| Autor: |
Ferreira, Bianca A., Coser, Elizabeth M., de la Roca, Stephane, Aoki, Juliana I., Branco, Nilson, Soares, Gustavo H. C., Lima, Mayara I. S., Coelho, Adriano C. |
| Předmět: |
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| Zdroj: |
PLoS Neglected Tropical Diseases; 5/20/2024, Vol. 18 Issue 5, p1-18, 18p |
| Abstrakt: |
In Brazil, Leishmania amazonensis is the etiological agent of cutaneous and diffuse cutaneous leishmaniasis. The state of Maranhão in the Northeast of Brazil is prevalent for these clinical forms of the disease and also has high rates of HIV infection. Here, we characterized the drug susceptibility of a L. amazonensis clinical isolate from a 46-year-old man with diffuse cutaneous leishmaniasis coinfected with HIV from this endemic area. This patient underwent several therapeutic regimens with meglumine antimoniate, liposomal amphotericin B, and pentamidine, without success. In vitro susceptibility assays against promastigotes and intracellular amastigotes demonstrated that this isolate had low susceptibility to amphotericin B, when compared with the reference strain of this species that is considered susceptible to antileishmanial drugs. Additionally, we investigated whether the low in vitro susceptibility would affect the in vivo response to amphotericin B treatment. The drug was effective in reducing the lesion size and parasite burden in mice infected with the reference strain, whereas those infected with the clinical isolate and a resistant line (generated experimentally by stepwise selection) were refractory to amphotericin B treatment. To evaluate whether the isolate was intrinsically resistant to amphotericin B in animals, infected mice were treated with other drugs that had not been used in the treatment of the patient (miltefosine, paromomycin, and a combination of both). Our findings demonstrated that all drug schemes were able to reduce lesion size and parasite burden in animals infected with the clinical isolate, confirming the amphotericin B-resistance phenotype. These findings indicate that the treatment failure observed in the patient may be associated with amphotericin B resistance, and demonstrate the potential emergence of amphotericin B-resistant L. amazonensis isolates in an area of Brazil endemic for cutaneous leishmaniasis. Author summary: The parasitic protozoan Leishmania amazonensis is the etiological agent responsible for cutaneous and diffuse cutaneous leishmaniasis. The latter is characterized by nodular lesions that spread over the body of the infected individual and is associated with a CD4/Th2 type immune response to the infection. Treatment failure is commonly reported for this clinical form of disease. Here, we characterized a L. amazonensis clinical isolate obtained from a patient with diffuse cutaneous leishmaniasis coinfected with HIV who had undergone unsuccessful therapeutic regimens with meglumine antimoniate, liposomal amphotericin B, and pentamidine. To evaluate whether the treatment failure was due to drug resistance in this clinical isolate, in vitro susceptibility assays were performed with the antileishmanial drugs currently available, followed by an investigation of treatment response in mice. In vivo studies demonstrated that mice infected with this clinical isolate did not respond to treatment with amphotericin B, but did respond to treatment with miltefosine, paromomycin, and a combination of both drugs, confirming an amphotericin B resistance phenotype of the isolate that was also observed in vitro. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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