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Influence of Antimicrobial Agents on Replication and Stage Conversion of Toxoplasma gondii

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 219))

Abstract

As yet, only a few drugs are available that are frequently used for the treatment of human toxoplasmosis. Pyrimethamine and sulfadiazine are regularly used in combination and are the first choice for most clinical conditions. However, due to severe side effects that are observed especially with sulfadiazine, other drugs, such as clindamycin, have successfully been used as alternative treatment. Since pyrimethamine might be teratogenic when used in the first weeks of pregnancy, spiramycin has been introduced as first-choice treatment during the first 16–20 weeks of pregnancy. In addition to these four well-established drugs, others such as tetracycline or cotrimoxazole have been studied as therapeutics against toxoplasmosis. Although their effectiveness has been demonstrated to some extent, they have not been accepted as general treatment (Joss 1992). None of these drugs has been shown to completely eliminate the parasite in the human host. Since persistent infection with cysts is the source of reactivated toxoplasmosis, new drugs have been developed that might even be more effective against the cyst stage. The hydroxynaphthoquinone atovaquone and macrolides such as azithromycin, clarithromycin, and roxithromycin are thought to inhibit the tachyzoite and the cyst stage as well, as has been shown in vitro or/and in vivo (Araujo et al. 1991,1992a,1992b; Blais et al. 1993a, Huskinson-Mark et al. 1991).

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References

  • Araujo FG, Shepard RM, Remington JS (1991) In vivo activity of the macrolide antibiotics azithromycin. roxithromycin and spiramycin against Toxoplasma gondii. Eur J Clin Microbiol Infect Dis 10:519–524

    Article  PubMed  CAS  Google Scholar 

  • Araujo FG, Huskinson-Mark J, Gutteridge WE, Remington JS (1992a) In vitro and in vivo activities of the hydroxynaphoquinone 566C80 against the cyst form of Toxoplasma gondii. Antimicrob Agents Chemother 36:326–330

    Article  PubMed  CAS  Google Scholar 

  • Araujo FG, Prokocimer P, Lin T, Remington JS (1992b) Activity of clarithromycin alone or in combination with other drugs for treatment of murine toxoplasmosis. Antimicrob Agents Chemother 36:2454–2457

    Article  PubMed  CAS  Google Scholar 

  • Beckers CJ, Roos OS, Donald RG, Luft BJ, Schwab JC, Cao Y, Joiner KA (1995) Inhibition of cytoplasmic and organellar protein synthesis in Toxoplasma gondii. Implications for the target of macrolide antibiotics. J Clin Invest 95:367–376

    Article  PubMed  CAS  Google Scholar 

  • Blais J, Garneau V, Chamberland S (1993a) Inhibition of Toxoplasma gondii protein synthesis by azithromycin. Antimicrob Agents Chemother 37:1701–1703

    Article  PubMed  CAS  Google Scholar 

  • Blais J, Tardif C, Chamberland S (1993b) Effect of clindamycin on intracellular replication, protein synthesis, and infectivity of Toxoplasma gondii. Antimicrob Agents Chemother 37:2571–2577

    Article  PubMed  CAS  Google Scholar 

  • Bohne W, Heesemann J, Gross U (1993) Induction of bradyzoite-specific Toxoplasma gondii antigens in gamma interferon-treated mouse macrophages. Infect Immun 61: 1141–1145

    PubMed  CAS  Google Scholar 

  • Bohne W, Heesemann J, Gross U (1994) Reduced replication of Toxoplasma gondii is necessary for induction of bradyzoite-specific antigens:a possible role for nitric oxide in triggering stage conversion. Infect Immun 62:1761–1767

    PubMed  CAS  Google Scholar 

  • Cantin L, Chamberland S (1993) In vitro evaluation of the activities of azithromycin alone and combined with pyrimethamine against Toxoplasma gondii. Antimicrob Agents Chemother 37: 1993–1996

    Article  PubMed  CAS  Google Scholar 

  • Chamberland S, Kirst HA, Current WL (1991) Comparative activity of macrolides against Toxoplasma gondii demonstrating utility of an in vitro microassay. Antimicrob Agents Chemother 35:903–909

    Article  PubMed  CAS  Google Scholar 

  • Chang HR, Pechere JC (1988) In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin (CP-62, 993), and (A-56268) on Toxoplasma gondii. Antimicrob Agents Chemother 32:524–529

    Article  PubMed  CAS  Google Scholar 

  • Chang HR, Comte R, Pechere JC (1990) In vitro and in vivo effects of doxycycline on Toxoplasma gondii. Antimicrob Agents Chemother 34:775–780

    Article  PubMed  CAS  Google Scholar 

  • Derouin F, Chastang C (1989) In vitro effects of folate inhibitors on Toxoplasma gondii. Antimicrob Agents Chemother 33:1753–1759

    Article  PubMed  CAS  Google Scholar 

  • Derouin F, Chastang C (1990) Activity in vitro against Toxoplasma gondii of azithromycin and clarithromycin alone and with pyrimethamine. J Antimicrob Chemother 25:708–711

    Article  PubMed  CAS  Google Scholar 

  • Derouin F, Nalpas J, Chastang C (1988) Mesure in vitro de I’effet inhibiteur de macrolides, lincosamides et synergestines sur la croissance de Toxoplasma gondii. Path Bioi 36: 1204–121O.

    CAS  Google Scholar 

  • Derouin F, Caroff B, Chau F, Prokocimer p, Pocidalo JJ (1992) Synergistic activity of clarithromycin and minocycline in an animal model of acute experimental toxoplasmosis. Antimicrob Agents Chemother 36:2852–2855

    Article  PubMed  CAS  Google Scholar 

  • Ferguson DJP, Huskinson-Mark J, Araujo FG, Remington JS (1994) An ultrastructural study of the effect of treatment with atovaquone in brains of mice chronically infected with the ME49 strain of Toxoplasma gondii. Int J Exp Path 75:111–116

    CAS  Google Scholar 

  • Fichera ME, Bhopale MK, Roos DS (1995) In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondii. Antimicrob Agents Chemother 39: 1530–1537

    Article  PubMed  CAS  Google Scholar 

  • Gross U, Bohne W (1994) Toxoplasma gondii: strain-and host cell dependent induction of stage conversion. J Euk Microbiol 41: 105–115

    Google Scholar 

  • Gross U, Bohne W, Soete M, Dubremetz JF (1996) Developmental differentiation between tachy-zoites and bradyzoites of Toxoplasma gondii. Parasitol Today 12:30–33

    Article  PubMed  CAS  Google Scholar 

  • Haverkos HW (1987) Assessment of therapy for toxoplasma encephalitis. Am J Med 82:907–914

    Article  PubMed  CAS  Google Scholar 

  • Holfels E, McAuley J, Mack D, Milhous WK, McLeod R (1994) In vitro effects of artemisinin ether, cycloguanil hydrochloride (alone and in combination with sulfadiazine). quinine sulfate, meflo-quine, primaquine phosphate, trifluoperazine hydrochloride, and verapamil on Toxoplasma gondii. Antimicrob Agents Chemother 38: 1392–1396

    Article  PubMed  CAS  Google Scholar 

  • Hudson AT (1993) Atovaquone — a novel broad-spectrum anti-infective drug. Parasitol Today 9:66–69

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Joss AWL (1992) Treatment. In: Ho-Yen DO, Joss AWL (eds) Human toxoplasmosis. Oxford University Press, Oxford, pp 119–143

    Google Scholar 

  • Lindsay DS, Blagburn BL, Hall JE, Tidwell RR (1991) Activity of pentamidine and pentamidine analogs against Toxoplasma gondii in cell cultures. Antimicrob Agents Chemother 35: 1914–1916

    Article  PubMed  CAS  Google Scholar 

  • Mack DG, McLeod R (1984) New micromethod to study the effect of antimicrobial agents on Toxoplasma gondii: comparison of sulfadoxine and sulfadiazine individually and in combination with pyrimethamine and study of clindamycin, metronidazole, and cyclosporin A. Antimicrob Agents Chemother 26:26–30

    Article  PubMed  CAS  Google Scholar 

  • Parmley SF, Gross U, Sucharczuk A, Windeck T, Sgarlato GD, Remington JS (1994) Two alleles of the gene encoding surface antigen P22 in 25 strains of Toxoplasma gondii. J Parasitol 80:293–301

    Article  PubMed  CAS  Google Scholar 

  • Pfefferkorn ER (1978) Toxoplasma gondii: the enzymatic defect of a mutant resistant to 5-fluorodeoxyuridine. Exp Parasitol 44:26–35

    Article  PubMed  CAS  Google Scholar 

  • Pfefferkorn ER, Borotz SE (1994) Comparison of mutants of Toxoplasma gondii selected for resistance to azithromycin, spiramycin, or clindamycin. Antimicrob Agents Chemother 38:31–37

    Article  PubMed  CAS  Google Scholar 

  • Pfefferkorn ER, Nothnagel RF, Borotz SE (1992) Parasiticidal effect of clindamycin on Toxoplasma gondii grown in cultured cells and selection of a drug-resistant mutant. Antimicrob Agents Chemother 36:1091–1096

    Article  PubMed  CAS  Google Scholar 

  • Pfefferkorn ER, Borotz SE, Nothnagel RF (1993) Mutants of Toxoplasma gondii resistant to atova-quone (566C80) or decoquinate. J Parasitol 79:559–564

    Article  PubMed  CAS  Google Scholar 

  • Piketty C, Derouin F, Rouveix B, Pocidalo JJ (1990) In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice. Antimicrob Agents Chemother 34:1467–1472

    Article  PubMed  CAS  Google Scholar 

  • Romand S, Pudney M, Derouin F, (1993) In vitro and in vivo activities of the hydroxynaphthoquinone atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, or minocycline against Toxoplasma gondii. Antimicrob Agents Chemother 37:2371–2378

    Article  PubMed  CAS  Google Scholar 

  • Sartorius C, Franklin RM (1991) The use of antisense oligonucleotides as chemotherapeutic agents for parasites. Parasitol Today 7:90–94

    Article  PubMed  CAS  Google Scholar 

  • Schoondermark-van de Ven E, Melchers W, Camps W, Eskes T, Meuwissen J, Galama J (1994) Effectiveness of spiramycin for treatment of congenital Toxoplasma gondii infection in rhesus monkeys. Antimicrob Agents Chemother 38:1930–1936

    Article  PubMed  CAS  Google Scholar 

  • Schoondermark-van de Ven E, Galama J, Vree T, Camps W, Baars I, Eskes T, Meuwissen J, Melchers W (1995) Study of treatment of congenital Toxoplasma gondii infection in rhesus monkeys with pyrimethamine and sulfadiazine. Antimicrob Agents Chemother 39: 137–144

    Article  PubMed  CAS  Google Scholar 

  • Soete M, Camus D, Dubremetz JF (1994) Experimental induction of bradyzoite-specific antigen expression and cyst formation by the RH strain of Toxoplasma gondii in vitro. Exp Parasitol 78:361–370

    Article  PubMed  CAS  Google Scholar 

  • Tabbara KF, O’Connor GR (1980) Treatment of ocular toxoplasmosis with clindamycin and sulfadiazine. Ophthalmology 87: 129–134

    PubMed  CAS  Google Scholar 

Download references

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© 1996 Springer-Verlag Berlin Heidelberg

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Gross, U., Pohl, F. (1996). Influence of Antimicrobial Agents on Replication and Stage Conversion of Toxoplasma gondii . In: Gross, U. (eds) Toxoplasma gondii. Current Topics in Microbiology and Immunology, vol 219. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-51014-4_21

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  • DOI: https://doi.org/10.1007/978-3-642-51014-4_21

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-51016-8

  • Online ISBN: 978-3-642-51014-4

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