Toxoplasmosis pp 191-198 | Cite as

Toxoplasma Gondii: Chemotherapy

  • Hernan R. Chang
Conference paper
Part of the NATO ASI Series book series (volume 78)

Abstract

Infection with Toxoplasma gondii is widespread and has been observed in man and in almost all warm-blooded animals. Most immunologically normal adults acutely infected with T. gondii present only self-limited symptoms and signs. This is in great contrast with the morbidity and mortality that is observed in children with congenital and acquired toxoplasmosis, and in immunocompromised patients, notably those affected by the acquired immune deficiency syndrome (AIDS). Prompt antimicrobial therapy is given to patients with the aim of inhibiting the replication of the parasite and to prevent or to reduce the tissue damage resulting from parasitic intracellular multiplication. This therapy, nevertheless, is inactive against the non-multiplying (extracellular) or metabolically inactive (cyst) form of the parasite. Therapy of toxoplasmosis is further complicated by the possibility of harmful effects of the drugs on the fetus during therapy of pregnant women infected for the first time with T. gondii. The high frequency of side effects observed in AIDS patients treated for toxoplasmic encephalitis may lead to withdrawal of therapy and this enhances the possibilities of recurrent disease. All these considerations, therefore, point out the need for safer alternatives in the therapy of toxoplasmosis.

Keywords

Malaria Adenine Pyrimidine Nucleoside Guanine 

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References

  1. Allegra CJ, Kovacs JA, Drake JC, Swan JC, Chabner BA, Masur H (1987) Potent in vitro and in vivo antitoxoplasma activity of the lipid-soluble antifolate trimetrexate. J Clin Invest 79: 478–482.PubMedCrossRefGoogle Scholar
  2. Araujo FG, Remington JS, (1974) Effect of clindamycin on acute and chronic toxoplasmosis in mice. Antimicrob Agents Chemother 5: 647–651.PubMedGoogle Scholar
  3. Araujo FG, Guptill DR, Remington JS (1987) In vivo activity of piritrexim against Toxoplasma gondii. J Inf Dis 156: 828–830.CrossRefGoogle Scholar
  4. Araujo FG, Guptill DR, Remington JS (1988) Azithromycin, amacrolide with potent activity against Toxoplasma gondii. Antimicrob Agents Chemother 32: 755–757.PubMedGoogle Scholar
  5. Araujo FG, Huskinson J, Remington JS (1991) Remarkable in vitro and in vivo activities of the hydroxynaphtoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrob Agents Chemother 35: 293–299.PubMedGoogle Scholar
  6. Araujo FG, Huskinson-Mark J, Gutteridge WE, Remington JS (1992) In vitro and in vivo activities of the hydroxynapthoquinone 566C80 against the cyst form of Toxoplasma gondii. Antimicrob Agents Chemother 36: 326–330.PubMedGoogle Scholar
  7. Chan J, Luft BJ (1986) Activity of roxithromycin (RU 28965), a macrolide, against Toxoplasma gondii infection in mice. Antimicrob Agents Chemother 30: 323–324.PubMedGoogle Scholar
  8. Chang HR, Pechere JCF (1987) Effect of roxithromycin on acute toxoplasmosis in mice. 31: 1147–1149.Google Scholar
  9. Chang HR, Pechere JC (1988a) In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin [CP-62,993], and A-56268) on Toxoplasma gondii. Antimicrob Agents Chemother 32:524–529.Google Scholar
  10. Chang HR, Pechere JC (1988b) Arteether, a qinghaosu derivative in toxoplasmosis. Trans Roy Soc Trop Med Hyg 82: 867.PubMedCrossRefGoogle Scholar
  11. Chang HR, Rudareanu FC, Pechere JC (1988) Activity of A-56268 (TE-031), a new macrolide against Toxoplasma gondii in mice. J Antimicrob Agents Chemother 22: 359–361.CrossRefGoogle Scholar
  12. Chang HR, Jefford CW, Pechere JC (1989) In vitro effects of three new 1,2,4-trioxanes (pentatroxane, thiahexatroxane, and hexatroxanone) on Toxoplasma gondii. Antimierob Agents Chemother 33: 1748–1752.Google Scholar
  13. Chang HR, Comte R, Pechere JC (1990) In vitro and in vivo effects of doxycycline on Toxoplasma gondii. Antimierob Agents Chemother 34:775–780.Google Scholar
  14. Chang HR, Grau GE, Pechere JC (1990) Role of TNF and IL-1 infections with Toxoplasma gondii. Immunology 69: 33–37.PubMedGoogle Scholar
  15. Chang HR, Comte R, Piguet PF, Pechere JC (1991) Activity of minocycline against Toxoplasma gondii in mice. J Antimierob Chemother 27: 639–645.CrossRefGoogle Scholar
  16. Chang HR, Pechere JC, Piguet PF (1992) Role of tumour necrosis factor in murine chronic toxoplasmic Toxoplasma gondii encephalitis. Immunol Infect Dis 2: 61–68.Google Scholar
  17. Freund YR, Slargato G, Jacob CO, Suzuki Y, Remington JS (1992) Polymorphisms in tumor necrosis factor α ( TNF- α) gene correlate with murine resistance to development of toxoplasmic encephalitis and with levels of TNF-a mRNA in infected brain tissue. J Exp Med 175: 683–688.PubMedCrossRefGoogle Scholar
  18. Harris C, Salgo MP, Tanowitz HB, Wittner M (1988) In vitro assessment of antimicrobial agents against Toxoplasma gondii. J Infect Dis 157: 14–22.PubMedCrossRefGoogle Scholar
  19. Huskinson-Mark J, Araujo FG, Remington JS (1991) Evaluation of the effect of drugs on the cyst form of Toxoplasma gondii. J Infect Dis 164: 170–177.PubMedCrossRefGoogle Scholar
  20. Israelski D, Remington JS (1991) Activity of γ interferon in combination with pyrimethamine or clindamycin in the treatment of murine toxoplasmosis. Eur J Clin Microbiol Infect Dis 9: 358–360.CrossRefGoogle Scholar
  21. Kovacs JA, Allegra CJ, Swan JC, Drake J, Parrillo JE, Chabner BA, Masur H (1988) Potent antipneumocystis and antitoxoplasma activities of piritrexim, a lipid-soluble antifolate. Antimicrob Agents Chemother 32: 430–433.PubMedGoogle Scholar
  22. Krug EC, Man JJ, Berens RL (1989) Purine metabolism in Toxoplasma gondii. J Biol Chem 264: 10601–10807.PubMedGoogle Scholar
  23. Luft BJ (1986) Potent in vivo activity of arprinocid, a purine analogue, against murine toxoplasmosis. J Infect Dis 154: 692–694.PubMedCrossRefGoogle Scholar
  24. McCabe RE, Luft BJ, Remington JS (1984) Effect of murine interferon γ in toxoplasmosis. J Infect Dis 150: 961–962.PubMedCrossRefGoogle Scholar
  25. Ou-Yang K, Krug EC, Marr JJ, Berens RL (1990) Inhibition of growth of Toxoplasma gondii by qinghaosu and derivatives. Antimierob Agents Chemother 34: 1961–1965.Google Scholar
  26. Pfefferkorn ER (1978) Toxoplasma gondii: the enzymic defect of a mutant resistant to 5-fluorodeoxyuridine. Exp Parasitol 44:26–35.Google Scholar
  27. Pfefferkorn ER, Pfeiferkorn LC (1977) Specific labeling of intracellular Toxoplasma gondii with uracil. J Protozool 24: 449–453.PubMedGoogle Scholar
  28. Pfefferkorn ER, Pfefferkorn LC (1978) The biochemical basis for resistance to adenine arabinoside in a mutant of T. gondii. J Parasitol 64: 488–492.CrossRefGoogle Scholar
  29. Pfefferkorn ER, Eckel ME, McAdams E (1988) Toxoplasma gondii: in vitro and in vivo studies with a mutant resistant to arprinocid-N-oxide. Exp Parasitol 65: 282–289.PubMedCrossRefGoogle Scholar
  30. Pfefferkorn ER, Eckel ME, McAdams E (1989) Toxoplasma gondii: the biochemical basis of resistance to emimycin. Exp Parasitol 69: 129–139.PubMedCrossRefGoogle Scholar
  31. Summers WA (1949) The effects of oral administration of aureomycin, sulfathiazole, sulfamerazine, and 4,4-diaminodiphenylsulfone on toxoplasmosis in mice. Am er J Trop Med 29: 889–893.Google Scholar
  32. Tabbara KF, Sakuragi S, O’Connor GR (1982) Minocycline in the chemotherapy of murine toxoplasmosis. Parasitology 84: 297–302.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • Hernan R. Chang
    • 1
  1. 1.Department of Genetics and MicrobiologyUniversity of Geneva Medical SchoolGeneva 4Switzerland

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