Atypical Mucocutaneous Leishmaniasis Caused by Leishmania braziliensis in an Acquired Immunodeficiency Syndrome Patient: T-cell Responses and Remission of Lesions Associated with Antigen Immunotherapy

An atypical case of acquired immunodeficiency syndrome-associated mucocutaneous lesions due to Leishmania braziliensis is described. Many vacuolated macrophages laden with amastigote forms of the parasite were found in the lesions. Leishmanin skin test and serology for leishmaniasis were both negative. The patient was resistant to therapy with conventional drugs (antimonial and amphotericin B). Interestingly, remission of lesions was achieved after an alternative combined therapy of antimonial associated with immunotherapy (whole promastigote antigens). Peripheral blood mononuclear cells were separated and stimulated in vitro with Leishmania antigens to test the lymphoproliferative responses (LPR). Before the combined immunochemotherapy, the LPR to leishmanial antigens was negligible (stimulation index - SI=1.4). After the first course of combined therapy it became positive (SI=4.17). The antigen responding cells were predominantly T-cells (47.5%) most of them with CD8+ phenotype (33%). Very low CD4+ cells (2.2%) percentages were detected. The increased T-cell responsiveness to leishmanial antigens after combined therapy was accompanied by interferon-g (IFN-g) production as observed in the cell culture supernatants. In this patient, healing of the leishmaniasis lesions was associated with the induction of a specific T-cell immune response, characterized by the production of IFN-g and the predominance of the CD8+ phenotype among the Leishmania-reactive T-cells.

Cell populations in lesions of cutaneous leishmaniasis of leishmania (L.) amazonensis- infected rhesus macaques, Macaca mulatta

The cellular nature of the infiltrate in cutaneous lesion of rhesus monkeys experimentally infected with Leishmania (L.) amazonensis was characterized by immunohistochemistry. Skin biopsies from infected animals with active or healing lesions were compared to non-infected controls (three of each type) to quantitate inflammatory cell types. Inflammatory cells (composed of a mixture of T lymphocyte subpopulations, macrophages and a small number of natural killer cells and granulocytes) were more numerous in active lesions than in healing ones. T-cells accounted for 44.7 ± 13.1% of the infiltrate in active lesions (versus CD2+= 40.3 ± 5.7% in healing lesions) and T-cell ratios favor CD8+ cells in both lesion types. The percentage of cells expressing class II antigen (HLA-DR+) in active lesions (95 ± 7.1%) was significantly higher (P < 0.005) from the healing lesions (42.7 ± 12.7%). Moreover, the expression of the activation molecules CD25 (@ 16%), the receptor for interleukin-2, suggests that many T cells are primed and proliferating in active lesions. Distinct histopathological patterns were observed in lesions at biopsy, but healing lesions contained more organized epithelioid granulomas and activated macrophages, followed by fibrotic substitution. The progression and resolution of skin lesions appears to be very similar to that observed in humans, confirming the potential for this to be used as a viable model to study the immune response in human cutaneous leishmaniasis.

Force of infection and evolution of lesions of canine tegumentary leishmaniasis in Northwestern Argentina

A clinical-serological follow-up was carried out in a canine population in endemic foci of Leishmania braziliensis spread in northwestern Argentina. Each dog was studied in at least two visits, 309±15 days (X±SE) apart. Some initially healthy dogs (n=52) developed seroconversion or lesions. The clinical evolution of the disease in dogs resembles in many aspects the human disease. Similarities include the long duration of most ulcers with occasional healing or appearance of new ones and the late appearance of erosive snout lesions in some animals. Yearly incidence rates of 22.7% for seroconversion and of 13.5% for disease were calculated as indicators of the force of infection by this parasite upon the canine population.

Leishmanial antigens in the diagnosis of active lesions and ancient scars of American tegumentary leishmaniasis patients

Cutaneous biopsies (n = 94) obtained from 88 patients with American tegumentary leishmaniasis were studied by conventional and immunohistochemical techniques. Specimens were distributed as active lesions of cutaneous leishmaniasis (n = 53) (Group I), cicatricial lesions of cutaneous leishmaniasis (n = 35) (Group II) and suggestive scars of healed mucosal leishmaniasis patients (n = 6) (Group III). In addition, active cutaneous lesions of other etiology (n = 24) (Group C1) and cutaneous scars not related to leishmaniasis (n = 10) (Group C2) were also included in the protocol. Amastigotes in Group I biopsies were detected by routine histopathological exam (30.2%), imprint (28.2%), culture (43.4%), immunofluorescence (41.4%) and immunoperoxidase (58.5%) techniques; and by the five methods together (79.3%). In Group II, 5.7% of cultures were positive. Leishmanial antigen was also seen in the cytoplasm of macrophages and giant cells (cellular pattern), vessel walls (vascular pattern) and dermal nerves (neural pattern). Positive reaction was detected in 49 (92.5%), 20 (57%) and 4 (67%) biopsies of Groups I, II and III, respectively. Antigen persistency in cicatricial tissue may be related to immunoprotection or, on the contrary, to the development of late lesions. We suggest that the cellular, vascular and neural patterns could be applied in the immunodiagnosis of active and cicatricial lesions in which leishmaniasis is suspected.

Worm load and septal fibrosis of the liver in Capillaria hepatica-infected rats

Inocula, varying from 15 to 1,000 embryonated Capillaria hepatica eggs, were administered to young adult rats by gastric tube, in an attempt to investigate the influence of worm load in the production of septal fibrosis of the liver. Low doses of 15, 30 or 50 eggs were sufficient to produce septal fibrosis, but it appeared with variable degrees of intensity and always with focal distribution. Septal fibrosis became diffuse, progressive with time, and already well developed 40 days after infection, when 100 eggs or more were administered. However, higher inocula (200, 500 and 1,000 eggs) did not intensify septal fibrosis, although the number of parasitic focal lesions proportionally augmented.

Quantitave and qualitative interferences of pentoxifillyne on hepatic Schistosoma mansoni granulomas: effects on extracellular matrix and eosinophil population

Mast cells and eosinophils actively participate in tissue repair and are prominent components of Schistosoma mansoni granulomas. Since pentoxifillyne (PTX) is an immunomodulatory and antifibrotic substance, we aimed to characterize, by morphological techniques, the effect of this drug on fibrosis developed inside murine hepatic schistosomal granulomatous reaction, beyond the quantification of eosinophil and mast cell populations. The drug (1 mg/100 g animal weight) was administrated from 35 to 90 days post-infection, when the animals were killed. The intragranulomatous interstitial collagen network was analyzed by confocal laser scanning microscopy, the number of eosinophils and mast cells was quantified and the results were validated by t-student test. Treatment did not interfere on the granuloma evolution but caused a significant decrease in the total and involutive number of hepatic granulomas (p = 0.01 and 0.001, respectivelly), and in the intragranulomatous accumulation of eosinophils (p = 0.0001). Otherwise, the number of mast cells was not significantly altered (p = 0.9); however, it was positively correlated with the number of granulomatous structures (r = 0.955). In conclusion, PTX does not affect development and collagen deposition in S. mansoni murine granuloma, but decreases the intragranulomatous eosinophil accumulation possibly due to its immunomodulatory capability, interfering in cellular recruitment and/or differentiation.

Surgical hepatosplenic mansonic schistosomiasis in adolescents: repercussions of the post-treatment schistosomotic burden on the hepatic functional reserve

Schistosomiasis mansoni affects the hepatic functional reserve. Clinical treatment with oxamniquine is not 100% effective and there has been found strain of this parasite resistant to this drug. The aims of this investigation were: (1) to examine the presence of residual parasite burden after medical and surgical treatment on adolescents with surgical schistosomiasis mansoni and (2) to assess the effect on the hepatic functional reserve in patients with and without residual infection. Twenty nine children with hepatosplenic schistosomiasis mansoni and bleeding esophageal varices were treated with oxamniquine. They underwent splenectomy, ligature of the left gastric vein and autologous implantation of spleen tissue into the greater omentum. After a mean post-operative follow up of five years they underwent rectal biopsy for schistosomotic egg search. They were divided in patients with and without infection. In 20 patients the submucosal egg search was negative, however, in 9 it was positive. The hepatic functional reserve in the patients without infection was as follows: 17 were Child-Pugh A and 3 Child-Pugh B. In the patients who were still infected 6 were Child-Pugh A and 3 Child-Pugh B. The chi2 analysis of the hepatic functional reserve showed chi2 = 3.19 - p= 0.07. From the results the following conclusion can be drawn: residual infection or reinfection in the follow up period had not interfered with the distribution of the hepatic functional reserve of the patients in this series. However, there was a trend for a decrease of this parameter in patients with residual infection.

An Autochthonous Case of Echinococcus vogeli Rausch & Bernstein, 1972 Polycystic Echinococcosis in the State of Rondônia, Brazil

The present case report refers to a patient from the State of Rondônia, North region of Brazil, attended with clinical suspicion of hepatic echinococcosis. Examination by imaging (ultrasonography and computerized tomography) revealed a conglomerate of cystic lesions, with mobile contents within the cyst. The serology (immunoblot) for Echinococcus sp. was positive (21 and 31 kDa bands). This case is the first reported in Rondônia, suggesting the need to investigate the polycystic echinococcosis in individuals with hepatic cysts from areas of tropical forest and hunting habits where wild life was present as wild dogs, cats and rodents, particularly Agouti paca (paca) and Dasyprocta aguti (agouti).

Valor diagnòstic de les lesions medul·lars a les síndromes neurològiques aïllades.

L’objectiu del treball és determinar la prevalença de lesions desmielinitzants a la medul·la espinal a les síndromes neurològiques aïllades i el valor afegit de la ressonància magnètica medul·lar. Es van incloure 113 pacients amb síndromes neurològiques aïllades a l’estudi. Els criteris diagnòstics d’esclerosi múltiple de McDonald 2005 es complien en un 43% dels pacients quan només eren valorades les lesions cerebrals, incrementant-se fins el 46% quan les lesions medul·lars eren també valorades. Aquests percentatges, en pacients amb síndromes neurològiques aïllades variaven del 47% al 53%. Com a conclusió considerem que la realització d’RM medul·lar als pacients amb síndromes neurològiques aïllades té una escassa contribució en la demostració de disseminació en l’espai, suggerint que no caldria realitzar una RM medul·lar als pacients amb síndrome neurològica aïllada no medul·lar, però es podria considerar quan les troballes cerebrals per RM no siguin concluents per a establir el diagnòstic d’Esclerosi Múltiple segons els criteris de McDonald 2005.

Osteoid osteoma and osteoid osteoma-mimicking lesions: biopsy findings, distinctive MDCT features and treatment by radiofrequency ablation.

OBJECTIVE: To report the biopsy findings of osteoid osteoma (OO) and OO-mimicking lesions, assess their distinctive multidetector computed tomography (MDCT) features and evaluate treatment by radiofrequency ablation (RFA). METHODS: In this multicentric retrospective study, 80 patients (54 male, 26 female, mean age 24.1 years, range 5-48) with presumed (clinical and MDCT features) OO were treated by percutaneous RFA between May 2002 and June 2009. Per-procedural biopsies were always performed. The following MDCT features were assessed: skeletal distribution and location within the bone, size, central calcification, surrounding osteosclerosis and periosteal reaction. Clinical success of RFA was evaluated. RESULTS: Histopathological diagnoses were: 54 inconclusive biopsies, 16 OO, 10 OO-mimicking lesions (5 chronic osteomyelitis, 3 chondroblastoma, 1 eosinophilic granuloma, 1 fibrous dysplasia). OO-mimicking lesions were significantly greater in size (p = 0.001) and presented non-significant trends towards medullary location (p = 0.246), moderate surrounding osteosclerosis (p = 0.189) and less periosteal reaction (p = 0.197), compared with OO. Primary success for ablation of OO-mimicking lesions was 100% at 1 month, 85.7% at 6 and 12 months, and 66.7% at 24 months. Secondary success was 100%. CONCLUSION: Larger size, medullary location, less surrounding osteosclerosis and periosteal reaction on MDCT may help differentiate OO-mimicking lesions from OO. OO-mimicking lesions are safely and successfully treated by RFA.

Imaging Properties of MS Lesions Correlate with Attention Deficits in Early Multiple Sclerosis

Introduction: Cognitive impairment affects 40-65% of multiple sclerosis (MS) patients, often since early stages of the disease (relapsing remitting MS, RRMS). Frequently affected functions are memory, attention or executive abilities but the most sensitive measure of cognitive deficits in early MS is the information processing speed (Amato, 2008). MRI has been extensively exploited to investigate the substrate of cognitive dysfunction in MS but the underlying physiopathological mechanisms remain unclear. White matter lesion load, whole-brain atrophy and cortical lesions' number play a role but correlations are in some cases modest (Rovaris, 2006; Calabrese, 2009). In this study, we aimed at characterizing and correlating the T1 relaxation times of cortical and sub-cortical lesions with cognitive deficits detected by neuropsychological tests in a group of very early RR MS patients. Methods: Ten female patients with very early RRMS (age: 31.6 ±4.7y; disease duration: 3.8 ±1.9y; EDSS disability score: 1.8 ±0.4) and 10 age- and gender-matched healthy volunteers (mean age: 31.2 ±5.8y) were included in the study. All participants underwent the following neuropsychological tests: Rao's Brief Repeatable Battery of Neuropsychological tests (BRB-N), Stockings of Cambridge, Trail Making Test (TMT, part A and B), Boston Naming Test, Hooper Visual Organization Test and copy of the Rey-Osterrieth Complex Figure. Within 2 weeks from neuropsychological assessment, participants underwent brain MRI at 3T (Magnetom Trio a Tim System, Siemens, Germany) using a 32-channel head coil. The imaging protocol included 3D sequences with 1x1x1.2 mm3 resolution and 256x256x160 matrix, except for axial 2D-FLAIR: -DIR (T2-weighted, suppressing both WM and CSF; Pouwels, 2006) -MPRAGE (T1-weighted; Mugler, 1991) -MP2RAGE (T1-weighted with T1 maps; Marques, 2010) -FLAIR SPACE (only for patient 4-10, T2-weighted; Mugler, 2001) -2D Axial FLAIR (0.9x0.9x2.5 mm3, 256x256x44 matrix). Lesions were identified by one experienced neurologist and radiologist using all contrasts, manually contoured and assigned to regional locations (cortical or sub-cortical). Lesion number, volume and T1 relaxation time were calculated for lesions in each contrast and in a merged mask representing the union of the lesions from all contrasts. T1 relaxation times of lesions were normalized with the mean T1 value in corresponding control regions of the healthy subjects. Statistical analysis was performed using GraphPad InStat software. Cognitive scores were compared between patients and controls with paired t-tests; p values ≤ 0.05 were considered significant. Spearmann correlation tests were performed between the cognitive tests, which differed significantly between patients and controls, and lesions' i) number ii) volume iii) T1 relaxation time iv) disease duration and v) years of study. Results: Cortical and sub-cortical lesions count, T1 values and volume are reported in Table 1 (A and B). All early RRMS patients showed cortical lesions (CLs) and the majority consisted of CLs type I (lesions with a cortical component extending to the sub-cortical tissue). The rest of cortical lesions were characterized as type II (intra-cortical lesions). No type III/IV lesions (large sub-pial lesions) were detected. RRMS patients were slightly less educated (13.5±2.5y vs. 16.3±1.8y of study, p=0.02) than the controls. Signs of cortical dysfunction (i.e. impaired learning, language, visuo-spatial skills or gnosis) were rare in all patients. However, patients showed on average lower scores on measures of visual attention and information processing speed (TMT-part A: p=0.01; TMT-part B: p=0.006; PASAT-included in the BRB-N: p=0.04). The T1 relaxation values of CLs type I negatively correlated with the TMT-part A score (r=0.78, p<0.01). The correlations of TMT-part B score and PASAT score with T1 relaxation time of lesions as well and the correlation between TMT-part A, TMT-part B and PASAT score with lesions' i) number ii) volume iii) disease duration and iv) years of study did not reach significance. In order to preclude possible influences from partial volume effects on the T1 values, the correlation between lesion volume and T1 value of CLs type I was calculated; no correlation was found, suggesting that partial volume effects did not affect the statistics. Conclusions: The present pilot study reports for the first time the presence and the T1 characteristics at 3 T of cortical lesions in very early RRMS (< 6 y disease duration). It also shows that CLS type I represents the most frequent cortical lesion type in this cohort of RRMS patients. In addition, it reveals a negative correlation between the attentional test TMT-part A and the T1 properties of cortical lesions type I. In other words, lower attention deficits are concomitant with longer T1-relaxation time in cortical lesions. In respect to this last finding, it could be speculated that long relaxation time correspond to a certain degree of tissue loss that is enough to stimulate compensatory mechanisms. This hypothesis is in line with previous fMRI studies showing functional compensatory mechanisms to help maintaining normal or sub-normal attention performances in RR MS patients (Penner, 2003).