Leishmaniasis and fluconazol

OBJECTIVE: Cutaneous Leishmaniasis (CL) is one of the highly prevalent endemic diseases in the Middle East. The disease is a complex skin infection imposing a heavy burden on many developing countries. This study aimed to evaluate the impact of adding oral fluconazole to topical cryotherapy on the treatment efficacy and time to achieve complete recovery of CL lesions. METHOD: This triple-blind randomized clinical trial included 52 participants with CL. Participants were allocated to receive either weekly cryotherapy with liquid nitrogen and oral fluconazole at a dose of 6 mg/kg daily at a maximum of 400 mg for 6 weeks as the interventional arm or weekly cryotherapy with liquid nitrogen plus the placebo for the same period of 6 weeks as the control arm...

UNLABELLED: Over a 6-month span, three patients under 5 years old with cutaneous leishmaniasis presented to the Pediatric Infectious Diseases Clinic at the University of Texas Southwestern Medical Center/Children's Health Dallas. None had traveled outside of northern Texas/southern Oklahoma; all had Leishmania mexicana infections confirmed by PCR. We provide case descriptions and images to increase the awareness of this disease among United States (US) physicians and scientists. Two patients responded to fluconazole, but the youngest required topical paromomycin...

Leishmaniasis is a parasitic infection that can involve the skin, mucosal membranes, and internal organs. It is endemic to the tropics. A forty-three-year-old male, diagnosed and treated for visceral leishmaniasis 15 years ago, presented with a complaint of a progressively growing lesion on his face for five years. A detailed history, clinical examination, and histopathological examination were done to reach a diagnosis of cutaneous leishmaniasis (CL). Treatment with oral fluconazole 300 mg daily for six months, followed by 50 mg miltefosine three times a day for another two months, led to complete resolution of symptoms, and the lesion on the face was cured...

UNLABELLED: Over a six-month span, three patients under five years old with cutaneous leishmaniasis presented to the Pediatric Infectious Diseases Clinic at the University of Texas Southwestern Medical Center/Children's Health Dallas. None had traveled outside of the United States (US); all had confirmed L. mexicana infections by PCR. We provide case descriptions and images to increase the awareness of this disease among US physicians and scientists. Two patients responded to fluconazole, but one required topical paromomycin...

In its 'Road map for neglected tropical diseases 2021-2030', the World Health Organization outlined its targets for control and elimination of neglected tropical diseases (NTDs) and research needed to achieve them. For many NTDs, this includes research for new treatment options for case management and/or preventive chemotherapy. Our review of small-molecule anti-infective drugs recently approved by a stringent regulatory authority (SRA) or in at least Phase 2 clinical development for regulatory approval showed that this pipeline cannot deliver all new treatments needed...

Histoplasmosis is an endemic mycosis in the Americas. However, its diagnosis is challenging due to the complexity and limited availability of conventional laboratory techniques-antigen tests, culture, and staining. Microscopic preparations often confuse with other pathogens, such as Leishmania spp. The genus Histoplasma capsulatum comprises three varieties: var. capsulatum , var. duboissi , and var. farciminosum , which cannot be distinguished using conventional techniques. An infant from a tropical region of Ecuador was hospitalized for fever, bloody diarrhea, and anemia persisting for two months...

Visceral leishmaniasis, caused by Leishmania donovani , is a life-threatening parasitic disease, but current antileishmanial drugs are limited and have severe drawbacks. There have been efforts to repurpose antifungal azole drugs for the treatment of Leishmania infection. Antifungal azoles are known to potently inhibit the activity of cytochrome P450 (CYP) 51 enzymes which are responsible for removing the C14α-methyl group of lanosterol, a key step in ergosterol biosynthesis in Leishmania . However, they exhibit varying degrees of antileishmanial activities in culture, suggesting the existence of unrecognized molecular targets for these compounds...

Diffuse cutaneous leishmaniasis (DCL) is a rare parasitic infection caused by the Leishmania species. Diffuse cutaneous leishmaniasis commonly presents as non-ulcerating papules and nodules over the face, neck, and arms. A middle-aged female presented with multiple nodular lesions on her face, neck, and chest region. Histopathology of the lesions showed multiple amastigotes, confirming the diagnosis of DCL. She was successfully treated with a combination course of rifampicin and fluconazole. Here, we report the first case of DCL in north India, a non-endemic area for cutaneous leishmaniasis...

Human leishmaniasis is an infectious disease caused by Leishmania protozoan parasites. Current chemotherapeutic options against the deadly disease have significant limitations. The ergosterol biosynthetic pathway has been identified as a drug target in Leishmania. However, remarkable differences in the efficacy of antifungal azoles that inhibit ergosterol biosynthesis have been reported for the treatment of leishmaniasis. To better understand the sterol biosynthetic pathway in Leishmania and elucidate the mechanism underlying the differential efficacy of antifungal azoles, we developed a new LC-MS/MS method to study sterol profiles in promastigotes of three Leishmania species, including two L...

Leishmaniasis is a zoonosis acquired from the bite of a sandfly that introduces the amastigote forms of leishmania into the bloodstream. It is a frequent infection in the countries of the Mediterranean basin and in Tunisia, where it is rife in an endemo-epidemic mode. However, it is rare after kidney transplantation. It constitutes a challenge due to the diagnostic difficulty, the variability and the polymorphism of the clinical picture in immunocompromised patients. We report seven observations of cutaneous leishmaniasis after kidney transplantation through which we try to identify diagnostic and therapeutic difficulties...

The present paper reported a first imported case of cutaneous leishmaniasis in a 10-year- old child who returned from Saudi Arabia to Malaysia. Six weeks after his travel to Malaysia, two erythematous dermal nodules were developed over his right cheek and chin. Occurrence of intracellular amastigote of Leishmania was observed through examination of skin biopsy with hematoxylin and eosin stain. Furthermore, molecular analysis of ribosomal internal transcribed spacer 1 (ITS1) of Leishmania spp. confirmed the child was infected with Leishmania tropica...

We describe 4 cases of cutaneous leishmaniasis in children in Australia. Treatment is challenging given lack of firm guidelines and limited access to conventional modalities used in endemic countries. Topical paromomycin or oral fluconazole were effective outpatient-based first-line treatments, however, topical paromomycin use was limited by expense to import or compound locally.

Failure of treatment of cutaneous leishmaniasis with antimonial drugs and miltefosine is frequent. Use of oral combination therapy represents an attractive strategy to increase efficacy of treatment and reduce the risk of drug resistance. We evaluated the potency of posaconazole, itraconazole, voriconazole, and fluconazole and the potential synergy of those demonstrating the highest potency, in combination with miltefosine (HePC), against infection with Leishmania (Viannia) panamensis. Synergistic activity was determined by isobolograms and calculation of the fractional inhibitory concentration index (FICI), based on parasite quantification using an ex vivo model of human peripheral blood mononuclear cells (PBMCs) infected with a luciferase-transfected, antimony and miltefosine sensitive line of L...

Cutaneous leishmaniasis, which is the most common form of leishmaniasis, classically presents as small erythematous papules and nodules that develop into ulcers with indurated, raised outer borders. However, lesions of cutaneous leishmaniasis can have pleomorphic and atypical presentations. The erysipeloid form is one of the rare, atypical presentations of cutaneous leishmaniasis. Reported is a case of a 58-year-old man from the hilly region of Nepal who presented with an atypical erythematous and edematous plaque over the left antecubital fossa...

Buruli ulcer and cutaneous leishmaniasis both have the similar cutaneous clinical presentation. Therefore, relying on clinical diagnosis can be challenging. We present a case of 45 years old woman diagnosed with cutaneous leishmaniasis, confirmed by skin biopsy. She received different modalities of anti-leishmanial treatment (fluconazole 450mg daily for 4 weeks, sodium stibogluconate (SSG) followed by thermal therapy, SSG/IV 20mg/kg for 30 days combined with paromomycin 15mg/kg IM for 17 days). These treatments were associated with partial improvement of the ulcer and failure of healing...

We report two cases of cutaneous leishmaniasis in natives of central region of Nepal. The first patient in our series, an adult female, presented with a small nodule on the philtrum of upper lip and the second case, a male child, presented with two crusted plaques on forehead. The final diagnosis was based on histopathological findings; however, species characterization was not possible because of its unavailability in the country. These patients responded well to the treatment with Miltefosine (First case) and Fluconazole (second case)...

BACKGROUND: Cutaneous leishmaniasis is endemic in Morocco. Mucosal involvement is rare. We report a case in Morocco of cutaneous leishmaniasis of the vermilion border of the upper lip extending to the oral mucosa due to Leishmania tropica. PATIENTS AND METHODS: A 15-year-old girl was seen with 2 ulcerated lesions, present for 4 months, situated on the left cheek and vermilion border and extending to the oral mucosa. The diagnosis of leishmaniasis was confirmed by direct examination revealing high numbers of Leishmania amastigotes...

This mini-review focuses on leishmanicidal drugs that were sourced from small molecules previously approved for other diseases. The mechanisms of action of these molecules are herein explored, to probe the origins of their inter-species growth inhibitory activities. It is shown how the transversal action of the azoles - fluconazole, posaconazole and itraconazole - in both fungi and Leishmania is due to the occurrence of the same target, lanosterol 14-α-demethylase, in these two groups of species. In turn, the drugs miltefosine and amphotericin B are presented as truly multi-target agents, acting on small molecules, proteins, genes and even organelles...

Histoplasmosis and leishmaniasis are neglected and endemic diseases in Argentina, and generally are found associated with immunosuppression. We report the case of an immunocompetent 16-years-old man with simultaneous occurrence of central nervous system histoplasmosis and cutaneous leishmaniasis. Upon admission, the patient showed a one-month old skin lesion in a leg and mild paraparesis. Imaging studies detected thickening and edema in the spinal cord and the cerebrospinal fluid analysis was within normal range...

Leishmaniasis is a vector borne disease transmitted by phlebotomine sandflies. Cutaneous leishmaniasis (CL) predominantly causes skin ulcers but may disseminate. CL may present a therapeutic challenge. The present study reports the case of a 15-year old boy with CL consisting of a single, ulcer on the leg, resistant to pentavalent antimony, oral fluconazole and topical ketoconazole therapy. Repeated photodynamic therapy using aminolevulinic acid resulted in complete healing of the ulcer, suggesting utility of this approach in resistant cases of CL...