patients with onchocerciasis. The aim was to establish pharmacokinetic parameters and to assess the most facile medium for use in monitoring compliance. Binding of ivermectin to plasma proteins in vitro was also investigated. The mean (+/- SEM) plasma values for the nine subjects were as follows: weight, 66.3 +/- 2.8 kg; dose, 11.11 +/- 0.4 mg; half-life, 56.50 +/- 7.01 hours; clearance, 142.5 +/- 22.6 L/kg; volume of distribution, 9.91 +/- 2.67 L/kg; area under the plasma concentration-time curve, 1545.3 +/- 190.5 ng/ml.hr; time to reach maximum concentration, 4.7 +/- 0.5 hours; and maximum concentration, 38.2 +/- 5.8 ng/ml. Ivermectin was not detected in the urine of any of the nine subjects. Low levels were found in saliva. Blood specimens remain the only reliable biologic fluid for assessment of compliance after ivermectin oral administration. Ivermectin binds specifically to human serum albumin.

The salmon louse, Lepeophtheirus salmonis, is a crustacean ectoparasite of salmonid fish. At present, sea louse control on salmon farms relies heavily upon chemical treatments. Drug efflux transport, mediated by ABC transporters such as P-glycoprotein (Pgp), represents a major mechanism for drug resistance in parasites. We report here the molecular cloning of a new Pgp from the salmon louse, called SL-PGY1. A partial Pgp sequence was obtained by searching sea louse ESTs, and extended by rapid amplification of cDNA ends (RACE). The open reading frame of SL-PGY1 encodes a protein of 1438 amino acids that possesses typical structural traits of P-glycoproteins, and shows a high degree of sequence homology to invertebrate and vertebrate P-glycoproteins. In the absence of drug exposure, SL-PGY1 mRNA expression levels did not differ between a drug-susceptible strain of L. salmonis and a strain showing a ~7-fold decrease in sensitivity against emamectin benzoate, the active component of the in-feed sea louse treatment SLICE (Merck Animal Health). Aqueous exposure of the hyposensitive salmon louse strain to emamectin benzoate (24h, 410 μg/L) provoked a 2.9-fold upregulation of SL-PGY1. Adult male lice of both strains showed a greater abundance of SL-PGY1 mRNA than adult females.

Pour-on formulations of endectocides are extensively used to treat and control systemic parasitic diseases in cattle, worldwide. The purpose of the present study was to investigate the influence of the natural licking behaviour of cattle on the plasma and faecal disposition of topically administered ivermectin. Twelve Holstein cattle were given one single intravenous (i.v.) (200 microg/kg) and topical (500 microg/kg) administration of ivermectin at a 5-month interval. For the pour-on administration, the animals were allocated into two groups (n=6): one control group (lickers) and one group where licking was prevented (non-lickers). Ivermectin plasma (total) clearance (270+/-57.4 ml/kg/day) was very homogeneous among the 12 cattle. In contrast, major differences between lickers and non-lickers were observed following pour-on administration. Prevention of licking resulted in an extended terminal plasma half-life (363+/-16.2 vs. 154+/-7.4 h in lickers) and in a lower and less variable systemic availability of ivermectin (19+/-4.9 vs. 33+/-18.5% in lickers). More importantly, nearly 70% of the pour-on dose was recovered as parent drug in the faeces of lickers vs. only 6.6% in non-lickers. Altogether, these results are consistent with an oral rather than percutaneous absorption of topical ivermectin in control animals, the non-systemically available fraction of ingested ivermectin providing a major contribution (80%) to the drug faecal output. The consequences of licking on the disposition of pour-on ivermectin are discussed in terms of environment, given the known ecotoxicity of this drug, and of cross-contamination. Animals licking themselves and each other could result in unexpected residues in edible tissues of untreated animals and in possible subtherapeutic drug concentrations, a factor in drug resistance. According to the Precautionary Principle, these considerations elicit concern over the use of topical drug formulations in cattle.

Skin snip surveys were undertaken in 126 villages, and 17,801 people were examined. The prevalence of microfilaridermia was <1% in all three foci. A total of 157,500 blackflies were collected and analyzed for the presence of Onchocerca volvulus larvae using a specific DNA probe, and vector infectivity rates were all below 0.5 infective flies per 1,000 flies. Except for a subsection of one focus, all infection and transmission indicators were below postulated thresholds for elimination. Treatment was therefore stopped in test areas of 5 to 8 villages in each focus. Evaluations 16 to 22 months after the last treatment in the test areas involved examination of 2,283 people using the skin snip method and a DEC patch test, and analysis of 123,000 black flies. No infected persons and no infected blackflies were detected in the test areas, and vector infectivity rates in other catching points were <0.2 infective flies per 1,000.