Paromomycin is an aminoglycoside antibiotic approved in 2006 for the treatment of visceral leishmaniasis caused by Leishmania donovani in Southeast Asia. Although this drug is not approved for the treatment of visceral and cutaneous leishmaniasis in Brazil, it is urgent and necessary to evaluate the potential of this drug as alternative for the treatment against species responsible for these clinical forms of the disease. In Brazil, Leishmania amazonensis is responsible for cutaneous and diffuse cutaneous leishmaniasis. The diffuse cutaneous form of the disease is difficult to treat and frequent relapses are reported, mainly when the treatment is interrupted. Here, we evaluated paromomycin susceptibility in vitro of a L. amazonensis clinical isolate from a patient with cutaneous leishmaniasis and the reference strain L. amazonensis M2269, as well as its in vivo efficacy in a murine experimental model . Although never exposed to paromomycin, a significant differential susceptibility between these two lines was found. Paromomycin was highly active in vitro against the clinical isolate in both forms of the parasite, while its activity against the reference strain was less active. In vivo studies in mice infected with each one of these lines demonstrated that paromomycin reduces lesion size and parasite burden and a direct correlation between the susceptibility in vitro and the effectiveness of this drug in vivo was found. Our findings indicate that paromomycin efficacy in vivo is dependent on intrinsic susceptibility of the parasite. Beyond that, this study contributes for the evaluation of the potential use of paromomycin in chemotherapy of cutaneous leishmaniasis in Brazil caused by L. amazonensis .

No abstract

No abstract

No abstract

Visceral leishmaniasis (VL) is a parasitic disease caused by the protozoan Leishmania (L.) infantum. In Brazil, the number of cases of the disease has increased in the last years. The treatment of leishmaniasis in Brazil consists of the use of pentavalent antimonials and amphotericin B. Recently, miltefosine has been shown to be highly effective against VL in Asia. Although, this drug is not used in the treatment of VL in Brazil, miltefosine is approved for use in the treatment of canine visceral leishmaniasis (CVL). In this study, we evaluate the susceptibility to miltefosine in vitro of isolates of L. (L.) infantum from dogs of municipality of Embu-Guaçu, located in the metropolitan region of the city of São Paulo.

The parasitic protozoan Leishmania (Leishmania) infantum is the etiological agent of human visceral leishmaniasis in South America, an infectious disease associated with malnutrition, anemia, and hepatosplenomegaly. In Brazil alone, around 2700 cases are reported each year. Treatment failure can occur as a result of drug, host, and/or parasite-related factors. Here, we isolated a Leishmania species from a pediatric patient with visceral leishmaniasis that did not respond to chemotherapy, experiencing a total of nine therapeutic relapses and undergoing a splenectomy. The parasite was confirmed as L. (L.) infantum after sequencing of the ribosomal DNA internal transcribed spacer, and the clinical isolate, in both promastigote and amastigote forms, was submitted to in vitro susceptibility assays with all the drugs currently used in the chemotherapy of leishmaniasis. The isolate was susceptible to meglumine antimoniate, amphotericin B, pentamidine, miltefosine, and paromomycin, similarly to another strain of this species that had previously been characterized. These findings indicate that the multiples relapses observed in this pediatric patient were not due to a decrease in the drug susceptibility of this isolate; therefore, immunophysiological aspects of the patient should be further investigated to understand the basis of treatment failure in this case.

No abstract

Visceral leishmaniasis (VL) is a parasitic disease caused by the protozoan L. (L.) infantum. The treatment of leishmaniasis in Brazil consists of the use of pentavalent antimonials and amphotericin B. Recently, miltefosine (MF) has been shown to be highly effective against VL in Asia. Although, this drug is not used in the treatment of VL in Brazil, MF is approved for use in the treatment of canine visceral leishmaniasis (CVL). In this study, we evaluate the susceptibility to MF in vitro of isolates of L. (L.) infantum from dogs of municipality of Embu-Guaçu, São Paulo.