Safety and Immunogenicity of Live Oral Cholera and Typhoid Vaccines Administered Alone or in Combination with Antimalarial Drugs, Oral Polio Vaccine, or Yellow Fever Vaccine

The effects of concomitant administration of antimalarial drugs, oral polio vaccine, or yellow fever vaccine on the immune response elicited by the Vibrio cholerae CVD103-HgR and Salmonella typhi Ty21a live oral vaccines were investigated. Healthy adults were immunized with CVD103- HgR alone or combined with Ty21a. Subjects were randomized to simultaneously receive mefloquine, chloroquine or proguanil, or oral polio or yellow fever vaccine. The vibriocidal antibody seroconversion rate was significantly reduced (P = .008) only in the group that received chloroquine with the CVD103-HgR. The geometric mean vibriocidal antibody titer was significantly decreased in the groups that received chloroquine (P = .001) or mefloquine (P = .02) compared with titers in groups that received CVD103-HgR alone. However, similar immunosuppressive effects were not observed in the groups immunized with Ty21a and CVD103-HgR. Only the concomitant administration of proguanil effected a significant (P = .013) decline in the anti-S. typhi lipopolysaccharide antibody response. These results indicate that chloroquine and proguanil should not be simultaneously administered with the CVD103-HgR and Ty21a vaccine strains, respectivel

Prevention of Birch Pollen-Related Food Allergy by Mucosal Treatment with Multi-Allergen-Chimers in Mice

Among birch pollen allergic patients up to 70% develop allergic reactions to Bet v 1-homologue food allergens such as Api g 1 (celery) or Dau c 1 (carrot), termed as birch pollen-related food allergy. In most cases, specific immunotherapy with birch pollen extracts does not reduce allergic symptoms to the homologue food allergens. We therefore genetically engineered a multi-allergen chimer and tested if mucosal treatment with this construct could represent a novel approach for prevention of birch pollen-related food allergy.BALB/c mice were poly-sensitized with a mixture of Bet v 1, Api g 1 and Dau c 1 followed by a sublingual challenge with carrot, celery and birch pollen extracts. For prevention of allergy sensitization an allergen chimer composed of immunodominant T cell epitopes of Api g 1 and Dau c 1 linked to the whole Bet v 1 allergen, was intranasally applied prior to sensitization.Intranasal pretreatment with the allergen chimer led to significantly decreased antigen-specific IgE-dependent β-hexosaminidase release, but enhanced allergen-specific IgG2a and IgA antibodies. Accordingly, IL-4 levels in spleen cell cultures and IL-5 levels in restimulated spleen and cervical lymph node cell cultures were markedly reduced, while IFN-γ levels were increased. Immunomodulation was associated with increased IL-10, TGF-β and Foxp3 mRNA levels in NALT and Foxp3 in oral mucosal tissues. Treatment with anti-TGF-β, anti-IL10R or anti-CD25 antibodies abrogated the suppression of allergic responses induced by the chimer.Our results indicate that mucosal application of the allergen chimer led to decreased Th2 immune responses against Bet v 1 and its homologue food allergens Api g 1 and Dau c 1 by regulatory and Th1-biased immune responses. These data suggest that mucosal treatment with a multi-allergen vaccine could be a promising treatment strategy to prevent birch pollen-related food allergy

Quark-Gluon Matter

A concise review of the experimental and phenomenological progress in high-energy heavy-ion physics over the past few years is presented. Emphasis is put on measurements at BNL-RHIC and CERN-SPS which provide information on fundamental properties of QCD matter at extreme values of temperature, density and low-x. The new opportunities accessible at the LHC, which may help clarify some of the current open issues, are also outlined.Comment: Minor changes to text. New refs. included. Updated figures with final dat

Bacteraemia among severely malnourished children infected and uninfected with the human immunodeficiency virus-1 in Kampala, Uganda

BACKGROUND: To establish the magnitude of bacteraemia in severely malnourished children, and describe the types of bacteria and antimicrobial sensitivity by HIV status. METHOD: Isolates were recovered from 76 blood specimens. Antibiotic susceptibility tests were performed using commercial antibiotic disks and demographic and clinical findings were recorded. RESULTS: Of the 450 children 63% were male; median age 17.0 months (inter quartile range, IQR 12–24) and 57% had oedema. 151 (36.7 %) of 411 tested HIV-positive; 76 (17.1%) of 445 blood specimens grew bacterial isolates; 58% were Gram negative – S. typhimurium (27.6%) and S. enteriditis (11.8%). Staph. aureus (26.3%) and Strep. pneumoniae (13.2%) were the main Gram positive organisms. There was no difference in the risk of bacteraemia by HIV status, age < 24 months, male sex, or oedema, except for oral thrush (OR 2.3 CI 1.0–5.1) and hypoalbuminaemia (OR 3.5 CI 1.0–12.1). Isolates from severely immuno-suppressed children (CD4% <15%) were more likely to grow Salmonella enteriditis (OR 5.4; CI 1.6 – 17.4). The isolates were susceptible (≥ 80%) to ciprofloxacin, ceftriaxone and gentamicin; with low susceptibility to chlorampenicol, ampicillin (< 50%) and co-trimoxazole (<25%). Suspicion of bacteraemia had 95.9% sensitivity and 99.2% specificity. Among bacteraemic children, mortality was higher (43.5% vs 20.5%) in the HIV-positive; OR 3.0 (95%CI 1.0, 8.6). CONCLUSION: Bacteraemia affects 1 in every 6 severely malnourished children and carries high mortality especially among the HIV-positive. Given the high level of resistance to common antibiotics, there is need for clinical trials to determine the best combinations of antibiotics for management of bacteraemia in severely malnourished children

Effectiveness and economic analysis of the whole cell/recombinant B subunit (WC/rbs) inactivated oral cholera vaccine in the prevention of traveller's diarrhoea

<p>Abstract</p> <p>Background</p> <p>Nowadays there is a debate about the indication of the oral whole-cell/recombinant B-subunit cholera vaccine (WC/rBS) in traveller's diarrhoea. However, a cost-benefit analysis based on real data has not been published.</p> <p>Methods</p> <p>A cost-effectiveness and cost-benefit study of the oral cholera vaccine (WC/rBS), Dukoral^®for the prevention of traveller's diarrhoea (TD) was performed in subjects travelling to cholera risk areas. The effectiveness of WC/rBS vaccine in the prevention of TD was analyzed in 362 travellers attending two International Vaccination Centres in Spain between May and September 2005.</p> <p>Results</p> <p>The overall vaccine efficacy against TD was 42,6%. Direct healthcare-related costs as well as indirect costs (lost vacation days) subsequent to the disease were considered. Preventive vaccination against TD resulted in a mean saving of 79.26 € per traveller.</p> <p>Conclusion</p> <p>According to the cost-benefit analysis performed, the recommendation for WC/rBS vaccination in subjects travelling to zones at risk of TD is beneficial for the traveller, regardless of trip duration and visited continent.</p

Identification of Critical Amino Acids in an Immunodominant IgE Epitope of Pen c 13, a Major Allergen from Penicillium citrinum

Background: Pen c 13, identified as a 33-kDa alkaline serine protease, is a major allergen secreted by Penicillium citrinum. Detailed knowledge about the epitopes responsible for IgE binding would help inform the diagnosis/prognosis of fungal allergy and facilitate the rational design of hypoallergenic candidate vaccines. The goal of the present study was to characterize the IgE epitopes of Pen c 13. Methodology/Principal Findings: Serum samples were collected from 10 patients with mold allergy and positive Pen c 13 skin test results. IgE-binding epitopes on rPen c 13 were mapped using an enzymatic digestion and chemical cleavage method, followed by dot-blotting and mass spectrometry. A B-cell epitope-predicting server and molecular modeling were used to predict the residues most likely involved in IgE binding. Theoretically predicted IgE-binding regions were further confirmed by site-directed mutagenesis assays. At least twelve different IgE-binding epitopes located throughout Pen c 13 were identified. Of these, peptides S16 (A 148 –E 166) and S22 (A 243 –K 274) were recognized by sera from 90 % and 100 % of the patients tested, and were further confirmed by inhibition assays. Peptide S22 was selected for further analysis of IgE-binding ability. The results of serum screening showed that the majority of IgE-binding ability resided in the C-terminus. One Pen c 13 mutant, G270A (T 261 –K 274), exhibited clearly enhanced IgE reactivity, whereas another, K274A, exhibited dramatically reduced IgE reactivity

Heat-Induced Structural Changes Affect OVA-Antigen Processing and Reduce Allergic Response in Mouse Model of Food Allergy

BACKGROUND AND AIMS: The egg protein ovalbumin (OVA) belongs to six most frequent food allergens. We investigated how thermal processing influences its ability to induce allergic symptoms and immune responses in mouse model of food allergy. METHODOLOGY/PRINCIPAL FINDINGS: Effect of increased temperature (70°C and 95°C) on OVA secondary structure was characterized by circular dichroism and by the kinetics of pepsin digestion with subsequent HPLC. BALB/c mice were sensitized intraperitoneally and challenged with repeated gavages of OVA or OVA heated to 70°C (h-OVA). Levels of allergen-specific serum antibodies were determined by ELISA (IgA and IgGs) or by β-hexosaminidase release test (IgE). Specific activities of digestive enzymes were determined in brush border membrane vesicles of jejunal enterocytes. Cytokine production and changes in regulatory T cells in mesenteric lymph nodes and spleen were assessed by ELISA and FACS. Heating of OVA to 70°C caused mild irreversible changes in secondary structure compared to boiling to 95°C (b-OVA), but both OVA treatments led to markedly different digestion kinetics and Tregs induction ability in vitro, compared to native OVA. Heating of OVA significantly decreased clinical symptoms (allergic diarrhea) and immune allergic response on the level of IgE, IL-4, IL-5, IL-13. Furthermore, h-OVA induced lower activities of serum mast cell protease-1 and enterocyte brush border membrane alkaline phosphatase as compared to native OVA. On the other hand h-OVA stimulated higher IgG2a in sera and IFN-γ secretion by splenocytes. CONCLUSIONS: Minor irreversible changes in OVA secondary structure caused by thermal processing changes both its digestion and antigenic epitopes formation, which leads to activation of different T cell subpopulations, induces shift towards Th1 response and ultimately reduces its allergenicity

Complex networks for climate model evaluation with application to statistical versus dynamical modeling of South American climate

Acknowledgments: This paper was developed within the scope of the IRTG 1740/TRP 2011/50151-0, funded by the DFG/FAPESP. Furthermore, this work has been financially supported by the Leibniz Society (project ECONS), and the Stordalen Foundation (JFD). For certain calculations, the software packages pyunicorn (Donges et al. 2013a) and igraph (Csa´rdi and Nepusz 2006) were used. The authors would like to thank Manoel F. Cardoso, Niklas Boers, and the reviewers for helpful comments on the manuscript. Open Access: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Peer reviewedPostprin

The potential for tree planting strategies to reduce local and regional ecosystem impacts of agricultural ammonia emissions

Trees are very effective at capturing both gaseous and particulate pollutants from the atmosphere. But while studies have often focussed on PM and NOx in the urban environment, little research has been carried out on the tree effect of capturing gaseous emissions of ammonia in the rural landscape. To examine the removal or scavenging of ammonia by trees a long-range atmospheric model (FRAME) was used to compare two strategies that could be used in emission reduction policies anywhere in the world where nitrogen pollution from agriculture is a problem. One strategy was to reduce the emission source strength of livestock management systems by implementing two ‘tree-capture’ systems scenarios – tree belts downwind of housing and managing livestock under trees. This emission reduction can be described as an ‘on-farm’ emission reduction policy, as ammonia is ‘stopped’ from dispersion outside the farm boundaries. The second strategy was to apply an afforestation policy targeting areas of high ammonia emission through two planting scenarios of increasing afforestation by 25% and 50%. Both strategies use trees with the aim of intercepting NH3 emissions to protect semi-natural areas. Scenarios for on-farm emission reductions showed national reductions in nitrogen deposition to semi-natural areas of 0.14% (0.2 kt N–NHx) to 2.2% (3.15 kt N–NHx). Scenarios mitigating emissions from cattle and pig housing gave the highest reductions. The afforestation strategy showed national reductions of 6% (8.4 kt N–NHx) to 11% (15.7 kt N–NHx) for 25% and 50% afforestation scenarios respectively. Increased capture by the planted trees also showed an added benefit of reducing long range effects including a decrease in wet deposition up to 3.7 kt N–NHx (4.6%) and a decrease in export from the UK up to 8.3 kt N–NHx (6.8%)