Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline.

Mucosal leishmaniasis (ML) is a severe form of tegumentary leishmaniasis associated with a persistent inflammatory response. High levels of TNF, IFN-γ, CXCL9 and CXCL10 are found in ML patients, and the association of pentoxifylline with antimony is more effective in decreasing the healing time in ML patients when compared to antimony alone. The present study aimed to investigate the existence of a correlation between cytokine and chemokine production and ML severity and evaluate the potential value of cytokine and chemokine production as marker of therapeutic response in ML patients. This prospective study included 86 subjects in an area of endemic Leishmania braziliensis transmission. Patients diagnosed with ML were classified into clinical stages ranging from I to V according to disease severity. TNF, IFN-γ, CXCL9 and CXCL10 levels were quantified in the supernatant of the mononuclear cell cultures by ELISA before and after treatment with antimony alone or antimony plus pentoxifylline. The median TNF level in the group with mild disease (Stages I-II) was 1064 pg/mL (142-3738 pg/mL), while, in the group with moderate or severe disease (Stages III-V), it was 1941 pg/mL (529-5294 pg/mL) (p = 0.008). A direct correlation was observed between ML clinical severity and levels of TNF production (r = 0.44, p = 0.007). Patients who were treated with antimony and pentoxifylline healed significantly faster than those treated with antimony alone (52 vs. 77 days, hazard ratio = 0.60; 95% confidence interval = 0.38-0.95, p = 0.013). Therapeutic failure was higher in the group that received antimony alone (25% vs. 7%; p = 0.041). There was a significant decrease in CXCL9 after therapy of ML in both groups (p = 0.013; p = 0.043). TNF levels are associated with the severity of mucosal diseases, and pentoxifylline associated with antimony should be the recommended therapy for ML in countries where liposomal amphotericin B is not available.

Phonotherapeutic Intervention in Patients With Mucosal Leishmaniasis Sequelae.

PURPOSE: To characterize the voice before and after speech-language intervention, with Humming nasal sound in patients with sequelae Mucosal Leishmaniasis (ML) and Cutaneous Leishmaniasis (CL). METHODS: Collection of phonation /a:/ from 44 patients with ML and CL for perceptual voice analysis and computed acoustic. The Wilcoxon nonparametric test and Fisher's exact test were used, with significance level of 5%. RESULTS: It was observed, prespeech therapy, that 27.7% of participants with ML presented asthenic vocal quality, and for the acoustics characteristics there was a statistically significant result for measures of frequency, frequency disturbance, noise, and subharmonic measurements, indicating phonatory instability, weakness, and noise emission giving the emission a feeling of vocal weakness. After therapy, the subharmonic segment measurements for the group with ML, showing reduction noise emission. Patients with CL had more grade 1 instability (36.4%), indicating tremor in vocal tract structures. After speech therapy, this group presented a reduction in the degree of roughness and reduction of the frequency disturbance measures, indicating a decrease in tension in the larynx and pharynx. CONCLUSION: Even after completing treatment for LM, patients may experience vocal changes due to the sequelae of the disease, like vocal alterations due to nasal lesions or in other locations that interfere in the correct vocal emission. As for participants with CL, no vocal changes would be expected, since these patients present thorax, leg and arm lesions that would not cause problems for the voice. Nevertheless, the two groups of participants presented vocal changes to different degrees before vocal therapy. However, it was observed that patients with ML present vocal alterations with more severe degrees. After the speech-language intervention, the participants of both groups showed vocal improvement, but the group with CL presented more vocal benefits, possibly due to the previous vocal alterations not being so severe.

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.

Mucosal leishmaniasis: A Retrospective Study of 327 Cases from an Endemic Area of Leishmania (Viannia) braziliensis.

Mucosal leishmaniasis (ML) is observed only in about 3% of patients with American tegumentary leishmaniasis (ATL) but has a high potential for destructive, disfiguring, and disabling sequelae. Prior reports of clinical and epidemiologic features of ML are limited by small numbers of cases. In this study, we evaluated changes in the demographic features and clinical presentation of ML in an endemic area of Leishmania braziliensis transmission over a period of 20 years. The charts of 327 patients with ML diagnosed between 1995 and 2014 were reviewed. The majority of patients (67%) were male. Age ranged from 8 months to 103 years, with a median age of 38.5 years (interquartile range: 22-58 years). The greatest number of patients was between 19 and 39 years (31%). Over the study period, there was an increase in patients with ML more than 60 years of age, an increase in ML with concomitant cutaneous lesions, a decrease in the period of time between the documentation of cutaneous lesions and the diagnosis of mucosal disease, and an increase in the frequency of patients presenting with stage I and V of ML. Moreover, there was a positive correlation between severity of mucosal disease and both age and the period of time between cutaneous lesion and mucosal disease. Response to therapy of ML remained similar over a period of 20 years. Despite the improvement in medical care during the study period, the prevalence of ML did not change and severe disease continues to be a major challenge for the management of these patients.

Differential aspects of stroke and congestive heart failure in quality of life reduction: a case series with three comparison groups.

BACKGROUND: To assess QOL of patients with stroke in comparison to other groups (caregivers and CHF patients), to identify which items of QOL are more affected on each group and what is the functional profile of patients with stroke. METHODS: Consecutive stroke or congestive heart failure (CHF) patients were evaluated and compared to their caregivers (caregivers). The NIH Stroke Scale (NIHSS) and EuroQoL-5D (EQ-5D) scale were applied. RESULTS: We evaluated 67 patients with stroke, 62 with CHF and 67 caregivers. For stroke patients, median NIHSS score was four. EQ-5D score was significantly worse in stroke, as compared to CHF and caregivers (0.52, 0.69 and 0.65, respectively). Mobility and usual activity domains were significantly affected in stroke and CHF patients as compared to caregivers; and self-care was more affected in stroke as compared with the other two groups. CONCLUSIONS: Despite a mild neurological deficit, there was a significantly worse QOL perception in stroke as compared to CHF patients, mostly in their perception of self-care.

Stroke history and Chagas disease are independent predictors of silent cerebral microembolism in patients with congestive heart failure.

BACKGROUND: Chagas disease is endemic in South and Central America, where 18 million individuals are infected by Trypanosoma cruzi, causing congestive heart failure (CHF) and cardioembolic stroke. Transcranial Doppler (TCD) is able to detect real-time microembolic signals (MES) to the brain vessels and may represent a surrogate marker of stroke risk. We aimed to determine predictors of MES in a population of patients with CHF. METHODS: Consecutive CHF patients from a university-based cardiomyopathy clinic underwent TCD recording of the middle cerebral artery for 60 min by a single investigator who was blinded to all clinical data including cardiomyopathy etiology. Predictors of MES were sought by multivariable logistic regression analysis. RESULTS: From April 2004 to February 2009, 144 patients were studied, including 62 (44.6%) patients with Chagas disease. MES were detected in 9 (6.2%) patients and were more frequent in patients with Chagas disease than in patients with other causes of CHF (12.9 vs. 1.2%, p = 0.005). In multivariate analysis corrected for age and left-ventricular ejection fraction, predictors of MES were Chagas disease (odds ratio = 1.15, 95% confidence interval = 1.05-1.26, p = 0.004) and stroke history (odds ratio = 1.27, 95% confidence interval = 1.08-1.50, p = 0.005). CONCLUSIONS: Chagas disease and stroke history are risk factors for MES independent of cardiac disease severity. Other mechanisms besides structural cardiac disease may be operative, increasing embolic risk in Chagas disease.

Chagas disease is independently associated with brain atrophy.

Chagas disease (CD) remains a major cause of cardiomyopathy and stroke in developing countries. Brain involvement in CD has been attributed to left ventricular dysfunction, resulting in chronic brain ischemia due to hypoperfusion and/or embolic infarcts. However, cognitive impairment in CD may occur independently of cardiac disease. Therefore, we aimed to investigate head computed tomography (CT) findings in patients with Chagas disease cardiomyopathy (CDC) in comparison with other cardiomyopathies (OC). We studied 73 patients with CDC (n = 41) or OC (n = 32) matched for age and gender. These patients underwent head CT, rated by an investigator blinded to all clinical information. Head CT was rated for the presence of lacunar or territorial infarcts, as well as for measuring the total volumes of the brain, cerebellum and ventricles. Total brain volume was smaller in CDC as compared to OC patients (1,135 +/- 150 vs. 1,332 +/- 198 cm(3), P < 0.001). Cerebellar and ventricular volumes did not differ between the groups. The prevalence of brain infarcts did not differ significantly between the groups. Chagas disease was the only independent predictor of brain atrophy in the multivariable analysis (OR = 1.38; 95% CI = 1.06-1.79, P = 0.017). Chagas disease is associated with brain atrophy independent of structural cardiac disease related to cardiomyopathy. Brain atrophy, rather than multiple infarcts, may represent the main anatomical substrate of cognitive impairment in Chagas disease.

Validation of the National Institutes of Health Stroke Scale, modified Rankin Scale and Barthel Index in Brazil: the role of cultural adaptation and structured interviewing.

BACKGROUND: We aimed to validate three widely used scales in stroke research in a multiethnic Brazilian population. METHODS: The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) were translated, culturally adapted and applied by two independent investigators. The mRS was applied with or without a previously validated structured interview. Interobserver agreement (kappa statistics) and intraclass correlation coefficients were calculated. RESULTS: 84 patients underwent mRS (56 with and 28 without a structured interview), 57 BI and 62 NIHSS scoring. Intraclass correlation coefficient was 0.902 for NIHSS and 0.967 for BI. For BI, interobserver agreement was good (kappa = 0.70). For mRS, the structured interview improved interobserver agreement (kappa = 0.34 without a structured interview; 0.75 with a structured interview). CONCLUSION: The NIHSS, BI and mRS show good validity when translated and culturally adapted. Using a structured interview for the mRS improves interobserver concordance rates.