Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-25T08:23:18.131Z Has data issue: false hasContentIssue false
  • English
  • Français

Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Published online by Cambridge University Press:  06 April 2009

R. M. Maizels  and
D. A. Denham
R. M. Maizels
Affiliation:
Wellcome Research Centre for Parasitic Infections, Department of Biology, Imperial College of Science, Technology and Medicine, Prince Consort Road, London SW7 2BB, UK
D. A. Denham
Affiliation:
London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT
Get access Rights & Permissions [Opens in a new window]

Summary

Anti-parasitic drugs may achieve their therapeutic effect either by direct activity against the pathogenic organism, or by altering host factors which lead to parasite killing. In this review, we discuss the evidence for an indirect mode of action for one major anti-filarial drug, diethylcarbamazine (DEC). The interpretation most consistent with existing data is that DEC alters arachidonic acid metabolism in microfilariae and in host endothelial cells. These changes may result in vasoconstriction and amplified endothelial adhesion leading to immobilization of microfilarial parasites, enhanced adherence and cytotoxic activity by host platelets and granulocytes. These events would represent activation of the innate, non-specific immune system, independent of the adaptive, antigen-specific, immune response. This model explains the paradox between rapid clearance in vivo and the lack of an in vitro effect, as well as the efficacy of DEC in non-immune animals.

Keywords

adhesionanthelminticsarachidonic acideosinophilsfilariasisfilaricideshelminthotoxicityleukotrienesmicrofilaricideneutrophilsplateletsprostanoids
Type
Research Article
Information
Parasitology , Volume 105 , Issue S1: Chemotherapy and the immune system , January 1992 , pp. S49 - S60
Copyright
Copyright © Cambridge University Press 1992

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Ackerman, S. J., Kephart, G. M., Francis, H., Awadzi, K., Gleich, G. J. & Ottesen, E. A. (1990). Eosinophil degranulation. An immunologic determinant in the pathogenesis of the Mazzotti reaction in human onchocerciasis. Journal of Immunology 14, 3961–9.CrossRefGoogle Scholar
Awadzi, K., Orme, M. L. E., Breckenridge, A. M. & Gilles, H. M. (1982). The chemotherapy of onchocerciasis. VII. The effect of prednisone on the Mazzotti reaction. Annals of Tropical Medicine and Hygiene 76, 331–8.Google ScholarPubMed
Bach, M. K. & Brashler, J. R. (1986). Inhibition of the leukotriene synthetase of rat basophil leukemia cells by diethylcarbamazine, and synergism between diethylcarbamazine and piriprost, a 5-lipoxygenase inhibitor. Biochemical Pharmacology 35, 425–33.CrossRefGoogle Scholar
Balaa, M. A. & Subramony, C. (1990). Diethylcarbamazine decreases ethanol-injury to the gastric mucosa of the rat. Eicosanoids 3, 201–3.Google Scholar
Batra, S., Chatterjee, R. K. & Srivastava, V. M. (1990). Antioxidant enzymes in Acanthocheilonema viteae and effect of antifilarial agents. Biochemical Pharmacology 40, 2363–9.CrossRefGoogle ScholarPubMed
Bianco, A. E. (1990). Onchocerciasis — river blindness. In Parasitic Helminths and Zoonoses in Africa (ed. Craig, P. S. & Macpherson, C. N. L.). London: Unwin Hyman.Google Scholar
Bianco, A. E., Nwachukwu, M. A., Townson, S., Doenhoff, M. J. & Muller, R. L. (1986). Evaluation of drugs against Onchocerca microfilariae in an inbred mouse model. Tropical Medicine and Parasitology 37, 39–45.Google Scholar
Callahan, H. L., Crouch, R. K. & James, E. R. (1988). Helminth anti-oxidant enzymes: a protective mechanism against host oxidants? Parasitology Today 4, 218–25.CrossRefGoogle ScholarPubMed
Callahan, H. L., Crouch, R. K. & James, E. R. (1990). Hydrogen peroxide is the most toxic oxygen species for Onchocerca cervicalis microfilariae. Parasitology 100, 407–15.CrossRefGoogle ScholarPubMed
Cesbron, J.-Y., Capron, A., Vargaftig, B. B., Lagarde, M., Pincemail, J., Braquet, P., Taelman, H. & Joseph, M. (1987). Platelets mediate the action of diethylcarbamazine on microfilariae. Nature 325, 533–6.CrossRefGoogle ScholarPubMed
Cesbron, J.-Y., Hayasaki, M., Joseph, M., Lustsch, C., Grzych, J.-M. & Capron, A. (1988). Onchocerca volvulus. Monoclonal anti-idiotype antibody as antigen signal for the microfilaricidal cytotoxicity of diethylcarbamazine-treated patients. Journal of Immunology 141, 279–85.CrossRefGoogle Scholar
Chandrashekar, R., Rao, U. R. & Subrahmanyam, D. (1984). Effect of diethylcarbamazine on serum-dependent cell-mediated immune reactions to microfilariae in vitro. Tropenmedizin und Parasitologie 35, 177–82.Google ScholarPubMed
Cookson, E., Blaxter, M. L. & Selkirk, M. E. (1992). Identification of the major soluble cuticular protein of Brugia filarial nematode parasites as a secretory homolog of glutathione peroxidase. Proceedings of the National Academy of Sciences, USA 89, 5837–5841.CrossRefGoogle ScholarPubMed
Coulaud, J. P., Larviäre, M., Gervais, M. C., Gaxotte, P., Aziz, A., Deloul, A. M. & Cenac, J. (1983). Traitement de l'onchocercose humaine par l'ivermectin. Bulletin de la Société de Pathologie Exotique 76, 681–8.Google Scholar
Davies, P., Bailey, P. J., Goldenberg, M. M. & Ford-Hutchinson, A. W. (1984). The role of arachidonic acid oxygenation products in pain and inflammation. Annual Review of Immunology 2, 335–57.CrossRefGoogle ScholarPubMed
Denham, D. A., Suswillo, R. R., Rogers, R. & McGreevy, P. B. (1978). Studies with Brugia pahangi 17. The anthelmintic effects of diethylcarbamazine. Journal of Parasitology 64, 463–8.CrossRefGoogle ScholarPubMed
Duke, B. O. L. (1974). The effect of levamisole on Onchocerca volvulus. Transactions of the Royal Society of Tropical Medicine and Hygiene 68, 71–4.CrossRefGoogle ScholarPubMed
Eltahir, K. E. H., Al-Kharji, A. M. H. & Ageel, A. M. (1991). Influence of diethylcarbamazine and mefloquine on PGI2 synthesis by the rat thoracic aorta and myometrial tissues. General Pharmacology 22, 837–46.CrossRefGoogle Scholar
Francis, H., Awadzi, K. & Ottesen, E. A. (1985). The Mazzotti reaction following treatment of onchocerciasis with diethylcarbamazine: clinical severity as a function of infection intensity. American Journal of Tropical Medicine and Hygiene 34, 529–36.CrossRefGoogle ScholarPubMed
Gallin, M., Edmonds, K., Ellner, J. J., Ertmann, K. D., White, A. T., Newland, H. S., Taylor, H. R. & Greene, B. M. (1988). Cell-mediated immune responses in human infection with Onchocerca volvulus. Journal of Immunology 140, 1999–2007.CrossRefGoogle ScholarPubMed
Gibson, D. W., Connor, D. H., Brown, H. L., Fuglsang, H., Anderson, J., Duke, B. O. L. & Buck, A. A. (1976). Onchocercal dermatitis: ultrastructural studies of microfilariae and host tissues, before and after treatment with diethylcarbamazine (Hetrazan). American Journal of Tropical Medicine and Hygiene 25, 74–87.CrossRefGoogle ScholarPubMed
Goetzl, E. J., Weller, P. F. & Sun, F. F. (1980). The regulation of human eosinophil function by endogenous mono-hydroxy-eicosatetrenoic acids (HETEs). Journal of Immunology 124, 926–93.CrossRefGoogle ScholarPubMed
Goldman, G., Welbourn, R., Kobzik, L., Valeri, C. R., Shepro, D. & Hechtman, H. B. (1992). Synergism between leukotriene B4 and thromboxane A2 in mediating acid-aspiration injury. Surgery 111, 55–61.Google ScholarPubMed
Goodwin, L. G. (1984). Chemotherapy. Transactions of the Royal Society of Tropical Medicine and Hygiene 78 (suppl.yes), 1–8.CrossRefGoogle ScholarPubMed
Greene, B. M., Taylor, H. R., Cupp, E. W., Murphy, R. P., White, A. T., Aziz, M. A., Schulz-Key, H., D'Anna, S. A., Newland, H. S., Goldschmidt, L. P., Auer, C., Hanson, A. P., Freeman, V., Reber, E. W. & Williams, P. N. (1985). Comparison of ivermectin and diethylcarbamazine in the treatment of onchocerciasis. New England Journal of Medicine 313, 133–8.CrossRefGoogle ScholarPubMed
Hamilton, R. G., Wagner, E., April, M., Winkelstein, J. A., Sobotka, A. K., Bleeker, E. & Adkinson, N. F. J. (1986). Dirofilaria immitis: Diethylcarbamazine-induced anaphylactoid reactions in infected dogs. Experimental Parasitology 61, 405–20.CrossRefGoogle ScholarPubMed
Hawking, F. (1979). Diethylcarbamazine and new compounds for the treatment of filariasis. Advances in Pharmacology and Chemotherapy 16, 129–94.CrossRefGoogle ScholarPubMed
Hawking, F. & Adams, W. E. (1964). Microfilaricidal action of diethylcarbamazine in vivo: first phase. Annales de la Société Belge de Médecine Tropicale 44, 279–84.Google ScholarPubMed
Hawking, F. & Laurie, W. (1949). Action of hetrazan on filariasis and onchocerciasis. Lancet 2, 146–7.CrossRefGoogle ScholarPubMed
Hawking, F., Sewell, P. & Thurston, J. P. (1948). Mode of action of hetrazan in filariasis. Lancet 2, 730–1.CrossRefGoogle ScholarPubMed
Hawking, F., Sewell, P. & Thurston, J. P. (1950). The mode of action of hetrazan on filarial worms. British Journal of Pharmacology 5, 217–38.Google ScholarPubMed
Hewitt, R. I., White, E., Wallace, W. S., Stewart, H. W., Kushner, S. & Subbarow, Y. (1947). Experimental chemotherapy of filariasis. II. Effect of piperazine derivatives against naturally acquired filarial infections in cotton rats and dogs. Journal of Laboratory and Clinical Medicine 32, 1304–13.Google Scholar
Hong, S.-C. L. & Levine, L. (1976). Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids. Proceedings of the National Academy of Sciences, USA 73, 1730–4.CrossRefGoogle ScholarPubMed
Howells, R. E., Mendis, A. M. & Bray, P. G. (1983). The mode of action of suramin on the filarial worm Brugia pahangi. Parasitology 87, 29–48.CrossRefGoogle ScholarPubMed
Ibe, B. O., Falck, J. R., Johnson, A. R. & Campbell, W. B. (1989). Regulation of synthesis of prostacyclin and HETEs in human endothelial cells. American Journal of Physiology 256, C1168–75.CrossRefGoogle ScholarPubMed
Jenkins, D. C. (1990). Ivermectin in the treatment of filarial and other nematode diseases of man. Tropical Diseases Bulletin 87, R1–9.Google Scholar
Johnson, P., Mackenzie, C. D., Denham, D. A. & Suswillo, R. R. (1988). The effect of diethylcarbamazine on the in vitro serum-mediated adherence of feline granulocytes to microfilariae of Brugia pahangi. Tropical Medicine and Parasitology 39, 291–4.Google ScholarPubMed
Kanesa-Thasan, N., Douglas, J. G. & Kazura, J. W. (1991). Diethylcarbamazine inhibits endothelial and microfilarial prostanoid metabolism in vitro. Molecular and Biochemical Parasitology 49, 11–20.CrossRefGoogle ScholarPubMed
Kephart, G. M., Gleich, G. J., Connor, D. H., Gibson, D. W. & Ackerman, S. J. (1984). Deposition of eosinophil granule major basic protein onto microfilariae of Onchocerca volvulus in the skin of patients treated with diethylcarbamazine. Laboratory Investigation 50, 51–61.Google ScholarPubMed
King, C. H., Greene, B. M. & Spagnuolo, P. J. (1983). Diethylcarbamazine citrate, an antifilarial drug, stimulates human granulocyte adherence. Antimicrobial Agents and Chemotherapy 24, 453–6.CrossRefGoogle ScholarPubMed
King, C. L. & Nutman, T. B. (1991). Regulation of the immune response in lymphatic filariasis and onchocerciasis. Immunology Today 12, A54–8.CrossRefGoogle ScholarPubMed
Kobayashi, J., Matsuda, H., Fujita, K., Sakai, T. & Shinoda, K. (1969). [Some observations on the mode of action of diethylcarbamazine on the cotton rat filaria.] In Japanese. Japanese Journal of Parasitology 18, 563–74.Google Scholar
Lammie, P. J., Eberhard, M. L., Leiva, L. E., Lowrie, R. C. J. & Katz, S. P. (1988). The effect of diethylcarbamazine treatment of Bancroftian filariasis on the immunological reactivity of microfilaraemic individuals. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 726–9.CrossRefGoogle ScholarPubMed
Lawrence, R. & Denham, D. A. (1992). Brugia pahangi infections in immune-compromised rats demonstrate that separate mechanisms control adult worm and microfilarial numbers. Parasite Immunology 14, 371–84.CrossRefGoogle ScholarPubMed
Lewis, R. A. & Austen, K. F. (1984). The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology. Journal of Clinical Investigation 73, 889–97.CrossRefGoogle ScholarPubMed
Limaye, A. P., Abrams, J. S., Silver, J. E., Ottesen, E. A. & Nutman, T. B. (1990). Regulation of parasite-induced eosinophilia: selectively increases interleukin 5 production in helminth-infected patients. Journal of Experimental Medicine 172, 399–402.CrossRefGoogle ScholarPubMed
Liu, L. X., Serhan, C. N. & Weller, P. F. (1990). Intravascular filarial parasites elaborate cyclooxygenase-derived eicosanoids. Journal of Experimental Medicine 172, 993–6.CrossRefGoogle ScholarPubMed
Liu, L. X. & Weller, P. F. (1990). Arachidonic acid metabolism in filarial parasites. Experimental Parasitology 71, 496–501.CrossRefGoogle ScholarPubMed
Longworth, D. L., Foster, D. W., Dvorak, A. M. & Weller, P. F. (1985). Incorporation of arachidonic acid by microfilariae of Brugia malayi. Journal of Infectious Diseases 152, 1317–23.CrossRefGoogle ScholarPubMed
Mackenzie, C. D. (1980). Eosinophil leukocytes in filarial infections. Transactions of the Royal Society of Tropical Medicine and Hygiene 74 (suppl.yes), 51–8.CrossRefGoogle Scholar
Mackenzie, C. D. & Kron, M. A. (1985). Diethylcarbamazine: a review of its action in onchocerciasis, lymphatic filariasis and inflammation. Tropical Diseases Bulletin 82, R1–37.Google Scholar
Maizels, R. M. & Lawrence, R. A. (1991). Immunological tolerance: the key feature in human filariasis? Parasitology Today 7, 271–6.CrossRefGoogle ScholarPubMed
Mathews, W. R. & Murphy, R. C. (1982). Inhibition of leukotriene biosynthesis in mastocytoma cells by diethylcarbamazine. Biochemical Pharmacology 31, 2129–32.CrossRefGoogle ScholarPubMed
Medina-De La Garza, C. E., Brattig, N. W., Tischendorf, F. W. & Jarrett, J. M. B. (1990). Serum-dependent interaction of granulocytes with Onchocerca volvulus microfilariae in generalized and chronic hyper-reactive onchocerciasis and its modulation by diethylcarbamazine. Transactions of the Royal Society of Tropical Medicine and Hygiene 84, 701–6.CrossRefGoogle ScholarPubMed
Morris, H. R., Taylor, G. W., Piper, P. J. & Tippins, J. R. (1980). Structure of slow-reacting substance of anaphylaxis from guinea-pig lung. Nature 285, 104–6.CrossRefGoogle ScholarPubMed
Nathan, C., Srimal, S., Farber, C., Sanchez, E., Kabbash, L., Asch, A., Gailit, J. & Wright, S. D. (1989). Cytokine induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins. Journal of Cell Biology 109, 1341–9.CrossRefGoogle ScholarPubMed
Needleman, P., Turk, J., Jakschik, B. A., Morrison, A. R. & Lefkowith, J. B. (1986). Arachidonic acid metabolism. Annual Review of Biochemistry 55, 69–102.CrossRefGoogle ScholarPubMed
Nelson, F. K., Greiner, D. L., Schultz, L. D. & Rajan, T.V. (1991). The immunodeficient scid mouse as a model for human lymphatic filariasis. Journal of Experimental Medicine 173, 659–63.CrossRefGoogle Scholar
Nogami, S., Tanaka, H. & Matsuda, H. (1982). [Antimicrofilarial effect of diethylcarbamazine on microfilariae of Litomosoides carinii in the nude mouse.] In Japanese. Japanese Journal of Parasitology 31, 415–22.Google Scholar
O'Banion, M. K., Winn, V. D. & Young, D. A. (1992). cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. Proceedings of the National Academy of Sciences, USA 89, 4888–92.CrossRefGoogle ScholarPubMed
O'Holohan, D. R. & Zaman, V. (1974). Treatment of Brugia malayi infection with levamisole. Journal of Tropical Medicine and Hygiene 77, 113–15.Google ScholarPubMed
Ogletree, M. L. (1987). Overview of physiological and pathophysiological effects of thromboxane A2. Federation Proceedings 46, 133–8.Google ScholarPubMed
Orange, R. P., Valentine, M. D. & Austen, K. F. (1968). Inhibition of the release of slow-reacting substance of anaphylaxis in the rat with diethylcarbamazine. Proceedings of the Society for Experimental Biology and Medicine 127, 127–32.CrossRefGoogle ScholarPubMed
Ottesen, E. A. (1985). Efficacy of diethylcarbamazine in eradicating infection with lymphatic-dwelling filariae in humans. Reviews of Infectious Diseases 7, 341–56.CrossRefGoogle ScholarPubMed
Ottesen, E. A. (1987). Description, mechanisms and control of reactions to treatment in the human filariases. Filariasis (Ciba Foundation Symposium 127), pp. 265–83. Chichester: John Wiley.Google Scholar
Pancré, V., Cesbron, J. Y., Auriault, C., Joseph, M., Chandenier, J. & Capron, A. (1988). IgE-dependent killing of Brugia malayi microfilariae by human platelets and its modulation by T cell products. International Archives of Allergy and Applied Immunology 85, 483–6.CrossRefGoogle ScholarPubMed
Partono, F., Cross, J. H., Clarke, Borahina M. D. & Oemijati, S. (1972). Observations on the diurnal diagnosis of filariasis after a single dose of hetrazan. South East Asian Journal of Tropical Medicine and Public Health 3, 366–70.Google ScholarPubMed
Partono, F., Oemijati, Purnomo S. & Soewarta, A. (1981). The long term effects of repeated diethylcarbamazine administration with special reference to microfilaraemia and elephantiasis. Acta Tropica 38, 217–25.Google Scholar
Partono, F., Soewarta, Purnomo A. & Oemijati, S. (1984). Low dosage diethylcarbamazine administered by villagers for the control of timorian filariasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 370–2.CrossRefGoogle ScholarPubMed
Partono, F., Maizels, R. M. & Purnomo, . (1989). Towards a filariasis free community: evaluation of filariasis control over an 11 year period in Flores, Indonesia. Transactions of the Royal Society of Tropical Medicine and Hygiene 83, 821–6.CrossRefGoogle Scholar
Piessens, W. F. & Beldekas, M. (1979). Diethylcarbamazine enhances antibody-mediated cellular adherence to Brugia malayi microfilariae. Nature 282, 845–7.CrossRefGoogle ScholarPubMed
Piessens, W. F., Ratowayanto, S., Piessens, P. W., Tuti, S., MuGreevy, P. B., Darwis, F., Palmieri, J. R., Koiman, I. & Dennis, D. T. (1981). Effect of treatment with diethylcarbamazine on immune responses to filarial antigens in patients infected with Brugia malayi. Acta Tropica 38, 227–34.Google ScholarPubMed
Piper, P. J. & Stewart, A. G. (1986). Coronary vasoconstriction in the rat, isolated perfused heart induced by platelet-activating factor is mediated by leukotriene. British Journal of Pharmacology 88, 595–605.CrossRefGoogle ScholarPubMed
Piper, P. J. & Temple, D. M. (1981). The effect of lipoxygenase inhibitors and diethylcarbamazine on the immunological release of slow reacting substance of anaphylaxis (SRS-A) from guinea-pig chopped lung. Journal of Pharmacy and Pharmacology 33, 384–6.CrossRefGoogle ScholarPubMed
Rácz, P., Tenner-Rácz, K., Büttner, D. W. & Albiez, E. J. (1982). Ultrastructural evidence for eosinophil-parasite adherence (EPA) reaction in human onchocercal lymphadenitis in the early period following diethylcarbamazine treatment. Tropenmedizin und Parasitologie 33, 213–18.Google ScholarPubMed
Razin, F., Romeo, L. C., Krilis, S., Liu, F.-T., Lewis, R. A., Corey, E. J. & Austen, K. F. (1984). An analysis of the relationship between 5-lipoxygenase product generation and the secretion of preformed mediators from mouse bone marrow-derived mast cells. Journal of Immunology 133, 938–45.CrossRefGoogle ScholarPubMed
Renoux, G. (1980). The general immunopharmacology of levamisole. Drugs 19, 89–99.CrossRefGoogle Scholar
Rivas-Alcalá, A. R., Greene, B. M., Taylor, H. R., Domíguez-Vázquez, A., Ruvalcaba-Macís, A. M., Lugo-Pfeiffer, C. & Beltrán-Hernandez, F. (1981). Chemotherapy of onchocerciasis: a controlled comparison of mebendazole, levamisole and diethylcarbamazine. Lancet 2, 485–90.CrossRefGoogle ScholarPubMed
Rogers, R. & Denham, D. A. (1976). Studies with Brugia pahangi. 12. The activity of levamisole. Journal of Helminthology 50, 21–8.CrossRefGoogle ScholarPubMed
Santiago-Stevenson, D., Oliver-Gonzalez, J. & Hewitt, R. I. (1947). Treatment of filariasis bancrofti with 1- diethylcarbamyl-4-methylpiperazine hydrochloride (‘hetrazan’). Journal of the American Medical Association 135, 708–12.CrossRefGoogle ScholarPubMed
Schardein, J. L., Lucas, J. A. & Dickerson, C. W. (1968). Ultrastructural changes in Litomosoides carinii microfilariae in gerbils treated with diethylcarbamazine. Journal of Parasitology 54, 351–8.CrossRefGoogle ScholarPubMed
Schofield, F. D. & Rowley, R. E. (1961). The effect of prednisone on persistent microfilarernia during treatment with diethylcarbamazine. American Journal of Tropical Medicine and Hygiene 10, 849–54.CrossRefGoogle ScholarPubMed
Sirois, P. (1985). Pharmacology of the leukotrienes. Advances in Lipid Research 21, 79–101.CrossRefGoogle ScholarPubMed
Staniunas, R. J. & Hammerberg, B.(1982).Diethylcarbamazine-enhanced activation of complement by intact microfilariae of Dirofilaria immitis and their in vitro products. Journal of Parasitology 68, 809–16.CrossRefGoogle ScholarPubMed
Stevens, R. L., Parsons, W. G., Austen, K. F., Hein, A. & Caulfield, J. P. (1985). Novel inhibition of proteoglycan synthesis and exocytosis by diethylcarbamazine in the swarm rat chondrocyte. Journal of Biological Chemistry 260, 5777–86.CrossRefGoogle ScholarPubMed
Stewart, A. G. & Piper, P. J. (1986). Platelet-activating factor-induced vasoconstriction in rat isolated perfused hearts: contribution of cyclo-oxygenase and lipoxygenase arachidonic acid metabolites. Pharmacological Research Communications 18 (suppl.yes), 163–72.CrossRefGoogle ScholarPubMed
Stingl, P., Pierce, P. F., Connor, D. H., Gibson, D. W., Straessle, T., Ross, M. A. & Ribas, J. L. (1988). Does dexamethasone suppress the Mazzotti reaction in patients with onchocerciasis? Acta Tropica 45, 77–85.Google ScholarPubMed
Subrahmanyam, D. (1987). Antifilarials and their mode of action. Ciba Symposium 127, 246–64.Google ScholarPubMed
Tanaka, H., Eshita, Y., Takaoka, M. & Fujii, G. (1977). Suppression of microfilaricidal activity of diethylcarbamazine by anti-lymphocytic serum in cotton rat filariasis. South East Asian Journal of Tropical Medicine and Public Health 8, 19–26.Google Scholar
Taylor, A. E. R. (1960). Observations on the Ultropak microscope on microfilariae of Litomosoides carinii circulating in the liver of a cotton rat, before and after the administration of Hetrazan. Transactions of the Royal Society of Tropical Medicine and Hygiene 54, 450–3.CrossRefGoogle Scholar
Turner, M. J. & Schaeffer, J. M. (1989). Mode of action of ivermectin. In Ivermectin and Abamectin (ed. Campbell, W. C.), pp. 73–88. New York: Springer- Verlag.CrossRefGoogle Scholar
Van Hoof, L., Henrard, C., Peel, F. & Wanson, M. (1947). Sur la chimiothérapie de l'onchocercose. Annales de Ia Société Beige de Médecine Tropicale 27, 173–7.Google Scholar
Waa, Vande E. A. (1991). Chemotherapy of filariases. Parasitology Today 7, 194–9.Google Scholar
Vickery, A. C., Nayar, J. K. & Tamplin, M. L. (1985). Diethylcarbamazine-mediated clearance of Brugia pahangi microfilariae in immunodeficient nude mice. American Journal of Tropical Medicine and Hygiene 34, 476–83.CrossRefGoogle ScholarPubMed
Weiner, D. J., Abraham, D. & D'Antonio, R. (1986). The effect of diethylcarbamazine on microfilariae of Litomosoides carinii in vitro and in vivo. Zeitschrift für Parasitenkunde 72, 805–13.CrossRefGoogle ScholarPubMed
Weiner, D. J. & Soulsby, E. J. L. (1982). Litomosoides carinii: effect of diethylcarbamazine in microfilaremias of Mastomys natalensis harboring old infections, new infections, and transfused microfilariae. Journal of Parasitology 68, 1105–9.CrossRefGoogle ScholarPubMed
Williams, J. F., Ghalib, H. W., Mackenzie, C. D., Elkhalifa, M. Y., Ayuya, J. M. & Kron, M. A. (1987). Cell adherence to microfilariae of Onchocerca volvulus: a comparative study. Filariasis (Ciba Foundation Symposium 127), pp. 146–63. Chichester: Wiley.Google Scholar
Wilson, T. (1950). Hetrazan in the treatment of filariasis due to Wuchereria malayi. Transactions of the Royal Society of Tropical Medicine and Hygiene 44, 49–66.CrossRefGoogle ScholarPubMed
Yazdanbakhsh, M., Duym, L., Aarden, L. & Partono, F. (1992). Serum interleukin-6 and adverse reactions to diethylcarbamazine in lymphatic filariasis. Journal of Infectious Diseases 166, 453–4.CrossRefGoogle ScholarPubMed
Zahner, H. (1983). Diethylcarbamazine dependent, complement mediated, adherence and cytotoxicity of cells on microfilariae of Litomosoides carinii. Acta Tropica 40, 129–38.Google ScholarPubMed
Zahner, H., Soulsby, E. J. L., Weidner, E. & Lämmler, G. (1978). Effect of diethylcarbamazine on the microfilariae of Litomosoides carinii in Mastomys natalensis: dynamics of cell adhesion, immobilization and elimination of microfilariae. Tropenmedizin und Parasitologie 29, 15–26.Google ScholarPubMed