Maurício Naoto Saheki

Influence of the nutritional status in the clinical and therapeutical evolution in adults and elderly with American Tegumentary Leishmaniasis

The objective of this study is to describe the nutritional status of adult and elderly patients with American Tegumentary Leishmaniasis (ATL). It was conducted a longitudinal study in 68 adult and elderly patients with ATL treating at the Surveillance Leishmaniasis Laboratory at the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (Fiocruz), from 2009 to 2012. The nutritional assessment included the body mass index (BMI) and serum albumin levels. The clinical evolution (epithelialization and wound healing) was measured up to two years after ATL treatment. Most of the sample was composed of men (71%), adults (73%), with household income of 1-5 minimum wages (79%), and incomplete elementary school (48.5%). The predominant ATL form was cutaneous (72%), and 39% presented comorbidities, the most frequent was hypertension (30.8%). The most prevalent clinical and nutritional events were: recent decrease in food intake (23.9%); nasal obstruction (22.1%); oral ulcer (14.7%), anorexia and dysphagia (13.2% each) and odynophagia (10.3%). The total healing time was 115.00 (IR=80-230) days for skin lesions, and 120.00 (IR=104.50-223.50) days for mucous membrane lesions. Low body weight in 10%, and hypoalbuminemia in 12% of the patients have been observed. Low body weight was associated with age, mucosal leishmaniasis (ML), nasal obstruction, recent decrease in food intake and hypoalbuminemia. As for serum albumin depletion, association with the ML, dyspnea, dysphagia, odynophagia, recent decrease in food intake, absence of complete healing of the skin lesions, and increased healing time for mucous membrane lesions, was observed. The ML and their events that affect the alimentary intake have been related to the impairment of the nutritional status. Additionally, serum albumin depletion negatively affected the healing of the lesions, suggesting that a nutritional intervention can increase the effectiveness of the ATL treatment.

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.

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.

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.

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.

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.

Pancreatic toxicity as an adverse effect induced by meglumine antimoniate therapy in a clinical trial for cutaneous leishmaniasis

SUMMARY American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial. In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA). Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb5+)/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit. We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients. Patients treated with MA 20 mg Sb5+ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group. Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL.

Factors associated to adherence to different treatment schemes with meglumine antimoniate in a clinical trial for cutaneous leishmaniasis.

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.

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.

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.