Onchocerca volvulus

Avermectins and Ivermectin. The avermectias are pentacycHc lactones isolated from fermentation products of Streptomjces avermitilis and ivermectin is a semisynthetic chemical, 22,23-dihydroavermectia (46). Ivermectin is effective in very low doses for the control of red spider mites on deciduous fmits, in baits for the control of imported fire ants, and as a parasiticide for Onchocerca volvulus in humans and for catde gmbs. These insecticides appear to function as agonists for the neuroinhibitory transmitter y-aminobutyric acid (GABA) (see Antiparasitic agents, avermectins). 

Many parasitic worms cause systemic infections outside the gastrointestinal tract. These include Strong loides stercoralis (threadworm), Trichinella spiralis Dracunculus medinensis and the several species of nematodes that cause filariasis (Mansonellaperstans and Onchocerca volvulus). 

Diethylcarbama2iae has limited antimicrofilarial activity against Onchocerca volvulus. Adults of W. bancrofti the filarial worm causiag elephantiasis, coil in the lymph system. Here females can attain a length of 10 cm. Over the years, tissue reactions result in obstmction to lymph return. Lymph nodes, lymph vessels, and the spleen become enlarged. The condition of elephantiasis is a late and unusual complication of filariasis, where the lower extremities of the body become edematous, enlarge, and over a period of time harden with a rough nodular skin. 

Table 4. Ivermectin and Diethylcarbamazine Against Onchocerca volvulus Infections ...

Keddie, E.M., Higazi, T. and Unnasch, T.R. (1998) The mitochondrial genome of Onchocerca volvulus, sequence, structure and phylogenetic analysis. Molecuhr and BiochemicalParasitohgy 95, 111—127. 

Brattig, N.W., Rathjens, U., Ernst, M., Geisinger, F., Tischendorf, F.W. and Renz, A. (2000) Lipopolysaccharide-like molecules from Wolbachia endobacteria of the filaria Onchocerca volvulus are candidate mediators in the sequence of inflammatory and anti-inflammatory responses of human monocytes. Microbes and Infection2, 1—11. 

Franz, M. and Buttner, D.W. (1983) The fine structure of adult Onchocerca volvulus. IV. The hypodermal chords of the female worm. Tropenmedizin und Parasitologic 34, 122-128. 

Henkle-Duhrsen, K., Eckelt, V.H., Wildenburg, G., Blaxter, M. and Walter, R.D. (1998) Gene structure, activity and localization of a catalase from intracellular bacteria in Onchocerca volvulus. Molecular and Biochemical Parasitology 96, 69-81. 

Kozek, W.J. and Figueroa, M. (1977) Intracytoplasmic bacteria in Onchocerca volvulus. American Journal of Tropical Medicine and Hygiene 26, 663—678. 

Lu, W.H., Egerton, G.L., Bianco, A.E. and Williams, S.A. (1998) Thioredoxin peroxidase from Onchocerca volvulus a major hydrogen peroxide detoxifying enzyme in filarial parasites. Molecular and Biochemical Parasitology 91, 221-235. 

Lustigman, S. (1993) Molting, enzymes and new targets for chemotherapy of Onchocerca volvulus. Parasitology Today 9, 294-297. 

Lustigman, S., Brotman, B., Huima, T., Prince, A.M. and McKerrow, J.H. (1992) Molecular-cloning and characterization of onchocystatin, a cysteine proteinase-inhibitor of Onchocerca volvulus. Journal of Biological Chemistry 267, 17339-17346. 

Sakwe, A.M. and Titanji, V.P.K. (1997) Evidence for increased hydroxylation of pyrrolidone amino acid residues in the cuticle of mature Onchocerca volvulus. Biochimica et Biophysica Acta- Molecular Basis of Disease 1360, 196-202. 

Wilson, W.R., Tuan, R.S., Shepley, K.J., Freedman, D.O., Greene, B.M., Awadzi, K. and Unnasch, T.R. (1994) The Onchocerca volvulus homologue of the multifunctional polypeptide protein disulfide isomerase. Molecular and Biochemical Parasitology 68, 103-117. 

Brydon, L.J., Gooday, G.W., Chappell, L.H. and King, T.P. (1987) Chitin in egg shells of Onchocerca gibsoni and Onchocerca volvulus. Molecular and Biochemical Parasitology 25, 267—272. 

Harrison, R.A., Wu, Y., Egerfou, G. and Bianco, A.E. (1999) DNA immunisation with Onchocerca volvulus chitinase induces partial protection against infection with L3 in mice. Vaccine 18, 647-655. 

Strote, G. and Bonow, I. (1991) Morphological demonstration of essential functional changes after in vitro and in vivo transition of infective Onchocerca volvulus to the post-infective stage. Parasitology Research 77, 526-535. 

Wu, Y., Adam, R, Williams, S.A. and Bianco, A.E. (1996) Chitinase genes expressed by infective larvae of the filarial nematodes, Acanthocheihnema viteae and Onchocerca volvulus. Molecular and Biochemical Parasitology 75, 207—219. 

Lobos, E., Weiss, N., Karam, M., Taylor, H.R., Ottesen, E.A. and Nutman, T.B. (1991) An immunogenic Onchocerca volvulus antigen a specific and early marker of infection. Science 251, 1603-1605. 

Kennedy, M.W., Garside, L.H., Goodrick, L.E., McDermott, L., Brass, A., Price, N.C., Kelly, S.M., Cooper, A. and Bradley, J.E. (1997) The Ov20 protein of the parasitic nematode Onchocerca volvulus. A structurally novel class of small helix-rich retinol-binding protein. Journal of Biological Chemistry 272, 29442-29448. 

Nirmalan, N., Cordeiro, N.J.V., Klager, S.L., Bradley, J.E. and Allen, J.E. (1999) Comparative analysis of glycosylated and non-glycosylated filarial homologues of the 20-kilodalton retinol binding protein from Onchocerca volvulus (Ov20). Infection and Immunity 67, 6239-6334. 

Tree, T.I.M., Gillespie, A.J., Shepley, K.J., Blaxter, M.L., Tuan, R.S. and Bradley, J.E. (1995) Characterisation of an immunodominant glycoprotein antigen of Onchocerca volvulus with homologues in other filarial nematodes and Caenorhabditis elegans. Molecular and Biochemical Parasitology 69, 185-195. 

Wanni, N.O., Strote, G., Rubaale, T. and Brattig, N.W. (1997) Demonstration of immunoglobulin G antibodies against Onchocerca volvulus excretory-secretory antigens in different forms and stages of onchocerciasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 91, 226-230. 

Wuhrer, M., Rickhoff, S., Dennis, R.D., Lochnit, G., Soboslay, P.T., Baumeister, S. and Geyer, R. (2000) Phosphocholine-containing, zwitterionic glycosphingo-lipids of adult Onchocerca volvulus as highly conserved antigenic structures of parasitic nematodes. BiochemicalJournal 348, 417-423. 

Nematode parasites present a serious problem for most animals and for humans in developing countries. These parasites produce various symptoms including ill thrift, poor growth, diarrhoea and, in around 1 % of cases, loss of life. The economic forces are such that new drugs for the treatment of nematode parasites have been developed first for animal use and only later for human use. A recent example is the development of the antibiotic anthelmintic, ivermectin, which was introduced first for the treatment of cattle nematode parasites and has subsequently been used to control river blindness , an eye condition seen in west Africa caused by farvae of Onchocerca volvulus. 

Ajuh, P.M., Cowell, P., Davey, M.J. and Shevde, S. (1994) Cloning of a cDNA encoding a putative nicotinic acetylcholine receptor subunit of the human filarial parasite Onchocerca volvulus. Gene 144, 127-129. 

Diethylcarbamazine is a derivative of piperazine. The mechanism of its action is not completely understood. However, it is highly likely that it causes a reduction in muscular activity, and even paralysis in hehninthes. It quickly gets rid of the parasites Brugia malayi, Loa loa, and Wuchereria bancrofti, and it is also used for diseases caused by Onchocerca volvulus and Mansonella strptocerca. Synonyms of this drug are hetrazan, notezine, banoside, and others. 

Onchocerciasis (River blindness) Onchocerca volvulus Suramin,- Diethylcarbamazine, or Ivermectin-... 

When CNS involvement occurs, the poor penetration of suramin and pentamidine into the CSF requires alternative forms of chemotherapy, such as melarsoprol in combination with suramin. In treating Onchocerca volvulus infections, suramin kills adult worms and is an alternative to ivermectin. Suramin is used after initial treatment with diethylcarbamazine, which is used to kill the microfilariae. It produces favorable results in pemphigus and prolongs the time to disease progression in hormone-refractory prostate cancer. 

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