Antonio Carlos Nicodemo

Leptospirosis pulmonary haemorrhage syndrome is associated with linear deposition of immunoglobulin and complement on the alveolar surface

Leptospirosis is a zoonotic infection associated with severe diseases such as leptospirosis pulmonary haemorrhage syndrome (LPHS). The cause of pulmonary haemorrhage is unclear. Understanding which mechanisms and processes are involved in LPHS will be important in treatment regimens under development for this life-threatening syndrome. In the present study, we evaluated 30 lung specimens from LPHS patients and seven controls using histology and immunohistochemistry (detection of IgM, IgG, IgA and C3) in order to describe the pathological features associated with this syndrome. Immunoglobulin deposits were detected on the alveolar surface in 18/30 LPHS patients. Three staining patterns were observed for the immunoglobulins and C3 in the lung tissues of LPHS patients: AS, delicate linear staining adjacent to the alveolar surface, which was indicative of a membrane covering the luminal surface of type I and II pneumocyte cells; S, heterogeneous staining which was sporadically distributed along the alveolar septum; and IA, weak, focal intra-alveolar granular staining. Human LPHS is associated with individual and unique histological patterns that differ from those of other causes of pulmonary haemorrhage. In the present study, it was found that the linear deposition of immunoglobulins (IgA, IgG and IgM) and complement on the alveolar surface may play a role in the pathogenesis of pulmonary haemorrhage in human leptospirosis.

Use of itraconazole in the treatment of mucocutaneous Leishmaniasis: A pilot study.

OBJECTIVE Mucocutaneous leishmaniasis is widely distributed in Brazil, with Leishmania (Viannia) braziliensis being the major etiologic agent. The currently recommended therapy is limited by its parenteral use, high toxicity, and variable efficacy. A clinical pilot study was conducted to analyze itraconazole as an oral alternative for the treatment of mucocutaneous leishmaniasis. METHODS Ten patients were enrolled to receive 4 mg/kg per day (up to 400 mg/d) itraconazole for 6 weeks on an outpatient regimen. Diagnosis was based on clinical otorhinolaryngologic examination, followed by a specific serologic reaction, the Montenegro test and pathologic analysis with immunohistochemical reaction. Healing of the lesions was confirmed by clinical otorhinolaryngologic examination. Side effects were monitored by general clinical assessment, hemoglobin determination, leukocyte counts, and liver function tests, all performed before, during, and 1 month after the end of treatment. RESULTS Six of 10 patients presented healed lesions 3 months after treatment, with a sustained therapeutic response for at least a median period of 14.5 months (range, 12-18 mo). Side effects were not observed. CONCLUSIONS This pilot study demonstrated that itraconazole can be an effective and well-tolerated alternative for the treatment of mucocutaneous leishmaniasis. Further randomized studies and double blind controlled trials are needed to assess the benefits of this drug in the treatment of mucocutaneous leishmaniasis.

HEMOPHAGOCYTIC SYNDROME ASSOCIATED WITH HEPATITIS A: CASE REPORT AND LITERATURE REVIEW

Virus-Associated Hemophagocytic Syndrome (VAHS) is a severe hematological disorder related to some viral infections. It is an illness characterized by persistent fever, pancytopenia, splenomegaly, hyperferritinemia and, the most important, hemophagocytosis observed in the bone marrow, liver and/or lymph nodes. VAHS associated with hepatitis A virus infection is rarely described, despite the high incidence of this viral infection in the population in general. There is no consensus in the literature regarding the optimal treatment of VAHS. In this article the clinical features, presumed pathogenesis, diagnostic criteria and treatment of VAHS are discussed, including description of cases of VAHS related to hepatitis A virus infection found in the medical literature.

Thrombocytopenia and leptospirosis

The present study has intended to contribute to the elucidation of the pathogenic mechanisms, involved in the thrombocytopenia and in the bleeding diathesis seen in the course of Leptospirosis. The group of cases included in the present prospective study consisted of 30 patients with Leptospirosis, admitted to the Infectious and Parasitic Diseases Ward, Hospital das Clínicas, Faculty of Medicine, University of São Paulo. The following possible mechanisms of thrombocytopenia have been considered and therefore investigated: platelet consumption, due to disseminated intravascular coagulation; immune-mediated platelet destruction, due to platelet-associated antibodies and an inhibited platelet production in the bone marrow. Thrombocytopenia occurred in 86.6% of 30 patients and did not seem to be immune-mediated by platelet-associated antibodies. Furthermore it did not seem to be due to a disseminated intravascular coagulation consumption. Although there was a statistically-significant correlation between bone marrow platelet production and platelet counts we think that the static microscopic examination of a bone marrow aspirate cannot accurately depict the dynamic mechanisms of platelet production when these cells are being consumed in peripheral blood. Vasculitis should be considered as the most important factor for the pathogenesis of the bleeding disturbances in Leptospirosis. However, we believe that thrombocytopenia, uremia and coagulation disorders, individually or as a group, should be included among the contributing factors that lead to and worsen bleeding episodes, which represent the leading cause of death in this disease.

Cranberries and lower urinary tract infection prevention

Lower urinary tract infections are very common diseases. Recurrent urinary tract infections remain challenging to treat because the main treatment option is long-term antibiotic prophylaxis; however, this poses a risk for the emergence of bacterial resistance. Some options to avoid this risk are available, including the use of cranberry products. This article reviews the key methods in using cranberries as a preventive measure for lower urinary tract infections, including in vitro studies and clinical trials.

Immune receptors and adhesion molecules in human pulmonary leptospirosis

Pulmonary involvement in leptospirosis has been increasingly reported in the last 20 years, being related to the severity and mortality of the disease. The pathogenesis of pulmonary hemorrhage in leptospirosis is not understood. Lung endothelial cells have been proposed as targets in the pathogenesis of lung involvement in leptospirosis through the activation of Toll-like receptor 2 or the complement system, which stimulates the release of cytokines that lead to the activation of adhesion molecules. The aim of this study was to investigate the involvement of immune pathways and of the intercellular and vascular cell adhesion molecules (intercellular adhesion molecule and vascular cell adhesion molecule, respectively) in the lungs of patients with pulmonary involvement of leptospirosis. We studied the lungs of 18 patients who died of leptospirosis and compared them with 2 groups of controls: normal and noninfectious hemorrhagic lungs. Using immunohistochemistry and image analysis, we quantified the expression of the C3a anaphylatoxin receptor, intercellular adhesion molecule, vascular cell adhesion molecule, and Toll-like receptor 2 in small pulmonary vessels and in the alveolar septa. There was an increased expression of intercellular adhesion molecule (P < .03) and C3a anaphylatoxin receptor (P < .008) in alveolar septa in the leptospirosis group compared with the normal and hemorrhagic controls. In the vessels of the leptospirosis group, there was an increased expression of intercellular adhesion molecule (P = .004), vascular cell adhesion molecule (P = .030), and Toll-like receptor 2 (P = .042) compared with the normal group. Vascular cell adhesion molecule expression in vessels was higher in the leptospirosis group compared with the hemorrhagic group (P = .015). Our results indicate that immune receptors and adhesion molecules participate in the phenomena leading to pulmonary hemorrhage in leptospirosis.

An Evaluation of clinical, serologic, anatomopathologic and immunohistochemical findings for fifteen patients with mucosal leishmaniasis before and after treatment

Treatment of mucosal leishmaniasis (ML) can be controlled by clinical examination and by serologic titers by the indirect immunofluorescence serologic reaction (IISR). We studied the correlation between the presence of antigen in tissue determined by immunohistochemistry, the IISR titers and the anatomopathologic findings in fifteen patients with ML before and after healing of the lesions as determined by otorhinolaryngologic evaluation, and evaluated these parameters to determine which of them could be useful during follow-up. Tissue antigens became negative in four patients (group A) after treatment, with a statistically significant reduction or negativity of IISR titers (p < 0.05). This did not occur in patients in whom the antigen persisted after treatment (group B), suggesting that serologic follow-up should be performed together with the search for tissue antigen, a combination which, to our knowledge, has not been used in previous studies. The negativity of tissue antigens and the behavior of IIRS titers in group A patients probably indicate a lower possibility of recurrence. Upon anatomopathologic examination the inflammatory process was found to persist after treatment even in group A, suggesting that the permanence of inflammatory activity even in clinically healed lesions is possibly correlated with the presence of the antigen or of some unknown factor.

Can We Use a Lower Dose of Liposomal Amphotericin B for the Treatment of Mucosal American Leishmaniasis

Liposomal amphotericin B has been used as an alternative treatment of mucosal leishmaniasis, but the optimal dose is not established. We retrospectively reviewed the clinical outcome of eight patients with mucosal leishmaniasis treated with liposomal amphotericin B. The mean total dose was 35 mg/kg (range 24-50 mg/kg), which resulted in the healing of all the lesions in all patients and no recurrences were observed during the follow-up period (mean 25 months; range 7-40 months).

Alteraçöes hematológicas na leptospirose

30 cases of leptospirosis admitted to the Clinica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo were studied for blood count alterations. 16 patients (53.3%) had a normal white blood cell count at the moment of admission. 12 patients (40%) presented a high white blood cell count and 2 (6.6%) had a low count. 29 patients (96.6%) had a high proportion of neutrophils and 25 patients (83.3%) presented a high number of immature forms. 24 patients had anemia. Thrombocytopenia was present in 26 patients (86.6%). The most characteristic changes found in bone marrow aspirate were the alterations of M:E ratio (myeloid-erythroid ratio) due to relative and/or absolute hyperplasia of the myeloid series, and/or relative and/or absolute hypoplasia of the erythroid series; erythropoiesis was predominantly micro-erythroblastic in many patients; mild to moderate plasmocytosis was found; and, regarding the interstitial series, increased macrophagic activity was noted. There was no direct correlation between the number of megakaryocytes and the blood platelet count, but there was a direct correlation between the bone marrow platelet production and blood platelet count. We believe that it is very difficult to have a good idea of the dynamic mechanisms that lead to medullar platelet production in the presence of platelet consumption, through a random test of the bone marrow.

Liposomal formulation of amphotericin B for the treatment of mucosal leishmaniasis in HIV-negative patients

BACKGROUND Studies assessing the efficacy of liposomal amphotericin B (LAB) in the treatment of patients with mucosal leishmaniasis (ML) are very scarce in the literature and an optimal dose regimen has not yet been defined. METHODS We performed a retrospective and descriptive analysis from records of 16 patients with ML treated with LAB. The mean daily dose of LAB was 2.5 mg/kg/day. RESULTS Healing of the lesion was observed in 14 (88%) of the 16 patients. The mean cumulative doses, excluding the two treatment failures, were 2265 mg and 33 mg/kg. CONCLUSION Liposomal amphotericin B in the cumulative dose of 30 to 35 mg/kg was able to achieve 100% effectiveness.