Unbalanced inflammatory reaction could increase tissue destruction and worsen skin infectious diseases - a comparative study of leishmaniasis and sporotrichosis.

The clinical presentations of skin diseases produced by different pathogens, as American tegumentary leishmaniasis (ATL) and sporotrichosis can be similar and possibly influenced by the skin immune system (SIS). The aim of the study was to understand the underlying mechanisms of skin inflammation produced by different pathogens. We used immunohistochemistry to analyze 96 patients: a- localized cutaneous leishmaniasis (LCL-ATL); b- sporotrichoid cutaneous leishmaniasis (SCL-ATL); c-lymphocutaneous (LC-SP); d- fixed (F-SP) sporotrichosis. LCL-ATL and SCL-ATL had a significantly higher percentage of CD8, FasL and NOS2 than sporotrichosis. In contrast, LC-SP had a substantially higher percentage of CD4, BCl2 and neutrophils than ATL lesions. These results indicated some differences in the profile of the in situ immune response suggesting that SIS is a complex, adaptable system capable of different responses to intracellular or extracellular pathogens. However, regardless of the etiological agents, the inflammatory reaction and clinical manifestations can be similar. SCL-ATL and LC-SP presented similarities in both clinical presentation and in situ inflammatory profile (CD3, CD22, neutrophils, macrophages). The clinical presentation of ATL and sporotrichosis could be explained by a combination of factors both of the host SIS and the etiological agent. The unbalanced host parasite relationship could result in atypical manifestations of skin disease.

Cytotoxic cell involvement in human cutaneous leishmaniasis: assessments in active disease, under therapy and after clinical cure.

Cutaneous leishmaniasis (CL) is an important public health issue worldwide. The control of Leishmania infection depends on cellular immune mechanisms, and the inflammatory response may contribute to pathogenesis. A beneficial role of CD8(+) T lymphocytes has been proposed; nevertheless, other studies suggest a cytotoxic role of CD8(+) T lymphocytes involved in tissue damage, showing controversial role of these cells. The goal of the current study was to understand the immunopathology of CL and determine the profile of cytotoxic cells--such as CD4(+) T, natural killer and natural killer T cells--that might be involved in triggering immunological mechanisms, and may lead to cure or disease progression. The frequencies of cytotoxic cell populations in peripheral blood, obtained from patients with active disease, during treatment and after clinical healing, were assessed by flow cytometry. Cytotoxicity could not be related to a deleterious role in Leishmania braziliensis infection, as patients with active CL showed similar percentages of degranulation to healthy individuals (HI). Cured patients exhibited a lower percentage of degranulating cells, which may be due to a downregulation of the immune response. The understanding of the immunopathological mechanisms involved in CL and the commitment of cytotoxic cells enables improvements in therapeutic strategies.

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.

Multifunctional CD4⁺ T cells in patients with American cutaneous leishmaniasis.

Leishmaniasis is a group of important parasitic diseases affecting millions worldwide. To understand more clearly the quality of T helper type 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total interferon (IFN)-γ-producing CD4(+) T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of multifunctional CD4(+) T cells (28% of the total Th1 response evaluated), whereas LaAg induced predominantly single-positive cells (68%), and 57% of those were IFN-γ single-positives. Multifunctional CD4(+) T cells showed the highest mean fluorescence intensity (MFI) for the three Th1 cytokines assessed and MFIs for IFN-γ and interleukin-2 from those cells stimulated with LbAg were significantly higher than those obtained after LaAg stimulation. These major differences observed in the generation of multifunctional CD4(+) T cells suggest that the quality of the Th1 response induced by L. amazonensis antigens can be involved in the mechanisms responsible for the high susceptibility observed in L. amazonensis-infected individuals. Ultimately, our results call attention to the importance of studying a Th1 response regarding its quality, not just its magnitude, and indicate that this kind of evaluation might help understanding of the complex and diverse immunopathogenesis of American tegumentary leishmaniasis.

Risk factors associated with dizziness during treatment of mucosal leishmaniasis with meglumine antimoniate: 16-year retrospective study of cases from Rio de Janeiro, Brazil.

OBJECTIVE: To evaluate dizziness in patients receiving meglumine antimoniate for the treatment of mucosal leishmaniasis. MATERIALS AND METHODS: We retrospectively studied 127 patients treated at the Laboratory of Leishmaniasis Surveillance, Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, between 1 January 1989 and 31 December 2004. RESULTS: A low dose of meglumine antimoniate (5 mg/kg/day) was used in 86.6 per cent of patients; a dose of 10 mg/kg/day or higher was used in 13.4 per cent of patients. Dizziness was reported by 4.7 per cent of patients. The adjusted odds ratios were 7.37 for dizziness in female patients, 4.9 for dizziness in patients aged 60 years or older, and 7.77 for dizziness in the presence of elevated serum lipase. CONCLUSION: We suggest that dizziness may be a side effect of meglumine antimoniate, particularly in elderly individuals, in females and in patients with elevated serum lipase.

Impairments in multibacillary leprosy; a study from Brazil.

This is a retrospective cohort study of 103 multibacillary leprosy patients (18% BB, 48% BL and 34% LL) followed during and after treatment, in a tertiary referral centre with an outpatient clinic in an endemic area in Brazil, for an average period of 65 months since the start of multidrug therapy (24-dose MDT). The objective of the study was to identify the role of overt neuritis (presence of pain in a peripheral nerve trunk, with or without enlargement or neural function damage), in the development of impairments. They were evaluated using the World Health Organization disability grade before treatment, at the end of the treatment, and at the end of the follow-up period. Thirty-four percent of patients presented overt neuritis during MDT, and 45% had overt neuritis episodes during the follow-up period; the most commonly affected nerves were ulnar, fibular and posterior tibial nerves, and the neuritic episodes were carefully treated with steroid therapy and physiotherapy. Impairments were associated with: affected (painful and/or thick) nerves at diagnosis (P < 0.005); delay in diagnosis (P = 0.010); impairments already present at the start of treatment (P = 0.00041 at the end of MDT, and P = 0.000013 at the end of follow-up); occurrence of overt neuritis episodes during MDT (P = 0.0016) or the whole follow-up (P = 0.015). These data draw attention to the importance of early diagnosis and of good neurological examination throughout the follow-up, as well as suggest the importance of neuritis in the induction of impairments in multibacillary leprosy.

Imunidade celular e humoral na hanseníase bordeline tuberculoid (BT) / Humoral and cellular immunity in bordeline tuberculoid (BT) leprosy

Foram estudados 20 pacientes com diagnóstico de hanseníase bordeline tuberculoid (BT), classificados segundo os critérios de Ridley & Jopling, bem como dois pacientes com forma Tuberculoid tuberculoid (TT), todos com baciloscopia negativa, exceto um, que apresentou índice baciloscópico 1+. Todos os pacientes foram avaliados quanto a sua capacidade de resposta imune humoral ao DBSA (antígeno sintético semelhante ao glicolipídeo fenólico I, específico do M, leprae) e 18 pacientes foram submetidos a testes de avaliaçåo da resposta imunocelular in vivo (teste Mitsuda) e in vitro (linfoproliferaçåo e produçåo de interferon-gama) frente ao Mycobacterium leprae. Observamos que 90 por cento dos pacientess apresentaram resultados negativos quanto à pesquisa de IgM anti-DBSA pelo método imunoenzimático ELISA (densidade óptica , 0,27), o que demonstra ser este teste inadequado para a detecçåo de pacientes paucibacilares. Quanto aos testes de imunidade celular, oito pacientes (44,4 por cento) apresentaram teste de Mitsuda positivo (>= 5mm), sendo os demais considerados negativos. Cerca de 89 por cento dos pacientes tiveram teste de Mitsuda maior ou igual a 3mm. Doze pacientes (66,7 por cento) tiveram resposta linfoproliferativa positiva (índice estimulatório >= 3,0) para o M. leprae. Vinte e dois por cento dos pacientes apresentaram níveis de interferon-gama acima do limite de positividade (40 U/ml). Houve 66,7 por cento de correlaçåo entre os testes de Mitsuda e interferon-gama; 55,6 por cento de correlaçåo entre os testes in vitro (linfoproliferaçåo e interferon-gama). Quando estes três testes foram considerados em conjunto, uma correlaçåo de 38,9 por cento foi observada. Este estudo demonstra a heterogeneidade do comportamento imunológico mediado por células e anticorpos em pacientes com hanseníase BT, apesar de todos histologicamente serem capazes de conter a multiplicaçåo bacilar e de formar granulomas epitelióides