A new immunochemotherapy schedule for visceral leishmaniasis in a hamster model

Santana, Fabiana; Silva, Danielle Aparecida Marino da; Katz, Simone; Orikaza, Cristina Mary; Oliveira, Kátia C.; Barbiéri, Clara Lúcia

doi:10.1007/s00436-022-07628-y

Cited by 4 publications

(2 citation statements)

References 75 publications

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“…To determine whether the relapses were due to drug resistance, we evaluated the in vitro susceptibility of both the promastigote and amastigote forms of the parasite to various antileishmanial drugs, SbV, AmB deoxycholate, and MF, to which the patient had previously been exposed, and PEN and PM, two drugs that the patient had not been previously exposed to. The EC 50 values for all drugs were determined in parallel with the LD strain that was originally isolated from a patient with VL in the Amazon region, and which has been used as a laboratory strain for several years [ 24 , 25 ]. This strain is considered to be susceptible to all these drugs.…”

Section: Resultsmentioning

confidence: 99%

In Vitro Drug Susceptibility of a Leishmania (Leishmania) infantum Isolate from a Visceral Leishmaniasis Pediatric Patient after Multiple Relapses

et al. 2023

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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.

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Section: Resultsmentioning

confidence: 99%

In Vitro Drug Susceptibility of a Leishmania (Leishmania) infantum Isolate from a Visceral Leishmaniasis Pediatric Patient after Multiple Relapses

et al. 2023

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“…Miltefosine in combination with L. braziliensis antigens, saponin, and monophosphoryl lipid-A enhances CD4+ T cells in splenocytes producing IFN-γ and TNF-α and a reduction of IL-10 and anti-Leishmania circulating IgG in hamsters ( 76 ). A combination of miltefosine and recombinant cysteine proteinase from Leishmania , rldccys1, significantly reduced the parasite load in infected hamsters ( 77 ). Notably, IL-2 reduced L. donovani parasite burdens by 50% while IL-12 treatment reduced parasitic burdens by 47% and IFN-γ decreased them by 40%.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy and immunochemotherapy in combating visceral leishmaniasis

et al. 2023

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Visceral leishmaniasis (VL), a vector-borne disease, is caused by an obligate intramacrophage, kinetoplastid protozoan parasite of the genus Leishmania. Globally, VL is construed of diversity and complexity concerned with high fatality in tropics, subtropics, and Mediterranean regions with ~50,000–90,000 new cases annually. Factors such as the unavailability of licensed vaccine(s), insubstantial measures to control vectors, and unrestrained surge of drug-resistant parasites and HIV-VL co-infections lead to difficulty in VL treatment and control. Furthermore, VL treatment, which encompasses several problems including limited efficacy, emanation of drug-resistant parasites, exorbitant therapy, and exigency of hospitalization until the completion of treatment, further exacerbates disease severity. Therefore, there is an urgent need for the development of safe and efficacious therapies to control and eliminate this devastating disease. In such a scenario, biotherapy/immunotherapy against VL can become an alternative strategy with limited side effects and no or nominal chance of drug resistance. An extensive understanding of pathogenesis and immunological events that ensue during VL infection is vital for the development of immunotherapeutic strategies against VL. Immunotherapy alone or in combination with standard anti-leishmanial chemotherapeutic agents (immunochemotherapy) has shown better therapeutic outcomes in preclinical studies. This review extensively addresses VL treatment with an emphasis on immunotherapy or immunochemotherapeutic strategies to improve therapeutic outcomes as an alternative to conventional chemotherapy.

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The Nexus between Leishmania & HIV: Debilitating Host Immunity and Hastening Comorbid Disease Burden

Dhulipalla,

Chouhan

2024

Experimental Parasitology

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A new immunochemotherapy schedule for visceral leishmaniasis in a hamster model

Cited by 4 publications

References 75 publications

In Vitro Drug Susceptibility of a Leishmania (Leishmania) infantum Isolate from a Visceral Leishmaniasis Pediatric Patient after Multiple Relapses

In Vitro Drug Susceptibility of a Leishmania (Leishmania) infantum Isolate from a Visceral Leishmaniasis Pediatric Patient after Multiple Relapses

Immunotherapy and immunochemotherapy in combating visceral leishmaniasis

The Nexus between Leishmania & HIV: Debilitating Host Immunity and Hastening Comorbid Disease Burden

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