Addressing a clinical challenge: guidelines for the diagnosis and treatment of leishmaniasis

Aronson, Naomi

doi:10.1186/s12916-017-0843-3

Cited by 19 publications

(16 citation statements)

References 13 publications

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“…Collectively, the therapies available for kinetoplastid diseases are inadequate, lack efficacy and possess extensive toxicity. Additionally, there is evidence of emerging or potential resistance in leishmaniasis [ 15 ], HAT [ 16 ], Chagas disease [ 17 ] and access to the drugs in remote areas is limited [ 18 , 19 , 20 ]. Despite the new drug leads currently in clinical trials for leishmaniasis [ 21 , 22 , 23 ], HAT [ 24 , 25 , 26 ] and Chagas disease [ 27 ], there exists a high attrition rate [ 28 , 29 ] and new molecules with novel mechanisms of action are required.…”

Section: Introductionmentioning

confidence: 99%

Screening a Natural Product-Based Library against Kinetoplastid Parasites

et al. 2017

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Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some of the world’s lowest socioeconomic communities. Current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the need to identify new treatments. In this study, the Davis open access natural product-based library was screened against kinetoplastids (Leishmania donovani DD8, Trypanosoma brucei brucei and Trypanosoma cruzi) using phenotypic assays. The aim of this study was to identify hit compounds, with a focus on improved efficacy, selectivity and potential to target several kinetoplastid parasites. The IC50 values of the natural products were obtained for L. donovani DD8, T. b. brucei and T. cruzi in addition to cytotoxicity against the mammalian cell lines, HEK-293, 3T3 and THP-1 cell lines were determined to ascertain parasite selectivity. Thirty-one compounds were identified with IC50 values of ≤10 µM against the kinetoplastid parasites tested. Lissoclinotoxin E (1) was the only compound identified with activity across all three investigated parasites, exhibiting IC50 values <5 µM. In this study, natural products with the potential to be new chemical starting points for drug discovery efforts for kinetoplastid diseases were identified.

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Section: Introductionmentioning

confidence: 99%

Screening a Natural Product-Based Library against Kinetoplastid Parasites

et al. 2017

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“…Among these, topical formulations could be a rational approach for the cure of patients with few, localized or non-complicated lesions caused by Leishmania spp. from the Old and New World [ 21 , 22 ]. In this study, we investigated a potential topical use of MF29, a drug derived from 3-haloacetmidobenzoic acid.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a New Topical Treatment for the Control of Cutaneous Leishmaniasis

et al. 2020

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Leishmania major (L. major) causes cutaneous leishmaniasis in the Old World. The infection mostly induces a localized lesion restricted to the sand fly bite. The costs and the side effects of current treatments render imperative the development of new therapies that are affordable and easy to administrate. Topical treatment would be the ideal option for the treatment of cutaneous leishmaniasis. MF29 is a 3-haloacetamidobenzoate that was shown in vitro to inhibit tubulin assembly in Leishmania. Here, we tested a topical cream formulated with MF29. BALB/c mice were infected in the ear dermis with L. major metacyclic promastigotes and once the lesion appeared, mice were treated with different concentrations of MF29 and compared to the control group treated with the cream used as the vehicle. We observed that topical application of MF29 reduced the progression of the infection while control groups developed an unhealing lesion that became necrotic. The treatment decreased the type 2 immune response. Comparison with SinaAmphoLeish, another topical treatment, revealed that MF29 treatment once a day was sufficient to control lesion development, while application SinaAmphoLeish needed applications twice daily. Collectively, our data suggest that MF-29 topical application could be a promising topical treatment for cutaneous leishmaniasis.

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“…The lack of an effective vaccine or drugs to prevent infection emphasizes that prevention is crucial to break the global rise of leishmaniasis 26,27 . Measures to prevent sand fly bites are advised for immunocompromised patients travelling to endemic areas 1,28 .…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, IBD is more common in the industrialized world, particularly Western Europe and North America 30 . Incidence of VL is currently on the rise in nonendemic regions due to increased international travel and migration 27 . In our case travel history to Mediterranean endemic regions supported suspicion of VL.…”

Section: Discussionmentioning

confidence: 99%

Visceral leishmaniasis in a patient with ulcerative colitis: A case report

et al. 2020

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Introduction.There is a rise of visceral leishmaniasis in immunocompromised patients due to increased availability of immunomodulatory drugs. In order to point at the occurrence of visceral leishmaniasis in patients with inflammatory bowel disease (IBD), we reported a case of female patient with a travel history to European Mediterranean countries, who was on immunosuppressive treatment due to ulcerative colitis. Case report. A 29-year-old female patient was admitted to hospital due to severe relapse of ulcerative colitis. Corticosteroid therapy was administered in addition to previous longterm azathioprine, with clinical response to the treatment. During the course of the disease she had recurrent high-grade fever with marked hepatosplenomegaly and pancytopenia. The diagnosis of leishmaniasis was established by positive serology tests and microscopic finding of amastigotes in bone marrow smears. The disseminated infection was responsive to treatment with liposomal amphotericin B, but therapy had to be discontinued due to urticarial rush. Subsequent therapy with antimony was administered, but it had to be stopped too due to liver toxicity. No further treatment for leishmaniasis was initiated as the clinical and laboratory data suggested that the patient had responded to the treatment. She was discharged from hospital in IBD remission and without signs of the infection. Conclusion. Visceral leishmaniasis should be considered in IBD patients with fever of unknown origin and relevant travel history in order to achieve favorable disease outcome.Uvod. Visceralna lajšmanioza je u porastu kod imunokompromitovanih bolesnika zbog povećane dostupnosti imunomodulatornih lekova. Da bi ukazali na mogućnost postojanja visceralne lajšmanioze kod bolesnika sa zapaljenskom bolesti creva, prikazali smo bolesnicu sa ulceroznim kolitisom lečenu imunosupresivnom terapijom, koja je prethodno boravila u evropskim, mediteranskim zemljama. Prikaz bolesnika. Bolesnica, starosti 29 godina, primljena je u bolnicu sa teškim relapsom ulceroznog kolitisa. Pored dugogodišnje terapije azatioprinom primenjeno je i lečenje kortikosteroidima na koje je dobijen klinički odgovor. U toku lečenja bolesnica je bila visokofebrilna sa izraženom hepatosplenomegalijom i pancitopenijom. Dijagnoza lajšmanioze postavljena je serološkim testovima i mikroskopskim nalazom amastigota u sternalnom punktatu. Na terapiju lipozomalnim amfotericinom B dobijen je povoljan odgovor, ali je lečenje moralo biti prekinuto zbog generalizovane urtikarije. Potom je primenjeno lečenje preparatom petovalentnog antimona, ali je i ono moralo biti prekinuto zbog hepatotoksičnosti. S obzirom na to da je kod bolesnice već dobijen terapijski odgovor, dalje lečenje lajšmanioze nije primenjivano. Na otpustu iz bolnice ulcerozni kolitis je bio u remisiji i nije bilo znakova lajšmanioze. Zaključak. Kod bolesnika sa zapaljenjskom bolesti creva i febrilnošću nejasnog uzroka, koji su prethodno putovali u endemske krajeve, treba razmotriti i postojanje visceralne lajšmanioze u cilju postizanja...

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Addressing a clinical challenge: guidelines for the diagnosis and treatment of leishmaniasis

Cited by 19 publications

References 13 publications

Screening a Natural Product-Based Library against Kinetoplastid Parasites

Screening a Natural Product-Based Library against Kinetoplastid Parasites

Evaluation of a New Topical Treatment for the Control of Cutaneous Leishmaniasis

Visceral leishmaniasis in a patient with ulcerative colitis: A case report

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