Immunochemotherapy in American cutaneous leishmaniasis: immunological aspects before and after treatment

Toledo, Vicente de Paulo Coelho Peixoto de; Mayrink, Wilson; Gollob, Kenneth J.; Oliveira, Milton Adriano Pelli de; Costa, Carlos Alberto da; Genaro, Odair; Pinto, Jorge; Afonso, Luís

doi:10.1590/s0074-02762001000100010

Cited by 50 publications

(64 citation statements)

References 41 publications

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“…CD4 + Leishmania reactive T-cells where preferentially expanded in all asymptomatic individuals confirming our previous results of higher CD4 + /CD8 + proportions associated with long term immunity in clinically CCL patients (Da-Cruz et al 2002). Also it has been hypothesized that CD8 + T cells expanded soon after the end of therapy (Da-Cruz et al 1994, Toledo et al 2001 could play a crucial role for the early control of the infection (Belkaid et al 2002). After exerting their effector functions (cytotoxic or IFN-γ production) (Brodskyn et al 1997) only part of these CD8 + T-cells should be maintained in a pool of central memory cells (Tanchot et al 1997, Wherry et al 2003, Rocha & Tanchot 2004).…”

Section: Discussionsupporting

confidence: 88%

“…However, the establishment of cellular mediated immune (CMI) responses, especially regulation of cytokine network involved in anti-leishmanial immunity, is likely to be associated with clinical outcome (Coutinho et al 1996, Rocha et al 1999, Toledo et al 2001). According to our results, the profiles of these CMI responses detected in subjects resistant to or recovered from leishmaniasis may provide a better understanding of the long-lived immune protection to the disease.…”

Section: Discussionmentioning

confidence: 99%

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T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis

Bittar

Nogueira

Vieira-Gonçalves

et al. 2007

Mem. Inst. Oswaldo Cruz

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Subclinical or asymptomatic infection is documented in individuals living in endemic areas for leishmaniasis suggesting that the development of an appropriate immune response can control parasite replication and maintain tissue integrity. A low morbidity indicates that intrinsic factors could favor resistance to Leishmania infection. Herein, leishmanial T-cell responses induced in subjects with low susceptibility to leishmaniasis as asymptomatic subjects were compared to those observed in cured cutaneous leishmaniasis (CCL) patients, who controlled the disease after antimonial therapy. All of them have shown maintenance of specific long-term immune responses characterized by expansion of higher proportions of CD4 + as compared to CD8 + Leishmania reactive T-lymphocytes. Asymptomatic subjects had lower indexes of in vitro Leishmania induced lymphoproliferative responses and interferon-gamma (IFN-γ) production in comparison to CCL patients. On the other hand, interleukin (IL-10) production was much higher in asymptomatics than in CCL, while no differences in IL-5 levels were found. In conclusion, long lived T-cell responses achieved by asymptomatic individuals differed from those who had developed symptomatic leishmaniasis in terms of intensity of lymphocyte activation (proliferation or IFN-γ) and regulatory mechanisms (IL-10). The absence of the disease in asymptomatics could be explained by their intrinsic ability to create a balance between immunoregulatory (IL-10) and effector cytokines (IFN-γ), leading to parasite destruction without producing skin tissue damage. The establishment of profiles of cell-mediated immune responses associated with resistance against Leishmania infection is likely to make new inroads into understanding the long-lived immune protection against the disease.Key words: asymptomatic infection -Leishmania (Viannia) braziliensis -cured leishmaniasis -cytokines -T-cell subsetslong term immunity (Grimaldi Jr & MacMahon-Pratt 1991). The spectrum of the clinical presentation ranges from self-healing or benign cutaneous lesions to more severe forms, such as disseminated lesions or mucosal involvement (Da-Cruz & Pirmez 2005).Studies conducted in mice and humans have unequivocally shown that a major T-cell driven component underlies the establishment of acquired immunity and protection against re-infection ( Coutinho et al. 1996, Louis et al. 1998, Bosque et al. 2000. Cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factoralpha (TNF-α) activate macrophages for killing parasites, while interleukin (IL)-4, IL-5, IL-10, and transforming grow factor-beta (TGF-β) favor intracellular parasite growth (Louis et al. 1998. In addition, IL-10 production by CD4 + CD25 + T-cells is required for maintenance of Leishmania after cure, which in turn preserves an adaptive immunity to L. (Leishmania) major (Belkaid et al. 2002).The majority of ATL patients develop cutaneous leishmaniasis (CL) (Oliveira-Neto et al. 2000), but occurrence of subclinical or asymptomatic infection strongly suggests that po...

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis

Bittar

Nogueira

Vieira-Gonçalves

et al. 2007

Mem. Inst. Oswaldo Cruz

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“…This vaccine has been used in the prevention of disease, as well as serving as an immunotherapeutic agent, thereby demonstrating that administration of the vaccine in association with antimonium salts could be therapeutic. Indeed, when compared with conventional therapy, L. amazonensis vaccine treatment reduced the time necessary for lesions in patients with cutaneous leishmaniasis to completely heal (Toledo et al 2001). Furthermore, Mayrink et al (2006) have shown that the association of a vaccine antigen with antimonium salts reduces both the total salt volume and the treatment length, thereby reducing the side effects otherwise associated with the use of antimonium salts.…”

Section: Discussionmentioning

confidence: 99%

Antigenic extracts of Leishmania braziliensis and Leishmania amazonensis associated with saponin partially protects BALB/c mice against Leishmania chagasi infection by suppressing IL-10 and IL-4 production

Grenfell

Silva

Testasicca

et al. 2010

Mem. Inst. Oswaldo Cruz

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This study evaluated two vaccine candidates for their effectiveness in protecting BALB/c mice against Leishmania chagasiinfection. These immunogenic preparations were composed of Leishmania amazonensisor Leishmania braziliensisantigenic extracts in association with saponin adjuvant. Mice were given three subcutaneous doses of one of these vaccine candidates weekly for three weeks and four weeks later challenged with promastigotes of L. chagasiby intravenous injection. We observed that both vaccine candidates induced a significant reduction in the parasite load of the liver, while the L. amazonensisantigenic extract also stimulated a reduction in spleen parasite load. This protection was associated with a suppression of both interleukin (IL)-10 and IL-4 cytokines by spleen cells in response to L. chagasiantigen. No change was detected in the production of IFN-γ. Our data show that these immunogenic preparations reduce the type 2 immune response leading to the control of parasite replication

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“…Immunochemotherapy (vaccine with antileishmanial drugs) is maybe an alternative treatment for those patients for whom SbV compounds are not indicated, clinical trial guidelines are being generate 7,11,16,28 .…”

Section: Discussionmentioning

confidence: 99%

“…This complex provides substantial benefits to the patient, including the reduction of outpatient visits, and ambulatory expenses, over standard therapy 7,11,28 .…”

mentioning

confidence: 99%

Two cases of visceral leishmaniasis in Colombia resistant to meglumine antimonial treatment

Vélez

Colmenares

Muñoz

2009

Rev. Inst. Med. trop. S. Paulo

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SUMMARYVisceral leishmaniasis (VL) affects over 500 000 people worldwide each year. The disease occurs in the Mediterranean basin, Central and South America and is caused by Leishmania infantum (syn L. chagasi). VL is an endemic disease in Colombia, particularly along the Caribbean coast and the Magdalena River Valley and 90% of VL cases occur in children under the age of five. The first line of treatment is chemotherapy with pentavalent antimonial compounds, including sodium stibogluconate (Pentostam®) and meglumine antimoniate (Glucantime®). These compounds are the ones most used in Colombia, at a dose of 20 mg/kg/day for 28 days. Nevertheless resistance of L. infantum to pentavalent antimonials is becoming an important problem.No cases of VL resistant to pentavalent antimonial compounds have previously been reported from Colombia. This report describes the two cases of VL resistance to antimonial compounds in a girl and a boy who did not respond to previous treatment with Pentacarinat® and Glucantime® regimens but were treated successfully with liposomal amphotericin B. Based on our findings, we recommend liposomal amphotericin B as the first line of treatment for VL due to its low toxicity, shorter administration period and the low price obtained by WHO.

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Immunochemotherapy in American cutaneous leishmaniasis: immunological aspects before and after treatment

Cited by 50 publications

References 41 publications

T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis

T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis

Antigenic extracts of Leishmania braziliensis and Leishmania amazonensis associated with saponin partially protects BALB/c mice against Leishmania chagasi infection by suppressing IL-10 and IL-4 production

Two cases of visceral leishmaniasis in Colombia resistant to meglumine antimonial treatment

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