Geospatial analysis of tegumentary leishmaniasis in Rio de Janeiro state, Brazil from 2000 to 2015: Species typing and flow of travelers and migrants with leishmaniasis.

BACKGROUND: We identified the species of Leishmania isolated from traveling and migrant patients attended in a reference center from 2000 to 2015, we performed the georeferencing of these species in Rio de Janeiro (RJ) state and we had knowledge about the human flows between the likely location of infection (LLI) and place of residence (PR) in RJ state, Brazil. METHODOLOGY/PRINCIPAL FINDINGS: This is a retrospective cross-sectional study including 171 patients diagnosed with ATL. Google Maps, OpenStreetMap, and Bing Maps were tools used to georeference LLI and PR. For etiological identification, we used isoenzyme electrophoresis, polymerase chain reaction-restriction fragment length polymorphism (molecular target hsp70C with restriction enzymes HaeIII and BstUI), and sequencing of the internal transcribed spacer of ribosomal DNA. ARCGIS software was used to create maps of the geographic distribution of Leishmania species in the state and municipality of RJ, together with flows between the LLI and PR. Isolates from 104 patients were identified as: L. (Viannia) braziliensis (80.8%), L. (V.) naiffi (7.7%), L. (V.) guyanensis (6.7%), L. (Leishmania) amazonensis (1%), and genetic variants of L. (V.) braziliensis (3.8%). The flow maps showed that the LLI included 4 countries, 19 Brazilian states, and 18 municipalities of RJ state. The Brazilian states with the highest density of cases were Amazonas (n = 32), Bahia (n = 18), and Ceará (n = 15). CONCLUSIONS/SIGNIFICANCE: This work is the first contribution to the knowledge of the routes of Leishmania species introduced in RJ state by migrants and travelers patients. L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) naiffi, L. (L.) amazonensis, and genetic variants of L. (V.) braziliensis were identified in RJ state. To determine whether the autochthonous transmission of these imported species is possible it is necessary the adaptation of these species to environmental conditions as well as the presence of reservoirs and phlebotomine vectors in this region.

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

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.

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

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.

Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil.

BACKGROUND: Although high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute. METHODS: A single-blind, non-inferiority, randomized controlled trial was conducted comparing high dose with low dose of antimony in subjects with ACL treated at a referral center in Rio de Janeiro, an endemic area of Leishmania (Viannia) braziliensis transmission. The primary outcome was clinical cure at 360 days of follow-up in the modified-intention-to-treat (mITT) and per-protocol (PP) populations. Non-inferiority margin was 15%. Secondary objectives included occurrence of epithelialization, adverse events and drug discontinuations. This study was registered in ClinicalTrials.gov: NCT01301924. RESULTS: Overall, 72 patients were randomly assigned to one of the two treatment arms during October 2008 to July 2014. In mITT, clinical cure was observed in 77.8% of subjects in the low dose antimony group and 94.4% in the high dose antimony group after one series of treatment (risk difference 16.7%; 90% CI, 3.7-29.7). The results were confirmed in PP analysis, with 77.8% of subjects with clinical cure in the low dose antimony group and 97.1% in the high dose antimony group (risk difference 19.4%; 90% CI, 7.1-31.7). The upper limit of the confidence interval exceeded the 15% threshold and was also above zero supporting the hypothesis that low dose is inferior to high dose of antimony after one series of treatment. Nevertheless, more major adverse events, a greater number of adverse events and major adverse events per subject, and more drug discontinuations were observed in the high dose antimony group (all p<0.05). Interestingly, of all the subjects who were originally allocated to the low dose antimony group and were followed up after clinical failure, 85.7% achieved cure after a further treatment with local therapy or low dose of antimony. CONCLUSIONS: Compared with high dose, low dose of antimony was inferior at the pre-specified margin after one series of treatment of ACL, but was associated with a significantly lower toxicity. While high dose of antimony should remain the standard treatment for ACL, low dose antimony treatment might be preferred when toxicity is a primary concern.

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.

First report on ototoxicity of meglumine antimoniate.

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.

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.

Intralesional meglumine antimoniate for treatment of cutaneous leishmaniasis patients with contraindication to systemic therapy from Rio de Janeiro (2000 to 2006).

We evaluated the effectiveness and safety of intralesional meglumine antimoniate (MA) in 24 not submitted to previous treatment patients with cutaneous leishmaniasis (CL) and with contraindication to systemic therapy. Each treatment consisted of one to four intralesional applications of MA at 15-day intervals. Patients' age ranged from 3 to 90 years; fourteen were females. Intralesional treatment in the absence of any relevant toxicity was successful in 20 (83.3%) patients. Three patients required additional treatment with amphotericin B and one required systemic MA. None of the patients developed mucosal lesions when followed up to 60 months. Intralesional MA is an effective and less toxic alternative treatment of patients with CL and contraindication to systemic therapy.

American cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis resistant to meglumine antimoniate, but with good response to pentamidine: a case report.

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 4 mg/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.

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.

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

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.