Evaluation of the efficacy of prolonged administration of azithromycin in a murine model of chronic toxoplasmosis

Dumas, Jean-Luc; Chang, Robert C.; Mermillod, Bernadette; Piguet, P F; Comte, Raymonde; Péchère, Jean-Claude

doi:10.1093/jac/34.1.111

Cited by 32 publications

(11 citation statements)

References 19 publications

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“…These results while in contrast to some reports in patients are in line with the poor antiparasitic activity of spiramycin and other macrolides in experimental studies [29][30][31][32], and confirm results of other studies that did not find an impact of antiparasitic treatment on avidity maturation [11,13]. The activity of azithromycin on cerebral toxoplasmosis is limited by its poor brain penetration [30]; in murine models of chronic infection, only long-term administration of spiramycin or azithromycin resulted in a significant reduction of brain cysts burdens [29,33].…”

Section: Discussionsupporting

confidence: 80%

Antiparasitic treatment suppresses production and avidity ofToxoplasma gondii-specific antibodies in a murine model of acute infection

Alvarado‐Esquivel¹,

Niewiadomski²,

Schweickert³

et al. 2011

European Journal of Microbiology and Immunology

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Infection with Toxoplasma gondii during pregnancy may result in congenital transmission of the parasite. Infection is commonly diagnosed using serological tests for IgG, IgM and IgA antibodies. Avidity of IgG antibodies is used to exclude acute infection. Few studies have investigated the impact of antiparasitic treatment on the production of anti-T. gondii antibody and the avidity of IgG antibodies. We therefore investigated the production of IgG, IgM, and IgA antibodies and IgG avidity in a murine model of acute infection with 10 cysts of T. gondii. All antibody classes increased following infection. Treatment of mice with py rime thamine/ sulfadiazine but not with spiramycin or azithromycin at dosages equivalent to those used in patients resulted in a significant decrease in the concentration of T. gondii-specific IgG and IgM antibodies postinfection. IgG and IgM antibody decreases were paralleled by a significant reduction in cyst numbers in brains of mice treated with pyrimethamine/sulfadiazine but not with other drugs. In contrast, treatment with atovaquone did significantly reduce the concentrations of IgM antibodies and resulted in reduced IgG avidity indices. T. gondii-specific DNA was not detected in blood between days 1 and 3. In conclusion, antiparasitic treatment with pyrimethamine/sulfadiazine and atovaquone appears to impact the generation of antibody responses against T. gondii. Future studies will have to determine the specific impact of antiparasitic treatment on antibody responses and the consequences for the management of patients infected with T. gondii.

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Section: Discussionsupporting

confidence: 80%

Antiparasitic treatment suppresses production and avidity ofToxoplasma gondii-specific antibodies in a murine model of acute infection

Alvarado‐Esquivel¹,

Niewiadomski²,

Schweickert³

et al. 2011

European Journal of Microbiology and Immunology

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“…9 Several different protozoan infections of humans have been shown in vitro and in vivo to be susceptible to azithromycin in varying degrees, including Acanthamoeba, 10 Cryptosporidium parvum, 11 Plasmodium falciparum, Plasmodium malariae, Plasmodium vivax, [12][13][14][15] and Toxoplasma gondii. [16][17][18][19][20] Studies involving T. gondii showed direct effects of the drug on the parasite's viability by inhibition of protein synthesis. 16 In addition, it was shown that azithromycin concentrates in the lysosomes of T. gondii-infected macrophages.…”

Section: Introductionmentioning

confidence: 99%

Activity of azithromycin against Leishmania major in vitro and in vivo.

Krolewiecki¹,

Leon²,

Scott³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. Azithromycin, an azalide antibiotic of the macrolide family, concentrates in the tissues and especially in macrophages. Because Leishmania parasites reside in these cells, we tested this antibiotic for a possible antileishmanial activity in vitro and in vivo. Azithromycin decreased the Leishmania major promastigote count in cell-free cultures at log phase approximately 50-fold. In macrophage cultures infected with L. major amastigotes, azithromycin caused a significant decrease in parasite levels with an ED 50 of 12 g/ml. The activity in vivo was evaluated after infection of the footpads of susceptible BALB/cByJ mice and resistant C57BL/6J mice with L. major. Treatment of BALB/cByJ mice with azithromycin, 100 to 200 mg/kg/d, resulted in a significant decrease in lesion size and in the number of parasites per lesion, whereas no effect was seen in the treated C57BL/6J mice. Azithromycin has activity against L. major in vitro and in vivo. Given the severity of the disease and the limitations of the available therapeutic agents, azithromycin may have a significant role in the treatment of this group of diseases.

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“… reported that the blood concentration of the drug in humans became stable (0·5–1·0 mg/ml) after 3 or 5 days of oral AZM. The 100 mg/kg/day dosage was used because it corresponds to the human dosage after size correction . Accumulating evidence indicates that early interaction between allogeneic T lymphocytes and residual recipient APCs immediately after allo‐BMT is critical for eliciting acute GVHD .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of azithromycin in preventing lethal graft-versus-host disease

Iwamoto

Azuma

Kumamoto

et al. 2013

Clinical and Experimental Immunology

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SummaryAcute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation (BMT) is initiated by donor T lymphocytes that recognize histocompatibility antigens presented by recipient dendritic cells (DCs). Current approaches to reduce GVHD are focused on suppressing donor T lymphocyte responses to alloantigens. However, these strategies may be inadequate in the setting of allogeneic transplants (particularly histoincompatible transplants), may increase the risk of tumour relapse and are associated with high rates of opportunistic infections. We hypothesized that inhibition of recipient DCs might suppress GVHD. We recently demonstrated in vitro that azithromycin, a macrolide antibiotic, also acts as a nuclear factor (NF)-kB inhibitor of murine DCs and inhibits their maturation and functions, including allogeneic responses. We investigated whether azithromycin could prevent alloreactions in a murine histoincompatibility model. Oral administration of azithromycin to recipient mice for 5 days during majorhistoincompatible BMT suppressed lethal GVHD significantly, whereas ex-vivo lymphocyte function was not affected by the drug. These data suggest that azithromycin has potential as a novel prophylactic drug for lethal GVHD.

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Evaluation of the efficacy of prolonged administration of azithromycin in a murine model of chronic toxoplasmosis

Cited by 32 publications

References 19 publications

Antiparasitic treatment suppresses production and avidity ofToxoplasma gondii-specific antibodies in a murine model of acute infection

Antiparasitic treatment suppresses production and avidity ofToxoplasma gondii-specific antibodies in a murine model of acute infection

Activity of azithromycin against Leishmania major in vitro and in vivo.

Efficacy of azithromycin in preventing lethal graft-versus-host disease

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