Figure 1 - uploaded by Dennis Tappe
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Cutaneous Old World leishmaniasis caused by Leishmania tropica in an Afghan woman. A , Initial presentation of the dry, plaque-like lesion with central nodule on the forearm. B , Intracellular parasites in vacuoles of a giant cell (arrowheads). Haematoxylin and eosin stain, magnification ×1,000. C , Leishmania in macrophages (arrowheads). Haematoxylin and eosin stain, magnification ×1,000. This figure appears in color at www.ajtmh.org .
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Citations
... Miltefosine is registered in Pakistan for use in leishmaniasis (produced and sold under the name Fosine). However, until now, only limited case studies have been conducted to evaluate the efficacy of miltefosine in CL caused by L. tropica which is generally considered to be less drug sensitive [24][25][26]. It is not (yet) included in the Pakistan national guidelines, although it is recommended by the WHO in the manual for case management of CL in the EMRO region (2014) as a second line treatment [27,28]. ...
... Our observational retrospective study showed that miltefosine is an effective treatment option in CL patients with contraindications to, or previously had failed antimonial treatment. The results of this study are comparable to the outcomes of miltefosine treatment in CL caused by L. major and in muco-cutaneous leishmaniasis [22,24,25,30,31,43,44]. We showed that the overall positive initial treatment response to miltefosine was 90.6% (95%CI: 80.7-96.5%) ...
Background
Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by Leishmania protozoa. In Pakistan, where CL caused by L . tropica is highly endemic, therapy with pentavalent antimonials is the standard of care, but has significant toxicity when used in systemic therapy, while are no evidence-based safer alternative treatment options for L . tropica . The efficacy of oral miltefosine has not been studied in CL caused by L . tropica . We evaluated effectiveness and tolerability of miltefosine in patients with previous treatment failure or with contraindications to systemic antimonial treatment.
Methods
A retrospective review was conducted of a cohort of CL patients who were treated with a 28-day course of miltefosine between December 2017 and August 2019, in urban Quetta, Pakistan, an area endemic for L . tropica . Descriptive analyses were performed, and effectiveness was assessed by initial response after treatment, and final cure at routine follow up visits, six weeks to three months post-treatment. Tolerability was assessed by routinely reported adverse events.
Results
Of the 76 CL patients in the cohort, 42 (55%) had contraindications to systemic antimonial treatment, and 34 (45%) had failure or relapse after antimonial treatment. Twelve patients defaulted during treatment and 12 patients were lost to follow up. In the remaining 52 patients, final cure rate was 77% (40/52). In those with contraindications to systemic antimonial treatment the final cure rate was 83% (24/29) and in the failure and relapse group 70% (16/23). Twenty-eight patients (40.0%) reported 39 mild to moderate adverse events with the main complaints being nausea (41.0%), general malaise (25.6%), and stomach pain (12.8%).
Conclusion
Results indicate that miltefosine is an effective second line treatment in CL in areas endemic for L . tropica . Prospective studies with systematic follow up are needed to obtain definitive evidence of effectiveness and tolerability, including identification of risk factors for miltefosine treatment failure.
... Miltefosine is the only oral drug prescribed against VL, and it was a major accomplishment in the field. It was originally developed as an anti-cancer drug and it has been proven highly efficacious for the treatment of CL, ML and VL (Bhattacharya et al, 2007;Tappe et al, 2010). It can be safely used in children and treats patients who were refractory to antimonials (Berman, 2008). ...
... For L. tropica, L. major and L. infantum/donovani CL, experience with miltefosine is limited to case reports (Neub et al. 2008;Tappe et al. 2010;Killingley et al. 2009;Faber et al. 2009;Poeppl et al. 2011) and small case series, with all reported patients cured ). In a case series of 24 patients with complicated Old World CL or ML treated with miltefosine, all patients were cured (Mosimann et al. 2016;Neumayr et al. 2012;Stoeckle et al. 2013). ...
Choosing a treatment regimen of tegumentary leishmaniasis is influenced by the size, number and location of the lesion(s) but mainly determined by the infecting Leishmania species.
... 42,45,46,81 Thermotherapy and photodynamic therapy were effective in L. tropica and L. major CL and is a valuable option for centers with the necessary equipment (ie, Thermomed Device). 54,55,82 Liposomal amphotericine (AmBisome, 3 mg/kg/day for five consecutive days and at day 10, with a total dose of 18 mg/kg) had a cure rate of 84% in 13 travelers and immigrants with L. tropica CL. 74 For L. tropica, L. major, and L. infantum/donovani CL, experience with miltefosine is limited to case reports [75][76][77]83,84 and small case series, with all patients cured. 58 Two patients with L. infantum ML were completely cured with miltefosine. ...
Treatment of cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) in travelers is still controversial. Over the last decade, national and international consortia have published recommendations for treating CL in travelers. These guidelines harmonize many issues, but there are some discrepancies.
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In this article, the authors provide practical treatment recommendations for imported CL and ML in Europe, drawn up from the review by the European experts.
Human leishmaniasis is a complex skin infection that imposes a heavy burden on many tropical and subtropical developing countries and is caused by over 20 species of Leishmania parasite and they are transmitted by several sandfly species. The disease is mainly associated with disfiguring scars and major social stigma during infection. Disease severity appears to depend on many factors, including parasite species, host, endemic area, socioeconomic status, and access to health facilities. Despite the many studies that have been conducted on current and new treatments, the treatment outcomes of leishmaniasis remain controversial, possibly because of the knowledge gaps that still exist. Varying responses to current leishmania treatments have become a major drawback in disease control. The lack of information on critical analyses of the results of such studies is a barrier to overall understanding. Based on the currently available literature on treatment outcomes, we discuss the most effective doses, drug susceptibilities/resistances, and treatment failures of Leishmania for monotherapy and combination therapy. This review focuses on the available therapies for leishmaniasis caused by different Leishmania species, with insights into their species-specific efficacy, which will inform the selection of drugs for the treatment and control of leishmaniasis. For this aim, the search was conducted in electronic databases of PubMed, Scopus, web of sciences and Google scholar. The specific search medical subject headings (MeSH) terms include “leishmaniasis,” “leishmaniasis Prevention,” “cutaneous leishmaniasis,” “Leishmaniasis Diagnosis”, “Leishmaniasis Treatment”, “Leishmaniasis Drug”, “Leishmaniasis Parasite”, “Leishmaniasis Cutaneous”, “Rural leishmaniasis”, “Urban leishmaniasis”, “Dry leishmaniasis”, “Wet leishmaniasis”, “Human leishmaniasis”, “ Leishmania donovani ”, “Leishmaniasis trials”, “leishmaniasis vectors”, “leishmaniasis reservoirs” were conducted and articles with English titles and abstracts were screened and selected, and finally related full-text articles were studied and used in writing a review article.
Complicated Old World cutaneous leishmaniasis (OWCL) andOld World mucosal leishmaniasis (OWML) constitute an indicationfor systemic treatment. To date, there no controlled clinicalstudies that compare treatment options for these diseases. We compiled a case series of 24 cases successfully treated withmiltefosine. We conclude that oral miltefosine is an effectivetreatment option for both OWCL and OWML. © The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
Leishmaniasis is a devastating and significantly under-recognized vector-borne disease causing serious global health burden. The disease is caused by Leishmania, a protozoan kinetoplastid parasite. Though the disease is most prevalent in certain endemic locales, the disease spans 88 countries in the tropics, subtropics, and Southern Europe (Herwaldt 1999). After disease is acquired through the bite of an infected phlebotomine sand fly, disease can manifest in various forms from cutaneous disease to mucocutaneous involvement to visceral disease in which splenomegaly, cachexia, and anemia are salient features and the disease is virtually fatal if untreated (CDC http://www.cdc.gov/parasites/leishmaniasis/disease.html).
The incidence of cutaneous and mucocutaneous Leishmaniasis (CL/MCL) is increasing globally, also in Germany, although the cases are imported and still low in number. The current evidence for the different therapies has many limitations due to lack of sufficient studies on the different Leishmania species with differing virulence. So far there is no international gold standard for the optimal management. The aim of the German joint working group on Leishmaniasis, formed by the societies of Tropical Medicine (DTG), Chemotherapy (PEG) and Dermatology (DDG), was to establish a guideline for the diagnosis and treatment of CL and MCL in Germany, based on evidence (Medline search yielded 400 articles) and, where lacking, on consensus of the experts. As the clinical features do not necessarily reflect the involved Leishmania species and, as different parasite species and even geographically distinct strains of the same species may require different treatments or varying dosages or durations of therapy, the guidelines suggest for Germany to identify the underlying parasite prior to treatment. Because of relevant differences in prognosis and ensuing therapy species should be identified in i) New World CL/MCL (NWCL/ MCL) to distinguish between L. mexicana-complex and subgenus Viannia, ii) in suspected infections with L. mexicana-complex to distinguish from L. amazonensis, and iii) in Old World CL (OWCL) to distinguish between L. infantum and L. major, L. tropica, or L. aethiopica. A state-of-the-art diagnostic algorithm is presented. For recommendations on localized and systemic drug treatment and physical procedures, data from the accessible literature were adjusted according to the involved parasite species and a clinical differentiation into uncomplicated or complex lesions. Systemic therapy was strictly recommended for i) complex lesions (e. g. > 3 infected lesions, infections in functionally or cosmetically critical areas such as face or hands, presence of lymphangitis), ii) lesions refractory to therapy, iii) NWCL by the subgenus Viannia or by L. amazonensis, iv) in MCL and v) in recalcitrant, or disseminating or diffuse cutaneous courses. In e. g. infection with L. major it encompasses miltefosine, fluconazole and ketoconazole, while antimony or allopurinol were here considered second choice. Local therapy was considered appropriate for i) uncomplicated lesions of OWCL, ii) L. mexicana-complex and iii) pregnant women. In e. g. infection with L. major it encompasses perilesional antimony, combined with cryotherapy, paromomycin 15 %/in methylbenzethoniumchlorid 12 % and thermotherapy. The group also stated that there is an urgent need for improving the design and the way of publishing of clinical trials in leishmaniasis.
A patient presenting with an atypical manifestation of cutaneous leishmaniasis after travel to Cyprus was successfully treated with miltefosine. The K26 typing revealed a hitherto undescribed strain of the Leishmania donovani/infantum complex as the causing agent.
We used a species-specific approach to treat 10 patients with cutaneous leishmaniasis diagnosed using polymerase chain reaction. Non-antimony treatments (oral miltefosine, ketoconazole, and liposomal amphotericin B) were chosen as an alternative to pentavalent antimony drugs based on likely or proven drug efficacy against the infecting species. Leishmania Viannia panamensis was diagnosed in three patients and treated successfully with oral ketoconazole. Miltefosine treatment cured two patients with L. infantum chagasi. A wide variety of Leishmania responded to liposomal amphotericin B administered for 5-7 days. Three patients with L. V. braziliensis, one patient with L. tropica, and two patients with L. infantum chagasi were treated successfully. One person with L. V. braziliensis healed slowly because of a resistant bacterial superinfection, and a second patient with L. infantum chagasi relapsed and was retreated with miltefosine. These drugs were reasonably well-tolerated. In this limited case series, alternative non-antimony-based regimens were convenient, safe, and effective.
