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Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus.

OBJECTIVE: To determine the distribution of ivermectin in plasma and tissues of onchocerciasis patients following a single oral dose of 150 micrograms kg-1. SETTING: Medical Department at Soba University Hospital, Khartoum. PATIENTS: Twenty five patients and fourteen healthy volunteers. METHODS: Serial blood samples were obtained from both groups. Tissue samples were removed from various patients as full thickness skin punch biopsies or during nodulectomy. Ivermectin concentration was determined by radioimmunoassay. RESULTS: The plasma pharmacokinetic variables for patients were; maximum plasma concentration 52.0 ng ml-1; time to achieve maximum concentration, 5.2 h.; elimination half life, 35.0 h; and the area under the plasma concentration curve versus time, 2852 ng.h.ml-1. In healthy volunteers, the plasma ivermectin distribution was similar to that in patients, and both groups showed a tendency for a second rise in plasma concentration of the drug suggestive of enterohepatic recirculation. Ivermectin was detected in tissues obtained from patients. Fat showed the highest and most persistent levels, whilst values for skin, nodular tissues, and worms were comparable. Subcutaneous fascia contained the lowest concentrations. CONCLUSIONS: Infection with O. volvulus does not affect the pharmacokinetics of ivermectin, and filarial infected tissues and parasites themselves do take up the drug. There may be prolonged retention of ivermectin because of depot formation in fat tissue.

Adipose Tissue↗

Immunopathogenesis of Onchocerca volvulus keratitis (river blindness): a novel role for endosymbiotic Wolbachia bacteria.

River blindness is thought to occur as a result of the host response to degenerating microfilariae in the eye. Utilizing a murine model of corneal inflammation (keratitis) to investigate the immune and inflammatory responses associated with river blindness, we recently demonstrated an important role for endotoxin-like products from endosymbiotic bacteria and for activation of Toll-like receptor 4 (TLR4). These observations have led to a new understanding of the pathogenesis of this disease

Animals↗

Identification of different radiolabelled antigens of the developmental stages of Onchocerca volvulus.

By using radioiodination methods which are thought to label preferentially the surface followed by SDS-PAGE and autoradiography, components of different developmental stages of O. volvulus have been identified. Between 2 and 10 polypeptide antigens were revealed on infective larvae (L3), females, males, eggs, nodular and skin microfilariae by using immunoblotting assays with human onchocerciasis sera. Antigen recognition did not vary with the density of skin microfilariae in the patients from whom the sera were obtained. Some of the antigens seemed to be stage specific; for example, antigens of 31 kDa which were detected only on skin microfilariae, or the 67.5 and 25 kDa components that occurred on the adult females, but were absent from adult males. Some of these antigens were also identified as glycoproteins. A 68 kDa glycoprotein was found in adult females, males and nodular microfilariae. Two glycoproteins of 74 and 45 kDa were found on egg shells, and a 18.5 kDa glycoprotein was recovered from L3. Type VI collagen was found with a specific antiserum on skin microfilariae, but not on eggs and females. Laminin was found on nodular mf. It is concluded that the changing antigenic profiles of the worm stages and the coating of these worms with connective tissue epitopes contribute to the evasion of host immunity.

Animals↗