Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-09T15:57:42.014Z Has data issue: false hasContentIssue false
  • English
  • Français

Interactions between immunity and chemotherapy in the treatment of the trypanosomiases and leishmaniases

Published online by Cambridge University Press:  06 April 2009

B. J. Berger  and
A. H. Fairlamb
B. J. Berger
Affiliation:
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, Keppel St, London, WC1E 7HT, UK
A. H. Fairlamb*
Affiliation:
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, Keppel St, London, WC1E 7HT, UK
*
*Correspondence author.
Get access Rights & Permissions [Opens in a new window]

Summary

The immune status of a host infected with Trypanosoma spp. or Leishmania spp. can play an important role in successful chemotherapy. In animal models, treatment of African trypanosomiasis with difluoromethylornithine or melarsoprol requires an appropriate antibody-mediated immune response. An intact immune system is also necessary for rapid clearance of trypanosomes from the bloodstream following treatment with suramin or quinapyramine. Similarly, an efficient cell-mediated immune response is required for maximal efficacy of pentavalent antimonials in the treatment of leishmaniasis. However, the potential relationship between parasite-induced or acquired immunosuppression and effective chemotherapy has been poorly studied. Macrophages which have been activated by bacterial cell wall components or gamma-interferon are known to display increased activity against Leishmania donovani or Trypanosoma cruzi. In experimental and clinical visceral leishmaniasis, use of macrophage activators together with pentavalent antimonials has lowered the dose of antimony required to cure the infection.

Keywords

trypanosomiasisleishmaniasischemotherapyimmunosuppressionimmunochemotherapy
Type
Research Article
Information
Parasitology , Volume 105 , Issue S1: Chemotherapy and the immune system , January 1992 , pp. S71 - S78
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

Adams, D. O. (1980). Effector mechanisms of cytologically activated macrophages. I. Secretion of neutral proteases and effect of protease inhibitors. Journal of Immunology 124, 286–300.CrossRefGoogle Scholar
Adinolfi, L. E., Bonventre, P. F., Pas, Vander M. & Epstein, D. A. (1985). Synergistic effect of glucantime and a liposome-encapsulated muramyl dipeptide analog in therapy of experimental visceral leishmaniasis. Infection and Immunity 48, 409–16.CrossRefGoogle Scholar
Allison, A. C. (1978). Macrophage activation and nonspecific immunity. International Review of Experimental Pathology 18, 303–46.Google ScholarPubMed
Avila, J. L., Biondo, F., Monzon, H. & Convit, J. (1982). Cutaneous leishmaniasis in mice: resistance to glucan immunotherapy, either alone or combined with chemotherapy. American Journal of Tropical Medicine and Hygiene 31, 53–9.CrossRefGoogle ScholarPubMed
Bacchi, C. J., Nathan, H. C., Hutner, S. H., Mccann, P. P. & Sjoerdsma, A. (1980). Polyamine metabolism: a potential therapeutic target in trypanosomes. Science 210, 332–4.CrossRefGoogle ScholarPubMed
Badaro, R., Falcoff, E., Badaro, F. S., Carvalho, E. M., Pedral-Sampaio, D., Barrai, A., Carvalho, J. S., Barral-Netto, M., Brandely, M., Silva, L., Bina, J. C., Teixeira, R., Falcoff, R., Rocha, H., HO, J. L. & Johnson, W. D. (1990). Treatment of visceral leishmaniasis with pentavalent antimony and interferon gamma. New England Journal of Medicine 322, 16–21.CrossRefGoogle ScholarPubMed
Berenguer, J., Moreno, S., Cerenado, E., Bernaldo De Quinas, J. C. L., Garica De La Fuente, A. & Bouza, E. (1989). Visceral leishmaniasis in patients infected with human immunodeficiency virus. Annals of Internal Medicine 111, 129–32.CrossRefGoogle ScholarPubMed
Bitonti, A. J., Mccann, P. P. & Sjoerdsma, A. (1986). Necessity of antibody response in the treatment of African trypanosomiasis with α-difluoromethylornithine. Biochemical Pharmacology 35, 331–4.CrossRefGoogle ScholarPubMed
Bitonti, A. J., Cross-Doersen, D. E. & Mccann, P. P. (1988). Effects of α-difluoromethylornithine on protein synthesis and synthesis of the variant-specific glycoprotein (VSG) in Trypanosoma brucei brucei. Biochemical Journal 250, 295–8.CrossRefGoogle ScholarPubMed
Black, S. J., Murray, M., Shapiro, S. Z., Kaminsky, R., Borowy, N. K., Musanga, R. & Otieno-Omondi, F. (1989). Analysis of Propionibacterium acnes-induced non-specific immunity to Trypanosoma brucei in mice. Parasite Immunology 11, 371–83.CrossRefGoogle ScholarPubMed
Campbell, G. H., Esser, K. M. & Weinbaum, F. I. (1977). Trypanosoma brucei infection in B-cell-deficient mice. Infection and Immunity 18, 434–8.CrossRefGoogle Scholar
Cantrell, W. (1955). The effects of coritsone and oxophenarsine on Trypanosoma equiperdum infections in the rat. Journal of Infectious Diseases 96, 259–67.CrossRefGoogle Scholar
Cohn, Z. A. (1978). The activation of mononuclear phagocytes: fact, fancy and future. Journal of Immunology 121, 813–16.CrossRefGoogle ScholarPubMed
Condom, M. J., Clotet, B., Sirera, G., Milla, F. & Foz, M. (1989). Asymptomatic leishmaniasis in the acquired immunodeficiency syndrome (AIDS). Annals of Internal Medicine 111, 767–8.CrossRefGoogle ScholarPubMed
Croft, S. L. (1988). Recent developments in the chemotherapy of leishmaniasis. Trends in Pharmacological Sciences 9, 376–81.CrossRefGoogle ScholarPubMed
Darji, A., Magez, R. L., Toreele, E., Palacios, J., Sileghem, M., Songa, E. B., Hamers, R. & Baetselier, P. D. (1992). Mechanisms underlying trypanosomeelicited immunosuppression. Annales de la Sociéte Belge de Médicine Tropicale 72S, 27–38.Google ScholarPubMed
Degee, A. L. W., Mccann, P. P. & Mansfield, J. M. (1983). Role of antibody in the elimination of trypanosomes after DL-α-difluoromethylornithine chemotherapy. Journal of Parasitology 69, 818–22.Google Scholar
Docampo, R. (1990). Sensitivity of parasites to free radical damage by antiparasitic drugs. Chemical- Biological Interactions 73, 1–27.CrossRefGoogle ScholarPubMed
Ehrlich, P. (1909). On the partial functions of the cell. In The Collected Papers of Paul Ehrlich, Vol. 3 (1960). (ed. Himmelweit, F.), pp. 183–194. London: Pergamon Press.Google Scholar
Fairlamb, A. H. (1989). Novel biochemical pathways in parasitic protozoa. Parasitoiogy 99, S93–S112.CrossRefGoogle ScholarPubMed
Fairlamb, A. H. (1990). Future prospects for the chemotherapy of human trypanosomiasis. 1. Novel approaches to the chemotherapy of trypanosomiasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 84, 613–17.CrossRefGoogle Scholar
Fairlamb, A. H. & Cerami, A. (1992). Metabolism and functions of trypanothione in the Kinetoplastida. Annual Review of Microbiology 46, 695–729.CrossRefGoogle ScholarPubMed
Ferreira, M. S., Nishioka, S. D. A., Rocha, A., Silva, A. M., Ferreira, R. G., Olivier, W. & Tostes, S. (1991). Acute fatal Trypanosoma cruzi meningoencephalitis in a human immunodeficiency virus-positive hemophiliac patient. American Journal of Tropical Medicine and Hygiene 45, 723–7.CrossRefGoogle Scholar
Franca, L. C. M., Fleury, R. N., Ramos, H. A., Lemos, S., Melarago, F. R. & Pasternak, J. (1969). Molesta de Chagas cronica associada a leucemia linfatica: ocorrencia de encefalite aguda corn alteracao do estado immunitario. Arquivo de Neuro-Psiquiatria 27, 59–66.CrossRefGoogle Scholar
Frommel, (1988). Trypanosoma brucei rhodesiense: Effect of immunosuppression on the efficacy of melarsuprol treatment of infected mice. Experimental Parasitology 67,364–6.CrossRefGoogle ScholarPubMed
Goodwin, L. G., Green, D. G., Guy, M. W. & Voller, A. (1972). Immunosuppression during trypanosomiasis. British Journal of Experimental Pathology 53, 40–3.Google ScholarPubMed
Grammiccia, M., Gradoni, L. & Troiani, M. (1992). HIV-Leishmania co-infections in Italy. Isoenzyme characterization of Leishmania causing visceral leishmaniasis in HIV patients. Transactions of the Royal Society of Tropical Medicine and Hygiene 86, 161–3.CrossRefGoogle Scholar
Haidaris, C. G. & Bonventre, P. F. (1981). Elimination of Leishmania donovani amastigotes by activated macrophages. Infection and Immunity 33, 918–26.CrossRefGoogle ScholarPubMed
Haidaris, C. G. & Bonventre, P. F. (1983). Efficacy of combined immunostimulation and chemotherapy in experimental leishmaniasis. American Journal of Tropical Medicine and Hygiene 32, 286–95.CrossRefGoogle Scholar
Harel-Bellan, A., Joskowicz, M., Fradelizi, D. & Eisen, H. (1983). Modification of T-cell proliferation and interleukin-2 production in mice infected with Trypanosoma cruzi. Proceedings of the National Academy of Sciences USA 80, 3466–9.CrossRefGoogle ScholarPubMed
Hawking, F. (1938). Contribution on the mode of action of germanin (Bayer 205). Annals of Tropical Medicine and Parasitology 33, 13–19.CrossRefGoogle Scholar
Henderson, G. B., Fairlamb, A. H. & Cerami, A. (1987). Trypanothione dependent peroxide metabolism in Crithidia fasciculata and Trypanosoma brucei. Molecular and Biochemical Parasitology 24, 39–45.CrossRefGoogle ScholarPubMed
Hoover, D. L., Nacy, C. A. & Meltzer, M. S. (1985). Human monocyte activation for cytotoxicity against intracellular Leishmania donovani amastigotes: induction of microbicidal activity by interferon- gamma. Cellular Immunology 94, 500–11.CrossRefGoogle ScholarPubMed
Iwobi, M. U., Doenhoff, M. J. & Neal, R. A. (1991). Immune-dependence of chemotherapy of experimental visceral leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 85, 56–7.CrossRefGoogle ScholarPubMed
Kaye, P. M. (1987). Antigen presentation and the response to parasitic infection. Parasitology Today 3, 293–9.CrossRefGoogle ScholarPubMed
Kierszenbaum, F., Wirth, J. J., Mccann, P. P. & Sjoerdsma, A. (1987). Impairment of macrophage function by inhibitors of ornithine decarboxylase activity. Infection and Immunity 55, 2461–4.CrossRefGoogle ScholarPubMed
Kohl, S., Pickering, L. K., Frankel, L. S. & Yaeger, R. G. (1982). Reactivation of Chagas' disease during therapy of acute lymphocytic leukaemia. Cancer 50, 827–8.3.0.CO;2-#>CrossRefGoogle Scholar
Kuhn, R. E. (1981). Immunology of Trypanosoma cruzi infections. In Parasitic Diseases, Vol. 1 (ed. Mansfield, J. M.), pp. 137–166. New York: Marcel Dekker.Google Scholar
Lelchuk, R., Cardoni, R. L. & Fuks, A. S. (1977a). Cell mediated immunity in Chagas' disease: alterations induced by treatment with a trypanocidal drug (nifurtimox). Clinical and Experimental Immunology 30, 434–8.Google ScholarPubMed
Lelchuk, R., Cardoni, R. L. & Lewis, S. (1977b). Nifurtimox-induced alterations in the cell-mediated immune response to PPD in guinea pigs. Clinical and Experimental Immunology 30, 469–73.Google ScholarPubMed
Liew, F. W. & Cox, F. E. G. (1990). Non-specific defence mechanism: the role of nitric oxide. Parasitology Today 7, A17–A20.CrossRefGoogle Scholar
Louis, J. P., Jannin, J., Hengy, C., Moulia-Pelat, J. P., Makuwa, M., Asonganzi, T., Novtoua, L., Fadat, G., Nguerenemo, P., Cattand, P. & Trebrica, A. (1991). Absence d'inter-relations epidemiologiques entres l'infection retrovirale a VIH et al trypanosomiase humaine africaine (THA). Bulletin de la Societé de Pathologie Exotique 84, 25–9.Google Scholar
Mansfield, J. M. (1981). Immunology and immunopathology of African trypanosomiasis. In Parasitic Diseases, Vol. 1 (ed. Mansfield, J. M.), pp. 167–226.New York: Marcel Dekker.Google Scholar
Mansfield, J. M. & Wallace, J. H. (1974). Suppression of cell-mediated immunity in experimental African trypanosomiasis. Infection and Immunity 10, 335–9.CrossRefGoogle ScholarPubMed
Metze, K., Lorand-Metze, I., Antonio De Almeida, E. & Lauar De Oraes, S. (1991). Reactivation of Chagas' myocarditis during therapy of Hodgkin's disease. Tropical and Geographical Medicine 43, 228–30.Google ScholarPubMed
Montalban, C., Calleja, J. L., Erice, A., Laguna, F., Clotet, B., Odzanczer, D., Covo, J., Mallolas, J., Yebra, M., Gallego, A. & The Cooperative group for the study of leishmaniasis in aids(1990). Visceral leishmaniasis in patients infected with human immunodeficiency virus. Journal of Infection 21, 261–70.CrossRefGoogle ScholarPubMed
Morello, A. (1988). The biochemistry of the mode of action of drugs and the detoxification mechanisms in Trypanosoma cruzi. Comparative Biochemistry and Physiology 90C, 1–12.Google Scholar
Mott, F. W. (1906). The changes produced in the nervous system by chronic trypanosome infections. Lancet 2, 870.Google Scholar
Murray, H. W., Masur, H. & Keithly, J. S. (1982). Cellmediated immune response in experimental visceral leishmaniasis. I. Correlation between resistance to Leishmania donovani and lymphokine-generating capacity. Journal of Immunology 129, 344–50.CrossRefGoogle ScholarPubMed
Murray, H. W., Rubin, B. Y. & Rothermel, C. D. (1983). Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine. Journal of Clinical Investigations 72, 1506–10.CrossRefGoogle ScholarPubMed
Murray, H. W., Berman, J. D. & Wright, S. D. (1988). Immunochemotherapy for intracellular Leishmania donovani infection: gamma-interferon plus pentavalent antimony. Journal of Infectious Diseases 157, 973–8.CrossRefGoogle ScholarPubMed
Nathan, C. N., Nogueira, N., Ellis, J. & Cohn, Z. (1979). Activation of macrophages in vivo and in vitro. Correlation between hydrogen peroxide release and killing of Trypanosoma cruzi. Journal of Experimental Medicine 149, 1056–68.CrossRefGoogle ScholarPubMed
Nathan, C. F., Murray, H. W., Wiebe, M. E. & Rubin, B. Y. (1983). Identification of interferon-gamma as the lymphokine that activates human microbicidal oxidative metabolism and antimicrobial activity. Journal of Experimental Medicine 158, 670–89.CrossRefGoogle ScholarPubMed
Nogueira, N. & Cohn, Z. A. (1978). Trypanosoma cruzi: in vitro induction of macrophage microbicidal activity. Journal of Experimental Medicine 148, 288–300.CrossRefGoogle ScholarPubMed
North, R. J. (1978). The concept of the activated macrophage. Journal of Immunology 121, 806–9.CrossRefGoogle ScholarPubMed
Osman, A. S., Jennings, F. W. & Holmes, P. H. (1992). The rapid development of drug-resistance by Trypanosoma evansi in immunosuppressed mice. Acta Tropica 50, 249–57.CrossRefGoogle ScholarPubMed
Penketh, P. G., Kennedy, W. P. K., Patton, C. L. & Sartorelli, A. C. (1987). Trypanosomatid hydrogen peroxide metabolism. FEBS Letters 221, 427–31.CrossRefGoogle Scholar
Pepin, J., Ethier, L., Kazade, C., Milford, F. & Ryder, R. (1992). The impact of human immunodeficiency virus infection on the epidemiology and treatment of Trypanosoma brucei gambiense sleeping sickness in Nioki, Zaire. American Journal of Tropical Medicine and Hygiene 47, 133–40.CrossRefGoogle ScholarPubMed
Peters, B. S., Fish, D., Golden, R., Evans, D. A., Bryceson, A. D. M. & Pinching, A. J. (1990). Visceral leishmaniasis in HIV infection and AIDS: clinical features and response to therapy. Quarterly Journal of Medicine 77, 1101–11.CrossRefGoogle ScholarPubMed
Raether, W. (1988). Chemotherapy and other control measures of parasitic diseases in domestic animals and man. In Parasitology in Focus (ed. Melhorn, H.), pp. 739–866. Berlin: Springer-Verlag.CrossRefGoogle Scholar
Reed, S. G. (1981). Immunology of Leishmania infections. In Parasitic Diseases, Vol. 1 (ed. Mansfield, J. M.), pp. 291–314. New York: Marcel Dekker.Google Scholar
Reed, S. G. (1988).In vivo administration of recombinant INF-γ induces macrophage activation, and prevents acute disease, immune suppression, and death in experimental Trypanosoma cruzi infections. Journal of Immunology 140, 4342–7.CrossRefGoogle Scholar
Reed, S. G., Nathan, C. F., Pihl, D. L., Rodricks, P., Shanebeck, K., Conlon, J. & Grabstein, K. H. (1987). Recombinant granulocyte/macrophage colony-stimulating factor activates macrophages to inhibit Trypanosoma cruzi and releases hydrogen peroxide. Comparison with interferon-gamma. Journal of Experimental Medicine 166, 1734–46.CrossRefGoogle ScholarPubMed
Reiner, N. E. (1987). Parasite accessory cell interactions in murine leishmaniasis. I. Evasion and stimulus- dependent suppression of the macrophage interleukin 1 response by Leishmania donovani. Journal of Immunology 138, 1919–25.CrossRefGoogle ScholarPubMed
Reiner, N. E., Ng, W. & Mcmaster, W. R. (1987). Parasite accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products. Journal of Immunology 138, 1926–32.CrossRefGoogle Scholar
Reiner, N. E., Ng, W., Ma, T. & Mcmaster, W. R. (1988). Kinetics of gamma-interferon binding and induction of major histocompatibility complex class II mRNA in leishmania-infected macrophages. Proceedings of the National Academy of Sciences USA 85, 4330-4.CrossRefGoogle ScholarPubMed
Rizzi, M., Arici, C., Bonaccorso, C. & Gavazzini, G. (1988). Visceral leishmaniasis in a patient with human immunodeficiency virus. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 565.CrossRefGoogle Scholar
Selim, M. M. (1990). Leishmaniasis. Currently recommended treatment. International Journal of Dermatology 29, 318–21.CrossRefGoogle ScholarPubMed
Sen, H. G., Dutta, B. N. & Ray, H. N. (1955). Effect of splenectomy on ‘Antrycide’ therapy of Trypanosoma evansi infection in rats. Nature 175, 778–9.CrossRefGoogle ScholarPubMed
Sileghem, M., Darji, A. & Betselier, P. D. (1991). In vitro simulation of immunosuppression caused by Trypanosoma brucei. Immunology 73, 246–8.Google ScholarPubMed
Snyder, D. S. & Unanue, E. R. (1982). Corticosteroids inhibit murine macrophage Ia expression and interleukin 1 production. Journal of Immunology 129, 1803–5.CrossRefGoogle ScholarPubMed
Sunkara, P. S., Prakash, N. J., Mayer, G. D. & Sjoerdsma, A. (1983). Tumour suppression with a combination of α-difluoromethylornithine and interferon. Science 219, 851–3.CrossRefGoogle ScholarPubMed
Von Jancso, N. & Von Jancso, H. (1934). Wirkungsmechanismus des Germanins (Bayer 205) bei Trypanosomen. Zentralblatt für Bakteriologie, Parasitenkunde und Infektionskrankheiten 132, 257–92.Google Scholar
Von Jancso, N. & Von Jancso, H. (1935). Chemitherapeutische Mittel mit opsinartiger Wirkung. Zeitschrift für Immunitatsforschung 84, 471–505.Google Scholar