Treatment of relapsing chronic infections of the respiratory tract: a comparative study of the effectiveness of non specific immunotherapy with the immunoadjuvant p40 and of vaccinotherapy

The treatment of relapsing chronic infections (RCI) encounters many difficulties. In the present study, the use of the immuno adjuvant P40 either alone or in association with vaccinotherapy for the treatment of RCI turned out to be very effective, whereas vaccinotherapy alone was not. It is hypothesized that cell-mediated immunity may play a major role in controlling RCI, since the clinical improvement of the patients kept up with the positivation of previously negative skin tests carried out with either the specific infecting agent or with recall-anti gens.

Effects of non-specific immunopotentiators in experimental Schistosoma mansoni infection: II. Corynebacterium parvum

The effects of Corynebacterium parvum on host protection, tissue reaction and "in vivo" chemotaxis in Schistosoma mansoni infected mice were studied. The C. parvum was given intraperitoneally using a dose of 0.7 mg, twice a week (for 4 weeks), thirty days before (prophylactic treatment) or after infection (curative treatment). The host protection was evaluated through the recovery of adult worms by liver perfusion and was lower in the prophylactic group as compared to the control group (p = 0.018), resulting in 44% protection. The "in vivo" leukocyte response in both prophylactic and curative groups was higher as compared to the infected/non treated group (p = 0.009 and p = 0.003, respectively). Tissue reactions were described in the experimental and control groups, but there were not remarkable differences among them. The possible biological implications and relevance of the findings for the defensive response of the host and control of schistosomiasis are discussed.

Intranasal sensitization with Blomia Tropicalis antigens induces allergic responses in mice characterized by elevated antigen-specific and non-specific serum ige and peripheral blood eosinophil counts

In order to evaluate the potential allergenicity of Blomia tropicalis (Bt) antigen, IgE production of both specific and non-specific for Bt antigen was monitored in BALB/c mice after exposure to the antigen by nasal route. It was evidenced that B. tropicalis contains a functional allergen in its components. The allergenic components, however, when administered intranasally without any adjuvant, did not function to induce IgE response within a short period. On the other hand, intranasal inoculation of Bt antigens augmented serum IgE responses in mice pretreated by a subcutaneous priming injection of the same antigens. Inoculation of Bt antigen without subcutaneous priming injections induced IgE antibody production only when the antigen was continuously administered for a long period of over 24 weeks. Even when the priming injection was absent, the Bt antigen inoculated with cholera toxin (CT) as a mucosal adjuvant also significantly augmented the Bt antigen-specific IgE responses depending on the dose of CT co-administered. The present study also demonstrated that Bt antigen/CT-inoculated mice showed increased non-specific serum IgE level and peripheral blood eosinophil rates without noticeable elevations of the total leukocyte counts. The immunoblot analysis demonstrated 5 main antigenic components reactive to IgE antibodies induced. These components at about 44-64 kDa position were considered to be an important candidate antigen for diagnosis of the mite-related allergy.

Kinetics of antigen specific and non-specific polyclonal B-cell responses during lethal Plasmodium yoelii malaria

In order to study the kinetics and composition of the polyclonal B-cell activation associated to malaria infection, antigen-specific and non-specific B-cell responses were evaluated in the spleens of mice infected with Plasmodium yoelii 17 XL or injected with lysed erythrocytes or plasma from P. yoelii infected mice or with P. falciparum culture supernatants. Spleen/body weigth ratio, numbers of nucleated spleen cells and Immunoglobulin-containing and Immunoglobulin-secreting cells increased progressively during the course of infection,in parallel to the parasitemia. A different pattern of kinetics was observed when anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell plaque forming cells response were studied: maximum values were observed at early stages of infection, whereas the number of total Immunoglobulin-containing and Immunoglobulin-secreting cells were not yet altered. Conversely, at the end of infection, when these latter values reached their maximum, the anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell specific responses were normal or even infranormal. In mice injected with Plasmodium-derived material, a higher increase in antigen-specific PFC was observed, as compared to the increase of Immunoglobulin-containing and Immunoglobulin-secreting cell numbers. This suggested a "preferential" (antigen-plus mitogen-induced) stimulation of antigen-specific cells rather than a generalized non-specific (mitogen-induced) triggering of B-lymphocytes. On the basis of these and previous results, it is suggested that polyclonal B-cell activation that takes place during the course of infection appears as a result of successive waves of antigen-specific B-cell activation.

Physiological indicators of stress in gestating sows under different cooling systems

The objective of this work was to determine physiological stress markers, neutrophil:lymphocyte ratio (N/L) and corticoid concentrations, in gestating sows under different cooling systems. A sprinkling cooling system (SS) and a system based on fan-assisted evaporative cellulose pad (PS) were used. SS showed higher N/L ratio (1.095) than PS (0.850). Corticoid concentrations showed high variability. Corticosteroids are more efficient short-term stress indicators while N/L ratio is a good medium and long-term stress indicator. According to N/L ratio, gestating sows under PS benefit from a higher level of welfare.

Effects of pneumonectomy on nitric oxide synthase expression and perivascular edema in the remaining lung of rats

Pneumonectomy is associated with high mortality and high rates of complications. Postpneumonectomy pulmonary edema is one of the leading causes of mortality. Little is known about its etiologic factors and its association with the inflammatory process. The purpose of the present study was to evaluate the role of pneumonectomy as a cause of pulmonary edema and its association with gas exchange, inflammation, nitric oxide synthase (NOS) expression and vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included in the study. Eleven animals died during or after the procedure, 21 were submitted to left pneumonectomy and 10 to sham operation. These animals were sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically significant difference in the expression of iNOS. The lumen-wall ratio and pO2/FiO2 ratio did not differ between the operated and sham groups after pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no elevation of immunohistochemical expression of iNOS or neutrophil density, suggesting the absence of correlation with the inflammatory process or oxidative stress. The increased expression of eNOS may suggest an intrinsic production of NO without signs of vascular reactivity.

Intestinal spirochetosis: first cases reported in Brazil and the use of immunohistochemistry as an aid in histopathological diagnosis

Colonization of the colon and rectum by intestinal spirochetes is detected for the first time in Brazil in 4 of 282 (1.41%) patients who had undergone sigmoidoscopy and/or colonoscopy with a histopathological diagnosis of chronic non specific-colitis. This frequency is probably understimated, since surgically obtained specimens were not considered in the present study. Histopathological diagnosis was performed using routine stains like hematoxylin-eosin which showed the typical, of 3-µm thick hematoxyphilic fringe on the brush border of the surface epithelium, and by silver stains like the Warthin-Starry stain. Immunohistochemical procedures using two, polyclonal, primary antibodies, one against Treponema pallidum and the other against Leptospira interrogans serovar copenhageni serogroup Icterohaemorrhagiae cross-reacted with spirochetal antigen/s producing a marked contrast of the fringe over the colonic epithelium, preserving the spiral-shaped morphology of the parasite. In one case with marked diarrhea, immunohistochemistry detected spirochetal antigen/s within a cell in an intestinal crypt, thus demonstrating that the infection can be more widely disseminated than suspected using routine stains. Immunohistochemical procedures, thus, greatly facilitate the histological diagnosis of intestinal spirochetosis and may contribute to a better understanding of the pathogenesis of the disease. Transmission and scanning electron microscopy performed in one case showed that the spirochete closely resembled the species designated as Brachyspira aalborgi.

Cerebrospinal fluid profiles in acquired immunodeficiency syndrome with and without neurocryptococcosis

Cryptococcosis is one of the most common fungal infections of the central nervous system (CNS) in AIDS patients and meningoencephalitis or meningitis is a frequently observed manifestation. However, systematic studies of cerebrospinal fluid (CSF) composition from AIDS patients with CNS cryptococcosis have been few. CSF samples from 114 HIV seropositive patients whose clinical complaint suggested CNS involvement, were analyzed; 32 samples from patients diagnosed as having neurocryptococcosis (Group 1) and 82 samples from patients with no identified neurological disfunction (Group 2). Based on cytological and biochemical results, two distinct profiles were observed: Normal (Group 1 = 31%, Group 2 = 39%); Abnormal (Group 1 = 69%, Group 2 = 61%). Lymphocytes were the most frequent cells in both groups. Our CSF cytological and biochemical findings showed that in AIDS patients liquoric abnormalities are quite frequent, non-specific and difficult to interpret. In these circumstances a systematic search to identify the etiologic agent using microbiological and/or immunological assays must be routinely performed

ELEVATED ALANINE AMINOTRANSFERASE (ALT) IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.

TOXOCARIASIS: SEROLOGICAL DIAGNOSIS BY INDIRECT ANTIBODY COMPETITION ELISA

Toxocariasis is caused by infection of man by Toxocara canis and Toxocara cati larvae, the common roundworm of dogs and cats. Because larvae are difficult to detect in tissues, diagnosis is mostly based on serology. Non specific reactions are observed mainly due to cross-reactivity with Ascaris sp antigens. This investigation aimed at developing and evaluating an indirect antibody competition ELISA (IACE) employing a specific rabbit IgG anti-Toxocara canis excretory-secretory antigens as the competition antibody, in order to improve indirect ELISA specificity performed for toxocariasis diagnosis. For that, the rabbit IgG was previously absorbed by Ascaris suum adult antigens. Sensitivity and specificity of IACE were first evaluated in 28 serum samples of mice experimentally infected with T. canis embryonated eggs. Adopting cut-off value established in this population before infection, sensitivity and specificity were 100% after 20 days post-inoculation. For human population IACE was evaluated using sera from 440 patients with clinical signs of toxocariasis and the cut-off value was established with 60 serum samples from apparently healthy individuals. Using as reference test the indirect ELISA performed by Adolfo Lutz Institute, sensitivity was 60.2%, specificity was 98% and concordance was 77.3%. Repeatability of IACE was evaluated by the inter-reactions variation coefficient (2.4%).

HANTAVIRUS PULMONARY SYNDROME (HPS) IN GUARIBA, SP, BRAZIL: REPORT OF 2 CASES

Human infections caused by a hantavirus were reported in different regions of the State of São Paulo (SP), Brazil during the first six months of 1998. Two cases of fatal pulmonary syndrome occurred in May of 1998 in the City of Guariba, located in the Northeastern Region of SP. Both patients worked in a corn storage barn infested by rodents. These patients, after 2 or 3 days of non-specific febrile illness, developed a severe interstitial pneumonia spreading widely in both lungs, causing respiratory failure and death. At autopsy both patients showed lung interstitial edema with immunoblast-like mononuclear cell infiltrates, consistent with a viral etiology. Hantavirus infection was diagnosed by ELISA in both cases and by RT-PCR in one of the patients. Aspects of the clinical presentation, physiopathology and differential diagnosis of Hantavirus Pulmonary Syndrome are discussed.

Review of genitourinary tuberculosis with focus on end-stage renal disease

Tuberculosis (TB) is a current public health problem, remaining the most common worldwide cause of mortality from infectious disease. Recent studies indicate that genitourinary TB is the third most common form of extra-pulmonary disease. The diagnosis of renal TB can be hypothesized in a non-specific bacterial cystitis associated with a therapeutic failure or a urinalysis with a persistent leukocyturia in the absence of bacteriuria. We report on the case of a 33-year-old man who presented on admission end stage renal disease (ESRD) secondary to renal TB and a past history of pulmonary TB with important radiologic findings. The diagnosis was based on clinical findings despite all cultures being negative. Empiric treatment with tuberculostatic drugs was started and the patient became stable. He was discharged with no symptom, but without renal function recovery. He is on maintenance hemodialysis three times a week. TB is an important cause of kidney disease and can lead to irreversible renal function loss.

Pathology of complete atrioventricular block in chronic chagas' myocarditis

Sclero-atrophy, fibrosis, vascular ectasia, phlebosclerosis and mild non-specific chronic inflammatory changes were observed in variable location and proportion involving the atrioventricular conducting tissue of the heart in five human cases of chronic Chagas' myocarditis associated with complete atrioventricular block. One case presented complete destruction of the A-V conduction system. In three cases the lesions were disseminated all along the conducting tissue but did not cause anywhere a complete disruption in the continuity of the system. The distal portion of the bundle branches were the most damaged sector of the system, exceptfor the fasciculi of the posterior division of the left bundle branch which were relatively preserved. One case exhibited bilateral sclero-atrophy of the bundle branches as the main change; and another showed early and mild fibrocalcific damage of the penetrating portion of the His bundle. The A-V node appeared as the least involved part of the conducting system in the cases studied. Demonstration of the lesions in this series of cases seems important because: a) it reveals that complete atrioventriculr block in chronic Chagas' disease results from disseminated lesions and not from focal disruptive change as has been commonly observed in cases of other etiologies; b) it shows that chronic inflammation can produce at the end variable and widespread vascular, degenerative andfibrotic alterations within the conducting tissue of the heart, which may lead to its total destruction.

T cell-dependent immunodepression in vivo in Schistosoma mansoni infected patients

T-cell function was evaluated in 29 patients with either hepatointestinal or hepatosplenic schistosomiasis by intradermal tests to recall antigens. Immunodepression was detected in 26% of the subjects with hepatointestinal schistosomiasis and in 50% of those with the hepatosplenic form. Cellular immunodepression was related to worm load and spleen size. This non specific T-cell immunodepression may represent a serious constraint to the elimination of intracellular pathogens both in hepatosplenic or hepatointestinal schistosomiasis.

Cerebrospinal fluid syndromes in HIV-positive patients with acute consciousness compromise

We reviewed the cerebrospinal fluid (CSF) syndromes of 100 consecutive HIV-positive patients presenting acute consciousness compromise in emergency rooms, and correlated them with clinical data. The most frequent CSF syndromes were: absolute protein-cytological dissociation (21), viral (19), neurocryptococcosis (7), relative protein-cytological dissociation (6) and septic (4), moderate hypoglycorrachia (4), severe hypoglycorrachia (4) and hydroelectrolytic disturbance (3). One fifth of the patients had CSF syndromes considered sufficient for diagnosis or an immediate clinical decision. The most common clinical data were infective and neurological. There was little correlation between the clinical data and the CSF syndromes. We conclude that in HIV-positive individuals presenting acute consciousness disturbances there are frequently non-specific results in the CSF analysis that must be weighed against a detailed history and thorough physical examination. Taking this into account, in about one fifth of cases the CSF analysis can offer useful information for treatment.