Good response to pentamidine isethionate in a case of Mucosal Leishmaniasis caused by Leishmania (Viannia) braziliensis that was difficult to treat: Case Report

Abstract In Brazil, meglumine antimoniate is the first drug of choice for mucosal leishmaniasis treatment followed by amphotericin B and pentamidine isethionate. We report the case of a patient with severe mucosal lesions caused by Leishmania (Viannia) braziliensis that were difficult to treat. Over a 14-year period, the patient showed low adherence and three treatment attempts with meglumine antimoniate failed. Additionally, there was an unsatisfactory response to liposomal amphotericin B and nephrotoxicity when using amphotericin B deoxycholate that persisted after new treatment attempt with liposomal amphotericin B. Finally, healing was achieved with pentamidine isethionate and maintained during nine months of monitoring.

Effect of secondary infection on epithelialisation and total healing of cutaneous leishmaniasis lesions

BACKGROUND Cutaneous leishmaniasis (CL) generally presents with a single or several localised cutaneous ulcers without involvement of mucous membranes. Ulcerated lesions are susceptible to secondary contamination that may slow the healing process. OBJECTIVE This study verified the influence of non-parasitic wound infection on wound closure (epithelialisation) and total healing. METHODS Twenty-five patients with a confirmed diagnosis of CL and ulcerated lesions underwent biopsy of ulcer borders. One direct microbial parameter (germ identification in cultures) and four indirect clinical parameters (secretion, pain, burning sensation, pruritus) were analysed. FINDINGS Biopsies of ten lesions showed secondary infection by one or two microorganisms (Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis, Streptococcus pyogenes and Candida parapsilosis). "Secretion" and "burning sensation" influenced epithelialisation time but not total healing time. Positive detection of germs in the ulcer border and "pain" and "pruritus" revealed no influence on wound closure. CONCLUSIONS Our borderline proof of clinical CL ulcer infection inhibiting CL wound healing supports the need to follow antimicrobial stewardship in CL ulcer management, which was recently proposed for all chronic wounds.

Intralesional treatment with meglumine antimoniate in three patients with New World cutaneous leishmaniasis and large periarticular lesions with comorbidities

Abstract Although New World cutaneous leishmaniasis is not itself a life-threatening disease, its treatment with systemic antimonials can cause toxicity that can be dangerous to some patients. Intralesional meglumine antimoniate provides a viable, less toxic alternative. Herein, we describe an alternative treatment with subcutaneous intralesional injections of meglumine antimoniate into large periarticular lesions of three patients with cutaneous leishmaniasis and comorbidities. This treatment was safe, successful, and well tolerated. This case series suggests that intralesional meglumine antimoniate is an effective therapy for cutaneous leishmaniasis, even with periarticular lesions. This hypothesis should be tested in controlled clinical trials.

Sporotrichoid leishmaniasis: a cross-sectional clinical, epidemiological and laboratory study in Rio de Janeiro State, Brazil

ABSTRACT Background Atypical presentations of cutaneous leishmaniasis include sporotrichoid leishmaniasis (SL), which is clinically described as a primary ulcer combined with lymphangitis and nodules and/or ulcerated lesions along its pathway. Aims To assess the differences between patients with sporotrichoid leishmaniasis and typical cutaneous leishmaniasis (CL). Methods From January 2004 to December 2010, 23 cases of SL (4.7%) were detected among 494 CL patients diagnosed at a reference center for the disease in Rio de Janeiro State, Brazil. These 23 cases were compared with the remaining 471 patients presenting CL. Results SL predominated in female patients (60.9%, p = 0.024), with older age (p = 0.032) and with lesions in upper limbs (52.2%, p = 0.028). CL affected more men (64.5%), at younger age, and with a higher number of lesions exclusively in lower limbs (34.8%). Conclusions Differences in clinical and epidemiological presentation were found between SL patients as compared to CL ones, in a region with a known predominance of Leishmania (Viannia) braziliensis. The results are similar to the features of most of the sporotrichosis patients as described in literature, making the differential diagnosis between ATL and sporotrichosis more important in overlapping areas for both diseases, like in Rio de Janeiro State.

Immune reconstitution inflammatory syndrome in HIV and sporotrichosis coinfection: report of two cases and review of the literature

We report 2 cases of patients with immune reconstitution inflammatory syndrome (IRIS) associated with cutaneous disseminated sporotrichosis and human immunodeficiency virus (HIV) coinfection. The patients received specific treatment for sporotrichosis. However, after 4 and 5 weeks from the beginning of antiretroviral therapy, both patients experienced clinical exacerbation of skin lesions despite increased T CD4+ cells (T cells cluster of differentiation 4 positive) count and decreased viral load. Despite this exacerbation, subsequent mycological examination after systemic corticosteroid administration did not reveal fungal growth. Accordingly, they were diagnosed with IRIS. However, the sudden withdrawal of the corticosteroids resulted in the recurrence of IRIS symptoms. No serious adverse effects could be attributed to prednisone. We recommend corticosteroid treatment for mild-to-moderate cases of IRIS in sporotrichosis and HIV coinfection with close follow-up.

First report onoototoxicity of meglumine antimoniate / Primeiro relato de ototoxicidade pelo antimoniato de meglumina

Introduction: Pentavalent antimonials are the first drug of choice in the treatment of tegumentary leishmaniasis. Data on ototoxicity related with such drugs is scarcely available in literature, leading us to develop a study on cochleovestibular functions. Case Report: A case of a tegumentary leishmaniasis patient, a 78-year-old man who presented a substantial increase in auditory threshold with tinnitus and severe rotatory dizziness during the treatment with meglumine antimoniate, is reported. These symptoms worsened in two weeks after treatment was interrupted. Conclusion: Dizziness and tinnitus had already been related to meglumine antimoniate. However, this is the first well documented case of cochlear-vestibular toxicity related to meglumine antimoniate.

Introdução: Antimoniais pentavalentes são os fármacos de primeira escolha no tratamento da leishmaniose tegumentar. Dados de ototoxicidade relacionados a tais fármacos são escassos na literatura, o que nos levou a desenvolver um estudo de funções cócleo-vestibulares. Relato de caso: Relatamos caso de paciente masculino de 78 anos com leishmaniose tegumentar, que apresentou aumento significativo dos limiares auditivos com zumbido e tontura rotatória grave durante o tratamento com antimoniato de meglumina. Os sintomas pioraram até duas semanas após a interrupção do tratamento. Conclusão: Tontura e zumbido já tinham sido associados ao antimoniato de meglumina. Entretanto, este é o primeiro caso bem documentado de toxicidade cócleo-vestibular relacionado ao antimoniato de meglumina.

Factors associaeed to adherence to different tratment schemes with meglumine aantimoniate in a clinical trial for cutaneous leishmaniasis / Fatores associados à adesão a diferentes esquemas de tratamento com antimoniato de meglumina em ensaio clínico para leishmaniose cutânea

The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.

O desfecho favorável ao tratamento de uma enfermidade é influenciado pela adesão à terapia. Objetivamos avaliar fatores associados à adesão ao tratamento dos pacientes incluídos em ensaio clínico de equivalência entre o esquema de tratamento padrão e alternativos com antimoniato de meglumina (AM) no tratamento da leishmaniose cutânea (LC) no estado do Rio de Janeiro. Entre 2008 e 2011, 57 pacientes com LC foram entrevistados através de questionário para coleta de dados socioeconômicos. Para monitorização da adesão foram utilizados os seguintes métodos: contagem de ampolas excedentes, cartão de acompanhamento, teste de Morisky e teste de Morisky modificado (sem a pergunta referente ao horário). Observou-se adesão de 82,1% (devolução de ampolas), 86,0% (cartão de acompanhamento), 66,7% (teste de Morisky) e 86,0% (teste de Morisky modificado). Houve forte concordância entre o método contagem de ampolas e cartão de acompanhamento, bem como teste de Morisky modificado. Verificou-se associação significativa entre maior adesão ao tratamento e baixa dose de AM, bem como com menor número de pessoas dormindo no mesmo quarto. Recomendamos a utilização do teste de Morisky modificado na avaliação da adesão ao tratamento da LC com AM por ser método simples e com bom desempenho quando comparado aos outros testes.

Ensaio clínico de não inferioridade, randomizado, controlado, cego, de antimoniato de meglumina em dose baixa versus dose alta para leishmaniose cutânea americana no Rio de Janeiro, Brasil / A randomized, controlled, single blind, non-inferiority trial of low dose versus high dose meglumine antimoniate for American cutaneous leishmaniasis in Rio de Janeiro, Brazil

Fundamento: Na atualidade, há um corpo crescente de pesquisas que apontam para novas drogas e esquemas alternativos de antimônio para o tratamento da leishmaniose tegumentar americana (LTA). [...] Embora o tratamento alternativo com dose baixa de antimônio venha sendo utilizado nos últimos 30 anos, a evidência disponível provém de dois estudos retrospectivos, dois estudos prospectivos e relatos de caso. Em nosso conhecimento, este é o terceiro estudo randomizado que compara dose baixa com a dose alta de antimônio pentavalente (Sb5+) para o tratamento da LTA. Métodos: Em um estudo de não inferioridade, randomizado, controlado, cego realizado no estado do Rio de Janeiro, uma área endêmica de transmissão de Leishmania (Viannia) braziliensis, o tratamento em dose baixa de antimoniato de meglumina (5 mg Sb5+/kg/dia durante 30 dias) foi comparado com o tratamento em dose alta (20 mg Sb5+/kg/dia durante 20 dias) para leishmaniose cutânea americana (LCA). Participantes com idade maior ou igual a 13 anos com diagnóstico parasitológico de LCA foram randomizados para tratamento com dose baixa ou dose alta de antimoniato de meglumina. Os investigadores foram mascarados para o tratamento alocado. O desfecho primário foi a cura clínica no dia 360 nas populações de intenção de tratar modificada (mITT) e por protocolo (PP). Os desfechos secundários foram tempo de epitelização, tempo de cura clínica, grau de redução da lesão e da úlcera no dia 30. A margem de não inferioridade predeterminada foi de 15 por cento. Este estudo foi registrado no endereço eletrônico ClinicalTrials.gov, registro número NCT01301924. Resultados: Entre outubro de 2008 e dezembro de 2011, um total de 60 pacientes com LCA foi alocado para receber tratamento com antimoniato de meglumina em dose baixa ou em dose alta (30 por grupo)...

Background: There is an expanding field of research focusing on alternative schemesof antimony and new drugs to treat American tegumentary leishmaniasis (ATL). [...] Although thealternative low dose antimony treatment has been used for the past 30 years, theavailable evidence comes from two retrospective, two prospective cohort studies andcase reports. To our knowledge, this is the third randomized trial comparing low doseand high dose pentavalent antimony (Sb5+) to treat ATL. Methods: In a randomized,controlled, single blind, non-inferiority trial undertaken in Rio de Janeiro State, Brazil,an endemic area of Leishmania (Viannia) braziliensis transmission, low dose regimen ofmeglumine antimoniate (5 mg Sb5+/kg/day for 30 days) was compared with high doseregimen (20 mg Sb 5+/kg/day for 20 days) to treat American cutaneous leishmaniasis(ACL). Participants aged more than or equal to 13 years with parasitologically confirmed ACL wererandomly assigned to low dose or high dose treatment with meglumine antimoniate.Investigators were masked to treatment allocation. The primary endpoint was clinicalcure at day 360 on modified intention to treat (mITT) and per protocol (PP) populations. Secondary endpoints were time to epithelization, time to clinical cure, adverse events,degree of total lesion and ulcer diameter reduction at day 30. The predetermined noninferioritymargin was 15 percent. This trial is registered with ClinicalTrials.gov, numberNCT01301924. Results: Between October, 2008, and December, 2011, a total of 60patients with ACL were randomly assigned to low dose or high dose treatment ofmeglumine antimoniate (30 per group)...

American cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis resistant to meglumine antimoniate, but with good response to pentamidine: a case report / Leishmaniose cutânea americana causada pela Leishmania (Viannia) braziliensis resistente ao antimoniato de meglumina e com boa resposta terapêutica à pentamidina: relato de um caso

Relatamos um caso de um militar brasileiro com leishmaniose cutânea, cuja lesão reativou após dois tratamentos sistêmicos com antimoniato de meglumina. Foi tratado com anfotericina B, mas precisou interromper por intolerância à medicação. Após isolamento de Leishmania sp, seis infiltrações intralesionais de antimoniato de meglumina foram realizadas, sem resposta. Promastigotas de Leishmania sp. foram novamente isoladas. Foi submetido a tratamento intramuscular com pentamidina (4mg/kg). Parasitas da primeira e segunda biópsias foram identificados como Leishmania (Viannia) braziliensis; os da primeira biópsia eram mais sensíveis ao antimoniato de meglumina in vitro do que os da segunda biópsia. A lesão não reativou.

This is a case report of a Brazilian soldier with cutaneous leishmaniasis. The lesion relapsed following two systemic treatments with meglumine antimoniate. The patient was treated with amphotericin B, which was interrupted due to poor tolerance. Following isolation of Leishmania sp., six intralesional infiltrations of meglumine antimoniate resulted in no response. Leishmania sp promastigotes were again isolated. The patient was submitted to intramuscular 4mg/kg pentamidine. Parasites from the first and second biopsies were identified as Leishmania (Viannia) braziliensis; those isolated from the first biopsy were more sensitive to meglumine antimoniate in vitro than those isolated from the second biopsy. No relapse was observed.

Histoplasmose cutânea primária: relato de caso em paciente imunocompetente e revisão de literatura / Primary cutaneous histoplasmosis: case report on an immunocompetent patient and review of the literature

É relatado um caso de histoplasmose cutânea primária em um homem de 45 anos, com apresentação de um nódulo eritematoso no dorso da mão direita acompanhado de linfadenomegalia regional indolor, que se desenvolveu após trauma local ocorrido durante treinamento militar em túnel habitado por morcegos. O exame histológico de biópsia da lesão cutânea mostrou um infiltrado granulomatoso, porém não evidenciou elementos fúngicos. O cultivo deste material incubado em Ágar Sabouraud mostrou crescimento de Histoplasma capsulatum. Não foi encontrada evidência de envolvimento sistêmico ou imunossupressão. O tratamento com 400mg diários de itraconazol oral durante 6 meses resultou na remissão completa da lesão, mantida um ano após o término do tratamento.

This report describes a case of primary cutaneous histoplasmosis in a 45-year-old male. The presentation consisted of an erythematous nodule on the back of the right hand, accompanied by nontender regional lymphadenomegaly that developed following local trauma that occurred during military training in a tunnel inhabited by bats. Histological examination of a biopsy specimen from the skin lesion showed granulomatous infiltrate, but did not show fungal elements. Culturing of this material, incubated in Sabouraud agar, showed growth of Histoplasma capsulatum. No evidence of systemic involvement or immunosuppression was found. Treatment with 400 mg/day of itraconazole orally for six months resulted in complete remission of the lesion, which was maintained one year after the end of the treatment.