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Asrat Hailu - One of the best experts on this subject based on the ideXlab platform.

  • Cutaneous Leishmaniasis Due to Leishmania aethiopica.
    EClinicalMedicine, 2019
    Co-Authors: Saskia Van Henten, Asrat Hailu, Gert Van Der Auwera, Wim Adriaensen, Helina Fikre, Hannah Akuffo, Ermias Diro, Johan Van Griensven
    Abstract:

    Leishmania aethiopica is the main causative species for cutaneous Leishmaniasis (CL) in Ethiopia. Despite its considerable burden, L. aethiopica has been one of the most neglected Leishmania species. In this review, published evidence on L. aethiopica history, geography, vector, reservoir, epidemiology, parasitology, and immunology is discussed and knowledge gaps are outlined. L. aethiopica endemic regions are limited to the highland areas, although nationwide studies on CL prevalence are lacking. Phlebotomus pedifer and P. longipes are the sandfly vectors and hyraxes are considered to be the main reservoir, but the role of other sandfly species and other potential reservoirs requires further investigation. Where and how transmission occurs exactly are also still unknown. Most CL patients in Ethiopia are children and young adults. Lesions are most commonly on the face, in contrast to CL caused by other Leishmania species which may more frequently affect other body parts. CL lesions caused by L. aethiopica seem atypical and more severe in their presentation as compared to other Leishmania species. Mucocutaneous Leishmaniasis and diffuse cutaneous Leishmaniasis are relatively common, and healing of lesions caused by L. aethiopica seems to take longer than that of other species. A thorough documentation of the natural evolution of L. aethiopica as well as in depth studies into the immunological and parasitological characteristics that underpin the atypical and severe clinical presentation are needed. Better understanding of CL caused by this parasite species will contribute to interventions related to transmission, prevention, and treatment.

  • Cutaneous Leishmaniasis Due to Leishmania aethiopica
    Elsevier, 2018
    Co-Authors: Saskia Van Henten, Asrat Hailu, Gert Van Der Auwera, Wim Adriaensen, Helina Fikre, Hannah Akuffo, Ermias Diro, Johan Van Griensven
    Abstract:

    Leishmania aethiopica is the main causative species for cutaneous Leishmaniasis (CL) in Ethiopia. Despite its considerable burden, L. aethiopica has been one of the most neglected Leishmania species. In this review, published evidence on L. aethiopica history, geography, vector, reservoir, epidemiology, parasitology, and immunology is discussed and knowledge gaps are outlined. L. aethiopica endemic regions are limited to the highland areas, although nationwide studies on CL prevalence are lacking. Phlebotomus pedifer and P. longipes are the sandfly vectors and hyraxes are considered to be the main reservoir, but the role of other sandfly species and other potential reservoirs requires further investigation. Where and how transmission occurs exactly are also still unknown. Most CL patients in Ethiopia are children and young adults. Lesions are most commonly on the face, in contrast to CL caused by other Leishmania species which may more frequently affect other body parts. CL lesions caused by L. aethiopica seem atypical and more severe in their presentation as compared to other Leishmania species. Mucocutaneous Leishmaniasis and diffuse cutaneous Leishmaniasis are relatively common, and healing of lesions caused by L. aethiopica seems to take longer than that of other species. A thorough documentation of the natural evolution of L. aethiopica as well as in depth studies into the immunological and parasitological characteristics that underpin the atypical and severe clinical presentation are needed. Better understanding of CL caused by this parasite species will contribute to interventions related to transmission, prevention, and treatment. Keywords: Cutaneous Leishmaniasis, Ethiopia, Leishmania aethiopic

  • Local Increase of Arginase Activity in Lesions of Patients with Cutaneous Leishmaniasis in Ethiopia
    2016
    Co-Authors: Tamrat Abebe, Asrat Hailu, Mihretu Woldeyes, Woinshet Mekonen, Kassahun Bilcha, Thomas Cloke, Lionel Fry, Nafisa-katrin Seich Al Basatena, Karina Corware, Manuel Modolell
    Abstract:

    Background: Cutaneous Leishmaniasis is a vector-borne disease that is in Ethiopia mainly caused by the parasite Leishmania aethiopica. This neglected tropical disease is common in rural areas and causes serious morbidity. Persistent nonhealing cutaneous Leishmaniasis has been associated with poor T cell mediated responses; however, the underlying mechanisms are not well understood. Methodology/Principal Findings: We have recently shown in an experimental model of cutaneous Leishmaniasis that arginase-induced L-arginine metabolism suppresses antigen-specific T cell responses at the site of pathology, but not in the periphery. To test whether these results translate to human disease, we recruited patients presenting with localized lesions of cutaneous Leishmaniasis and assessed the levels of arginase activity in cells isolated from peripheral blood and from skin biopsies. Arginase activity was similar in peripheral blood mononuclear cells (PBMCs) from patients and healthy controls. In sharp contrast, arginase activity was significantly increased in lesion biopsies of patients with localized cutaneou

  • Treatment of Cutaneous Leishmaniasis Caused by Leishmania aethiopica: A Systematic Review
    PLoS neglected tropical diseases, 2016
    Co-Authors: Johan Van Griensven, Endalamaw Gadisa, Abraham Aseffa, Asrat Hailu, Abate Mulugeta Beshah, Ermias Diro
    Abstract:

    Leishmania aethiopica is the etiological agent of cutaneous Leishmaniasis (CL) in Ethiopia and can cause severe and complicated cases such as diffuse CL (DCL), mucocutaneous Leishmaniasis or extensive CL, requiring systemic treatment. Despite the substantial burden, evidence-based treatment guidelines are lacking. We conducted a systematic review of clinical studies reporting on treatment outcomes of CL due to L aethiopica in order to help identify potentially efficacious medications on CL that can be taken forward for clinical trials. We identified a total of 24 records reporting on 506 treatment episodes of CL presumably due to L aethiopica. The most commonly used drugs were antimonials (n = 201), pentamidine (n = 150) and cryotherapy (n = 103). There were 20 case reports/series, with an overall poor study quality. We only identified two small and/or poor quality randomized controlled trials conducted a long time ago. There were two prospective non-randomized studies reporting on cryotherapy, antimonials and pentamidine. With cryotherapy, cure rates were 60-80%, and 69-85% with antimonials. Pentamidine appeared effective against complicated CL, also in cases non-responsive to antimonials. However, all studies suffered from methodological limitations. Data on miltefosine, paromomycin and liposomal amphotericin B are extremely scarce. Only a few studies are available on DCL. The only potentially effective treatment options for DCL seem to be antimonials with paromomycin in combination or pentamidine, but none have been properly evaluated. In conclusion, the evidence-base for treatment of complicated CL due to L aethiopica is extremely limited. While antimonials remain the most available CL treatment in Ethiopia, their efficacy and safety in CL should be better defined. Most importantly, alternative first line treatments (such as miltefosine or paromomycin) should be explored. High quality trials on CL due to L aethiopica are urgently needed, exploring group sequential methods to evaluate several options in parallel.

  • Phytochemistry and antiLeishmanial activity of the leaf latex of Aloe calidophila Reynolds.
    Phytotherapy research : PTR, 2014
    Co-Authors: Fetene Abeje, Asrat Hailu, Daniel Bisrat, Kaleab Asres
    Abstract:

    Leishmaniasis is a major protozoal disease threatening the lives of 350 million people throughout the world. However, the therapeutic options for the disease are limited. In the present study, the antiprotozoal activity of the latex obtained from the Ethiopian plant Aloe calidophila Reynolds was evaluated by in vitro testing against Leishmania aethiopica and Leishmania major. It was found that the latex possesses moderate activity against both parasites with IC50 values of 64.05 and 82.29 µg/mL, respectively. Phytochemical investigation resulted in the isolation of three anthrones identified as aloinoside, aloin, and microdontin on the basis of IR, MS, 1H NMR, and 13C NMR spectral data. The isolated compounds showed strong antiLeishmanial activity with IC50 values ranging from 1.76 to 6.32 µg/mL against L. aethiopica and from 2.09 to 8.85 µg/mL against L. major. Although these values were higher than those of amphotericin B (IC50 = 0.109 and 0.067 µg/mL), the selectivity indices (813.35 and 694.90, respectively, against L. aethiopica and L. major) of aloinoside were much better than those of the standard drug (423.49 and 688.96). The results indicate that the isolated compounds have the potential to be used as a scaffold for the development of safe and cost-effective antiLeishmanial agents. Copyright © 2014 John Wiley & Sons, Ltd.

Hannah Akuffo - One of the best experts on this subject based on the ideXlab platform.

  • Cutaneous Leishmaniasis Due to Leishmania aethiopica.
    EClinicalMedicine, 2019
    Co-Authors: Saskia Van Henten, Asrat Hailu, Gert Van Der Auwera, Wim Adriaensen, Helina Fikre, Hannah Akuffo, Ermias Diro, Johan Van Griensven
    Abstract:

    Leishmania aethiopica is the main causative species for cutaneous Leishmaniasis (CL) in Ethiopia. Despite its considerable burden, L. aethiopica has been one of the most neglected Leishmania species. In this review, published evidence on L. aethiopica history, geography, vector, reservoir, epidemiology, parasitology, and immunology is discussed and knowledge gaps are outlined. L. aethiopica endemic regions are limited to the highland areas, although nationwide studies on CL prevalence are lacking. Phlebotomus pedifer and P. longipes are the sandfly vectors and hyraxes are considered to be the main reservoir, but the role of other sandfly species and other potential reservoirs requires further investigation. Where and how transmission occurs exactly are also still unknown. Most CL patients in Ethiopia are children and young adults. Lesions are most commonly on the face, in contrast to CL caused by other Leishmania species which may more frequently affect other body parts. CL lesions caused by L. aethiopica seem atypical and more severe in their presentation as compared to other Leishmania species. Mucocutaneous Leishmaniasis and diffuse cutaneous Leishmaniasis are relatively common, and healing of lesions caused by L. aethiopica seems to take longer than that of other species. A thorough documentation of the natural evolution of L. aethiopica as well as in depth studies into the immunological and parasitological characteristics that underpin the atypical and severe clinical presentation are needed. Better understanding of CL caused by this parasite species will contribute to interventions related to transmission, prevention, and treatment.

  • Cutaneous Leishmaniasis Due to Leishmania aethiopica
    Elsevier, 2018
    Co-Authors: Saskia Van Henten, Asrat Hailu, Gert Van Der Auwera, Wim Adriaensen, Helina Fikre, Hannah Akuffo, Ermias Diro, Johan Van Griensven
    Abstract:

    Leishmania aethiopica is the main causative species for cutaneous Leishmaniasis (CL) in Ethiopia. Despite its considerable burden, L. aethiopica has been one of the most neglected Leishmania species. In this review, published evidence on L. aethiopica history, geography, vector, reservoir, epidemiology, parasitology, and immunology is discussed and knowledge gaps are outlined. L. aethiopica endemic regions are limited to the highland areas, although nationwide studies on CL prevalence are lacking. Phlebotomus pedifer and P. longipes are the sandfly vectors and hyraxes are considered to be the main reservoir, but the role of other sandfly species and other potential reservoirs requires further investigation. Where and how transmission occurs exactly are also still unknown. Most CL patients in Ethiopia are children and young adults. Lesions are most commonly on the face, in contrast to CL caused by other Leishmania species which may more frequently affect other body parts. CL lesions caused by L. aethiopica seem atypical and more severe in their presentation as compared to other Leishmania species. Mucocutaneous Leishmaniasis and diffuse cutaneous Leishmaniasis are relatively common, and healing of lesions caused by L. aethiopica seems to take longer than that of other species. A thorough documentation of the natural evolution of L. aethiopica as well as in depth studies into the immunological and parasitological characteristics that underpin the atypical and severe clinical presentation are needed. Better understanding of CL caused by this parasite species will contribute to interventions related to transmission, prevention, and treatment. Keywords: Cutaneous Leishmaniasis, Ethiopia, Leishmania aethiopic

  • Natural and acquired resistance to Leishmania: cellular activation by Leishmania aethiopica of mononuclear cells from unexposed individuals is through the stimulation of natural killer (NK) cells.
    Clinical and experimental immunology, 2008
    Co-Authors: Hannah Akuffo, K. Maasho, R. Howe
    Abstract:

    Cells from normal non-Leishmania-exposed individuals could respond in vitro by proliferation and interferon-gamma (IFN-gamma) production to Leishmania aethiopica stimulation. The main cell type that appeared to be activated following such stimulation was CD3-, CD16+/56+, i.e. NK cells. Of the few CD3+ cells responding, an involvement of CD8+ cells was evident in the absence of activation of CD4+ cells in normal individuals, while a different feature was observed when patients' cells were investigated. Cells from patients with L. aethiopica infection did not show this NK response, but rather the CD4+ cells were the prominent responding cells. No evidence of the involvement of superantigens or cells utilizing the gamma delta T cell receptor (gamma delta cells) in the response of unexposed individuals was noted.

  • Contribution of non-Leishmania-specific immunity to resistance to Leishmania infection in humans.
    Clinical and experimental immunology, 2008
    Co-Authors: Hannah Akuffo, Sven Britton
    Abstract:

    Lymphocytes of individuals from a country non-endemic for Leishmania (Sweden), responded with a vigorous interferon-gamma (IFN-gamma) and IL-6 response when exposed to live or dead promastigotes of Leishmania aethiopica. This response was sometimes as strong as when the same cells were exposed to the mitogen (phytohaemagglutinin (PHA)). Furthermore, supernatants of cells exposed to Leishmania promastigotes were able to inhibit the amastigote form of the same parasite. In some few instances there was no such reactivity to Leishmania parasites. It is proposed that most individuals have such a first line cytokine response which is enough to prevent further spread and growth of the parasites. In exposed individuals who display disease symptoms, this non-Leishmania-specific response is overcome (by dose) or is weak (for genetic reasons). In the latter instances curbing of parasite growth would depend on acquired immunity.

  • Evaluation of amastigote reactive cells in human cutaneous Leishmaniasis caused by Leishmania aethiopica
    Clinical and experimental immunology, 2003
    Co-Authors: Kerima Maasho, Sven Britton, Diane Mcmahon-pratt, J. Raita, M. Raud, Lynn Soong, Hannah Akuffo
    Abstract:

    SUMMARY Lymphoproliferative responses to three affinity chromatography purified amastigote antigens of Leishmania pifanoi, P-2, P-4 and P-8, were evaluated in peripheral blood mononuclear cells (PBMC) from patients with Ethiopian cutaneous Leishmaniasis. Antigen-stimulated cells were analysed for the percentage of CD4 + , CD8 + and CD16/56 + cells and the expressed levels of gamma interferon (IFN g ) and interleukin (IL)-10 were determined in culture supernatants. The amastigote antigens induced cellular responses in Leishmaniasis patients with heterologous Leishmania parasite infection. These responses were compared to those of freeze-thawed L. aethiopica promastigote antigen stimulation. The membrane protein (P-8), and to a lesser extent the megasomal/cytoplasmic cysteine proteinase(P-2), induced proliferation with high levels of IFN g and IL-10 production in cells from patients with active L. aethiopica lesions. CD16/56 + NK cells were the main cell types induced to proliferate in response to P-8 and P-2 stimulation, followed by CD8 + cell populations. P-4 had no such effect. This contrasts from previous studies of New World human Leishmaniasis where P-4 and P-8 were stimulatory. The success of a particular molecule in the induction of a response with a protective phenotype may be dependent on the infecting Leishmania spp. To our knowledge, there are no studies that directly compare the New versus Old World cutaneous Leishmaniasis in respect of NK cell and IL-10 responses. Our studies indicate that some Leishmanial molecules are recognized across the species, while others are apparently more species specific.

Endalamaw Gadisa - One of the best experts on this subject based on the ideXlab platform.

  • Enhanced production of pro-inflammatory cytokines and chemokines in Ethiopian cutaneous Leishmaniasis upon exposure to Leishmania aethiopica
    Cytokine, 2020
    Co-Authors: Menberework Chanyalew, Endalamaw Gadisa, Abraham Aseffa, Markos Abebe, Birtukan Endale, Selfu Girma, Geremew Tasew, Ger Van Zandbergen, Uwe Ritter, Tamás Laskay
    Abstract:

    The clinical course and outcome of cutaneous Leishmaniasis (CL) vary due to the infecting Leishmania species and host genetic makeup that result in different immune responses against the parasites. The host immune response to Leishmania aethiopica (L.aethiopica), the causative agent of CL in Ethiopia, is poorly understood. To contribute to the understanding of the protective immune response in CL due to L.aethiopica, we characterized the cytokine response to L. aethiopica in patients with the localized form of CL (LCL) and age-and sex-matched apparently healthy controls. By applying a whole blood based in vitro culture we found enhanced release of TNF, IL-6, MCP-1 or CCL2, IP-10 or CXCL10, MIP-1β or CCL4 and IL-8 or CXCL8- but not of IL-10CL patients in response to L. aethiopica compared to the controls. No difference was observed between LCL cases and controls in the secretion of these cytokines and chemokines in whole blood cultures treated with the TLR-ligands LPS, MALP-2 or polyI: C. The observed increased secretion of the pro-inflammatory cytokines/chemokines reflects an enhanced response against the parasites by LCL patients as compared to healthy controls rather than a generally enhanced ability of blood leukocytes from LCL patients to respond to microbial constituents. Our findings suggest that the enhanced production of pro-inflammatory cytokines/chemokines is associated with localized cutaneous Leishmaniasis caused by L.aethiopica.

  • Treatment of Cutaneous Leishmaniasis Caused by Leishmania aethiopica: A Systematic Review
    PLoS neglected tropical diseases, 2016
    Co-Authors: Johan Van Griensven, Endalamaw Gadisa, Abraham Aseffa, Asrat Hailu, Abate Mulugeta Beshah, Ermias Diro
    Abstract:

    Leishmania aethiopica is the etiological agent of cutaneous Leishmaniasis (CL) in Ethiopia and can cause severe and complicated cases such as diffuse CL (DCL), mucocutaneous Leishmaniasis or extensive CL, requiring systemic treatment. Despite the substantial burden, evidence-based treatment guidelines are lacking. We conducted a systematic review of clinical studies reporting on treatment outcomes of CL due to L aethiopica in order to help identify potentially efficacious medications on CL that can be taken forward for clinical trials. We identified a total of 24 records reporting on 506 treatment episodes of CL presumably due to L aethiopica. The most commonly used drugs were antimonials (n = 201), pentamidine (n = 150) and cryotherapy (n = 103). There were 20 case reports/series, with an overall poor study quality. We only identified two small and/or poor quality randomized controlled trials conducted a long time ago. There were two prospective non-randomized studies reporting on cryotherapy, antimonials and pentamidine. With cryotherapy, cure rates were 60-80%, and 69-85% with antimonials. Pentamidine appeared effective against complicated CL, also in cases non-responsive to antimonials. However, all studies suffered from methodological limitations. Data on miltefosine, paromomycin and liposomal amphotericin B are extremely scarce. Only a few studies are available on DCL. The only potentially effective treatment options for DCL seem to be antimonials with paromomycin in combination or pentamidine, but none have been properly evaluated. In conclusion, the evidence-base for treatment of complicated CL due to L aethiopica is extremely limited. While antimonials remain the most available CL treatment in Ethiopia, their efficacy and safety in CL should be better defined. Most importantly, alternative first line treatments (such as miltefosine or paromomycin) should be explored. High quality trials on CL due to L aethiopica are urgently needed, exploring group sequential methods to evaluate several options in parallel.

  • treatment response of cutaneous Leishmaniasis due to Leishmania aethiopica to cryotherapy and generic sodium stibogluconate from patients in silti ethiopia
    Transactions of The Royal Society of Tropical Medicine and Hygiene, 2012
    Co-Authors: Edessa Negera, Endalamaw Gadisa, Teklu Kuru, Lashitew Gedamu, Jemal Hussein, Howard Engers, Abraham Aseffa
    Abstract:

    Cutaneous Leishmaniasis in Ethiopia is caused mainly by Leishmania aethiopica. In this study, the response of L. aethiopica to sodium stibogluconate (SSG) and liquid nitrogen in Silti has been investigated. Patients were divided into two groups by the treating physician and were treated with either liquid nitrogen or SSG. Punch biopsy samples were collected from 54 patients with mean age of 20.61 (± 9.87 SD) years for histological characterization. The histological spectrum found to be type-1, type-2, type-3 and type-4 were 37.0%, 3.7%, 37.0% and 22.2% respectively. One hundred and three patients with a mean age of 18.4 (± 11.7 SD) years were treated with liquid nitrogen. The mean duration of the lesions before the onset of treatment was 8.5 months (± 6.7 SD). Of the 103 patients 80.6% (83/103) were cured, 13.6% (14/103) were dropouts and 5.8% (6/103) did not respond. Twenty patients with a mean age of 19.55 (+1.64 SD) years were treated with Pentostam on conventional dose. Of the 20 patients 85.0% (17/20) were cured, 10.0% (2/20) were unresponsive and 5.0% (1/20) were dropouts. The per protocol cure rate for cryotherapy and Pentostam was 93.3% and 89.5% respectively. Hence, liquid nitrogen can be used as one of the treatment options especially in resource poor settings.

  • Leishmania aethiopica: development of specific and sensitive PCR diagnostic test.
    Experimental parasitology, 2011
    Co-Authors: Teklu Kuru, Endalamaw Gadisa, Lashitew Gedamu, Nick Janusz, Abraham Aseffa
    Abstract:

    PCR has proved useful for rapid diagnosis and typing of Leishmania. Lack of specificity to discriminate between species and/or sensitivity to detect from clinical samples has always been an issue. Previously developed primers either require PCR-RFLP analysis for Leishmania aethiopica discrimination or lack sensitivity to detect L. aethiopica from clinical samples. Here we report the development and validation of L. aethiopica specific PCR primers (V5F/V10R) based on cysteine protease B (cpb), a multicopy and polymorphic gene of Leishmania. V5F/V10R primers differentiate L. aethiopica from Leishmania tropica, Leishmania major, Leishmania donovani and Leishmania infantum by direct PCR. In addition, they are sensitive enough to detect L. aethiopica from biopsy samples. The primers can be very useful for epidemiological studies, species typing and diagnosis of L. aethiopica directly from clinical samples. Implementation of these primers in routine L. aethiopica diagnosis can improve detection rate, save time, money and labor required for culturing Leishmania.

  • A zoonotic focus of cutaneous Leishmaniasis in Addis Ababa, Ethiopia
    Parasites & vectors, 2009
    Co-Authors: Wossenseged Lemma, Endalamaw Gadisa, Girume Erenso, Meshesha Balkew, Teshome Gebre-michael, Asrat Hailu
    Abstract:

    Background Cutaneous Leishmaniasis (CL) is endemic in the highlands of Ethiopia, and almost always caused by Leishmania aethiopica. Hitherto, Addis Ababa (the capital city of Ethiopia) was not considered endemic for CL, mainly due to absence of epidemiological and field ecological studies. This report summarizes the preliminary epidemiological investigation that proved the existence of active transmission in southeastern Addis Ababa.

Abraham Aseffa - One of the best experts on this subject based on the ideXlab platform.

  • Enhanced production of pro-inflammatory cytokines and chemokines in Ethiopian cutaneous Leishmaniasis upon exposure to Leishmania aethiopica
    Cytokine, 2020
    Co-Authors: Menberework Chanyalew, Endalamaw Gadisa, Abraham Aseffa, Markos Abebe, Birtukan Endale, Selfu Girma, Geremew Tasew, Ger Van Zandbergen, Uwe Ritter, Tamás Laskay
    Abstract:

    The clinical course and outcome of cutaneous Leishmaniasis (CL) vary due to the infecting Leishmania species and host genetic makeup that result in different immune responses against the parasites. The host immune response to Leishmania aethiopica (L.aethiopica), the causative agent of CL in Ethiopia, is poorly understood. To contribute to the understanding of the protective immune response in CL due to L.aethiopica, we characterized the cytokine response to L. aethiopica in patients with the localized form of CL (LCL) and age-and sex-matched apparently healthy controls. By applying a whole blood based in vitro culture we found enhanced release of TNF, IL-6, MCP-1 or CCL2, IP-10 or CXCL10, MIP-1β or CCL4 and IL-8 or CXCL8- but not of IL-10CL patients in response to L. aethiopica compared to the controls. No difference was observed between LCL cases and controls in the secretion of these cytokines and chemokines in whole blood cultures treated with the TLR-ligands LPS, MALP-2 or polyI: C. The observed increased secretion of the pro-inflammatory cytokines/chemokines reflects an enhanced response against the parasites by LCL patients as compared to healthy controls rather than a generally enhanced ability of blood leukocytes from LCL patients to respond to microbial constituents. Our findings suggest that the enhanced production of pro-inflammatory cytokines/chemokines is associated with localized cutaneous Leishmaniasis caused by L.aethiopica.

  • Treatment of Cutaneous Leishmaniasis Caused by Leishmania aethiopica: A Systematic Review
    PLoS neglected tropical diseases, 2016
    Co-Authors: Johan Van Griensven, Endalamaw Gadisa, Abraham Aseffa, Asrat Hailu, Abate Mulugeta Beshah, Ermias Diro
    Abstract:

    Leishmania aethiopica is the etiological agent of cutaneous Leishmaniasis (CL) in Ethiopia and can cause severe and complicated cases such as diffuse CL (DCL), mucocutaneous Leishmaniasis or extensive CL, requiring systemic treatment. Despite the substantial burden, evidence-based treatment guidelines are lacking. We conducted a systematic review of clinical studies reporting on treatment outcomes of CL due to L aethiopica in order to help identify potentially efficacious medications on CL that can be taken forward for clinical trials. We identified a total of 24 records reporting on 506 treatment episodes of CL presumably due to L aethiopica. The most commonly used drugs were antimonials (n = 201), pentamidine (n = 150) and cryotherapy (n = 103). There were 20 case reports/series, with an overall poor study quality. We only identified two small and/or poor quality randomized controlled trials conducted a long time ago. There were two prospective non-randomized studies reporting on cryotherapy, antimonials and pentamidine. With cryotherapy, cure rates were 60-80%, and 69-85% with antimonials. Pentamidine appeared effective against complicated CL, also in cases non-responsive to antimonials. However, all studies suffered from methodological limitations. Data on miltefosine, paromomycin and liposomal amphotericin B are extremely scarce. Only a few studies are available on DCL. The only potentially effective treatment options for DCL seem to be antimonials with paromomycin in combination or pentamidine, but none have been properly evaluated. In conclusion, the evidence-base for treatment of complicated CL due to L aethiopica is extremely limited. While antimonials remain the most available CL treatment in Ethiopia, their efficacy and safety in CL should be better defined. Most importantly, alternative first line treatments (such as miltefosine or paromomycin) should be explored. High quality trials on CL due to L aethiopica are urgently needed, exploring group sequential methods to evaluate several options in parallel.

  • treatment response of cutaneous Leishmaniasis due to Leishmania aethiopica to cryotherapy and generic sodium stibogluconate from patients in silti ethiopia
    Transactions of The Royal Society of Tropical Medicine and Hygiene, 2012
    Co-Authors: Edessa Negera, Endalamaw Gadisa, Teklu Kuru, Lashitew Gedamu, Jemal Hussein, Howard Engers, Abraham Aseffa
    Abstract:

    Cutaneous Leishmaniasis in Ethiopia is caused mainly by Leishmania aethiopica. In this study, the response of L. aethiopica to sodium stibogluconate (SSG) and liquid nitrogen in Silti has been investigated. Patients were divided into two groups by the treating physician and were treated with either liquid nitrogen or SSG. Punch biopsy samples were collected from 54 patients with mean age of 20.61 (± 9.87 SD) years for histological characterization. The histological spectrum found to be type-1, type-2, type-3 and type-4 were 37.0%, 3.7%, 37.0% and 22.2% respectively. One hundred and three patients with a mean age of 18.4 (± 11.7 SD) years were treated with liquid nitrogen. The mean duration of the lesions before the onset of treatment was 8.5 months (± 6.7 SD). Of the 103 patients 80.6% (83/103) were cured, 13.6% (14/103) were dropouts and 5.8% (6/103) did not respond. Twenty patients with a mean age of 19.55 (+1.64 SD) years were treated with Pentostam on conventional dose. Of the 20 patients 85.0% (17/20) were cured, 10.0% (2/20) were unresponsive and 5.0% (1/20) were dropouts. The per protocol cure rate for cryotherapy and Pentostam was 93.3% and 89.5% respectively. Hence, liquid nitrogen can be used as one of the treatment options especially in resource poor settings.

  • Leishmania aethiopica: development of specific and sensitive PCR diagnostic test.
    Experimental parasitology, 2011
    Co-Authors: Teklu Kuru, Endalamaw Gadisa, Lashitew Gedamu, Nick Janusz, Abraham Aseffa
    Abstract:

    PCR has proved useful for rapid diagnosis and typing of Leishmania. Lack of specificity to discriminate between species and/or sensitivity to detect from clinical samples has always been an issue. Previously developed primers either require PCR-RFLP analysis for Leishmania aethiopica discrimination or lack sensitivity to detect L. aethiopica from clinical samples. Here we report the development and validation of L. aethiopica specific PCR primers (V5F/V10R) based on cysteine protease B (cpb), a multicopy and polymorphic gene of Leishmania. V5F/V10R primers differentiate L. aethiopica from Leishmania tropica, Leishmania major, Leishmania donovani and Leishmania infantum by direct PCR. In addition, they are sensitive enough to detect L. aethiopica from biopsy samples. The primers can be very useful for epidemiological studies, species typing and diagnosis of L. aethiopica directly from clinical samples. Implementation of these primers in routine L. aethiopica diagnosis can improve detection rate, save time, money and labor required for culturing Leishmania.

  • outbreak of cutaneous Leishmaniasis in silti woreda ethiopia risk factor assessment and causative agent identification
    Transactions of The Royal Society of Tropical Medicine and Hygiene, 2008
    Co-Authors: Edessa Negera, Endalamaw Gadisa, Teklu Kuru, Lashitew Gedamu, Asrat Hailu, Jemal Hussein, Howard Engers, Lawrence Yamuah, Abraham Aseffa
    Abstract:

    Summary An outbreak of skin lesions was reported in June 2005 in the district of Silti woreda, 150 km south of Addis Ababa, by the Christian Children's Fund (CCF) and confirmed to be cutaneous Leishmaniasis (CL) by our group from the Armauer Hansen Research Institute in July 2005. A house-to-house survey of 1907 residents in three kebeles of Silti woreda conducted in April 2006 showed a prevalence of 4.8%. RFLP analysis of the internal transcribed spacer RNA (ITS1) showed that Leishmania aethiopica was the causative agent. In the survey, it was found that the age group 11–20 years was the most affected. Environmental factors such as proximity of the house to the gorge where hyraxes reside, presence of the plants Adhatoda schimperiana and Acacia spp. in the compound and sharing the same room with domestic animals were significantly associated with developing CL. The prevalence of active disease was higher in Kibet town (10.4%) compared to the rural kebeles. The identified risk factors of CL in the area need further study. The appearance of Leishmaniasis in Silti, which was not known to be endemic for the disease, underlines the need to initiate a Leishmaniasis control program in Ethiopia to limit its expansion.

Lashitew Gedamu - One of the best experts on this subject based on the ideXlab platform.

  • treatment response of cutaneous Leishmaniasis due to Leishmania aethiopica to cryotherapy and generic sodium stibogluconate from patients in silti ethiopia
    Transactions of The Royal Society of Tropical Medicine and Hygiene, 2012
    Co-Authors: Edessa Negera, Endalamaw Gadisa, Teklu Kuru, Lashitew Gedamu, Jemal Hussein, Howard Engers, Abraham Aseffa
    Abstract:

    Cutaneous Leishmaniasis in Ethiopia is caused mainly by Leishmania aethiopica. In this study, the response of L. aethiopica to sodium stibogluconate (SSG) and liquid nitrogen in Silti has been investigated. Patients were divided into two groups by the treating physician and were treated with either liquid nitrogen or SSG. Punch biopsy samples were collected from 54 patients with mean age of 20.61 (± 9.87 SD) years for histological characterization. The histological spectrum found to be type-1, type-2, type-3 and type-4 were 37.0%, 3.7%, 37.0% and 22.2% respectively. One hundred and three patients with a mean age of 18.4 (± 11.7 SD) years were treated with liquid nitrogen. The mean duration of the lesions before the onset of treatment was 8.5 months (± 6.7 SD). Of the 103 patients 80.6% (83/103) were cured, 13.6% (14/103) were dropouts and 5.8% (6/103) did not respond. Twenty patients with a mean age of 19.55 (+1.64 SD) years were treated with Pentostam on conventional dose. Of the 20 patients 85.0% (17/20) were cured, 10.0% (2/20) were unresponsive and 5.0% (1/20) were dropouts. The per protocol cure rate for cryotherapy and Pentostam was 93.3% and 89.5% respectively. Hence, liquid nitrogen can be used as one of the treatment options especially in resource poor settings.

  • Leishmania aethiopica: development of specific and sensitive PCR diagnostic test.
    Experimental parasitology, 2011
    Co-Authors: Teklu Kuru, Endalamaw Gadisa, Lashitew Gedamu, Nick Janusz, Abraham Aseffa
    Abstract:

    PCR has proved useful for rapid diagnosis and typing of Leishmania. Lack of specificity to discriminate between species and/or sensitivity to detect from clinical samples has always been an issue. Previously developed primers either require PCR-RFLP analysis for Leishmania aethiopica discrimination or lack sensitivity to detect L. aethiopica from clinical samples. Here we report the development and validation of L. aethiopica specific PCR primers (V5F/V10R) based on cysteine protease B (cpb), a multicopy and polymorphic gene of Leishmania. V5F/V10R primers differentiate L. aethiopica from Leishmania tropica, Leishmania major, Leishmania donovani and Leishmania infantum by direct PCR. In addition, they are sensitive enough to detect L. aethiopica from biopsy samples. The primers can be very useful for epidemiological studies, species typing and diagnosis of L. aethiopica directly from clinical samples. Implementation of these primers in routine L. aethiopica diagnosis can improve detection rate, save time, money and labor required for culturing Leishmania.

  • outbreak of cutaneous Leishmaniasis in silti woreda ethiopia risk factor assessment and causative agent identification
    Transactions of The Royal Society of Tropical Medicine and Hygiene, 2008
    Co-Authors: Edessa Negera, Endalamaw Gadisa, Teklu Kuru, Lashitew Gedamu, Asrat Hailu, Jemal Hussein, Howard Engers, Lawrence Yamuah, Abraham Aseffa
    Abstract:

    Summary An outbreak of skin lesions was reported in June 2005 in the district of Silti woreda, 150 km south of Addis Ababa, by the Christian Children's Fund (CCF) and confirmed to be cutaneous Leishmaniasis (CL) by our group from the Armauer Hansen Research Institute in July 2005. A house-to-house survey of 1907 residents in three kebeles of Silti woreda conducted in April 2006 showed a prevalence of 4.8%. RFLP analysis of the internal transcribed spacer RNA (ITS1) showed that Leishmania aethiopica was the causative agent. In the survey, it was found that the age group 11–20 years was the most affected. Environmental factors such as proximity of the house to the gorge where hyraxes reside, presence of the plants Adhatoda schimperiana and Acacia spp. in the compound and sharing the same room with domestic animals were significantly associated with developing CL. The prevalence of active disease was higher in Kibet town (10.4%) compared to the rural kebeles. The identified risk factors of CL in the area need further study. The appearance of Leishmaniasis in Silti, which was not known to be endemic for the disease, underlines the need to initiate a Leishmaniasis control program in Ethiopia to limit its expansion.

  • Leishmania kinetoplastida species typing with isoenzyme and pcr rflp from cutaneous Leishmaniasis patients in ethiopia
    Experimental Parasitology, 2007
    Co-Authors: Endalamaw Gadisa, Abebe Genetu, Dagim Jirata, Teklu Kuru, Abraham Aseffa, Kifle Dagne, Lashitew Gedamu
    Abstract:

    Cutaneous Leishmaniasis (CL) is an increasing public health problem in Ethiopia. There is a concern that it is spreading with increased incidence. In this study, we used isoenzyme electrophoresis and internal transcribed spacer one (ITS1) PCR-RFLP techniques to identify Leishmania species from CL patients in Ethiopia. We obtained isolates from 55 localized cutaneous Leishmaniasis (LCL), 3 diffused cutaneous Leishmaniasis (DCL) and 36 biopsy samples from 34 LCL and 2 DCL cases from All Africa Leprosy and Tuberculosis Rehabilitation and Training Center (ALERT) and clinically diagnosed CL cases from Ochollo village. Both isoenzyme and ITS1 PCR-RFLP techniques showed that Leishmania aethiopica (L. aethiopica) was the aetiologic agent in all cases. Our study also showed that ITS1 PCR-RFLP could identify Leishmania species from biopsy samples and suggests the method could be used for epidemiological surveillance of Leishmaniasis in Ethiopia and for species-specific diagnosis.

  • Leishmania aethiopica: identification and characterization of cathepsin L-like cysteine protease genes.
    Experimental parasitology, 2006
    Co-Authors: Teklu Kuru, Abebe Genetu, Dagim Jirata, Abraham Aseffa, Stephen D. Barr, Yohannes Mengistu, Lashitew Gedamu
    Abstract:

    There is limited information on the biology and pathogenesis of Leishmania aethiopica, causative agent of cutaneous Leishmaniasis (CL) in Ethiopia. In this study we have identified and characterized two cathepsin L-like cysteine protease genes, Laecpa and Laecpb, from L. aethiopica. The predicted amino acid sequence of Laecpa and Laecpb is more than 75% identical with homologous cathepsin L-like cysteine protease genes of other Leishmania species and less than 50% identical with human cathepsin L. Laecpa is expressed predominantly in the stationary, and to a lower level, during the amastigote stage while Laecpb is specifically expressed in the stationary stage of L. aethiopica development. Phylogenetic analysis showed that the two genes are grouped into separate clades which are the result of gene duplication. The isolation of these genes will be useful in developing Leishmania species specific diagnostics for molecular epidemiological studies and serves as a first step to study the role of cysteine proteases in L. aethiopica pathogenesis.