Visceral Leishmaniasis in the BALB/c Mouse: A Comparison of the Efficacy of a Nonionic Surfactant Formulation of Sodium Stibogluconate with Those of Three Proprietary Formulations of Amphotericin B

ABSTRACT In this study, treatment efficacies of a nonionic surfactant vesicle formulation of sodium stibogluconate (SSG-NIV) and of several formulations of amphotericin B were compared in a murine model of visceral leishmaniasis. Treatment with multiple doses of AmBisome, Abelcet, and Amphocil (total dose, 12.5 mg of amphotericin B/kg of body weight) resulted in a significant suppression of parasite burdens in liver (P < 0.0005) and spleen (P < 0.0005) compared with those of controls, with Abelcet having the lowest activity. Only AmBisome and Amphocil gave significant suppression of parasites in bone marrow (compared to control values,P < 0.005). In the acute-infection model, single-dose treatments of SSG-NIV (296 mg of SbV/kg), SSG solution (296 mg of SbV/kg), or AmBisome (8 mg of amphotericin B/kg) were equally effective against liver parasites (compared to control values,P < 0.0005). SSG-NIV and AmBisome treatment also significantly suppressed parasites in bone marrow and spleen (P < 0.005), with SSG-NIV treatment being more suppressive (>98% suppression in all three sites). Free-SSG treatment failed to suppress spleen or bone marrow parasites. Infection status influenced treatment outcome. In the chronic-infection model, the AmBisome single-dose treatment was less effective in all three infection sites and the SSG-NIV single-dose treatment was less effective in the spleen. The results of this study suggest that the antileishmanial efficacy of SSG-NIV compares favorably with those of the novel amphotericin B formulations.

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The Cured Immune Phenotype Achieved by Treatment of Visceral Leishmaniasis in the BALB/c Mouse with a Nonionic Surfactant Vesicular Formulation of Sodium Stibogluconate Does Not Protect against Reinfection

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.1.61-65.1999 ◽

1999 ◽

Vol 6 (1) ◽

pp. 61-65 ◽

Cited By ~ 6

Author(s):

K. C. Carter ◽

A. J. Baillie ◽

A. B. Mullen

Keyword(s):

Immune Response ◽

T Cells ◽

Single Dose ◽

Visceral Leishmaniasis ◽

Nonionic Surfactant ◽

Leishmania Donovani ◽

Prophylactic Treatment ◽

Cell Populations ◽

Sodium Stibogluconate ◽

Single Dose Treatment

ABSTRACT Single-dose treatment with sodium stibogluconate solution (SSG) and treatment with a nonionic surfactant vesicular formulation of sodium stibogluconate (SSG-NIV) were compared for the ability to protect BALB/c mice against infection with Leishmania donovani.Prophylactic treatment with SSG-NIV protected against infection, although its effects were time and organ dependent; protection was not obtained with SSG. Protection against reinfection with L. donovani was observed only in mice cured by treatment with SSG-NIV. However, this protective effect was probably due to the presence of residual drug rather than an immune effect, since prophylactic SSG-NIV treatment gave similar results. Transfer of enriched spleen T-cell populations from L. donovani-infected mice or from infected SSG-NIV-treated mice gave no protection against L. donovani infection in the recipients. T cells from infected mice, but not from infected SSG-NIV-treated mice, were infectious to recipients. SSG-NIV treatment was equally effective against visceral leishmaniasis in immunocompetent and SCID mice, whereas SSG treatment was less effective in the latter. The results of this study suggest that the high antileishmanial activity of SSG-NIV is due to favorable modification of SSG delivery and does not require a fully functional immune response. Cure of visceral leishmaniasis by SSG-NIV treatment in the BALB/c mouse did not protect against reinfection.

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Single-dose treatment shows effectiveness for Indian visceral leishmaniasis

The Lancet ◽

10.1016/s0140-6736(05)74529-3 ◽

2000 ◽

Vol 356 (9235) ◽

pp. 1086 ◽

Cited By ~ 3

Author(s):

Angela Pirisi

Keyword(s):

Single Dose ◽

Visceral Leishmaniasis ◽

Dose Treatment ◽

Single Dose Treatment

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Comparison of the efficacies of various formulations of amphotericin B against murine visceral leishmaniasis.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.10.2089 ◽

1997 ◽

Vol 41 (10) ◽

pp. 2089-2092 ◽

Cited By ~ 62

Author(s):

A B Mullen ◽

K C Carter ◽

A J Baillie

Keyword(s):

Bone Marrow ◽

Body Weight ◽

Visceral Leishmaniasis ◽

Amphotericin B ◽

Murine Model ◽

Leishmania Donovani ◽

Significant Suppression ◽

Dosing Regimen ◽

Multiple Dosing ◽

Lipid Complex

The antileishmanial efficacies of four proprietary amphotericin B (AmB) formulations (Fungizone, AmBisome, Abelcet, and Amphocil) and an experimental nonionic surfactant vesicle (NIV) formulation were compared in a murine model of acute visceral leishmaniasis. By a multiple-dosing regimen, groups of Leishmania donovani-infected BALB/c mice were treated (2.5 mg of AmB per kg of body weight) on days 7 to 11 postinfection with one of the AmB formulations, and parasite burdens were determined on day 18 postinfection. All of the formulations caused significant suppression parasite burdens in spleens (P < 0.01 to 0.0005) and livers (P < 0.0005) compared with those in the spleens and livers of the controls. In addition, a significant suppression of parasite burdens in bone marrow (P < 0.0005) compared to the burdens in the bone marrow of the controls was obtained for all the formulations except Abelcet, which was inactive at this site. On the basis of their overall efficacies (activity against liver, spleen, and bone marrow parasites), the formulations could be ranked as follows: Amphocil = AmBisome > AmB-NIV > Abelcet > Fungizone. On the basis of spectrophotometric measurements, AmB was shown to exist in a predominantly aggregated state in all of the formulations. Although incubation in 50% serum altered the degree of aggregation, the AmB remained predominantly aggregated, indicating that the AMB-lipid complex in all of the formulations was physically stable. The results of the study showed that antiparasitic efficacy is associated positively with the degree of AmB aggregation in the presence of serum.

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