Disseminated infection due to Nocardia transvalensis coincident with Cryptococcus neoformans variety gattii meningitis.

A case of meningitis due to Cryptococcus neoformans var. gattii coincident with disseminated Nocardia transvalensis infection is reported. Nocardia infection initially progressed despite high-dose antimicrobial therapy. Although a specific immunologic defect could not be defined, in vitro lymphocyte proliferation in response to stimulation with the Nocardia isolate was reduced. It is proposed that coinfection with Cryptococcus neoformans may have contributed to the observed impairment of lymphocyte function, leading to disseminated Nocardia disease and a suboptimal treatment response.

Typhoid in 1993.

Typhoid remains a disease of major importance world-wide although improvements in public health have made it an exotic disease in developed countries like Australia. Effective antibiotic therapy with the advent of chloramphenicol, which was first used to treat typhoid in the 1940s, has also dramatically altered the natural course of the disease and reduced its mortality rate from around 25% to as low as 1%. The main areas of recent change include the emergence of resistance to previously effective antibiotics, more aggressive intervention in the management of severe typhoid and some of its complications such as perforation, and the development of an oral typhoid vaccine that may replace the equally effective but more unpleasant parenteral vaccination that has been widely used since World War.

Chronic liver disease in asymptomatic hepatitis C antibody positive blood donors.

The risks of acquisition of hepatitis C infection, the histological spectrum of liver disease, and the presence of viraemia were investigated in anti-hepatitis C virus (HCV) antibody positive blood donors. All 357 (0.64%) blood donors to the South Australian Red Cross Transfusion Service found to have anti-HCV antibody during the first seven months of testing in 1990 were assessed, and 70 (19.6%) were found to have elevated alanine transaminase levels. These subjects were referred for participation in the study; 31 presented for enrollment. Sixteen (52%) of the 31 patients had previously used intravenous drugs, four (13%) had been transfused, two (6%) had a history of occupational exposure to blood, and three (10%) had tattoos and ear-piercing as possible risk factors for acquisition of hepatitis C. There was no history of parenteral exposure in six (16%). None of these donors had clinical evidence of liver disease, but in all 24 of the 31 who had a liver biopsy there was histological evidence of significant liver damage. Twelve had evidence of chronic active hepatitis. All 24 subjects biopsied were viraemic as judged by the presence of HCV RNA in serum.

HIV-related gastrointestinal disease.

Gastrointestinal disease is common in patients infected with HIV and can represent the first significant clinical illness. Diarrhoea, dysphagia, abdominal pain, jaundice or gastrointestinal bleeding may be the result of opportunistic infection, AIDS-related neoplasia, or infection with HIV alone. The spectrum of gastrointestinal tract and liver involvement in HIV infection is broad and has been well reviewed recently. This article is selective in that the main emphasis is placed on the variety of ways that HIV may first declare itself with symptoms in the gastrointestinal tract.

Enteropathy in HIV infection.

Enteropathy occurs frequently in persons infected with human immunodeficiency virus (HIV), and symptoms related to the gut are a major cause of debility. The pathogens associated with disease are diverse, often difficult to detect, and frequently poorly responsive to any therapeutic intervention. This brief review examines HIV-related enteropathy from the perspective of symptomatology, and discusses some of the recent advances in diagnosis of specific gut disorders.

Anti-gliadin antibody specificity for gluten-derived peptides toxic to coeliac patients.

The specificities of serum and intestinal antibodies from coeliac and normal individuals towards gluten-derived peptides, known to be toxic in coeliac disease, has been investigated. Though untreated coeliacs had high serum antibody levels towards gliadin and some gluten-derived peptides, antibody specificities to various toxic gluten-derived peptides were similar to normal patients. Further, no significant binding in any patient group was found to the alpha-gliadin-derived peptides B1342 (Wieser, Belitz & Ashkenazi, 1984) or the 12 amino-acid A-gliadin peptide (Kagnoff, 1985). There appears to be no direct relationship between the toxicities and the antigenic reactivity of gluten-derived peptides. Thus, the intestinal damage in coeliac disease is probably not primarily caused by antibody-dependent mechanisms. The specificities of several monoclonal antibodies which bound to wheat prolamins as well as prolamins from other coeliac-toxic cereals have also been investigated with these toxic gluten-derived peptides, in order to identify possible common epitopes. No monoclonal antibody tested bound the B1342 and 12-amino-acid A-gliadin peptide. However the monoclonal antibodies which were specific for the coeliac-toxic cereal prolamins did show the strongest binding to other coeliac-toxic gluten-derived peptides.

Does anxiety reduce the secretion rate of secretory IgA in saliva?

The effects of anxiety, depression and psychological stress on the secretion rate of salivary immunoglobulin (Ig)A were examined in a cross-sectional study of 114 registered nurses. A single, timed (five minutes) sample of whole unstimulated saliva was collected from each nurse; at the time of collection, psychosocial data for each nurse were collected by questionnaire. Nurses who reported more frequent episodes of anxiety had significantly lower mean secretion rates of salivary IgA than did nurses who reported only occasional episodes of anxiety. The concentration of secretory IgA in saliva decreased as the salivary volume increased. It was not possible to demonstrate whether anxiety influenced IgA secretion in saliva independently of its effects on salivary flow.

Variation of serum and intestinal gluten antibody specificities in coeliac disease.

Protein blotting techniques were used to investigate the gluten specificity of IgA and IgG antibodies in sera and intestinal aspirates from patients with coeliac disease and normal controls. Initially, discontinuous SDS polyacrylamide gel electrophoresis was used to separate the flour proteins. All normal and coeliac sera contained antibodies which bound to various of the gliadin proteins. In only a few sera was binding found to the high molecular weight glutenin subunits, while none was detected to the salt-soluble wheat proteins. Polyacrylamide gradient gel electrophoresis was then used to further separate the gliadin proteins. Almost all normal sera examined showed similar gliadin specificity, binding uniformly to all gliadin groups. While approximately a quarter of the coeliac sera showed even binding to all of the gliadin proteins, the majority showed antibody binding intensely to discrete groups of gliadin bands. We were unable to identify any gliadin band(s) which only bound antibodies from coeliac patients in comparison with normal subjects. The specificities of IgG and IgA serum antibodies were identical for each patient examined, but some differences between serum and intestinal IgA specificities were found for certain patients.

In vitro immunoglobulin synthesis by human intestinal lamina propria lymphocytes.

The concentration of IgG and IgA was measured in the supernatants of peripheral blood mononuclear cells and of cells harvested from the intestinal lamina propria, which were cultured in vitro in the presence or absence of mitogens. The lamina propria mononuclear cells were harvested by collagenase digestion of macroscopically normal mucosa from 10 fresh surgical resections for carcinoma. Secretion of IgA in cultures of unstimulated lamina propria mononuclear cells greatly exceeded that of IgG. The addition of pokeweed mitogen increased Ig secretion by cultures of peripheral blood mononuclear cells but decreased Ig secretion by lamina propria mononuclear cells. The addition of concanavalin A suppressed Ig synthesis by pokeweed mitogen stimulated cells more in cultures of peripheral blood mononuclear cells than in lamina propria mononuclear cells. Cycloheximide inhibited Ig secretion by more than 90% in cultures of peripheral blood mononuclear cells, but there was less inhibition in cultures of lamina propria mononuclear cells. In the four unstimulated cultures of lamina propria mononuclear cells examined, over 75% of the Ig was secreted in the first three to four days of culture. The results indicate that lamina propria mononuclear cells are refractory to the inductive and suppressive signals of mitogens, and represent an activated cell population which is committed to Ig secretion before being cultured.

Antibodies in serum and secretions 1 year after salmonella gastroenteritis.

The antibody response in serum and intestinal fluid in eight patients 1 year after their recovery from salmonella gastroenteritis was measured by solid phase radioimmunoassay and compared to the immune response within a few weeks of infection, reported previously in these and other patients. High concentrations of intestinal antibody were found in six patients compared to the concentrations found in 10 control subjects. By contrast the serum antibody concentration in the patients was only marginally higher than in the controls. The use of IgA and IgG specific antisera in the assay confirmed the presence of IgA antibody in the absence of IgG antibody in the gastrointestinal secretions, and the predominance of IgG antibody in the serum. The prolonged immune response in the gut after acute bacterial gastroenteritis supports the possibility of effective immunization against diseases entering via the gut.

Escherichia coli antibody-secreting cells in the human intestine.

Mononuclear cells were isolated from the mucosa and submucosa of small intestine and colon of 22 subjects with localized, anatomically remote disease and four subjects with Crohn's disease (nine specimens) by sequential treatment with EDTA and collagenase. The effects of isolation techniques on cell yields and viability were examined. Secretion of specific IgA, IgM and IgG antibodies to common faecal Escherichia coli strains by individual mononuclear cells was studied using a haemolytic plaque assay. A majority of specific antibody secreting cells secreted IgA antibody. This response was greatest and most consistent in the distal colon but extended from stomach to rectum. There was no evidence of a primary defect in IgA antibody response in the few subjects with Crohn's disease available for study.

Antibody response to the lipopolysaccharide and protein antigens of Salmonella typhi during typhoid infection. I. Measurement of serum antibodies by radioimmunoassay.

Serum antibody responses to the lipopolysaccharide and protein antigens of S. typhi in typhoid patients were studied using a solid-phase radioimmunoassay technique. Sera from 24 adult typhoid patients and 20 non-typhoid adult controls were compared. As a group, sera from typhoid patients showed increased IgA, IgG and IgM immunoglobulin levels and gave significantly higher anti-LPS and anti-protein antibody titres in all three major immunoglobulin classes than did non-typhoid controls. Levels of antibodies against LPS or protein in sera of typhoid patients were highly variable with a skew distribution. A good correlation was found between antibody titres to the LPS antigen and those to a protein antigen. No correlation, however, was found between the anti-LPS antibody titres measured by radioimmunoassay and the anti-O antibody titres measured by the Widal agglutination test. Titration of anti-LPS or anti-protein antibodies by radioimmunoassay was found to be more sensitive and specific than Widal test for the serological diagnosis of typhoid fever. The advantages of measuring antibody response by radioimmunoassay over conventional Widal test are discussed.

Antibody response to the lipopolysaccharide and protein antigens of Salmonella typhi during typhoid infection. II. Measurement of intestinal antibodies by radioimmunoassay.

Antibodies to the lipopolysaccharide (LPS) and protein antigens of S. typhi in secretions of small intestine obtained from 12 typhoid patients, four typhoid carriers and 16 non-typhoid control subjects were measured by a solid-phase radioimmunoassay technique. Intestinal secretions obtained from typhoid patients as a group had significantly higher anti-LPS and anti-protein antibodies than those from the control group. These antibodies were both IgM and IgA classes. There was no correlation between the IgM or IgA antibody levels in serum and those in the intestinal secretions. In the intestinal secretions obtained from typhoid carriers, on the other hand, only IgA-class antibodies to the LPS and protein antigens of S. typhi were present at high levels.

Whipple's disease: a case with circulating immune complexes.

A patient with Whipple's disease was studied for 56 wk from diagnosis, during which time he received continuous antibiotic therapy. Intramucosal bacillary bodies detected by electron microscopy disappeared within 12 wk and a threefold fall in antibody titer to Hemophilus influenza type B bacillus occurred during this period. Circulating immune complexes of IgG class were consistently detected during the first 28 wk of treatment but not subsequently. IgM class immune complexes were detected at a time when mucosal recovery had occurred and when IgG complexes were no longer detectable. A further rise of IgM immune complexes could be induced by enteric challenge with bovine serum albumin in our patient but not in control subjects. The detection of serum immune complexes in Whipple's disease may reflect the entry of foreign antigen through intestinal mucosa. These observations also support the possibility of an underlying defect of antigen exclusion in this disorder, which persists despite apparent mucosal recovery.

Measurement of intestinal antibody by radioimmunoassay.

The study of antibody responses in the intestine has been greatly hampered by lack of reproducible sensitive assays. An assay for measuring antibody against bacteria capable of regularly detecting gut antibody in gastroenteritis is described. It is based on absorption of antibody onto bacteria and measurement of the amount of antibody bound using radiolabelled anti-immunoglobulin antibody. Anti-light chain antibody is used to detect all classes of antibody as well as partially degraded antibody which retains the capacity to bind; anti-alpha and anti-gamma antibody is used to measure IgA and IgG antibody. The sensitivity of the assay depends on the use of anti-immunoglobulin antibody purified by affinity chromatography and allows measurement of nanogram amounts of antibody. Its specificity and kinetics are described and the particular advantages it provides in the measurement of antibacterial antibody in the intestine are discussed.

The antibody response to bacterial gastroenteritis in serum and secretions.

The antibody responses to bacterial gastroenteritis in jejunal aspirates and sera from sixteen adults and nine children were examined using a radioimmunoassay. Twelve adults served as controls. A clear antibody response was apparent in both intestinal aspirates and sera. While the absolute concentrations of antibody were much higher in sera, the proportion of immunoglobulin committed to specific antibodies was similar in both the intestinal fluids and sera. The antibody responses in the intestine and in the serum were very similar in the group as a whole, but they varied widely in individual subjects. Over a period of 1 month intestinal antibody levels in adults remained constant but in children they showed a decrease. In two subjects high levels of intestinal antibody were still apparent after 1 year. The organism responsible for the infection was still present in the gut of five subjects 1 month after clinical recovery from infection in the presence of local antibody. The relevance of these results and their implications for further study of the immune response to bacterial gastroenteritis are discussed.