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Biomedical subjects

C Ahrén

Publications and source records attributed to C Ahrén.

At least 19 recordsLinked to original sources

Dose-dependent circulating immunoglobulin A antibody-secreting cell and serum antibody responses in Swedish volunteers to an oral inactivated enterotoxigenic Escherichia coli vaccine.

The immunogenicity of different preparations of an oral inactivated enterotoxigenic Escherichia coli (ETEC) vaccine was evaluated in Swedish volunteers previously unexposed to ETEC infection. The vaccine preparations consisted of recombinant cholera toxin B subunit (CTB) and various amounts of formalin-killed whole bacteria expressing the most prevalent colonization factor antigens (CFAs). Significant immunoglobulin A (IgA) antibody-secreting cell (ASC) responses against CTB and the various CFA components were seen in a majority of volunteers after two doses of ETEC vaccine independent of the vaccine lot given. The IgA ASC responses against CTB were significantly higher after the second than after the first immunization, whereas the CFA-specific IgA ASC responses were almost comparable after the first and second doses of ETEC vaccine. Two immunizations with one-third of a full dose of CFA-ETEC bacteria induced lower frequencies of IgA ASC responses against all the different CFAs than two full vaccine doses, i.e., 63 versus 80% for CFA/I, 56 versus 70% for CS1, 31 versus 65% for CS2, and 56 versus 75% for CS4. The proportion of vaccinees responding with rises in the titer of serum IgA antibody against the various CFA antigens was also lower after immunization with the reduced dose of CFA-ETEC bacteria. These findings suggest that measurements of circulating IgA ASCs can be used not only for qualitative but also for quantitative assessments of the immunogenicity of individual fimbrial antigens in various preparations of ETEC vaccine.

Administration, Oral↗

Induction of systemic antifimbria and antitoxin antibody responses in Egyptian children and adults by an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine.

We assessed serologic responses to an oral, killed whole-cell enterotoxigenic Escherichia coli plus cholera toxin B-subunit (ETEC-rCTB) vaccine in 73 Egyptian adults, 105 schoolchildren, and 93 preschool children. Each subject received two doses of vaccine or placebo 2 weeks apart, giving blood before immunization and 7 days after each dose. Plasma antibodies to rCTB and four vaccine-shared colonization factors (CFs) were measured by enzyme-linked immunosorbent assay. Immunoglobulin A (IgA) antibodies to rCTB and CFA/I were measured in all subjects, and those against CS1, CS2, and CS4 were measured in all children plus a subset of 33 adults. IgG antibodies to these five antigens were measured in a subset of 30 to 33 subjects in each cohort. Seroconversion was defined as a >2-fold increase in titer after vaccination. IgA and IgG seroconversion to rCTB was observed in 94 to 95% of adult vaccinees, with titer increases as robust as those previously reported for these two pediatric cohorts. The proportion showing IgA seroconversion to each CF antigen among vaccinated children (range, 70 to 96%) and adults (31 to 69%), as well as IgG seroconversion in children (44 to 75%) and adults (25 to 81%), was significantly higher than the corresponding proportion in placebo recipients, except for IgA responses to CS2 in adults. IgA anti-CF titers peaked after one dose in children, whereas in all age groups IgG antibodies rose incrementally after each dose. Independently, both preimmunization IgA titer and age were inversely related to the magnitude of IgA responses. In conclusion, serologic responses to the ETEC-rCTB vaccine may serve as practical immune outcome measures in future pediatric trials in areas where ETEC is endemic.

Administration, Oral↗

Measurement of specific IgA in faecal extracts and intestinal lavage fluid for monitoring of mucosal immune responses.

Currently available methods for the evaluation of antigen-specific immune responses in the intestine, i.e. measurement of IgA in intestinal lavage and antibody secreting cells (ASC) in peripheral blood, are not applicable to large-scale immunogenicity studies or to kinetic studies where repeated sampling is required. Simple and reliable methods need to be developed. Intestinal lavage and faecal samples were collected from 12 mice on days 0, 14, 21, 28 and 35 following initial immunization with four doses of cholera toxin (CT) by the gastric or rectal routes. The concentrations of anti-CT IgA in the faecal extracts showed a high level of correlation with those in the lavage samples (Spearman's correlation coefficient=0.85, P<0. 0001) regardless of the route of CT administration. Moreover, the kinetics of the immune response as reflected in the faecal extracts mirrored those in the lavage samples regardless of immunization route. As compared to gastric immunization, rectal administration of CT yielded higher levels of anti-CT IgA in both intestinal lavage fluids and in faecal extracts. The use of rectal immunization and the measurement of IgA in faecal extracts for monitoring mucosal immune responses may be relevant for the development of effective enteric vaccines.

Adult↗

Plasma nitrate as an index of nitric oxide formation in patients with acute infectious diseases.

In humans, the role of nitric oxide (NO) in host defence is controversial. We prospectively studied plasma levels of nitrate, the stable end-product of NO formation, during acute infection in 43 patients controlled with regard to dietary nitrate/nitrite. During acute gastroenteritis the mean plasma nitrate level was significantly increased compared with at recovery 4-5 weeks later (118 vs. 32.5 micromol/l; p < 0.001), in contrast with the findings in patients with acute pneumonia (PN; 34.6 vs. 42.8 micromol/l) or febrile urinary tract infection (UTI; 27.7 vs. 31.3 micromol/l). In a second group of 20 retrospectively studied patients with severe PN or UTI, of whom 70% were bacteraemic, no significantly increased nitrate levels could be demonstrated during the acute stage of infection. These findings indicate that increased NO production, as measured by plasma nitrate, is not a general finding in patients with acute infectious diseases, but may rather be associated with certain pathogens or sites of infection.

Acute Disease↗

Mucosal antibodies can be measured in air-dried samples of saliva and feces.

IgA antibodies reflecting airways or intestinal mucosal immune responses can be found in saliva and feces, respectively, and IgG antibodies reflecting serum antibodies can be found in saliva. In this study, antibodies were detected in samples of saliva and feces which had been air-dried at room temperature (+20 degrees C) or +37 degrees C, and stored at these temperatures for up to 6 months. In saliva the antibody levels increased, while the antibodies in feces decreased upon storage. The individual IgA antibody concentrations which were adjusted by using the ratios of specific IgA/total IgA were relatively stable in both saliva and feces, and correlated with corresponding antibody levels in samples which had been stored at -20 degrees C. The results indicate that air-dried saliva and feces can be used for semiquantitative measurements of mucosal antibodies, even after prolonged storage at high temperatures and lack of refrigeration.

Feces↗

Intestinal immune responses to an inactivated oral enterotoxigenic Escherichia coli vaccine and associated immunoglobulin A responses in blood.

An inactivated oral enterotoxigenic Escherichia coli (ETEC) vaccine against ETEC diarrhea was given to 25 adult Swedish volunteers. The vaccine consisted of formalin-killed E. coli bacteria expressing the most common colonization factor antigens (CFAs), i.e., CFA/I, -II, and -IV, and recombinantly produced cholera B subunit (CTB). Immunoglobulin A (IgA) antibody responses in intestinal lavage fluid to CTB and CFAs were determined and compared with corresponding responses in stool extracts and serum as well as with IgA antibody-secreting cell (ASC) responses in peripheral blood. Two doses of vaccine induced significant IgA responses to the different CFAs in lavage fluid in 61 to 87% of the vaccinees and in stool in 38 to 81% of them. The most frequent responses were seen against CFA/I. The magnitudes of the antibody responses against CTB and CFA/I in stool correlated significantly (CTB, P < 0.01; CFA/I, P < 0. 05) with those in intestinal lavage. Intestinal lavage responses against CFAs were best reflected by the ASC responses, with the sensitivity of the ASC assay being 80 to 85%, followed by stool (sensitivity of 50 to 88%) and serum antibody (sensitivity of 7 to 65%) analyses. CTB-specific immune responses were seen in >90% of the vaccinees in all assays.

Administration, Oral↗

Optimization of the intestinal lavage procedure for determination of intestinal immune responses.

Optimal conditions to process, concentrate and store intestinal lavage fluid were studied in samples collected from volunteers before and after oral immunization with a prototype vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhoea. Total IgA and specific IgA antibody titres against enterotoxin and colonization factor antigen were determined in 22 lavage samples which were either enzyme-inhibited or heat-inactivated and then subjected to different long-term storage conditions. Samples were analysed within 1 month of collection and also after 3, 6 and 24 months of storage. Total IgA concentrations and specific IgA antibody levels were higher in lavage samples treated with enzyme inhibitors (soybean trypsin inhibitor and phenylmethylsulfonyl fluoride) than in those heat-inactivated. Similarily, concentration of the lavage fluid by freeze-drying was superior to concentration against polyethylene glycol. Specific antibody titres remained elevated after storage for at least 6 months but declined after 2 years in frozen compared with freeze-dried samples.

Administration, Oral↗

Campylobacter jejuni/coli and enterotoxigenic Escherichia coli (ETEC) in faeces from children and adults in Tanzania.

The occurrence of Campylobacter and enterotoxigenic E. coli (ETEC) was studied in faecal samples from Tanzanian children (< 5 years of age), adolescents and adults (only Campylobacter) with and without diarrhoea. The Campylobacter strains isolated were tested for subspecies, enterotoxigenicity and serotype. Out of 394 children with diarrhoea 18% were infected with Campylobacter and 20% with ETEC. In 278 samples tested for Campylobacter and 136 tested for ETEC from asymptomatic children the corresponding numbers were 12 and 5%, respectively. In children < 18 months with diarrhoea Campylobacter was noted in 22% and ETEC in 18%, whereas the figures were 11 and 4% respectively in asymptomatic children. In the age group 18 months to 5 years Campylobacter was demonstrated in 2% of the children with diarrhoea and 27% had ETEC, while the figures were 15 and 8% for asymptomatic children. Among adults the prevalence of Campylobacter-positive samples was 1% both for symptomatic and asymptomatic individuals. There were no seasonal differences in the prevalences of both Campylobacter and ETEC either in the symptomatic or the asymptomatic group. Campylobacter jejuni was the dominating Campylobacter species among both symptomatic and asymptomatic individuals. C. jejuni strains from patients with diarrhoea were significantly more often enterotoxigenic than were C. coli strains. The serotype pattern regarding Campylobacter was in general similar for symptomatic and asymptomatic individuals. We conclude that Campylobacter and ETEC are common causes of bacterial diarrhoea in Tanzanian children, and that Campylobacter infections are more important in children younger than 18 months, than in older ones.

Adolescent↗

Follow-up after screening for colorectal neoplasms with fecal occult blood testing in a controlled trial.

PURPOSE: The aim of this study was to investigate the number of new colorectal neoplasms during the first seven years after the end of rescreening in a prospective randomized screening study. METHODS: 27,700 inhabitants of Göteborg born between 1918 and 1922 (60-64 years old) who were randomly allocated to a control or a test group in 1982 were followed up. All people in the latter group were offered six fecal occult blood tests and rescreening 16 to 22 months later. RESULTS: One hundred one carcinomas were diagnosed in the screened group and 128 in the control group during the seven years of follow-up. The number of carcinomas in the test group was half that in the control group during the first two years of follow-up, but equal during the rest of the follow-up period. The distribution of carcinomas according to Dukes classification was significantly better among the participants compared with the refusers (P < 0.02) but there was no difference in the Dukes distribution when the test and control groups as a whole were compared. The number of adenomas in the two groups during seven years of follow-up was the same. CONCLUSION: The results indicate that screening and rescreening of a population has little influence upon the stage of the carcinomas in the test group compared with a control group during the first seven years of follow-up. The number of carcinomas was higher in the control than in the test group during the follow-up, probably because of a lead time effect during the screening.

Adenoma↗

Results of screening, rescreening, and follow-up in a prospective randomized study for detection of colorectal cancer by fecal occult blood testing. Results for 68,308 subjects.

All 68,308 inhabitants of Göteborg born between 1918 and 1931 were randomly divided into a test and a control group. The subjects in the test group were invited to perform Hemoccult II fecal occult blood testing on 3 days and to repeat the test after 16 to 24 months. In the prevalence screening 21,347 (63%) performed the test, and in the rescreening 19,991 (60%). Investigation of the 942 (4.4%) with positive tests in the prevalence screening showed 47 cancers and 129 subjects with adenomas > or = 1.0 cm. In the rescreening 5.1% had a positive test, and 34 cancers and 122 subjects with adenomas (> or = 1.0 cm) were found among those. Cancer had also been diagnosed in 19 subjects in the interval between the two screening occasions and in 15 subjects among the non-responders. Forty-four cancers had been diagnosed in the control group during the same period. Cancers detected by screening were at a less advanced stage than in the control group. It is too early to show any effect of screening on mortality from colorectal cancer.

Adenoma↗

Intestinal antibody response after oral immunization with a prototype cholera B subunit-colonization factor antigen enterotoxigenic Escherichia coli vaccine.

A prototype oral enterotoxigenic Escherichia coli (ETEC) vaccine containing formalin-inactivated whole bacteria expressing colonization factor antigens CFA/I and CFA/II and cholera B subunit (CTB) has been tested for safety and immunogenicity in 20 adult Swedish volunteers. When given in three doses with 2-week intervals the vaccine was found to be safe and to give rise to specific IgA antibody responses in intestinal lavage fluid in most of the volunteers (CFA/I 82%, CFA/II 82% and CTB 91%). The frequencies and magnitudes of these responses, which were already maximal after two doses, were comparable with those previously found in patients convalescing from severe ETEC diarrhoea. All the vaccinated volunteers also responded with antitoxin IgA as well as IgG antibodies in serum, whereas the serum antibody responses against the CFAs were weaker and mainly of the IgA isotype.

Administration, Oral↗

Antibody-secreting cells in human peripheral blood after oral immunization with an inactivated enterotoxigenic Escherichia coli vaccine.

Vaccine antigen-specific antibody-secreting cell (ASC) responses in peripheral blood of healthy adult volunteers were studied after oral immunization with a prototype enterotoxigenic Escherichia coli (ETEC) vaccine by means of the enzyme-linked immunospot technique. Three doses of vaccine consisting of formalin-killed ETEC bacteria expressing fimbrial colonization factor antigens I and II (CFA/I and CFA/II) in combination with purified cholera toxin B subunit (CTB) were given 2 weeks apart. The ASC responses were detected 7 days after each immunization. Immunoglobulin A (IgA) was the predominant isotype produced by CFA/I- as well as CFA/II-specific ASCs. Moderate CFA/I- and CFA/II-specific IgM-secreting ASC (IgM-ASC) responses were also seen, whereas IgG-ASC responses to either of the CFAs were negligible. The ASC responses to CTB, on the other hand, comprised both IgA- and IgG-ASCs, with few if any specific IgM-ASCs. Almost 90% of the volunteers developed CFA-specific ASC responses after vaccination. Maximal CFA-specific ASC responses were usually observed after a single dose or two doses of vaccine. A third dose of vaccine did not result in increased but rather resulted in decreased magnitudes of CFA-specific ASC responses. Furthermore, it was found that CTB did not function as a mucosal adjuvant, since CFA-specific ASC responses were not enhanced by the simultaneous administration of CTB. These results suggest that two oral doses of ETEC vaccine induce a strong mucosal immune response, as reflected by the presence of large numbers of antigen-specific mucosal B cell immunoblasts in the blood.

Administration, Oral↗

Colonization factors of enterotoxigenic Escherichia coli isolated from children with diarrhea in Argentina.

A prospective study was performed to evaluate the presence of colonization factor antigens (CFAs) in enterotoxigenic Escherichia coli (ETEC) strains isolated from 1,211 children with diarrhea in Argentina. One hundred nine ETEC strains that were isolated from seven different laboratories in various regions of the country were tested for CFAs by using monoclonal antibodies against CFA/I and E. coli surface antigens CS1, CS2, and CS3 of CFA/II and CS4 and CS5 of CFA/IV; a polyclonal antiserum against CS6 was used. The CFAs searched for were found in 52% of the ETEC strains: 23% of the strains carried CFA/I, 17% carried CFA/IV, and 12% carried CFA/II. All of the CFA/I strains produced heat-stable enterotoxin, and several of them were of the prevalent serotypes O153:H45 and O78:H12. Among the 19 strains expressing CFA/IV, 16 expressed CS5 and CS6 and produced the heat-stable enterotoxin and most were of serotype O128:H21; the remaining 3 strains produced CS6 only. No ETEC strains expressing CS4 were found. Most (11 of 13) of the CFA/II-carrying ETEC strains expressed CS1 and CS3, and 10 of them were of the O6:K15:H16 serotype and produced both heat-labile and heat-stable toxins. As many as 24 of the 109 CFA-negative ETEC strains gave mannose-resistant hemagglutination with erythrocytes from different species; 4 strains had high surface hydrophobicity, suggesting the presence of additional, as yet undefined, colonization factors in up to 25% of the ETEC isolates.

Antigens, Bacterial↗

Long-term follow-up of patients with continent ileostomies.

Thirty-six patients were evaluated after having continent ileostomies for 16 to 20 years. Follow-up included clinical examination, response to a questionnaire, blood tests, and radiologic studies of the gallbladder. In addition, reservoir biopsies from 15 patients were examined. The patients were in excellent general health, all but one having gained weight postoperatively. There was no increased risk for gallstone formation or for urinary tract stone development. Although 11 of the 36 patients had reservoirs that were not provided with a valve, 92 percent of all patients were continent. Working capacity was normal in most patients and no harmful effects of the reservoir were revealed by morphologic or biochemical studies. In conclusion, no deleterious long-term effects were found as a result of the continent ileostomy.

Activities of Daily Living↗

Clinical disease activity and inflammatory activity in the rectum in relation to mucosal inflammation assessed by colonoscopy. A study of children and adolescents with chronic inflammatory bowel disease.

The relationship between clinical disease activity, rectal inflammatory activity and mucosal inflammation established at total colonoscopy has been studied in 36 young patients with ulcerative colitis (UC) and 24 with Crohn's colitis (CC). Semiformed stools, diarrhea and frequent bowel movements seem to be better indicators of extensive mucosal inflammation of a moderate or severe degree than blood in faeces. There were, however, several patients with a discrepancy between the degree of clinical disease activity and the extent and degree of mucosal inflammation at endoscopic and histologic assessment. In about one-third of the patients with UC and in about half of the patients with CC, who had mucosal inflammatory activity of a moderate or severe degree, the rectal inflammatory activity was of a lower degree. Total colonoscopy seems to be necessary in order to establish the extent and degree of mucosal inflammation.

Adolescent↗

Serum antibody responses to bacterial enteropathogens in Swedish travelers to south-east Asia.

The possibility that serological analysis may be more sensitive than bacteriological examinations of stool samples to detect enteric infections was evaluated in 80 Swedish travellers to South-East Asia. Serum and faecal specimens were collected before, during and after their travel. Serological analyses of pre-travel and any later serum specimen identified infection with enterotoxinogenic Escherichia coli (ETEC), Salmonella or Campylobacter jejuni in 28% of the travellers. The seroconversion rate was 72% in travellers excreting the homologous pathogen in their stool; all symptomatic cases and half of those who had an asymptomatic infection seroconverted. Bacteriological examinations of stool samples collected repeatedly during travel identified an enteropathogen in 20% of the travellers. However, the isolation rate decreased to 11%, when only a single routine faecal specimen was examined. Our findings suggest that serological analyses of pre- and post-travel specimens are sufficiently specific and may be at least as sensitive as conventional bacteriology to identify infections with bacterial enteropathogens in travellers. However, reliable serodiagnosis requires collection of pre-travel sera and might therefore only be useful in prospective studies of travellers' diarrhoea.

Adult↗