Safety and efficacy of miltefosine monotherapy and pentoxifylline associated with pentavalent antimony in treating mucosal leishmaniasis.

INTRODUCTION: Mucosal Leishmaniasis (ML) is a difficult to treat and severe form of Leishmaniasis. In general, more than 40% of subjects with ML have therapeutic failure upon the use of pentavalent antimony (Sbv) at 20mg/kg/day during 30 days. Additionally, Sbv is a toxic drug that requires parenteral administration, and many patients will need several courses to be cured. In cases that cannot be treated or cured by Sbv, the alternative is amphotericin B, another toxic and parenteral drug. As a consequence, many ML patients will be cured only after years of disease and may present several morbidities due to the aggressiveness of the disease or toxicity related to the treatment. Areas covered: We aimed to review clinical trials with Miltefosine or Sbv associated with pentoxifylline in the treatment of ML. Expert commentary: There are few studies to define more effective and safer therapy in mucosal disease caused by Leishmania, with an urgent need to supporting and funding well designed trials. Miltefosine monotherapy, as well as pentoxifylline combined with Sbv are promising therapeutic approaches to increase the cure rate of this neglected disease.

Differential Gene Expression and Infection Profiles of Cutaneous and Mucosal Leishmania braziliensis Isolates from the Same Patient.

BACKGROUND: Leishmaniasis is a complex disease in which clinical outcome depends on factors such as parasite species, host genetics and immunity and vector species. In Brazil, Leishmania (Viannia) braziliensis is a major etiological agent of cutaneous (CL) and mucosal leishmaniasis (MCL), a disfiguring form of the disease, which occurs in ~10% of L. braziliensis-infected patients. Thus, clinical isolates from patients with CL and MCL may be a relevant source of information to uncover parasite factors contributing to pathogenesis. In this study, we investigated two pairs of L. (V.) braziliensis isolates from mucosal (LbrM) and cutaneous (LbrC) sites of the same patient to identify factors distinguishing parasites that migrate from those that remain at the primary site of infection. METHODOLOGY/PRINCIPAL FINDINGS: We observed no major genomic divergences among the clinical isolates by molecular karyotype and genomic sequencing. RT-PCR revealed that the isolates lacked Leishmania RNA virus (LRV). However, the isolates exhibited distinct in vivo pathogenesis in BALB/c mice; the LbrC isolates were more virulent than the LbrM isolates. Metabolomic analysis revealed significantly increased levels of 14 metabolites in LbrC parasites and 31 metabolites in LbrM parasites that were mainly related to inflammation and chemotaxis. A proteome comparative analysis revealed the overexpression of LbrPGF2S (prostaglandin f2-alpha synthase) and HSP70 in both LbrC isolates. Overexpression of LbrPGF2S in LbrC and LbrM promastigotes led to an increase in infected macrophages and the number of amastigotes per cell at 24-48 h post-infection (p.i.). CONCLUSIONS/SIGNIFICANCE: Despite sharing high similarity at the genome structure and ploidy levels, the parasites exhibited divergent expressed genomes. The proteome and metabolome results indicated differential profiles between the cutaneous and mucosal isolates, primarily related to inflammation and chemotaxis. BALB/c infection revealed that the cutaneous isolates were more virulent than the mucosal parasites. Furthermore, our data suggest that the LbrPGF2S protein is a candidate to contribute to parasite virulence profiles in the mammalian host.

[Recidivant laryngeal leishmaniasis: an unusual case in an immunocompetent patient treated with corticosteroids]. / Leishmaniosis laríngea recidivante: un caso inusual en un paciente inmunocompetente tratado con corticoides.

Leishmaniosis is a chronic parasitic disease, which in Argentina is mainly caused by protozoa belonging to the Leishmania (Viannia) braziliensis complex, leading to cutaneous and mucosal pathologies. We report a rare case of laryngeal leishmaniosis in a 29 year-old man from Jujuy province, Argentina, who had been misdiagnosed with other pathologies, carrying this infectious disease for about 20 years. During 2008, the patient was admitted with complaints of progressive hoarseness of the voice and dyspnea. He also reported having received tuberculostatics, antifungal and corticosteroids treatments since 2002. Different biopsies and direct laryngoscopic exams revealed inespecific granulomatous larynx, TBC-related laryngitis, laryngitis related to Histoplasma infection, extra-nodal Natural Killer-cell lymphoma. Finally, the patient was evaluated at the University Hospital and the final diagnosis was: granulomatous larynx, intra and extra-cytoplasmic Leishmania spp amastigotes, negative for TBC and Histoplasma cultures, and chronic laryngitis related to Leishmania infection, according to the laryngeal endoscopy, microbiological and histopathological exams, respectively. The patient received pentavalent antimonial treatment and his condition improved after 2 months of follow-up. Primary laryngeal leishmaniosis is rare and this localization does not belong to the most prevalent mucosal leishmaniosis. However, this parasitic disease warrants special concern, especially in patients who received prolonged corticosteroid treatments, in order to avoid a misdiagnosis of this disease.

Leishmaniose mucosa: aspectos clínicos e epidemiológicos: [revisão] / Mucosal leishmaniasis: epidemiological and clinical aspects: [review]

A leishmaniose tem sido documentada em diversos países, sendo estimada uma prevalência mundial de 12 milhões, com 400.000 casos novos de doença por ano. A leishmaniose tegumentar americana encontra-se situada entre as grandes endemias existentes no Brasil e na América Latina. OBJETIVO: O objetivo deste estudo é complementar o conhecimento sobre leishmaniose mucosa, apresentando a experiência dos Serviços de Imunologia e de Otorrinolaringologia do Hospital Universitário Professor Edgar Santos da Universidade Federal da Bahia. COMENTÁRIOS: A leishmaniose cutânea é a forma mais comum de leishmaniose tegumentar americana, contudo, concomitantemente ou após anos de doença cutânea podem ocorrer lesões mucosas. A leishmaniose mucosa é causada principalmente pela L. braziliensis braziliensis e, apesar de a mucosa nasal ser a área principalmente acometida, lesões podem também ser documentadas nos lábios, boca, na faringe e na laringe. Fatores do parasito, bem como da resposta imune do hospedeiro podem estar envolvidos na patogênese da lesão tissular na leishmaniose mucosa.

Leishmaniasis has been documented in several countries, with an estimated prevalence of 12 million people and an incidence at around 400,000 new cases per year. Leishmaniasis in the New World is one the major endemic diseases in Brazil and Latin America. OBJECTIVE: The aim of this study was to add to the current knowdlegde on mucosal leishmaniasis, bringing the experience of the Imunology and Otolaryngology Departments in the Professor Edgar Santos University Hospital of the Federal University of Bahia. CONCLUSION: Cutaneous leishmaniasis is the most common form of New World Leishmaniasis; mucosal legions may occur simultaneously or after years of disease. Mucosal leishmaniasis is caused mainly by L. braziliensis braziliensis; although the nasal mucosa is the most affected area, lesions may be found on the lips, mouth, pharynx and larynx. In addition to parasite-related factors, the host immune response may be involved in the pathogenicity of lesions in mucosal leishmaniasis.

Mucosal leishmaniasis: epidemiological and clinical aspects.

UNLABELLED: Leishmaniasis has been documented in several countries, with an estimated prevalence of 12 million people and an incidence at around 400,000 new cases per year. Leishmaniasis in the New World is one the major endemic diseases in Brazil and Latin America. OBJECTIVE: The aim of this study was to add to the current knowledge on mucosal leishmaniasis, bringing the experience of the Immunology and Otolaryngology Departments in the Professor Edgar Santos University Hospital of the Federal University of Bahia. CONCLUSION: Cutaneous leishmaniasis is the most common form of New World Leishmaniasis; mucosal legions may occur simultaneously or after years of disease. Mucosal leishmaniasis is caused mainly by L. braziliensis braziliensis; although the nasal mucosa is the most affected area, lesions may be found on the lips, mouth, pharynx and larynx. In addition to parasite-related factors, the host immune response may be involved in the pathogenicity of lesions in mucosal leishmaniasis.

Análisis de la Intradermoreacción de montenegro e inmunoflourescencia indirecta en pacientes con leishmaniasis cutánea y mucocutánea de zonas endémicas del Paraguay / Analysis of the intradermo reaction of montenegro and indirect inmunoflourescence in patients with cutaneous and mucocutaneous leishmaniasis in endemic zones of Paraguay

Estudio prospectivo, de corte transversal donde fueron incluídos 102 pacientes con diagnóstico clínico y serológico de Leishmania Cutánea (LC) y Mucocutánea (LMC), que concurrieron al Laboratorio Central de Salud Pública, durante los años 1996 y 97, para la determinación del título de anticuerpos IgG anti-leismania se utilizó la Inmunoflourescencia Indirecta (IFI) y la Intradermoreacción de Montenegro (IDRM)

Isolamento de corynebacterium diphtheriae de úlceras cutâneo-mucosas por Leishmania / Isolation of Corynebacterium diphtheriae from mucocutaneous ulcers due to Leishmania

Descrevemos o isolamento do C. diphtheriae em uma regiäo endêmica da leishmaniose cutâneo-mucosa por Leishmania braziliensis braziliensis. Materiais das lesöes cutâneas foram obtidos de dezesseis pacientes. Nove deles foram portadores do bacilo (56%). Os microrganismos suspeitos foram identificados pelos testes de fluorescência sob luz ultravioleta, teste de virulência "in vitro" (por imunodifusäo radial simples), pesquisa da enzima pirazina-carboxilamidase (Pyz) e por imunofluorescência direta e indireta