Liver morphology with emphasis on bile ducts changes and survival analysis in mice submitted to multiple Schistosoma mansoni infections and chemotherapy

In an attempt to be as close as possible to the infected and treated patients of the endemic areas of schistosomiasis (S. mansoni) and in order to achieve a long period of follow-up, mice were repeatedly infected with a low number of cercariae. Survival data and histological variables such as schistosomal granuloma, portal changes, hepatocellular necrosis, hepatocellular regeneration, schistosomotic pigment, periductal fibrosis and chiefly bile ducts changes were analysed in the infected treated and non treated mice. Oxamniquine chemotherapy in repeatedly infected mice prolonged survival significantly when compared to non-treated animals (chi-square 9.24, p = 0.0024), thus confirming previous results with a similar experimental model but with a shorter term follow-up. Furthermore, mortality decreased rapidly after treatment suggesting an abrupt reduction in the severity of hepatic lesions. A morphological and immunohistochemical study of the liver was carried out. Portal fibrosis, with a pattern resembling human Symmers fibrosis was present at a late phase in the infected animals. Bile duct lesions were quite close to those described in human Mansonian schistosomiasis. Schistosomal antigen was observed in one isolated altered bile duct cell. The pathogenesis of the bile duct changes and its relation to the parasite infection and/or their antigens are discussed.

Liver dysfunction in patients bitten by Crotalus durissus terrificus (Laurenti, 1768) snakes in Botucatu (State of São Paulo, Brazil)

Thirty-two patients bitten by venomous snakes sixteen by Bothrops spp. and sixteen by Crotalus durissus terrificus were studied. The group comprised thirty males and two females, aged eight to sixty-three years (mean 33±15). Bromsulphalein tests were increased in the majority of patients bitten by Crotalus durissus terrificus. The correlation coefficient of Spearman was positive between bromsulphalein tests and alanine aminotransferase levels, and between alanine aminotransferase and aspartate aminotransferase levels only in the Crotalus group. The only patient who died was bitten by Crotalus durissus terrificus and showed hydropic degeneration and mitochondrial injury in the liver. It was concluded that the hepatic damage might have been caused by at least two possible mechanisms: venom effect on liver mitochondria and cytokine effects on hepatocyte, specially interleukin-6.

Studies on human anti-rabies immunization in Brazil: II - Preliminary evaluation of the 2-1-1 schedule for human pre-exposure anti-rabies immunization, employing suckling mouse brain vaccine

This study reports preliminary results of virus neutralizing antibody (VNA) titers obtained on different days in the course of human anti-rabies immunization with the 2-1-1 schedule (one dose is given in the right arm and one dose in the left arm at day 0, and one dose is apllied on days 7 and 21), recommended by WHO for post-exposure treatment with cell culture vaccines. A variant schedule (double dose on day zero and another on day 14) was also tested, both employing suckling mouse brain vaccine. A complete seroconversion rate was obtained after only 3 vaccine doses, and almost all patients (11 of 12) presented titers higher than 1.0 IU/ml. Both neutralizing response and seroconversion rates were lower in the group receiving only 3 doses, regardless of the sample collecting day. Although our results are lower than those found with cell culture vaccines, the geometry mean of VNA is fully satisfactory, overcoming the lower limit recommended by WHO of 0.5 IU/ml. The 2-1-1 schedule could be an alternative one for pre exposure immunization, shorter than the classical 3+1 regimen (one dose on days 0, 2, 4 and 30) with only three visits to the doctor, instead of four.

Hyperimmune antirabies sera titration by standard mouse neutralization and counterimmunoelectrophoresis tests, comparing results of different laboratories

To determine the rabies antibody level of twenty-four hyperimmune equine sera, Standard Mouse Neutralization (SMN) and Couterimmunoelectrophoresis (CIE) tests were carried out, both at the Instituto Butantan (IB) and Instituto Panamericano de Protección de Alimentos y Zoonosis (INPPAZ). Statistical analysis has shown a correlation (r) of 0.9317 between the SMN and CIE performed at the IB, while at the INPPAZ it scored 0.974. Comparison of CIE data of both laboratories yielded a correlation of 0.845. The CIE technique has shown to be as sensitive and efficient as the SMN in titrating antirabies hyperimmune equine sera. Based on CIE results, a simple, rapid and inexpensive technique, tilers of sera antibody can be reliably estimated in SMN test.

Leishmania (Viannia) panamensis - induced cutaneous leishmaniasis in susceptible and resistant mouse strains

We studied the susceptibility to Leishmania (Viannia) panamensis in strains of mice. The C57BL/6 strain was resistant and showed self-controlled lesion at the injected foot pad. The BALB/c and DBA/2J strains were susceptible and showed a foot swelling that started day 20 post-infection and progressed to a tumour-like lesion in later period of observation. The CBA/HJ strain was found to be of intermediary resistance. In contrast to other known cutaneous leishmaniasis in mice, the lesion in L. (V.) panamensis-infected mice was restricted to the inoculation site in the skin. In addition, we studied the development of cellular response and antibodies against Leishmania antigen in BALB/c and C57BL/6 strains. The proliferative response of lymph node cells against L. (V.) panamensis antigen was biphasic in both strains. An initial response was seen on day 20, followed by a refractory period between 40 and 80 days and a second response around fourth month post-infection. The response in the latter period was higher in C57BL/6 strain than in BALB/c strain. BALB/c strain presented much higher anti-Leishmania antibody level than C57BL/6 strain. The model and the correlation of immunological variables and the course of the infection are discussed.

Histopathology and immunocytochemical study of type 3 and type 4 complement receptors in the liver and spleen of dogs naturally and experimentally infected with Leishmania (Leishmania) chagasi

The objective of this study was to compare the histopathological changes and expression of CR3 and CR4 in the liver and spleen of dogs naturally and experimentally infected with L. chagasi. The basic histopathological lesions observed mainly in naturally infected dogs were: epithelioid hepatic granulomas, hyperplasia and hypertrophy of Kupffer cells, Malpigui follicles and mononucleated cells of the red pulp of the spleen. Sections from the liver and spleen by immunocytochemistry technique showed the presence of CD11b,c\CD 18 antigens in the control and infected animals and no qualitative or quantitative differences in the liver. Nevertheless, CD18 was always increased in the spleen of naturally and experimentally infected dogs. These results indicate that there is a difference in the activaton of CD 18 in both experimental and natural cases of canine visceral leishmaniasis that should play an important role in the immunological response to Leishmania chagasi infection.

ANTIGENIC RELATEDNESS OF SELECTED FLAVIVIRUSES: STUDY WITH HOMOLOGOUS AND HETEROLOGOUS IMMUNE MOUSE ASCITIC FLUIDS

The antigenic relationship of 9 flaviviruses, Yellow fever (YF) , Wesselsbron (WSL) , Uganda S (UGS) , Potiskum (POT), West Nile (WN) , Banzi (BAN) , Zika (ZK) , Dengue type 1 (DEN-1) and Dengue type 2 (DEN-2), was assessed by cross-haemagglutination-inhibition (Cross-HI) and cross-complement fixation (Cross-CF) reactions between each of the viruses and their homologous immune mouse ascitic fluids. Titre ratios were calculated using the heterologous and homologous titres. Cross-CF reactions revealed wider antigenic variations among viruses than Cross-HI reactions. There was no significant antigenic variation between WSL, POT and YF viruses using either of those methods. However, definite differences in antigenicity were observed between them and UGS, BAN and ZK viruses. There were no significant differences between UGS, BAN and ZK or between DEN-1 and DEN-2. The serological relationship among flaviviruses is important in establishing diagnosis and epidemiology of these infections in Africa.

AN ELISA SUITABLE FOR THE DETECTION OF RABIES VIRUS ANTIBODIES IN SERUM SAMPLES FROM HUMAN VACCINATED WITH EITHER CELL-CULTURE VACCINE OR SUCKLING-MOUSE-BRAIN VACCINE

An indirect ELISA for determination of post-vaccination rabies antibody was applied. Purified rabies virus was used as antigen to coat plates, and staphylococcal protein A linked with horseradish peroxidase was used for detecting IgG antibody in human sera. Sera from humans, vaccinated with cell-culture vaccine or suckling-mouse-brain vaccine, were examined. ELISA results were compared to those obtained from the virus neutralization test. The mean and standard deviation of OD were determined for 126 negative sera (pre-vaccination) and for 73 sera from vaccinated persons showing antibody titers lower than 0.5 IU/ml. Results were defined as ELISA -positive, -negative or -doubtful. Establishment of a doubtful region reduced the number of sera otherwise classified as positive (false-positive sera). In this way, the sensitivity, specificity and agreement values were respectively 87.5%, 92.4% and 88.5%. No significant differences were observed in these values when the group vaccinated with cell-culture vaccine and the group vaccinated with suckling-mouse-brain vaccine were compared. It was shown that much of the disagreement between the values obtained by neutralization test and ELISA occurred in sera obtained at the beginning of the immunization process, and was probably due to the presence of IgM in the serum samples, detected only by the former test. This ELISA method can be used as a screening test in rabies laboratories regardless of the kind of vaccine used for immunization.

Human polyclonal anti-hepatitis B surface antigen immunoglobulin reduces the frequency of acute rejection after liver transplantation for chronic hepatitis B

BACKGROUND: Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg) has been shown to reduce hepatitis B virus (HBV) recurrence after liver transplantation (LT) and to decrease the frequency of acute cellular rejection (ACR). However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM: To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS: 260 patients (158 males, 43 ± 14 years old) submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12) that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10). Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS: HBIg-treated patients (group I) had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS: Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT.

Liver abscess caused by Ascaris lumbricoides: case report

A case is reported of a woman who lived in a rural area with a chronic illness that consisted of weight loss and abdominal pain in the epigastrium and upper right quadrant. The initial diagnosis was a mass in the liver, which was later, demonstrated, both by direct and histological examination, to be an abscess caused by Ascaris lumbricoides. Eggs of Ascaris lumbricoides and abundant Charcot-Leyden Crystals were found.

Liver histology in co-infection of hepatitis C virus (HCV) and Hepatitis G virus (HGV)

As little is known about liver histology in the co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV), HGV RNA was investigated in 46 blood donors with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6) and HCV isolated infection (n = 16). Besides staging and grading of inflammation at portal, peri-portal and lobular areas (Brazilian Consensus), the fibrosis progression index was also calculated. All patients had no symptoms or signs of liver disease and prevalence of HGV / HCV co-infection was 15.2%. Most patients had mild liver disease and fibrosis progression index, calculated only in patients with known duration of infection, was 0.110 for co-infection and 0.130 for isolated HCV infection, characterizing these patients as "slow fibrosers". No statistical differences could be found between the groups, although a lesser degree of inflammation was always present in co-infection. In conclusion co-infection HCV / HGV does not induce a more aggressive liver disease, supporting the hypothesis that HGV is not pathogenic.

Liver abscess due to Salmonella enteritidis in a returned traveler with HIV infection: case report and review of the literature

Bacteremia due to non-typhi Salmonella is more frequent in patients infected with the human immunodeficiency virus (HIV). However, focal complications have been rarely described. We report a case of liver abscess due to Salmonella enteritidis in an HIV-infected patient who recently returned to Sao Paulo, Brazil, from a trip in the Caribbean. A good clinical and radiological response was seen with both percutaneous catheter drainage and antibiotic treatment. To our knowledge, this is the first culture proven case of non-typhi Salmonellaliver abscess in an HIV-infected patient in Brazil.

Primary liver AIDS-related lympoma

Non-Hodgkin's lymphomas (NHL) are the second most frequent malignancies in AIDS patients. The majority of NHL associated with AIDS involves extranodal sites, especially the digestive tract and the central nervous system. Primary liver lymphoma (PLL) is an uncommon neoplasm among these patients. Ultrasonography and computed tomography scans may be helpful in the diagnosis of focal hepatic lymphoma. Image-guided fine-needle biopsy with histopathology of the liver lesions is the gold standard for the diagnosis of hepatic lymphoma. We report a case of PLL as the initial manifestation of AIDS in a patient without any previous infection by hepatitis C or B virus, presented as multiple and large hepatic masses.