Treatment Of Tegumentary Leishmaniasis Research Articles

Susceptibility to paromomycin in clinical isolates and reference strains of Leishmania species responsible for tegumentary leishmaniasis in Brazil

Treatment of tegumentary leishmaniasis in Brazil is limited to pentavalent antimonial, amphotericin B and pentamidine. These drugs, administered parenterally, cause several side effects and have a varied clinical response, depending on the species of Leishmania. Urgent expansion of the therapeutic arsenal against the disease is therefore necessary. Paromomycin is an aminoglycoside antibiotic that has already been approved for the treatment of visceral leishmaniasis in Southeast Asia. Here, we provide an in vitro evaluation of the activity of paromomycin in fifteen clinical isolates from patients with tegumentary leishmaniasis at a reference center for the treatment of the disease. Furthermore, the in vitro susceptibility to this drug in reference strains of Leishmania species that are endemic in Brazil has also been evaluated. Among the clinical isolates, nine were typed as Leishmania (Viannia) braziliensis, five as L. (Leishmania) amazonensis and one as L. (V.) guyanensis. Although never exposed to paromomycin, we found variable susceptibility among these isolates and reference strains in promastigotes and intracellular amastigotes, with the drug being more active in the amastigote form of the parasite. This study provides a preclinical dataset that is useful for the evaluation of paromomycin in the treatment of tegumentary leishmaniasis caused by species that are endemic in Brazil.

Poloxamer 407 (Pluronic® F127)-based polymeric micelles for amphotericin B: In vitro biological activity, toxicity and in vivo therapeutic efficacy against murine tegumentary leishmaniasis

In the present study, a Poloxamer 407-based amphotericin B (AmpB)-containing polymeric micelles system (AmpB/M) was employed in the treatment of Leishmania amazonensis-infected BALB/c mice. Initially, the in vitro antileishmanial activity (IC50 value) of AmpB/M and B-AmpB/M (empty micelles) against stationary promastigotes and amastigotes-like forms of the parasites was determined, and results were of 1.83 ± 0.4 and 22.1 ± 0.7 μM, respectively, for the promastigotes, and of 2.27 ± 0.5 and 33.98 ± 2.6 μM, respectively, for the amastigotes-like. The cytotoxic concentration (CC50) values of these products were also evaluated, and we found the results of 119.5 ± 9.6 and 134.7 ± 10.3 μM, respectively. With these values, the selectivity index (SI) was calculated and results were of 65.3 and 5.4, respectively, for the promastigotes, and of 59.3 and 3.96, respectively, for the amastigotes-like of the parasites. Free AmpB showed IC50 values of 1.2 ± 0.3 and 2.5 ± 0.5 μM for the promastigotes and amastigotes-like, respectively, whereas the CC50 value was of 9.5 ± 0.4 μM. The SI values of this drug were of 7.9 and 3.8, respectively, for the promastigote and amastigote-like stages of the parasites. After, animals were infected and received saline or were treated subcutaneously with free AmpB, AmpB/M or B-AmpB/M. In the results, free AmpB-treated and infected mice showed reductions in their body weight, which were associated with hepatic and renal damage; however, no organic alteration was observed in the AmpB/M-treated animals. In addition, these animals showed significant reductions in their lesion average size and in the parasite burden in all evaluated infected tissue and organs, when compared to the other groups; as well as significantly higher levels of antileishmanial IFN-γ, IL-12, GM-CSF and nitrite, which were associated with low production of IL-4, IL-10 and IgG1 isotype antibodies. In conclusion, this AmpB/M system could be considered as an alternative for future studies in the treatment of tegumentary leishmaniasis.

Varicella zoster virus reactivation during or immediately following treatment of tegumentary leishmaniasis with antimony compounds.

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.

Effect of imidocarb and levamisole on the experimental infection of BALB/c mice by Leishmania ( Leishmania) amazonensis

The adverse effects from using currently available drugs for the treatment of leishmaniasis have motivated the search for new therapeutical agents. The aim of this work was to evaluate the effect of imidocarb and levamisole on the treatment of BALB/c mice experimentally infected by Leishmania ( Leishmania) amazonensis. BALB/c mice were infected with 10 6 promastigotes of L. ( L.) amazonensis (IFLA/BR/67/PH8) and, starting on day 51, mice were treated subcutaneously with imidocarb (IMD, 34 mg/kg), imidocarb plus levamisole (IMD + LVS, 34 and 12 mg/kg, respectively), only levamisole (LVS, 12 mg/kg) or without treatment (control). Lesion size and swelling were weekly monitored for 10 weeks after the beginning of the treatment. On day 121 post-infection, serum levels of specific IgG from infected mice were evaluated, as well as histopathological and morphometric alterations in the footpad, lymph nodes and spleen of these animals. The data obtained in this study demonstrated that, when compared to controls, mice treated with IMD had lower levels of IgG anti- L. ( L.) amazonensis (34.45%), smaller vacuolar area in macrophages (3.75%), lower number of megakaryocytes in spleen (63.19%) and lower parasite burden in the footpad (30.2%). Thus, the evaluated parameters suggest the use of imidocarb as a potential drug in the treatment of tegumentary leishmaniasis.