Bone marrow fibrosis (pseudo-myelofibrosis) in human kala-azar

Thirty cases of human kala-azar were diagnosed by iliac crest biopsy and myeloculture. Histological analysis of 12 patients showed diffuse thickening of reticulin fibers. To the best of our knowledge, this is the third report describing secondary bone marrow fibrosis (myelofibrosis-like) associated with kala-azar. Patients with positive bone marrow fibrosis (pbmf = 12) were compared to patients without detectable bone marrow fibrosis (wbmf = 18). There were no significant differences in clinical and blood parameters following treatment. All patients showed regression of hepatosplenomegaly.Our findings suggest that associated bone marrow fibrosis is transient and did not interfere in the evolution of treated patients.

Pathogenesis of hepatic septal fibrosis associated with Capillaria hepatica infection of rats

Septal fibrosis is a common form of hepatic fibrosis, but its etiology and pathogenesis are poorly understood. Rats infected with the helminth Capillaria hepatica constitute a good experimental model of such fibrosis. To investigate the pathogenetic contribution of the several parasitic factors involved, the following procedures were performed in rats: a) regarding the role of eggs, these were isolated and injected either into the peritoneal cavity or directly into the liver parenchyma; b) for worms alone, 15-day-old infection was treated with mebendazole, killing the parasites before oviposition started; c) for both eggs and worms, rats at the 30th day of infection were treated with either mebendazole or ivermectin. Eggs only originated focal fibrosis from cicatricial granulomas, but no septal fibrosis. Worms alone induced a mild degree of perifocal septal fibrosis. Systematized septal fibrosis of the liver, similar to that observed in the infected controls, occurred only in the rats treated with mebendazole or ivermectin, with dead worms and immature eggs in their livers. Thus, future search for fibrogenic factors associated with C. hepatica infection in rats should consider lesions with both eggs and worms.

Morphometric study of the fibrosis and mast cell count in the circular colon musculature of chronic Chagas patients with and without megacolon

A morphometric study of the circular colon musculature was performed, in which the mast cell count was determined and the connective fibrous tissue in this layer was measured. The objective was to gain better understanding of Chagas megacolon morphology and contribute towards the knowledge of fibrosis pathogenesis in Chagas megas. An evaluation was made of 15 distal sigmoid rings from Chagas patients with megacolon (MCC), 15 without megacolon (CSMC) and 15 non-Chagas patients (NC). The rings were fixed in formol, embedded in paraffin, and 7mm thick sections were cut and stained using Azan-Heidenhain and Giemsa. The mast cell count and fibrosis were greater in the MCC group than in the CSMC and NC groups (p < 0.05; Kruskal-Wallis test) and there was no significant difference between the latter two. The fibrosis and increased mast cell count in the colon musculature of the MCC group possibly indicates that there is a relationship between mastocytosis and fibrosis, as has already been demonstrated in other pathologies.

Production of septal fibrosis of the liver by means of foreign protein injections into rats

Similarities and differences in antigenic humoral responses and electrophoretic patterns between Capillaria hepatica and pig-serum were investigated as a contribution to the understanding of hepatic fibrosis induced by the parenteral administration of foreign proteins. Only two out of 10 rats receiving repeated intraperitoneal injections of an extract of Capillaria hepatica-infected mouse liver presented septal hepatic fibrosis (20%). Under the same experimental conditions, 4 out of 9 rats (44.4%) developed septal fibrosis following whole pig-serum administration. Injections of normal mouse liver extracts did not result in hepatic fibrosis. Since a 100% septal fibrosis rate is observed in experimentally Capillaria hepatica-infected rats, it appeared that Capillaria hepatica products continuously released from inside the liver creates a much more effective fibrosis inducing mechanism than the parenteral administration of such factors. Thus, repeated peritoneal administration of a foreign protein to rats would not reveal the full fibrogenic potential it may have under natural conditions.

Capillaria hepatica-induced hepatic fibrosis in rats: paradoxical effect of repeated infections

Multiple exposures to parasitic agents are considered an important factor in the genesis of the most severe forms of the diseases they cause. Capillaria hepatica-induced septal fibrosis of the liver in rats usually runs without signs of portal hypertension or hepatic failure. After determining the hepatic profile of 15 animals during the course of a single infection, we submitted 20 rats to multiple Capillaria hepatica infections to determine whether repeated exposures would augment fibrosis production, transforming septal hepatic fibrosis into a true cirrhosis. Ten single-infection rats served as controls. A total of 5 exposures, with 45-day intervals, were made. Histological changes were followed by means of surgical liver biopsies, collected prior to infection and to each re-infection. Functional changes were minimal and transient. Although a slight recrudescence of fibrosis was observed after the first two re-infections and when the single-infected control group was re-infected at the end of the experiment, subsequent re-infections failed to increase the amount of fibrosis. On the contrary, there occurred quantitative and qualitative evidence of collagen degradation and suppression of parasite development. These paradoxical results are in keeping with the hypothesis that a complex immunological modulation participates in the mechanism of hepatic fibrosis induced by Capillaria hepatica infection in rats.

Comparative clinical and ultrasound study of egg-negative and egg-positive individuals from Schistosoma mansoni low morbidity endemic areas, and hospitalized patients with hepatosplenic disease

Two hundred and twenty three subjects from a Schistosoma mansoni low morbidity endemic area and nine hospitalized hepatosplenic patients were submitted to stool test and clinical examination and abdomen ultrasound assessments. According to stool examination and ultrasound results, they were grouped as follows: G1 - 63 Schistosoma mansoni egg-negative individuals; G2 - 141 egg-positive patients and without evidence of periportal fibrosis; G3 - 19 egg-positive patients with periportal echogenicity (3-6mm); and G4 - 9 hepatosplenic patients with periportal echogenicity (> 6mm). Hepatomegaly detected by physical examination of the abdomen evaluated in the midclavicular line was verified in G1, G2 and G3, respectively, in 11.1, 12.1 and 26.3%. In G1, G2 and G3, periportal thickening occurred only in schistosomal patients (8.5%). Mild pathological alterations in patients that cannot yet be detected by clinical examination were detectable in the liver by ultrasound and can be due to fibrosis. The degree of mild periportal fibrosis was diminished in 57.9% of patients 12 months after treatment of schistosomiasis with oxamniquine. At ultrasonography, the mean liver left lobe measurement of G3 was larger than that of G1, and that of G4 larger than that of G1 and G2. The mean size of the spleen of G4 was significantly larger than that of the other three groups, and that of G3 larger than that of G1 and G2.

Role of partial hepatectomy on Capillaria hepatica-induced hepatic fibrosis in rats

It is known that hepatic fibrosis may regress following partial hepatectomy, since the hepatic parenchyma regenerates very rapidly, but not the excess of fibrous tissue. The present study evaluated this hypothesis by observing the behavior of systematized septal fibrosis induced by either 30 or 90-day-old Capillaria hepatica infection, in rats subjected to partial hepatectomy. The results revealed that the morphology of the fibrosis was unaffected, but its relative quantity within the microscope field appeared significantly decreased, as a consequence of the increased liver tissue mass following regeneration.

Guidelines for the diagnosis and treatment of schistosomal myeloradiculopathy

Schistosomal myeloradiculopathy is the most severe and disabling ectopic form of Schistosoma mansoni infection. The prevalence of SMR in centres in Brazil and Africa that specialise in attending patients with non traumatic myelopathy is around 5%. The initial signs and symptoms of the disease include lumbar and/or lower limb pain, paraparesis, urinary and intestinal dysfunctions, and impotence in men. The cerebrospinal fluid of SMR patients shows an increase in protein concentration and in the number of mononuclear cells in 90% of cases; eosinophils have been reported in 40%. The use of magnetic resonance imaging is particularly valuable in the diagnosis of Schistosomal myeloradiculopathy. The exclusion of other myelopathies and systemic diseases remains mandatory. Early diagnosis and treatment with steroids and schistosomicides provide a cure for most patients, whilst delayed treatment can result in irreversible physical disabilities or death. To improve awareness concerning Schistosomal myeloradiculopathy amongst public health professionals, and to facilitate the control of the disease, the Brazilian Ministry of Health has launched a program of education and control of this ectopic form of schistosomiasis. The present paper reviews current methods for the diagnosis of SMR and outlines protocols for treatment of the disease.

Comparison between clinical and ultrasonographic findings in cases of periportal fibrosis in an endemic area for schistosomiasis mansoni in Brazil

INTRODUCTION: Abdominal palpation and ultrasound findings among patients from an endemic area for schistosomiasis in Brazil who had been followed up for 27 years were compared. METHODS: In 2004, 411 patients from Brejo do Espírito Santo, in the State of Bahia, were selected for the present investigation after giving their written informed consent. Based on clinical data, they were divided into three groups: 41 patients with evidence of liver fibrosis in 2004 (Group 1); 102 patients with evidence of liver fibrosis in the past (1976-1989) but not in 2004 (Group 2); and 268 patients without evidence of liver fibrosis at any time during the 27-year follow-up (Group 3). All of the patients underwent abdominal ultrasound in which the examiner did not know the result from the clinical examination. The data were stored in a database. RESULTS: The prevalence of periportal fibrosis on ultrasound was 82.9%, 56.9% and 13.4% in Groups 1, 2 and 3, respectively. In the presence of hard, nodular liver or prominent left lobe and a hard palpable spleen, ultrasound revealed periportal fibrosis in 70.9%. However, periportal fibrosis was diagnosed using ultrasound in 25.4% of the patients in the absence of clinical evidence of liver involvement. Thus, ultrasound diagnosed periportal fibrosis 3.1 times more frequently than clinical examination did. CONCLUSIONS: Although clinical examination is important in evaluating morbidity due to Manson's schistosomiasis in endemic areas, ultrasound is more accurate in diagnosing liver involvement and periportal fibrosis.

High prevalence of methicillin-resistant Staphylococcus aureus with SCCmec type III in cystic fibrosis patients in southern, Brazil

INTRODUCTION: Bacterial colonization of the lungs is the main cause of morbidity in cystic fibrosis (CF). Pathogens such as Staphylococcus aureus are very well adapted to the pulmonary environment and may persist for years in the same patient. Genetic determinants of these bacteria, such as the presence of SCCmec have recently emerged as a problem in this population of patients. METHODS: Staphylococcus aureus isolates obtained from different clinical materials coming from CF and non-CF patients attended at a cystic fibrosis reference hospital were compared according to SCCmec type and antibiotic susceptibility profile. RESULTS: Three hundred and sixty-four single-patient Staphylococcus aureus isolates were collected, of which 164 (45%) were from CF patients. Among the latter, 57/164 (44.5%) were MRSA, and among the non-CF patients, 89/200 (35%) were MRSA. Associated pathogens were found in 38 CF patients. All 57 MRSA from CF patients harbored the multiresistant cassette type III. In contrast, 31/89 MRSA from non-CF patients harbored SCCmec type I (35%) and 44/89 harbored type III (49%). The antibiotic susceptibility pattern was similar between CF and non-CF patients. CONCLUSIONS: The high prevalence of multiresistant SCCmec type III among CF patients compared with non-CF patients in our institution may make it difficult to control disease progression through antibiotic therapy for promoting the survival of this kind of patient.

Capillaria hepatica-induced septal fibrosis in rats: a contribution to the study of liver fibrogenesis

INTRODUCTION: Septal fibrosis of the liver regularly develops in rats infected with the nematode Capillaria hepatica. Curative treatment of the infection prevents the development of septal fibrosis when intervention occurs up to postinfection day (PID) 15, but not later. The present investigation aimed to demonstrate which parasitic factors are present when the process of septal fibrosis can no longer be prevented by curative treatment. METHODS: Wistar rats were infected with 600 embryonated eggs of C. hepatica administered by gavage and treated with ivermectin and mebendazole in separate groups at PIDs 10, 12, 15, 17 or 20. Rats from each group and their nontreated controls, were killed and examined 40 days after the end of treatment. RESULTS: Findings by PID 15 were compatible with the stage of complete maturation of infection, when worms and eggs were fully developed and a complex host-parasite multifocal necroinflammatory reaction showed greater intensity, but with no signs of septal fibrosis, which appeared from PID 17 onward. CONCLUSIONS: Since the worms spontaneously died by PID 15, not only septal fibrosis production, but also its maintenance and further development appeared dependent on the presence of eggs, which were the only parasitic factor remaining thereafter.

Dynamics of Capillaria-hepatica-induced hepatic septal fibrosis in rats

INTRODUCTION: The pathogenesis of septal hepatic fibrosis, induced in rats by Capillaria hepatica infection, was studied with the aid of a large collection of stored paraffin blocks, representative of the different evolutive phases of fibrosis which appeared in 100% of infected rats. METHODS: Studies were conducted involving histology, immunohistochemistry, immunofluorescence and morphometric methods, in order to observe the dynamic behavior of the cellular and matrix components of fibrosis, over a one year period of evolution. RESULTS: Observation verified that septal fibrosis originates from several portal spaces simultaneously. Its origin and progression involve blood vessel proliferation (angiogenesis), multiplication of actin-positive cells (pericytes and myofibroblasts) and progressive collagen deposition. By the end of 4-5 months, a progressive decrease in all these components was observed, when signs of regression of septal fibrosis became more evident over time. CONCLUSIONS: Besides indicating the fundamental role played by angiogenesis in the pathogenesis of fibrosis, these morphological data concerning the dynamics of this C. hepatica experimental model proved to be adequate for future investigations regarding the functional aspects of fibrosis induction, progression and regression.

Endomyocardial fibrosis associated with mansoni schistosomiasis

Endomyocardial fibrosis (EMF) is a neglected tropical disease that affects millions of people worldwide. EMF is the most common cause of restrictive cardiomyopathy, caused by deposition of fibrous tissue on endocardial surfaces. EMF is a major cause of death in areas where it is endemic, but the pathogenesis of the disease is poorly understood. Schistosomiasis mansoni is a parasitic disease endemic in Brazil, where EMF has also been described. The association between EMF and schistosomiasis has been suggested in various publications, seeking a possible correlation between endocardial and periportal fibroses. This report describes a case of EMF associated with schistosomiasis.