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Pierre-marie Girard - One of the best experts on this subject based on the ideXlab platform.
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Combination of PS-15, epiroprim, or pyrimethamine with dapsone in prophylaxis of Toxoplasma gondii and Pneumocystis carinii dual infection in a rat model
Antimicrobial agents and chemotherapy, 1996Co-Authors: Monique Brun-pascaud, F. Chau, Louis Garry, D Jacobus, Francis Derouin, Pierre-marie GirardAbstract:In a rat model of dual infection, we studied such dihydrofolate reductase (DHFR) inhibitors as PS-15 (25 mg/kg of body weight), epiroprim (100 mg/kg), and pyrimethamine (3 mg/kg) alone or in combination with various doses of dapsone (50, 25, or 5 mg/kg) for the prevention of Pneumocystosis and toxoplasmosis. Rats latently infected with Pneumocystis carinii were immunosuppressed by corticosteroids for 7 weeks, and the drugs were administered from the initiation of the corticosteroid treatment. At week 5, the rats were inoculated intraperitoneally with the RH strain of Toxoplasma gondii. Infections were monitored by the counting of P. carinii cysts in lung homogenates and the titration of T. gondii in organs by quantitative culture and an indirect immunofluorescence assay. Fourteen of the 15 untreated rats died after T. gondii challenge, with P. carinii infection in the lungs and T. gondii infection in the lungs, liver, spleen, and brain. Of the three tested DHFR inhibitors, only PS-15 exhibited anti-P. carinii activity; none prevented toxoplasmosis in 100% of the rats. After the DHFR inhibitors were combined with dapsone (50 or 25 mg/kg), both Pneumocystosis and toxoplasmosis were completely prevented. On the basis of these results, PS-15 and epiroprim combined with dapsone are candidates for use for the prevention of both Pneumocystosis and toxoplasmosis.
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experimental evaluation of combined prophylaxis against murine Pneumocystosis and toxoplasmosis
The Journal of Infectious Diseases, 1994Co-Authors: Monique Brunpascaud, F. Derouin, Pierre-marie Girard, Francoise Chau, Annemarie Simonpoli, J J PocidaloAbstract:: Prophylactic efficacy of antimicrobial agents against Pneumocystosis and toxoplasmosis was examined in a model of concurrent Pneumocystis carinii and Toxoplasma gondii infections in rats. Corticosteroid-treated rats naturally infected by P. carinii were challenged with the RH strain of T. gondii. Infection was assessed by counting P. carinii cysts in lung and by titration of T. gondii in tissues by tissue culture. Untreated rats died after challenge, with P. carinii infection in lungs and T. gondii infection in liver, spleen, lungs, and brain. In rats that received trimethoprim-sulfamethoxazole or pyrimethamine plus dapsone, T. gondii was eradicated and P. carinii pneumonia prevented. Roxithromycin, 200 or 400 mg/kg, provided significant protection against toxoplasmosis but had no efficacy against P. carinii. Atovaquone, 100 or 200 mg/kg, had only partial efficacy against Pneumocystosis and toxoplasmosis. These results definitively confirm use of trimethoprim-sulfamethoxazole and pyrimethamine plus dapsone for prophylaxis against combined infection in immunocompromised hosts.
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Treatment of Pneumocystosis: preclinical evaluation
Revue de pneumologie clinique, 1991Co-Authors: Pierre-marie Girard, Brun-pascaud M, Roux PAbstract:There are now three methods to evaluate treatments of Pneumocystosis: (1) the animal model, using adult rats under corticosteroids; the intensity of infection is assessed on pulmonary appositions and can then be evaluated after administration of a potential treatment compared with a reference; (2) the in vitro propagation of P. carinii observed from rat lung extracts cultured on cell lines; this method, however, is limited by the difficulties encountered in quantifying the parasitic types; (3) the inhibition by the drugs tested of enzymes involved in folate synthesis is a method that is still under evaluation. The animal model remains the reference method.
E. Dei Cas - One of the best experts on this subject based on the ideXlab platform.
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Pneumocystis carinii and pneumocystis wakefieldiae in wild rattus norvegicus trapped in Thailand
Journal of Eukaryotic Microbiology, 2010Co-Authors: M. Chabé, V. Herbreteau, J.p. Hugot, N. Bouzard, L. Deruyter, S. Morand, E. Dei CasAbstract:This work reports for the first time the presence of two Pneumocystis species in wild Rattus norvegicus specimens from Thailand. Pneumocystis DNA was detected in 57.7% (15/26) wild rats without apparent association with typical Pneumocystosis. Pneumocystis carinii was found alone in five rats (19.2%), Pneumocystis wakefieldiae was detected alone in six rats (23.1%), and two rats were infected by both species (7.7%). In addition, a new P. wakefieldiae variant sequence has been identified in three wild R. norvegicus specimens caught in the same geographical area. The high frequency of Pneumocystis in wild rats documented in this study and the apparent scarcity of severe Pneumocystosis were consistent with an efficient circulation of rat Pneumocystis species in ecosystems.
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Surfactant changes during experimental Pneumocystosis are related to Pneumocystis development
The European respiratory journal, 1998Co-Authors: El Moukhtar Aliouat, E. Dei Cas, R. Escamilla, C Cariven, C Vieu, C Mullet, Mc PrevostAbstract:Pneumocystosis-related surfactant changes have been reported in both humans and corticosteroid-treated experimental hosts. As corticosteroids induce an increase in pulmonary surfactant, some findings could be considered as controversial. The aim of this study was to investigate whether the surfactant composition changes during experimental Pneumocystosis were related to the Pneumocystis development. In this work two corticosteroid-untreated animal models were used: rabbits, which develop spontaneous Pneumocystosis at weaning; and severe combined immunodeficiency mice, which were intranasally inoculated with Pneumocystis carinii. Surfactant phospholipid and protein content was explored by bronchoalveolar lavage. The in vitro effect of surfactant on P. carinii growth was also explored. In the two models, the surfactant phospholipid/protein ratio was significantly increased, whereas parasite rates were low. This ratio decreases with the slope increase of the parasite growth curve. These early surfactant changes suggested that Pneumocystis proliferation requires alveolar lining fluid changes, and that normal surfactant is not suitable for parasite development. In this way, in vitro experiments presented here have revealed an inhibitory effect of synthetic or seminatural surfactants on the P. carinii growth. Further studies are needed to determine how Pneumocystis induces the reported early modifications of the surfactant, and why the parasite development is inhibited by pulmonary surfactant.
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Animal models of Pneumocystosis.
FEMS immunology and medical microbiology, 1998Co-Authors: E. Dei Cas, M Brun-pascaud, V Bille-hansen, A Allaert, E M AliouatAbstract:As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were essentially developed by using rats, mice, rabbits and ferrets. The rat treated with corticosteroids for 9-12 weeks is a useful PCP model. Like laboratory rats, conventional mice develop PCP after prolonged corticosteroid administration. The ferret (Mustela putorius furo) also develop PCP under corticosteroid regime. Whilst bronchoalveolar lavage (BAL) is really difficult to perform on live laboratory rodents, serial BAL sampling can be performed on live ferrets. Rabbits currently develop spontaneous PCP at weaning without corticosteroid administration. For this reason this model has been used for studying the host immune response as well as Pneumocystis-surfactant interactions. Pigs and horses also develop spontaneous PCP. Treated with corticosteroids, piglets develop extensive PCP and could be used as a non-rodent model. Pneumocystis was detected in many non-human primates. Primates could represent a source of parasites taxonomically related to P. carinii sp. f. hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown, are important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis infections. Extensive PCP can be obtained within 5-7 weeks, whilst 9-12 weeks are needed in the classical model. The severe combined immunodeficiency (SCID) mouse inoculated by nasal route and the athymic nude rats intratracheally inoculated were used to test the infectivity of Pneumocystis samples coming from cultures or from different hosts. They were also used to test the anti-Pneumocystis activity of antimicrobial molecules.
J J Pocidalo - One of the best experts on this subject based on the ideXlab platform.
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experimental evaluation of combined prophylaxis against murine Pneumocystosis and toxoplasmosis
The Journal of Infectious Diseases, 1994Co-Authors: Monique Brunpascaud, F. Derouin, Pierre-marie Girard, Francoise Chau, Annemarie Simonpoli, J J PocidaloAbstract:: Prophylactic efficacy of antimicrobial agents against Pneumocystosis and toxoplasmosis was examined in a model of concurrent Pneumocystis carinii and Toxoplasma gondii infections in rats. Corticosteroid-treated rats naturally infected by P. carinii were challenged with the RH strain of T. gondii. Infection was assessed by counting P. carinii cysts in lung and by titration of T. gondii in tissues by tissue culture. Untreated rats died after challenge, with P. carinii infection in lungs and T. gondii infection in liver, spleen, lungs, and brain. In rats that received trimethoprim-sulfamethoxazole or pyrimethamine plus dapsone, T. gondii was eradicated and P. carinii pneumonia prevented. Roxithromycin, 200 or 400 mg/kg, provided significant protection against toxoplasmosis but had no efficacy against P. carinii. Atovaquone, 100 or 200 mg/kg, had only partial efficacy against Pneumocystosis and toxoplasmosis. These results definitively confirm use of trimethoprim-sulfamethoxazole and pyrimethamine plus dapsone for prophylaxis against combined infection in immunocompromised hosts.
Monique Brun-pascaud - One of the best experts on this subject based on the ideXlab platform.
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Combination of PS-15, epiroprim, or pyrimethamine with dapsone in prophylaxis of Toxoplasma gondii and Pneumocystis carinii dual infection in a rat model
Antimicrobial agents and chemotherapy, 1996Co-Authors: Monique Brun-pascaud, F. Chau, Louis Garry, D Jacobus, Francis Derouin, Pierre-marie GirardAbstract:In a rat model of dual infection, we studied such dihydrofolate reductase (DHFR) inhibitors as PS-15 (25 mg/kg of body weight), epiroprim (100 mg/kg), and pyrimethamine (3 mg/kg) alone or in combination with various doses of dapsone (50, 25, or 5 mg/kg) for the prevention of Pneumocystosis and toxoplasmosis. Rats latently infected with Pneumocystis carinii were immunosuppressed by corticosteroids for 7 weeks, and the drugs were administered from the initiation of the corticosteroid treatment. At week 5, the rats were inoculated intraperitoneally with the RH strain of Toxoplasma gondii. Infections were monitored by the counting of P. carinii cysts in lung homogenates and the titration of T. gondii in organs by quantitative culture and an indirect immunofluorescence assay. Fourteen of the 15 untreated rats died after T. gondii challenge, with P. carinii infection in the lungs and T. gondii infection in the lungs, liver, spleen, and brain. Of the three tested DHFR inhibitors, only PS-15 exhibited anti-P. carinii activity; none prevented toxoplasmosis in 100% of the rats. After the DHFR inhibitors were combined with dapsone (50 or 25 mg/kg), both Pneumocystosis and toxoplasmosis were completely prevented. On the basis of these results, PS-15 and epiroprim combined with dapsone are candidates for use for the prevention of both Pneumocystosis and toxoplasmosis.
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Lack of activity of artemether for prophylaxis and treatment of Toxoplasma gondii and Pneumocystis carinii infections in rat.
Parasite (Paris France), 1996Co-Authors: Monique Brun-pascaud, F. Chau, F. Derouin, P. M. GirardAbstract:Artemisinin and its derivatives have been found effective in vivo against Plasmodium and in vitro against Toxoplasma gondii and Pneumocystis carinii . We tested the activity of artemether for prophylaxis and treatment in the rat model of concurrent T. gondii and P. carinii infection. Artemether at doses of 18 and 100 mg/kg administered (s.c.) in prophylaxis did not prevent toxoplasmosis or Pneumocystosis, while trimethoprim-sulfamethoxazole (reference treatment) was effective for prevention of both infections. Similar results were obtained in curative studies. These results do not support the use of artemether for prevention or treatment of toxoplasmosis or Pneumocystosis.
F. Derouin - One of the best experts on this subject based on the ideXlab platform.
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Lack of activity of artemether for prophylaxis and treatment of Toxoplasma gondii and Pneumocystis carinii infections in rat.
Parasite (Paris France), 1996Co-Authors: Monique Brun-pascaud, F. Chau, F. Derouin, P. M. GirardAbstract:Artemisinin and its derivatives have been found effective in vivo against Plasmodium and in vitro against Toxoplasma gondii and Pneumocystis carinii . We tested the activity of artemether for prophylaxis and treatment in the rat model of concurrent T. gondii and P. carinii infection. Artemether at doses of 18 and 100 mg/kg administered (s.c.) in prophylaxis did not prevent toxoplasmosis or Pneumocystosis, while trimethoprim-sulfamethoxazole (reference treatment) was effective for prevention of both infections. Similar results were obtained in curative studies. These results do not support the use of artemether for prevention or treatment of toxoplasmosis or Pneumocystosis.
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experimental evaluation of combined prophylaxis against murine Pneumocystosis and toxoplasmosis
The Journal of Infectious Diseases, 1994Co-Authors: Monique Brunpascaud, F. Derouin, Pierre-marie Girard, Francoise Chau, Annemarie Simonpoli, J J PocidaloAbstract:: Prophylactic efficacy of antimicrobial agents against Pneumocystosis and toxoplasmosis was examined in a model of concurrent Pneumocystis carinii and Toxoplasma gondii infections in rats. Corticosteroid-treated rats naturally infected by P. carinii were challenged with the RH strain of T. gondii. Infection was assessed by counting P. carinii cysts in lung and by titration of T. gondii in tissues by tissue culture. Untreated rats died after challenge, with P. carinii infection in lungs and T. gondii infection in liver, spleen, lungs, and brain. In rats that received trimethoprim-sulfamethoxazole or pyrimethamine plus dapsone, T. gondii was eradicated and P. carinii pneumonia prevented. Roxithromycin, 200 or 400 mg/kg, provided significant protection against toxoplasmosis but had no efficacy against P. carinii. Atovaquone, 100 or 200 mg/kg, had only partial efficacy against Pneumocystosis and toxoplasmosis. These results definitively confirm use of trimethoprim-sulfamethoxazole and pyrimethamine plus dapsone for prophylaxis against combined infection in immunocompromised hosts.