scholarly journals Efficacy and Tolerability of Miltefosine in the Treatment of Cutaneous Leishmaniasis

2020 ◽  
Author(s):  
JeanAnne M Ware ◽  
Elise M O’Connell ◽  
Thomas Brown ◽  
Lauren Wetzler ◽  
Kawsar R Talaat ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Standard Of Care ◽  
Leishmania Species ◽  
Response To Treatment ◽  
Prior History ◽  
Leishmania Braziliensis ◽  
Alternative Treatment Option ◽  
Leishmania Panamensis

Abstract Background Cutaneous leishmaniasis (CL) is a neglected tropical disease causing an estimated 1 million new cases annually. While antimonial compounds are the standard of care worldwide, they are associated with significant adverse effects. Miltefosine, an oral medication, is United States (US) Food and Drug Administration approved to treat CL caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis. Evidence of efficacy in other species and side-effect profiles in CL has been limited. Methods Twenty-six patients with CL were treated with miltefosine at the US National Institutes of Health. Species included L. braziliensis (n = 7), L. panamensis (n = 5), Leishmania mexicana (n = 1), Leishmania infantum (n = 3), Leishmania aethiopica (n = 4), Leishmania tropica (n = 2), Leishmania major (n = 1), and unspeciated (n = 3). Demographic and clinic characteristics of the participants, response to treatment, and associated adverse events were analyzed. Results Treatment with miltefosine resulted in cure in 77 % (20/26) of cases, with cures among all species. Common adverse events included nausea/vomiting (97%) and lack of appetite (54%). Clinical management or dose reduction was required in a third of cases. Gout occurred in 3 individuals with a prior history of gout. Most laboratory abnormalities, including elevated creatinine and aminotransferases, were mild and normalized after treatment. Conclusions Our data suggest that miltefosine has good but imperfect efficacy to a wide variety of Leishmania species. While side effects were common and mostly mild to moderate, some resulted in discontinuation of therapy. Due to oral administration, broad efficacy, and manageable toxicities, miltefosine is a viable alternative treatment option for CL, though cost and lack of local availability may limit its widespread use.

scholarly journals Sensitive Molecular Diagnostics for Cutaneous Leishmaniasis

2017 ◽  
Vol 4 (2) ◽  
Author(s):  
Orli Sagi ◽  
Anat Berkowitz ◽  
Shlomi Codish ◽  
Victor Novack ◽  
Aviv Rashti ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Point Of Care ◽  
Leishmania Species ◽  
Rapid Diagnosis ◽  
Clinical Samples ◽  
Leishmania Braziliensis ◽  
Multiplex Qpcr ◽  
Highly Sensitive ◽  
Pcr Multiplex

Abstract Background Rapid diagnosis of cutaneous leishmaniasis (CL) and identification of Leishmania species is highly important for the disease management. In Israel, CL is caused mainly by Leishmania major and Leishmania tropica species. Methods We established an easy to handle point of care lesion-swabbing, combined with a highly sensitive multiplex real time PCR (multiplex qPCR) for accurate and rapid diagnosis of Leishmania species. Results Using three probes: one general for: Leishmania species, and two specific for L major, and L tropica, we screened 1783 clinical samples collected during two years. Leishmania species was found in 1086 individuals, 1008 L major, and 70 L tropica. Eight samples positive for Leishmania species only, were further tested using a second set of multiplex qPCR developed, and were found positive for Leishmania braziliensis and Leishmania infantum/donovani (2 and 6 samples, concomitantly). Conclusions Taken together, the test enabled diagnostics and better treatment of Leishmania infections from the Old World (1078 samples) and the New World (8 samples), and the subtyping of the dominant strains in the region, as well as in returning travelers’.

scholarly journals Molecular Identification of Species Caused Cutaneous Leishmaniasis in Southern Zone of Iran

2019 ◽  
Author(s):  
Afshin Barazesh ◽  
Mohammad Hossein Motazedian ◽  
Moradali Fouladvand ◽  
Gholamreza Hatam ◽  
Saeed Tajbakhsh ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Synergistic Effects ◽  
Leishmania Species ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Skin Ulcers ◽  
Identification Of Species ◽  
Main Factor

Background: Leishmania major and Leishmania tropica are two main species causing cutaneous leishmaniasis (CL) in Iran. Recently, Crithidia spp. has also been reported in the wound of patients with CL. In this study, we determined the species causing CL in the southern of Iran and the role of Crithidia spp. in creating skin ulcers. Methods: In this cross-sectional study from Apr to Sep 2016, 66 patients with CL referred to Diagnostic Lab of Leishmaniasis, Valfajr Health Center, Shiraz, Iran, were selected. After DNA extraction from the Giemsa stained smears, all samples were amplified in two separate steps using specific primers, firstly, to differentiate Leishmania species and then to identify Crithidia spp. Results: Two species L. major and L. tropica were responsible for 60 and 6 cases, respectively. Moreover, in two patients, mixed infection with Crithidia was confirmed. In mix infection cases, the morphology of the cutaneous ul­cers was not different from the wounds of other patients. Conclusion: Leishmania major is responsible for the most common CL in southern Iran. In addition, in two patients with L. major and L. tropica, mix infection with Crithidia was confirmed. The potential role of Crithidia as the main factor for CL and the probability of this parasite to have synergistic effects on Leishmania, as a hypothesis, requires more comprehensive researches on the ambiguity of this protozoon.

scholarly journals Analysis of the Immune Responses of Mice to Infection with Leishmania braziliensis

1998 ◽  
Vol 66 (2) ◽  
pp. 827-829 ◽  
Author(s):  
Gregory K. DeKrey ◽  
Hermenio C. Lima ◽  
Richard G. Titus
Keyword(s):  
Immune Responses ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Leishmania Braziliensis ◽  
Dependent Mechanism

ABSTRACT Leishmania major and Leishmania braziliensis both cause cutaneous leishmaniasis, but the former kills BALB/c mice while the latter is killed by the mice. This killing of L. braziliensis occurred by a gamma interferon-dependent mechanism, potentially made possible by the observed lack of high interleukin-4 production.

scholarly journals Molecular Characterisation of Leishmania Species from Stray Dogs and Patients in Saudi Arabia

2020 ◽  
Author(s):  
Abdullah D Alanazi ◽  
Abdulazi S Alouffi ◽  
Mohamed S Alyousif ◽  
Abdulsadah A Rahi ◽  
Magda A Ali ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Leishmania Species ◽  
Sand Fly ◽  
Human Populations ◽  
Nested Polymerase Chain Reaction ◽  
Stray Dogs ◽  
Control And Prevention

Abstract Background: Leishmania major and Leishmania tropica cause cutaneous leishmaniasis in humans and dogs in several parts of the world, with a large number of cases recorded in the Middle East. However, when they occur in sympatry, the role of each species of Leishmania in the epidemiology of cutaneous leishmaniasis (CL) is not clear. Methods: To determine the frequency of occurrence and to identify the species of Leishmania that infect humans and stray dogs in Riyadh and Al-Qaseem (Saudi Arabia), 311 stray dogs and 27 human patients who were suspected for Leishmania were examined for CL by a nested polymerase chain reaction (nPCR).Results: The use of nPCR detected seven patients (25.9%) who were positive for cutaneous leishmaniasis. Five patients from Riyadh were infected by L. major and two from Al-Qaseem by L. tropica. In addition, five dogs (1.6%) were infected by L. tropica. Conclusions: This is one of the first molecular studies of leishmaniasis to be conducted in Saudi Arabia. The relationship between the sand-fly vectors and the reservoirs of both Leishmania spp. is still scarcely known in this region, and epidemiological investigations are required in order to progress towards control and prevention of the infection in canine and human populations.

scholarly journals Integrated Analysis Reveals That miR-193b, miR-671, and TREM-1 Correlate With a Good Response to Treatment of Human Localized Cutaneous Leishmaniasis Caused by Leishmania braziliensis

2018 ◽  
Vol 9 ◽  
Author(s):  
Sara Nunes ◽  
Icaro Bonyek Silva ◽  
Mariana Rosa Ampuero ◽  
Almério Libório Lopes de Noronha ◽  
Lígia Correia Lima de Souza ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Response To Treatment ◽  
Integrated Analysis ◽  
Leishmania Braziliensis

scholarly journals Leishmaniasis recidivans in Ethiopia: cutaneous and mucocutaneous features

2017 ◽  
Vol 11 (01) ◽  
pp. 106-110 ◽  
Author(s):  
Federica Dassoni ◽  
Frehiwot Daba ◽  
Bernard Naafs ◽  
Aldo Morrone
Keyword(s):  
Cutaneous Leishmaniasis ◽  
New World ◽  
Leishmania Braziliensis ◽  
Leishmania Tropica ◽  
Clinical Form ◽  
Leishmania Aethiopica ◽  
Mucosal Involvement ◽  
Leishmania Panamensis ◽  
First Time ◽  
Leishmania Guyanensis

Cutaneous leishmaniasis (CL) is endemic in Ethiopia. An unusual clinical form of this disease is leishmaniasis recidivans (LR), a prolonged, relapsing form of cutaneous leishmaniasis resembling tuberculosis of the skin that may persist for many years with a chronic and relapsing course. This rare variant has been shown to be caused by Leishmania tropica species in the Old World and by Leishmania braziliensis, Leishmania amazonensis, Leishmania panamensis, and Leishmania guyanensis in the New World, as reported in various studies. To our knowledge, there are no reports from Ethiopia, and mucocutaneous involvement of LR has not been described to date. This was a retrospective analysis of the patients seen at the Italian Dermatological Center in Mekelle on the Tigrean highlands over a three-year period (2008–2011). Seven patients with typical clinical features of LR were seen. Two of them presented with signs of mucosal involvement. To date, Leishmania aethiopica is shown to be the only species causing CL that is endemic in the Ethiopian highlands. Therefore, it had to be assumed that the lesions in these patients were caused by this species. The aims of this communication are to report, for the first time, the presence of LR, most likely due to Leishmania aethiopica, in Ethiopia, and to report mucosal involvement in this rare clinical form of CL.

Influence of Intestinal Helminth Burden on Clinical Manifestations, Therapeutic Response, and Leishmania braziliensis Load in Patients with New World Cutaneous Leishmaniasis

2021 ◽  
Author(s):  
Brady Page ◽  
Alex Lago ◽  
Juliana Almeida Silva ◽  
Albert Schriefer ◽  
Jamile Lago ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Therapeutic Response ◽  
Helminth Infection ◽  
Clinical Manifestations ◽  
Response To Treatment ◽  
Stool Examination ◽  
Clinical Aspects ◽  
Intestinal Helminth ◽  
Leishmania Braziliensis ◽  
Cure Rate

Leishmania braziliensis is the most important cause of cutaneous leishmaniasis (CL) in the Americas. A Th1-type immune response is required to control Leishmania infection, but an exaggerated inflammatory response leads to the development of ulcers seen in CL. Infection with intestinal helminths has the potential to inhibit the Th1 response in a manner that depends both on the species of helminth present as well as the burden of helminthiasis. We conducted a prospective cohort study of CL patients from an endemic area between January and December 2017 with either negative or high intestinal helminth burden to characterize relationships between helminth burden, L. braziliensis quantification within CL lesions, clinical aspects of CL, and therapeutic response. Of 234 participants with leishmaniasis who underwent stool examination at the time of diagnosis, 45% had detectable helminth infection. The overall cure rate after 90 days was 66%, with a median time to resolution of disease of 40 days (interquartile range: 30–65 days). There was no significant association between the type of helminth infection or the magnitude of intestinal helminth burden at the time of diagnosis and L. braziliensis genomic DNA (gDNA) detected in biopsies from CL lesions. Likewise, there was no association between helminth burden and response to treatment after 90 days. Considering quantification of parasite DNA in CL lesions, participants who were cured at 90 days had a median of 0.017 ng/mg gDNA, and participants who failed therapy had a median of 0.091 ng/mg gDNA (P = 0.03). The results indicate that cutaneous Leishmania load may influence therapeutic response in CL.

scholarly journals Comparative genomic studies and in-silco strategies on Leishmania brazilensis, Leishmania infantum and Leishmania major: Conserved features, putative functions and potential drug target

2013 ◽  
Vol 1 (2) ◽  
pp. 62-66 ◽  
Author(s):  
N. R. Rakesh ◽  
S. Pradeep
Keyword(s):  
Leishmania Infantum ◽  
Drug Target ◽  
Drug Users ◽  
Leishmania Major ◽  
Leishmania Species ◽  
Docking Studies ◽  
World Health ◽  
Gene Location ◽  
Comparative Genomic ◽  
Leishmania Braziliensis

Leishmaniasis is a parasitic disease found largely in the tropics, which the World Health Organization has estimated infects 12 million people worldwide each year. More recently cases have been reported in Europe among intravenous drug users with HIV. At least 20 Leishmania species infect humans. New world parasite Leishmania. braziliensis is the causative agent of mucocutaneous Leishmaniasis. The old world species Leishmania. major and Leishmania. infantum, which are present in Africa, Europe and Asia, are parasites that cause cutaneous and visceral Leishmaniasis respectively. Aim of this Study is determination of major common genes and Protein identified Gene location on each of the chromosomes, and identification of a common protein drug target Promastigote surface antigen with available lead molecule acetylglucosamine (6-(acetylamino)-6-deoxyhexopyranose) and docking studies on those considered Leishmania species.DOI: http://dx.doi.org/10.3126/ijasbt.v1i2.8077 Int J Appl Sci Biotechnol, Vol. 1(2): 63-67

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