Long-term follow-up of patients with Leishmania (Viannia) braziliensis infection and treated with Glucantime®

Netto, Eduardo Martins; Marsden, Philip D.; Llanos-Cuentas, Alejandro; Costa, Jackson Maurício Lopes; Cuba, César Augusto Cuba; Barreto, A. C.; Badaró, Roberto; Johnson, Warren D.; Jones, Thomas C.

doi:10.1016/0035-9203(90)90321-5

Cited by 58 publications

(33 citation statements)

References 9 publications

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“…We then asked whether viral infection could lead to reactivation of leishmaniasis following healing, a pathological situation often observed in humans (45). LCMV injection subsequent to lesion healing induced reactivation of the disease, with a reappearance of both lesion pathology and increased parasite numbers, overriding the protective adaptive immune response essential in C57BL/6 mice reinfected with Lgy (Fig.…”

Section: Viral Coinfection Modulates Macrophage Responsiveness To Ifn-γmentioning

confidence: 99%

Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis

Rossi

Castiglioni

Hartley

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

103

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The presence of the endogenous Leishmania RNA virus 1 (LRV1) replicating stably within some parasite species has been associated with the development of more severe forms of leishmaniasis and relapses after drug treatment in humans. Here, we show that the disease-exacerbatory role of LRV1 relies on type I IFN (type I IFNs) production by macrophages and signaling in vivo. Moreover, infecting mice with the LRV1-cured Leishmania guyanensis (LgyLRV1 − ) strain of parasites followed by type I IFN treatment increased lesion size and parasite burden, quantitatively reproducing the LRV1-bearing (LgyLRV1 + ) infection phenotype. This finding suggested the possibility that exogenous viral infections could likewise increase pathogenicity, which was tested by coinfecting mice with L. guyanensis and lymphocytic choriomeningitis virus (LCMV), or the sand fly-transmitted arbovirus Toscana virus (TOSV). The type I IFN antiviral response increased the pathology of L. guyanensis infection, accompanied by down-regulation of the IFN-γ receptor normally required for antileishmanial control. Further, LCMV coinfection of IFN-γ-deficient mice promoted parasite dissemination to secondary sites, reproducing the LgyLRV1 + metastatic phenotype. Remarkably, LCMV coinfection of mice that had healed from L. guyanensis infection induced reactivation of disease pathology, overriding the protective adaptive immune response. Our findings establish that type I IFN-dependent responses, arising from endogenous viral elements (dsRNA/LRV1), or exogenous coinfection with IFN-inducing viruses, are able to synergize with New World Leishmania parasites in both primary and relapse infections. Thus, viral infections likely represent a significant risk factor along with parasite and host factors, thereby contributing to the pathological spectrum of human leishmaniasis.Leishmania RNA virus 1 | Totiviridae | arboviruses | trypanosomatid protozoan parasite | Leishmania subgenus Viannia

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Section: Viral Coinfection Modulates Macrophage Responsiveness To Ifn-γmentioning

confidence: 99%

Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis

Rossi

Castiglioni

Hartley

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

103

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“…Current problems however are (i) the fact that, although insecticides are quite useful in controlling phlebotomine sand flies in the domestic environment, sustained vector control utilizing large scale insecticide spraying in developing countries is costly and not feasible (Dye 1996); (ii) Leishmania spp. readily acquires resistance to antimonial drugs (Jackson et al 1990, Grogl et al 1992; and (iii) response to treatment varies considerable, probably depending on the parasite species involved and the clinical form or stage of the disease (Marsden 1985, Netto et al 1990, Navin et al 1992.…”

Section: Epidemiological and Clinical Features Of Leishmania (Vianniamentioning

confidence: 99%

Epidemiological and clinical features of Leishmania (Viannia) braziliensis American cutaneous and mucocutaneous leishmaniasis in the State of Espírito Santo, Brazil

Falqueto¹,

Sessa²,

Ferreira³

et al. 2003

Mem. Inst. Oswaldo Cruz

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“…2 However, clinical failure-defined as presence of ulcer or granulomatous lesionoccurs in up to 42% of patients, 3 and relapses have been documented in as many as 19% of patients after 3-10 years of follow-up. 4 The paucity of parasites in the mucosal destructive lesion highlights the current poor understanding of the pathogenesis of mucosal leishmaniasis. Mononuclear cells from patients with mucosal disease recognize Leishmania antigens by proliferation and secretion of Th1 cytokines.…”

Section: Introductionmentioning

confidence: 99%

Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony.

Lessa¹,

Machado²,

Lima³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

159

128

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Abstract. Mucosal leishmaniasis is characterized by an intense inflammatory reaction and tissue damage with few parasites in the lesion. On the basis of previous observations that suggest a possible role of tumor necrosis factor alpha (TNF-␣) in the pathology of this disease, an open-label study was performed to evaluate the efficacy of the treatment with an inhibitor of TNF-␣ (pentoxifylline) associated to antimony therapy in 10 patients with refractory mucosal leishmaniasis. Patients were treated with pentavalent antimony (20 mg per kilogram of body weight per day) plus orally administered pentoxifylline 400 mg 3 times daily for 30 days. Nine of 10 patients fulfilled the criteria for cure: they experienced complete reepithelization of the mucosal tissue 90 days after therapy and displayed no evidence of relapse at 1 year of follow-up. The TNF-␣ levels before therapy (776 Ϯ 342 pg/mL) fell to 94 Ϯ 57 pg/mL (P Ͻ 0.05) within 60 days after therapy. Our results indicate that pentoxifylline plus antimony therapy should be considered in all patients with mucosal leishmaniasis that is refractory to treatment.

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Long-term follow-up of patients with Leishmania (Viannia) braziliensis infection and treated with Glucantime®

Cited by 58 publications

References 9 publications

Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis

Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis

Epidemiological and clinical features of Leishmania (Viannia) braziliensis American cutaneous and mucocutaneous leishmaniasis in the State of Espírito Santo, Brazil

Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony.

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