We investigated the faecal carriage prevalence of extended-spectrum β-lactamase production in
Escherichia coli
(EP-EC) and/or
Klebsiella pneumoniae
(EP-KP) and risk factors associated with carriage ...among adult study subjects in Finland, Germany, Latvia, Poland, Russia and Sweden (partner countries). The aim was to get indicative data on the prevalence of ESBL-carriage in specific populations in the region. Faecal samples were collected from four study populations and screened on ChromID-ESBL and ChromID-OXA-48 plates. Positive isolates were further characterised phenotypically. Our results show a large variation in carrier prevalence ranging from 1.6% in Latvia to 23.2% in Russia for EP-EC
.
For the other partner countries, the prevalence of EP-EC were in increasing numbers, 2.3% for Germany, 4.7% for Finland, 6.6% for Sweden, 8.0% for Poland and 8.1% for all partner countries in total. Carriers of EP-KP were identified only in Finland, Russia and Sweden, and the prevalence was < 2% in each of these countries. No carriers of carbapenemase-producing isolates were identified. This is the first study reporting prevalence of carriers (excluding traveller studies) for Finland, Latvia, Poland and Russia. It contributes with important information regarding the prevalence of EP-EC and EP-KP carriage in regions where studies on carriers are limited.
Lower respiratory tract infections (LRTI) are the leading cause of death world-wide, with Streptococcus pneumoniae (Pnc) as the most prevalent pathogen. Local immune mechanisms appear central to ...protection against the disease, yet they are poorly characterized. Infections at other, non-respiratory mucosal sites are associated with a transient circulation of mucosa-originating lymphocytes from the mucosal site to blood and back to the mucosa. The present study explored whether pathogen-specific plasmablasts appear in the circulation also in patients with infection of the lower respiratory tract. 16 patients with bacteremic Pnc pneumonia and 14 healthy volunteers were explored for circulating plasmablasts secreting antibodies against their own pathogenic Pnc strain isolated in blood cultures (patients) or against several pathogenic strains from pneumonia patients (14 controls) or a mixture of nine different purified pneumococcal polysaccharides (8 controls). Both patients and volunteers were studied for all plasmablasts. The cells were identified with ELISPOT as Pnc-specific antibody-secreting cells (ASC) and as all immunoglobulin-secreting cells (ISC). High numbers of circulating Pnc-specific ASC were found in the acute phase of the disease in all patients with pneumonia (median 97 ASC/10(6) PBMC), but in none of the controls. IgG isotype predominated in 9/16 patients. The numbers of ISC were significantly higher in the patients than in the healthy controls, yet Pnc-specific ASC only accounted for 0.7% of all the patients' ISC.The present study is the first to show that antigen-specific plasmablasts appear in the circulation in pneumonia, suggesting that pulmonary lypmhocytes recirculate in humans. Assessing these cells provides a novel tool for studying immune response to antigens encountered at the LRT.
The performance of the interferon gamma release assays (IGRAs) and tuberculin skin test (TST) was reviewed retrospectively in patients with psoriasis, inflammatory musculoskeletal diseases, or ...miscellaneous inflammatory conditions. The study was carried out over a 22-month period using 109 records of patients with psoriasis (n=21), musculoskeletal disease (n=74), or other inflammatory conditions (n=14). Forty-four (48%) of 109 patients were on immunosuppressive therapy and 38/109 (35%) on systemic glucocorticoid therapy. The agreement between the IGRAs was substantial (κ=0.71) whilst that between the IGRAs and TST was low (κ=0.32). Logistic regression models revealed that IGRAs associated with risk factors for latent tuberculosis infection better than TST. TST was influenced by age, BCG vaccination, sex, and glucocorticoid therapy. We found that IGRAs performed equally well with low level of indeterminate results (1-2%). IGRAs were superior to TST because the latter was influenced by BCG-vaccination status and immunosuppressive therapy.
Background Despite 155000 deaths and over 90 million cases - and the current emergence of antimicrobial resistance - no vaccines are available against non-typhoidSalmonellae(NTS). We recently ...presented immunological arguments for using the oralSalmonellaTyphi Ty21a as surrogate vaccine against NTS strains: Ty21a elicits intestinal antibodies against typhoidal O-9,12 antigen, and numerous NTS strains share one or both of these structures withS. Typhi. The Vi polysaccharide vaccine can, presumably because of contaminating typhoidal lipopolysaccharide, also elicit a humoral response to O-9,12, although a lower one in magnitude than the Ty21a. In this study, the Vi vaccine was explored for cross-reactive immune response to various NTS strains, and compared to that elicited by the Ty21a vaccine. Materials and methods Volunteers immunized with the Vi polysaccharide (Typherix®;n=25) were investigated for circulating plasmablasts secreting antibodies reactive with six NTS serotypes. The results were compared to those for 25 age- and gender-matched volunteers vaccinated with Ty21a (Vivotif®), as partly presented in our previous study. The cross-reactive plasmablasts elicited by the Vi vaccine were also analyzed for homing receptor expressions. Results 49 out of 50 vaccinees showed a cross-reactive plasmablast response againstS.Enteritidis sharing both O-9 and O-12 antigens withS.Typhi (mean: 95%CI 37: 19-55 and 363: 234-493 plasmablasts/106PBMC in the Vi and the Ty21a group, respectively). The response against strains only sharing O-12 was weaker (22: 8-38 and 222: 105-338 againstS.Typhimurium). Strains without typhoidal O-antigens generated no significant reactivity. The cross-reactive plasmablasts elicited by the Vi vaccine had systemic homing properties. Conclusions The Vi vaccine elicited an immune response cross-reactive with several NTS strains. This response was lower than that in Ty21a-vaccinated volunteers. The clinical significance of these responses deserves further research with respect to both gastrointestinal and invasive NTS (iNTS) disease.
Background Since protective efficacy of the current typhoid vaccines--oral whole-cell SalmonellaTyphi Ty21a and parenteral Vi-capsular polysaccharide preparation--is not optimal, and no vaccines are ...available against paratyphoid or non-typhoidalSalmonella(NTS) serotypes, new approaches deserve to be explored. The immunological mechanisms elicited by the two typhoid vaccines are mainly targeted against different structures. We studied whether these vaccines would enhanceS.Typhi-specific immune response and cross-reactivity against otherSalmonellae, if administered concomitantly. Materials and methods Volunteers were immunized simultaneously with Ty21a and Vi vaccines (Ty21a+Vi group) or with either of the two singly (Ty21a and Vi groups). All volunteers were investigated for circulating specific and cross-reactive plasmablasts, identified by ELISPOT as IgA, IgG or IgM antibody-secreting cells (ASC) reactive withS. Typhi,S. Paratyphi A/B/C, or selected NTS serotypes (S. Enteritidis,S. Typhimurium). Results In the Ty21a+Vi group, no specific or cross-reactive plasmablasts were detected before vaccination. After vaccination, the number ofS. Typhi-specific plasmablasts (878 ASC/106PBMC, 95%CI 554-1201) proved higher than in the Ty21a (339 ASC/106PBMC;p<0.001) and Vi (149 ASC/106PBMC;p<0.001) groups. Likewise, cross-reactive responses in the Ty21a+Vi group were higher than in the Ty21a and Vi groups (Ty21a+Vi vs Ty21a: ASC againstS. Paratyphi A/B,S. Enteritidis andS. Typhimuriump<0.05, againstS. Paratyphi Cp<0.01; Ty21a+Vi vs Vi: againstS. Paratyphi C not significant, othersp<0.0001). A gut-directed homing profile was seen among O antigen-specific and a systemic one among Vi antigen-specific plasmablasts. Conclusions Concomitant administration of Ty21a and Vi vaccines is well tolerated and induces an additive immune response to the two vaccines. Thus it enhances the magnitude of both typhoid-specific plasmablast responses and those cross-reacting with paratyphoid and most important NTS serotypes. The data encourage concomitant use of Ty21 and Vi vaccines for those at risk.
Highlights * There are no vaccines againstSalmonellaParatyphi in clinical use. * Some studies show efficacy with Ty21a-vaccine against paratyphoid A/B fever. * Ty21a elicited gut-directed ...plasmablasts cross-reactive withSalmonellaParatyphi. * Plasmablasts reactive withSalmonellaParatyphi were also seen in typhoid fever. * The data reveal a cross-reactive potential of Ty21a against paratyphoid fever.
Highlights * There are no vaccines available against non-typhoid Salmonella (NTS). * Intestinal antibodies against O-antigens have proven protective in animal studies. * Oral typhoid vaccine Ty21a ...effectively elicits intestinal antibodies to O-antigens. * These antibodies cross-react with common NTS strains, such asSalmonellaEnteritidis. * Ty21a may have cross-protective efficacy against numerous NTS strains.
Background The two typhoid vaccines, the parenteral Vi capsular polysaccharide and the oral live whole-cell Salmonella Typhi Ty21a vaccine, provide similar levels of protection in field trials. ...Sharing no antigens, they are thought to confer protection by different mechanisms. This is the first head-to-head study to compare the humoral immune responses to these two vaccines. Methods 50 age- and gender-matched volunteers were immunized, 25 with the Vi and 25 with the Ty21a vaccine. Circulating plasmablasts reactive with whole-cell Salmonella Typhi or one of the typhoidal antigenic structures, Vi, O-9,12, and H-d antigens, were identified as antibody-secreting cells (ASC) with ELISPOT. Homing receptor (HR) expressions were determined. These results were compared with ASC in four patients with typhoid fever. Antibodies to S. Typhi lipopolysaccharides were assessed in cultures of ALS (antibodies in lymphocyte supernatants) and in serum with ELISA. Results In 49 out of 50 vaccinees, no typhoid-specific plasmablasts were seen before vaccination. On day 7, response to Vi antigen was mounted in 24/25 volunteers in the Vi, and none in the Ty21a group; response to S. Typhi and O-9,12 was mounted in 49/50 vaccinees; and to H-d in 3/50. The numbers of typhoid-specific plasmablasts (total of ASC to Vi, O-9,12 and H-d antigens) proved equal in the vaccination groups. The HR expressions indicated a mainly systemic homing in the Vi and intestinal in the Ty21a group, the latter resembling that in natural infection. Plasmablasts proved more sensitive than serum and ALS in assessing the immune response. Conclusions The typhoid-specific humoral responses to Vi and Ty21a vaccines are similar in magnitude, but differ in expected localization and antigen-specificity. The unforeseen O antigen-specific response in the Vi group is probably due to lipopolysaccharide contaminating the vaccine preparation. Only the response to Ty21a vaccine was found to imitate that in natural infection. Trial Registration Current Controlled Trials Ltd. c/o BioMed Central ISRCTN68125331
An increasing amount of evidence indicates that a small extracellular chondroitin/dermatan sulfate proteoglycan, decorin, is indirectly involved in angiogenesis. Given that angiogenesis is a sine qua ...non for tumor growth and progression, we attempted to examine whether human malignant vascular tumors differ from human benign vascular tumors in terms of their decorin expression and synthesis. CD31 immunostaining demonstrated that the human malignant vascular tumors Kaposi's sarcoma and angiosarcoma were filled with capillary-like structures, whereas in benign cavernous and capillary hemangiomas, blood vessels were not as abundantly present. By utilizing in situ hybridization and immunocytochemical assays for decorin, we showed that there was no detectable decorin mRNA expression or immunoreactivity within the tumor mass in the Kaposi's sarcoma or angiosarcoma group. Instead, decorin was expressed in the connective tissue stroma lining the sarcoma tissue. In contrast to sarcomas, in hemangiomas, decorin mRNA expression and immunoreactivity were observed also within the tumor mass, particularly in the connective tissue stroma surrounding the clusters of intratumoral blood vessels. Finally, distribution of type I collagen was found to be similar to that of decorin in these tumor tissues. Our findings can be explained with different states of angiogenesis in dissimilar growths. In sarcomas, angiogenesis is extremely powerful, whereas in hemangiomas, angiogenesis has ceased. Thus, decorin is likely to possess a suppressive effect on human tumor angiogenesis in vivo, as previously described by studies using different experimental models. Decorin certainly provides a usable biomarker for distinguishing between benign and malignant vascular tumors in patients.
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